十一年前,Wendy Saunders和Vincent de Graaf这对年轻的荷兰设计师,被一艘"中国"字样的游船引发了对这个遥远国度的好奇心。从旅游的初衷,到留下来工作并选择创业,是因为他们敏锐地发现,在设计业刚刚起步的中国蕴藏着很多可...十一年前,Wendy Saunders和Vincent de Graaf这对年轻的荷兰设计师,被一艘"中国"字样的游船引发了对这个遥远国度的好奇心。从旅游的初衷,到留下来工作并选择创业,是因为他们敏锐地发现,在设计业刚刚起步的中国蕴藏着很多可以施展才华的机会。"就是这样一些自由的想法让我们创立了AIM。"和很多年轻的工作室一样,在艰难的创业初期,AIM很难得到建筑设计的机会,在尝试过设计竞标等收效甚微的方式之后,他们选择以室内设计为突破口,随着室内设计作品完成和影响,逐渐发展到规划建筑、景观到室内软装全方位的设计,并在商业、办公、酒店等多元化设计领域有所建树。展开更多
Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily ou...Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily outpatient visit data from rabies post-exposure prophylaxis clinics in Jinan and corresponding meteorological data were collected from January 1,2020,to December 31,2022.A generalized additive model was used to quantitatively assess the relationship between these factors.A total of 202,010 patients visited these clinics during this period.Results:Daily mean,maximum,and minimum temperatures,and relative humidity were positively associated with outpatient visits.A 1°C increase in mean,maximum,and minimum temperatures corresponded to increases in daily visits of 1.65%(95%Confidence Interval(CI):1.55–1.76),1.59%(95%CI:1.50–1.69),and 1.27%(95%CI:1.17–1.36)respectively.Each 1%increase in relative humidity was associated with a 0.18%(95%CI:0.15–0.20)increase in visits.Mean pressure was negatively associated with outpatient visits,the outpatient visits decreased by 0.91%(95%CI:−1.71 to−0.11)for every 1 kPa increased in mean pressure.Conclusion:The change of meteorological factors will lead to the increase of outpatient visits in rabies exposure treatment clinic.展开更多
BACKGROUND Syngeneic orthotopic tumor models offer an optimal functional tumor–immune interface for hepatocellular carcinoma research.Yet,unpredictable growth kinetics and spontaneous regression pose major obstacles....BACKGROUND Syngeneic orthotopic tumor models offer an optimal functional tumor–immune interface for hepatocellular carcinoma research.Yet,unpredictable growth kinetics and spontaneous regression pose major obstacles.Efficient induction protocols and continuous monitoring are therefore essential.Routine exploratory surgeries are ethically untenable,making non-invasive imaging modalities attractive alternatives.High-resolution magnetic resonance imaging and microcomputed tomography deliver detailed insights but incur substantial equipment costs,radiation risks,time demands,and require specialized expertise—challenges that limit their routine use.In contrast,ultrasound(US)imaging emerges as a cost-effective,radiation-free,and rapid approach,facilitating practical and ethical longitudinal assessment of tumor progression in preclinical studies.AIM To optimize the orthotopic hepatocellular carcinoma model and evaluate the potential of US imaging for accurate and cost-effective tumor monitoring.METHODS Hepatocellular carcinoma was induced in 28 Sprague Dawley rats by implanting 5×10^(6) N1S1 cells into the left lateral hepatic lobe.Tumor progression was monitored weekly via US.Upon reaching 100-150 mm^(3),an experimental group(n=14)received Sorafenib(40 mg/kg)orally on alternate days for 28 days;efficacy was compared to untreated controls.US accuracy was validated against micro-computed tomography,gross caliper measurements and histopathological analysis.Reliability and operator proficiency in US assessment were also evaluated.RESULTS US images procured 7-day post-surgery revealed a well-defined hypoechoic nodule at the left liver lobe tip,confirming successful tumor induction(mean volume 130±39 mm^(3)).Only three animals exhibited spontaneous regression by week 2,underscoring the model’s stability.Sorafenib treatment elicited a marked tumor reduction(678±103 mm^(3))vs untreated control(6005±1760 mm^(3)).US assessment demonstrated robust intra and interobserver reproducibility with high sensitivity and specificity for tumor detection.Moreover,US derived volumes correlated strongly with gross caliper measurements,histopathological analysis,and microcomputed tomography imaging,validating its reliability as a non-invasive monitoring tool in preclinical hepatocellular carcinoma studies.CONCLUSION The results demonstrate that US imaging is a reliable,cost-effective,and animal sparing approach with an easy tomaster protocol,enabling monitoring of tumor progression and therapeutic response in orthotopic liver tumor models.展开更多
