Pyrus pyrifolia Nakai‘Whangkeumbae'is a sand pear fruit with excellent nutritional quality and taste.However,the industrial development of pear fruit is significantly limited by its short shelf life.Salicylic aci...Pyrus pyrifolia Nakai‘Whangkeumbae'is a sand pear fruit with excellent nutritional quality and taste.However,the industrial development of pear fruit is significantly limited by its short shelf life.Salicylic acid(SA),a well-known phytohormone,can delay fruit senescence and improve shelf life.However,the mechanism by which SA regulates CONSTANS-LIKE genes(COLs)during fruit senescence and the role of COL genes in mediating fruit senescence in sand pear are poorly understood.In this study,22 COL genes were identified in sand pear,including four COLs(Pp COL8,Pp COL9a,Pp COL9b,and Pp COL14)identified via transcriptome analysis and 18 COLs through genome-wide analysis.These COL genes were divided into three subgroups according to the structural domains of the COL protein.Pp COL8,with two B-box motifs and one CCT domain,belonged to the first subgroup.In contrast,the other three Pp COLs,Pp COL9a,Pp COL9b,and Pp COL14,with similar conserved protein domains and gene structures,were assigned to the third subgroup.The four COLs showed different expression patterns in pear tissues and were preferentially expressed at the early stage of fruit development.Moreover,the expression of Pp COL8 was inhibited by exogenous SA treatment,while SA up-regulated the expression of Pp COL9a and Pp COL9b.Interestingly,Pp COL8 interacts with Pp MADS,a MADS-box protein preferentially expressed in fruit,and SA up-regulated its expression.While the production of ethylene and the content of malondialdehyde(MDA)were increased in Pp COL8-overexpression sand pear fruit,the antioxidant enzyme(POD and SOD)activity and the expression of Pp POD1 and Pp SOD1 in the sand pear fruits were down-regulated,which showed that Pp COL8 promoted sand pear fruit senescence.In contrast,the corresponding changes were the opposite in Pp MADS-overexpression sand pear fruits,suggesting that Pp MADS delayed sand pear fruit senescence.The co-transformation of Pp COL8 and Pp MADS also delayed sand pear fruit senescence.The results of this study revealed that Pp COL8 can play a key role in pear fruit senescence by interacting with Pp MADS through the SA signaling pathway.展开更多
This paper describes the investigation of the release mechanism of the cationic drug coated with Sureleaseafter curing compared with nonionic and anionic drug.The release rate of cured propafenone hydrochloride pelle...This paper describes the investigation of the release mechanism of the cationic drug coated with Sureleaseafter curing compared with nonionic and anionic drug.The release rate of cured propafenone hydrochloride pellets coated with Sureleasewas increased significantly compared with uncured ones.The changes in release rate after seal-coating proved the migration of drug into the polymer film.Based on a comparative study of ammonia permeation tests and the impact of ammonia on drug with different properties,it was shown that the change in release of the cationic drug after curing was related to the combination of cationic drug and ammonia in Surelease.Also,the scanning electron microscopy results showed that curing and dissolution can both prevent polymer film coalescence.During coating,the evaporated ammonia combined with the cationic drug and the polymer film coalesced.However,the combined ammonia could be decomposed during curing and interrupt the coalescence of the polymer-coat,leading to increased release.In an optimized process,the ammonia in the Sureleasecan be evaporated quickly and the ionization of the drug will be reduced.All these factors can contribute to the formation of the polymer film.展开更多
The education and research of traditional Chinese medicine(TCM)in Malaysia started coincidentally circa Malaysia’s independence movement.Before the independence,much of the development focused on establishing treatme...The education and research of traditional Chinese medicine(TCM)in Malaysia started coincidentally circa Malaysia’s independence movement.Before the independence,much of the development focused on establishing treatment centers and Chinese medical halls to provide TCM treatment.Periodicals and journals advocating TCM and its advancement were published between the 1940s and 1960s,but many did not survive after a few issues.The challenge posed by the Immigration Ordinance 1952 further united TCM practitioners and TCM associations to establish the Chinese Medical Institute of Malaya.The trend gained momentum,and many educational institutes were set up in each of Malaysia.From the 1970s,Malaysia started hosting regional and international TCM conferences.In 2000,TCM education in Malaysia had finally gained recognition from the government.ATCM program standard was thus released by the Malaysian Qualifications Agency(MQA).To date,there are seven private higher education institutions which offer TCM programs based on the MQA standards and have established international collaborations with other universities.It is projected that Malaysia’s TCM education and research will grow further as a result of China’s Belt and Road initiative.展开更多
The optimality of a density estimation on Besov spaces Bsr,q(R) for the Lp risk was established by Donoho, Johnstone, Kerkyacharian and Picard (“Density estimation by wavelet thresholding,” The Annals of Statistics,...The optimality of a density estimation on Besov spaces Bsr,q(R) for the Lp risk was established by Donoho, Johnstone, Kerkyacharian and Picard (“Density estimation by wavelet thresholding,” The Annals of Statistics, Vol. 24, No. 2, 1996, pp. 508-539.). To show the lower bound of optimal rates of convergence Rn(Bsr,q, p), they use Korostelev and Assouad lemmas. However, the conditions of those two lemmas are difficult to be verified. This paper aims to give another proof for that bound by using Fano’s Lemma, which looks a little simpler. In addition, our method can be used in many other statistical models for lower bounds of estimations.展开更多
The increasing number of TCM practitioners and herbal suppliers,both of which accelerated by the formation of various TCM institutions,substantiated the creation of regional traditional Chinese medicine(TCM)associatio...The increasing number of TCM practitioners and herbal suppliers,both of which accelerated by the formation of various TCM institutions,substantiated the creation of regional traditional Chinese medicine(TCM)associations in post-World War II Malaya.In response to the restrictions and levies imposed by the British colonial government,these regional associations united and formed a national organisation now known as the Federation of Chinese Physicians and Medicine Dealers Association of Malaya(FCPMDAM).The current designated TCM practitioner body,the Malaysian Chinese Medical Association(MCMA)were also originally established to nurture local talents in the face of import restrictions.Owing to difference with MCMA,a separate association named the Federation of Chinese Physicians and Acupuncturists Associations of Malaysia(FCPAAM)was setup in 2003 to absorb self-studied and patrimonial-educated TCM practitioners.展开更多
