Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targ...Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer(BCa), remains poorly elucidated.Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzymelinked immunosorbent assays(ELISA) and immunohistochemistry(IHC).Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages(CD163~+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients.Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues,potentially influencing the treatment responses of affected individuals.展开更多
With the continuous development of technology, face recognition technology has played an important role in police work. In order to get a clear face image, image preprocessing technology is needed. This paper mainly p...With the continuous development of technology, face recognition technology has played an important role in police work. In order to get a clear face image, image preprocessing technology is needed. This paper mainly proposes illumination compensation technology and reconstruction technology based on symmetry.展开更多
A Generative Adversarial Neural(GAN)network is designed based on deep learning for the Super-Resolution(SR)reconstruction task of temperaturefields(comparable to downscaling in the meteorologicalfield),which is limite...A Generative Adversarial Neural(GAN)network is designed based on deep learning for the Super-Resolution(SR)reconstruction task of temperaturefields(comparable to downscaling in the meteorologicalfield),which is limited by the small number of ground stations and the sparse distribution of observations,resulting in a lack offineness of data.To improve the network’s generalization performance,the residual structure,and batch normalization are used.Applying the nearest interpolation method to avoid over-smoothing of the climate element values instead of the conventional Bicubic interpolation in the computer visionfield.Sub-pixel convolution is used instead of transposed convolution or interpolation methods for up-sampling to speed up network inference.The experimental dataset is the European Centre for Medium-Range Weather Forecasts Reanalysis v5(ERA5)with a bidirectional resolution of 0:1°×0:1°.On the other hand,the task aims to scale up the size by a factor of 8,which is rare compared to conventional methods.The comparison methods include traditional interpolation methods and a more widely used GAN-based network such as the SRGAN.Thefinal experimental results show that the proposed scheme advances the performance of Root Mean Square Error(RMSE)by 37.25%,the Peak Signal-to-noise Ratio(PNSR)by 14.4%,and the Structural Similarity(SSIM)by 10.3%compared to the Bicubic Interpolation.For the traditional SRGAN network,a relatively obvious performance improvement is observed by experimental demonstration.Meanwhile,the GAN network can converge stably and reach the approximate Nash equilibrium for various initialization parameters to empirically illustrate the effectiveness of the method in the temperature fields.展开更多
High-temperature ionothermal synthesis has been proven effective in preparing environment-friendly carbon nitride(CN)-based photocatalysts in either triazine or heptazine form for CO_(2)reduction reaction(CO_(2)RR).Ho...High-temperature ionothermal synthesis has been proven effective in preparing environment-friendly carbon nitride(CN)-based photocatalysts in either triazine or heptazine form for CO_(2)reduction reaction(CO_(2)RR).However,such a process is usually energy-intensive and suffers from partial carbonization that results in non-porous catalysts and degenerating their activities.Herein,we report the preparation of highly porous CN polymers(porous C_(6)N_(7),C_3N_3,C_(4.5)N_5)through a low-temperature solvothermal polymerization of cyameluric chloride itself or cyanuric chloride itself,or both,respectively.As such,it avoids unfavorable carbonization and allows for fine control of its chemical structure and significantly enlarged surface area(up to 669 m^(2)g^(-1)).The pincer-like 2,2′-bipyridine sites of porous C_(6)N_(7)alter the photocatalytic CO_(2)reduction pathways via stabilizing the^(*)HCO intermediates,which promotes further hydrogenation to produce CH_(4)in a high selectivity.Benefiting from the carbonization-free polymerization,high porosity,and^(*)HCO intermediate activation,porous C_(6)N_(7)gave a superior CO_(2)RR to CH_(4)performance(17.18μmol g^(-1)h^(-1))as well as high stability(5 successive cycles),outperforming the bulk and state-of-the-art counterparts of CN.This opens an avenue for the rational construction of efficient porous CN-based photocatalytic systems,demonstrating their great potential in energy conversion reactions.展开更多
Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control,noninvasiveness,and high efficiency.Geneticall...Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control,noninvasiveness,and high efficiency.Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation.Therefore,optogenetic techniques can provide new insights into oral biological processes at different levels,ranging from the subcellular and cellular levels to neural circuits and behavioral models.Here,we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research,focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo(orofacial movement,licking,eating,and drinking),such as channelrhodopsin(ChR),archaerhodopsin(Arch),and halorhodopsin from Natronomonas pharaonis(NpHR).We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis.In addition,optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies.Although the scope of optogenetic tools is increasing,there are limited large animal experiments and clinical studies in dental research.Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019(COVID-19),studying oral bacterial biofilms,enhancing craniomaxillofacial and periodontal tissue regeneration,and elucidating the possible pathogenesis of dry sockets,xerostomia,and burning mouth syndrome.展开更多
Transition-metal-catalyzed remote sp^(2)C-H functionalization of aryl sulfonic acids was hardly ever real-ized owing to competitive ortho-C-H functionalization of aryl sulfonates and electron-deficient nature of pheny...Transition-metal-catalyzed remote sp^(2)C-H functionalization of aryl sulfonic acids was hardly ever real-ized owing to competitive ortho-C-H functionalization of aryl sulfonates and electron-deficient nature of phenyl ring.Herein,with the assistance of a practical biaryl indolyl directing template,palladium-catalyzed remote sp^(2)C-H alkylation of aryl sulfonic acids have been achieved in moderate to good yields with exclusive meta selectivity.Moreover,remote meta-selective C-H alkynylation of aryl sulfonic acids was also accomplished with a rhodium catalyst.These meta-C-H functionalized products proved to be the superior synthetic precursors,which are difficult to access using the conventional strategy.展开更多
Type 2 diabetes mellitus(T2DM)exacerbates irreversible bone loss in periodontitis,but the mechanism of impaired bone regeneration caused by the abnormal metabolic process of T2DM remains unclear.Exosomes are regarded ...Type 2 diabetes mellitus(T2DM)exacerbates irreversible bone loss in periodontitis,but the mechanism of impaired bone regeneration caused by the abnormal metabolic process of T2DM remains unclear.Exosomes are regarded as the critical mediator in diabetic impairment of regeneration via organ or tissue communication.Here,we find that abnormally elevated exosomes derived from metabolically impaired liver in T2DM are significantly enriched in the periodontal region and induced pyroptosis of periodontal ligament cells(PDLCs).Mechanistically,fatty acid synthase(Fasn),the main differentially expressed molecule in diabetic exosomes results in ectopic fatty acid synthesis in PDLCs and activates the cleavage of gasdermin D.Depletion of liver Fasn effectively mitigates pyroptosis of PDLCs and alleviates bone loss.Our findings elucidate the mechanism of exacerbated bone loss in diabetic periodontitis and reveal the exosome-mediated organ communication in the“liver-bone”axis,which shed light on the prevention and treatment of diabetic bone disorders in the future.展开更多
The increased coronavirus disease 2019(COVID-19)breakthrough cases pose the need of booster vaccination.We conducted a randomised,double-blinded,controlled,phase 2 trial to assess the immunogenicity and safety of the ...The increased coronavirus disease 2019(COVID-19)breakthrough cases pose the need of booster vaccination.We conducted a randomised,double-blinded,controlled,phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine(BBIBP-CorV)followed by a recombinant protein-based vaccine(NVSI-06-07),using homologous boost with BBIBP-CorV as control.Three groups of healthy adults(600 individuals per group)who had completed two-dose BBIBP-CorV vaccinations 1–3 months,4–6 months and≥6 months earlier,respectively,were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost.Immunogenicity assays showed that in NVSI-06-07 groups,neutralizing antibody geometric mean titers(GMTs)against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination,whereas only 4.20–16.78 folds of increases were observed in control groups.For Omicron variant,the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14,however,a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster.Similar results were obtained for other SARS-CoV-2 variants of concerns(VOCs),including Alpha,Beta and Delta.Both heterologous and homologous boosters have a good safety profile.Local and systemic adverse reactions were absent,mild or moderate in most participants,and the overall safety was quite similar between two booster schemes.Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs,including Omicron.展开更多
