A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death ...A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.展开更多
Presently,integrating multi-omics information into a prediction model has become a ameliorate strategy for genomic selection to improve genomic prediction accuracy.Here,we set the genomic and transcriptomic data as th...Presently,integrating multi-omics information into a prediction model has become a ameliorate strategy for genomic selection to improve genomic prediction accuracy.Here,we set the genomic and transcriptomic data as the training population data,using BSLMM,TWAS,and eQTL mapping to prescreen features according to |β_(b)|>0,top 1%of phenotypic variation explained(PVE),expression-associated single nucleotide polymorphisms(eSNPs),and egenes(false discovery rate(FDR)<0.01),where these loci were set as extra fixed effects(named GBLUP-Fix)and random effects(GFBLUP)to improve the prediction accuracy in the validation population,respectively.The results suggested that both GBLUP-Fix and GFBLUP models could improve the accuracy of longissimus dorsi muscle(LDM),water holding capacity(WHC),shear force(SF),and pH in Huaxi cattle on average from 2.14 to 8.69%,especially the improvement of GFBLUP-TWAS over GBLUP was 13.66%for SF.These methods also captured more genetic variance than GBLUP.Our study confirmed that multi-omics-assisted large-effects loci prescreening could improve the accuracyofgenomic prediction.展开更多
Inflammatory bowel disease(IBD)represents a chronic inflammatory condition profoundly impacting the gastrointestinal tract.Its prevalence has markedly risen in both developed and developing nations over recent decades...Inflammatory bowel disease(IBD)represents a chronic inflammatory condition profoundly impacting the gastrointestinal tract.Its prevalence has markedly risen in both developed and developing nations over recent decades.Despite the absence of definitive etiological elucidation,therapeutic strategies predominantly revolve around pharmacological interventions aimed at symptom mitigation.Alginate(AG)is a polysaccharide of marine origin that has garnered significant attention due to its inherent biocompatibility,pH sensitivity,and cross-linking.Its exploration within drug delivery systems for IBD treatment stems from its natural sourcing,non-cytotoxic nature,and economic viability.Notably,AG demonstrates facile interpolymeric cross-linking,facilitating the formation of a cohesive network conducive to sustained drug release kinetics.AG-based carrier systems for sustained drug release,and targeted drug delivery have been widely studied.This article reviews the pathogenesis of IBD and the current drugs,AG-based drug delivery systems and their properties in alleviating IBD.The prospect of further development of AG in the field of biopharmaceutical and drug delivery is prospected.展开更多
AIM:To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress(WRS) and its prevention by growth hormone releasing peptide-6(GHRP-6).METHODS:Male Wistar rats were subjected to c...AIM:To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress(WRS) and its prevention by growth hormone releasing peptide-6(GHRP-6).METHODS:Male Wistar rats were subjected to conscious or unconscious(anesthetized) WRS,simple restraint(SR),free swimming(FS),non-water fluid immersion,immersion without water contact,or rats were placed in a cage surrounded by sand.To explore the sensitivity structures that influence the stress reaction besides skin stimuli,a group the rats had their eyes occluded.Cervical bilateral trunk vagotomy or atropine injection was performed in some rats to assess the parasympathetic role in mucosal damage.Gastric mucosal lesions,acid output and heart rate variability were measured.Plasma renin,endothelin-1 and thromboxane B2 and gastric heat shock protein 70 were also assayed.GHRP-6 was injected [intraperitoneal(IP) or intracerebroventricular(ICV)] 2 h before the onset of stress to observe its potential prevention of the mucosal lesion.RESULTS:WRS for 6 h induced serious gastric mucosal lesion [lesion area,WRS 81.8 ± 6.4 mm 2 vs normal control 0.0 ± 0.0 mm 2,P < 0.01],decreased the heart rate,and increased the heart rate variability and gastric acid secretion,suggesting an increase in vagal nervecarrying stimuli.The mucosal injury was inversely correlated with water temperature(lesion area,WRS at 35 ℃ 56.4 ± 5.2 mm 2 vs WRS at 23 ℃ 81.8 ± 6.4 mm 2,P < 0.01) and was consciousness-dependent.The injury could not be prevented by eye occlusion,but could be prevented by avoiding contact of the rat body with the water by dressing it in an impermeable plastic suit.When water was replaced by vegetable oil or liquid paraffin,there were gastric lesions in the same grade of water immersion.When rat were placed in a cage surrounded by sand,there were no gastric lesions.All these data point to a remarkable importance of cutenuous information transmitted to the high neural center that by vagal nerves reaching the gastric mucosa.FS alone also induced serious gastric injury,but SR could not induce gastric injury.Bilateral vagotomy or atropine prevented the WRS-induced mucosal lesion,indicating that increased outflow from the vagal center is a decisive factor in WRS-induced gastric injury.The mucosal lesions were prevented by prior injection of GHRP-6 via IP did,but not via ICV,suggesting that the protection is peripheral,although a sudden injection is not equivalent to a physiological release and uptake,which eventually may affect the vagal center.CONCLUSION:From the central nervous system,vagal nerves carry the cutaneous stimuli brought about by the immersion restraint,an experimental model for inducing acute gastric erosions.GHRP-6 prevents the occurrence of these lesions.展开更多
