BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。展开更多
Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-p...Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.展开更多
Tuning the coordination atoms of central metal is an effective means to improve the electrocatalytic activity of atomic catalysts.Herein,iridium(Ir) is proposed to be asymmetrically anchored by sp-N and pyridinic N of...Tuning the coordination atoms of central metal is an effective means to improve the electrocatalytic activity of atomic catalysts.Herein,iridium(Ir) is proposed to be asymmetrically anchored by sp-N and pyridinic N of hydrogen-substituted graphdiyne(HsGDY),and coordinated with OH as an Ir atomic catalyst(Ir_(1)-N-HsGDY).The electron structures,especially the d-band center of Ir atom,are optimized by these specific coordination atoms.Thus,the as-synthesized Ir_(1)-N-HsGDY exhibits excellent electrocatalytic performances for oxygen reduction and hydrogen evolution reactions in both acidic and alkaline media.Benefiting from the unique structure of HsGDY,IrN_(2)(OH)_(3) has been developed and demonstrated to act as the active site in these electrochemical reactions.All those indicate the fresh role of the sp-N in graphdiyne in producing a new anchor way and contributing to promote the electrocatalytic activity,showing a new strategy to design novel electrochemical catalysts.展开更多
Surface/interface engineering of a multimetallic nanostructure with diverse electrocatalytic properties for direct liquid fuel cells is desirable yet challenging.Herein,using visible light,a class of quaternary Pt_(1)...Surface/interface engineering of a multimetallic nanostructure with diverse electrocatalytic properties for direct liquid fuel cells is desirable yet challenging.Herein,using visible light,a class of quaternary Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)ultrathin nanosheets is fabricated and used as high-performance anode electrocatalysts for formic acid-/alcohol-air fuel cells.The modified electronic structure of Pt,enhanced hydroxyl adsorption,and abundant exterior defects afford Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C high intrinsic anodic electrocatalytic activity to boost the power densities of direct formic acid-/methanol-/ethanol-/ethylene glycol-/glycerol-air fuel cells,and the corresponding peak power density of Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C is respectively 129.7,142.3,105.4,124.3,and 128.0 mW cm^(-2),considerably outperforming Pt/C.Operando in situ Fourier transform infrared reflection spectroscopy reveals that formic acid oxidation on Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C occurs via a CO_(2)-free direct pathway.Density functional theory calculations show that the presence of Ag,Bi,and Te in Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)suppresses CO^(*)formation while optimizing dehydrogenation steps and synergistic effect and modified Pt effectively enhance H_(2)O dissociation to improve electrocatalytic performance.This synthesis strategy can be extended to 43 other types of ultrathin multimetallic nanosheets(from ternary to octonary nanosheets),and efficiently capture precious metals(i.e.,Pd,Pt,Rh,Ru,Au,and Ag)from different water sources.展开更多
The formation of multiple oxygen intermediates supporting efficient oxygen evolution reaction(OER)are affinitive with hydroxyl adsorption.However,ability of the catalyst to capture hydroxyl and maintain the continuous...The formation of multiple oxygen intermediates supporting efficient oxygen evolution reaction(OER)are affinitive with hydroxyl adsorption.However,ability of the catalyst to capture hydroxyl and maintain the continuous supply at active sits remains a tremendous challenge.Herein,an affordable Ni2P/FeP2 heterostructure is presented to form the internal polarization field(IPF),arising hydroxyl spillover(HOSo)during OER.Facilitated by IPF,the oriented HOSo from FeP2 to Ni2P can activate the Ni site with a new hydroxyl transmission channel and build the optimized reaction path of oxygen intermediates for lower adsorption energy,boosting the OER activity(242 mV vs.RHE at 100 mA cm-2)for least 100 h.More interestingly,for the anion exchange membrane water electrolyzer(AEMWE)with low concentration electrolyte,the advantage of HOSo effect is significantly amplified,delivering 1 A cm^(-2)at a low cell voltage of 1.88 V with excellent stability for over 50 h.展开更多
