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Grass carp belongs to Cypriniformes, Cyprinidae, and Cyprinus family, and is typically referred to as the four famous domestic fishes, black carp, silver carp, and bighead carp, respectively. The annual production of Chinese grass carp is consistently among the highest, with an output of 5.905 million tons in 2022, accounting for 24.3% of total of freshwater fish production. Reproduction is the core process of fish reproduction. Normal gonad development is a prerequisite for fish reproduction. At present, there are few reports on the sex differentiation of Chinese grass carp. Studying the differentiation and development of grass carp gonads can provide a typical model for gonadal development of cyprinid fish. In contrast, the start and completion time of gonadal differentiation are one of the key factors inducing sex reversal in fish using hormones. Research on gonadal differentiation and development in grass carp can also lay the foundation for the establishment of a unisexual population of grass carp.Sex-related genes play important roles in biological processes such as sex determination, gonadal differentiation, and reproduction and development in fish. In most differentiated teleost fish, genes such as dmrt1, sox9, foxl2, amh, and cyp19a1a, are considered the key genes involved in sex regulation. cyp19a1a plays a key role in the gonadal differentiation and ovarian development of teleost fish by aromatizing androgens into estrogen via aromatase activity. This gene is specifically expressed in the gonads and is used served as a characteristic gene for sex differentiation towards females. Anti-Müllerian hormone (amh) regulates the structure of reproductive organs and the differentiation and development of reproductive cells. In fish such as carp, rainbow trout, and grass carp, the expression level of the amh gene in the testes is significantly higher than that in the ovaries, and is often used as a characteristic gene for male differentiation.To explore the sex differentiation and developmental patterns of grass carp gonads, this study analyzed the tissue structure and expression differences of sex characteristic genes cyp19a1a and amh in the gonads of grass carp at 1, 2, 3, 4, 5, 6, 12, 24, 36, and 48 months of age using tissue sectioning technology and real-time fluorescence quantification technology. The results of tissue sectioning showed that grass carp exhibited reproductive ridges at 1-month-old. At 2 months of age, primitive germ cells were first observed in the reproductive crest, marking the formation of their primitive gonads. At 3-month- old, ovarian cavities and lobules were observed in the gonads of female grass carp. At 4-month-old, oogonia was observed, indicating anatomical differentiation at 3-month-old and cytological differentiation at 4-month-old. At the age of 4 and 5 months, ductus deferens and spermatogonia were respectively observed in male grass carp gonads, indicating anatomical differentiation at 4 months and cytological differentiation at 5 months. The ovaries of 24, 36, and 48-month-old grass carp were in the first, second, third, and fourth stages of development, respectively, while the testes were in the second, second, third, and fourth stages of development, respectively. At 48 months of age, the gonads of grass carp have matured. The fluorescence quantitative results showed that the expression level of the female characteristic gene cyp19a1a in the ovary showed an overall trend of first increasing, then decreasing, and then increasing again. The expression level of this gene was significantly upregulated at 2 months of age (P < 0.05), and reached its peak at 3, 6, and 48 months of age. During these three periods, anatomical changes were observed in the female gonads in the tissue sections, with a large proliferation of oocytes and the gonads tending to mature. The expression level of the male characteristic gene amh in the testes showed an overall trend of first increasing and then decreasing. At 2 months of age, the expression level of this gene was significantly upregulated (P < 0.05). At 5 months of age, it reached the peak when there were a large proliferation of spermatogonia in the gonads, and then remained low expression until gonadal maturity.In summary, this study confirmed that the initiation time of grass carp gonadal development is approximately 2 months old, and the differentiation time of male and female gonads is approximately 3 and 4 months old, respectively. By the age of 6 months, both male and female grass carp gonads completely differentiated. These results not only enrich the reproductive physiology data of grass carp but also provide a reference basis for the study of hormone-induced sex reversal technology in grass carp.

Abstract This survey aimed to investigate the availability of drugs for stable chronic obstructive pulmonary disease (COPD) treatment in Chinese hospitals and to determine whether drug availability significantly varied among hospitals with different characteristics. A well-constructed questionnaire was designed according to the Chinese Guidelines for the Diagnosis and Management of COPD (revised version 2021). Both inhaled drugs (monotherapy, double therapy and triple therapy) and oral drugs (expectorants, theophylline, antibiotics, and bacterial lysates) were included in this survey. Doctors from different hospitals completed the survey via WeChat. The availability of each category and kind of drug was analyzed based on final valid responses. Subgroup analyses were also conducted to reveal drug availability in hospitals with different characteristics. A total of 1018 hospitals with different characteristics were enrolled in this survey, with 53.73% of which establishing independent respiratory departments. Insufficient supply of COPD-related drugs was observed, with only short-acting β2 agonists (80.6%), expectorants (88.2%) and antibiotics (84.3%) reaching 80%. Results of subgroup analyses suggested that primary hospitals were associated with poorer availability of all kinds of drugs than secondary and tertiary hospitals (all p

Abstract The primary challenge in commercializing perovskite solar cells (PSCs) mainly stems from fragile and moisture-sensitive nature of halide perovskite materials. In this study, we propose an asynchronous cross-linking strategy. A multifunctional cross-linking initiator, divinyl sulfone (DVS), is firstly pre-embedded into perovskite precursor solutions. DVS, also as a special co-solvent, facilitates intermediate-dominated perovskite crystallization manipulation, favouring formamidine-DVS based solvate transition. Subsequently, DVS-embedded perovskite as-cast films are post-treated with a nucleophilic reagent, glycerinum, to trigger controllably three-dimensional co-polymerization. The resulting cross-linking scaffold provides enhanced water-resistance, releases residual tensile strain, and suppresses deep-level defects. We achieve a maximum efficiency over 25% (certified 24.6%) and a maximum VOC of 1.229 V, corresponding to mere 0.30 V deficit, reaching 97.5% of the theoretical limit, which is the highest reported in all perovskite systems. This strategy is generally applicable with enhanced efficiencies approaching 26%. All-around protection significantly improves PSC’s operational longevity and thermal endurance.

Abstract Largemouth bass (Micropterus salmoides, LMB) is an important aquaculture species due to its excellent flesh quality and environmental adaptability. It has been continuously introduced to many countries and cultured for decades. Here, an LMB population was used for selective breeding to improve growth rate and feed adaptability. After five generations of breeding, the growth rate improved by 38%, and feed adaptability improved by 22% compared to the non-breeding population. To study the underlying genetic mechanism, 100 LMB from the breeding population and 100 from the non-breeding population were sampled for whole-genome resequencing. The population genetics analysis shows that the breeding population has a higher inbreeding coefficient and linkage disequilibrium (LD) level, a lower nucleic acid diversity and effective population size (Ne). Using $$F_{ST}$$ (fixation index), we found that the average $$F_{ST}$$ value between the two populations was 0.07, with the highest $$F_{ST}$$ value reaching 0.38, which overlaps with the trypsin gene. Additionally, other genes exhibiting high $$F_{ST}$$ values are associated with functions such as neural development, glucose metabolism, and growth. Using $$F_{ST}$$ and nucleic acid diversity as criteria, we identified 698 genes that are positively selected in the breeding population, and gene functional enrichment analysis shows that 36 genes are related to the olfactory receptor pathway. Overall, our study found that multiple genes were selected in the LMB breeding population. These genes may be associated with adaptation and digestion of artificial feed in fish.

