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Objective To analyze the reasons of late HIV diagnosis in Chengdu, and to provide scientific basis for promoting early detection. Methods A cross - sectional survey was used, and the questionnaires were conducted among HIV/AIDS cases in 9 districts in Chengdu. The socio - demographic data, AIDS knowledge awareness, health seeking habits, testing behavior and other information were collected. The chi - square test and binary Logistic regression model were used to analyze the influencing factors. In - depth interviews were conducted, and the sample size was determined according to the principle of "information saturation". Results A total of 757 HIV/AIDS cases were investigated, of which 258 (34. 1% ) were found late diagnosis. Multivariate Logistic regression analysis showed that the risk of late diagnosis was higher in age group 30 - 49 years old ( aOR = 3. 350, 95% CI: 1.725 -6.506) and "50 years old ( aOR = 3. 913, 95% CI: 1. 876 -8. 161) than 18 -29 years old. Passive detection ( aOR =2. 002, 95% CI: 1. 098 -3. 649) had a higher risk of late diagnosis than active detection. High school education or higher (aOR =0.472, 95% CI: 0.289 -0.770) had a lower risk of late diagnosis than middle school education or lower. Among the 258 late diagnosis cases, 218 (84. 5% ) never had the idea of HIV testing in the past, mainly because they had not heard of AIDS ( 106 cases/48. 6% ) and felt that AIDS was far away from them ( 82 cases/357. 6% ) . Among the 40 cases who had ever considering taking an HIV test, 17 (42.5%) did not take, mainly because they were worried about their privacy being exposed ( 12 casesZ70. 6% ), worried about what others think during the test process ( 7 cases/41. 2% ), and worried about being discriminated against if they tested positive (7 cases/41. 2% ). In - depth interviews were conducted on 16 patients with late diagnosis. The reasons for late diagnosis mainly included $ never heard of AIDS, serious misunderstanding of AIDS cognition, lack of risk perception awareness, and fluke mentality. Conclusion In order to effectively reduce the level of late HIV diagnosis, it is necessary to promote high - quality AIDS health education, improve the awareness of AIDS knowledge and risk perception after high risk behaviors, and encourage people with high risk behaviors to take the initiative to receive HIV testing as soon as possible. Building a supportive social environment to avoid giving up active testing for fear of discrimination is also essential. [ABSTRACT FROM AUTHOR]

The prevalence of AIDS and mortality rates among HIV-infected individuals in Guangxi remain relatively high, potentially due to impaired CD4 + cell recovery. This study aims to identify factors hindering CD4 + cell recovery in people living with HIV. We conducted a retrospective study on people living with HIV in Guangxi, China, with data collection extending to the end of 2023. CD4 + T cells were categorized into "immunological responders" and "non-responders" based on CD4 + cell recovery after treatment. Multivariate logistic regression was used to analyze factors associated with the development of immunological non-responders. Recovery of CD4 + T lymphocytes was assessed using the Generalized Additive Mixed Model (GAMM) and Generalized Estimating Equations (GEE). Additionally, multivariate Cox regression identified factors influencing survival rates. Our findings indicated a 52.44% incidence of immunological non-responders after two years of treatment. Factors such as age, sex, education, occupation, infection route, pre-treatment CD4 + T cell count, HIV subtype, and treatment regimen were linked to immunological non-response. Specifically, male gender, education up to high school, farming occupation, heterosexual transmission, CRF01_AE subtype, pre-treatment CD4 + T cell count < 200/µL, and the 3TC + EFV + TDF regimen were identified as significant risk factors. Statistically significant differences in CD4 + T lymphocyte recovery rates were observed among different HIV subtypes (P < 0.05). Beyond age, sex, ethnicity, occupation, subtype, and treatment regimen, being an immunological non-responder was found to be a risk factor for both mortality and accelerated disease progression. The study highlights the complexity of factors affecting CD4 + cell recovery post-HIV treatment in Guangxi and underscores the need for vigilant clinical monitoring of people living with HIV, particularly those with low pre-treatment CD4 + T cell levels. [ABSTRACT FROM AUTHOR]

Background Cognitive impairment constitutes a prevailing issue in the schizophrenia spectrum, severely impacting patients' functional outcomes. A global cognitive score, sensitive to the stages of the spectrum, would benefit the exploration of potential factors involved in the cognitive decline. Methods First, we performed principal component analysis on cognitive scores from 768 individuals across the schizophrenia spectrum, including first-degree relatives of patients, individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophrenia patients, alongside 124 healthy controls. The analysis provided 10 g-factors as global cognitive scores, validated through correlations with intelligence quotient and assessed for their sensitivity to the stages on the spectrum using analyses of variance. Second, using the g-factors, we explored potential mechanisms underlying cognitive impairment in the schizophrenia spectrum using correlations with sociodemographic, clinical, and developmental data, and linear regressions with genotypic data, pooled through meta-analyses. Results The g-factors were highly correlated with intelligence quotient and with each other, confirming their validity. They presented significant differences between subgroups along the schizophrenia spectrum. They were positively correlated with educational attainment and the polygenic risk score (PRS) for cognitive performance, and negatively correlated with general psychopathology of schizophrenia, neurodevelopmental load, and the PRS for schizophrenia. Conclusions The g-factors appeared as valid estimators of global cognition, enabling discerning cognitive states within the schizophrenia spectrum. Educational attainment and genetics related to cognitive performance may have a positive influence on cognitive functioning, while general psychopathology of schizophrenia, neurodevelopmental load, and genetic liability to schizophrenia may have an adverse impact. [ABSTRACT FROM AUTHOR]

Diabetic wounds have become a global healthcare burden owing to impaired angiogenesis and persistent infections. Extracellular vesicles (EVs) can improve diabetic wounds, though their targeting ability is limited. In this study, we investigated the performance of a novel hydrogel dressing comprised of gelatin methacryloyl, glycoengineered EVs, and polylysine in treating infected diabetic wounds. High‐throughput single‐cell RNA sequencing (scRNA‐seq) and immunofluorescence staining revealed that E‐selectin (SELE) levels were higher in diabetic wounds than in non‐diabetic wounds. Mesenchymal stromal cells (MSCs) were transfected with a lentivirus containing fucosyltransferase VII (FUT7) and a CD63‐P19‐Nluc vector to enhance the expression of sialyl Lewis X (sLeX), the ligand of E‐selectin, on the surface of EVs (s‐EVs) derived from transfected MSCs (s‐MSCs). s‐EVs can target human umbilical vein endothelial cells (HUVECs) under lipopolysaccharide stimulation and promote the function of stimulated HUVECs in vitro. To promote and sustain the release of s‐EVs, we fabricated a gelatin methacryloyl (Gel)/poly‐L‐lysine methacryloyl (PL)‐5 hydrogel with good antibacterial ability, biocompatibility and mechanical properties. In a mouse experiment, s‐EV@Gel/PL‐5 exhibited excellent angiogenesis and anti‐inflammatory abilities and further promoted the healing of infected diabetic wounds. Our findings demonstrated the potential of the s‐EV@Gel/PL‐5 hydrogel in the clinical treatment of diabetic infectious wounds. [ABSTRACT FROM AUTHOR]

Accurate estimation of nitrogen dioxide (NO2) levels at high spatio‐temporal resolution is crucial for atmospheric research and public health assessments. This study introduces a novel machine learning (ML) framework enhanced with uncertainty quantification (UQ) to predict hourly NO2 concentrations over East Asia. Benefiting from tropospheric NO2 columns from the Geostationary Environment Monitoring Spectrometer (GEMS), along with land use, meteorological, and topographic data, our model demonstrates robust and reliable performance, evidenced by an R2 of 0.84 and RMSE of 2.93 ppb through cross‐validation. Unlike traditional ML regressions tasks, our framework not only provides a single NO2 estimate but also diagnoses data and model uncertainties for each pixel. Higher uncertainties are observed in regions with complex terrain and sparse monitoring. Hourly and Intra‐annual variations in concentration predictions and associated uncertainties are both significant. The explicit UQ informs decision‐making and highlights the need for cautious interpretation in atmospheric data‐driven predictions. Plain Language Summary: Our study aims to improve understanding of near‐surface nitrogen dioxide (NO2) levels, crucial for accessing health risks. Machine learning (ML) has emerged as a powerful tool in converting satellite‐derived NO2 columns to near‐surface concentrations. However, previous estimates were based on polar‐orbiting satellites, which yield only a single daily result. In contrast, we use data products from the Geostationary Environment Monitoring Spectrometer (GEMS), the first sensor providing continuous monitoring over Asia with hourly updates on NO2 columns during daylight. Importantly, while these ML models proficiently predict NO2 levels at the stations, they tend to lack a comprehensive uncertainty assessment, leading to potential overreliance on their spatial performance. Our work developed a way to not only capture hourly variations of near‐surface NO2 concentrations but also to quantify the certainty about these estimates across the entire space. This enhances air quality decision‐making and underscores the need for careful environmental prediction analysis. Key Points: Quantify data and model uncertainties in machine learning, revealing data surpasses model—critical for accurate assessmentsDerive hourly NO2 concentrations from GEMS NO2 columns, refining spatial‐temporal resolutionInform site construction decisions, cautioning against overestimating machine learning's spatial generalization capabilities [ABSTRACT FROM AUTHOR]