An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18...An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18 years and older from the United Arab Emirates(UAE),who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment.The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV.The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant,and the exploratory outcome was cross-immunogenicity against other circulating strains.Between May 25 and 30,2022,516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group.Interim results showed a similar safety profile between two booster groups,with low incidence of adverse reactions of grade 1 or 2.For immunogenicity,by day 14 post-booster,the fold rises in neutralizing antibody geometric mean titers(GMTs)from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain(19.67 vs 4.47-fold),Omicron BA.1.1(42.35 vs 3.78-fold),BA.2(25.09 vs 2.91-fold),BA.4(22.42 vs 2.69-fold),and BA.5 variants(27.06 vs 4.73-fold).Similarly,the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV.Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants,including Omicron and its sub-lineages.展开更多
Silk fibroin(SF)as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity,tunable biodegradability,and high biocompatibility.Nowadays,various techniques have b...Silk fibroin(SF)as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity,tunable biodegradability,and high biocompatibility.Nowadays,various techniques have been developed for the applications of SF in bioengineering.Most of the literature reviews focus on the SF-based biomaterials and their different forms of applications such as films,hydrogels,and scaffolds.SF is also valuable as a coating on other substrate materials for biomedicine;however,there are few reviews related to SF-coated biomaterials.Thus,in this review,we focused on the surface modification of biomaterials using SF coatings,demonstrated their various preparation methods on substrate materials,and introduced the latest procedures.The diverse applications of SF coatings for biomedicine are discussed,including bone,ligament,skin,mucosa,and nerve regeneration,and dental implant surface modification.SF coating is conducive to inducing cell adhesion and migration,promoting hydroxyapatite(HA)deposition and matrix mineralization,and inhibiting the Notch signaling pathway,making it a promising strategy for bone regeneration.In addition,SF-coated composite scaffolds can be considered prospective candidates for ligament regeneration after injury.SF coating has been proven to enhance the mechanical properties of the substrate material,and render integral stability to the dressing material during the regeneration of skin and mucosa.Moreover,SF coating is a potential strategy to accelerate nerve regeneration due to its dielectric properties,mechanical flexibility,and angiogenesis promotion effect.In addition,SF coating is an effective and popular means for dental implant surface modification to promote osteogenesis around implants made of different materials.Thus,this review can be of great benefit for further improvements in SF-coated biomaterials,and will undoubtedly contribute to clinical transformation in the future.展开更多
This paper studies a dynamic multi-user wireless network,where users have no knowledge of the arrival rate and size of data block and suffer from a constraint on long-term average power consumption.Considering such a ...This paper studies a dynamic multi-user wireless network,where users have no knowledge of the arrival rate and size of data block and suffer from a constraint on long-term average power consumption.Considering such a network,we address the problem of dynamically optimizing channel/power allocation,so as to minimize the long-term average data backlog.The design problem is shown to be a constrained Markov decision process.In order to solve the problem without knowledge on dynamics of the system,we introduce post-decision states and propose a resource allocation algorithm based on reinforcement learning.Since the channel/power allocation problem is coupled,the multiuser decision problem suffers from curses of dimensions(of state/action/outcome space).This makes centralized decision-making and optimization on channel/power allocation suffer from a long convergence time.As a countermeasure,a partially distributed resource allocation framework is proposed.The multiuser power allocation problem is decoupled into single-user decision problems,while channel allocation optimization is performed in a centralized manner.In order to further reduce computational complexity,we propose a low-complexity reinforcement learning method.Simulation results reveal that the proposed algorithm outperforms the state-of-the-art myopic optimizations in terms of energy efficiency and the backlog performance.展开更多
基金supported by the Research fund of Anhui Institute of Translational Medicine (No. 2021zhyx-C62)。
文摘Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer(BCa), remains poorly elucidated.Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzymelinked immunosorbent assays(ELISA) and immunohistochemistry(IHC).Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages(CD163~+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients.Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues,potentially influencing the treatment responses of affected individuals.
