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Constructed wetlands (CWs) are a promising method to treat effluent from wastewater treatment plants (WWTPs). However, low carbon/nitrogen (C/N) ratios of the influent inhibit denitrification in CWs, resulting in poor nitrogen removal efficiency. Herein, we compared traditional (control), biochar (BC), and β-cyclodextrin-functionalized biochar (BC@β-CD) CW systems to investigate nitrogen removal from influent with low C/N ratios, and the mechanisms that enhance this process. The highest nitrogen removal rates were observed in the BC@β-CD group, with rates 45.89% and 42.48% higher than those of the control, accompanied by a 70.57% and 85.45% decrease in nitrous oxide release, when the C/N ratio decreased from 4 to 2, respectively. Metagenomic and enzymatic analyses indicated that BC@β-CD enhances nitrogen removal by coordinately promoting carbon metabolism and increasing denitrification enzyme activities, without affecting microbial species diversity in CWs. Structural equation modeling confirmed that the foremost advantages of BC@β-CD were effective electron generation and transportation resulting from increased activities of nicotinamide adenine dinucleotide (NADH) dehydrogenase and the electron transfer system (ETS), thereby strategically reallocating more carbon metabolic flow to support denitrification. Our results show that the application of BC@β-CD in CWs to optimize the reallocation of electrons from carbon metabolism is a feasible strategy to enhance denitrification under low C/N conditions.

Abstract The T315I mutation poses a significant threat to patients with chronic phase chronic myeloid leukemia (CP-CML). This study aimed to establish a nomogram to predict the risk of T315I mutation in CP-CML patients. The training cohort included 1,466 patients from 24 hematology centers, and the validation cohort included 820 patients from an additional 20 centers. Peripheral blood blast (PBB), additional chromosomal abnormality (ACA), dasatinib use, non-EMR at 3 months, and BCR::ABLIS > 1% at 6 months were identified as independent risk factors through multivariate Cox regression analysis. The performance of the nomogram was assessed via receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The area under the ROC curve (AUC) values at 5, 10, and 15 years were 0.874, 0.925, and 0.930 for the training cohort, and 0.864, 0.814, and 0.803 for the validation cohort, respectively. The calibration curves for both cohorts were close to the ideal diagonal, and the decision curves indicated clinical net benefit. In conclusion, we developed a nomogram to predict the 5-year, 10-year, and 15-year T315I-free survival probabilities of CP-CML patients. This tool can aid clinicians in the early prediction and timely management of high-risk CP-CML patients with the T315I mutation.

Abstract The objective of this study is to establish a nomogram for predicting low triiodothyronine syndrome (LTS), and clarify the risk factors of LTS. In this study, 109 LTS patients and 331 non-LTS patients were included as the subjects. The general biochemical information of the subjects was collected, and the relevant factors of LTS were evaluated. Concordance index (C-index), Calibration plot, Hosmer-Lemeshow test (H-L test), and Receiver Operating Characteristic (ROC) curve were used to assess the nomogram model. The results of the multiple logistic regression analysis showed that the chronic heart failure (CHF) (OR: 1.978, 95% CI: 1.006–3.892), interleukin-6 (IL-6) (OR: 2.018, 95%CI: 1.043–3.901), infection (OR: 2.136, 95%CI: 1.154–3.955), C-reactive protein (CRP) (OR: 2.720, 95%CI: 1.311–5.641), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR: 3.121, 95%CI: 1.691–5.759) might be the relevant independent risk factors for LTS (P