Chemical looping dry reforming of methane (CL-DRM) is a highly efficient process that converts two major greenhouse gases (CH4 and CO2) into syngas ready for the feedstock of liquid fuel production. One of the major obstacles facing this technology now is creating oxygen carriers that are stable and reactive. We fabricated high-performance Sr0.98Fe0.7Co0.3O3-δ perovskite-structured oxygen carrier by combining A-site defects and B-site doping of SrFeO3-δ. During isothermal CL-DRM tests at 850 °C, Sr0.98Fe0.7Co0.3O3-δ achieved 87% CH4 conversion and 94% CO selectivity in the CH4 partial oxidation reaction, followed by a syngas yield of 8.5 mmol/g, and CO yield of 4.2 mmol/g in CO2 decomposition. A-site defect engineering of the perovskite creates abundant oxygen vacancies and enhances oxygen storage capacity (OSC). Co-doping of the B-site of Sr0.98FeO3-δ increases oxygen mobility and CH4/CO2 activation, resulting in high activity in the CL-DRM process. This methodology resulted in high ionic mobility and facilitated the rapid diffusion of oxygen in the bulk phase, thereby increasing the redox properties of SrFeO3-δ. The oxygen carrier exhibits excellent structural stability and regeneration ability in successive redox cycles. This strategy offers a simple but very effective pathway to tailor OSC, oxygen mobility, and oxygen vacancies of perovskite-structured materials for chemical looping or redox-involved processes.

Abstract Background Postoperative neurocognitive disorders (PNDs) frequently occur following orthopedic surgery and are closely associated with adverse prognosis. PNDs are an emerging concept that includes both postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). The prevention of combined use of peripheral nerve block (PNB) and general anesthesia (GA) on POCD and/or POD incidence following orthopedic surgery remains unknown. We aimed to investigate the effect of this combined anesthesia method on POCD/POD incidence after orthopedic surgery, compared with GA. Methods The databases of PubMed, Web of Science, Embase via Ovid, and the Cochrane Central Register of Controlled Trials were searched for all available randomized controlled trials (RCTs). The incidence of POD/POCD was the primary outcome. Continuous and dichotomous outcomes are represented as standardized mean differences [SMD, 95% confidence interval (CI)] and risk ratios [RR, 95%CI], respectively. Results Meta-analysis of twelve RCTs with a total of 1488 patients revealed that compared with GA, PNB plus GA decreased the incidence of POCD (RR: 0.58, 95%CI: 0.35 to 0.95, P = 0.03, I2 = 0%), while the incidence of POD had no significant difference (RR: 0.87, 95%CI: 0.54 to 1.40, P = 0.57, I2 = 67%). Compared with GA alone, a significant decrease of intraoperative and postoperative opioid consumption (SMD: -1.54, 95%CI: -2.26 to -0.82, P

Abstract This study was performed on Micropterus salmoides to determine growth-linked gene and single nucleotide polymorphism (SNP) markers under carbohydrate diet and varying temperature through RNA-seq and whole-genome re-sequencing. The results showed that growth-related genes were primarily enriched in the fat digestion and absorption signaling pathway, playing a role in lipid transport and metabolism. Fatty acid binding protein 6, bile salt-activated lipase-like, lysophosphatidylcholine acyltransferase 2, phospholipase A2, minor isoenzyme-like, and phospholipase A2, group IB (pancreas) were identified as the crucial genes. The differentially expressed genes between high and low temperatures were enriched in the pentose phosphate pathway, with carbohydrate transport and metabolism were most affected by temperature. Major facilitator superfamily domain containing 10, phosphogluconate dehydrogenase, fructose-1,6-bisphosphatase 1a, and spinster homolog 3 transcript variant X1(spns3) were the shared genes affected by temperature. From all the common genes, 10 growth-associated SNP markers were identified. The TT genotype at rs7781 was associated with lower body weight, while AA genotype at rs31434173 and CC genotype at rs31435313 showed positive correlation with body weight. Analogously, the GG genotype at rs31436887 and AA genotype at rs31438769 also found to characterize better growth performance. At low temperature, individuals with the AA genotype at rs11506587 and rs31435313 exhibited the slowest growth. For the genotypes labeled with rs11510589, the GG individual grew faster than the AA individual, whereas the opposite phenomenon occurred in these genotypes when labeled with rs11511314. The genotypes at rs32970704 and rs32967921 showed no growth correlation. The AA genotype at rs31435313 in spns3 had the slowest growth under a carbohydrate-rich diet regardless of the temperature. Our study presents candidate genes and SNP markers associated with growth influenced by carbohydrate and temperature, providing basis for the development of M. salmoides strain that better accepts carbohydrate diets at varying temperature.

Abstract This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project.

Abstract This study investigates the particle’s geodesic motion and accretion around the spherically symmetric Reissner–Nordström black hole coupled with a nonlinear electrodynamics field. The formation of the disc-like structure in the accretion process arises from the geodesic motion exhibited by particles near the black hole. In the equatorial plane, we analyze the circular orbits of particles and their stability in detail. The analysis of the fluid’s critical flow, maximum accretion rate, radiant flux energy, radioactive efficiency, and radiant temperature are also examined near the central object. We analyze the perturbations experienced by particles throughout, employing restoring forces and the oscillatory behavior of the particles around the black hole. Our results show that the NED parameter $$\zeta $$ ζ affects the circular geodesics of particles and the maximum accretion rate of the Reissner–Nordström black hole coupled with nonlinear electrodynamics.

Abstract Background Medical dispute is a global public health issue, which has been garnering increasing attention. In this study, we used machine learning (ML) method to establish a dispute prediction model and explored the clinical-application efficiency of this model in effectively reducing the occurrence of medical disputes. Methods Retrospective study of All disputes filed by Gansu Medical Mediation Committee from 2019 to 2021 and patients with the same hospital level as that of the dispute group and hospitalization year were randomly selected as the control group in 1:1 ratio. SPSS software was used for univariate feature selection of the 14 factors that may cause disputes, and factors with statistical differences were selected. The data were divided into training and test sets in a 7:3 ratio. Six ML models were selected, and Python was used to establish a dispute prediction model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC), sensitivity, specificity, accuracy, precision, average precision (AP), and F1 score were used to characterize the fitting and accuracy of the models, while decision curve analysis (DCA) was used to evaluate their clinical utility. Results A total of 1189 patients in the dispute and control groups were extracted. Following 11 influencing factors were selected: the inpatient department, doctor title, patient age, patient gender, patient occupation, payment method, hospitalization days, hospitalization times, discharge method, blood transfusion volume, and hospitalization espenses. Compared to other models, the AUC (0.945, 95% CI 0.913–0.981), Sensitivity (0.887), Accuracy (0.887), AP (0.834), and F1 score (0.880) of the random forest model were higher than those of other models, while the DCA curve indicated its high clinical benefits. Conclusions Inpatient department, hospitalization expenses, and discharge type are the primary influencing factors of dispute. Random forest exhibited high dispute prediction and clinical-application value and is expected to be promoted for offline dispute prediction.

The characteristics of biomarker compounds and their occurrence states in different layers of the Permian Fengcheng Formation shale in Mahu Sag, Junggar Basin are poorly understood. By using experimental techniques such as rock pyrolysis, gas chromatography-mass spectrometry, fluorescence thin sections, and argon ion polishing electron microscopy, the material basis of hydrocarbon source rocks in different intervals, the distribution characteristics and significance of biomarker compounds, and different occurrence states of shale oil are clarified. This is of great significance for the next step in exploration and deployment in the Mahu Sag. The shale of the Fengcheng Formation in the Mahu Sag is mainly medium to good hydrocarbon source rocks, with type Ⅱ organic matter and in a mature evolutionary stage. The composition characteristics of biomarker compounds show high abundance of Pr and Ph, β-carotane, and C29 rearranged steranes. The C27-C28-C29 regular steranes exhibit an inverted "L" distribution, indicating that the organic matter is mainly contributed by lower aquatic organisms such as algae. Lower Pr/Ph ratios and higher gammacerane indices reflect a saline reducing sedimentary environment. Maturity parameters such as C31αβ22S/(22S+22R), C29M/C29H, and C29ββ/(ββ+αα) for hopanes and steranes indicate that the hydrocarbon source rocks are in the mature stage. In addition, the shale of the second member of the Fengcheng Formation has greater hydrocarbon generation potential and better source rock material basis than that in the first and third members. Meanwhile, biomarker compound parameters such as C20/C23TT, C21/C23TT, and Ga/C30H indicate that the second member has more contributions from algae and other organisms, and a more reducing and saline environment. The hydrocarbons in the second member are mainly in a free occurrence state, residing in intergranular and intragranular pores. The study shows that the second member of the Fengcheng Formation is more favorable for shale oil enrichment and preservation, showing a better prospect for shale oil exploration and development.