The newly-discovered Donglufang Moe Cu porphyry-skarn deposit is located in the southern Yidun Terrane, southeast Tibet, with more than 80 million tonnes(Mt) of reserves(grading 0.15 wt.% Mo and0.48 wt.% Cu) hosted in...The newly-discovered Donglufang Moe Cu porphyry-skarn deposit is located in the southern Yidun Terrane, southeast Tibet, with more than 80 million tonnes(Mt) of reserves(grading 0.15 wt.% Mo and0.48 wt.% Cu) hosted in Triassic strata and Late Cretaceous granodiorite porphyry. Ree Os dating of molybdenum ore yielded a weighted mean age of 84.9 ± 1.0 Ma and an isochron age of 85.2 ± 0.6 Ma.LA-ICP-MS Ue Pb dating of zircons from the granodiorite porphyry yielded206 Pb/238 U ages ranging from 87.4 Ma to 84.2 Ma with a weighted mean206 Pb/238 U age of 85.1 ±0.5 Ma, indicating a temporal linkage between granitic magmatism and Moe Cu mineralization. Geochemical analyses show that the granodiorite porphyries are I-type granites with Si O_2 contents of 64.3 -66.7 wt.%. These rocks are typically metaluminous with high K_2 O/Na_2 O ratios, low Mg O(1.32 -1.56 wt.%), Cr(5.6 -12.9 ppm), Ni(3.79 -10.81 ppm), Mg#(43 -52) values, and high Sr(304 -844 ppm), Sr/Y(21.2 -50.8) and La/Yb ratios(37.0 -60.1). They are enriched in light rare-earth elements(LREE) relative to heavy rare-earth elements(HREE), with slightly negative Eu anomalies, and are enriched in Th, U and large ion lithophile elements(LILE, e.g., K and Rb), and depleted in high field strength elements(HFSE, e.g., Nb, Ta, P and Ti). They also show negative zircon εHf(t) values(-6.7 to -2.3) and negative whole rock εNd(t) values(à5.2 to-4.3), as well as old Hfe Nd model ages, indicating the magmas were derived from a thickened ancient lower crust within the garneteamphibolite facies. Considering the tectonic evolution of the Yidun Terrane, geochemical characteristics of granodiorite porphyry, and the ages of mineralization obtained in this study. We suggest that the Donglufang deposit was formed in a post-collisional setting, which has a genetic relationship with the emplacement of the granodiorite porphyry. The present study provide key information for the exploration of the Late Cretaceous metallogeny in the Yidun Terrane.展开更多
Background: Fatty acids are important traits that affect meat quality and nutritive values in beef cattle. Detection of genetic variants for fatty acid composition can help to elucidate the genetic mechanism underpinn...Background: Fatty acids are important traits that affect meat quality and nutritive values in beef cattle. Detection of genetic variants for fatty acid composition can help to elucidate the genetic mechanism underpinning these traits and promote the improvement of fatty acid profiles. In this study, we performed a genome-wide association study(GWAS) on fatty acid composition using high-density single nucleotide polymorphism(SNP) arrays in Chinese Wagyu cattle.Results: In total, we detected 15 and 8 significant genome-wide SNPs for individual fatty acids and fatty acid groups in Chinese Wagyu cattle, respectively. Also, we identified nine candidate genes based on 100 kb regions around associated SNPs. Four SNPs significantly associated with C14:1 cis-9 were embedded with stearoyl-CoA desaturase(SCD), while three SNPs in total were identified for C22:6 n-3 within Phospholipid scramblase family member 5(PLSCR5), Cytoplasmic linker associated protein 1(CLASP1), and Chymosin(CYM). Notably, we found the top candidate SNP within SCD can explain ~ 7.37% of phenotypic variance for C14:1 cis-9.Moreover, we detected several blocks with high LD in the 100 kb region around SCD. In addition, we found three significant SNPs within a 100 kb region showing pleiotropic effects related to multiple FA groups(PUFA,n-6, and PUFA/SFA), which contains BAI1 associated protein 2 like 2(BAIAP2 L2), MAF bZIP transcription factor F(MAFF),and transmembrane protein 184 B(TMEM184 B).Conclusions: Our study identified several significant SNPs and candidate genes for individual fatty acids and fatty acid groups in Chinese Wagyu cattle, and these findings will further assist the design of breeding programs for meat quality in cattle.展开更多
The separation stability under high-humidity is significant in practical applications for air filters.Herein,hydrophobic polyvinyl chloride(PVC)nanofiber filters with bead-on-string structure are designed to steadily ...The separation stability under high-humidity is significant in practical applications for air filters.Herein,hydrophobic polyvinyl chloride(PVC)nanofiber filters with bead-on-string structure are designed to steadily remove particle matter under high relative humidity of 90%-95%.The developed hydrophobic filters possess comparable separation performance with the hydrophilic one,but greatly enhanced stability.After the introduction of beadon-string structure,the filtration performance can be furtherly improved due to the formed large cavities and hydrophobicity.Such hydrophobic PVC filters can be promising candidates for air purification in practical applications especially in wet seasons.展开更多