The extreme temperature range (ETR) is the span between the highest and lowest temperature of a given year, and is a manifestation of extreme temperature variability. It is regarded as having significant environmental and societal impacts, but the influences of human activities on changes in the ETR remain unclear. Here we performed a detection and attribution analysis of the changes in the ETR over the land areas of the Northern Hemisphere (NH) for the period 1960–2018, based on the optimal fingerprinting approach. We found that anthropogenic forcing could be detected and separated from natural forcing, and greenhouse gas forcing could be detected and separated from anthropogenic aerosol forcing, in the spatiotemporal pattern of the NH and in the regional average of the high latitudes. It is estimated that anthropogenic forcing (greenhouse gas emissions) contributed to 129% (152%) of the significant decreasing trend in the NH-averaged ETR. Moreover, compared to the average of 1999–2018, the NH (North America)-averaged ETR was projected to further significantly decrease by 6.7 °C (14.0 °C) in 2081–2100 under the SSP5-8.5 scenario, based on attribution-constrained projection, the magnitude of which was larger than in the models’ raw outputs. In contrast, the ETR was projected to increase significantly in the Mediterranean and adjacent regions under the SSP5-8.5 scenario, and in Central Europe, West Africa, Central Asia, South Asia, and parts of China under the SSP1-1.9 scenario. These results have important implications for understanding and predicting the effects of human activities on changes in extreme temperature variability and for adaptation to these changes in the future.

With the development and popularization of Internet information technology, search engines have become an important channel for the majority of Internet users to find and obtain the information they need. Network attention is an important manifestation of users’ potential demand or realistic concern for a certain thing or phenomenon. The article takes Dujiangyan Scenic Area in Sichuan Province, China as a case study, uses the network search data from the Baidu Index platform from 2017 to 2022, applies geographical spatial statistical analysis methods to study the spatiotemporal characteristics of tourist network attention to Dujiangyan Scenic Area, and explores the factors influencing the spatiotemporal characteristics of tourist network attention. The research found that there is a significant correlation between network attention and changes in the actual number of tourists received. The network attention to Dujiangyan Scenic Area is relatively dispersed in terms of time distribution, with differences in the distribution of tourist network attention over time caused by climate comfort, holiday system, and festival activities. The network attention to Dujiangyan Scenic Area exhibits relatively dispersed spatial distribution characteristics, with the population size of tourist source areas, spatial distance, Internet development level, and economic development level being the main factors influencing the spatial distribution characteristics of tourist network attention. Tourist attractions can enhance the effectiveness of tourism network marketing, develop differentiated tourism marketing and promotion strategies by utilizing the spatiotemporal distribution characteristics of network attention.

Patent ductus arteriosus (PDA) is one of the most common forms of congenital heart disease (CHD). Infectious endocarditis (IE) is a rare but serious complication of PDA. PDA combined with pulmonary artery aneurysm (PAA) due to IE is rare in children. In this report, we report a rare pediatric PDA case, complicated with PAA due to IE. Transcatheter closure of PDA without the surgical intervention of PAA was performed, with a favorable prognosis.

ABSTRACT This study aimed to assess the correlation between estimated pulse wave velocity (ePWV) and mortality rates related to all‐cause and cardiovascular disease (CVD) among individuals diagnosed with chronic kidney disease (CKD) in the United States. A total of 4669 participants with CKD were identified from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. We calculated the incidence of CKD using an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. Our study examined the association between ePWV and mortality risk based on weighted Kaplan–Meier plots and multivariate Cox regression. Linear testing between ePWV and mortality from all causes and CVD was performed using restricted cubic splines and Cox regression. This study included 4669 patients with CKD from the NHANES, representing 37 million Americans with CKD. There was a mean age of 71.9 years, and 48.1% of participants were male. With every increase of 1 m/s in ePWV measurement, there is a corresponding 31% (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.28–1.34) increase in the rate of mortality from all causes and a 32% (HR: 1.32, 95% CI: 1.27–1.37) increase in the rate of mortality from CVD. A significantly higher rate of cardiovascular and all‐cause mortality was observed in patients with CKD with elevated ePWV than in those with lower ePWV, as shown in the weighted Kaplan–Meier plots. Patients with CKD have a significant relationship between ePWV and all‐cause and cardiovascular mortality.