Objectives To assess the profiles and determinants of drug resistance in HIV-1-infected individuals undergoing ART in Guangxi. Methods Samples and data were collected from HIV-1-infected individuals experiencing virological failure post-ART from 14 cities in Guangxi. Sequencing of the HIV-1 pol gene was conducted, followed by analysis for drug resistance mutations using the Stanford University HIV Drug Resistance Database. Logistic regression was employed to identify potential risk factors associated with both HIV drug resistance and mortality. Results A total of 8963 individuals with pol sequences were included in this study. The overall prevalence of HIV-1 drug resistance (HIVDR) was 42.43% (3808/8963), showing a decrease from 59.62% to 41.40% from 2016 to 2023. Factors such as being aged ≥50 years, male, Han nationality, lower education levels, occupations including workers, peasants and children, AIDS, pre-treatment CD4 T cell counts <200 cells/mm3, infection with CRF01_AE and CRF55_01B subtypes, and ART regimen lamivudine/zidovudine/nevirapine were associated with higher susceptibility to HIVDR. The common mutations were M184V (17.38%) and K103N (22.14%). Additionally, the prevalence of M184V, S68G, M41L and G190A were different between the Han and Zhuang populations. Factors including age, gender, ethnicity, education level, occupation, infectious route, clinical stage, viral load, subtype, ART regimen and HIVDR showed significant associations with mortality. Conclusions The factors contributing to drug resistance in the HIV-1 ART individuals in Guangxi appear to be notably intricate. Continuous reinforcement of drug resistance surveillance is imperative, accompanied by the optimization of ART regimens to mitigate virological failures effectively. [ABSTRACT FROM AUTHOR]

When the ultra-high-speed elevator car-counterweight system runs opposite each other, significant piston effects are caused, seriously affecting the elevator operation's stability. In order to explore the aerodynamic characteristics of the whole operation process of a car-counterweight system under multi-parameters, this study first establishes a three-dimensional transient model of the car-counterweight system and a multi-region dynamic layering numerical simulation method based on this model is proposed. Then, the actual elevator experiment validates the correctness of the model and the method. Finally, the influence rules of key parameters on the car's aerodynamic characteristics and ventilation effect are analyzed, and the car's aerodynamic characteristics at intersection time are analyzed emphatically. The results show that with the increase in the blocking ratio, the pressure drag and viscous drag have similar change trends at each stage, but the influence of pressure drag is more significant. The air displacement ratio increases by 34.1%, 75.8%, and 117.3%, respectively. With the increase in the hoistway height, the air displacement ratio decreases by 0.9%, 2.4%, and 2.9%, respectively. The spacing significantly affects the car's aerodynamic characteristics at the intersection time. The drag peak increases by 6.8%, 13.6%, and 20.5% and the lift peak by 21.2%, 47.8%, and 82.5%, respectively. [ABSTRACT FROM AUTHOR]

Due to the non-streamlined blunt body shape of the elevator car, intense aerodynamic loads and noise are generated in the annular space when the elevator operates at high speed in a narrow hoistway. This article uses large-eddy simulation and Curle acoustic theory to establish a numerical model of the wellbore flow field under different guiding shapes of the elevator car. First, the mechanism of action between the flow guide shape, vortex characteristics, and aerodynamic load was studied, and the influence of operating speed on aerodynamic load under different flow guide shapes was analyzed. Second, the distribution and spectral characteristics of noise in the annular space under different flow guide shapes were studied from the near field and far field scales. Finally, it can be concluded that increasing the guide surface can significantly reduce the pressure difference between the upper and lower parts of the car, weakening the separation of the tail airflow. The number of guide surfaces, installation position, and vertex offset significantly impact drag and lateral force, with the optimal reduction of 34.65% and 57.6%, respectively. The maximum sound source intensity of near-field noise is mainly concentrated at the arc transition in the upper part of the annular space, and the frequency is mainly concentrated in the range of 500–1000 Hz. The sound pressure level is linearly related to the logarithm of the longitudinal distance, and the noise attenuation speed becomes faster with the increase in the number of guiding surfaces. [ABSTRACT FROM AUTHOR]

Glomerulonephritis (GN) is the most common cause of end-stage renal failure worldwide; in most cases, it cannot be cured and can only delay the progression of the disease. At present, the main treatment methods include symptomatic therapy, immunosuppressive therapy, and renal replacement therapy. However, effective treatment of GN is hindered by issues such as steroid resistance, serious side effects, low bioavailability, and lack of precise targeting. With the widespread application of nanoparticles in medical treatment, novel methods have emerged for the treatment of kidney diseases. Targeted transportation of drugs, nucleic acids, and other substances to kidney tissues and even kidney cells through nanodrug delivery systems can reduce the systemic effects and adverse reactions of drugs and improve treatment effectiveness. The high specificity of nanoparticles enables them to bind to ion channels and block or enhance channel gating, thus improving inflammation. This review briefly introduces the characteristics of GN, describes the treatment status of GN, systematically summarizes the research achievements of nanoparticles in the treatment of primary GN, diabetic nephropathy and lupus nephritis, analyzes recent therapeutic developments, and outlines promising research directions, such as gas signaling molecule nanodrug delivery systems and ultrasmall nanoparticles. The current application of nanoparticles in GN is summarized to provide a reference for better treatment of GN in the future. [ABSTRACT FROM AUTHOR]

AbstractThe influence of pre-corrosion on the corrosion inhibition performance and corrosion inhibition mechanism of quinoline quaternary ammonium salt (QQAS) on Q235 carbon steel in 1 wt% HCl solution at 60 °C were investigated by weight loss experiment, molecular dynamics simulation. The results of IR vibrational spectra and NMR hydrogen spectra indicate the successful synthesis of QQAS. The results of weight loss experiments show that the corrosion inhibition performance of the synthesized QQAS increase with the increasing of the concentration under the condition of Q235 carbon steel with and without pre-corrosion. But the pre-corrosion obviously decreases the corrosion inhibition efficiency by 17.28% when the concentration is 50 mg·L−1. Analysis of thermodynamic parameters shows that the adsorption of QQAS on the steel surface is a spontaneous and exothermic process, which conforms to the Langmuir isothermal formula and is mainly based on chemical adsorption. The results of molecular dynamics simulation indicate that pre-corrosion changes the equilibrium adsorption conformations of QQAS molecules, and decreases the adsorption energies, and decreases the density of the film for the different oxidization extent of Q235 carbon steel. As a result, the corrosion inhibition performance of QQAS is decreased by the pre-corrosion. The results are in good agreement with the results of weight loss experiments. The corrosion inhibition performance of QQAS is the best when the number of QQAS molecules is 18. The corrosion inhibition mechanism is a single molecular layer adsorption mechanism. The results of this study can provide a reference for studying the corrosion inhibition performance and corrosion inhibition mechanism of corrosion inhibitors under the action of pre-corrosion. [ABSTRACT FROM AUTHOR]

The Guizhou Caohai Wetland plays a crucial role as a wintering site for migratory birds in the Yunnan–Guizhou Plateau and ranks among the largest wintering spots globally for black-necked cranes (Grus nigricollis). To better understand the factors influencing waterbird populations and ecosystem changes, we conducted a comprehensive analysis of historical waterbird population variations over a 30-year period spanning from 1992 to 2022. The current investigation revealed a downward trend in the abundance index curve of the total number of waterbirds during this observation period. Among the five waterbird guilds examined, dabbling ducks, diving ducks, and coots (Fulica atra) experienced declines in their populations, while wading birds and shorebirds saw an increase. Moreover, we observed a rise in species richness within the community over time, accompanied by smaller compositional changes. Additionally, the findings indicated positive growth trends in wintering endangered species such as black-necked cranes and common cranes (Grus grus) in Caohai. Furthermore, we observed an increase in the occurrence and persistence of rare species, such as Eurasian spoonbills (Platalea leucorodia), black-faced spoonbills (Platalea minor), and black storks (Ciconia nigra) wintering in Caohai. These occurrences suggest that the wetland environment provides favorable conditions for a diverse range of species. Despite the rise in species richness, these trends in the abundance and species composition of wintering waterbirds over the past thirty years are still of concern. This study serves as fundamental scientific support for waterbird conservation and the restoration of ecological wetlands in the Guizhou Caohai Wetland. [ABSTRACT FROM AUTHOR]