Abstract Perovskite solar cells (PSCs) are an ideal candidate for next‐generation photovoltaic applications but face many challenges for their wider application, including uncontrolled fast crystallization, trap‐assisted nonradiative recombination, and inefficient charge transport. Herein, a multistage regulation (MSR) strategy for addressing these challenges is proposed via the introduction of fluorine‐rich small molecules with multiple active points (i.e., 1‐[Bis(trifluoromethanesulfonyl)methyl]‐ 2,3,4,5,6‐pentafluorobenzene (TFSP)) into the precursor solution of the perovskite film. The addition of TFSP effectively delays and regulates the crystallization and growth process of the perovskite film for larger grains and fewer defects, and it effectively improves the coverage of self‐assembled molecules for efficient charge transport. The multiple active points of TFSP induce a strong binding affinity with uncoordinated defects in the perovskite film. Moreover, the high fluorine content of TFSP induces strong electronegativity to establish a high binding strength between the perovskite film and electron transport layer. Finally, PSCs prepared by the MSR strategy demonstrated an optimal power conversion efficiency (PCE) of 25.46% and maintained 91.16% of the initial PCE under nonpackaged air conditions and at a relative humidity of 45% after 3000 h.

Understanding the genomic variation in Pekin duck under artificial selection is important for improving the utilization of duck genetic resources. Here, the genomic changes in Pekin duck were analyzed by using the genome resequencing data from 96 individual samples, including 2 conservation populations and 4 breeding populations with different breeding backgrounds. The population structure, runs of homozygosity (ROH), effective population number (Ne), and other genetic parameters were analyzed. The breeding populations showed lower genetic diversity compared to the conservation populations. Maple Leaf duck and Cherry Valley duck retained low genetic diversity compared to other breeding populations, with Cherry Valley duck showing the lowest diversity and the highest inbreeding coefficient. This suggested that Cherry Valley and Maple Leaf ducks have undergone intensive selection compared to other breeding populations. By the analysis of runs of homozygosity (ROHs), some genes (e.g., IGF1R) associated with growth traits were identified. By the analysis of the selection signal, strong selection characteristics in certain genomic regions during the breeding of Peking duck across different selected lines were observed. In addition, copy number variations (CNVs) in Pekin duck populations were analyzed. Six regions of interest were identified, containing RPA1, DOT1L, SLC25A42, RALYL, TRPA1, and IGFBP2. Furthermore, the allele frequency distribution of these genes showed significant differences between breeding populations and conservation populations, indicating that these candidate genes could have undergone strong selection pressure during long-term selection for improved production. These findings contribute to a deeper understanding of the distinct evolutionary processes in Pekin ducks under artificial selection and provide valuable insights for future breeding strategies.

Herein, the effect of multicomponent composite encapsulation on the stability of perovskite thin films and perovskite solar cells, as well as lead leakage upon water immersion, is investigated. The encapsulation is simple and low cost since it is entirely deposited by solution processed techniques in the ambient atmosphere. It consists of a spray‐coated composite layer sandwiched between two spin‐coated layers. The composite layer contains hygroscopic nanomaterials, oxygen scavengers, and lead adsorbing nanomaterials, which enables reduced lead leakage and improved stability of encapsulated perovskite during storage in ambient, immersion in water, as well as illumination in dry air. The encapsulation layers show high transmittance and did not have a significant effect on the short‐circuit current density and open‐circuit voltage despite the deposition of encapsulation in ambient air. The encapsulated devices retain 80% of their initial performance after 4 h of immersion in water.

BackgroundSpinal cord injury (SCI) is a globally prevalent neurological condition, often resulting in motor, sensory, and autonomic dysfunctions that lead to permanent disability. However, outdated epidemiological data hinder the development and implementation of effective public health policies. This study aimed to examine and compare trends in the burden of spinal cord injury—specifically incidence, prevalence, and years lived with disability (YLD)—in China and worldwide from 1990 to 2021, and to project these trends over the next 15 years.MethodsThis study analyzed the characteristics of the SCI burden in China and globally, examining changes in incidence, prevalence, and years lived with disability (YLD) using open data from the Global Burden of Disease database covering 1990 to 2021. Additionally, Joinpoint and age-period-cohort (APC) analyses were conducted to provide insights into the epidemiological characteristics of the SCI burden. The autoregressive integrated moving average (ARIMA) model was then applied to project SCI trends for the next 15 years.ResultsIn 2021, the prevalence and incidence of SCI in China reached 2,766,277 and 99,363 cases, respectively, marking increases of 63.27 and 43.27% since 1990. From 1990 to 2021, the age-standardized prevalence rate (ASPR) of SCI decreased significantly, with an estimated annual percentage change (EAPC) of −0.34 (95% CI: −0.60 to-0.07). At the gender level, SCI prevalence and incidence were higher in men than in women. Joinpoint analysis revealed a significant decrease in the APC of the age-standardized incidence rate (ASIR) from 1990 to 2011 (APC = −0.98, p

AbstractDiabetic foot ulcer (DFU) is a severe complication of diabetes. Due to conservative or delayed treatment, the majority of DFU patients frequently miss the optimal treatment window, thereby leading to amputation. Despite being a rare pathogen with low virulence, Enterococcus avium (E. avium) exhibits some antibiotic resistance and can be fatal for immunocompromised patients. This report describes a DFU case, caused by E. avium infection due to exposure to poultry. Wound microbiota was dynamically monitored using bacterial culture followed by 16S rRNA gene sequencing throughout the illness. Combination of antibiotics was administered to control the secondary infection.Case reportA 56-year-old man presented with a two-week history of redness, swelling, heat, pain, and pus discharge from a ruptured wound on his left heel. The patient was diagnosed with osteomyelitis and a Wagner grade 3 diabetic foot ulcer infection, complicated by the soft tissue infection in the left heel. Strain identification and antibiotic susceptibility tests were immediately performed after admission. The patient underwent three debridement procedures at the DFU site. However, we observed recurrent bacterial infections, based on the clinical progression. Second-generation sequencing detected various pathogens. After targeted treatment with Vacuum sealing drainage (VSD) combined with antibiotic bone cement, the patient’s condition stabilised. A skin graft was subsequently performed. Antibiotics were used to control the infection and blood glucose level was controlled throughout the treatment.ConclusionThus, this report provides a comprehensive description of a DFU case, caused by E. avium. Antibiotics and surgical measures should be adjusted according to the pathogens responsible for wound infections in DFU patients. It is important to reduce the mortality and prevent irreversible amputations.