Although traditional Chinese medicine(TCM)has been a part of the Malaya and the Malaysia people’s method of maintaining health and well-being for many centuries,it was never been enrolled in the public health-care sy...Although traditional Chinese medicine(TCM)has been a part of the Malaya and the Malaysia people’s method of maintaining health and well-being for many centuries,it was never been enrolled in the public health-care system.However,the rising cost of Western drugs and the increasing number of people frequenting TCM has driven the government to search for cheaper options and to look into its safe practice.In 1992,the government mandated all TCM herbal products to be registered with the National Pharmaceutical Control Bureau.All TCM products sold in Malaysia are now Good Manufacturing Practice certified.The government has also established a Traditional and Complementary Medicine Division within the Ministry of Health.Between 2008 and 2014,a traditional and complementary medicine unit was set up in major hospitals in all states.TCM is one of the main services offered by the unit.In 2016,the government enacted the Traditional and Complementary Medicine Act to regulate the TCM practice.Subsequently,a 10-vear blueprint has been drawn to support the development of all traditional and complementary medicines in Malaysia.This article aims to provide a brief overview on the regulatory development of TCM in Malaysia.展开更多
Traditional Chinese Medicine(TCM)in British Malaya developed concurrently with the influx of Chinese immigrants.To cater for tins growing community,Chinese medical halls which sell Chinese herbs were established in ma...Traditional Chinese Medicine(TCM)in British Malaya developed concurrently with the influx of Chinese immigrants.To cater for tins growing community,Chinese medical halls which sell Chinese herbs were established in major townships.Consultation and various TCM treatments were also offered by contract TCM practitioners in some of these medical halls.As the needs for TCM services continued to grow,dedicated TCM institutions were set up subsequently.The establishment of these institutions marked the beginning of professional TCM services in the history of Malaysia.展开更多
Genetically encoded circuits have been successfully utilized to assess and characterize target variants with desirable traits from large mutant libraries.Adenosylcobalamin is an essential coenzyme that is required in ...Genetically encoded circuits have been successfully utilized to assess and characterize target variants with desirable traits from large mutant libraries.Adenosylcobalamin is an essential coenzyme that is required in many intracellular physiological reactions and is widely used in the pharmaceutical and food industries.High-throughput screening techniques capable of detecting adenosylcobalamin productivity and selecting superior adenosylcobalamin biosynthesis strains are critical for the creation of an effective microbial cell factory for the production of adenosylcobalamin at an industrial level.In this study,we developed an RNA-protein hybrid biosensor whose input part was an endogenous RNA riboswitch to specifically respond to adenosylcobalamin,the inverter part was an orthogonal transcriptional repressor to obtain signal inversion,and the output part was a fluorescent protein to be easily detected.The hybrid biosensor could specifically and positively correlate adenosylcobalamin concentrations to green fluorescent protein expression levels in vivo.This study also improved the operating concentration and dynamic range of the hybrid biosensor by systematic optimization.An individual cell harboring the hybrid biosensor presented over 20-fold higher fluorescence intensity than the negative control.Then,using such a biosensor combined with fluorescence-activated cell sorting,we established a high-throughput screening platform for screening adenosylcobalamin overproducers.This study demonstrates that this platform has significant potential to quickly isolate high-productive strains to meet industrial demand and that the framework is acceptable for various metabolites.展开更多
Vitamin B_(12)is a complex compound synthesized by microorganisms.The industrial production of vitamin B_(12)relies on specific microbial fermentation processes.E.coli has been utilized as a host for the de novo biosy...Vitamin B_(12)is a complex compound synthesized by microorganisms.The industrial production of vitamin B_(12)relies on specific microbial fermentation processes.E.coli has been utilized as a host for the de novo biosynthesis of vitamin B_(12),incorporating approximately 30 heterologous genes.However,a metabolic imbalance in the intricate pathway significantly limits vitamin B_(12)production.In this study,we employed multivariate modular metabolic engineering to enhance vitamin B_(12)production in E.coli by manipulating two modules comprising a total of 10 genes within the vitamin B_(12)biosynthetic pathway.These two modules were integrated into the chromosome of a chassis cell,regulated by T7,J23119,and J23106 promoters to achieve combinatorial pathway optimization.The highest vitamin B_(12)titer was attained by engineering the two modules controlled by J23119 and T7 promoters.The inclusion of yeast powder to the fermentation medium increased the vitamin B_(12)titer to 1.52 mg/L.This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain’s isopropyl-β-D-1-thiogalactopyranoside(IPTG)tolerance.Ultimately,vitamin B_(12)titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter.The strategies reported herein will expedite the development of industry-scale vitamin B_(12)production utilizing E.coli.展开更多
Video camouflaged object detection(VCOD)has become a fundamental task in computer vision that has attracted significant attention in recent years.Unlike image camouflaged object detection(ICOD),VCOD not only requires ...Video camouflaged object detection(VCOD)has become a fundamental task in computer vision that has attracted significant attention in recent years.Unlike image camouflaged object detection(ICOD),VCOD not only requires spatial cues but also needs motion cues.Thus,effectively utilizing spatiotemporal information is crucial for generating accurate segmentation results.Current VCOD methods,which typically focus on exploring motion representation,often ineffectively integrate spatial and motion features,leading to poor performance in diverse scenarios.To address these issues,we design a novel spatiotemporal network with an encoder-decoder structure.During the encoding stage,an adjacent space-time memory module(ASTM)is employed to extract high-level temporal features(i.e.,motion cues)from the current frame and its adjacent frames.In the decoding stage,a selective space-time aggregation module is introduced to efficiently integrate spatial and temporal features.Additionally,a multi-feature fusion module is developed to progressively refine the rough prediction by utilizing the information provided by multiple types of features.Furthermore,we incorporate multi-task learning into the proposed network to obtain more accurate predictions.Experimental results show that the proposed method outperforms existing cutting-edge baselines on VCOD benchmarks.展开更多