We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar sample.Emission from a pulsar is identified as non-nulling if(i)the e...We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar sample.Emission from a pulsar is identified as non-nulling if(i)the emission does not cease across the whole pulse profile,and(ii)the emission is detectable.For(i),we adopt a model for switching in the plasma charge density,and emission persists if the charge density is non-zero.For(ii),we assume that detectable emission originates from source points where it is emitted tangentially to the magnetic field-line and parallel to the line-of-sight.We find that pulsars exhibiting non-nulling emission possess obliquity angles with an average of 42°.5,and almost half the samples maintain a duty cycle between 0.05 and 0.2.Furthermore,the pulsar population is not fixed but dependent on the obliquity angle,with the population peaking at 20°.In addition,three evolutionary phases are identified in the pulsar population as the obliquity angle evolves,with the majority of samples having an obliquity angle between 20°and 65°.Our results also suggest that emission from a pulsar may evolve between nulling and non-nulling during its lifetime.展开更多
One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing prom...One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.展开更多
Introduction: Vaccination plays a pivotal role in mitigating the repercussions of the COVID-19 pandemic. However, vaccination campaigns encounter obstacles, especially in developing countries like the Democratic Repub...Introduction: Vaccination plays a pivotal role in mitigating the repercussions of the COVID-19 pandemic. However, vaccination campaigns encounter obstacles, especially in developing countries like the Democratic Republic of the Congo (DRC). This study aimed at investigating the roles of vaccine hesitancy, refusal, and access barriers, while identifying individual-level factors associated with non-vaccination in Mbujimayi, DRC. Methods: A community-based cross-sectional survey was conducted in three health districts and included 1496 residents. Attitudes and behaviors related to seeking COVID-19 vaccination were assessed using a standardized questionnaire. Hierarchical logistic regression modeling was used to assess factors potentially affecting non-compliance with vaccination. Results: Among participants (median age = 33, IQR = 23.3, M/F sex ratio = 0.7), 60% displayed misconceptions about COVID-19 or its vaccine, while only 35.2% perceived COVID-19 as a significant health threat. Vaccination coverage was estimated at 49.1% (95% CI: 47.5;52.6), with 71.8% of vaccinated individuals having received one dose. Among the unvaccinated individuals, 50.9% expressed no intention to be vaccinated in the future, citing hesitation (30.4%) or refusal (39.6%) mainly due to side effects or distrust of vaccines. Conversely, 32.7% of the unvaccinated persons expressed access barriers despite willingness to be vaccinated. Misconceptions about COVID-19 and its vaccines were the main drivers of vaccination non-compliance. Conclusion: These findings demonstrate significant vaccine non-compliance driven by hesitancy, refusal, and access barriers. Strategies to enhance vaccination coverage and pandemic preparedness should address misconceptions, sociodemographic barriers, and geographic disparities.展开更多
Non-communicable diseases (NCDs) account for 63% of mortalities. Approximately 80% of these NCD-related deaths occur in LMICs. A quasi-experimental study utilizing a non-equivalent pre-and post-test was conducted from...Non-communicable diseases (NCDs) account for 63% of mortalities. Approximately 80% of these NCD-related deaths occur in LMICs. A quasi-experimental study utilizing a non-equivalent pre-and post-test was conducted from May 2022 to March 2023 with 370 study participants. Multistage cluster and random sampling were used to select ten community units, and therefore, 150 CHVs were chosen for the control unit, and 150 were used to form the interventional group. Data was collected from the KOBO app. Six (6) homogenous FGDs comprised ten members, and 10 KII were conducted across study sites. Quantitative data was analyzed using SPSS version 28.0, and qualitative data was audio-recorded, transcribed, and analyzed via N-Vivo 12. The study shows that 59.3% of respondents have minimal information, and 92.7% (n = 139) have no clear understanding of NCDs, with a pre-intervention capacity of 48.8%. Independent sample t-test showed a significant difference in capacity from a pre-intervention average of 48.75 (SD ± 5.7)%, which increased to 68.28 (SD ± 7.6)%, p < 0.001. A well-designed community interventional model plays a pivotal role in grassroots healthcare delivery but requires optimization for NCD management.展开更多
Malignant non-Hodgkins lymphoma (MHNL) of the uterus is uncommon. We report a case diagnosed on the basis of histologic and immunohistochemical studies of a hysterectomy specimen induced by a very painful pelvic mass ...Malignant non-Hodgkins lymphoma (MHNL) of the uterus is uncommon. We report a case diagnosed on the basis of histologic and immunohistochemical studies of a hysterectomy specimen induced by a very painful pelvic mass in a 50-year-old patient with no previous history of the disease. It was classified as Ann Arbor IV Bb after imaging, given the medullary infiltration and signs of clinical and biological evolutivity: the patient had received two courses of chemotherapy, CHOP protocol. She died 23 days after the second treatment due to a hypertensive crisis.展开更多
Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no prop...Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.展开更多
To improve the accuracy of predicting non-invasive blood glucose concentration in the near-infrared spectrum, we utilized the Particle Swarm Optimization (PSO) algorithm to optimize hyperparameters for the Multi-Kerne...To improve the accuracy of predicting non-invasive blood glucose concentration in the near-infrared spectrum, we utilized the Particle Swarm Optimization (PSO) algorithm to optimize hyperparameters for the Multi-Kernel Learning Support Vector Machine (MKL-SVR). With these optimized hyperparameters, we established a non-invasive blood glucose regression model, referred to as the PSO-MKL-SVR model. Subsequently, we conducted a comparative analysis between the PSO-MKL-SVR model and the PSO-SVR model. In a dataset comprising ten volunteers, the PSO-MKL-SVR model exhibited significant precision improvements, including a 16.03% reduction in Mean Square Error and a 0.29% increase in the Squared Correlation Coefficient. Moreover, there was a 0.14% higher probability of the Clark’s Error Grid Analysis falling within Zone A. Additionally, the PSO-MKL-SVR model demonstrated a faster operational speed compared to the PSO-SVR model.展开更多
Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients i...Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.展开更多
Non-communicable diseases (NCDs) are a significant global health challenge, contributing to 50% of worldwide morbidity and 63% of mortality. The burden is particularly substantial in low—and middle-income countries (...Non-communicable diseases (NCDs) are a significant global health challenge, contributing to 50% of worldwide morbidity and 63% of mortality. The burden is particularly substantial in low—and middle-income countries (LMICs), where 80% of NCD-related deaths occur. A quasi-experimental study addressed this challenge from May 2022 to March 2023. This study utilized a non-equivalent pre-and post-test design, with 300 participants in the quantitative and 70 in the qualitative. The study employed multistage cluster and random sampling to select ten community units, resulting in 150 community health volunteers (CHVs) in the control unit and 150 in the intervention group. Data collection was facilitated through the KOBO app. Qualitative data analysis involved six homogeneous focus group discussions (FGDs) and ten key informant interviews (KIIs), audio-recorded, transcribed, and analyzed using N-Vivo 12. Despite efforts to implement screening programs and improve linkages to care, significant barriers persist. This article reviews these barriers, drawing on current literature and empirical evidence. Key obstacles identified include limited awareness, inadequate healthcare infrastructure, cultural beliefs, financial constraints, fragmented healthcare systems, and challenges linking individuals to appropriate care services. The article explores strategies to overcome these barriers, emphasizing the importance of collaborative approaches involving stakeholders at various levels. Addressing these challenges aims to strengthen NCD screening and linkages to care, ultimately improving health outcomes for populations globally. Several recommendations emerge from the study’s findings and literature review. Raising awareness about NCDs and preventive measures is crucial and can be achieved through targeted health education campaigns and community outreach programs. Addressing healthcare infrastructure deficiencies, such as inadequate facilities and workforce shortages, is essential to ensure access to quality care. Cultural beliefs and practices also play a significant role in shaping health-seeking behavior. Engaging with local communities and incorporating cultural sensitivity into healthcare delivery can help bridge the gap between traditional beliefs and modern healthcare practices. Financial constraints pose a significant barrier to healthcare services, particularly in LMICs. Innovative financing mechanisms, such as health insurance schemes or subsidies, can help alleviate this burden and improve access to care. Furthermore, the fragmented nature of healthcare systems can hinder effective NCD management. Enhancing coordination and integration between primary care providers, specialists, and community health workers is essential to ensure seamless care delivery and patient follow-up. Finally, strengthening linkages between screening programs and care services is critical for the timely diagnosis and management of NCDs. This requires establishing robust referral systems and ensuring continuity of care for patients throughout their healthcare journey. In conclusion, addressing the multifaceted barriers to NCD screening and care linkage is essential for improving health outcomes globally. By implementing targeted interventions and fostering collaboration among stakeholders, progress can be made towards reducing the burden of NCDs and promoting population health.展开更多
Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July...Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.展开更多
This research considered the effect of non-natural aging on the microstructural characteristics and mechanical properties of as-cast aluminum 6063 alloys. The samples were developed through a sand casting process and ...This research considered the effect of non-natural aging on the microstructural characteristics and mechanical properties of as-cast aluminum 6063 alloys. The samples were developed through a sand casting process and machined into tensile and impact test samples before carrying out solution heat treatment at 550?C (0.83 T<sub>m</sub>) on two parts of the samples while retaining one part as the control. The two parts were further divided into sets denoted A and B and were aged at 180?C (0.27 T<sub>m</sub>) and 160?C (0.24 T<sub>m</sub>), respectively, for 12 hours. The results showed that sample A has the optimal yield strength and ultimate tensile strength of 192 and 206 MPa, respectively. Likewise, the sample gave the highest impact strength value of about 9.63 J/mm<sup>2</sup>. The observed results were supported by the optical micrograph, which revealed that the sample has evenly dispersed precipitates in its microstructure. This is deemed responsible for the observed increase in strength of the sample.展开更多
The ultrasound pressure-strain loop (PSL) technique is a non-invasive method of examining myocardial work, which takes into account the effect of cardiac afterload on deformation and combines the overall longitudinal ...The ultrasound pressure-strain loop (PSL) technique is a non-invasive method of examining myocardial work, which takes into account the effect of cardiac afterload on deformation and combines the overall longitudinal strain force of the left ventricle with the changes in the left ventricular pressure, allowing earlier detection of possible subclinical cardiac damage in patients, and a more accurate and non-invasive assessment of the patient’s myocardial work performance. In this article, we will discuss the progress of PSL applications in cardiovascular diseases.展开更多
Hanoi’s rapid urbanization has led to a surge in private vehicle ownership, particularly motorcycles, amidst inadequate public transportation infrastructure. Despite government efforts, many still prefer motorized tr...Hanoi’s rapid urbanization has led to a surge in private vehicle ownership, particularly motorcycles, amidst inadequate public transportation infrastructure. Despite government efforts, many still prefer motorized transport, citing mobility and safety concerns, exacerbated by insufficient pedestrian infrastructure. This study examines the motivations behind this reliance on motorized vehicles, particularly motorcycles, in Hanoi. Findings reveal safety and convenience as primary factors driving motorized transport use, especially for accessing bus stations. Economic incentives could promote non-motorized travel and public transport adoption. Policy implications highlight the importance of addressing economic factors and improving access infrastructure to manage motorized vehicle reliance and foster sustainable urban mobility in Hanoi.展开更多
基金the National Natural Science Foundation of China,No.82070869 and 82270914.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。
基金supported by the National Key R&D Program of China(2019YFA0904900)the National Natural Science Foundation of China(21877112,21837002,21721004)。
文摘Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.
基金supported by the National Natural Science Foundation of China(22172090,21790051)the National Key Research and Development Project of China(2022YFA1204500,2022YFA1204501)+2 种基金the Natural Science Foundation of Shan-dong Province(ZR2021MB015)the Open Funds of the State Key Laboratory of Electroanalytical Chemistry(SKLEAC202202)the Young Scholars Program of Shandong University。
文摘Tuning the coordination atoms of central metal is an effective means to improve the electrocatalytic activity of atomic catalysts.Herein,iridium(Ir) is proposed to be asymmetrically anchored by sp-N and pyridinic N of hydrogen-substituted graphdiyne(HsGDY),and coordinated with OH as an Ir atomic catalyst(Ir_(1)-N-HsGDY).The electron structures,especially the d-band center of Ir atom,are optimized by these specific coordination atoms.Thus,the as-synthesized Ir_(1)-N-HsGDY exhibits excellent electrocatalytic performances for oxygen reduction and hydrogen evolution reactions in both acidic and alkaline media.Benefiting from the unique structure of HsGDY,IrN_(2)(OH)_(3) has been developed and demonstrated to act as the active site in these electrochemical reactions.All those indicate the fresh role of the sp-N in graphdiyne in producing a new anchor way and contributing to promote the electrocatalytic activity,showing a new strategy to design novel electrochemical catalysts.
