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Abstract Background Bipolar disorder is a complex polygenic disorder that is characterized by recurrent episodes of depression and mania, the heterogeneity of which is likely complicated by epigenetic modifications that remain to be elucidated. Methods We performed transcriptomic analysis of peripheral blood RNA from monozygotic (MZ) twins discordant for bipolar disorder to identify disease-associated differentially expressed long noncoding RNAs (DE-lncRNAs), which were further validated in the PsychENCODE brain RNA-seq dataset. We then performed behavioral tests, electrophysiological assays, chromatin immunoprecipitation, and PCR to investigate the function of DE-lncRNAs in the mouse and cell models. Statistical analyses were performed using GraphPad Prism 9.0 or SPSS. Results We identified a bipolar disorder-associated upregulated long non-coding RNA (lncRNA), AP1AR-DT. We observed that overexpression of AP1AR-DT in the mouse medial prefrontal cortex (mPFC) resulted in a reduction of both the total spine density and the spontaneous excitatory postsynaptic current (sEPSC) frequency of mPFC neurons as well as depressive and anxiety-like behaviors. A combination of the results of brain transcriptome analysis of AP1AR-DT overexpressing mice brains with the known genes associated with bipolar disorder revealed that NEGR1, which encodes neuronal growth regulator 1, is one of the AP1AR-DT targets and is reduced in vivo upon gain of AP1AR-DT in mice. We further demonstrated that overexpression of recombinant Negr1 in the mPFC neurons of AP1AR-DT OE mice ameliorates depressive and anxiety-like behaviors and normalizes the reduced excitatory synaptic transmission induced by the gain of AP1AR-DT. We finally identified that AP1AR-DT reduces NEGR1 expression by competing for the transcriptional activator NRF1 in the overlapping binding site of the NEGR1 promoter region. Conclusions The epigenetic and pathophysiological mechanism linking AP1AR-DT to the modulation of depressive and anxiety-like behaviors and excitatory synaptic function provides etiological implications for bipolar disorder.

Abstract Objective This study aims to assess the prognostic and diagnostic value of inflammatory indexes related to gestational diabetes mellitus (GDM) from the second trimester to the third trimester of pregnancy. Materials and methods In this study, we randomly selected 65 pregnant women diagnosed with GDM at our hospital from December 2022 to June 2023 to form the GDM group (n = 65). Additionally, 65 pregnant women at the same gestational weeks without GDM were selected as the Normal group (n = 65). We collected gestational information and serum samples at 24 and 36 weeks of gestation from the participants. The levels of NLRP3, IL-1Ra, and TBP-2 were determined using enzyme-linked immunosorbent assay (ELISA) to explore their changes during pregnancy. Further, this study analyzed the changes in the levels of NLRP3, IL-1Ra, and TBP-2 at 24 and 36 weeks of gestation in GDM patients and their correlation with gestational diabetes mellitus. Results The study showed that pre-pregnancy body mass index (BMI), neonatal weight, gestational hypertension, and macrosomia are significantly associated with the occurrence of GDM (P

Abstract Purpose This study aimed to explore the prognostic factors and survival patterns based on the histological type for the perimenopausal endometrial carcinoma (PIPEC) patients treated with hysterectomy. Methods The PIPEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Methods of random survival forest (RSF) and Cox regression were used to identify the possible prognostic factors of PIPEC patients. Then overall survival (OS) and cancer-specific survival (CSS) of PIPEC data were analyzed by histological types with regional lymph nodes status and SEER-stage to investigate the survival patterns of the PIPEC patients. Results A total of 14,178 PIPEC patients were included in the study. We found tumor size, grade, histology, SEER-stage, AJCC-stage, AJCC-T stage, metastasis to distant organs and regional lymph nodes status had a significant survival outcome for PIPEC both for OS and CSS (all p

Abstract Background Bed rest during pregnancy can lead to reduced physical activity, impairing lower limb venous blood flow and increasing the risk of deep vein thrombosis (DVT) and muscle atrophy. We investigated the clinical efficacy of foam rolling intervention (FRI) in enhancing lower limb venous blood flow, mitigating the risk of DVT and muscle atrophy in pregnant women on bed rest. Methods This single-blind, randomised controlled trial enrolled 86 pregnant women with long-term bed rest for foetal protection (≥ 7 days), gestational age ≥ 20 weeks, and maternal age 0.05), however, the peak blood velocities of the popliteal veins were significantly higher in the control group (P = 0.031). On the seventh day post-intervention, the experimental group had significantly higher mean and peak blood velocities in femoral and popliteal veins, significantly (P

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that commonly affects children and adolescents with a poor prognosis. The terminal unfolded protein response (UPR) is an emerging anti-cancer approach, although its role in pediatric T-ALL remains unclear. In our pediatric T-ALL cohort from different centers, a lower QRICH1 expression was found associated with a worse prognosis of pediatric T-ALL. Overexpression of QRICH1 significantly inhibited cell proliferation and stimulated apoptosis of T-ALL both in vitro and in vivo. Upregulation of QRICH1 significantly downregulated 78 KDa glucose-regulated protein (GRP78) and upregulated CHOP, thus activating the terminal UPR. Co-overexpression of GRP78 in T-ALL cells overexpressing QRICH1 partially reverted the inhibited proliferation and stimulated apoptosis. QRICH1 bound to the residues Asp212 and Glu155 of the nucleotide-binding domain (NBD) of GRP78, thereby inhibiting its ATP hydrolysis activity. In addition, QRICH1 was associated with endoplasmic reticulum (ER) stress in T-ALL, and overexpression of QRICH1 reversed drug resistance. Overall, low QRICH1 expression is an independent risk factor for a poor prognosis of pediatric T-ALL. By inhibiting GRP78, QRICH1 suppresses pediatric T-ALL.

Abstract Background Calcific aortic valve stenosis (CAVS) is one of the most challenging heart diseases in clinical with rapidly increasing prevalence. However, study of the mechanism and treatment of CAVS is hampered by the lack of suitable, robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposition. Here, we aim to establish a mouse model to mimic the development and features of CAVS. Methods The model was established via aortic valve wire injury (AVWI) combined with vitamin D subcutaneous injected in wild type C57/BL6 mice. Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradient. Histopathological specimens were collected and examined in respect of valve thickening, calcium deposition, collagen accumulation, osteogenic differentiation and inflammation. Results Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time dependent manner and tended to be stable at 28 days. Compared with the sham group, simple AVWI or the vitamin D group, the hybrid model group showed typical pathological features of CAVS, including hemodynamic alterations, increased aortic valve thickening, calcium deposition, collagen accumulation at 28 days. In addition, osteogenic differentiation, fibrosis and inflammation, which play critical roles in the development of CAVS, were observed in the hybrid model. Conclusions We established a novel mouse model of CAVS that could be induced efficiently, robustly and economically, and without genetic intervention. It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effective pharmacological targets.