Phloem-feeding insects cause massive losses in agriculture and horticulture.Host plant resistance to phloem-feeding insects is often mediated by changes in phloem composition,which deter insect settling and feeding an...Phloem-feeding insects cause massive losses in agriculture and horticulture.Host plant resistance to phloem-feeding insects is often mediated by changes in phloem composition,which deter insect settling and feeding and decrease viability.Here,we report that rice plant resistance to the phloem-feeding brown planthopper(BPH)is associated with fortification of the sclerenchyma tissue,which is located just beneath the epidermis and a cell layer or two away from the vascular bundle in the rice leaf sheath.We found that BPHs prefer to feed on the smooth and soft region on the surface of rice leaf sheaths called the long-cell block.We identified Bph30 as a rice BPH resistance gene that prevents BPH stylets from reaching the phloem due to the fortified sclerenchyma.Bph30 is strongly expressed in sclerenchyma cells and enhances cellulose and hemicellulose synthesis,making the cell walls stiffer and sclerenchyma thicker.The structurally fortified sclerenchyma is a formidable barrier preventing BPH stylets from penetrating the leaf sheath tissues and arriving at the phloem to feed.Bph30 belongs to a novel gene family,encoding a protein with two leucine-rich domains.Another member of the family,Bph40,also conferred resistance to BPH.Collectively,the fortified sclerenchyma-mediated resistance mechanism revealed in this study expands our understanding of plant-insect interactions and opens a new path for controlling planthoppers in rice.展开更多
Atmospheric reanalysis reproduces the past atmospheric conditions through assimilation of historical meteorological observations with fixed version of a numerical weather prediction(NWP)model and data assimilation(DA)...Atmospheric reanalysis reproduces the past atmospheric conditions through assimilation of historical meteorological observations with fixed version of a numerical weather prediction(NWP)model and data assimilation(DA)system.It is widely used in weather,climate,and even business-related research and applications.This paper reports the development of CMA’s first-generation global atmospheric reanalysis(RA)covering 1979–2018(CRA-40;CRA refers to CMA-RA).CRA-40 is produced by using the Global Spectral Model(GSM)/Gridpoint Statistical Interpolation(GSI)at a 6-h time interval and a TL574 spectral(34-km)resolution with the model top at 0.27 hPa.A large number of reprocessed satellite data and widely collected conventional observations were assimilated during the reanalyzing process,including the reprocessed atmospheric motion vector(AMV)products from FY-2C/D/E/G satellites,dense conventional observations(at about 120 radiosonde and 2400 synoptic stations)over China,as well as MWHS-2 and GNSS-RO observations from FY-3C.The reanalysis fitting to observations is improved over time,especially for surface pressure with root-mean-square error reduced from 1.05 hPa in 1979 to 0.8 hPa,and for upper air temperature from 1.65 K in 1979 to 1.35 K,in 2018.The patterns of global analysis increments for temperature,specific humidity,and zonal wind are consistent with the changes in the observing system.Near surface temperature from the model’s 6-h forecast reflects the global warming trend reasonably.The CRA-40 precipitation pattern matches well with those of GPCP and other reanalyses.CRA-40 also successfully captures the QBO and its vertical and temporal development,hemispherical atmospheric circulation change,and moisture transport by the East Asian summer monsoon.CRA is now operationally running in near real time as a climate data assimilation system in CMA.展开更多
This paper presents a detailed description of integration, quality assurance procedure, and usage of global aircraft observations for China's first generation global atmospheric reanalysis(CRA) product(1979–2018)...This paper presents a detailed description of integration, quality assurance procedure, and usage of global aircraft observations for China's first generation global atmospheric reanalysis(CRA) product(1979–2018). An integration method named "classified integration" is developed. Aircraft observations from nine different sources are integrated into the Integrated Global Meteorological Observation Archive from Aircraft(IGMOAA), a new dataset from the National Meteorological Information Center(NMIC) of the China Meteorological Administration(CMA). IGMOAA consists of global aircraft temperature, wind, and humidity data from the surface to 100 h Pa, extending from 1973 to the present. Compared with observations assimilated in the Climate Forecast System Reanalysis(CFSR) of NCEP,the observation number of IGMOAA increased by 12.9% between 2010 and 2014, mainly as a result of adding more Chinese Aircraft Meteorological Data Relay(AMDAR) data. Complex quality control procedures for aircraft observations of NCEP are applied to detect data errors. Observations are compared with ERA-Interim reanalysis from 1979 to 2018 to investigate data quality of different types and aircraft, and subsequently to develop the blacklists for CRA. IGMOAA data have been assimilated in CRA in 2018 and are real-time updated at the CMA Data-as-a-Service(CMADaa S) platform. For CRA, the fits to observations improve over time. From 1994 to 2018, root-meansquare error(RMSE) of observations relative to CRA background decreases from 1.8 to 1.0℃ for temperature above 300 h Pa, and from 4.5 to 3 m s^(-1) for zonal wind. The RMSE for humidity appears to exhibit an apparent seasonal variation with larger errors in summer and smaller ones in winter.展开更多