Objective: To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China.Methods: We carried out a retrospective analysis on pren...Objective: To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China.Methods: We carried out a retrospective analysis on prenatal diagnosis of amniotic fluid samples collected from pregnant women who may have next generation with high risks of medium or severe thalassemia between 2005 and 2016. Diverse fetal thalassemia genotypes and mutated alleles in Han and Li people were analyzed and cmpared. Results: We examined 536 amniotic fluid samples from Han people and 588 from Li people, among which 406 Han and 500 Li samples were found to carry at least one thalassemia gene mutation, with a detection rate of 75.75% and 85.03%, respectively. Among all α-and β-thalassemia mutant alleles detected, the most frequently found mutations in Han and Li samples were SEA-type of α-thalassemia and 41/42(–CTTT) of β-thalassemia, respectively. A total of 75 severe thalassemia cases were identified in Han samples and 53 in Li samples. In most of these severe cases, parents chose to terminate pregnancy after being informed of thalassemia-related risks. Conclusions: The thalassemia mutations shows ethnic and area specificity, and that prenatal diagnosis for high-risk thalassemia carrier pregnant women is an efficient approach to prevent and control the occurrence of severe thalassemia in the high-prevalence areas.展开更多
Resuscitation promoting factor E （RpfE） is one of the five Rpf-like proteins in Mycobacterium tuberculos＆ （M. tuberculosis）. These Rpf-like proteins are secretory, which make them candidates for recognition by th...Resuscitation promoting factor E （RpfE） is one of the five Rpf-like proteins in Mycobacterium tuberculos＆ （M. tuberculosis）. These Rpf-like proteins are secretory, which make them candidates for recognition by the host immune system. In this study, the RpfE gene was amplified from M. tuberculosis, cloned into the expression vectors pDE22 and pPRO EXHT, and were expressed in Mycobacterium vaccae （M. vaccae） and Escherichia coli DHSa, respec- tively. Both recombinant RpfE proteins were purified by Ni-Sepharose affinity chromatography, and were given to C57BL/6 mice. The RpfE proteins elicited T cell proliferation, and stimulated the production of gamma interferon （IFN-y）, interleukin-10 （IL-10） and IL-12. Our results indicated that the RpfE protein expressed in M. vaccae could more efficiently stimulate cellular immune response, making it a promising candidate as a subunit vaccine.展开更多
Background A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle.To prioritize the putative variants and genes,we ra...Background A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle.To prioritize the putative variants and genes,we ran a com-prehensive genome-wide association studies(GWAS)analysis for 21 agronomic traits using imputed whole-genome variants in Simmental beef cattle.Then,we applied expression quantitative trait loci(eQTL)mapping between the genotype variants and transcriptome of three tissues(longissimus dorsi muscle,backfat,and liver)in 120 cattle.Results We identified 1,580 association signals for 21 beef agronomic traits using GWAS.We then illuminated 854,498 cis-eQTLs for 6,017 genes and 46,970 trans-eQTLs for 1,903 genes in three tissues and built a synergistic network by integrating transcriptomics with agronomic traits.These cis-eQTLs were preferentially close to the transcription start site and enriched in functional regulatory regions.We observed an average of 43.5%improvement in cis-eQTL discovery using multi-tissue eQTL mapping.Fine-mapping analysis revealed that 111,192,and 194 variants were most likely to be causative to regulate gene expression in backfat,liver,and muscle,respectively.The transcriptome-wide association studies identified 722 genes significantly associated with 11 agronomic traits.Via the colocalization and Mendelian randomization analyses,we found that eQTLs of several genes were associated with the GWAS signals of agronomic traits in three tissues,which included genes,such as NADSYN1,NDUFS3,LTF and KIFC2 in liver,GRAMD1C,TMTC2 and ZNF613 in backfat,as well as TIGAR,NDUFS3 and L3HYPDH in muscle that could serve as the candidate genes for economic traits.Conclusions The extensive atlas of GWAS,eQTL,fine-mapping,and transcriptome-wide association studies aid in the suggestion of potentially functional variants and genes in cattle agronomic traits and will be an invaluable source for genomics and breeding in beef cattle.展开更多
Background:Genomic selection(GS)has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes.Besides genome,transcriptome and metabolome information are i...Background:Genomic selection(GS)has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes.Besides genome,transcriptome and metabolome information are increasingly considered new sources for GS.Difficulties in building the model with multi-omics data for GS and the limit of specimen availability have both delayed the progress of investigating multi-omics.Results:We utilized the Cosine kernel to map genomic and transcriptomic data as n×n symmetric matrix(G matrix and T matrix),combined with the best linear unbiased prediction(BLUP)for GS.Here,we defined five kernel-based prediction models:genomic BLUP(GBLUP),transcriptome-BLUP(TBLUP),multi-omics BLUP(MBLUP,M=ratio×G+(1-ratio)×T),multi-omics single-step BLUP(mss BLUP),and weighted multi-omics single-step BLUP(wmss BLUP)to integrate transcribed individuals and genotyped resource population.The predictive accuracy evaluations in four traits of the Chinese Simmental beef cattle population showed that(1)MBLUP was far preferred to GBLUP(ratio=1.0),(2)the prediction accuracy of wmss BLUP and mss BLUP had 4.18%and 3.37%average improvement over GBLUP,(3)We also found the accuracy of wmss BLUP increased with the growing proportion of transcribed cattle in the whole resource population.Conclusions:We concluded that the inclusion of transcriptome data in GS had the potential to improve accuracy.Moreover,wmss BLUP is accepted to be a promising alternative for the present situation in which plenty of individuals are genotyped when fewer are transcribed.展开更多