An azidobenziodoxole (BIN3)‐mediated tunable radical reaction system for selective chlorination and bromination of tertiary and secondary C(sp3)−H bonds of alkyl substrates using haloform as the halogen donor was developed. Reactions of various substrates with BIN3 under visible light irradiation without any photo or metal catalysts gave C−H chlorinated or brominated products. These reactions are selective, and compatible with many functional groups. Mechanistic studies suggest that haloform serves as the halogen atom donor and HN3 generated in situ from the reaction of BIN3 and water relays the radical chain reaction as the hydrogen atom donor. HN3 reacts with CHX2⋅ to form CH2X2 and N3⋅, which propagates a radical chain by abstracting a hydrogen atom of the alkane substrate. [ABSTRACT FROM AUTHOR]

SUMMARY: The potato's most devastating disease is late blight, which is caused by Phytophthora infestans. Whereas various resistance (R) genes are known, most are typically defeated by this fast‐evolving oomycete pathogen. However, the broad‐spectrum and durable R8 is a vital gene resource for potato resistance breeding. To support an educated deployment of R8, we embarked on a study on the corresponding avirulence gene Avr8. We overexpressed Avr8 by transient and stable transformation, and found that Avr8 promotes colonization of P. infestans in Nicotiana benthamiana and potato, respectively. A yeast‐two‐hybrid (Y2H) screen showed that AVR8 interacts with a desumoylating isopeptidase (StDeSI2) of potato. We overexpressed DeSI2 and found that DeSI2 positively regulates resistance to P. infestans, while silencing StDeSI2 downregulated the expression of a set of defense‐related genes. By using a specific proteasome inhibitor, we found that AVR8 destabilized StDeSI2 through the 26S proteasome and attenuated early PTI responses. Altogether, these results indicate that AVR8 manipulates desumoylation, which is a new strategy that adds to the plethora of mechanisms that Phytophthora exploits to modulate host immunity, and StDeSI2 provides a new target for durable resistance breeding against P. infestans in potato. Significance Statement: StDeSI2, identified as a key host target of AVR8 in potato, plays a positive role in regulating late blight resistance. The present research enriches our knowledge about a new strategy that P. infestans uses to control host defense, and StDeSI2 promises to provide a new target for potato breeding against late blight. [ABSTRACT FROM AUTHOR]

Ultra-high-speed elevators are affected by various factors during operation, resulting in complex airflow disturbances and significant piston effects. To explore the aerodynamic characteristics and ventilation effects of the car at different stages of operation under multiple parameters, this paper first establishes a multi-parameter numerical model for the elevator system and verifies the numerical model through elevator experiments, and then analyzed the general variation characteristics of the pneumatic load during the car's acceleration, constant speed, and deceleration phases. On this basis, the influence of blockage ratio, hoistway and car height, and operating acceleration on multiple types of aerodynamic loads and hoistway ventilation was studied, with a special analysis of the viscous drag and pressure drag of the car. The results show that increasing the blockage ratio significantly increases the ventilation of the hoistway, with an increase in 1 and 0.7 factors in the acceleration and constant velocity stages, respectively. In the deceleration stage, the drag changes the most, with an increase in 3.1 factors, which hinders the ventilation of the hoistway. Meanwhile, the average lateral lift increased by 0.6 factors and the fluctuation increased, exacerbating the lateral vibration of the car. Viscous drag and pressure drag exhibit similar trends at each stage, but pressure drag is much higher than viscous drag. The height of the hoistway has a significant impact on the total drag of the car by increasing the pressure drag. In contrast, car height has the most significant effect on lateral lift and viscous drag. [ABSTRACT FROM AUTHOR]

Background: A universal set of disability weights(DWs) is mainly based on the survey of North America, Australia and Europe, whereas the participants in Asia was limited. The debate hasn't yet settled whether a universal DW is desirable or useful.The focus of the debate is its representativenes-s.After all, the DWs come from people's subjective evaluation of pain, and they may vary according to cultural background.The differences of the DWs could have implications for the magnitude or ranking of disease burdens.The DWs of Anhui Province has not been completely presented.This paper aims to obtain the DWs suitable for the general population of Anhui Province of China, and attempts to explore the differences between different DWs by comparing the DWs with the similar-cultural background and the DWs with cross-cultural background. Methods: A web-based survey was conducted to estimate the DWs for 206 health states of Anhui province in 2020. Paired comparison (PC) data were analyzed and anchored by probit regression and fitting loess model. We compared the DWs in Anhui with other provinces in China and those in Global burden of disease (GBD) and Japan. Results: Compared with Anhui province, the proportion of health states which showed 2 times or more differences ranged from 1.94% (Henan) to 11.17% (Sichuan) in China and domestic provinces. It was 19.88% in Japan and 21.51% in GBD 2013 respectively. In Asian countries or regions, most of the health states with top 15 DWs belonged to the category of mental, behavioral, and substance use disorders. But in GBD, most were infectious diseases and cancer. The differences of DWs in neighboring provinces were smaller than other geographically distant provinces or countries. Conclusion: PC responses were largely consistent across very distinct settings,but the exceptions do need to be faced squarely.The differences of DWs among similar-cultural regions were smaller than cross-cultural regions. There is an urgent need for relevant gold standards. [ABSTRACT FROM AUTHOR]

Hydrogels are promising wound dressings due to their extracellular matrix-like properties and tunable structure-function characteristics. Besides the physical isolation effect, hydrogel dressings are highly expected to possess tissue-adhesive performance and antibacterial capacity, which are beneficial for their clinical translations. Herein, a guar gum (GG)-based nanocomposite hydrogel was fabricated by mixing methacrylated GG (GGMA), acrylic acid, acrylated 3-aminophenylboronic acid, mangiferin (MF)-loaded cetyltrimethyl ammonium chloride (CTAC) micelles (MF@CTAC) and radical initiator. This hydrogel exhibited stable and tunable mechanical property as well as excellent biocompatibility. Borate crosslinking and physical interactions of the hydrogel produced a certain degree of self-healing ability, good tissue adhesive and hemostatic capacity. MF endowed the hydrogel with good antioxidant ability and excellent synergistic antibacterial ability with CATC. In vivo experiments indicated that the hydrogel significantly accelerated wound healing with a narrower wound edge, thicker granulation tissue, maturer epidermis and dermis tissue, higher collagen deposition level, milder inflammatory response, and enhanced angiogenesis. The hydrogel without adding antibiotics and other exogenous active ingredients showed great application potential as a versatile wound dressing material. [ABSTRACT FROM AUTHOR]

Over the past decade, metabolomic research in livestock and poultry has gained considerable momentum; however, quail metabolomics still lags behind that of livestock species such as chickens, pigs, and cattle. Quails are important models due to their low-cost protein sources—both eggs and meat—and practical benefits such as minimal space requirements, high egg production, disease resistance, and rapid reproduction. Therefore, it is necessary to systematically understand the effects of various factors on quail metabolism to provide a theoretical basis for accurate feeding and breeding practices. In this study, liquid chromatography with tandem mass spectroscopy (LC-MS/MS)-based metabolomics was used to examine the effects of age, breed, and sex on the serum metabolic profile of quails. A total of 550 metabolites were identified. Relative to breed and sex, we found that age played a crucial role in influencing quail serum metabolites. At 20 days of age (D20), quails had high levels of serum thymidine and alpha-D-glucose, while at 70 days of age (D70), the lipids, including 3-isothujone, 15-deoxy-d-12,14-PGJ2, and 2-aminobut-2-enoate dominated the serum. Additionally, xanthine, hypoxanthine, diaminopimelic acid, and 2-deoxy-scyllo-inosose appeared to be specific metabolites of Japanese quail (JAPQ). Serum levels of N-acetylglutamic acid, hydroxypyruvic acid, carnosine, alloepipregnanolone, lumichrome, 6-hydroxynicotinate, and myristic acid were higher in D70 Hengyan white feather quails (HYWQ) than those in D70 JAPQ. Notably, this study also identified 2-hydroxy-2-ethylsuccinic acid and riboflavin as potential specific metabolites in female quails. Furthermore, integration analysis showed that amino acid biosynthesis and metabolism, as well as ABC transporters, were the key pathways distinguishing D20 from D70. Purine metabolism, pyrimidine metabolism, ABC transporters, and TCA cycle were the key pathways distinguishing HYWQ from JAPQ. Differences in energy metabolism and amino acid biosynthesis and metabolism were observed between males and females. These findings enhance our understanding of the dynamic changes in quail serum metabolites influenced by various factors and address the knowledge gap regarding serum metabolic changes at different stages in quails. [ABSTRACT FROM AUTHOR]