BackgroundEvidence indicates a negative link between glucosamine and age-related cognitive decline and sarcopenia. However, the causal relationship remains uncertain. This study aims to verify whether glucosamine is causally associated with cognitive function and sarcopenia.MethodForty-eight genetic variants linked to glucosamine use were extracted from the MRC-IEU consortium. Besides, we gathered cognition proxy indicators [cognitive performance and fluid intelligence score (FIS)], and sarcopenia-related indicators, namely, appendicular lean mass (ALM), whole body fat-free mass (WBFM), low hand grip strength, facial aging (FA), moderate to vigorous physical activity levels, usual walking pace and DNA methylation GrimAge acceleration from the large publicly available genome-wide association studies. Initially, Mendelian randomization (MR) analyses were conducted to ascertain the causal impact of glucosamine on cognition and sarcopenia-related traits. Subsequently, the two-step MR and multivariable MR (MVMR) were employed to examine whether any mediators causally mediated the observed associations.ResultMR analysis indicated that glucosamine was associated with increased cognitive performance (p = 8.46E-04), FIS (p = 7.50E-04), ALM (p = 6.45E-08), WBFM (p = 1.97E-03), usual walking pace (p = 2.55E-07), and moderate to vigorous physical activity levels (p = 3.29E-03), but associated with decreased FA risk (p = 3.77E-05) and DNA methylation GrimAge acceleration (p = 0.001). However, there were no significant causal associations between glucosamine and low hand grip strength. Multivariable MR showed that glucosamine continued to have a significant effect on cognitive performance, FIS, ALM, WBFM, usual walking pace, and moderate to vigorous physical activity levels after controlling for osteoarthritis (OA) and body mass index (BMI) (p < 0.05). We further found that C-reactive protein levels (CRP) may mediate the association of glucosamine and ALM, WBFM, usual walking pace, and physical activity (p < 0.05), and basal metabolic rate (BMR) may mediate the association of glucosamine and cognitive performance, FIS, ALM, WBFM, and usual walking pace (p < 0.05).ConclusionRegular glucosamine use enhances cognitive function and postpones sarcopenia for preserving the functional capacities necessary, and the impact of glucosamine on cognition and sarcopenia could be partially attributed to the mediation of BMR and CRP.

Abstract Machine vision techniques are widely applied for object identification in daily life and industrial production, where images are captured and processed by sensors, memories, and processing units sequentially. Neuromorphic optoelectronic synapses, as a preferable option to promote the efficiency of image recognition, are hotly pursued in non‐ionizing radiation range, but rarely in ionizing radiation including X‐rays. Here, the study proposes an X‐ray optoelectronic synapse using amorphous Ga2O3 (a‐Ga2O3) thin film. Boosted by the interfacial VO2+ defects and its slow neutralization rate, the enhanced electron tunneling process at metal/a‐Ga2O3 interface produces remarkable X‐ray‐induced post‐synaptic current, contributing to a sensitivity of 20.5, 64.3, 164.1 µC mGy−1 cm−2 for the 1st, 5th, and 10th excitation periods, respectively. Further, a 64 × 64 imaging sensor is constructed on a commercial amorphous Si (a‐Si) thin film transistor (TFT) array. The image contrast can be apparently improved under a series of X‐ray pulses due to an outstanding long‐term plasticity of the single pixel, which is beneficial to the subsequent image recognition and classification based on artificial neural network. The merits of large‐scale production ability and good compatibility with modern microelectronic techniques belonging to amorphous oxide semiconductors may promote the development of neuro‐inspired X‐ray imagers and corresponding machine vision systems.

The Jacalin-related lectins (JRLs) gene family play a crucial role in regulating plant development and responding to environmental stress. However, a systematic bioinformatics analysis of the JRL gene family in Gramineae plants has been lacking. In this study, we identified 101 JRL proteins from five Gramineae species and classified them into eight distinct clades. Most of the AtJRL proteins clustered in the same group and were differentiated from the Gramineae JRL proteins. The analysis of protein motifs, gene structures and protein domain revealed that the JRL genes play diverse functions in Gramineae plants. Duplication events indicated that tandem duplication significantly contributed to the expansion of the JRL family, with most JRL members underwent purifying selection. Tissue expression profile analysis showed that most OsJRL genes were highly expressed in the roots, while ZmJRL genes exhibited high expression in inflorescences. Furthermore, the expression level of OsJRL and ZmJRL genes were influenced by drought, cold, heat and salt stresses, respectively, implying that these genes play important roles in response to various abiotic stresses. RT-qPCR results demonstrated that OsJRL4 was up-regulated under PEG6000 and NaCl stresses, while OsJRL12 and OsJRL26 were down-regulated under PEG6000. These findings provide comprehensive insights into the JRL gene family in Gramineae plants and will facilitate further functional characterization of JRLs.

Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×1010viral particles) and B.1.1.529 variant (5×1010viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×1010viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.

The detoxified pneumolysin derivative ΔA146Ply has been proven to have a direct anti-triple negative breast cancer effect by our group, but its work model remains unclear. In this study, we focused on its ability to inhibit triple-negative breast cancer metastasis. We found that ΔA146Ply suppressed the migration and invasion of triple-negative breast cancer cells by activating mannose receptor and toll-like receptor 4. Their activation triggers the activation of the mammalian target of rapamycin signalling, sequentially leading to autophagy, transforming growth factor-β1, and epithelial-mesenchymal transition inhibition. Furthermore, the combination of doxorubicin and ΔA146Ply significantly inhibited triple-negative breast cancer progression and prolonged survival in tumour-bearing mice. Taken together, our study provides an alternative microbiome-based mannose receptor-targeted therapy for triple-negative breast cancer and a novel theoretical and experimental basis for the downstream signalling pathway of the mannose receptor.

Abstract Unraveling the regulatory mechanisms that govern complex traits is pivotal for advancing crop improvement. Here we present a comprehensive regulome atlas for rice (Oryza sativa), charting the chromatin accessibility across 23 distinct tissues from three representative varieties. Our study uncovers 117,176 unique open chromatin regions (OCRs), accounting for ~15% of the rice genome, a notably higher proportion compared to previous reports in plants. Integrating RNA-seq data from matched tissues, we confidently predict 59,075 OCR-to-gene links, with enhancers constituting 69.54% of these associations, including many known enhancer-to-gene links. Leveraging this resource, we re-evaluate genome-wide association study results and discover a previously unknown function of OsbZIP06 in seed germination, which we subsequently confirm through experimental validation. We optimize deep learning models to decode regulatory grammar, achieving robust modeling of tissue-specific chromatin accessibility. This approach allows to predict cross-variety regulatory dynamics from genomic sequences, shedding light on the genetic underpinnings of cis-regulatory divergence and morphological disparities between varieties. Overall, our study establishes a foundational resource for rice functional genomics and precision molecular breeding, providing valuable insights into regulatory mechanisms governing complex traits.

Abstract Introduction Emerging infectious diseases (EIDs) can disrupt the healthcare system, causing regulatory changes that affect the healthcare-seeking process and potentially increase patient-physician dissatisfaction. This study aimed to collect and analyze patients’ and physicians’ complaints during an EID outbreak to inform potential clues regarding medical quality and patient safety enhancement in future dealing with EIDs, employing text mining methodologies. Methods In this descriptive study, complaint records from January 2020 to February 2023 at West China Hospital, a national medical facility in China, were analyzed. Patient and physician complaints have been retrospectively retrieved from the record from the medical department, and then categorized into distinct groups based on reporting reasons, encompassing COVID-19-related policies, healthcare access, availability of medical resources, and financial concerns. Results During the COVID-19 pandemic, 541 COVID-19-related complaints were identified: 330 (61.00%) from patients and 211 (39.00%) from physicians. The monthly volume of complaints fluctuated, starting at 10 in 2020, peaking at 21 in 2022, and dropping to 14 in 2023. Most complaints from inpatients were expressed by older males aged 40 to 65 (38.82%, 210/541). The primary source of complaints was related to mandatory COVID-19 policies (79.30%, 429/541), followed by concerns regarding timely healthcare services (31.61%, 171/541). Few complaints were expressed regarding the insufficiency of medical resources (2.77%, 15/541) and the high costs (4.25%, 23/541). The frequency of complaints expressed by doctors and patients in the emergency department was higher compared with other departments (24.58%, 133/541). Conclusions Increased complaints may serve as a primitive and timely resource for investigating the potential hazards and drawbacks associated with policies pertaining to EIDs. Prompt collection and systematical analysis of patient and physician feedback could help us accurately evaluate the efficacy and repercussions of these policies. Implementing complaints-based assessment might improve care standards in forthcoming healthcare environments grappling with EIDs.