Objective To investigate the effect of emodin on lipopolysaccharides （LPS）-induced corneal injury in rats. Methods Three parallel incisions on the central surface of corneal epithelium were made and LPS was applied...Objective To investigate the effect of emodin on lipopolysaccharides （LPS）-induced corneal injury in rats. Methods Three parallel incisions on the central surface of corneal epithelium were made and LPS was applied on them to induce corneal injury in Wistar rats. All rats were randomly divided into emodin group （n=40） and keratitis group （n=40）. Rats in the emodin group received subconjunctival injection of emodin and rats in the keratitis group received its vehicle 30 minutes before LPS exposure. At different time points-1 3, 6, 12, and 24 hours after LPS exposure, the symptoms of all rats were observed and the severity of their ocular inflammation was examined with a slit lamp microscope, then 8 rats in each group were killed through cervical dislocation and their eyes were enucleated and prepared to observe pathological changes of corneal tissue under a light microscope. The activation of nuclear factor-loB （NF-κB） under different condi- tions was determined by Western blot. Immunocytochemistry staining with an antibody against intercellular adhesion molecule-1 （ICAM-1） was performed to identify positive cells in corneal tissues. Results The model of acute keratitis was successfully established in Wistar rats. LPS could induce a typical corneal inflammatory response, such as hyperemia, corneal edema and opacity, which were observed in model rats. Compared with keratitis group, both ocular behaviors and damages of the corneal structure were improved in emodin group. Furthermore, the activation of NF-κB and the expression of ICAM-1 induced by LPS were markedly inhibited in emodin group. Conclusion Emodin can inhibit the activation of NF-κB and the expression of ICAM-I induced by LPS in corneas, protect against acute corneal injury, and improve symptoms in rats.展开更多
BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are r...BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are refractory to traditional therapies and tumor necrosis factor antagonists.However,some rare but lifethreatening adverse effects warrant pharmacovigilance.We describe the first fatal case of vedolizumab-associated severe diffuse interstitial lung disease in China.CASE SUMMARY We present a case of new-onset diffuse parenchymal lung disease developing under treatment with vedolizumab in a patient with UC.After two doses of vedolizumab,he developed persistent fever and progressively worsening dyspnea.Extensive workups,including bronchoalveolar lavage,transbronchial lung biopsy and metagenomic next-generation sequencing,identified no infectious causes,and other potential causes(such as tumors and cardiogenic pulmonary edema)were also excluded.As a result,a diagnosis of vedolizumabrelated interstitial lung disease was established.Unfortunately,although corticosteroids and empiric antibiotics were administered,the patient eventually died of respiratory failure.CONCLUSION Vedolizumab-related interstitial lung disease in patients with UC is rare but potentially lethal.Gastroenterologists and pulmonologists should be aware of vedolizumab-related adverse drug reactions.展开更多
Hearing loss is one of the most common birth defects,with inherited genetic defects play an important role,contributing to about 60%of deafness occurring in infants.However,hearing impairment is genetically heterogene...Hearing loss is one of the most common birth defects,with inherited genetic defects play an important role,contributing to about 60%of deafness occurring in infants.However,hearing impairment is genetically heterogeneous,with both common and rare forms occurring due to mutations in estimated 500 genes.Due to the large number and presumably low mutation frequencies of those genes,it would be highly expensive and time-consuming to address this issue by conventional gene-by-gene Sanger sequencing.Next-generation sequencing is a revolutionary technology that allows the simultaneous screening of mutations in a large number of genes.It is cost effective compared to classical strategies of linkage analysis and direct sequencing when the number or size of genes is large,and thus has become a highly efficient strategy for identifying novel causative genes and mutations involved in heritable disease.In this review, we describe major NGS methodologies currently used for genetic disorders and highlight applications of these technologies in studies of molecular diagnosis and the discovery of genes implicated in non-syndromic hearing loss.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.:82122043,81972052,81902213,82201537,and 81730065)the China Postdoctoral Science Foundation(Grant Nos.:2021M693946 and 2019M653967).
文摘A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.
基金This research was supported by the National Natural Science Foundations of China(31872975)the Science and Technology Project of Inner Mongolia Autonomous Region,China(2020GG0210)the Program of National Beef Cattle and Yak Industrial Technology System,China(CARS-37).