Hemp seed cake (HSC) (Cannabis sativa L.) is a high-quality plant-derived protein source rich in polyunsaturated fatty acid (PUFA). To assess the effects of HSC addition in diets on the growth and meat quality in broiler chicken, a total of 240 female three-yellow chickens (50 days of age) were randomly assigned to four groups and fed with varying levels of HSC (0% (HSC0), 5% (HSC5), 10% (HSC10), and 20% (HSC20)) for 9 weeks. As a result, the daily feed intake, weight gain and feed conversion efficiency were significantly increased in the HSC20 group. Moreover, the meat quality traits, including the meat colour, water-holding capacity, intramuscular fat content, and proportion of n-3 PUFA significantly improved, and the expression of lipid synthesis genes, were increased in the HSC20 group. Meanwhile, the development of immune organs and the anti-inflammatory capabilities were enhanced in the HSC20 group. In addition, the blood lipid of chicken was reduced by improving the lipid metabolism in the HSC20 group. Therefore, adding 20% HSC in the feed had a notable effect on the growth, antioxidant and immune capabilities, blood lipid metabolism, and meat performance of the female three-yellow chickens. These findings provide significant information for improving the production performance of broiler chickens through the effective utilization of HSC. [ABSTRACT FROM AUTHOR]

Plumage color is an important characteristic of chicken breeds, and molecular genetic research is significant for resource conservation and product quality control. Anyi tile-like gray chicken is a high-quality local chicken breed resource generated through long-term natural selection and artificial breeding in China. However, the molecular mechanisms underlying plumage color formation in Anyi tile-like gray chickens remain unclear. In this study, nontargeted liquid chromatography and tandem mass spectrometry (LC–MS/MS) was performed to identify serum metabolites associated with plumage color in 93 Anyi tile-like gray chickens, including 60 tile-like gray and 33 black chickens. Notably, 12 serum metabolites were significantly enriched in Anyi tile-like gray chickens, including deoxyuridine and inosine, which were the key biomarkers distinguishing tile-like gray chickens from black chickens. Additionally, nine serum metabolites were significantly enriched in black chickens. Moreover, we identified 225 significant SNPs (P < 9.71 × 10−8) on chromosomes 1, 2, 3, 4, 11, 15, and 21 that were associated with deoxyuridine, inosine, 3-hydroxybenzoic acid, and L-methionine S-oxide through metabolome genome-wide association studies (mGWAS). Importantly, chromosome 1 harbored a region, 172.79-kb, which was the most likely quantitative trait locus (QTL) interval. RNA sequencing (RNA-seq) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that SFMBT2 was the only differentially expressed gene in the QTL interval, and its expression was correlated with the abundance of specific serum metabolites. Conclusively, SFMBT2 -mediated changes in serum metabolites contribute to plumage color development in Anyi tile-like gray chicken. This study provides important insights into the interaction between serum metabolites and host genes, and offers a theoretical basis for the breeding of Anyi tile-like gray chickens. [ABSTRACT FROM AUTHOR]

Methyl tetrahydrofuran-2-carboxylate (MeTHFC) and its derivatives are widely used as raw materials and intermediates in chemical industries. An efficient and clean method for the synthesis of MeTHFC was proposed, which included the oxidative esterification of biomass-based furfural into methyl furoate and the selective hydrogenation of methyl furoate into MeTHFC. The hydrogenation of biomass-derived methyl furoate was investigated on Ni–SiO2 catalysts with the different Ni contents prepared by a deposition–precipitation method. The Ni–SiO2 catalyst with 50 wt% Ni loading displayed an excellent performance with a high conversion under mild reaction conditions. Moreover, this catalyst presented a slight decrease of conversion, probably due to the increasing Ni0 particle size and Ni leaching during 200 h time-on-stream. Characterization results revealed that the formation of Ni phyllosilicates was responsible for high Ni dispersion and specific surface area in the Ni–SiO2 catalysts, which facilitate their hydrogenation performance. [ABSTRACT FROM AUTHOR]

Background: CBT and its modifications are effective for depression, but its efficacy for preventing depressive relapse/recurrence remains unclear.Methods: A systematic review and meta-analysis was conducted scrutinizing the efficacy of CBT and its modifications for preventing depressive relapse/recurrence in randomized controlled trials. The retrieval database included PubMed, Web of Science, MEDLINE, and three major Chinese databases (CNKI, VIP, Wanfang), and the retrieval period was from January 1, 2009, to July 1, 2022. Data were analyzed by RevMan 5.4 and Stata 16.Results: A total of 28 randomized controlled trials with 3938 participants were included. The relapse/recurrence rates in CBT and its modifications and the control group were 31.6 % and 41.3 %, respectively; CBT and its modifications significantly reduced the risk of developing a new depressive episode (RR, 0.73, 95%CI, 0.64-0.83). Stratified by follow-up time, both CBT and its modifications significantly reduced the relapse/recurrence of depression at ≤12 months (RR, 0.61, 95%CI, 0.47-0.79) and > 12 months (RR, 0.74, 95%CI, 0.59-0.93) compared with other active treatments. The beneficial effects of CBT and its modifications alone in reducing depressive relapse/recurrence were equivalent to those of antidepressant medication alone (RR, 1.01, 95 % CI, 0.79-1.28). Meta-regression results showed that the intervention method (P = 0.005) was one of the sources of heterogeneity.Limitations: Further subgroup analysis is limited by the literature.Conclusion: CBT and its modifications are reliable interventions for preventing relapse/recurrence in patients with depression. Further research is needed to determine the specific conditions for CBT and its applications in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to evaluate morphological features of corneal flap/cap and the correlations with corneal higher-order aberrations (HOAs) changes after femtosecond laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE). Methods: This was a retrospective study. Pre- and postoperative (1 and 3 months) corneal HOAs were assessed with Pentacam HR. The corneal flap/cap thickness at 32 points (± 1.5 mm, ± 2 mm, ± 2.5 mm, and ± 3 mm from the corneal vertex on meridian 0°/45°/90°/135°) were measured using anterior segment optical coherence tomography at 3 months postoperatively. Morphological features of corneal flap/cap including predictability (P), uniformity (U), and symmetry (S) were calculated and used for correlation analysis with corneal HOAs changes. Results: Eighty-six eyes (44 patients) and ninety-six eyes (50 patients) were involved in FS-LASIK and SMILE groups, respectively. Significant thicker corneal flap/cap than the predicted was observed at each measuring point and meridian in both groups (difference > 2.225 μm, the within-subject standard deviation over 6-mm optical zone). There was no statistically significant difference in predictability of corneal flap/cap thickness, while U6 mm (P <.0001), U0 (P <.001), U45 (P =.002), U90 (P <.0001), U135 (P =.004), S6 mm (P <.0001), S0 (P <.001), and S90 (P <.0001) over 6 mm zone were less in SMILE than in FS-LASIK. The changes of corneal tHOAs, Z (3, − 1), Z (3, 1), and SA were significantly correlated with morphological features of corneal flap/cap. Conclusion: Both FS-LASIK and SMILE had good predictability in flap or cap thickness, while the uniformity and symmetry of SMILE cap were better than FS-LASIK flap. The quality of flap/cap was closely associated with the changes of corneal HOAs. [ABSTRACT FROM AUTHOR]

Background: Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood.Methods: Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms.Results: Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase.Conclusions: Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. [ABSTRACT FROM AUTHOR]

Background: Strawberries are an important economic fruit crop world-wide. In strawberry cultivation, continuous cropping (CC) can seriously threaten yield and quality. However, our understanding of the gene expression changes in response to CC and during subsequent defense processes is limited. In this study, we analyzed the impact of CC on the transcriptome of strawberry roots using RNA-Seq technology to elucidate the effect of CC and the subsequent molecular changes. Results: We found that CC significantly affects the growth of strawberry plants. The transcriptome analysis identified 136 differentially expressed genes (DEGs), including 49 up-regulated and 87 down-regulated DEGs. A Gene Ontology (GO) analysis indicated that the up-regulated DEGs were mainly assigned to defense-related GO terms, and most down-regulated DEGs were assigned to nutrient-related GO terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the responsive DEGs were classified in a large number of important biological pathways, such as phenylalanine metabolism, starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism and plant-pathogen interaction. We also found that four WRKY transcription factors and three peroxidase genes involved in plant defense pathways were up-regulated in the roots of strawberry plants subjected to CC. Conclusion: Several unigenes involved in plant defense processes, such as CNGCs, WRKY transcription factors, PR1, and peroxidase genes with highly variable expression levels between non-CC and CC treatments may be involved in the regulation of CC in strawberry. These results indicate that strawberry roots reallocate development resources to defense mechanisms in response to CC. This study will further deepen our understanding of the fundamental regulatory mechanisms of strawberry resource reallocation in response to CC. [ABSTRACT FROM AUTHOR]