Abstract The study of drug–target interaction plays an important role in the process of drug development. The subject of DTI forecasting has advanced significantly in the last several years, yielding numerous significant research findings and methodologies. Heterogeneous data sources provide richer information and comprehensive perspectives for drug–target interaction prediction, so many existing methods rely on heterogeneous networks, and graph embedding technology becomes an important technology to extract information from heterogeneous networks. These approaches, however, are less concerned with potential noisy information in heterogeneous networks and more focused on the extent of information extraction in those networks. Based on this, a potential DTI predictive network model called FBRWPC is proposed in this paper. It uses a fine-grained similarity selection program to first integrate similarity on similar networks and then a bidirectional random walk graph embedding learning method with restart to obtain an updated drug target interaction matrix. Through the use of similarity selection and fine-grained selection similarity integration, the framework can effectively filter out the noise present in heterogeneous networks and enhance the model's prediction performance. The experimental findings demonstrate that, even after being split up into four distinct types of data sets, FBRWPC can still retain great prediction performance, a sign of the model's resilience and good generalization.

Abstract Background Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019. Methods This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019. Results In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65–69, 75–79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature. Conclusions Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

Abstract As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3′-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer. Graphical Abstract

Abstract HIF‐1α (hypoxia induced factor‐1α), a vital protective signal against hypoxia, has a short lifetime after myocardial infarction (MI). Increasing HIF‐1α stability by inhibiting its hydroxylation with prolyl hydroxylases inhibitors such as DPCA (1,4‐dihydrophenonthrolin‐4‐one‐3‐carboxylic acid) presents positive results. However, the optimal inhibitor administration profile for MI treatment is still unexplored. Here, injectable, thermosensitive hydrogels with programmable DPCA release are designed and synthesized. Hydrogel degradation and slow DPCA release are coupled to form a feedback loop by attaching pendant DPCA to polymer backbone, which serve as additional crosslinking points through π–π and hydrophobic interactions. Pendant carboxyl groups are added to the copolymer to accelerate DPCA release. Burst release in the acute phase for myocardial protection and extended near zero‐order release across the inflammatory and fibrotic phases with different rates are achieved. All DPCA‐releasing hydrogels upregulate HIF‐1α, decrease apoptosis, promote angiogenesis, and stimulate cardiomyocyte proliferation, leading to preserved cardiac function and ventricular geometry. Faster hydrogel degradation induced by faster DPCA release results in a HIF‐1α expression eight times of healthy control and better therapeutic effect in MI treatment. This research demonstrates the value of precise regulation of HIF‐1α expression in treating MI and other relevant diseases and provides an implantable device‐based modulation strategy.

The hydrological cycle is anticipated to become increasingly variable due to intensified global climate extremes and frequent floods. Understanding the evolution and driving mechanisms of floods in the context of climatic extremes is essential, particularly on the Loess Plateau (LP) where anthropogenic activities are significant. Here, we examined the spatiotemporal variability of climate extremes and their impacts on flood processes on the LP during 1956–2015. We employed a paired year approach to quantitatively assess the driving role of anthropogenic activities on flood changes in 11 major basins. Our findings indicated a general decline in extreme precipitation indices, while temperature has increased across most of the LP. Both annual runoff (Q) and high flow (Q5) magnitude significantly decreased in all basins. We identified that the major climatic indices driving Q5 included erosive precipitation amount, flood season precipitation, heavy precipitation amount, and maximum 7-day precipitation amount. Importantly, anthropogenic activities have mitigated the impact of climate extremes on Q5 regimes. Compared the post-2000 with reference period (1956–1979), under similar climatic conditions, we observed a reduction in the average Q5 magnitude by 30.19–78.14% and a decrease in the average Q5 duration by 46.48–100.00% across the basins. The contributions of climate variability and anthropogenic activities to Q5 magnitude changes among 11 basins ranged from –37.58% to 22.02% and –56.84% to –15.08%, respectively, highlighting the crucial role of ecological restoration in reducing Q5 magnitude. These results underscore the importance of ecological restoration in flood regulation and offer valuable insights for basin management in the Yellow River Basin.

Background: Zika virus (ZIKV) infection during pregnancy presents a significant health risk in women of reproductive age and their offspring due to severe neurological complications. It is meaningful to assess its global burden and temporal trends. Methods: This study extracted annual incidence cases and rates of ZIKV among women of reproductive age (15–49 years) between 2011 and 2021 from Global Burden of Diseases (GBD) 2021, including global level, 21 GBD regions, 5 socio-demographic index (SDI) regions, 7 age groups, and 204 countries and territories. Relative percent change in cases and estimated annual percentage change (EAPC) of incidence rates were used to quantify the temporal trends. Results: The incidence rate of ZIKV infection exhibited a pronounced peak in 2016 at 174.27 per 100,000 population, with an EAPC of 158.30 % from 2011 to 2016 and −51.86 % from 2016 to 2021 at 3.06 per 100,000 population. And only 5 out of the 21 GBD regions reported ZIKV infection in 2021, predominantly concentrated in Latin America and Caribbean. The outbreaks were primarily concentrated in low-middle and middle SDI regions. In 2021, at the global level, the incidence rates of ZIKV infection among women of reproductive age were similar across different age groups, ranging from 2.41 to 3.39 per 100,000 population. The proportion of ZIKV infection cases was slightly higher in women aged 25–29 and 30–34 years compared to other age groups in 2021, whereas a higher proportion of cases were observed in younger age groups in 2011 and 2016. Conclusions: Women of reproductive age in Latin America and Caribbean continue to face the threat of ZIKV. Regions with lower SDI had a disproportionately severe burden. Future public health strategies should focus on high-risk areas and populations of reproductive age, enhancing surveillance, prevention, and education efforts to further mitigate the public health threat posed by ZIKV.

Abstract In the past century, scholars from both domestic and international communities have delved into the study of numerical weather prediction models to promptly understand meteorological factors and mitigate the impacts of extreme weather events on humanity. Effective and precise prediction models enable the forecasting of meteorological conditions in the upcoming days, empowering individuals to implement proactive measures to minimize the adverse effects of extreme weather (Liang et al., 2021). The WRF (Weather Research and Forecasting) modeling system is commonly used for forecasting meteorological elements. However, uncertainties terribly hamper the correctness of the forecasting results. To this end, the present study was conducted to build a secondary model on the basis of the WRF forecast model. The WRF‐BPNN model was proposed for verification after constructing the network, the temperature vertical profile and the mixing ratio vertical profile were predicted, and the results on the validation set were tested. The results showed that the WRF‐BPNN model could effectively predict the temperature profile and mixing ratio profile, presenting better performance than the traditional WRF model.

Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. These chronic infections are characterized by high expression of the HPV E6 and E7 oncogenes and the absence of the L1 and L2 capsid proteins. The regulation of HPV gene expression plays a crucial role in both the viral life cycle and rare oncogenic events. Alternative splicing of HPV mRNA is a key mechanism in post-transcriptional regulation. Through alternative splicing, HPV mRNA is diversified into various splice isoforms with distinct coding potentials, encoding multiple proteins and influencing the expression of HPV genes. The spliced mRNAs derived from a donor splicing site within the E6 ORF and one of the different acceptor sites located in the early mRNA contain E6 truncated mRNAs, named E6*. E6* is one of the extensively studied splicing isoforms. However, the role of E6* proteins in cancer progression remains controversial. Here, we reviewed and compared the alternative splicing events occurring in the genomes of HR-HPV and LR-HPV. Recently, new HPV alternative splicing regulatory proteins have been continuously discovered, and we have updated the regulation of HPV alternative splicing. In addition, we summarized the functions of known splice isoforms from three aspects: anti-tumorigenic, tumorigenic, and other cancer-related functions, including not only E6*, but also E6^E7, E8^E2, and so on. Comprehending their contributions to cancer development enhances insights into the carcinogenic mechanisms of HPV and explores the potential utility of alternative splicing in the diagnosis and treatment of cervical cancer.

Dimensional data directly reflects the growth rate of individual fish, an important economic trait of interest to fish researchers. Efficiently obtaining large-scale fish dimension data would be valuable for both selective breeding and production. To address this, our study proposes a custom dimension measurement method for fish using the YOLOv5-keypoint framework with multi-attention mechanisms. We optimized the YOLOv5 framework, incorporated the SimAM attention mechanism to achieve more accurate and faster fish detection, and added customizable landmarks to the network structure, enabling flexible configuration of the number and location of feature points in the training dataset. This method is applicable to various aquacultural species and other objects. We tested the effectiveness of the method using the economically important grass carp (Ctenopharyngodon idella). The proposed method outperforms pure YOLOv5, Faster R-CNN, and SSD in terms of precision and recall rates, achieving an impressive average precision of 0.9781. Notably, field trials confirmed the method's exceptional measurement accuracy, exceeding 97% compatibility with manual measurements, while demonstrating a real-time speed of 38 frames per second on the NVIDIA RTX A4000. This enables efficient and accurate large-scale surface dimension measurements of economic fish. To facilitate massive measurements in agricultural research, we have implemented this method as an online platform, called Mode-recognition Ruler (MrRuler, http://bioinfo.ihb.ac.cn/mrruler). The platform identifies objects in a single image at an average speed of 0.486 ​± ​0.005 ​s, based on a dataset of 10,000 images. MrRuler includes two preset carp models and allows users to upload training datasets for custom models of their targets of interest.

Abstract Ionic conductive hydrogels (ICHs) have recently gained prominence in biosensing, indicating their potential to redefine future biomedical applications. However, the integration of these hydrogels into sensor technologies and their long‐term efficacy in practical applications pose substantial challenges, including a synergy of features, such as mechanical adaptability, conductive sensitivity, self‐adhesion, self‐regeneration, and microbial resistance. To address these challenges, this study introduces a novel hydrogel system using an imidazolium salt with a ureido backbone (UL) as the primary monomer. Fabricated via a straightforward one‐pot copolymerization process that includes betaine sulfonate methacrylate (SBMA) and acrylamide (AM), the hydrogel demonstrates multifunctional properties. The innovation of this hydrogel is attributed to its robust mechanical attributes, outstanding strain responsiveness, effective water retention, and advanced self‐regenerative and healing capabilities, which collectively lead to its superior performance in various applications. Moreover, this hydrogel exhibited broad‐spectrum antibacterial activity. Its potential for biomechanical monitoring, especially in tandem with contact and noncontact electrocardiogram (ECG) devices, represents a noteworthy advancement in precise real‐time cardiac monitoring in clinical environments. In addition, the conductive properties of the hydrogel make it an ideal substrate for electrophoretic patches aimed at treating infected wounds and consequently enhancing the healing process.

Objectives To estimate the interaction between economic status (ES) and healthy lifestyle in long COVID among Chinese older people infected with SARS-CoV-2.Design A cross-sectional study based on the Peking University Health Cohort in Anning, Yunnan.Setting All primary health institutions in Anning, Yunnan Province, China, from April to May 2023.Participants A total of 4804 people aged 60 and older infected with SARS-CoV-2 were included in this study.Primary and secondary outcome measures Long COVID was measured by participants’ self-reported symptoms using structured questionnaires. ES was measured by last-month personal income, and participants’ ES was defined as low if their income was below the per capita monthly income of local residents. Lifestyle score was equal to the number of healthy behaviours (including smoking, drinking, weight, exercise and diet) and grouped using the median score as the cut-off point. Univariate and multivariate logistic models were employed to estimate the association of ES with long COVID. Interaction between ES and lifestyle in long COVID was assessed by multiplicative interaction term.Results We enrolled a total of 4804 participants infected with SARS-CoV-2, of whom 57.3% (2754 of 4804) had at least one long COVID symptom. Fatigue (1546, 56.1%), cough (1263, 45.9%) and muscle pain (880, 32.0%) were the top three common symptoms. Patients with low ES had a 48% (adjusted OR: 1.48; 95% CI 1.22, 1.82) increased risk of long COVID. A significant interaction was observed between ES and lifestyle (p value for interaction

Bone defect repair and tumor recurrence are the main challenges in the postoperative treatment of bone tumors. The incorporation of zoledronate (ZOL) into scaffolds presents a promising approach, attributed to its osteogenic and anti-tumor properties. However, there are still some unfavorable factors that make it difficult to eradicate tumor cells at the surgical site, including drug rapid release, the insufficient anti-tumor efficacy of ZOL and the multidrug resistance of chemotherapy. Herein, a novel nano drug delivery platform mesoporous silicon-coated graphene oxide (GO/MSN) and ZOL loaded nanoparticle (GO/MSN-ZOL) were developed. Then PLLA/ GO/MSN-ZOL scaffold that integrates photothermal therapy (PTT) and chemotherapy was fabricated using poly (L-lactic acid) as raw materials by selective laser sintering (SLS) technology. The GO not only imparted scaffold with photothermal properties for localized tumor cell ablation but also significantly enhanced its anti-tumor efficacy through synergistic effects in combination with chemotherapy. The mesoporous structure and large specific surface area of MSN contribute to the sustained release of ZOL. Additionally, GO could promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), which in combine with ZOL’s osteoclast inhibition, enhances the bone repair capacity. This study offers a straightforward and promising strategy for treating tumor-related bone defects.