基金supported by the National Natural Science Foundation of China(21571038,22035004)the Education Department of Guizhou Province(2021312)+2 种基金the Foundation of Guizhou Province(2019-5666)the National Key R&D Program of China(2017YFA0700101)the State Key Laboratory of Physical Chemistry of Solid Surfaces(Xiamen University,202009)。
文摘Surface/interface engineering of a multimetallic nanostructure with diverse electrocatalytic properties for direct liquid fuel cells is desirable yet challenging.Herein,using visible light,a class of quaternary Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)ultrathin nanosheets is fabricated and used as high-performance anode electrocatalysts for formic acid-/alcohol-air fuel cells.The modified electronic structure of Pt,enhanced hydroxyl adsorption,and abundant exterior defects afford Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C high intrinsic anodic electrocatalytic activity to boost the power densities of direct formic acid-/methanol-/ethanol-/ethylene glycol-/glycerol-air fuel cells,and the corresponding peak power density of Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C is respectively 129.7,142.3,105.4,124.3,and 128.0 mW cm^(-2),considerably outperforming Pt/C.Operando in situ Fourier transform infrared reflection spectroscopy reveals that formic acid oxidation on Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C occurs via a CO_(2)-free direct pathway.Density functional theory calculations show that the presence of Ag,Bi,and Te in Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)suppresses CO^(*)formation while optimizing dehydrogenation steps and synergistic effect and modified Pt effectively enhance H_(2)O dissociation to improve electrocatalytic performance.This synthesis strategy can be extended to 43 other types of ultrathin multimetallic nanosheets(from ternary to octonary nanosheets),and efficiently capture precious metals(i.e.,Pd,Pt,Rh,Ru,Au,and Ag)from different water sources.
基金This work is financially supported by National Natural Science Foundation of China(52174283 and 52274308)Innovation Fund Project for Graduate Student of China University of Petroleum(East China)(22CX04023A)the Fundamental Research Funds for the Central Universities。
文摘The formation of multiple oxygen intermediates supporting efficient oxygen evolution reaction(OER)are affinitive with hydroxyl adsorption.However,ability of the catalyst to capture hydroxyl and maintain the continuous supply at active sits remains a tremendous challenge.Herein,an affordable Ni2P/FeP2 heterostructure is presented to form the internal polarization field(IPF),arising hydroxyl spillover(HOSo)during OER.Facilitated by IPF,the oriented HOSo from FeP2 to Ni2P can activate the Ni site with a new hydroxyl transmission channel and build the optimized reaction path of oxygen intermediates for lower adsorption energy,boosting the OER activity(242 mV vs.RHE at 100 mA cm-2)for least 100 h.More interestingly,for the anion exchange membrane water electrolyzer(AEMWE)with low concentration electrolyte,the advantage of HOSo effect is significantly amplified,delivering 1 A cm^(-2)at a low cell voltage of 1.88 V with excellent stability for over 50 h.
基金supported by the National SKA Program of China No.2020SKA0120200the National Key Program for Science and Technology Research and Development No.2022YFC2205201+2 种基金the National Natural Science Foundation of China(NSFC,grant Nos.12288102,12041303,and 12041304)the Major Science and Technology Program of Xinjiang Uygur Autonomous Region No.2022A03013-2the open program of the Key Laboratory of Xinjiang Uygur Autonomous Region No.2020D04049。
文摘We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar sample.Emission from a pulsar is identified as non-nulling if(i)the emission does not cease across the whole pulse profile,and(ii)the emission is detectable.For(i),we adopt a model for switching in the plasma charge density,and emission persists if the charge density is non-zero.For(ii),we assume that detectable emission originates from source points where it is emitted tangentially to the magnetic field-line and parallel to the line-of-sight.We find that pulsars exhibiting non-nulling emission possess obliquity angles with an average of 42°.5,and almost half the samples maintain a duty cycle between 0.05 and 0.2.Furthermore,the pulsar population is not fixed but dependent on the obliquity angle,with the population peaking at 20°.In addition,three evolutionary phases are identified in the pulsar population as the obliquity angle evolves,with the majority of samples having an obliquity angle between 20°and 65°.Our results also suggest that emission from a pulsar may evolve between nulling and non-nulling during its lifetime.
文摘One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.