Optimizing the supply of biosynthetic precursors and cofactors is usually an effective metabolic strategy to improve the production of target compounds.Here,the combination of optimizing precursor synthesis and balanc...Optimizing the supply of biosynthetic precursors and cofactors is usually an effective metabolic strategy to improve the production of target compounds.Here,the combination of optimizing precursor synthesis and balancing cofactor metabolism was adopted to improve tryptophan production in Escherichia coli.First,glutamine synthesis was improved by expressing heterologous glutamine synthetase from Bacillus subtilis and Bacillus megaterium in the engineered Escherichia coli strain KW001,resulting in the best candidate strain TS-1.Then icd and gdhA were overexpressed in TS-1,which led to the accumulation of 1.060 g/L tryptophan.Subsequently,one more copy of prs was introduced on the chromosome to increase the flux of 5-phospho-α-D-ribose 1-diphosphate followed by the expression of mutated serA and thrA to increase the precursor supply of serine,resulting in the accumulation of 1.380 g/L tryptophan.Finally,to maintain cofactor balance,sthA and pntAB,encoding transhydrogenase,were overexpressed.With sufficient amounts of precursors and balanced cofactors,the engineered strain could produce 1.710 g/L tryptophan after 48 h of shake-flask fermentation,which was 2.76-times higher than the titer of the parent strain.Taken together,our results demonstrate that the combination of optimizing precursor supply and regulating cofactor metabolism is an effective approach for high-level production of tryptophan.Similar strategies could be applied to the production of other amino acids or related derivatives.展开更多
Optical absorption and photocatalytic activity can be enhanced by surface plasmon resonance (SPR) effect,but the charge transfer (CT) mechanism between the dispersed noble metal nanoparticles (NPs) and the semiconduct...Optical absorption and photocatalytic activity can be enhanced by surface plasmon resonance (SPR) effect,but the charge transfer (CT) mechanism between the dispersed noble metal nanoparticles (NPs) and the semiconductor matrix has been ignored.Herein,we adduce a direct and strong evidence in Ag-nanoparticle-dispersed BaTiO3 (Ag/BTO) composite films through X-ray photoelectron and photoluminescence spectra which reveals the CT from BTO trapped by Ag NPs under UV light and from Ag NPs to BTO under visible light.Owing to the broadened optical absorption and efficient CT from Ag NPs to BTO,the Ag25/BTO film manifests the optimal photocatalytic activity under the irradiation of visible light rather than UV-Vis light.Our work provides a helpful insight to design highly efficient plasmonic photocatalyst through considering the synergetic effect of the CT between metal and semiconductor on the enhanced photocatalytic activity.展开更多
The chemical complexity of traditional Chinese medicines(TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform(TCMs-C...The chemical complexity of traditional Chinese medicines(TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform(TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included:(1) selection of herbal drugs of target based on TCMs knowledge base;(2) chemome profiling of TCMs extract library by LC-MS;(3) cytological profiling of TCMs extract library by high-content cell-based imaging;(4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes;(5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs(Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.展开更多
Iron plays a crucial role in improving the oxygen evolution reaction(OER)activity of hydroxide materials.Increasing the number of iron active sites at the solid–liquid interface is beneficial to enhancing the OER per...Iron plays a crucial role in improving the oxygen evolution reaction(OER)activity of hydroxide materials.Increasing the number of iron active sites at the solid–liquid interface is beneficial to enhancing the OER performance of catalysts but still challenging.Here,by systematic exploring the activity trends of M(OH)_(x)and Cu-M(OH)_(x)(M=Mn,Cu,Ni,Fe,and Co),we discover that the Cu doping can promote the deposition of Fe active sites on metal hydroxide and Cu-Co(OH)2 shows the most favorable iron adsorption capacity.When loaded on a conductive substrate(cobalt foam(CF),the M-Cu-Co(OH)2/CF(Co(OH)_(2))prepared by molten salt method)exhibits an attractive low overpotential of 337 mV at 1,000 mA·cm^(−2).Using in anion exchange membrane(AEM)water electrolyzer,the single cell with M-Cu-Co(OH)_(2)/CF as anode catalyst performs a stable cell voltage of 2.02 V to reach 1,000 mA·cm^(−2)over 24 h,indicating a great application potential for actual electrolytic water.Therefore,the promoted adsorption of copper on iron provides a new perspective for further enhancing the OER activity of other metal hydroxides.展开更多
Chiral superstructures in confined spaces are subtly affected by the complex interplay among various noncovalent interactions,details of which are still in adequately understood.Herein,we report the threedimensional c...Chiral superstructures in confined spaces are subtly affected by the complex interplay among various noncovalent interactions,details of which are still in adequately understood.Herein,we report the threedimensional confined assembly of the chiral block copolymers of polystyrene-block-poly(D-lactide)andits enantiomer in emulsion droplets and demonstrate unprecedented successive microphase transformations from single helices to double helices with inverted helicity,and then to twisted cylinders in the constructedcolloidal particles.Theabovehierarchical structural transformations of chiral microphases are kinetically dependent and can further transform into thermodynamically stable achiral cylinders with saddle-shaped topology upon solvent annealing.The formation and subsequent structural transformations as well as thefinal degeneration of chiral architectures provide guidance to understand the chiral evolution at different length scales within spherical confined space and to fabricate biomimetic systems.展开更多
The development of electrocatalysts for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)is crucial for sustainable energy and environmental initiatives.This work establishes an atomically-dispersed R...The development of electrocatalysts for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)is crucial for sustainable energy and environmental initiatives.This work establishes an atomically-dispersed Ru-based model to investigate the promoting mechanism by the Ru-Integration effect in RuCo bimetallic nanoparticles supported on nitrogen-doped carbon(RuCo@NC).Specially,the Ru content in RuCo@NC plays a vital role for both HER and OER.The optimized catalyst shows an outstanding performance,requiring only 217 and 97 mV overpotential to reach a current density of 10 mA·cm^(−2)for OER and HER respectively in alkaline conditions.Combined with advanced characterizations such as spherical aberration-corrected scanning transmission electron microscopy,X-ray absorption spectroscopy,in-situ Raman spectroscopy,and density functional theory calculations,it is found that Ru plays multiple crucial roles:(1)Ru restricts the growth of large Co NPs,while the small-sized Co NPs facilitate the formation of carbon nanotubes,which significantly enhances the mass/electron transfer;(2)Ru not only tunes the surface properties of Co but also acts as an active site for HER.As a result,when using RuCo@NC as an overall water splitting catalyst,it only needs a potential of 1.62 V to reach a current density of 100 mA·cm^(−2).This work offers valuable insights into designing Ru-based electrocatalysts for water splitting.展开更多