Abstract In this paper, we investigate the polarization images of a synchrotron-emitting fluid ring surrounding a static hairy black hole within the framework of Horndeski’s theory. Our findings indicate that the characteristics of these polarization images are predominantly influenced by the hairy parameter, alongside the magnetic field near the black hole, the fluid’s velocity, and the observer’s inclination angle. Specifically, the hairy parameter primarily affects the polarized intensity and the apparent radius of the ring in the images. Conversely, the impacts of the magnetic field, fluid velocity, and inclination angle on the polarization images are found to be independent of the hairy parameter and closely resemble those observed in the context of Schwarzschild black holes. Additionally, the polarization direction is significantly influenced by the magnetic field orientation, while the inclination angle crucially determines the apparent flatness of the images. Variations in the fluid velocity direction also markedly affect the trend in polarized intensity. Furthermore, we explore how these parameters influence the Stokes $$Q-U$$ Q - U loops, revealing distinct behaviors in response to changes in the aforementioned variables. This comprehensive analysis enhances our understanding of the intricate dynamics and observational signatures of black holes within alternative gravitational theories.

Abstract We report the numerical and experimental studies of the two-dimensional Brillouin gain spectrum (BGS) distribution deformation induced by the self-phase modulation in the Brillouin optical time domain reflectometry (BOTDR) with a 20.6 km sensing distance. The BGS distribution deformation is investigated by analyzing the evolution of the point spread function along the fiber in the two-dimensional model of the BOTDR. In the simulation and experimental results, the specific deformation degree of the BGS distribution induced by the self-phase modulation is related to the pump pulse profile, pump pulse peak power, BGS demodulation method, and detected scattered light component. By comprehensively analyzing the evolution of the point spread function induced by the self-phase modulation and using the image deconvolution, a typical BOTDR sensor with a 25 ns pump pulse reaches the 20 cm spatial resolution over the 20.6 km sensing fiber.

Abstract Background Innominate artery aneurysms (IAAs) are rare and may result in rupture, distal arterial embolization, or local compression without timely treatment. Rupture is the most dangerous of these complications. This article reports a case of innominate artery bifurcation pseudoaneurysm. Case presentation The patient was a 45-year-old man who was admitted to the emergency department due to chest discomfort. The computed tomographic angiography (CTA) imaging indicated the presence of a 3.6*2.4 cm saccular aneurysm in the bifurcation of the innominate artery, involving both the right proximal subclavian and common carotid arteries. The patient’s vital signs were normal, there was equal blood pressure in the upper arms and no neurological dysfunction was observed. Gadolinium-enhanced magnetic resonance angiography indicated that the circle of Willis was intact. The treatment involved open surgery combined with endovascular therapy. The external carotid artery was first transposed to the right subclavian artery (RSA) and an 8-mm woven Dacron graft was inserted in the middle. The covered stent graft was then placed in the proximal part of the innominate artery to close the entrance of the aneurysm. Lastly, an occluder was implanted at the origin of the RSA. There were no perioperative or postoperative complications. At 1-year follow-up, no aneurysm was observed on CTA and the right vertebral artery was patent. Conclusions This study indicated that the combined use of endovascular therapy and open repair surgery is an effective strategy to treat innominate artery bifurcation pseudoaneurysm.

Abstract Heat extremes frequently hit different regions synchronously during boreal summer over the Eurasian continent. A remarkable coupling is first revealed between Eurasian heat extreme occurrence and individual extratropical intraseasonal oscillation (EISO). Further, the combined EISOs facilitate and largely increase the occurrence probabilities of synchronous Eurasian heat extremes. These dominant combined EISOs together contribute 20–45% to the total heat extreme days over the five Eurasian regions where the climatological heat extremes occur most frequently. A multi-model hindcast further shows that the subseasonal prediction exhibits higher skills for synchronous heat extremes over the combined-EISO hotspot regions when the associated combined EISOs are active, supporting the notion that the monitoring and prediction of EISOs are crucial for heat extremes’ early warning. Skillful prediction of EISOs opens a pathway for heat extremes’ prediction by extending it from the weather to the subseasonal timescales.

Abstract The current research on the integrity of critical structures of rail vehicles mainly focuses on the design stage, which needs an effective method for assessing the service state. This paper proposes a framework for predicting the remaining useful life (RUL) of in-service structures with and without visible cracks. The hypothetical distribution and delay time models were used to apply the equivalent crack growth life data of heavy-duty railway cast steel knuckles, which revealed the evolution characteristics of the crack length and life scores of the knuckle under different fracture failure modes. The results indicate that the method effectively predicts the RUL of service knuckles in different failure modes based on the cumulative failure probability curves for different locations and surface crack lengths. This study proposes an RUL prediction framework that supports the dynamic overhaul and state maintenance of knuckle fatigue cracks.

Abstract Achieving effective manipulation of perpendicular exchange bias effect remains an intricate endeavor, yet it stands a significance for the evolution of ultra-high capacity and energy-efficient magnetic memory and logic devices. A persistent impediment to its practical applications is the reliance on external magnetic fields during the current-induced switching of exchange bias in perpendicularly magnetized structures. This study elucidates the achievement of a full electrical manipulation of the perpendicular exchange bias in the multilayers with an ultrathin antiferromagnetic layer. Owing to the anisotropic epitaxial strain in the 2-nm-thick IrMn3 layer, the considerable exchange bias effect is clearly achieved at room temperature. Concomitantly, a specific global uncompensated magnetization manifests in the IrMn3 layer, facilitating the switching of the irreversible portion of the uncompensated magnetization. Consequently, the perpendicular exchange bias can be manipulated by only applying pulsed current, notably independent of the presence of any external magnetic fields.

Abstract Laser-based light detection and ranging (LIDAR) offers a powerful tool to real-timely map spatial information with exceptional accuracy and owns various applications ranging from industrial manufacturing, and remote sensing, to airborne and in-vehicle missions. Over the past two decades, the rapid advancements of optical frequency combs have ushered in a new era for LIDAR, promoting measurement precision to quantum noise limited level. For comb LIDAR systems, to further improve the comprehensive performances and reconcile inherent conflicts between speed, accuracy, and ambiguity range, innovative demodulation strategies become crucial. Here we report a dispersive Fourier transform (DFT) based LIDAR method utilizing phase-locked Vernier dual soliton laser combs. We demonstrate that after in-line pulse stretching, the delay of the flying pulses can be identified via the DFT-based spectral interferometry instead of temporal interferometry or pulse reconstruction. This enables absolute distance measurements with precision starting from 262 nm in single shot, to 2.8 nm after averaging 1.5 ms, in a non-ambiguity range over 1.7 km. Furthermore, our DFT-based LIDAR method distinctly demonstrates an ability to completely eliminate dead zones. Such an integration of frequency-resolved ultrafast analysis and dual-comb ranging technology may pave a way for the design of future LIDAR systems.

Abstract As a typical failure phenomenon in transformers, sulfur corrosion has garnered significant attention in the field of high‐voltage engineering. Grain boundary character distribution (GBCD) copper windings have been introduced to enhance sulfur corrosion resistance by slowing down intergranular corrosion. In this study, the sulfur corrosion behaviour and mechanisms of the GBCD copper windings under various temperatures were experimentally and theoretically studied. Results show that GBCD can enhance the corrosion resistance of copper in liquid environments. With the increase in temperatures, the insulating properties of oil and papers in traditional copper windings experience notable degradation, while GBCD copper windings show more stable insulating behaviours. In addition, modelling of grain boundary energy indicates that the grain boundary structure of GBCD copper windings has a lower average interface energy of 0.170 eV/Å2. Calculations of reaction thermodynamics show that GBCD copper windings possess a higher failure temperature (135.2°C) and inhibition degree (activation energy) of the sulfur corrosion (32,557.62 J/mol), revealing the stability and enhanced sulfur corrosion resistance at elevated temperatures.