文摘Introduction: Vaccination plays a pivotal role in mitigating the repercussions of the COVID-19 pandemic. However, vaccination campaigns encounter obstacles, especially in developing countries like the Democratic Republic of the Congo (DRC). This study aimed at investigating the roles of vaccine hesitancy, refusal, and access barriers, while identifying individual-level factors associated with non-vaccination in Mbujimayi, DRC. Methods: A community-based cross-sectional survey was conducted in three health districts and included 1496 residents. Attitudes and behaviors related to seeking COVID-19 vaccination were assessed using a standardized questionnaire. Hierarchical logistic regression modeling was used to assess factors potentially affecting non-compliance with vaccination. Results: Among participants (median age = 33, IQR = 23.3, M/F sex ratio = 0.7), 60% displayed misconceptions about COVID-19 or its vaccine, while only 35.2% perceived COVID-19 as a significant health threat. Vaccination coverage was estimated at 49.1% (95% CI: 47.5;52.6), with 71.8% of vaccinated individuals having received one dose. Among the unvaccinated individuals, 50.9% expressed no intention to be vaccinated in the future, citing hesitation (30.4%) or refusal (39.6%) mainly due to side effects or distrust of vaccines. Conversely, 32.7% of the unvaccinated persons expressed access barriers despite willingness to be vaccinated. Misconceptions about COVID-19 and its vaccines were the main drivers of vaccination non-compliance. Conclusion: These findings demonstrate significant vaccine non-compliance driven by hesitancy, refusal, and access barriers. Strategies to enhance vaccination coverage and pandemic preparedness should address misconceptions, sociodemographic barriers, and geographic disparities.
文摘Non-communicable diseases (NCDs) account for 63% of mortalities. Approximately 80% of these NCD-related deaths occur in LMICs. A quasi-experimental study utilizing a non-equivalent pre-and post-test was conducted from May 2022 to March 2023 with 370 study participants. Multistage cluster and random sampling were used to select ten community units, and therefore, 150 CHVs were chosen for the control unit, and 150 were used to form the interventional group. Data was collected from the KOBO app. Six (6) homogenous FGDs comprised ten members, and 10 KII were conducted across study sites. Quantitative data was analyzed using SPSS version 28.0, and qualitative data was audio-recorded, transcribed, and analyzed via N-Vivo 12. The study shows that 59.3% of respondents have minimal information, and 92.7% (n = 139) have no clear understanding of NCDs, with a pre-intervention capacity of 48.8%. Independent sample t-test showed a significant difference in capacity from a pre-intervention average of 48.75 (SD ± 5.7)%, which increased to 68.28 (SD ± 7.6)%, p < 0.001. A well-designed community interventional model plays a pivotal role in grassroots healthcare delivery but requires optimization for NCD management.
文摘Malignant non-Hodgkins lymphoma (MHNL) of the uterus is uncommon. We report a case diagnosed on the basis of histologic and immunohistochemical studies of a hysterectomy specimen induced by a very painful pelvic mass in a 50-year-old patient with no previous history of the disease. It was classified as Ann Arbor IV Bb after imaging, given the medullary infiltration and signs of clinical and biological evolutivity: the patient had received two courses of chemotherapy, CHOP protocol. She died 23 days after the second treatment due to a hypertensive crisis.
文摘Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.
文摘To improve the accuracy of predicting non-invasive blood glucose concentration in the near-infrared spectrum, we utilized the Particle Swarm Optimization (PSO) algorithm to optimize hyperparameters for the Multi-Kernel Learning Support Vector Machine (MKL-SVR). With these optimized hyperparameters, we established a non-invasive blood glucose regression model, referred to as the PSO-MKL-SVR model. Subsequently, we conducted a comparative analysis between the PSO-MKL-SVR model and the PSO-SVR model. In a dataset comprising ten volunteers, the PSO-MKL-SVR model exhibited significant precision improvements, including a 16.03% reduction in Mean Square Error and a 0.29% increase in the Squared Correlation Coefficient. Moreover, there was a 0.14% higher probability of the Clark’s Error Grid Analysis falling within Zone A. Additionally, the PSO-MKL-SVR model demonstrated a faster operational speed compared to the PSO-SVR model.
文摘Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.