文摘Presently,integrating multi-omics information into a prediction model has become a ameliorate strategy for genomic selection to improve genomic prediction accuracy.Here,we set the genomic and transcriptomic data as the training population data,using BSLMM,TWAS,and eQTL mapping to prescreen features according to |β_(b)|>0,top 1%of phenotypic variation explained(PVE),expression-associated single nucleotide polymorphisms(eSNPs),and egenes(false discovery rate(FDR)<0.01),where these loci were set as extra fixed effects(named GBLUP-Fix)and random effects(GFBLUP)to improve the prediction accuracy in the validation population,respectively.The results suggested that both GBLUP-Fix and GFBLUP models could improve the accuracy of longissimus dorsi muscle(LDM),water holding capacity(WHC),shear force(SF),and pH in Huaxi cattle on average from 2.14 to 8.69%,especially the improvement of GFBLUP-TWAS over GBLUP was 13.66%for SF.These methods also captured more genetic variance than GBLUP.Our study confirmed that multi-omics-assisted large-effects loci prescreening could improve the accuracyofgenomic prediction.
基金supported by the China Postdoctoral Science Foundation(Grant No.2021MD703801)Youth Talent Cultivation Fund Project of Dalian Medical University(Grant No.508021)Open Foundation of the State Key Laboratory of Marine Food Processing&Safety Control(Grant No.SKL2023M03).
文摘Inflammatory bowel disease(IBD)represents a chronic inflammatory condition profoundly impacting the gastrointestinal tract.Its prevalence has markedly risen in both developed and developing nations over recent decades.Despite the absence of definitive etiological elucidation,therapeutic strategies predominantly revolve around pharmacological interventions aimed at symptom mitigation.Alginate(AG)is a polysaccharide of marine origin that has garnered significant attention due to its inherent biocompatibility,pH sensitivity,and cross-linking.Its exploration within drug delivery systems for IBD treatment stems from its natural sourcing,non-cytotoxic nature,and economic viability.Notably,AG demonstrates facile interpolymeric cross-linking,facilitating the formation of a cohesive network conducive to sustained drug release kinetics.AG-based carrier systems for sustained drug release,and targeted drug delivery have been widely studied.This article reviews the pathogenesis of IBD and the current drugs,AG-based drug delivery systems and their properties in alleviating IBD.The prospect of further development of AG in the field of biopharmaceutical and drug delivery is prospected.
基金Supported by National Natural Science Foundation of China, No.81071072,No.31171088(to Cao JM) and No.81000060(to Gao X)
文摘AIM:To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress(WRS) and its prevention by growth hormone releasing peptide-6(GHRP-6).METHODS:Male Wistar rats were subjected to conscious or unconscious(anesthetized) WRS,simple restraint(SR),free swimming(FS),non-water fluid immersion,immersion without water contact,or rats were placed in a cage surrounded by sand.To explore the sensitivity structures that influence the stress reaction besides skin stimuli,a group the rats had their eyes occluded.Cervical bilateral trunk vagotomy or atropine injection was performed in some rats to assess the parasympathetic role in mucosal damage.Gastric mucosal lesions,acid output and heart rate variability were measured.Plasma renin,endothelin-1 and thromboxane B2 and gastric heat shock protein 70 were also assayed.GHRP-6 was injected [intraperitoneal(IP) or intracerebroventricular(ICV)] 2 h before the onset of stress to observe its potential prevention of the mucosal lesion.RESULTS:WRS for 6 h induced serious gastric mucosal lesion [lesion area,WRS 81.8 ± 6.4 mm 2 vs normal control 0.0 ± 0.0 mm 2,P < 0.01],decreased the heart rate,and increased the heart rate variability and gastric acid secretion,suggesting an increase in vagal nervecarrying stimuli.The mucosal injury was inversely correlated with water temperature(lesion area,WRS at 35 ℃ 56.4 ± 5.2 mm 2 vs WRS at 23 ℃ 81.8 ± 6.4 mm 2,P < 0.01) and was consciousness-dependent.The injury could not be prevented by eye occlusion,but could be prevented by avoiding contact of the rat body with the water by dressing it in an impermeable plastic suit.When water was replaced by vegetable oil or liquid paraffin,there were gastric lesions in the same grade of water immersion.When rat were placed in a cage surrounded by sand,there were no gastric lesions.All these data point to a remarkable importance of cutenuous information transmitted to the high neural center that by vagal nerves reaching the gastric mucosa.FS alone also induced serious gastric injury,but SR could not induce gastric injury.Bilateral vagotomy or atropine prevented the WRS-induced mucosal lesion,indicating that increased outflow from the vagal center is a decisive factor in WRS-induced gastric injury.The mucosal lesions were prevented by prior injection of GHRP-6 via IP did,but not via ICV,suggesting that the protection is peripheral,although a sudden injection is not equivalent to a physiological release and uptake,which eventually may affect the vagal center.CONCLUSION:From the central nervous system,vagal nerves carry the cutaneous stimuli brought about by the immersion restraint,an experimental model for inducing acute gastric erosions.GHRP-6 prevents the occurrence of these lesions.