Abstract Background Surgery in geriatric patients often poses risk of major postoperative complications. Acute kidney injury (AKI) is a common complication following noncardiac surgery and is associated with increased mortality. Early identification of geriatric patients at high risk of AKI could facilitate preventive measures and improve patient prognosis. This study used machine learning methods to identify important features and predict AKI following noncardiac surgery in geriatric patients. Methods The data for this study were obtained from a prospective cohort. Patients aged ≥ 65 years who received noncardiac surgery from June 2019 to December 2021 were enrolled. Data were split into training set (from June 2019 to March 2021) and internal validation set (from April 2021 to December 2021) by time. The least absolute shrinkage and selection operator (LASSO) regularization algorithm and the random forest recursive feature elimination algorithm (RF-RFE) were used to screen important predictors. Models were trained through extreme gradient boosting (XGBoost), random forest, and LASSO. The SHapley Additive exPlanations (SHAP) package was used to interpret the machine learning model. Results The training set included 6753 geriatric patients. Of these, 250 (3.70%) patients developed AKI. The XGBoost model with RF-RFE selected features outperformed other models with an area under the precision-recall curve (AUPRC) of 0.505 (95% confidence interval [CI]: 0.369–0.626) and an area under the receiver operating characteristic curve (AUROC) of 0.806 (95%CI: 0.733–0.875). The model incorporated ten predictors, including operation site and hypertension. The internal validation set included 3808 geriatric patients, and 96 (2.52%) patients developed AKI. The model maintained good predictive performance with an AUPRC of 0.431 (95%CI: 0.331–0.524) and an AUROC of 0.845 (95%CI: 0.796–0.888) in the internal validation. Conclusions This study developed a simple machine learning model and a web calculator for predicting AKI following noncardiac surgery in geriatric patients. This model may be a valuable tool for guiding preventive measures and improving patient prognosis. Trial registration The protocol of this study was approved by the Committee of Ethics from West China Hospital of Sichuan University (2019–473) with a waiver of informed consent and registered at www.chictr.org.cn (ChiCTR1900025160, 15/08/2019).

Background Bladder cancer is characterized by a high recurrence rate and mortality, posing a significant challenge to clinical management. Recently, cuproptosis, a novel form of regulated cell death, has been identified as a potential target for therapeutic intervention in various diseases. The contribution of cuproptosis-related microRNAs (miRNAs) in bladder cancer pathogenesis, however, remains largely unexplored. Therefore, the current study aims to construct a miRNA signature related to cuproptosis for predicting the prognosis and facilitating personalized therapeutic strategies in bladder cancer patients. Methods In this study, we retrieved transcriptomic data and clinical information pertaining to bladder cancer from publicly available databases, including the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We identified a set of 19 cuproptosis-related genes through a comprehensive review of relevant literature. Using multivariate Cox regression and LASSO analysis, we constructed a cuproptosis-related miRNA prognostic signature. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were used to validate the accuracy of prediction. Additionally, we developed a nomogram incorporating clinical characteristics and the miRNA signature to further assess its prognostic value. We evaluated the tumor microenvironment (TME) of every patient using immune ESTIMATE, CIBERSORT, and ssGSEA algorithms. We also investigated the differences in tumor mutation burden (TMB) and drug sensitivity between two groups. Finally, we validated the prognostic value of this miRNA signature using the OncomiR dataset. Results We developed a panel of eight cuproptosis-associated miRNAs to serve as a prognostic signature. The predictive validity of this signature was determined using Kaplan-Meier and ROC curves, and was found to be acceptable in both the TCGA training, test and total dataset. The prognostic value of this signature was confirmed by univariate and multivariate Cox regression analysis, indicating its applicability as a prognostic factor. The immune cell infiltration was significantly associated with an immunosuppressive phenotype of TME in the high-risk group of patients; meanwhile, patients in the high-risk group had a lower TMB resulted in shorter survival. Notably, higher estimate scores and IC50 value for chemotherapy drugs were observed in the high-risk group, indicating poor response to immune therapy and chemotherapy.

BackgroundStaphylococcus epidermidis is an important conditionally pathogenic bacterium. SarZ, belonging to the SarA family protein, has been demonstrated in S. aureus to promote the expression of invasive virulence factors while inhibiting biofilm formation. However, the regulatory role of SarZ on S. epidermidis virulence is not completely understood.ResultsIn this study, we successfully deleted the sarZ gene by allelic replacement in S. epidermidis. The sarZ mutant strain exhibited remarkably increased hemolytic activity and drastically impaired biofilm formation, suggesting that SarZ is key regulator of virulence in S. epidermidis. Through butanol extraction of the spent medium and HPLC-MS/MS analysis, production of phenol soluble modulins (PSMs) possessing cytolytic effect was found to be elevated significantly in the mutant. Subsequent qRT-PCR experiments demonstrated that expression of the psm genes, especially the β-type, was upregulated dramatically in the mutant. Meanwhile, transcription of icaA gene responsible for biofilm formation was sharply diminished. The sarZ psmβ double mutant was further generated and displayed a significantly decreased hemolytic activity compared with the sarZ mutant. EMSA assays implied that recombinant SarZ protein can directly bind to the promoter regions of the psmβ and ica operon. DNase I footprinting assays further pinpointed two SarZ-binding sites on the psmβ operon promoter.ConclusionTaken together, the results confirmed that SarZ is a pivotal regulator of virulence in S. epidermidis and might respectively regulate the hemolytic activity and biofilm formation mainly by directly controlling the transcription of psm genes, particularly the β-type, and the ica operon.

BackgroundCognition disorders not only lead to adverse health consequences but also contribute to a range of socioeconomic challenges and diminished capacity for performing routine daily activities. In the digital era, understanding the impact of digital exclusion on cognitive function is crucial, especially in developing countries. ObjectiveThis study aimed to evaluate the association between digital exclusion and cognitive function among elderly populations in developing countries. MethodsUsing data from CHARLS (China Health and Retirement Longitudinal Study) from 2011 to 2020 and MHAS (Mexican Health & Aging Study) from 2012 to 2021, we defined digital exclusion as self-reported absence from the internet. Cognitive function was assessed through 5 tests: orientation, immediate verbal recall, delayed verbal recall, serial 7s, and figure recall. Cognitive function was assessed in 2 categories: worse cognition (a categorical variable that classifies cognition as either better or worse compared to the entire cohort population) and cognitive scores (a continuous variable representing raw cognitive scores across multiple follow-up waves). Logistic regression analyses and generalized estimating equation (GEE) analyses were used to examine the relationship between cognitive function and digital exclusion, adjusting for potential confounders, including demographics, lifestyle factors, history of chronic diseases, basic activities of daily living (BADL) disability, instrumental activities of daily living (IADL) disability, and basic cognitive abilities. ResultsAfter excluding participants with probable cognitive impairment at baseline and those who did not have a complete cognitive assessment in any given year (ie, all tests in the cognitive assessment must be completed in any follow-up wave), a total of 24,065 participants in CHARLS (n=11,505, 47.81%) and MHAS (n=12,560, 52.19%) were included. Of these, 96.78% (n=11,135) participants in CHARLS and 70.02% (n=8795) in MHAS experienced digital exclusion. Adjusted logistic regression analyses revealed that individuals with digital exclusion were more likely to exhibit worse cognitive performance in both CHARLS (odds ratio [OR] 2.04, 95% CI 1.42-2.99; P.05). The fully adjusted mean differences in global cognitive scores between the 2 groups were 0.98 (95% CI 0.70-1.28; P