Graphene-based elastomer composites with a segregated structure were prepared by electrostatic self-assembly. The morphology and microstructures of the composites were characterised by scanning electron microscope (SEM) and transmission electrical microscope (TEM). The segregated network leads to a low gas permeability coefficient for BIIR composites. With the incorporation as low as 0.4 wt-% GTA-GO, the helium permeability coefficient decreased about 63% when compared with that of neat BIIR. The tensile strength and percentage elongation increased with an increase in the GTA-GO content. This is attributed to the complete exfoliation, uniform dispersion and the segregated structure of GTA-GO in the BIIR matrix. These results demonstrate that such electrostatic self-assembly method between latex and sheet-fillers is an effective strategy to design and produce polymeric nanocomposites with good gas barrier properties. The results will effectively promote the application of barrier polymer in the production of protective clothing, gas storage devices and coatings. [ABSTRACT FROM AUTHOR]

Hydrogel dressings with multiple functions are ideal options for wound repair. This study developed hydrogel dressings by interpenetrating the physically crosslinked xanthan gum (XG)/carboxylated chitosan (CCS) network and the chemically crosslinked polyacrylamide (PAAm) network via a one-pot method. The XG-CCS/PAAm hydrogels were found to display tunable mechanical properties, due to the formation of strong network structure. The hydrogels exhibited the strongest tensile strength of 0.6 MPa at an XG/CCS ratio of 40/60, while the largest compressive strength of 4.5 MPa is achieved at an XG/CCS ratio of 60/40. Moreover, the hydrogel with an XG/CCS ratio of 60/40 exhibited desirable adhesion strength on porcine skin, which was 3.7 kPa. It also had a swelling ratio, as high as 1200 %. After loading with cephalexin, the XG-CCS/PAAm hydrogels can deliver the antibacterial drugs following a first-order kinetic. As a result, both E. coli and S. aureus can be completely inactivated by the cefalexin-loaded hydrogels after 12 h. Furthermore, the XG-CCS/PAAm hydrogels were found to exhibit excellent biocompatibility as well as effective wound healing ability, as proven by the in vitro and in vivo tests. In this regard, XG-CCS/PAAm hydrogels can act as promising multifunctional wound dressings. [ABSTRACT FROM AUTHOR]

Due to the nonlinear, underactuated, and strongly coupled characteristics of tower cranes, issues such as inaccurate load positioning and severe swinging are prone to occur during transportation, making the control problem extremely complex. To address these issues, this paper has designed a super-twisting robust sliding mode controller based on the nonlinear marine predator algorithm (NMPA) to ensure the accurate positioning of the desired location during the transportation process of the tower crane while reducing the oscillation of the load. First, a nonlinear dynamic model of a four-degree-of-freedom tower crane considering friction is constructed. Second, to address the difficulty of effectively controlling the underactuated tower crane system model due to its nonlinearity and strong coupling, the super-twisting algorithm is introduced, and a super-twisting sliding mode controller for anti-swing positioning during the crane transportation process is designed. Then, the parameters of the super-twisting sliding mode controller are optimized using the NMPA to suppress sliding mode chattering and quickly achieve the system’s steady state. Finally, the stability of the nonlinear tower crane system is analyzed using Lyapunov’s theory and LaSalle’s invariance principle to ensure the closed-loop stability of the error dynamics. The simulation results show that the proposed control method exhibits excellent load anti-sway performance and robustness. [ABSTRACT FROM AUTHOR]

The atmospheric 10–20-day quasi-biweekly mode (QBWM) significantly modulates the active–break spells of the South Asian monsoon. Current knowledge, however, is limited concerning the diversity of the QBWM in the Indian Ocean (IO). Based on extended empirical orthogonal function analysis, two dominant summer modes are constructed in the IO. The first mode (QBWM1) generally depicts IO basin-dependent variability, while the second mode (QBWM2) exhibits a close relationship with the northwestern Pacific. QBWM1 initiates in the equatorial western IO and propagates toward the eastern IO along the equator. Two Rossby wave cells evolve in the off-equatorial eastern IO when convection encounters the Maritime Continent, and subsequently the northern cell develops and moves westward in the South Asian monsoon region. In contrast, QBWM2 originates in the northwestern Pacific and passes westward across the South Asian monsoon region in the form of convectively coupled Rossby waves. The maintenance mechanism of the peculiar IO basin-dependent QBWM1 is understood in terms of moisture dynamics. Significant moisture anomalies are found to precondition convection initiation in the western IO and subsequent eastward movement along the equator. Afterward, two off-equatorial moisture centers are generated in the double Rossby wave cells along with convection dissipation in the eastern IO, and the moisture anomalies are delivered from the southern cell toward the convection initiation area in the western IO via a moisture conveyor belt without coupling with convection. Moisture budget analysis indicates that the horizontal moisture advection associated with QBWM1 is regulated by the mean clockwise circulation in the tropical IO. [ABSTRACT FROM AUTHOR]

Rapid industrialization and urbanization have caused frequent haze pollution episodes during winter in eastern China. Considering that the vertical profile of the aerosol properties changes significantly with altitude, investigating aerosol aloft information via satellite remote sensing is essential for studying regional transport, climate radiative effects, and air quality. Through a synergic approach between lidar, the AErosol RObotic NETwork sunphotometer observations, and WRF-Chem simulations, several transboundary aloft transport events of haze aerosols to Xuzhou, eastern China, are investigated in terms of source, type, and composition and the impact on optical properties. Upper-air aerosol layers are short-lived tiny particles that increase the total aerosol optical depth (AOD). The aloft aerosols not only play a critical role during the haze event, enhancing the scattering of aerosol particles significantly but also cause a rise in the AOD and the Ångström exponent (AE), which increases the proportion of fine particles, exacerbating the pollution level near the surface. Based on the model simulation results, our study highlights that the transported aloft aerosols lead to the rapid formation of secondary inorganic substances, such as secondary sulfates, nitrates, and ammonium salts, which strongly contribute to haze event formation. Moreover, the results provide evidence that the haze frequency events associated with polluted dust outbreaks were higher for 2014–2015 winter. A closer analysis shows that the advected dust layers over Xuzhou originated from Inner Mongolia and the Xinjiang Uygur Autonomous Region. The study of the occurrence frequency, height, thickness, and optical properties of aloft anthropogenic haze in China will further deepen our understanding and provide a strong basis to assess aerosol impact on transport and the Earth–atmosphere radiative balance. [ABSTRACT FROM AUTHOR]

Improving productivity to reduce the cost of biologics manufacturing and ensure that therapeutics can reach more patients remains a major challenge faced by the biopharmaceutical industry. Chinese hamster ovary (CHO) cell lines are commonly prepared for biomanufacturing by single cell cloning post-transfection and recovery, followed by lead clone screening, generation of a research cell bank (RCB), cell culture process development, and manufacturing of a master cell bank (MCB) to be used in early phase clinical manufacturing. In this study, it was found that an additional round of cloning and clone selection from an established monoclonal RCB or MCB (i.e., re-cloning) significantly improved titer for multiple late phase monoclonal antibody upstream processes. Quality attributes remained comparable between the processes using the parental clones and the re-clones. For two CHO cells expressing different antibodies, the re-clone performance was successfully scaled up at 500-L or at 2000-L bioreactor scales, demonstrating for the first time that the re-clone is suitable for late phase and commercial manufacturing processes for improvement of titer while maintaining comparable product quality to the early phase process. [ABSTRACT FROM AUTHOR]