基金financially supported by the National Basic Research Program of China (No. 2015CB452605)the Natural Science Foundation of China (No. 41602089)Fundamental Research Funds for the Central Universities (No. 20170713174019)
文摘The newly-discovered Donglufang Moe Cu porphyry-skarn deposit is located in the southern Yidun Terrane, southeast Tibet, with more than 80 million tonnes(Mt) of reserves(grading 0.15 wt.% Mo and0.48 wt.% Cu) hosted in Triassic strata and Late Cretaceous granodiorite porphyry. Ree Os dating of molybdenum ore yielded a weighted mean age of 84.9 ± 1.0 Ma and an isochron age of 85.2 ± 0.6 Ma.LA-ICP-MS Ue Pb dating of zircons from the granodiorite porphyry yielded206 Pb/238 U ages ranging from 87.4 Ma to 84.2 Ma with a weighted mean206 Pb/238 U age of 85.1 ±0.5 Ma, indicating a temporal linkage between granitic magmatism and Moe Cu mineralization. Geochemical analyses show that the granodiorite porphyries are I-type granites with Si O_2 contents of 64.3 -66.7 wt.%. These rocks are typically metaluminous with high K_2 O/Na_2 O ratios, low Mg O(1.32 -1.56 wt.%), Cr(5.6 -12.9 ppm), Ni(3.79 -10.81 ppm), Mg#(43 -52) values, and high Sr(304 -844 ppm), Sr/Y(21.2 -50.8) and La/Yb ratios(37.0 -60.1). They are enriched in light rare-earth elements(LREE) relative to heavy rare-earth elements(HREE), with slightly negative Eu anomalies, and are enriched in Th, U and large ion lithophile elements(LILE, e.g., K and Rb), and depleted in high field strength elements(HFSE, e.g., Nb, Ta, P and Ti). They also show negative zircon εHf(t) values(-6.7 to -2.3) and negative whole rock εNd(t) values(à5.2 to-4.3), as well as old Hfe Nd model ages, indicating the magmas were derived from a thickened ancient lower crust within the garneteamphibolite facies. Considering the tectonic evolution of the Yidun Terrane, geochemical characteristics of granodiorite porphyry, and the ages of mineralization obtained in this study. We suggest that the Donglufang deposit was formed in a post-collisional setting, which has a genetic relationship with the emplacement of the granodiorite porphyry. The present study provide key information for the exploration of the Late Cretaceous metallogeny in the Yidun Terrane.
基金supported by the National Natural Science Foundations of China(31372294 and 31702084)Chinese Academy of Agricultural Sciences of Technology Innovation Project(CAAS-XTCX2016010,CAAS-ZDXT2018006,ASTIP-IAS-TS-9,ASTIP-IAS-TS-16 and ASTIP-IAS03)for the design of the study and data collectionpartly supported by Beijing City Board of Education Foundation(PXM2016_014207_000012)for the data analysis and interpretation of the study
文摘Background: Fatty acids are important traits that affect meat quality and nutritive values in beef cattle. Detection of genetic variants for fatty acid composition can help to elucidate the genetic mechanism underpinning these traits and promote the improvement of fatty acid profiles. In this study, we performed a genome-wide association study(GWAS) on fatty acid composition using high-density single nucleotide polymorphism(SNP) arrays in Chinese Wagyu cattle.Results: In total, we detected 15 and 8 significant genome-wide SNPs for individual fatty acids and fatty acid groups in Chinese Wagyu cattle, respectively. Also, we identified nine candidate genes based on 100 kb regions around associated SNPs. Four SNPs significantly associated with C14:1 cis-9 were embedded with stearoyl-CoA desaturase(SCD), while three SNPs in total were identified for C22:6 n-3 within Phospholipid scramblase family member 5(PLSCR5), Cytoplasmic linker associated protein 1(CLASP1), and Chymosin(CYM). Notably, we found the top candidate SNP within SCD can explain ~ 7.37% of phenotypic variance for C14:1 cis-9.Moreover, we detected several blocks with high LD in the 100 kb region around SCD. In addition, we found three significant SNPs within a 100 kb region showing pleiotropic effects related to multiple FA groups(PUFA,n-6, and PUFA/SFA), which contains BAI1 associated protein 2 like 2(BAIAP2 L2), MAF bZIP transcription factor F(MAFF),and transmembrane protein 184 B(TMEM184 B).Conclusions: Our study identified several significant SNPs and candidate genes for individual fatty acids and fatty acid groups in Chinese Wagyu cattle, and these findings will further assist the design of breeding programs for meat quality in cattle.
基金funding from by the National Natural Science Foundation of China(21706076,21536005,51621001)the National Natural Science Foundation of the Guangdong Province(2014A030312007)+1 种基金Guangzhou Technology Project(201804010210)the State Key Laboratory of Pulp and Paper Engineering(201835)。
文摘The separation stability under high-humidity is significant in practical applications for air filters.Herein,hydrophobic polyvinyl chloride(PVC)nanofiber filters with bead-on-string structure are designed to steadily remove particle matter under high relative humidity of 90%-95%.The developed hydrophobic filters possess comparable separation performance with the hydrophilic one,but greatly enhanced stability.After the introduction of beadon-string structure,the filtration performance can be furtherly improved due to the formed large cavities and hydrophobicity.Such hydrophobic PVC filters can be promising candidates for air purification in practical applications especially in wet seasons.