Objective: Mitomycin C (MMC), a DNA-damaging chemotherapeutic, is commonly used clinically for recurrent cervical carcinoma (CC), either alone or in combination. MMC generates DNA damage resulting in CC cell death yet also induces increased AKT-BAD phosphorylation associated with drug resistance and reduced clinical benefit. The present study evaluates the efficacy of combined MMC and a BAD phosphorylation inhibitor in CC. Methods: The association and function of phosphorylation of BAD on serine 99 (pBADS99) for cell survival of both MMC-resistant or sensitive-CC cells was explored. BAD was mutated to BADS99A to examine the requirement of BADS99 for CC cell survival and a novel small-molecule inhibitor of pBADS99 was utilized. Cell proliferation, survival, foci formation, and patient-derived organoids (PDOs) assays were utilized to determine efficacy, synergy and related mechanisms. Results: MMC IC50 was positively correlated to the cell line pBADS99/BAD ratio. Increased BADS99 phosphorylation was observed in both MMC-sensitive or -resistant CC cells after MMC treatment. Inhibition of pBADS99 in CC cell lines produced synergistic apoptosis through BAD-mediated apoptotic pathways and enhanced DNA damage in response to MMC. The concurrent use of pharmacological inhibition of pBADS99 and MMC was synergistic, resulting in diminished cell viability and inducing apoptotic cell death in MMC-sensitive and -resistant CC cell lines or patient-derived organoids. Conclusion: A combination of MMC with inhibition of BAD phosphorylation potentiated efficacy compared to single agent treatment. The potential further development of such strategies may provide outcome benefits to patients with CC.

Acute respiratory distress syndrome (ARDS) is a critical disorder characterized by immune-related damage to epithelial cells; however, its underlying mechanism remains elusive. This study investigated the effects of alterations in microRNA (miRNA) expression in mast cell-derived exosomes on human bronchial epithelial (HBE) cells and ARDS development in cellular and mouse models challenged with lipopolysaccharide. Lipopolysaccharide-treated mast cell-derived exosomes reduced glutathione peroxidase 4 (GPX4) expression and increased long-chain acyl-CoA synthetase 4 (ACSL4), 15-lipoxygenase (ALOX15), and inflammatory mediator levels in HBE cells. miRNA sequencing revealed a reduction in mast cell-derived exosomal miR-744 levels, which was associated with the regulation of ACSL4, ALOX15, and GPX4 expression. This downregulation of exosomal miR-744 expression reduced miR-744 levels and promoted ferroptosis in HBE cells, whereas the experimental upregulation of miR-744 reversed these adverse effects. Down-regulation of miR-744 induced the expression of markers for ferroptosis and inflammation in HBE cells and promoted pulmonary ferroptosis, inflammation, and injury in LPS-stimulated mice. In vivo, treatment with ACSL4, ALOX15, and GPX4 inhibitors mitigated these effects, and experimental miR-744 expression rescued the lipopolysaccharide-induced changes in HBE cells and mouse lungs. Notably, miR-744 levels were reduced in the plasma and exosomes of patients with ARDS. We concluded that decreased mast cell-derived exosomal miR-744 levels trigger epithelial cell ferroptosis, promoting lung inflammation and damage in ARDS. This study provides new mechanistic insights into the development and sustained pulmonary damage associated with ARDS and highlights potential therapeutic strategies.

Abstract Realizing spin transport between heavy metal and two‐dimensional (2D) magnetic materials at high Curie temperature (TC) is crucial to advanced spintronic information storage technology. Here, environmentally stable 2D nonlayered Fe3O4 nanosheets are successfully synthesized using a reproducible process and found that they exhibit vortex magnetic domains at room temperature. A Verwey phase transition temperature (TV) of ≈110 K is identified for ≈3 nm thick nanosheet through Raman characterization and spin Hall device measurement of the Pt/Fe3O4 bilayer. The anisotropic magnetoresistance ratio decreases near TV, while both the spin Hall magnetoresistance ratio and spin mixing conductance (Gr) increase at TV. As the temperature approaches 112 K, the anomalous Hall effect ratio tends to become zero. The maximum Gr reaches ≈5 × 1015 Ω−1m−2 due to the clean and flat interface between Pt and 2D nanosheet. The observed spin transport behavior in Pt/Fe3O4 spin Hall devices indicates that 2D Fe3O4 nanosheets possess potential for high‐power micro spintronic storage devices applications.

Photodynamic therapy (PDT), as one of the most promising cancer therapy methods, is still limited by several drawbacks, such as tissue hypoxia and shallow light penetration of blue-violet light (200–450 nm), and red light (750 nm) is more penetrating to tissues than blue-violet light, but still lower than near-red light (750–1350 nm). Therefore, we proposed a synergistic therapy system by combining the near-infrared light-triggered PDT with nitric oxide (NO)-based gas therapy to enhance the anti-tumor effects. Upconversion nanoparticles (UCNPs) were loaded with the photosensitizers of ZnPc and the NO donors of l-arginine (L-Arg) to obtain the nanocomposites of UCN@mSiO2@ZnPc@L-Arg. Under 980 nm laser irradiation, reactive oxygen species (ROS) could be produced for PDT and react with l-Arg to produce NO, which is previously reported to have a greater killing effect on tumor cells than ROS and also plays an important role in promoting PDT in our study. Both the in vitro and in vivo tests demonstrated that the combined therapy of PDT with NO therapy could enhance the tumor killing effect significantly compared with the unique application of PDT. The UCNPs-based nanocomposites are expected to be widely used in biomedicine for tumor inhibition.

High-performance wide-bandgap (WBG) perovskite solar cells are used as top cells in perovskite/silicon or perovskite/perovskite tandem solar cells, which possess the potential to overcome the Shockley-Queisser limitation of single-junction perovskite solar cells (PSCs). However, WBG perovskites still suffer from severe nonradiative recombination and large open-circuit voltage (Voc) losses, which restrict the improvement of PSC performance. Herein, we introduce 3,3′-diethyl-oxacarbo-cyanine iodide (DiOC2(3)) and multifunctional groups (C=N, C=C, C-O-C, C-N) into perovskite precursor solutions to simultaneously passivate deep level defects and reduce recombination centers. The multifunctional groups in DiOC2(3) coordinate with free Pb2+ at symmetric sites, passivating Pb vacancy defects, effectively suppressing nonradiative recombination, and maintaining considerable stability. The results reveal that the power conversion efficiency (PCE) of the 1.68 eV WBG perovskite solar cell with an inverted structure increases from 18.51% to 21.50%, and the Voc loss is only 0.487 V. The unpackaged device maintains 95% of its initial PCE after 500 h, in an N2 environment at 25°C.

BackgroundMental health challenges are encountered by frail older adults as the population ages. The extant literature is scant regarding the correlation between depressive symptoms and social participation among frail older adults.MethodsThis study is based on an analysis of data from China Health and Retirement Longitudinal Study (CHARLS) participants aged 60 and older who are frail. A frailty index (FI) was developed for the purpose of assessing the frailty level of the participants. Additionally, latent class analysis (LCA) was employed to classify the participants’ social engagement patterns in 2015 and 2018. The study used ordered logistic regression to examine the relationship between social participation type and depressive symptoms. We also used Latent Transition Analysis (LTA) methods to explore the impact of changes in social activity types on depressive symptoms after three years of follow-up in 2018. In addition, the response surface analysis (RSM) investigation explored the relationship among FI, depression, and social participation.ResultsA total of 4,384 participants completed the baseline survey; three years later, 3,483 were included in the follow-up cohort. The baseline survey indicates that female older adults in rural areas who are single, have lower incomes, shorter sleep durations, and lighter weights exhibited more severe depressive symptoms. Social participation patterns were categorized into five subgroups by LCA. The findings indicate that individuals classified as “board game enthusiasts” (OR, 0.62; 95% CI, 0.47-0.82) and those as “extensive social interaction” (OR,0.67; 95% CI, 0.49-0.90) have a significantly lower likelihood of developing depressive symptoms compared to the “socially isolated” group. We also discovered that “socially isolated” baseline participants who transitioned to the “helpful individual” group after three years had significantly greater depressed symptoms (OR, 1.56; 95% CI, 1.00-2.44). More social activity types and less FI are linked to lower depression in our study.ConclusionThe results of the study emphasize the importance of social participation patterns and the number of social participation types in relation to the severity of depression among frail older adults individuals. This study’s findings may provide important insights for addressing depressive symptoms in frail older adults person.