Influenza is a significant global public health challenge,with seasonal epidemics imposing substantial burdens on healthcare systems and vulnerable populations,causing 3 to 5 million severe cases and 290,000 to 650,00...Influenza is a significant global public health challenge,with seasonal epidemics imposing substantial burdens on healthcare systems and vulnerable populations,causing 3 to 5 million severe cases and 290,000 to 650,000 respiratory-related deaths worldwide each year[1].Vaccines are an effective means of preventing influenza.In recent years,China has made progress in vaccine development and immunization strategies.The population is recommended to receive influenza vaccines annually;however,their coverage remain suboptimal[2].The World Health Organization(WHO)highlights that all countries should consider implementing seasonal influenza immunization programs,with priority groups determined based on local epidemiological contexts.In alignment with the Immunization Agenda 2030,the use of seasonal influenza vaccines contributes to strengthening the life course of immunization and serves as a critical component for addressing influenza pandemics,as outlined in the WHO Global Influenza Strategy 2019-2030.展开更多
Lysosomal diseases(LDs)are a group of rare inherited disorders belonging to inborn metabolism errors.LDs are characterized by the excessive storage of undegraded substrates,most often due to the enzymatic deficiency r...Lysosomal diseases(LDs)are a group of rare inherited disorders belonging to inborn metabolism errors.LDs are characterized by the excessive storage of undegraded substrates,most often due to the enzymatic deficiency resulting from disease-causing gene variants.LDs lead to dysregulated cellular pathways and imbalanced molecular homeostasis and can affect multiple organs and tissues.Despite being rare,LDs account for a significant incidence when considered collectively.Due to complex molecular and genetic fingerprints,considerable challenges in LD management must be overcome.Diagnosis can be signifi-cantly delayed due to the broad and nonspecific clinical manifestations and the lack of specific bio-markers.Available treatments fail to fully stop the disease progression and can alter the disease's typical phenotypes with novel manifestations.Therefore,a paradigm shift is crucial to better understand LDs and provide actionable insights.Herein,we comprehensively review the literature to demonstrate that multi-omics approaches are promising for pathophysiology elucidation,biomarker discovery,and pre-cision therapy in LDs.We recommend adopting longitudinal study designs integrated with a multi-omics-empowered framework to facilitate mechanistic delineation,biomarker discovery,and treat-ment development.Relevant approaches exploring the association between LDs and common neuro-degenerative disorders are also discussed,paving a potential path for improved therapeutic development and ultimately improving the patient's quality of life.展开更多
Biotechnological strategies for plastic depolymerization and recycling have emerged as transformative approaches to combat the global plastic pollution crisis,aligning with the principles of a sustainable and circular...Biotechnological strategies for plastic depolymerization and recycling have emerged as transformative approaches to combat the global plastic pollution crisis,aligning with the principles of a sustainable and circular economy.Despite advances in engineering PET hydrolases,the degradation process is frequently compromised by product inhibition and the heterogeneity of final products,thereby obstructing subsequent PET recondensation and impeding the synthesis of high-value derivatives.In this work,we utilized previously devised computational strategies to redesign a thermostable DuraMHETase,achieving an apparent melting temperature of 72℃ in complex with MHET and a 6-fold higher in total turnover number(TTN)toward MHET than the wild-type enzyme at 60℃.The fused enzyme system composed of DuraMHETase and TurboPETase demonstrated higher efficiency than other PET hydrolases and the separated dual enzyme systems.Furthermore,we identified both exo-and endo-PETase activities in DuraMHETase,whereas the endo-activity was previously unobserved at ambient temperatures.These results expand the functional scope of MHETase beyond mere intermediate hydrolysis,and may provide guidance for the development of more synergistic approaches to plastic biodepolymerization and recycling.展开更多