Summary: Blue‐light (BL) phototropin receptors (phot1 and phot2) regulate plant growth by activating NPH3/RPT2‐like (NRL) family members. Little is known about roles for BL and phots in regulating plant immunity. We showed previously that Phytophthora infestans RXLR effector Pi02860 targets potato (St)NRL1, promoting its ability to enhance susceptibility by facilitating proteasome‐mediated degradation of the immune regulator StSWAP70. This raises the question: do BL and phots negatively regulate immunity?We employed coimmunoprecipitation, virus‐induced gene silencing, transient overexpression and targeted mutation to investigate contributions of phots to regulating immunity.Whereas transient overexpression of Stphot1 and Stphot2 enhances P. infestans colonization of Nicotiana benthamiana, silencing endogenous Nbphot1 or Nbphot2 reduces infection. Stphot1, but not Stphot2, suppressed the INF1‐triggered cell death (ICD) immune response in a BL‐ and NRL1‐dependent manner. Stphot1, when coexpressed with StNRL1, promotes degradation of StSWAP70, whereas Stphot2 does not. Kinase‐dead Stphot1 fails to suppress ICD, enhance P. infestans colonization or promote StSWAP70 degradation. Critically, BL enhances P. infestans infection, which probably involves phots but not other BL receptors such as cryptochromes and F‐box proteins ZTL1 and FKF1.We demonstrate that Stphot1 and Stphot2 play different roles in promoting susceptibility, and Stphot1 kinase activity is required for BL‐ and StNRL1‐mediated immune suppression. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is an important etiologic agent, triggering an increased trend of disease outbreak in fish farming. In this investigation, we evaluated pathological response in the midgut and liver of three types of grass carps after gut infection. Severe pathological levels of tissue necrosis were observed in common grass carp (GC) and gynogenetic grass carp (GGC), but mild pathological symptom was detected in hybrid grass carp (DRGC), along with the dramatically increased number of goblet cells. Moreover, three types of grass carps showed upregulated levels of immune gene patterns and antioxidant abilities, whereas inflammatory cytokine expression levels in hybrid grass carp (DRGC) were lower than that of gynogenetic grass carp (GGC) and common grass carp (GC). These results suggested that DRGC may exhibit a disease tolerance against A. hydrophila-induced tissue inflammation. [ABSTRACT FROM AUTHOR]

The transformation of China's economy from extensive growth to high-quality development is essentially an increase in green total factor productivity (GTFP). China currently has a range of environmental regulation tools, and the question of whether environmental regulation can promote improvement in China's GTFP requires theoretical and empirical analysis. This article first divides environmental regulation into three types: administrative, market-based and information-based. It then builds an empirical model of the effect of environmental regulation on GTFP. Slacks based measure-data envelope analysis (SBM-DEA) and the Malmquist index are used to measure the GTFP of 30 provinces in China from 2005 to 2018, and a measurement model of the impact of environmental regulation on GTFP is established. The results show that: (1) there are significant differences in GTFP in eastern, central and western China; (2) there is a non-linear relationship between environmental regulations and GTFP. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of 2.2 mm clear corneal incision (CCI) features in surgically induced astigmatism (SIA) and higher‐order aberrations (HOAs) after cataract surgery. Methods: Right eyes of 92 subjects receiving 2.2 mm incision cataract surgery were involved. A total of 38 eyes were categorized as the intact incision group, and 54 eyes were the defective incision group. Pre‐ and postoperative (1 month and 6 months) corneal astigmatism and HOAs on anterior and posterior corneal surfaces, corneal volume, and corneal thickness (CT) were measured using Pentacam. The CCI features including incision length (IL), incision angles, distance from incision to central cornea (Dis‐En/Ex), and CT at incision site were quantified using AS‐OCT. Results: The defective incision group showed shorter IL and larger incision angles [false discovery rate (FDR) – p < 0.05]. Changes in CT at incision site were more pronounced for the defective incision group (FDR – p < 0.05). Some SIA parameters were related to the certain specific CCI features, especially IL (FDR – p < 0.05). Both groups exhibited significant increased 6 mm posterior corneal tHOAs at 1 month (Bonferroni corrected – p < 0.01) and the defective incision group showed increased 6 mm posterior tHOAs at 6 months (Bonferroni corrected – p = 0.023). There were characteristic correlations between Zernike terms and CCI features including IL, CT, Dis‐En/Ex, and incision angles at 1 month, especially over 6 mm zone. Conclusion: The CCI deformities can affect corneal recovery and induce more HOAs at 1 month postoperatively. Such effects became minor, but could persist until 6 months. The IL combined with Angle‐En/Ex was important factor influencing CCI integrity and corneal optical quality. [ABSTRACT FROM AUTHOR]

To apply signal processing and machine learning skills and knowledge in processing the EEG and MEG signal and further localize and evaluate the source of the finger stimulation. Cognitive control is usually applied in information processing and behavioral response. In the preprocessing, baseline correction is implemented to analyze the pre-stimuli, combining ERP to mark the event related potential, studying the time-locked only behavior. Z-score transform, coherence and spec trum are calculated and analyzed in the functional connectivity analysis. In addition to the functional analysis, Bayes Optimizer evaluates the neuro imaging according to the hierarchical Bayes. The introduction of the application is described from both user and developer's prospects. Results: Introduction of both user and developers aspects, on its modules from pre-processing, functional analysis and results visualization and evaluation is conducted with one specific clinical data case, including the correlation is higher especially on gamma band and the MVAR coherence on the whole source space depicting the relation between different regions, especially on somatosensory (compared by thalamus) when stimulated by finger activity, phase-lock property of the E/MEG signal and etc. Compared to a manual selection, the scaling parameter prediction can be improved with support vector machine (SVM). The evaluation results with Bayes Optimization, location prediction is superior in the somatosensory area and in the thalamus, the total reconstructed source space is larger, one of the realization of cognitive system comparing different kernels and classifiers. The SVM and discriminant classifier gives similar results evaluating the dipole localization and the parameter choice related as well to the shape parameter, noise level, hyperprior and etc. Approaches of Brain Q are found to be suitable for pre-processing for the EEG and MEG data. The system is capable of functional analysis including coherence and spectral related computation. Machine learning techniques are conducted as well to analyze and evaluate the result of the dipole reconstruction and help to predict the better model parameters and the localization of the origin dipoles. A case on finger stimulation clinical data is conducted and the results of the analysis temporarily and spatially manifests its functionality for users and potential extensions for developers. [ABSTRACT FROM AUTHOR]

Background: Lupus enteritis (LEn) is a rare complication of systemic lupus erythematosus (SLE). Timely diagnosis and treatment of LEn are necessary to prevent the most serious consequences - intestinal perforation, gastrointestinal bleeding, and death. We compared the clinical features of SLE patients with and without LEn.Methods: The clinical data of LEn inpatients at Suining Central Hospital from July 2012 to June 2020 were examined. These LEn patients were matched (1:2 ratio) with concurrently hospitalized SLE patients who did not have LEn. The two groups were compared using multivariate logistic regression.Results: We compared SLE inpatients with LEn (n = 43) and SLE inpatients without LEn (n = 86) at our institution. Multivariate logistic regression showed that ascites (odds ratio [OR]: 9.961, 95%CI: 2.215-44.802, P = 0.003), hydronephrosis (OR: 28.060, 95%CI: 2.303-341.962, P = 0.009), leukopenia (OR: 5.890, 95%CI: 1.813-19.135, P = 0.003), reduced complement C3 level (OR: 4.791, 95%CI: 1.605-14.300, P = 0.005), and elevated immunoglobin (Ig)A level (OR: 4.040, 95%CI: 1.307-12.487, P = 0.015) were independently associated with LEn. Within the LEn group, abdominal pain was the most common abdominal symptom (88.4%), and increased mesenteric fat attenuation (74.4%) and bowel wall thickening (58.1%) were the most common computed tomography (CT) findings. Most LEn patients (88.4%) required high-dose glucocorticoid therapy (≥ 80 mg methylprednisolone/day), and cyclophosphamide was the most commonly used immunosuppressant (62.8%).Conclusions: Abdominal pain was the most common clinical symptom of LEn. Abdominal CT provides important information for detection and diagnosis of LEn. Ascites, hydronephrosis, leukopenia, hypocomplementemia (C3), and increased IgA were independently associated with LEn. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating type 2 diabetes mellitus (T2DM) in clinical studies. Accumulating evidence has suggested that the therapeutic effects of MSCs are not due to their direct differentiation into functional β-cells but are instead mediated by their paracrine functions. Among them, exosomes, nano-sized extracellular vesicles, are important substances that exert paracrine functions. However, the underlying mechanisms of exosomes in ameliorating T2DM remain largely unknown. Methods: Bone marrow mesenchymal stem cell (bmMSC)-derived exosomes (bmMDEs) were administrated to T2DM rats and high-glucose-treated primary islets in order to detect their effects on β-cell dedifferentiation. Differential miRNAs were then screened via miRNA sequencing, and miR-146a was isolated after functional verification. TargetScan, reporter gene detection, insulin secretion assays, and qPCR validation were used to predict downstream target genes and involved signaling pathways of miR-146a. Results: Our results showed that bmMDEs reversed diabetic β-cell dedifferentiation and improved β-cell insulin secretion both in vitro and in vivo. Results of miRNA sequencing in bmMDEs and subsequent functional screening demonstrated that miR-146a, a highly conserved miRNA, improved β-cell function. We further found that miR-146a directly targeted Numb, a membrane-bound protein involved in cell fate determination, leading to activation of β-catenin signaling in β-cells. Exosomes derived from miR-146a-knockdown bmMSCs lost the ability to improve β-cell function. Conclusions: These findings demonstrate that bmMSC-derived exosomal miR-146a protects against diabetic β-cell dysfunction by acting on the NUMB/β-catenin signaling pathway, which may represent a novel therapeutic strategy for T2DM. [ABSTRACT FROM AUTHOR]