文摘Non-communicable diseases (NCDs) are a significant global health challenge, contributing to 50% of worldwide morbidity and 63% of mortality. The burden is particularly substantial in low—and middle-income countries (LMICs), where 80% of NCD-related deaths occur. A quasi-experimental study addressed this challenge from May 2022 to March 2023. This study utilized a non-equivalent pre-and post-test design, with 300 participants in the quantitative and 70 in the qualitative. The study employed multistage cluster and random sampling to select ten community units, resulting in 150 community health volunteers (CHVs) in the control unit and 150 in the intervention group. Data collection was facilitated through the KOBO app. Qualitative data analysis involved six homogeneous focus group discussions (FGDs) and ten key informant interviews (KIIs), audio-recorded, transcribed, and analyzed using N-Vivo 12. Despite efforts to implement screening programs and improve linkages to care, significant barriers persist. This article reviews these barriers, drawing on current literature and empirical evidence. Key obstacles identified include limited awareness, inadequate healthcare infrastructure, cultural beliefs, financial constraints, fragmented healthcare systems, and challenges linking individuals to appropriate care services. The article explores strategies to overcome these barriers, emphasizing the importance of collaborative approaches involving stakeholders at various levels. Addressing these challenges aims to strengthen NCD screening and linkages to care, ultimately improving health outcomes for populations globally. Several recommendations emerge from the study’s findings and literature review. Raising awareness about NCDs and preventive measures is crucial and can be achieved through targeted health education campaigns and community outreach programs. Addressing healthcare infrastructure deficiencies, such as inadequate facilities and workforce shortages, is essential to ensure access to quality care. Cultural beliefs and practices also play a significant role in shaping health-seeking behavior. Engaging with local communities and incorporating cultural sensitivity into healthcare delivery can help bridge the gap between traditional beliefs and modern healthcare practices. Financial constraints pose a significant barrier to healthcare services, particularly in LMICs. Innovative financing mechanisms, such as health insurance schemes or subsidies, can help alleviate this burden and improve access to care. Furthermore, the fragmented nature of healthcare systems can hinder effective NCD management. Enhancing coordination and integration between primary care providers, specialists, and community health workers is essential to ensure seamless care delivery and patient follow-up. Finally, strengthening linkages between screening programs and care services is critical for the timely diagnosis and management of NCDs. This requires establishing robust referral systems and ensuring continuity of care for patients throughout their healthcare journey. In conclusion, addressing the multifaceted barriers to NCD screening and care linkage is essential for improving health outcomes globally. By implementing targeted interventions and fostering collaboration among stakeholders, progress can be made towards reducing the burden of NCDs and promoting population health.
文摘Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.
文摘This research considered the effect of non-natural aging on the microstructural characteristics and mechanical properties of as-cast aluminum 6063 alloys. The samples were developed through a sand casting process and machined into tensile and impact test samples before carrying out solution heat treatment at 550?C (0.83 T<sub>m</sub>) on two parts of the samples while retaining one part as the control. The two parts were further divided into sets denoted A and B and were aged at 180?C (0.27 T<sub>m</sub>) and 160?C (0.24 T<sub>m</sub>), respectively, for 12 hours. The results showed that sample A has the optimal yield strength and ultimate tensile strength of 192 and 206 MPa, respectively. Likewise, the sample gave the highest impact strength value of about 9.63 J/mm<sup>2</sup>. The observed results were supported by the optical micrograph, which revealed that the sample has evenly dispersed precipitates in its microstructure. This is deemed responsible for the observed increase in strength of the sample.
文摘The ultrasound pressure-strain loop (PSL) technique is a non-invasive method of examining myocardial work, which takes into account the effect of cardiac afterload on deformation and combines the overall longitudinal strain force of the left ventricle with the changes in the left ventricular pressure, allowing earlier detection of possible subclinical cardiac damage in patients, and a more accurate and non-invasive assessment of the patient’s myocardial work performance. In this article, we will discuss the progress of PSL applications in cardiovascular diseases.
文摘Hanoi’s rapid urbanization has led to a surge in private vehicle ownership, particularly motorcycles, amidst inadequate public transportation infrastructure. Despite government efforts, many still prefer motorized transport, citing mobility and safety concerns, exacerbated by insufficient pedestrian infrastructure. This study examines the motivations behind this reliance on motorized vehicles, particularly motorcycles, in Hanoi. Findings reveal safety and convenience as primary factors driving motorized transport use, especially for accessing bus stations. Economic incentives could promote non-motorized travel and public transport adoption. Policy implications highlight the importance of addressing economic factors and improving access infrastructure to manage motorized vehicle reliance and foster sustainable urban mobility in Hanoi.