文摘十一年前,Wendy Saunders和Vincent de Graaf这对年轻的荷兰设计师,被一艘"中国"字样的游船引发了对这个遥远国度的好奇心。从旅游的初衷,到留下来工作并选择创业,是因为他们敏锐地发现,在设计业刚刚起步的中国蕴藏着很多可以施展才华的机会。"就是这样一些自由的想法让我们创立了AIM。"和很多年轻的工作室一样,在艰难的创业初期,AIM很难得到建筑设计的机会,在尝试过设计竞标等收效甚微的方式之后,他们选择以室内设计为突破口,随着室内设计作品完成和影响,逐渐发展到规划建筑、景观到室内软装全方位的设计,并在商业、办公、酒店等多元化设计领域有所建树。
基金supported by Chinese Association of Preventive Medicine-Vaccine and Immunization Youth Talent Support Project(CPMAQT-YM0314)Shandong medical and health science and technology development plan project(202012050267)Shandong Center for Disease Control and Prevention-Youth Innovation Fund Project(QC-202301).
文摘Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily outpatient visit data from rabies post-exposure prophylaxis clinics in Jinan and corresponding meteorological data were collected from January 1,2020,to December 31,2022.A generalized additive model was used to quantitatively assess the relationship between these factors.A total of 202,010 patients visited these clinics during this period.Results:Daily mean,maximum,and minimum temperatures,and relative humidity were positively associated with outpatient visits.A 1°C increase in mean,maximum,and minimum temperatures corresponded to increases in daily visits of 1.65%(95%Confidence Interval(CI):1.55–1.76),1.59%(95%CI:1.50–1.69),and 1.27%(95%CI:1.17–1.36)respectively.Each 1%increase in relative humidity was associated with a 0.18%(95%CI:0.15–0.20)increase in visits.Mean pressure was negatively associated with outpatient visits,the outpatient visits decreased by 0.91%(95%CI:−1.71 to−0.11)for every 1 kPa increased in mean pressure.Conclusion:The change of meteorological factors will lead to the increase of outpatient visits in rabies exposure treatment clinic.
基金Supported by Amrita Vishwa Vidyapeetham Seed Grant,No.K-PHAR-24-722DST INSPIRE Fellowship,No.IF190226.
文摘BACKGROUND Syngeneic orthotopic tumor models offer an optimal functional tumor–immune interface for hepatocellular carcinoma research.Yet,unpredictable growth kinetics and spontaneous regression pose major obstacles.Efficient induction protocols and continuous monitoring are therefore essential.Routine exploratory surgeries are ethically untenable,making non-invasive imaging modalities attractive alternatives.High-resolution magnetic resonance imaging and microcomputed tomography deliver detailed insights but incur substantial equipment costs,radiation risks,time demands,and require specialized expertise—challenges that limit their routine use.In contrast,ultrasound(US)imaging emerges as a cost-effective,radiation-free,and rapid approach,facilitating practical and ethical longitudinal assessment of tumor progression in preclinical studies.AIM To optimize the orthotopic hepatocellular carcinoma model and evaluate the potential of US imaging for accurate and cost-effective tumor monitoring.METHODS Hepatocellular carcinoma was induced in 28 Sprague Dawley rats by implanting 5×10^(6) N1S1 cells into the left lateral hepatic lobe.Tumor progression was monitored weekly via US.Upon reaching 100-150 mm^(3),an experimental group(n=14)received Sorafenib(40 mg/kg)orally on alternate days for 28 days;efficacy was compared to untreated controls.US accuracy was validated against micro-computed tomography,gross caliper measurements and histopathological analysis.Reliability and operator proficiency in US assessment were also evaluated.RESULTS US images procured 7-day post-surgery revealed a well-defined hypoechoic nodule at the left liver lobe tip,confirming successful tumor induction(mean volume 130±39 mm^(3)).Only three animals exhibited spontaneous regression by week 2,underscoring the model’s stability.Sorafenib treatment elicited a marked tumor reduction(678±103 mm^(3))vs untreated control(6005±1760 mm^(3)).US assessment demonstrated robust intra and interobserver reproducibility with high sensitivity and specificity for tumor detection.Moreover,US derived volumes correlated strongly with gross caliper measurements,histopathological analysis,and microcomputed tomography imaging,validating its reliability as a non-invasive monitoring tool in preclinical hepatocellular carcinoma studies.CONCLUSION The results demonstrate that US imaging is a reliable,cost-effective,and animal sparing approach with an easy tomaster protocol,enabling monitoring of tumor progression and therapeutic response in orthotopic liver tumor models.