Background: Treatment outcomes for acute promyelocytic leukemia (APL) have improved with all-trans-retinoic acid and arsenic trioxide, yet relapse remains a concern, especially in pediatric patients. The prognostic value of minimal residual disease (MRD) post-induction and the impact of arsenic levels during induction on MRD are not fully understood. Objectives: To evaluate the relationship between post-induction MRD levels and relapse-free survival (RFS) in pediatric APL patients, and to investigate the correlation between blood arsenic concentration levels during induction therapy and MRD status. Design: A retrospective analysis of pediatric APL patients enrolled in a clinical trial from September 2011 to July 2020. Methods: We assessed the relationship between RFS and post-induction MRD levels using the log-rank test. The optimal MRD cut-off was determined using the “surv_cutpoint” function in the survminer R package. Arsenic concentration levels were monitored in 16 patients on days 7 and 14 of induction therapy, and Spearman correlation was used to analyze the relationship between arsenic concentrations and MRD levels. Results: Among 176 pediatric APL patients, with a median follow-up of 6 years, 4 relapsed. Patients with MRD >3.1% had significantly lower RFS compared to those with MRD ⩽3.1% (94.6% vs 100%, p = 0.023). In addition, a negative correlation was found between blood arsenic concentration levels and post-induction MRD levels. Lower arsenic concentrations were associated with higher MRD levels, with significant correlations observed for trough concentrations ( R = −0.666, p = 0.005) and peak concentrations ( R = −0.499, p = 0.049) on day 7. Conclusion: Our study highlights the prognostic significance of post-induction MRD assessment in pediatric APL. We also demonstrate a negative correlation between blood arsenic concentration levels and MRD, suggesting that lower arsenic concentrations during induction therapy may contribute to a higher MRD burden. These findings may inform strategies to optimize treatment and improve outcomes in pediatric APL. Trial registration: www.clinicaltrials.gov (NCT02200978).

Abstract The sustainable development of sports facilities and their integration with the ecological environment are crucial in addressing global environmental challenges. This study examines the coupling coordination between sports facilities and the ecological environment in nine prefecture-level cities in Fujian Province, China, from 2013 to 2020, within the framework of China’s “Dual Carbon” strategy. Using a multidisciplinary approach that integrates economics, sociology, and geography, the study employs the entropy method and coupling coordination models to analyze the temporal evolution and spatial distribution of the coupling coordination between sports facilities and the ecological environment. The findings reveal that the overall trend of coupling coordination is positive, with the degree of coordination improving over time from severe imbalance in 2013 to high-quality coordination by 2020. Economic factors, such as per capita GDP, positively influence the coupling coordination, while factors like population density and regional GDP have a negative impact. Coastal cities, such as Xiamen and Zhangzhou, demonstrate stronger regional correlations and play a critical role in improving the overall coupling level of the province. This research provides several recommendations for promoting orderly and optimal development, considering the distinct characteristics of sports facilities and the ecological environment.

Abstract The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.

Abstract Background The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro. Results Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P 0.50, P

Introduction Elderly patients are at a high risk of postoperative delirium (POD), leading to increased postoperative morbidity and mortality. The use of dexmedetomidine and depth of anaesthesia may influence POD. This study aims to determine the effects of dexmedetomidine infusion versus normal saline placebo during light versus deep anaesthesia on POD among elderly patients undergoing major non-cardiac surgery.Methods and analysis This prospective, multicentre, randomised, controlled, factorial trial will be conducted at three tertiary hospitals in Jiangsu, China. We will recruit a total of 420 patients who are at least 60 years old and undergoing major non-cardiac surgery (thoracic, abdominal, urology, orthopaedic and spine surgery) under general anaesthesia. Patients will be randomised (1:1:1:1) to receive one of four anaesthesia regimens: (1) dexmedetomidine and light anaesthesia, (2) dexmedetomidine and deep anaesthesia, (3) placebo and light anaesthesia or (4) placebo and deep anaesthesia. Dexmedetomidine will be infused at 0.5 µg/kg/h throughout surgery, and intraoperative bispectral index target will be 55 for light anaesthesia and 40 for deep anaesthesia. The primary outcome is the occurrence of POD during the first 7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method two times per day. The secondary outcomes include days with POD, type of POD, pain scores at rest and on movement at 24 and 48 hours postoperatively, patient-controlled intravenous fentanyl consumption during 0–24 and 24–48 hours postoperatively, hypotension, bradycardia, postoperative nausea and vomiting, non-delirium complications, length of postoperative hospital stay, 30-day cognitive function and 30-day mortality. Data will be analysed on a modified intention-to-treat basis.Ethics and dissemination This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and each participating centre. The trial results will be published in a peer-reviewed journal.Trial registration Chinese Clinical Trial Registry (ChiCTR2300073271)