文摘With the continuous development of technology, face recognition technology has played an important role in police work. In order to get a clear face image, image preprocessing technology is needed. This paper mainly proposes illumination compensation technology and reconstruction technology based on symmetry.
基金supported by the National Natural Science Foundation of China under Grant Nos.61772280 and 62072249.
文摘A Generative Adversarial Neural(GAN)network is designed based on deep learning for the Super-Resolution(SR)reconstruction task of temperaturefields(comparable to downscaling in the meteorologicalfield),which is limited by the small number of ground stations and the sparse distribution of observations,resulting in a lack offineness of data.To improve the network’s generalization performance,the residual structure,and batch normalization are used.Applying the nearest interpolation method to avoid over-smoothing of the climate element values instead of the conventional Bicubic interpolation in the computer visionfield.Sub-pixel convolution is used instead of transposed convolution or interpolation methods for up-sampling to speed up network inference.The experimental dataset is the European Centre for Medium-Range Weather Forecasts Reanalysis v5(ERA5)with a bidirectional resolution of 0:1°×0:1°.On the other hand,the task aims to scale up the size by a factor of 8,which is rare compared to conventional methods.The comparison methods include traditional interpolation methods and a more widely used GAN-based network such as the SRGAN.Thefinal experimental results show that the proposed scheme advances the performance of Root Mean Square Error(RMSE)by 37.25%,the Peak Signal-to-noise Ratio(PNSR)by 14.4%,and the Structural Similarity(SSIM)by 10.3%compared to the Bicubic Interpolation.For the traditional SRGAN network,a relatively obvious performance improvement is observed by experimental demonstration.Meanwhile,the GAN network can converge stably and reach the approximate Nash equilibrium for various initialization parameters to empirically illustrate the effectiveness of the method in the temperature fields.
基金supported by the National Natural Science Foundation of China (52173212 and 52103275)Hunan Province Funds for Distinguished Young Scientists (2022JJ10080)+3 种基金financial support from the European Research Council (ERC)Consolidator (PARIS-101043485)the Swedish Research Council (2022-04533)the Wallenberg Academy Fellow Program (KAW 2017.0166)from the Knut&Alice Wallenberg Foundation in Swedenthe Olle Engkvists Foundation (213-0206)in Sweden。
文摘High-temperature ionothermal synthesis has been proven effective in preparing environment-friendly carbon nitride(CN)-based photocatalysts in either triazine or heptazine form for CO_(2)reduction reaction(CO_(2)RR).However,such a process is usually energy-intensive and suffers from partial carbonization that results in non-porous catalysts and degenerating their activities.Herein,we report the preparation of highly porous CN polymers(porous C_(6)N_(7),C_3N_3,C_(4.5)N_5)through a low-temperature solvothermal polymerization of cyameluric chloride itself or cyanuric chloride itself,or both,respectively.As such,it avoids unfavorable carbonization and allows for fine control of its chemical structure and significantly enlarged surface area(up to 669 m^(2)g^(-1)).The pincer-like 2,2′-bipyridine sites of porous C_(6)N_(7)alter the photocatalytic CO_(2)reduction pathways via stabilizing the^(*)HCO intermediates,which promotes further hydrogenation to produce CH_(4)in a high selectivity.Benefiting from the carbonization-free polymerization,high porosity,and^(*)HCO intermediate activation,porous C_(6)N_(7)gave a superior CO_(2)RR to CH_(4)performance(17.18μmol g^(-1)h^(-1))as well as high stability(5 successive cycles),outperforming the bulk and state-of-the-art counterparts of CN.This opens an avenue for the rational construction of efficient porous CN-based photocatalytic systems,demonstrating their great potential in energy conversion reactions.
基金supported by the National Natural Science Foundation of China(No.82370991)the Health Department of Zhejiang Province(Nos.2021KY194 and 2022KY872),China.