基金supported by the Chinese Association of Preventive Medicine-Vaccine and Immunization Youth Talent Support Project(CPMAQT-YM0314)。
文摘Influenza is a significant global public health challenge,with seasonal epidemics imposing substantial burdens on healthcare systems and vulnerable populations,causing 3 to 5 million severe cases and 290,000 to 650,000 respiratory-related deaths worldwide each year[1].Vaccines are an effective means of preventing influenza.In recent years,China has made progress in vaccine development and immunization strategies.The population is recommended to receive influenza vaccines annually;however,their coverage remain suboptimal[2].The World Health Organization(WHO)highlights that all countries should consider implementing seasonal influenza immunization programs,with priority groups determined based on local epidemiological contexts.In alignment with the Immunization Agenda 2030,the use of seasonal influenza vaccines contributes to strengthening the life course of immunization and serves as a critical component for addressing influenza pandemics,as outlined in the WHO Global Influenza Strategy 2019-2030.
基金Graphical abstract and Figs.1-4 were createdwith BioRender.com.
文摘Lysosomal diseases(LDs)are a group of rare inherited disorders belonging to inborn metabolism errors.LDs are characterized by the excessive storage of undegraded substrates,most often due to the enzymatic deficiency resulting from disease-causing gene variants.LDs lead to dysregulated cellular pathways and imbalanced molecular homeostasis and can affect multiple organs and tissues.Despite being rare,LDs account for a significant incidence when considered collectively.Due to complex molecular and genetic fingerprints,considerable challenges in LD management must be overcome.Diagnosis can be signifi-cantly delayed due to the broad and nonspecific clinical manifestations and the lack of specific bio-markers.Available treatments fail to fully stop the disease progression and can alter the disease's typical phenotypes with novel manifestations.Therefore,a paradigm shift is crucial to better understand LDs and provide actionable insights.Herein,we comprehensively review the literature to demonstrate that multi-omics approaches are promising for pathophysiology elucidation,biomarker discovery,and pre-cision therapy in LDs.We recommend adopting longitudinal study designs integrated with a multi-omics-empowered framework to facilitate mechanistic delineation,biomarker discovery,and treat-ment development.Relevant approaches exploring the association between LDs and common neuro-degenerative disorders are also discussed,paving a potential path for improved therapeutic development and ultimately improving the patient's quality of life.
文摘Biotechnological strategies for plastic depolymerization and recycling have emerged as transformative approaches to combat the global plastic pollution crisis,aligning with the principles of a sustainable and circular economy.Despite advances in engineering PET hydrolases,the degradation process is frequently compromised by product inhibition and the heterogeneity of final products,thereby obstructing subsequent PET recondensation and impeding the synthesis of high-value derivatives.In this work,we utilized previously devised computational strategies to redesign a thermostable DuraMHETase,achieving an apparent melting temperature of 72℃ in complex with MHET and a 6-fold higher in total turnover number(TTN)toward MHET than the wild-type enzyme at 60℃.The fused enzyme system composed of DuraMHETase and TurboPETase demonstrated higher efficiency than other PET hydrolases and the separated dual enzyme systems.Furthermore,we identified both exo-and endo-PETase activities in DuraMHETase,whereas the endo-activity was previously unobserved at ambient temperatures.These results expand the functional scope of MHETase beyond mere intermediate hydrolysis,and may provide guidance for the development of more synergistic approaches to plastic biodepolymerization and recycling.