Abstract Background The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. Methods Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. Results (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P

旨在为低温压榨鲜青花椒油的工业生产、贮藏和质量控制提供借鉴，利用超高效液相色谱-二极管阵列检测器-高分辨质谱（UPLC-DAD-HRMS）技术对低温压榨鲜青花椒油中色素进行测定，并研究贮藏过程中光、氧、温度对低温压榨鲜青花椒油的色素含量和色泽L*、a*、b*的影响。结果表明：从低温压榨鲜青花椒油中鉴定出32种叶绿素和10种类胡萝卜素；叶绿素中主要含有叶绿素a、C132-羟基-叶绿素a、叶绿素b和脱镁叶绿素a；类胡萝卜素中主要含有叶黄素和β-胡萝卜素；叶绿素总量为9.44 mg/kg，类胡萝卜素总量为4.95 mg/kg。贮藏过程中影响低温压榨鲜青花椒油中色素降解最主要的因素是光，其次是温度，氧气几乎没有影响。另外，a*可以作为衡量低温压榨鲜青花椒油色素含量及色泽控制的指标。Aiming to contribute to the industrial production, storage and quality control of cold-pressed fresh green Huajiao oil, the change of pigment in cold-pressed fresh green Huajiao oil was analyzed by ultra-high performance liquid chromatography-diode array detector-high resolution mass spectrometry (UPLC-DAD-HRMS), and the effects of light, oxygen, temperature on the pigment content and color(L*, a*, b*) of fresh green Huajiao oil in storage were determined. The results showed that 32 chlorophylls and 10 carotenoids were identified from the cold-pressed fresh green Huajiao oil. The main chlorophylls were chlorophyll a, C132-hydroxy chlorophyll a, chlorophyll b and pheophytin a; the main carotenoids were lutein and β-carotene. The total chlorophyll content was 9.44 mg/kg, and the total carotenoid content was 4.95 mg/kg. During storage, the main factor affecting the degradation of pigment in fresh green Huajiao oil was light, followed by temperature, and oxygen had little effect. In addition, the color index a* can be used as an index for pigment content and color control.

In radioactivity analysis, counting efficiency(E) and background(to be precise, it should be deterministic background) are usually discussed, but apparent counting efficiency(E') and random background are rarely mentioned. However, the influence of background(including both deterministic background and random background) on apparent counting efficiency must be considered, especially for samples with low radioactivity. The relation between E and E' can be described as the equation E' = E + ΔB/A, where A is the sample radioactivity, and ΔB is the residue background, including two parts: the counting rate of residual deterministic background caused by inaccurate deduction of background and the counting rate of random background that cannot be deducted. In this paper, E' was studied on the following assumptions: E was fixed at 90%; A was changing from 0.1 to 100, with a step of 0.1(relative unit, similarly hereinafter); and ΔB was set to be fixed, or to follow a specific distribution. The simplest continuous distribution(uniform distribution) and the most commonly used continuous distribution(normal distribution) were chosen for this research, and the function “random number generator ” of the software Excel was used to simulate the random variable ΔB. Specifically speaking, the random variable ΔB was assumed to follow ±0.1·U(0,1), ±0.1·U(−0.5,0.5), ±0.1·N(0.5,1), or ±0.1·N(0,1), where U stands for uniform distribution and N for normal distribution. The influence of background on apparent counting efficiencies is divided into two aspects: one is the systematic error introduced by inaccurate background deduction, which makes all apparent counting efficiencies deviate from the counting efficiency in the same direction; the other is the accidental error caused by background fluctuations, which makes apparent counting efficiency fluctuate within a certain range. Regardless of the error type, the influence of background on apparent counting efficiency will increase as the radioactivity of the sample decreases. For samples with high radioactivity, the difference between apparent counting efficiency and counting efficiency is so small that it can be ignored, therefore it is not necessary to distinguish between the two concepts of apparent counting efficiency and counting efficiency; but for samples with low radioactivity, they must be used differently. Unless there is no standard sample with high radioactivity, it is not recommended to use the inefficient method, which is reported in Lin’s paper(ACS Earth Space Chem, 2022, 6(7): 1868-1875), to obtain counting efficiency by measuring a large number of samples with low radioactivity. It is advisable to obtain counting efficiency by measuring standard samples with sufficiently high radioactivity, in which the influence of background can be negligible.