基金supported by Major Science and Technology Program of Hainan Province(No.ZDKJ2017007)International Science&Technology Cooperation Program of China(No.2014DFA30180)+2 种基金Hainan Provincial Natural Science Foundation of China(No.2019CXTD408)National Natural Science Foundation of China(No.81060016,31140021,81260032,81460034,81660433)Hainan Provincial Science and Technology Department(No.YJJC20120007,2012-GH009,ZDZX2013003 and KJHZ2014-11).
文摘Objective: To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China.Methods: We carried out a retrospective analysis on prenatal diagnosis of amniotic fluid samples collected from pregnant women who may have next generation with high risks of medium or severe thalassemia between 2005 and 2016. Diverse fetal thalassemia genotypes and mutated alleles in Han and Li people were analyzed and cmpared. Results: We examined 536 amniotic fluid samples from Han people and 588 from Li people, among which 406 Han and 500 Li samples were found to carry at least one thalassemia gene mutation, with a detection rate of 75.75% and 85.03%, respectively. Among all α-and β-thalassemia mutant alleles detected, the most frequently found mutations in Han and Li samples were SEA-type of α-thalassemia and 41/42(–CTTT) of β-thalassemia, respectively. A total of 75 severe thalassemia cases were identified in Han samples and 53 in Li samples. In most of these severe cases, parents chose to terminate pregnancy after being informed of thalassemia-related risks. Conclusions: The thalassemia mutations shows ethnic and area specificity, and that prenatal diagnosis for high-risk thalassemia carrier pregnant women is an efficient approach to prevent and control the occurrence of severe thalassemia in the high-prevalence areas.
基金supported by National Natural Science Foundation of China (No.30470097,No.30500432)
文摘Resuscitation promoting factor E （RpfE） is one of the five Rpf-like proteins in Mycobacterium tuberculos＆ （M. tuberculosis）. These Rpf-like proteins are secretory, which make them candidates for recognition by the host immune system. In this study, the RpfE gene was amplified from M. tuberculosis, cloned into the expression vectors pDE22 and pPRO EXHT, and were expressed in Mycobacterium vaccae （M. vaccae） and Escherichia coli DHSa, respec- tively. Both recombinant RpfE proteins were purified by Ni-Sepharose affinity chromatography, and were given to C57BL/6 mice. The RpfE proteins elicited T cell proliferation, and stimulated the production of gamma interferon （IFN-y）, interleukin-10 （IL-10） and IL-12. Our results indicated that the RpfE protein expressed in M. vaccae could more efficiently stimulate cellular immune response, making it a promising candidate as a subunit vaccine.
基金supported by grants from the Central Public-interest Scientific Institution Basal Research Fund(2020-YWF-YB-02)the Young Scientists Fund of the National Natural Science Foundation of China(32202652)+1 种基金China Agriculture Research System of MOF and MARA(CARS-37)the Science and Technology Project of Inner Mongolia Autonomous Region(2020GG0210).
文摘Background A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle.To prioritize the putative variants and genes,we ran a com-prehensive genome-wide association studies(GWAS)analysis for 21 agronomic traits using imputed whole-genome variants in Simmental beef cattle.Then,we applied expression quantitative trait loci(eQTL)mapping between the genotype variants and transcriptome of three tissues(longissimus dorsi muscle,backfat,and liver)in 120 cattle.Results We identified 1,580 association signals for 21 beef agronomic traits using GWAS.We then illuminated 854,498 cis-eQTLs for 6,017 genes and 46,970 trans-eQTLs for 1,903 genes in three tissues and built a synergistic network by integrating transcriptomics with agronomic traits.These cis-eQTLs were preferentially close to the transcription start site and enriched in functional regulatory regions.We observed an average of 43.5%improvement in cis-eQTL discovery using multi-tissue eQTL mapping.Fine-mapping analysis revealed that 111,192,and 194 variants were most likely to be causative to regulate gene expression in backfat,liver,and muscle,respectively.The transcriptome-wide association studies identified 722 genes significantly associated with 11 agronomic traits.Via the colocalization and Mendelian randomization analyses,we found that eQTLs of several genes were associated with the GWAS signals of agronomic traits in three tissues,which included genes,such as NADSYN1,NDUFS3,LTF and KIFC2 in liver,GRAMD1C,TMTC2 and ZNF613 in backfat,as well as TIGAR,NDUFS3 and L3HYPDH in muscle that could serve as the candidate genes for economic traits.Conclusions The extensive atlas of GWAS,eQTL,fine-mapping,and transcriptome-wide association studies aid in the suggestion of potentially functional variants and genes in cattle agronomic traits and will be an invaluable source for genomics and breeding in beef cattle.