文摘Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control,noninvasiveness,and high efficiency.Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation.Therefore,optogenetic techniques can provide new insights into oral biological processes at different levels,ranging from the subcellular and cellular levels to neural circuits and behavioral models.Here,we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research,focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo(orofacial movement,licking,eating,and drinking),such as channelrhodopsin(ChR),archaerhodopsin(Arch),and halorhodopsin from Natronomonas pharaonis(NpHR).We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis.In addition,optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies.Although the scope of optogenetic tools is increasing,there are limited large animal experiments and clinical studies in dental research.Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019(COVID-19),studying oral bacterial biofilms,enhancing craniomaxillofacial and periodontal tissue regeneration,and elucidating the possible pathogenesis of dry sockets,xerostomia,and burning mouth syndrome.
基金Financial support from the National Natural Science Foundation of China(No.22171145 to Z.Jin,32072440 to X.Xu)is gratefully acknowledged.
文摘Transition-metal-catalyzed remote sp^(2)C-H functionalization of aryl sulfonic acids was hardly ever real-ized owing to competitive ortho-C-H functionalization of aryl sulfonates and electron-deficient nature of phenyl ring.Herein,with the assistance of a practical biaryl indolyl directing template,palladium-catalyzed remote sp^(2)C-H alkylation of aryl sulfonic acids have been achieved in moderate to good yields with exclusive meta selectivity.Moreover,remote meta-selective C-H alkynylation of aryl sulfonic acids was also accomplished with a rhodium catalyst.These meta-C-H functionalized products proved to be the superior synthetic precursors,which are difficult to access using the conventional strategy.
基金supported by the Major Program of the National Natural Science Foundation of China(81991500,81991502,81991504)Shaanxi provincial key research and development program(2023-ZDLSF-49)the National Postdoctoral Program for Innovative Talents of China(BX20220394).
文摘Type 2 diabetes mellitus(T2DM)exacerbates irreversible bone loss in periodontitis,but the mechanism of impaired bone regeneration caused by the abnormal metabolic process of T2DM remains unclear.Exosomes are regarded as the critical mediator in diabetic impairment of regeneration via organ or tissue communication.Here,we find that abnormally elevated exosomes derived from metabolically impaired liver in T2DM are significantly enriched in the periodontal region and induced pyroptosis of periodontal ligament cells(PDLCs).Mechanistically,fatty acid synthase(Fasn),the main differentially expressed molecule in diabetic exosomes results in ectopic fatty acid synthesis in PDLCs and activates the cleavage of gasdermin D.Depletion of liver Fasn effectively mitigates pyroptosis of PDLCs and alleviates bone loss.Our findings elucidate the mechanism of exacerbated bone loss in diabetic periodontitis and reveal the exosome-mediated organ communication in the“liver-bone”axis,which shed light on the prevention and treatment of diabetic bone disorders in the future.
基金funded by Lanzhou Institute of Biological Products Company Limited.We would like to thank Prof.Guoyong Yuan from the University of Hong Kong for providing SARS-CoV-2 Omicron virus applied in live-virus neutralization assay。
文摘The increased coronavirus disease 2019(COVID-19)breakthrough cases pose the need of booster vaccination.We conducted a randomised,double-blinded,controlled,phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine(BBIBP-CorV)followed by a recombinant protein-based vaccine(NVSI-06-07),using homologous boost with BBIBP-CorV as control.Three groups of healthy adults(600 individuals per group)who had completed two-dose BBIBP-CorV vaccinations 1–3 months,4–6 months and≥6 months earlier,respectively,were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost.Immunogenicity assays showed that in NVSI-06-07 groups,neutralizing antibody geometric mean titers(GMTs)against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination,whereas only 4.20–16.78 folds of increases were observed in control groups.For Omicron variant,the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14,however,a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster.Similar results were obtained for other SARS-CoV-2 variants of concerns(VOCs),including Alpha,Beta and Delta.Both heterologous and homologous boosters have a good safety profile.Local and systemic adverse reactions were absent,mild or moderate in most participants,and the overall safety was quite similar between two booster schemes.Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs,including Omicron.
基金The study was funded by Lanzhou Institute of Biological Products Co.,Ltd(LIBP)of Sinopharm,and Beijing Institute of Biological Products Co.,Ltd(BIBP)of Sinopharm.X.J.G.,X.Y.M.,H.W.,and J.Zhang are employees of the funders.The funders did not participate in design of the trial,analysis of the data,or writing of the manuscript.