Abstract The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.

n-Caproate, which is produced via chain elongation (CE) using waste biomass, can supply various fossil-derived products, thus advancing the realization of carbon neutrality. Ammonia released from the degradation of nitrogen-rich waste biomass can act as a nutrient or an inhibitor in anaerobic bioprocesses, including CE, with the distinction being primarily dependent on its concentration. Currently, the optimal concentration of ammonia and the threshold of toxicity for open-culture n-caproate production using ethanol as an electron donor, along with the underlying mechanisms, remain unclear. This study revealed that the optimal concentration of ammonia for n-caproate production was 2.0 g∙L−1, whereas concentrations exceeding this threshold markedly suppressed the CE performance. Exploration of the mechanism revealed the involvement of two forms of ammonia (i.e., ammonium ions and free ammonia) in this inhibitory behavior. High ammonia levels (5.0 g∙L−1) induced excessive ethanol oxidation and suppressed the reverse β-oxidation (RBO) process, directly leading to the enhanced activities of enzymes (phosphotransacetylase and acetate kinase) responsible for acetate formation and diminished activities of butyryl-coenzyme A (CoA):acetyl-CoA transferase, caproyl-CoA:butyryl-CoA transferase, and caproyl-CoA:acetyl-CoA transferase that are involved in the syntheses of n-butyrate and n-caproate. Furthermore, the composition of the microbial community shifted from Paraclostridium dominance (at 0.1 g∙L−1 ammonia) to a co-dominance of Fermentimonas, Clostridium sensu stricto 12, and Clostridium sensu stricto 15 at 2.0 g∙L−1 ammonia. However, these CE-functional bacteria were mostly absent in the presence of excessive ammonia (5.0 g∙L−1 ammonia). Metagenomic analysis revealed the upregulation of functions such as RBO, fatty acid synthesis, K+ efflux, adenosine triphosphatase (ATPase) metabolism, and metal cation export in the presence of 2.0 g∙L−1 ammonia, collectively contributing to enhanced n-caproate production. Conversely, the aforementioned functions (excluding metal cation export) and K+ influx were suppressed by excessive ammonia, undermining both ammonia detoxification and n-caproate biosynthesis. The comprehensive elucidation of ammonia-driven mechanisms influencing n-caproate production, as provided in this study, is expected to inspire researchers to devise effective strategies to alleviate ammonia-induced inhibition.

The power battery in an electric vehicle is an essential part, and the damage to the battery will have a substantial impact on its thermal characteristics. In order to improve the reliability of the air-cooled lithium-ion battery packs in the high temperature environments, this paper offers a more useful and general optimization strategy for the design of the thermal management system for the batteries which have a damaged battery. To ensure the optimal heat dissipation and prolong the battery string operation, the damaged batteries should be swapped out with the backup batteries. The relationship between the target and the design variables which was established using the quadratic polynomial response function is examined. The experimental cases are selected using the optimal Latin hypercube design approach. After optimizing through the multi-island genetic approach, the error between the simulation results and the prediction results is only 0.06 %. The maximum temperature and the maximum temperature difference of the ideal structure are reduced by 4.58 % and 28.05 %, respectively. Then, the backup battery is selected as the sole battery that has the highest temperature of the ideal structure, and each broken battery is replaced by the backup battery when the damaged position is determined. Finally, a parametric equation connecting the temperature and the flow rate is created, and the inlet flow rate is tuned to match the optimal heat dissipation state of the battery pack. The results of the battery thermal management system having a damaged battery in various situations have an important significance for adjusting the operating conditions of the cooling system for the batteries.