基金supported by the National Natural Science Foundation of China(32272654)the Natural Science Foundation of Hebei Province China(C2023204016)+2 种基金the Hebei Province Introduced Overseas-Scholar Fund China(C20220361)the S&T Program of Hebei China(20326330D)the Hebei Province Outstanding Youth Fund China(2016,2019)。
文摘Pyrus pyrifolia Nakai‘Whangkeumbae'is a sand pear fruit with excellent nutritional quality and taste.However,the industrial development of pear fruit is significantly limited by its short shelf life.Salicylic acid(SA),a well-known phytohormone,can delay fruit senescence and improve shelf life.However,the mechanism by which SA regulates CONSTANS-LIKE genes(COLs)during fruit senescence and the role of COL genes in mediating fruit senescence in sand pear are poorly understood.In this study,22 COL genes were identified in sand pear,including four COLs(Pp COL8,Pp COL9a,Pp COL9b,and Pp COL14)identified via transcriptome analysis and 18 COLs through genome-wide analysis.These COL genes were divided into three subgroups according to the structural domains of the COL protein.Pp COL8,with two B-box motifs and one CCT domain,belonged to the first subgroup.In contrast,the other three Pp COLs,Pp COL9a,Pp COL9b,and Pp COL14,with similar conserved protein domains and gene structures,were assigned to the third subgroup.The four COLs showed different expression patterns in pear tissues and were preferentially expressed at the early stage of fruit development.Moreover,the expression of Pp COL8 was inhibited by exogenous SA treatment,while SA up-regulated the expression of Pp COL9a and Pp COL9b.Interestingly,Pp COL8 interacts with Pp MADS,a MADS-box protein preferentially expressed in fruit,and SA up-regulated its expression.While the production of ethylene and the content of malondialdehyde(MDA)were increased in Pp COL8-overexpression sand pear fruit,the antioxidant enzyme(POD and SOD)activity and the expression of Pp POD1 and Pp SOD1 in the sand pear fruits were down-regulated,which showed that Pp COL8 promoted sand pear fruit senescence.In contrast,the corresponding changes were the opposite in Pp MADS-overexpression sand pear fruits,suggesting that Pp MADS delayed sand pear fruit senescence.The co-transformation of Pp COL8 and Pp MADS also delayed sand pear fruit senescence.The results of this study revealed that Pp COL8 can play a key role in pear fruit senescence by interacting with Pp MADS through the SA signaling pathway.
文摘This paper describes the investigation of the release mechanism of the cationic drug coated with Sureleaseafter curing compared with nonionic and anionic drug.The release rate of cured propafenone hydrochloride pellets coated with Sureleasewas increased significantly compared with uncured ones.The changes in release rate after seal-coating proved the migration of drug into the polymer film.Based on a comparative study of ammonia permeation tests and the impact of ammonia on drug with different properties,it was shown that the change in release of the cationic drug after curing was related to the combination of cationic drug and ammonia in Surelease.Also,the scanning electron microscopy results showed that curing and dissolution can both prevent polymer film coalescence.During coating,the evaporated ammonia combined with the cationic drug and the polymer film coalesced.However,the combined ammonia could be decomposed during curing and interrupt the coalescence of the polymer-coat,leading to increased release.In an optimized process,the ammonia in the Sureleasecan be evaporated quickly and the ionization of the drug will be reduced.All these factors can contribute to the formation of the polymer film.
文摘The education and research of traditional Chinese medicine(TCM)in Malaysia started coincidentally circa Malaysia’s independence movement.Before the independence,much of the development focused on establishing treatment centers and Chinese medical halls to provide TCM treatment.Periodicals and journals advocating TCM and its advancement were published between the 1940s and 1960s,but many did not survive after a few issues.The challenge posed by the Immigration Ordinance 1952 further united TCM practitioners and TCM associations to establish the Chinese Medical Institute of Malaya.The trend gained momentum,and many educational institutes were set up in each of Malaysia.From the 1970s,Malaysia started hosting regional and international TCM conferences.In 2000,TCM education in Malaysia had finally gained recognition from the government.ATCM program standard was thus released by the Malaysian Qualifications Agency(MQA).To date,there are seven private higher education institutions which offer TCM programs based on the MQA standards and have established international collaborations with other universities.It is projected that Malaysia’s TCM education and research will grow further as a result of China’s Belt and Road initiative.
文摘The optimality of a density estimation on Besov spaces Bsr,q(R) for the Lp risk was established by Donoho, Johnstone, Kerkyacharian and Picard (“Density estimation by wavelet thresholding,” The Annals of Statistics, Vol. 24, No. 2, 1996, pp. 508-539.). To show the lower bound of optimal rates of convergence Rn(Bsr,q, p), they use Korostelev and Assouad lemmas. However, the conditions of those two lemmas are difficult to be verified. This paper aims to give another proof for that bound by using Fano’s Lemma, which looks a little simpler. In addition, our method can be used in many other statistical models for lower bounds of estimations.
文摘The increasing number of TCM practitioners and herbal suppliers,both of which accelerated by the formation of various TCM institutions,substantiated the creation of regional traditional Chinese medicine(TCM)associations in post-World War II Malaya.In response to the restrictions and levies imposed by the British colonial government,these regional associations united and formed a national organisation now known as the Federation of Chinese Physicians and Medicine Dealers Association of Malaya(FCPMDAM).The current designated TCM practitioner body,the Malaysian Chinese Medical Association(MCMA)were also originally established to nurture local talents in the face of import restrictions.Owing to difference with MCMA,a separate association named the Federation of Chinese Physicians and Acupuncturists Associations of Malaysia(FCPAAM)was setup in 2003 to absorb self-studied and patrimonial-educated TCM practitioners.