Epilepsy is a chronic neurological disease. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient diagnosed as epilepsy caused by ATP1A2 gene mutation. Induced pluripotent stem cells (iPSCs) were developed using non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSC line (SDCHi007-A) displayed pluripotent cell morphology, high expression levels of pluripotency markers, differentiation potential in vitro, normal karyotype, and remaining the original ATP1A2 gene mutation.

Abstract Tulips (Tulipa gesneriana) are one of the most widely cultivated bulbous plants with substantial ornamental value. However, the lack of well-documented reference genomes has limited the research progress and molecular breeding of tulips. In the present study, a full-length transcriptome of a commercial tulip cultivar was obtained using single-molecule long-read sequencing (PacBio Iso-Seq). In total, 244,357 full-length transcripts were identified, which had an average length of 2,044 bp and an N50 value of 3,861; 67,350 of these were annotated to databases. An inaugural integrated analysis of the transcriptome and phytohormone profiles during flower opening and petal senescence was performed using Illumina RNA-seq, coupled with Mfuzz (an R pakage, http://mfuzz.sysbiolab.eu ) and weighted gene coexpression network analysis (WGCNA). A total of 16 gene coexpression and six transcription factor (TF) modules were constructed. Additionally, 26 hormone analogs were comprehensively profiled. Finally, a prominently novel gene, Tulipa gesneriana Homeobox12-like (TgHB12-like), which encodes an homeodomain–leucine zipper (HD-zip) TF, was identified as a pivotal regulator of petal senescence. Overall, this work facilitates the identification of hormones and TFs in plants related to flower opening and senescence in tulips. It also provides an important and valuable genetic basis for further research in them.

Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT. This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy. To achieve this goal, we first synthesized TRANSFERRIN (Tf) biomimetic mineralized nano-tellurium (Tf-Te) as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly. The autophagy inhibitor hydroxychloroquine (HCQ) and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ. After entering breast cancer cells through the “self-guidance system”, Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation, to efficiently induce PTT/PDT effect. Meanwhile, the disulfide bond broke down in response to GSH, and the nanoparticles disintegrated to release Fe2+ and HCQ at fixed points. They simultaneously induce lysosomal alkalinization and increased osmotic pressure, effectively inhibit autophagy, and synergistically enhance the therapeutic effect of phototherapy. In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6% on 4T1 tumor-bearing mice. This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

This study aimed to evaluate the quality characteristics of Shui ethnic red sour soup, using Miao ethnic red sour soup as a reference. The physicochemical components, free amino acids, and aroma compounds of Miao and Shui ethnic red sour soups were analyzed and compared using national standard methods, amino acid analysis, and headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results showed that the contents of total acids, reducing sugars, fats, and proteins in Shui ethnic red sour soup were higher than those in Miao ethnic red sour soup. Nineteen free amino acids were detected in both types of red sour soup, and the content of savory amino acids in Shui ethnic red sour soup was twice that of Miao ethnic red sour soup. Proline and glutamic acid, with taste activity values (TAV) > 1, were identified as the key savory amino acids in both types of red sour soup. A total of 101 volatile compounds were detected in the red sour soups. Moreover, using orthogonal least squares-discriminant analysis (OPLS-DA) and variable importance in projection (VIP) selection, thirty-two key differential compounds, including hexadecanoic acid propyl ester, 4-ethyl-2-methoxyphenol, 5-cyclohexyl-2-pentanone, and sorbic acid, were identified in the red sour soups. Based on the relative odor activity value (ROAV), it was found that the sour taste was more pronounced in Miao ethnic red sour soup, while the fruity aroma was more prominent in Shui ethnic red sour soup. Both types of red sour soup contained salicyl methyl ether as the main contributor to the fatty aroma, but the volatile compounds responsible for the wine-like aroma differed. Ethanol was the main contributor in Miao ethnic red sour soup, while 4-ethylphenol was the main contributor in Shui ethnic red sour soup. In addition, sensory evaluation showed that Shui ethnic red sour soup received higher scores than Miao ethnic red sour soup. In conclusion, the Shui ethnic red sour soup exhibits superior quality and flavor, and has wider market development value.

Abstract The progress of aquaculture heavily depends on the efficient utilization of diverse genetic resources to enhance production efficiency and maximize profitability. Single nucleotide polymorphisms (SNPs) have been widely used in the study of aquaculture genomics, genetics, and breeding research since they are the most prevalent molecular markers on the genome. Currently, a large number of SNP markers from cultured fish species are scattered in individual studies, making querying complicated and data reuse problematic. We compiled relevant SNP data from literature and public databases to create a fish SNP database, FishSNP ( http://bioinfo.ihb.ac.cn/fishsnp ), and also used a unified analysis pipeline to process raw data that the author of the literature did not perform SNP calling on to obtain SNPs with high reliability. This database presently contains 45,690,243 (45 million) nonredundant SNP data for 13 fish species, with 30,288,958 (30 million) of those being high-quality SNPs. The main function of FishSNP is to search, browse, annotate and download SNPs, which provide researchers various and comprehensive associated information.

Summary: Background: Dengue remains a global threat to public health, however, its disease burden among children and adolescents has always been poorly quantified. Therefore, we aimed to systematically estimate the global, regional, and national burden and temporal trends of dengue infection in children and adolescents from 1990 to 2021. Methods: Data on the number and rate of incidence and disability-adjusted life-years (DALYs) of dengue infection among children and adolescents under 20 years were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) of the age-standardised incidence rate (ASIR) and age-standardised DALYs rate (ASDR), by age, sex, and different countries and regions, were calculated to quantify the temporal trends of dengue burden. The association between development levels (measured using the socio-demographic index [SDI]) and dengue burden was also determined. Findings: From 1990 to 2021, the global burden of dengue incidence and its associated DALYs was consistently higher in children and adolescents than in the entire population. Globally, among children and adolescents, there were 21,641,016 incident cases in 2021, an increase of 64.43% compared to 13,241,719 in 1990. The ASIR per 100,000 population increased from 587.81 in 1990 to 812.16 in 2021, with an EAPC of 1.39% (95% confidence interval [CI], 1.13%–1.65%). Besides, the number of dengue-associated DALYs among children and adolescents increased by 16.36%, from 910,458.60 in 1990 to 1,059,428.31 in 2021. The increase in DALYs was less pronounced than incidence, with the ASDR per 100,000 population increasing from 40.17 in 1990 to 41.50 in 2021, and the EAPC was only 0.67% (95% CI, 0.40%–0.95%). The incidence and DALYs burden of dengue in children and adolescents was highest in middle SDI regions, followed by low-middle SDI regions, with the lowest burden in high SDI regions. Furthermore, Tropical Latin America had an extremely high ASIR (6040.29 per 100,000 population in 2021), and Southeast Asia had an extremely high ASDR (298.20 per 100,000 population in 2021), much higher than other regions around the world. Interpretation: The global dengue burden in children and adolescents is high and has been increasing from 1990 to 2021, even though the distribution patterns vary across different countries and territories. This study first reported the global disease burden and temporal trends of children and adolescents, which has significant implications for policymakers and public health officials, as it underscores the need for age- and region-specific strategies to mitigate the growing global burden of dengue. Funding: National Natural Science Foundation of China.