文摘An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18 years and older from the United Arab Emirates(UAE),who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment.The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV.The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant,and the exploratory outcome was cross-immunogenicity against other circulating strains.Between May 25 and 30,2022,516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group.Interim results showed a similar safety profile between two booster groups,with low incidence of adverse reactions of grade 1 or 2.For immunogenicity,by day 14 post-booster,the fold rises in neutralizing antibody geometric mean titers(GMTs)from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain(19.67 vs 4.47-fold),Omicron BA.1.1(42.35 vs 3.78-fold),BA.2(25.09 vs 2.91-fold),BA.4(22.42 vs 2.69-fold),and BA.5 variants(27.06 vs 4.73-fold).Similarly,the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV.Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants,including Omicron and its sub-lineages.
基金supported by the National Natural Science Foundation of China (No.82101062)the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (No.2023KY132)the Zhejiang Provincial Key Research and Development Program of China (No.2021C03113).
文摘Silk fibroin(SF)as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity,tunable biodegradability,and high biocompatibility.Nowadays,various techniques have been developed for the applications of SF in bioengineering.Most of the literature reviews focus on the SF-based biomaterials and their different forms of applications such as films,hydrogels,and scaffolds.SF is also valuable as a coating on other substrate materials for biomedicine;however,there are few reviews related to SF-coated biomaterials.Thus,in this review,we focused on the surface modification of biomaterials using SF coatings,demonstrated their various preparation methods on substrate materials,and introduced the latest procedures.The diverse applications of SF coatings for biomedicine are discussed,including bone,ligament,skin,mucosa,and nerve regeneration,and dental implant surface modification.SF coating is conducive to inducing cell adhesion and migration,promoting hydroxyapatite(HA)deposition and matrix mineralization,and inhibiting the Notch signaling pathway,making it a promising strategy for bone regeneration.In addition,SF-coated composite scaffolds can be considered prospective candidates for ligament regeneration after injury.SF coating has been proven to enhance the mechanical properties of the substrate material,and render integral stability to the dressing material during the regeneration of skin and mucosa.Moreover,SF coating is a potential strategy to accelerate nerve regeneration due to its dielectric properties,mechanical flexibility,and angiogenesis promotion effect.In addition,SF coating is an effective and popular means for dental implant surface modification to promote osteogenesis around implants made of different materials.Thus,this review can be of great benefit for further improvements in SF-coated biomaterials,and will undoubtedly contribute to clinical transformation in the future.
基金This work was supported in part by National Natural Science Foundation of China under Grant 61901216,61631020 and 61827801Natural Science Foundation of Jiangsu Province under Grant BK20190400+1 种基金Open Research Fund of National Mobile Communications Research Laboratory,Southeast University(No.2020D08)Foundation of Graduate Innovation Center in NUAA under Grant kfjj20190408。
文摘This paper studies a dynamic multi-user wireless network,where users have no knowledge of the arrival rate and size of data block and suffer from a constraint on long-term average power consumption.Considering such a network,we address the problem of dynamically optimizing channel/power allocation,so as to minimize the long-term average data backlog.The design problem is shown to be a constrained Markov decision process.In order to solve the problem without knowledge on dynamics of the system,we introduce post-decision states and propose a resource allocation algorithm based on reinforcement learning.Since the channel/power allocation problem is coupled,the multiuser decision problem suffers from curses of dimensions(of state/action/outcome space).This makes centralized decision-making and optimization on channel/power allocation suffer from a long convergence time.As a countermeasure,a partially distributed resource allocation framework is proposed.The multiuser power allocation problem is decoupled into single-user decision problems,while channel allocation optimization is performed in a centralized manner.In order to further reduce computational complexity,we propose a low-complexity reinforcement learning method.Simulation results reveal that the proposed algorithm outperforms the state-of-the-art myopic optimizations in terms of energy efficiency and the backlog performance.