文摘Although traditional Chinese medicine(TCM)has been a part of the Malaya and the Malaysia people’s method of maintaining health and well-being for many centuries,it was never been enrolled in the public health-care system.However,the rising cost of Western drugs and the increasing number of people frequenting TCM has driven the government to search for cheaper options and to look into its safe practice.In 1992,the government mandated all TCM herbal products to be registered with the National Pharmaceutical Control Bureau.All TCM products sold in Malaysia are now Good Manufacturing Practice certified.The government has also established a Traditional and Complementary Medicine Division within the Ministry of Health.Between 2008 and 2014,a traditional and complementary medicine unit was set up in major hospitals in all states.TCM is one of the main services offered by the unit.In 2016,the government enacted the Traditional and Complementary Medicine Act to regulate the TCM practice.Subsequently,a 10-vear blueprint has been drawn to support the development of all traditional and complementary medicines in Malaysia.This article aims to provide a brief overview on the regulatory development of TCM in Malaysia.
文摘Traditional Chinese Medicine(TCM)in British Malaya developed concurrently with the influx of Chinese immigrants.To cater for tins growing community,Chinese medical halls which sell Chinese herbs were established in major townships.Consultation and various TCM treatments were also offered by contract TCM practitioners in some of these medical halls.As the needs for TCM services continued to grow,dedicated TCM institutions were set up subsequently.The establishment of these institutions marked the beginning of professional TCM services in the history of Malaysia.
基金supported by the National Key R&D Program of China[Grant number 2021YFC2100700]the National Natural Science Foundation of China[Grant numbers 22178372,32300069]+3 种基金TIB-VIB Joint Center of Synthetic Biology[Grant number TSBICIP-IJCP-002]the National Science Fund for Distinguished Young Scholars[Grant number 22325807]the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project[Grant numbers TSBICIP-KJGG-011,TSBICIP-CXRC-055]the Yellow River Delta Industry Leading Talents[Grant number DYRC20190212].
文摘Genetically encoded circuits have been successfully utilized to assess and characterize target variants with desirable traits from large mutant libraries.Adenosylcobalamin is an essential coenzyme that is required in many intracellular physiological reactions and is widely used in the pharmaceutical and food industries.High-throughput screening techniques capable of detecting adenosylcobalamin productivity and selecting superior adenosylcobalamin biosynthesis strains are critical for the creation of an effective microbial cell factory for the production of adenosylcobalamin at an industrial level.In this study,we developed an RNA-protein hybrid biosensor whose input part was an endogenous RNA riboswitch to specifically respond to adenosylcobalamin,the inverter part was an orthogonal transcriptional repressor to obtain signal inversion,and the output part was a fluorescent protein to be easily detected.The hybrid biosensor could specifically and positively correlate adenosylcobalamin concentrations to green fluorescent protein expression levels in vivo.This study also improved the operating concentration and dynamic range of the hybrid biosensor by systematic optimization.An individual cell harboring the hybrid biosensor presented over 20-fold higher fluorescence intensity than the negative control.Then,using such a biosensor combined with fluorescence-activated cell sorting,we established a high-throughput screening platform for screening adenosylcobalamin overproducers.This study demonstrates that this platform has significant potential to quickly isolate high-productive strains to meet industrial demand and that the framework is acceptable for various metabolites.
基金supported by the National Key R&D Program of China(2018YFA0903700)the National Natural Science Foundation of China(22178372,22208367)+2 种基金National Science Fund for Distinguished Young Scholars(22325807)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-011,TSBICIP-CXRC-055,TSBICIP-PTJJ-007)Youth Innovation Promotion Association,Chinese Academy of Sciences(2020182).
文摘Vitamin B_(12)is a complex compound synthesized by microorganisms.The industrial production of vitamin B_(12)relies on specific microbial fermentation processes.E.coli has been utilized as a host for the de novo biosynthesis of vitamin B_(12),incorporating approximately 30 heterologous genes.However,a metabolic imbalance in the intricate pathway significantly limits vitamin B_(12)production.In this study,we employed multivariate modular metabolic engineering to enhance vitamin B_(12)production in E.coli by manipulating two modules comprising a total of 10 genes within the vitamin B_(12)biosynthetic pathway.These two modules were integrated into the chromosome of a chassis cell,regulated by T7,J23119,and J23106 promoters to achieve combinatorial pathway optimization.The highest vitamin B_(12)titer was attained by engineering the two modules controlled by J23119 and T7 promoters.The inclusion of yeast powder to the fermentation medium increased the vitamin B_(12)titer to 1.52 mg/L.This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain’s isopropyl-β-D-1-thiogalactopyranoside(IPTG)tolerance.Ultimately,vitamin B_(12)titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter.The strategies reported herein will expedite the development of industry-scale vitamin B_(12)production utilizing E.coli.
文摘Video camouflaged object detection(VCOD)has become a fundamental task in computer vision that has attracted significant attention in recent years.Unlike image camouflaged object detection(ICOD),VCOD not only requires spatial cues but also needs motion cues.Thus,effectively utilizing spatiotemporal information is crucial for generating accurate segmentation results.Current VCOD methods,which typically focus on exploring motion representation,often ineffectively integrate spatial and motion features,leading to poor performance in diverse scenarios.To address these issues,we design a novel spatiotemporal network with an encoder-decoder structure.During the encoding stage,an adjacent space-time memory module(ASTM)is employed to extract high-level temporal features(i.e.,motion cues)from the current frame and its adjacent frames.In the decoding stage,a selective space-time aggregation module is introduced to efficiently integrate spatial and temporal features.Additionally,a multi-feature fusion module is developed to progressively refine the rough prediction by utilizing the information provided by multiple types of features.Furthermore,we incorporate multi-task learning into the proposed network to obtain more accurate predictions.Experimental results show that the proposed method outperforms existing cutting-edge baselines on VCOD benchmarks.
基金This work was supported by the Major Program of Guangdong Basic andApplied Research,China(2019B030302006)the National Program onResearch and Development of Transgenic Plants of China(2016ZX08009-003)+1 种基金grants from the National Natural Science Foundationof China(31630063)the National Key Research and DevelopmentProgram of China(2016YFD0100600 and 2016YFD0100900).