Summary: Imaging transcriptomics offers opportunities to uncover the genetic profiles underlying brain imaging-derived phenotypes (IDPs) but lacks explanation from gene to IDPs. Here, we present a protocol for combining imaging transcriptomics with gene set variation analysis (GSVA) to detect spatio-molecular profiles underlying IDPs in the human cerebellum. We describe the steps for data preparation, model training, model evaluation, key gene identification, and GSVA. Our protocol broadens the way to interpret the biological pathways shaping a wide range of neuroimaging-derived cerebellar properties.For complete details on the use and execution of this protocol, please refer to Wang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Study region: the Yellow River Basin Study focus: Non-stationary hydrological conditions are becoming increasingly common due to climate change and human activities, and pose a novel challenge to the management of water resources and related risks, especially for large basins. However, prevalent research on drought assessment often ignores the non-stationary characteristics of hydrological processes. In this study, we investigated the stationarity of the runoff of the Yellow River Basin (YRB), the second-longest basin in China. We used an approach for assessing non-stationary droughts based on the generalized additive model for location, scale, and shape to establish a standardized runoff index containing covariates (SRI_cov) to identify hydrological droughts in the basin from 1986 to 2015. New hydrological insights for the region: The results show that the runoff was non-stationary in the YRB. Based on SRI_cov, hydrological drought predominantly occurred in the entire YRB in spring. From 1986, the number of months in which droughts occurred in the YRB exhibited a general trend of increase and peaked around 2002. After that, the total number of droughts significantly decreased but extreme droughts had become more prominent since 2005. The drought was more severe in the middle reaches of the Yellow River, and was characterized by a high frequency, intensity, and severity. Our analysis enhances the understanding of hydrological modeling and drought assessment under non-stationary conditions.

ABSTRACT: This study aimed to explore the probiotic characteristics of Lacticaseibacillus rhamnosus SN21-1 and Lactiplantibacillus plantarum SN21-2 by genotype and phenotype analysis, assess their safety in vitro and in vivo, and investigate the effects of L. rhamnosus SN21-1 and L. plantarum SN21-2 on Salmonella typhimurium-infected broilers in an in vivo experiment. L. rhamnosus SN21-1 and L. plantarum SN21-2 showed antimicrobial activity against pathogens, including S. Typhimurium, resistance to simulated gastrointestinal digestive fluid, and adhesion to HT-29 cells. In addition, L. rhamnosus SN21-1 and L. plantarum SN21-2 showed no resistance to most common antimicrobial agents and no haemolysis in vitro. Whole-genome sequence analyses of L. rhamnosus SN21-1 and L. plantarum SN21-2 provided basic genomic information, functional genes underlying the probiotic characteristics, and evidence of safety. Furthermore, feeding with L. rhamnosus SN21-1 or L. plantarum SN21-2 for 28 d had no significant effect on the growth or blood biochemical parameters of the broilers, and hematoxylin-eosin staining revealed no liver, spleen, heart, or kidney damage. Additionally, L. rhamnosus SN21-1 or L. plantarum SN21-2 did not translocate to the blood, liver, spleen, heart, or kidney of the broilers. Moreover, L. rhamnosus SN21-1 and L. plantarum SN21-2 significantly reduced S. Typhimurium counts in the faeces and caecal contents of S. Typhimurium-infected broilers and reduced small intestinal bleeding in S. Typhimurium-infected broilers. Consequently, L. rhamnosus SN21-1 and L. plantarum SN21-2 have excellent probiotic characteristics and are safe for use as anti-S. typhimurium probiotics in broilers.

ABSTRACTOptical Water Type (OWT) analysis is crucial for comprehending water composition and quality, key factors in assessing water quality over extensive areas. However, China’s inland waters lack a standardized system for such analysis. To quantitatively analyze the classification results, our study compared three K-means clustering methods, for analyzing 1310 spectral data from various Chinese lakes and reservoirs, thereby addressing this gap. The innovative split-merge K-means method identified 13 distinct OWTs that more closely adhere to the principles of minimizing intra-class distance and maximizing inter-class distance. These were categorized into four groups: clear water, turbid water, eutrophic water, and special type water. Additionally, we developed a method based on Spectral Angle Distance (SAD) to evaluate the classification capabilities of 12 satellite sensors. The results show that Sentinel-3 OLCI (Ocean and Land Color Instrument), MERIS (Medium Resolution Imaging Spectrometer), and Sentinel-2 MSI (Multispectral Instrument) have the best water classification capabilities, making them well-suited for large-scale monitoring of OWT changes. Conversely, other sensors, such as the Sustainable Development Scientific Satellite-1 (SDGSAT-1), Landsat-8, GaoFen-6, GaoFen-1, GaoFen-2, Landsat-5, Landsat-7, Moderate Resolution Imaging Spectroradiometer (MODIS), and HuanJing-1, necessitate the consolidation of water types for effective categorization, indicative of their more limited classification capabilities.

AbstractAim This study aimed to compare the efficacy and safety of excimer laser (EL)-based combination regimens in improving repigmentation.Methods A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, and Embase on July 1, 2023, to include randomized controlled trials of EL combination treatments for vitiligo that met the criteria. The primary outcome measure was a repigmentation rate ≥ 75%, and the secondary outcome measures were a repigmentation rate of ≤ 25% and adverse events.Results Eleven studies involving 348 patients were included. Network Meta-Analysis showed that EL combined with antioxidants (SUCRA = 98.8%), EL combined with calcipotriol (SUCRA = 59.8%) and EL combined with tacalcitol (SUCRA = 59.6%) were the three optimal interventions achieving repigmentation rates ≥ 75%. EL alone (SUCRA = 77.6%), EL combined with tacalcitol (SUCRA = 61.7%) and EL combined with antioxidants (SUCRA = 57.2%) were the three interventions with the highest rates of treatment failure. Adverse events in all groups mainly included erythema, burning sensation and hyperpigmentation. Based on the results of the current study, EL combination therapies were safe with mild adverse events.Conclusion EL combined with antioxidants was the preferred regimen for vitiligo, whereas EL alone was the regimen with the highest rate of treatment failure in vitiligo.