基金funds from the National Natural Science Foundations of China(32172693)the Program of National Beef Cattle and Yak Industrial Technology System(CARS-37)。
文摘Background:Genomic selection(GS)has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes.Besides genome,transcriptome and metabolome information are increasingly considered new sources for GS.Difficulties in building the model with multi-omics data for GS and the limit of specimen availability have both delayed the progress of investigating multi-omics.Results:We utilized the Cosine kernel to map genomic and transcriptomic data as n×n symmetric matrix(G matrix and T matrix),combined with the best linear unbiased prediction(BLUP)for GS.Here,we defined five kernel-based prediction models:genomic BLUP(GBLUP),transcriptome-BLUP(TBLUP),multi-omics BLUP(MBLUP,M=ratio×G+(1-ratio)×T),multi-omics single-step BLUP(mss BLUP),and weighted multi-omics single-step BLUP(wmss BLUP)to integrate transcribed individuals and genotyped resource population.The predictive accuracy evaluations in four traits of the Chinese Simmental beef cattle population showed that(1)MBLUP was far preferred to GBLUP(ratio=1.0),(2)the prediction accuracy of wmss BLUP and mss BLUP had 4.18%and 3.37%average improvement over GBLUP,(3)We also found the accuracy of wmss BLUP increased with the growing proportion of transcribed cattle in the whole resource population.Conclusions:We concluded that the inclusion of transcriptome data in GS had the potential to improve accuracy.Moreover,wmss BLUP is accepted to be a promising alternative for the present situation in which plenty of individuals are genotyped when fewer are transcribed.
基金Supported by Technology Foundation of Shandong Education Department (J08LH59)
文摘Objective To investigate the effect of emodin on lipopolysaccharides （LPS）-induced corneal injury in rats. Methods Three parallel incisions on the central surface of corneal epithelium were made and LPS was applied on them to induce corneal injury in Wistar rats. All rats were randomly divided into emodin group （n=40） and keratitis group （n=40）. Rats in the emodin group received subconjunctival injection of emodin and rats in the keratitis group received its vehicle 30 minutes before LPS exposure. At different time points-1 3, 6, 12, and 24 hours after LPS exposure, the symptoms of all rats were observed and the severity of their ocular inflammation was examined with a slit lamp microscope, then 8 rats in each group were killed through cervical dislocation and their eyes were enucleated and prepared to observe pathological changes of corneal tissue under a light microscope. The activation of nuclear factor-loB （NF-κB） under different condi- tions was determined by Western blot. Immunocytochemistry staining with an antibody against intercellular adhesion molecule-1 （ICAM-1） was performed to identify positive cells in corneal tissues. Results The model of acute keratitis was successfully established in Wistar rats. LPS could induce a typical corneal inflammatory response, such as hyperemia, corneal edema and opacity, which were observed in model rats. Compared with keratitis group, both ocular behaviors and damages of the corneal structure were improved in emodin group. Furthermore, the activation of NF-κB and the expression of ICAM-1 induced by LPS were markedly inhibited in emodin group. Conclusion Emodin can inhibit the activation of NF-κB and the expression of ICAM-I induced by LPS in corneas, protect against acute corneal injury, and improve symptoms in rats.
基金Supported by the Dalian Municipal Science and Technology Innovation Foundation,No.2020JJ27SN072.
文摘BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are refractory to traditional therapies and tumor necrosis factor antagonists.However,some rare but lifethreatening adverse effects warrant pharmacovigilance.We describe the first fatal case of vedolizumab-associated severe diffuse interstitial lung disease in China.CASE SUMMARY We present a case of new-onset diffuse parenchymal lung disease developing under treatment with vedolizumab in a patient with UC.After two doses of vedolizumab,he developed persistent fever and progressively worsening dyspnea.Extensive workups,including bronchoalveolar lavage,transbronchial lung biopsy and metagenomic next-generation sequencing,identified no infectious causes,and other potential causes(such as tumors and cardiogenic pulmonary edema)were also excluded.As a result,a diagnosis of vedolizumabrelated interstitial lung disease was established.Unfortunately,although corticosteroids and empiric antibiotics were administered,the patient eventually died of respiratory failure.CONCLUSION Vedolizumab-related interstitial lung disease in patients with UC is rare but potentially lethal.Gastroenterologists and pulmonologists should be aware of vedolizumab-related adverse drug reactions.
基金supported by grants from the Project of the National Natural Science Foundation of China(Grant Nos.30801285,81230020,81200751,81070792,81000415, 81360159)grants from China Postdoctoral Science Foundation(No.2012M,2013T52187860947)a grant from Minister of Science and Technology of China(2012BAI09B02)
文摘Hearing loss is one of the most common birth defects,with inherited genetic defects play an important role,contributing to about 60%of deafness occurring in infants.However,hearing impairment is genetically heterogeneous,with both common and rare forms occurring due to mutations in estimated 500 genes.Due to the large number and presumably low mutation frequencies of those genes,it would be highly expensive and time-consuming to address this issue by conventional gene-by-gene Sanger sequencing.Next-generation sequencing is a revolutionary technology that allows the simultaneous screening of mutations in a large number of genes.It is cost effective compared to classical strategies of linkage analysis and direct sequencing when the number or size of genes is large,and thus has become a highly efficient strategy for identifying novel causative genes and mutations involved in heritable disease.In this review, we describe major NGS methodologies currently used for genetic disorders and highlight applications of these technologies in studies of molecular diagnosis and the discovery of genes implicated in non-syndromic hearing loss.