文摘Phloem-feeding insects cause massive losses in agriculture and horticulture.Host plant resistance to phloem-feeding insects is often mediated by changes in phloem composition,which deter insect settling and feeding and decrease viability.Here,we report that rice plant resistance to the phloem-feeding brown planthopper(BPH)is associated with fortification of the sclerenchyma tissue,which is located just beneath the epidermis and a cell layer or two away from the vascular bundle in the rice leaf sheath.We found that BPHs prefer to feed on the smooth and soft region on the surface of rice leaf sheaths called the long-cell block.We identified Bph30 as a rice BPH resistance gene that prevents BPH stylets from reaching the phloem due to the fortified sclerenchyma.Bph30 is strongly expressed in sclerenchyma cells and enhances cellulose and hemicellulose synthesis,making the cell walls stiffer and sclerenchyma thicker.The structurally fortified sclerenchyma is a formidable barrier preventing BPH stylets from penetrating the leaf sheath tissues and arriving at the phloem to feed.Bph30 belongs to a novel gene family,encoding a protein with two leucine-rich domains.Another member of the family,Bph40,also conferred resistance to BPH.Collectively,the fortified sclerenchyma-mediated resistance mechanism revealed in this study expands our understanding of plant-insect interactions and opens a new path for controlling planthoppers in rice.
基金Supported by the China Meteorological Administration Special Public Welfare Research Fund(GYHY201506002)National Innovation Project for Meteorological Science and Technology(CMAGGTD003-5).
文摘Atmospheric reanalysis reproduces the past atmospheric conditions through assimilation of historical meteorological observations with fixed version of a numerical weather prediction(NWP)model and data assimilation(DA)system.It is widely used in weather,climate,and even business-related research and applications.This paper reports the development of CMA’s first-generation global atmospheric reanalysis(RA)covering 1979–2018(CRA-40;CRA refers to CMA-RA).CRA-40 is produced by using the Global Spectral Model(GSM)/Gridpoint Statistical Interpolation(GSI)at a 6-h time interval and a TL574 spectral(34-km)resolution with the model top at 0.27 hPa.A large number of reprocessed satellite data and widely collected conventional observations were assimilated during the reanalyzing process,including the reprocessed atmospheric motion vector(AMV)products from FY-2C/D/E/G satellites,dense conventional observations(at about 120 radiosonde and 2400 synoptic stations)over China,as well as MWHS-2 and GNSS-RO observations from FY-3C.The reanalysis fitting to observations is improved over time,especially for surface pressure with root-mean-square error reduced from 1.05 hPa in 1979 to 0.8 hPa,and for upper air temperature from 1.65 K in 1979 to 1.35 K,in 2018.The patterns of global analysis increments for temperature,specific humidity,and zonal wind are consistent with the changes in the observing system.Near surface temperature from the model’s 6-h forecast reflects the global warming trend reasonably.The CRA-40 precipitation pattern matches well with those of GPCP and other reanalyses.CRA-40 also successfully captures the QBO and its vertical and temporal development,hemispherical atmospheric circulation change,and moisture transport by the East Asian summer monsoon.CRA is now operationally running in near real time as a climate data assimilation system in CMA.
基金Supported by the National Innovation Project for Meteorological Science and Technology (CMAGGTD003-5)China Meteorological Administration Special Public Welfare Research Fund (GYHY201506002)National Key Research and Development Program of China (2017YFC1501801)。
文摘This paper presents a detailed description of integration, quality assurance procedure, and usage of global aircraft observations for China's first generation global atmospheric reanalysis(CRA) product(1979–2018). An integration method named "classified integration" is developed. Aircraft observations from nine different sources are integrated into the Integrated Global Meteorological Observation Archive from Aircraft(IGMOAA), a new dataset from the National Meteorological Information Center(NMIC) of the China Meteorological Administration(CMA). IGMOAA consists of global aircraft temperature, wind, and humidity data from the surface to 100 h Pa, extending from 1973 to the present. Compared with observations assimilated in the Climate Forecast System Reanalysis(CFSR) of NCEP,the observation number of IGMOAA increased by 12.9% between 2010 and 2014, mainly as a result of adding more Chinese Aircraft Meteorological Data Relay(AMDAR) data. Complex quality control procedures for aircraft observations of NCEP are applied to detect data errors. Observations are compared with ERA-Interim reanalysis from 1979 to 2018 to investigate data quality of different types and aircraft, and subsequently to develop the blacklists for CRA. IGMOAA data have been assimilated in CRA in 2018 and are real-time updated at the CMA Data-as-a-Service(CMADaa S) platform. For CRA, the fits to observations improve over time. From 1994 to 2018, root-meansquare error(RMSE) of observations relative to CRA background decreases from 1.8 to 1.0℃ for temperature above 300 h Pa, and from 4.5 to 3 m s^(-1) for zonal wind. The RMSE for humidity appears to exhibit an apparent seasonal variation with larger errors in summer and smaller ones in winter.
基金This work was supported by the National Key R&D Program of China(2018YFA0900300)the Tianjin Science Fund for Distinguished Young Scholars(17JCJQJC45300)the Science and Technology Service Network(STS)Initiative of the Chinese Academy of Sciences(CAS)(KFJ-STS-ZDTP-065).
文摘Optimizing the supply of biosynthetic precursors and cofactors is usually an effective metabolic strategy to improve the production of target compounds.Here,the combination of optimizing precursor synthesis and balancing cofactor metabolism was adopted to improve tryptophan production in Escherichia coli.First,glutamine synthesis was improved by expressing heterologous glutamine synthetase from Bacillus subtilis and Bacillus megaterium in the engineered Escherichia coli strain KW001,resulting in the best candidate strain TS-1.Then icd and gdhA were overexpressed in TS-1,which led to the accumulation of 1.060 g/L tryptophan.Subsequently,one more copy of prs was introduced on the chromosome to increase the flux of 5-phospho-α-D-ribose 1-diphosphate followed by the expression of mutated serA and thrA to increase the precursor supply of serine,resulting in the accumulation of 1.380 g/L tryptophan.Finally,to maintain cofactor balance,sthA and pntAB,encoding transhydrogenase,were overexpressed.With sufficient amounts of precursors and balanced cofactors,the engineered strain could produce 1.710 g/L tryptophan after 48 h of shake-flask fermentation,which was 2.76-times higher than the titer of the parent strain.Taken together,our results demonstrate that the combination of optimizing precursor supply and regulating cofactor metabolism is an effective approach for high-level production of tryptophan.Similar strategies could be applied to the production of other amino acids or related derivatives.