ABSTRACTThe oil content, fatty acid, oil quality and oxidation stability of seeds of four woody oil plants (pecan, Camellia oleifera, Torreya grandis and walnut) were analyzed. The results showed that pecan oil had the strongest antioxidant activity, the variation range of FFA, peroxide value(PV), UV absorption, carbonyl value(CV) and OSI were the lowest; C. oleifera oil and T. grandis oil were the next, and walnut oil had the greatest variation range; besides, pecan oil contained higher tocopherol and total phenol(TP) content. Correlation analysis showed that, OSI was significantly positively correlated with OA, tocopherol and TP, and significantly negatively correlated with PA, LA, LOA and PV. The oxidation stability from superior to inferior is pecan oil, C. oleifera oil, T. grandis oil and walnut oil. Meanwhile, the oil content of pecan kernel was the highest, the fatty acid composition of pecan oil fulfills human dietary needs, it’s an high-quality edible oil.Abbreviations: PA: palmitic acid; POA: palmitoleic acid; SA: stearic acid; OA: oleic acid; LA: linoleic acid; LOA: linolenic acid; AA: arachidic acid; EA: cis-11-eicosenoic acid; UFA: unsaturated fatty acid;SFA: saturated fatty acid; FFA: free fatty acid; PV: peroxide value; CV: carbonyl value; TP: total phenols; OSI: oil stability index; UV: ultraviolet.

ABSTRACTThe aim of this study was to investigate acid hydrolysis-bound phenols from Rosa roxburghii Tratt and their biological activities in vitro. The optimal extraction parameters were as follows: HCl concentration of 7 mol/L, extraction time of 10 h and material-liquid ratio of 1:40 g/mL. The highest yield of bound polyphenols was 495.64 ± 11.66 mg GAE/100 g DW. There were 24 phenolic compounds and 14 flavonoids released by acid hydrolysis. The antioxidant study showed that the RRT-BPs had a certain scavenging ability of free radicals in a dose-dependent manner. RRT-BPs showed good inhibitory activity against α-glucosidase and pancreatic lipase, respectively, and RRT-PBs acted as anticompetitive and mixed inhibitors against α-glucosidase and pancreatic lipase, respectively. Our study suggests that acid-hydrolysed bound phenols have good prebiotic properties and can be used as a supplement to existing alkaline-hydrolysed bound phenols to prevent chronic diseases such as diabetes and obesity.

IntroductionWith the rising demand for medical services and the associated burden, work-related stress and mental health issue have garnered increased attention among healthcare workers. Anxiety, cognitive impairment, and their comorbidities severely impact the physical and mental health as well as the work status of healthcare workers. The network analysis method was used to identify the anxiety and cognitive impairment among mental healthcare workers using the Generalized Anxiety Disorder Scale (GAD-7) and the Perceived Deficit Questionnaire for Depression (PDQ-D). We sought to identify the core symptoms associated with the comorbidity of anxiety and cognitive impairment in mental healthcare workers.MethodsThe study was conducted by Shandong Daizhuang Hospital and Qingdao Mental Health Center in China from September 13, 2022, to October 25, 2022, involving a total of 680 healthcare workers as participants. GAD-7 and PDQ-D were utilized to assess anxiety and cognitive impairment, respectively. Regularized partial correlation network analysis was employed to examing the expected influence and predictability of each item within the network. Statistical analysis and visualization of the network were performed using R software.ResultsThe mean total score for anxiety was 3.25, while the mean total score for cognitive symptoms was 15.89. PDQ17 “Remembering numbers”, PDQ12 “Trouble get started” and PDQ20 “Trouble make decisions” emerged as central symptoms in the anxiety-cognition network. GAD6 “Irritable”, GAD5 “Restlessness” and GAD1 “Nervousness or anxiety” were identified as the most critical bridge symptoms connecting anxiety and cognition. Gender was found to be unrelated to the global strength of the network, edge weight distribution, or individual edge weights.ConclusionUtilizing central and bridge symptoms (i.e., Remembering numbers, Trouble get started, Trouble make decisions, Irritable, Restlessness and Nervousness or anxiety) as primary intervention points may aid in mitigating the serious health consequences of anxiety, cognitive impairment, and comorbidities anxiety and cognitive impairment for mental healthcare workers.

Abstract The mechanism involved in major depressive disorder (MDD) is well‐studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single‐cell RNA‐sequencing (scRNA‐seq) and assay for transposase‐accessible chromatin using sequencing (ATAC‐seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA‐seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen‐activated protein kinases (MAPK) pathway is identified. E‐twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

Land subsidence caused by excessive groundwater withdrawal has become a global hazard, which demands further researches and the potential measures to control. Using the FlowTrac Ⅱ consolidation test system, six compression tests were designed to investigate the stress state and stress paths of sand within confined aquifers under conditions of withdrawal and recharging. The deformation characteristics of aquifer sand were studied under different withdrawal-recharging patterns. During pumping and recharge processes, sand deformation responses were observed to lag behind changes in applied stress. The characteristics of this hysteresis effect on deformation were summarized. The alternating phenomenon of rebound and compression of sand deformation under the recharging process is analyzed. When the recharging effect was relatively small than withdrawing effect under the stable withdrawal-recharging pattern, the compression deformation was observed in the recharging process. The research results provide a rational explanation for the continuous compression deformation of the aquifer during groundwater level recovery and offer experimental evidence for the rational design of artificial groundwater recharge in engineering construction.

Regarding the fault detection problem of the displacement sensor, an enhanced fireworks algorithm with information crossover and conversion factor (EFWA-IC) is proposed in this paper. In EFWA-IC, an information crossover strategy is proposed to maintain population diversity. This strategy is based on the predatory behavior of carnivores in nature. In addition, a conversion factor is set to control whether the explosion operator is executed or not to provide a more reasonable search. To fully evaluate the performance of EFWA-IC, a range of tests are carried out based on the CEC2017 and 23 classical test functions. The results show that the performance of EFWA-IC is better than other state-of-the-art optimization algorithms in terms of solution accuracy, convergence speed, and stability. Finally, EFWA-IC is utilized to optimize the particle filter (PF) to establish a fault detection model of displacement sensor in the continuous casting mold. The simulation experiment result of field data manifests that EFWA–IC–PF can accurately detect faults in the displacement sensor. For bias faults, the RMSE of the EFWA–IC–PF model is 0.14468, and the false alarm rate (FAR) and missed detection rate (MDR) are 1 % and 0.5 %, respectively. For stuck faults, the RMSE is 1.00148, and the FAR and MDR are 0.88 % and 1 %, respectively.