The placenta is important for pregnancy maintenance, and autophagy is documented to be essential for placental development. Autophagy is responsible for degrading and recycling cellular misfolded proteins and damaged organelles. Mitophagy is a selective type of autophagy, where the autophagic machinery engulfs the damaged mitochondria for degradation, and there is reciprocal crosstalk between autophagy and mitochondria. Within these processes, 5'-AMP-activated protein kinase (AMPK) plays an important role. However, the role of AMPK regulation in both autophagy and mitochondria in primary human trophoblasts is unknown. In this study, we address this question by investigating changes in mRNA expression and the abundance of autophagy- and mitochondria-related proteins in isolated human trophoblasts after treatment with AMPK agonists and antagonists. We found that compared to the control group, autophagy was slightly suppressed in the AMPK agonist group and significantly enhanced autophagy in the AMPK antagonist group. However, the expressions of genes related to autophagosome-lysosome fusion were reduced, while genes related to lysosomal function were unchanged in both groups. Furthermore, mitophagy and mitochondrial fusion/fission were both impaired in the AMPK agonist and antagonist groups. Although mitochondrial biogenesis was enhanced in both groups, the function of mitochondrial fatty acid oxidation was increased in the AMPK agonist group but decreased in the AMPK antagonist group. Overall, our study demonstrates that AMPK regulation negatively modulates autophagy and consequently affects mitophagy, mitochondrial fusion/fission, and function in primary human trophoblasts. [ABSTRACT FROM AUTHOR]

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity. [ABSTRACT FROM AUTHOR]

For patients with acute myeloid leukemia (AML) who are not candidates for allogeneic stem cell transplantation (SCT) or do not have a human leukocyte antigen (HLA)-matched donor, it is unclear whether autologous SCT (ASCT) has a better prognosis after the first complete response (CR1) compared to further chemotherapy treatment. A meta-analysis evaluating ASCT compared to further chemotherapy for AML patients in CR1 was performed. The Medline, Embase, Cochrane Controlled Trials Registry, Cochrane Library, Web of Science, and National Knowledge Infrastructure of China databases were searched for relevant literature as of May 26, 2023. Eligible studies included prospectively enrolled adults with AML and randomized first-time respondent patients who did not have a matched sibling donor. Fourteen randomized controlled trials were identified and included 4281 participants, of which 1499 patients received ASCT and 2782 underwent chemotherapy and continued follow-up. In patients with AML in CR1, a lower relapse rate was associated with ASCT compared to chemotherapy [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.41–0.57]. Significant disease-free survival (DFS; OR = 1.37, 95% CI = 1.02–1.84) and relapse-free survival (RFS; OR = 2.78, 95% CI = 1.28–6.02) ASCT benefits were documented, and there was no difference in the overall survival (OS) when the studies were pooled (OR = 1.12, 95% CI = 0.85–1.48). The study results indicated that after the first remission, AML patients receiving autologous stem cell transplantation had higher DFS and RFS, similar OS, and lower relapse compared to patients undergoing chemotherapy treatment. This indicated that autologous stem cell transplantation may have a better prognosis. [ABSTRACT FROM AUTHOR]

The pronounced summertime quasi‐biweekly oscillation (QBWO) in the tropical northwestern Pacific usually originates from equatorial convective anomalies (ECAs) in the western Pacific. In this study, ECAs in relation to the QBWO are investigated in terms of the equatorial moisture dynamics. The results show that the development of ECAs is preconditioned by significant moisture anomalies associated with zonal moisture advection along the equator. Prior to initiation, an equatorially westward‐moving moisture precursor at a speed of approximately 5° longitude per day could be traced back to 140°W. A moisture budget analysis indicates that the successive westward movement of the moisture precursor is primarily due to the interaction between the zonal gradient of moisture anomalies and the mean easterly trade winds. The equatorial moisture dynamics likely maintain the quasi‐biweekly variability of ECAs regarding the QBWO in the tropical northwestern Pacific. Plain Language Summary: The quasi‐biweekly oscillation (QBWO) is one of the dominant intra‐seasonal modes activating in the tropical northwestern Pacific during summer. Compared with previous QBWO studies that mainly focused on the striking off‐equatorial evolution associated with unstable equatorial Rossby waves, the present study investigates an earlier signal at the equator, i.e., convective anomalies that force the generation of the equatorial Rossby wave. Specifically, we elucidate the moisture dynamics of the equatorial convective anomalies in relation to the QBWO and propose maintenance mechanism of quasi‐biweekly variability in the equatorial western Pacific. The improved understandings may provide insights into the monitoring and prediction of the QBWO. Key Points: A moisture precursor from the mid‐Pacific preconditions the equatorial convective anomalies in relation to the QBWOThe westward movement of the moisture precursor is due to the zonal transport by the easterly trade windsThe equatorial moisture dynamics maintain a quasi‐biweekly mode in the western Pacific [ABSTRACT FROM AUTHOR]

The proton-coupled folate transporter (PCFT, SLC46A1) is required for folate intestinal absorption and transport across the choroid plexus. Recent work has identified a F392V mutation causing hereditary folate malabsorption. However, the residue properties responsible for this loss of function remains unknown. Using site-directed mutagenesis, we observed complete loss of function with charged (Lys, Asp, and Glu) and polar (Thr, Ser, and Gln) Phe-392 substitutions and minimal function with some neutral substitutions; however, F392M retained full function. Using the substituted-cysteine accessibility method (with N-biotinyl aminoethyl methanethiosulfonate labeling), Phe-392 mutations causing loss of function, although preserving membrane expression and trafficking, also resulted in loss of accessibility of the substituted cysteine in P314C-PCFT located within the aqueous translocation pathway. F392V function and accessibility of the P314C cysteine were restored by insertion of a G305L (suppressor) mutation. A S196L mutation localized in proximity to Gly-305 by homology modeling was inactive. However, when inserted into the inactive F392V scaffold, function was restored (mutually compensatorymutations), as was accessibility of the P314C cysteine residue. Reduced function, documented with F392H PCFT, was due to a 15-fold decrease in methotrexate influx Vmax, accompanied by a decreased influx Kt (4.5-fold) and Ki (3-fold). The data indicate that Phe-392 is required for rapid oscillation of the carrier among its conformational states and suggest that this is achieved by dampening affinity of the protein for its folate substrates. F392V and other inactivating Phe-392 PCFT mutations lock the protein in its inward-open conformation. Reach (length) and hydrophobicity of Phe-392 appear to be features required for full activity. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). Methods: HucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta [MAP 1LC3B]), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting. Results: HucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism. Conclusions: These findings demonstrate that HucMDEs improved hepatic glucose and lipid metabolism in T2DM rats by activating autophagy via the AMPK pathway, which provides novel evidence suggesting the potential for HucMDEs in clinically treating T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Voriconazole and genus beta human papillomavirus (HPV) are independently associated with the development of photo‐exposed cutaneous squamous cell carcinoma (SCC) but have not been evaluated concurrently. The objective of this study is to determine the prevalence and type of detectable HPV DNA in voriconazole‐associated SCC. Methods: SCCs from immunosuppressed patients, in those with and without voriconazole exposure, were evaluated by PCR analysis for HPV DNA and compared to SCC from non‐immunosuppressed patients. An additional expanded PCR analysis of all SCC that developed in the voriconazole group was also performed. Results: HPV DNA was detected by PCR in all groups regardless of the immunosuppression status (80.5%) with beta HPV most prevalent (64.3–78.6%). However, immunosuppressed patients were significantly more likely to be infected by beta HPV types 5, 8, 14, 20, and 21 (P‐value 0.014), and represented the majority of beta HPV types found in the voriconazole group. Conclusions: In this retrospective study, beta HPV 5, 8, 14, 20, and 21 were commonly detected in voriconazole‐associated SCC. The results indicate a possible role of beta HPV in the pathogenesis of cutaneous SCC in photo‐exposed areas. Further studies are needed to establish the role of HPV and voriconazole in the pathogenesis of the lesion. [ABSTRACT FROM AUTHOR]