Summary: Background: Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The complete pathogenesis of the virus remains to be determined. Unraveling the molecular mechanisms governing SARS-CoV-2 interactions with host cells is crucial for the formulation of effective prophylactic measures and the advancement of COVID-19 therapeutics. Methods: We analyzed human lung single-cell RNA sequencing dataset to discern the association of butyrophilin subfamily 3 member A2 (BTN3A2) expression with COVID-19. The BTN3A2 gene edited cell lines and transgenic mice were infected by live SARS-CoV-2 in a biosafety level 3 (BSL-3) laboratory. Immunoprecipitation, flow cytometry, biolayer interferometry and competition ELISA assays were performed in BTN3A2 gene edited cells. We performed quantitative real-time PCR, histological and/or immunohistochemical analyses for tissue samples from mice with or without SARS-CoV-2 infection. Findings: The BTN3A2 mRNA level was correlated with COVID-19 severity. BTN3A2 expression was predominantly identified in epithelial cells, elevated in pathological epithelial cells from COVID-19 patients and co-occurred with ACE2 expression in the same lung cell subtypes. BTN3A2 targeted the early stage of the viral life cycle by inhibiting SARS-CoV-2 attachment through interactions with the receptor-binding domain (RBD) of the Spike protein and ACE2. BTN3A2 inhibited ACE2-mediated SARS-CoV-2 infection by reducing ACE2 in vitro and in vivo. Interpretation: These results reveal a key role of BTN3A2 in the fight against COVID-19. Identifying potential monoclonal antibodies which mimic BTN3A2 may facilitate disruption of SARS-CoV-2 infection, providing a therapeutic avenue for COVID-19. Funding: This study was supported by the National Natural Science Foundation of China (32070569, U1902215, and 32371017), the CAS “Light of West China” Program, and Yunnan Province (202305AH340006).

ObjectiveThe purpose of this study was to understand the relationship between the multiple chronic conditions (MCC), mental health and cognitive function of older adults in the community, and to propose a hypothesis that depressive symptom mediate the number of chronic diseases and cognitive impairment in older adults.MethodParticipants aged 65 years and older from 35 communities in 14 cities in Guangxi, China were recruited. The residents’ depressive symptom (PHQ-9) and cognitive status (AD-8) were evaluated, Chi-square test was used to explore the effects of different socio-demographic characteristics on depressive symptom and cognitive impairment. Pearson correlation analysis and the process model 4 were used to explore the relationship between the number of chronic diseases, depressive symptom and cognitive impairment.ResultA total of 11,582 older adults were included in our analysis. The rate of MCC reaching 26.53%. Hypertension combined with diabetes accounts for the highest proportion of two chronic diseases (13.2%). Among the combination of three chronic diseases, the highest incidence of coexisting hypertension combined with cervical/lumbar spondylosis, and rheumatoid arthritis (7.1%). In this study, depression symptoms accounted for 12.9% of older adults aged 65 and above, and cognitive impairment accounted for 27.4%. Female, older age, reside in urban areas, lower educational levels, no spouse, live alone, and MCC were risk factors for depressive symptom and cognitive impairment in older adults (P

Abstract Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Abstract The clinical benefit of tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) is limited due to drug resistance. Here, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, p53 binds to the promoter of stearoyl-CoA desaturase 1 (SCD1) and represses its transcription. High expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

BackgroundPost-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD.MethodsA total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment.ResultsThere were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p