ObjectivesThe application of artificial intelligence (AI) in healthcare is an important public health issue. However, few studies have investigated the perceptions and attitudes of healthcare professionals toward its applications in nursing. This study aimed to explore the knowledge, attitudes, and concerns of healthcare professionals, AI-related professionals, and others in China toward AI in nursing.MethodsWe conducted an online cross-sectional study on nursing students, nurses, other healthcare professionals, AI-related professionals, and others in China between March and April 2024. They were invited to complete a questionnaire containing 21 questions with four sections. The survey followed the principle of voluntary participation and was conducted anonymously. The participants could withdraw from the survey at any time during the study.ResultsThis study obtained 1,243 valid questionnaires. The participants came from 25 provinces and municipalities in seven regions of China. Regarding knowledge of AI in nursing, 57% of the participants knew only a little about AI, 4.7% did not know anything about AI, 64.7% knew only a little about AI in nursing, and 13.4% did not know anything about AI in nursing. For attitudes toward AI in nursing, participants were positive about AI in nursing, with more than 50% agreeing and strongly agreeing with each question on attitudes toward AI in nursing. Differences in the numbers of participants with various categories of professionals regarding knowledge and attitudes toward AI in nursing were statistically significant (p

Abstract The Vietnam upwelling is a crucial circulation feature in the South China Sea. Although previous studies have shown that various coastal upwellings around the world may intensify under global warming, future changes in the Vietnam upwelling remain unclear. To address this knowledge gap, we analyzed the long‐term trend in the Vietnam upwelling under a high‐emission scenario for the period 2006–2100, using simulation results from a global eddy‐resolving climate model. In this model, the summertime Vietnam upwelling is projected to intensify in the 21st century and is statistically significant between 12°N and 14°N. A volume flux budget analysis indicates that wind stress curl is the most important contributor to the intensification. The geostrophic flow, to some extent, may suppress the upwelling intensification. The projected increase in upwelling is shown to significantly reduce local ocean warming and freshening and thus may have vital impacts on the local climate and circulation.

Storm-induced episodic sediment redistribution in coastal systems can reshape geomorphic bodies, disrupt ecosystems, and cause economic damage. However, cold-wave-storm-induced hydrodynamic changes and residual sediment transport in large, exposed subaqueous deltas, such as the Yangtze Delta, are poorly understood because it is typically expensive and difficult to obtain systematic field data in open coast settings during storm events. We conducted a successful field survey of waves, currents, changes in water depth, and turbidity at a station (time-averaged water depth of 20 m) in the offshore subaqueous Yangtze Delta over 10 days during winter, covering two storms and two fair-weather periods. During the storm events, strong northerly winds drove southward longshore currents (~0.2 m/s) and resulted in increased wave height and sediment resuspension, thereby leading to massive southward sediment transport. In contrast, both southward and northward transports were limited during the fair-weather periods. A better understanding of the storm-induced sediment transport can be obtained by using an approximately half-day lag in sediment transport behind wind force, given the time needed to form waves and longshore drift, the inertia of water motion, and the slow settling velocity of fine-grained sediment. Our results directly support previous findings of southward sediment transport from the Yangtze Delta during winter, which is deposited in the Zhejiang–Fujian mud belt in the inner shelf of the East China Sea. In addition, the southward sediment transport from the Yangtze Delta occurs mainly during episodic storm events, rather than during the winter monsoon, and winter storms dominate over typhoons in driving southward sediment transport from the delta. This study highlights the importance of storms, especially during winter storms, in coastal sediment redistribution, which is of particular significance when considering the projected increase in storm intensity with global warming.

Understanding the mechanisms, especially those associated with phytohormones, of plant drought adaptation is crucial for sustaining agricultural production in the era of climate change. Arabidopsis histidine kinases (AHKs), an integral part of the cytokinin signaling pathway, and more axillary growth 2 (MAX2), a key component of the strigolactone and karrikin signaling pathways are reported to act as negative and positive regulators, respectively, in plant adaption to drought. However, the potential interaction between these singaling pathways in plant drought adaptation is not fully understood. To address this query, we assessed drought tolerance levels and associated phenotypic and physiological traits of the max2 single mutant, ahk2 ahk3 double mutant, ahk2 ahk3 max2 triple mutant, and wild-type (WT) Arabidopsis thaliana plants. Our findings revealed a distinct hierarchy in drought tolerance among these genotypes, as indicated by the differences in plant growth and stress survival rates. Specifically, the max2 mutant displayed the lowest drought tolerance level, followed by WT, ahk2 ahk3 max2, and ahk2 ahk3 plants. Additionally, the observed changes in leaf relative water content, leaf surface temperature, and cuticle formation were coherently aligned with the observed hierarchy of drought tolerance levels. Under drought conditions, the max2 mutant exhibited higher oxidative stress and membrane damage, as evidenced by increased levels of reactive oxygen species (ROS), malondialdehyde, and electrolyte leakage. In contrast, the ahk2 ahk3 and ahk2 ahk3 max2 mutants showed low and intermediate levels, respectively, for these parameters. The max2 mutant displayed reduced sensitivity, whereas ahk2 ahk3 and ahk2 ahk3 max2 mutants demonstrated high and intermediate sensitivities, respectively, to exogenous abscisic acid (ABA) treatments. Additionally, the expression analysis of several genes associated with the investigated drought tolerance-related traits showed a positive correlation between the transcript levels and corresponding trait(s) in both mutant and WT plants under drought conditions. Our results collectively indicate the presence of an antagonistic interaction between AHK and MAX2 signaling pathways in plant drought adaptation, impacting ABA responsiveness, leaf water retention, cuticle development, and ROS homestasis. The findings of this study provide a valuable foundation for developing agricultural methods to improve plant drought resilience.

Purpose: This study aims to identify the key factors influencing health-related quality of life (HRQoL) of pediatric acute myeloid leukemia (AML) patients following their initial diagnosis and examine their impact on the five-year survival prognosis. Methods: A chart review and follow-up were conducted for children with AML who participated in a prospective cohort study between 2017 and 2020. We identified factors influencing HRQoL through Pediatric Quality of Life Inventory™ (PedsQL™ 4.0), PedsQL™ Cancer Module 3.0 (CM 3.0) and PedsQL™ Family Impact Module 2.0 (FIM 2.0), as well as assessed the impact of impaired HRQoL on the overall outcomes of patients. Results: Sixty-four subjects enrolled in the study had complete HRQoL outcome data, and 61 of them completed the 5-year follow-up. In CM 3.0, age was positively associated with parental proxy reports (p = 0.040), whereas divorced families were negatively associated with child self-reports (p = 0.045). A positive medical history correlates with FIM 2.0 (p = 0.025). Residence (p = 0.046), the occupation of caregivers (p = 0.014), disease severity (p = 0.024), and the only child (p = 0.029) exhibited statistically significant associations with the impairment of HRQoL. Impaired HRQoL scores shown by the PedsQL™4.0 parent proxy report (p = 0.013) and FIM 2.0 (p = 0.011) were associated with a reduced 5-year survival rate. Conclusions: This study demonstrated that early impairment of HRQoL in pediatric acute myeloid leukemia patients has predictive value for long-term prognosis. Once validated, these findings may provide some guidance to clinicians treating children with AML.