Increasing cell culture productivity of recombinant proteins via process improvements is the primary focus for research groups within biologics manufacturing. Any recommendations to improve a manufacturing process obviously must be effective, but also be robust, scalable, and with product quality comparable to the original process. In this study, we report that three different GS−/− CHO cell lines developed in media containing a standard concentration of the selection agent methionine sulfoximine (MSX), but then exposed to increased MSX concentrations during seed train expansion, achieved titer increases of 10–19%. This result was observed in processes already considerably optimized. Expanding the cells with a higher MSX concentration improved cell line production stability with increased culture age. Production cultures in 500‐L and 1000‐L bioreactors replicated laboratory results using 5‐L bioreactors, demonstrating process robustness and scalability. Furthermore, product quality attributes of the final drug substance using the higher MSX process were comparable with those from cells expanded in media with the standard selection MSX concentration. Subsequent mechanistic investigations confirmed that the cells were not altered at the genetic level in terms of integration profiles or gene copy number, nor transcriptional levels of glutamine synthetase, heavy chain, or light chain genes. This study provides an effective and applicable strategy to improve the productivity of therapeutic proteins for biologics manufacturing. [ABSTRACT FROM AUTHOR]

• Mg species optimized microstructure, active species dispersion and basic sites. • Mg enhanced the ability to capture CO 2 and intermediate active species. • Zr and Mg synergistically promote CO 2 conversion and methanol selectivity. • CO 2 hydrogenation to methanol conforms to the formate path with Mg modification. Optimizing the microstructure of copper-based catalysts for CO 2 hydrogenation to methanol is an attractive and widely reported strategy, but there are still certain barriers to improving both carbon dioxide conversion rate and methanol product selectivity. Herein, Cu/ZnO/ZrO 2 /MgO (CZZ 1-x M x) catalysts were synthesized by co-precipitation method for CO 2 hydrogenation to methanol. Furthermore, the structural features and reaction processes were systematically characterized by XRD, TEM, nitrogen adsorption/desorption, H 2 -TPR, CO 2 -TPD and in-situ DRIFT. The results showed that Mg species optimized the microstructure of the catalyst, increased the dispersion of active species and constructed appropriate basic sites. This further enhanced the capture of reactive species and improved the CO 2 hydrotreating to methanol reaction performance, which was accompanied by a simultaneous increase in CO 2 conversion and methanol yield. It could be convinced that the highest space time yield (STY) of methanol (305.3 g MeOH kg cat −1 h−1) was obtained at 220 °C, WHSV = 18,000 mL g cat −1 h−1 and 3 MPa (X CO2 = 7.28%, S MeOH = 71.8%) for the optimized CZZ 0.8 M 0.2 catalyst, which exhibited twice the CO 2 conversion than Cu/ZnO/ZrO 2. This work elaborated a scheme for the preparation of efficient methanol catalysts. providing reference for the research of CO 2 hydrogenation to methanol process. [Display omitted] It can effectively enhance the adsorption of CO 2 with appropriate Mg added of copper-based catalysts. Moreover, The synergistic effect between Zr and Mg can promote CO 2 conversion and methanol selectivity. [ABSTRACT FROM AUTHOR]

While chronic forms of psychosis, like schizophrenia, are more explored, accurately identifying individuals at early stages of psychosis and determining who will progress to schizophrenia remains a challenge. So far, there are no specific biomarkers available. Genetic factors have shown promises in predicting clinical outcomes. Polygenic risk scores have been investigated but rare variants have not been explored in ultra-high risk patients or in first episodes of psychosis. We have decided to turn our attention to overlooked variants which were historically challenging to study, such as tandem repeats (TRs). TRs are sequences of DNA bases repeated multiple times in a head-to-tail manner. They constitute 6% of the human genome and play a role in many biological processes, including brain function and behavior. Investigating TRs, especially the rare ones, could contribute to understanding the etiology of psychosis, and potentially serve as future biomarkers and drug targets. This study aimed to investigate TRs in early stages of psychosis and to explore their characteristics, and potential functional implications. The investigation began with a French/Quebecker cohort consisting of 318 first-episodes of psychosis/ultra-high risk patients and 78 help seekers who did not convert to psychosis. The samples were sequenced using Illumina Seq and the genome-wide TR identification was done by Expansion Hunter de novo (EHdn). The quality control was done by Expansion Hunter to ensure unbiased calls. Outliers were identified using EHdn, and only the expanded TRs with a z-score greater than 2 were selected for further analysis. The identified TRs were then characterized in terms of their size, base, and region distribution. We use the 1000 Genomes Project samples to filter the TRs based on their frequency. The potential functional implications of the exonic TRs were assessed using enrichment analysis, gene-set confrontation analysis, pathway analysis, and functional enrichment analysis. We identified 7798 rare TRs. They were enriched in cytosine and exhibiting abnormal motif size distributions. Among them, a subset of 302 TRs located in the exonic regions was chosen for subsequent analysis. Functional enrichment analysis revealed that theseTRs were associated with genes involved in neuronal communication, neurotransmitter regulation, and the construction and maintenance of neuronal membranes. Enrichment clusters related to lipids, including phospholipids, sphingolipids, and cholesterol, highlighted the significance of TRs in the structural integrity and fluidity of neuronal membranes. Moreover, the TRs were implicated in key processes such as synaptic catecholamine uptake, coupled glutamate signaling, and neuron projection axonogenesis. Additionally, we observed that TRs within exonic regions exhibited upregulation during critical periods of neurodevelopment, including late prenatal development, early infancy, and adolescence. This study provides valuable insights into the potential correlation between TRs and the early phases of psychosis. The unique characteristics of the identified TRs, their association with genes involved in neuronal communication, and their temporal alignment with critical neurodevelopmental periods support their role in the pathogenesis of psychosis. However, further analysis is necessary to gain a deeper understanding of the precise role of TRs and to demonstrate their pathogenicity in the context of psychosis. [ABSTRACT FROM AUTHOR]

Sustained activation of STAT3 is closely related to the cancer development, but the inhibitors for STAT3 overexpression are still in the clinical research stage. In this study, a series of 2,6-disubstituted purine derivatives were designed and synthesized, and their biological activities, as small molecule inhibitors of STAT3, were assessed. Compound PD26-TL07 exhibited remarkable antiproliferative activity against three cancer cell lines (IC 50 values for HCT-116, SW480 and MDA-MB-231 were 1.77 ± 0.35, 1.51 ± 0.19, and 1.25 ± 0.38 μM, respectively). Moreover, detailed biological assays revealed that PD26-TL07 could effectively inhibited STAT3 phosphorylation, and had little inhibition to others'. The newly discovered PD26-TL07 displayed an expecting anticancer effect both in vitro and in vivo. The molecular docking models revealed that PD26-TL07 could bind to the SH2 domain of STAT3. Three additional compounds (PD26-BZ01 , PD26-TL03 and PD26-AS06) were also able to inhibit this phosphorylation. This study described novel 2,6-disubstituted purine derivatives as potent anticancer agents targeting STAT3. Image 1 • A series of 2,6-disubstituted purine derivatives were discovered as STAT3 small molecular inhibitors. • PD26-TL07 could selectively inhibit STAT3 phosphorylation with IC 50 value of 2.28 μM. • PD26-TL07 exhibited potent antitumor activity in vitro and in vivo. [ABSTRACT FROM AUTHOR]

This study was designed to observe the compensation between cyclooxygenase‐2 pathway and 5‐lipoxygenase pathway in chronic aluminum overload‐induced liver injury rats. A rat hepatic injury model of chronic aluminum injury was established by the intragastric administration of aluminum gluconate (Al3 + 200 mg/kg per day, 5 days a week for 20 weeks). The COX‐2 inhibitor [meloxicam (1 mg/kg)] and 5‐LOX inhibitor [caffeic acid (30 mg/kg)] were intragastrically administered 1 h after aluminum administration. The histopathology was detected by hematoxylin‐eosin staining. A series of biochemical indicators were measured with biochemistry assay or ELISAs. The expressions of COX‐2 and 5‐LOX were measured by immunohistochemistry. Our experimental results showed that aluminum overload caused a significant damage to the liver and also significantly increased the expressions of COX‐2, 5‐LOX and the levels of inflammation and oxidative stress. The administration of meloxicam and caffeic acid significantly protected livers against histopathological injury, significantly decreased plasma ALT, AST, and ALP levels, significantly decreased TNF‐α, IL‐6, IL‐1β levels, and oxidative stress. However, the administration of caffeic acid did not significantly increase the expression of COX‐2 compared with the model group. On the other hand, the administration of meloxicam also did not significantly increase the expression of 5‐LOX compared with the model group. Our results indicate that there is no compensation between COX‐2 pathway and 5‐LOX pathway by inhibiting either COX‐2 or 5‐LOX in chronic aluminum overload‐induced liver injury rat. [ABSTRACT FROM AUTHOR]