基金National Natural Science Foundation of China，Specialized Research Fund for the Doctoral Program of Higher Education
文摘Optical absorption and photocatalytic activity can be enhanced by surface plasmon resonance (SPR) effect,but the charge transfer (CT) mechanism between the dispersed noble metal nanoparticles (NPs) and the semiconductor matrix has been ignored.Herein,we adduce a direct and strong evidence in Ag-nanoparticle-dispersed BaTiO3 (Ag/BTO) composite films through X-ray photoelectron and photoluminescence spectra which reveals the CT from BTO trapped by Ag NPs under UV light and from Ag NPs to BTO under visible light.Owing to the broadened optical absorption and efficient CT from Ag NPs to BTO,the Ag25/BTO film manifests the optimal photocatalytic activity under the irradiation of visible light rather than UV-Vis light.Our work provides a helpful insight to design highly efficient plasmonic photocatalyst through considering the synergetic effect of the CT between metal and semiconductor on the enhanced photocatalytic activity.
基金supported by National Key R&D Program of China (2022YFC3500302)National Natural Science Foundation of China (No. 82173963)+1 种基金Key R&D Project of Shandong Province (No. 2021CXGC010507, China)Open Research Fund of Chengdu University of Traditional Chinese Medicine State Key Laboratory Southwestern Chinese Medicine Resources (No. 2022ZYXK2011015, China)。
文摘The chemical complexity of traditional Chinese medicines(TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform(TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included:(1) selection of herbal drugs of target based on TCMs knowledge base;(2) chemome profiling of TCMs extract library by LC-MS;(3) cytological profiling of TCMs extract library by high-content cell-based imaging;(4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes;(5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs(Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.
基金supported by the National Natural Science Foundation of China(No.52174283)Innovation Fund Project for Graduate Student of China University of Petroleum(East China)(No.22CX04026A)the Fundamental Research Funds for the Central Universities.
文摘Iron plays a crucial role in improving the oxygen evolution reaction(OER)activity of hydroxide materials.Increasing the number of iron active sites at the solid–liquid interface is beneficial to enhancing the OER performance of catalysts but still challenging.Here,by systematic exploring the activity trends of M(OH)_(x)and Cu-M(OH)_(x)(M=Mn,Cu,Ni,Fe,and Co),we discover that the Cu doping can promote the deposition of Fe active sites on metal hydroxide and Cu-Co(OH)2 shows the most favorable iron adsorption capacity.When loaded on a conductive substrate(cobalt foam(CF),the M-Cu-Co(OH)2/CF(Co(OH)_(2))prepared by molten salt method)exhibits an attractive low overpotential of 337 mV at 1,000 mA·cm^(−2).Using in anion exchange membrane(AEM)water electrolyzer,the single cell with M-Cu-Co(OH)_(2)/CF as anode catalyst performs a stable cell voltage of 2.02 V to reach 1,000 mA·cm^(−2)over 24 h,indicating a great application potential for actual electrolytic water.Therefore,the promoted adsorption of copper on iron provides a new perspective for further enhancing the OER activity of other metal hydroxides.
基金the National Natural Science Foundation of China(nos.51525302 and 21802049)the China Postdoctoral Science Foundation(no.2017M622403)the Innovation and Talent Recruitment Base of New Energy Chemistry and Devices(no.B21003).
文摘Chiral superstructures in confined spaces are subtly affected by the complex interplay among various noncovalent interactions,details of which are still in adequately understood.Herein,we report the threedimensional confined assembly of the chiral block copolymers of polystyrene-block-poly(D-lactide)andits enantiomer in emulsion droplets and demonstrate unprecedented successive microphase transformations from single helices to double helices with inverted helicity,and then to twisted cylinders in the constructedcolloidal particles.Theabovehierarchical structural transformations of chiral microphases are kinetically dependent and can further transform into thermodynamically stable achiral cylinders with saddle-shaped topology upon solvent annealing.The formation and subsequent structural transformations as well as thefinal degeneration of chiral architectures provide guidance to understand the chiral evolution at different length scales within spherical confined space and to fabricate biomimetic systems.
基金supported by National Natural Science Foundation of China(Nos.22472023,22202037 and 22102105)the Fundamental Research Funds for the Central Universities(Nos.2412024QD014 and 2412023QD019)This work was also supported by the Science and Technology Development Plan Project of Jilin Province,China(No.20240101192JC).
文摘The development of electrocatalysts for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)is crucial for sustainable energy and environmental initiatives.This work establishes an atomically-dispersed Ru-based model to investigate the promoting mechanism by the Ru-Integration effect in RuCo bimetallic nanoparticles supported on nitrogen-doped carbon(RuCo@NC).Specially,the Ru content in RuCo@NC plays a vital role for both HER and OER.The optimized catalyst shows an outstanding performance,requiring only 217 and 97 mV overpotential to reach a current density of 10 mA·cm^(−2)for OER and HER respectively in alkaline conditions.Combined with advanced characterizations such as spherical aberration-corrected scanning transmission electron microscopy,X-ray absorption spectroscopy,in-situ Raman spectroscopy,and density functional theory calculations,it is found that Ru plays multiple crucial roles:(1)Ru restricts the growth of large Co NPs,while the small-sized Co NPs facilitate the formation of carbon nanotubes,which significantly enhances the mass/electron transfer;(2)Ru not only tunes the surface properties of Co but also acts as an active site for HER.As a result,when using RuCo@NC as an overall water splitting catalyst,it only needs a potential of 1.62 V to reach a current density of 100 mA·cm^(−2).This work offers valuable insights into designing Ru-based electrocatalysts for water splitting.