Although the unforeseen shocks of the global inflation crisis of 2021-2022 rattled business practitioners, investors, and policy-makers, prior research on this phenomenon is centered on ‘mainstream’ business organizations, while the scholarly attention on informal micro-entrepreneurship businesses in the context of crisis management has been relatively sparse. This qualitative study intends to fill this gap in entrepreneurial crisis management literature by investigating the first-hand account of the adversity of the crisis and management practices as the inflation crisis unfolds. Based on semi-structured interviews and the interpretative phenomenological analysis (IPA) method with 16 informal micro-entrepreneurs from four different informal microenterprise sectors (service, trade, manufacturing, and agricultural) in Thailand, the findings revealed that this sector endured inflationary constraints related to customer base, profit margin, cash holding, and household borrowing. This study simultaneously demonstrates how informal micro-entrepreneurs bricolage responses by optimizing inventory agility and transformative supplier partnerships that shaped the immediate adjustments and doubling down on customer services, offering disruptive products and services, and digital shifting contributed to developing long-term resilient practices to navigate the inflation crisis. Furthermore, to advance our theoretical understanding for bolstering inflation crisis preparedness of micro-entrepreneurship via strategic policy responses with implications for policy-makers are also discussed.

In order to optimize the parameters for reversing masculinization and establish the techniques for sex induction of pseudo-males and creation of all-female fry in largemouth bass (Micropterus salmodies, LMB), 15-day-old LMB (1.00 ± 0.10 cm in length, 0.10 ± 0.01 g in weight) were fed a diet supplemented with either 17α-methyltestosterone (MT) or letrozole (LE) and their combination. The experimental groups were M20 (20 mg/kg MT), L20 (20 mg/kg LE) and M10L10 (10 mg/kg MT and 10 mg/kg LE). The control group, named C, was not feed MT or LE. After 60 days, exogenous hormone in the diets was stopped and the effects of MT and LE on growth, male ratio, and gonadal development in LMB were evaluated. At 12-month-old, blood and gonadal tissue samples were collected to measure sex steroid hormones levels, analyze expression levels of dmrt1 and cyp19a1a genes, as well as examine the gonads morphology. The results showed no significant differences in growth between the experimental groups and the control group after a 60-day feeding period with the formulated diet (p > 0.05). The sex reversal ratio of M20, L20, M10L10 were 95.00%, 80.00%, 76.47%, respectively. The gonadal tissue sections showed that the gonadal structure of masculinized fish morphologic resembled that of control male fish. At 12-month-old, the sex reversal ratio in M20, L20, M10L10 and C groups were 100%, 86.67%, 73.33% and 50.00%, respectively. The testicular of pseudo-male fish in the M20 group exhibited well-developed morphology similarities to that of the control group males. However, the testes of pseudo-male fish in the L20 and M10L10 groups were smaller size Estradiol (E2) levels in the experimental groups was significantly lower than those in the control group females (p < 0.05), while testosterone (T) levels were significantly higher than that of the control group (p < 0.05). Compared to the female fish in the control group, pseudo-male fish from all experimental groups showed significantly upregulated expression of dmrt1 (p < 0.05), and significantly downregulated expression of cyp19a1a (p < 0.05). Pseudo-males selected from group M20 exhibited a significantly higher proportion of female offspring (92.00%) compared to the control group (46.50%). In summary, 20 mg/kg MT was the optimal inducing concentration.

Abstract Background Citrus canker is a significant bacterial disease caused by Xanthomonas citri subsp. citri (Xcc) that severely impedes the healthy development of the citrus industry. Especially when citrus fruit is infected by Xcc, it will reduce or even lost its commercial value. However, due to the prolonged fruiting cycle and intricate structure, much less research progress had been made in canker disease on fruit than on leaf. In fact, limited understanding has been achieved on canker development and the response to Xcc infection in fruit. Results Herein, the progression of canker disease on sweet orange fruit was tracked in the field. Results indicated that typical lesions initially appear on the sepal, style residue, nectary disk, epicarp, and peduncle of young fruits after petal fall. The susceptibility of fruits to Xcc infection diminished as the fruit developed, with no new lesions forming at the ripening stage. The establishment of an efficient method for inoculating Xcc on fruit as well as the artificial inoculation throughout the fruit's developmental cycle clarified this infection pattern. Additionally, microscopic observations during the infection process revealed that Xcc invasion caused structural changes on the surface and cross-section of the fruit. Conclusions An efficient system for inoculation on citrus fruit with Xcc was established, by which it can serve for the evaluation of citrus germplasm for canker disease resistance and systematic research on the interactions between Xcc and citrus fruits.

Abstract The issues of health assessment and lifespan prediction have always been prominent challenges in the large‐scale application of lithium‐ion batteries (LIBs). This paper reviews the multiscale modeling techniques and their applications in battery health analysis, including atomic scale computational chemistry, particle scale reaction simulations, electrode scale structural models, macroscale electrochemical models, and data‐driven models at the system level. Multiscale modeling offers a profound insight into material behavior and the aging process of batteries, thereby providing a valuable reference for both estimation and management strategies of battery state of health. To extend the battery lifespan, the utilization of artificial intelligence for material discovery and manufacturing process optimization, the implementation of end‐cloud collaborative battery management systems, and the design of a multiscale simulation integration platform are considered. A management framework aimed at extending battery life is further proposed. This framework offers a promising roadmap for addressing health analysis challenges in LIBs, ultimately leading to more reliable, efficient, and durable solutions for next‐generation batteries.

Abstract Background Chicken is one of the most numerous and widely distributed species around the world, and many studies support the multiple ancestral origins of domestic chickens. The research regarding the yellow skin phenotype in domestic chickens (regulated by BCO2) likely originating from the grey junglefowl serves as crucial evidence for demonstrating the multiple origins of chickens. However, beyond the BCO2 gene region, much remains unknown about the introgression from the grey junglefowl into domestic chickens. Therefore, in this study, based on whole-genome data of 149 samples including 4 species of wild junglefowls and 13 local domestic chicken breeds, we explored the introgression events from the grey junglefowl to domestic chickens. Results We successfully detected introgression regions besides BCO2, including two associated with growth trait (IGFBP2 and TKT), one associated with angiogenesis (TIMP3) and two members of the heat shock protein family (HSPB2 and CRYAB). Our findings suggest that the introgression from the grey junglefowl may impact the growth performance of chickens. Furthermore, we revealed introgression events from grey junglefowl at the BCO2 region in multiple domestic chicken breeds, indicating a phenomenon where the yellow skin phenotype likely underwent strong selection and was retained. Additionally, our haplotype analysis shed light on BCO2 introgression event from different sources of grey junglefowl into domestic chickens, possibly suggesting multiple genetic flows between the grey junglefowl and domestic chickens. Conclusions In summary, our findings provide evidences of the grey junglefowl contributing to the genetic diversity of domestic chickens, laying the foundation for a deeper understanding of the genetic composition within domestic chickens, and offering new perspectives on the impact of introgression on domestic chickens.

Abstract Background The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. Methods We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. Results The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. Conclusion Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.