Neurodevelopmental cell communication plays a crucial role in neuroblastoma prognosis. However, determining the impact of these communication pathways on prognosis is challenging due to limited sample sizes and patchy clinical survival information of single cell RNA-seq data. To address this, we have developed the cell communication pathway prognostic model (CCPPM) in this study. CCPPM involves the identification of communication pathways through single-cell RNA-seq data, screening of prognosis-significant pathways using bulk RNA-seq data, conducting functional and attribute analysis of these pathways, and analyzing the post-effects of communication within these pathways. By employing the CCPPM, we have identified ten communication pathways significantly influencing neuroblastoma, all related to axongenesis and neural projection development, especially the BMP7-(BMPR1B-ACVR2B) communication pathway was found to promote tumor cell migration by activating the transcription factor SMAD1 and regulating UNK and MYCBP2. Notably, BMP7 expression was higher in neuroblastoma samples with distant metastases. In summary, CCPPM offers a novel approach to studying the influence of cell communication pathways on disease prognosis and identified detrimental communication pathways related to neurodevelopment.

Abstract An immune-related gene signature (IRGS) was established to better understand the molecular and immunologic characteristics of microsatellite instable (MSI) and microsatellite stable (MSS) endometrial carcinoma (EC), and provide potential immunotherapy directions for MSS patients. Top 20 immune-related hub genes were screened by weight gene coexpression network analysis (WGCNA), and an IRGS was further established through Cox regression analysis. The molecular and immune characteristics were clarified in IRGS high and low risk groups. Expression and MS status validation of the IRGS were conducted through quantitative real-time Polymerase Chain Reaction (rt-qPCR) and immunohistochemistry (IHC) analysis. The IRGS includes 2 oncogenes (AGTR1 and HTR3C) and 2 tumor suppressor genes (CD3E and SERPIND1). Patients in IRGS high-risk group were more with MSS status, higher tumor grade, later FIGO stage, serous histology and elder ages compared with IRGS low-risk group (P

The optimization control of the selective catalytic reduction (SCR) denitrification system holds significant importance in the power generation industry. This paper presents an engineering fastest controller combined with active disturbance rejection control (EFC-ADRC) to enhance the control performance in SCR denitrification process. Compared with EFC, EFC-ADRC strategy has better performance in disturbances rejection when using the extended state observer(ESO) to compensate for uncertain disturbances. Two optimization methods are adopted including online Simultaneous Perturbation Stochastic Approximation (SPSA) and offline whale optimization algorithm (WOA), to tune the filter parameters in EFC by matching the time-varying characteristics of the process. Finally, the superior performance of the proposed control strategy in terms of set point tracking and disturbance rejection is verified through simulation experiments.

Current single-model methods for fine-grained image classification suffer from insufficient generalisation ability, while multi-model fusion methods suffer from weight curing. The study suggests and experimentally tests a dynamic weight multi-model fusion strategy for transfer learning-based fine-grained picture classification. The results of the experiment showed that the suggested fusion model enhanced recognition accuracy by 1.33%, 1.19%, and 0.83% compared to the single model on the medical dataset and 3.25%, 1.34%, and 7.28% on the agronomy dataset, respectively. Furthermore, when compared to the comparison method, the models under the proposed method of the study improved recognition accuracy by 0.18%, 0.61%, 0.43%, and 0.43% on the medical dataset, and the experimental time consumed was 3.25 minutes less than that of the sum-of-maximum-probabilities method; however, the fusion models of the proposed method of the study had higher recognition accuracy than that of the comparison met Overall, the proposed dynamic weight multi-model fusion method for fine-grained image classification using migration learning has better performance and generalisation ability, which can improve performance while reducing time cost, and has higher application value for the actual fine-grained image classification task.

Abstract The elevation in the optic nerve sheath (ONS) pressure (ONSP) due to microgravity-induced headward fluid shift is the primary hypothesized contributor to SANS. This longitudinal study aims to quantify the axial plane of the optic nerve subarachnoid space area (ONSSA), which is filled with cerebrospinal fluid (CSF) and expands with elevated ONSP during and after head-down tilt (HDT) bed rest (BR). 36 healthy male volunteers (72 eyes) underwent a 90-day strict 6° HDT BR. Without obtaining the pre-HDT data, measurements were performed on days 30, 60, and 90 during HDT and at 6 recovery time points extended to 180-days (R + 180) in a supine position. Portable B-scan ultrasound was performed using the 12 MHz linear array probe binocularly. The measurements of the ONS and the calculation of the ONSSA were performed with ImageJ 1.51 analysis software by two experienced observers in a masked manner. Compared to R + 180, the ONSSA on HDT30, HDT60, and HDT90 exhibited a consistently significant distention of 0.44 mm2 (95% CI: 0.13 to 0.76 mm2, P = 0.001), 0.45 mm2 (95% CI: 0.15 to 0.75 mm2, P = 0.001), and 0.46 mm2 (95% CI: 0.15 to 0.76 mm2, P

Abstract Endophytic fungi play an important role in the growth and development of traditional Chinese medicine plants. We isolated a strain of Acrocalymma vagum from the endophytic fungi of the traditional Chinese plants Paris. To accurately identify this endophytic fungal species of interest, we sequenced the mitochondrial genome of A. vagum, which is the first discovered mitochondrial genome in Massarineae. The A. vagum mitochondrial genome consists of a 35,079-bp closed circular DNA molecule containing 36 genes. Then, we compared the general sequence characteristics of A. vagum with those of Pleosporales, and the second structure of the 22 tRNAs was predicted. The phylogenetic relationship of A. vagum was constructed using two different data sets (protein-coding genes and amino acids). The phylogenetic tree shows that A. vagum is located at the root of Pleosporales. The analysis of introns shows that the number of introns increases with the increase in branch length. The results showed that monophyly was confirmed for all families in Pleosporales except for Pleosporaceae. A. vagum is an ancient species in the Pleosporales, and Pleosporaceae may require further revision. In Pleosporales, the number of introns is positively correlated with branch length, providing data for further study on the origin of introns.

Abstract Two-dimensional (2D) XY ferromagnets have drawn pronounced interest in recent years, but the characteristic of easy-plane magnetization restricts their application in spintronics to some extent. Here, we propose a general strategy for constructing multiferroic van der Waals heterostructures, aiming to achieve electrical control over the magnetic anisotropy in 2D XY ferromagnets. The validity of this strategy is verified by the heterostructure composed of ferromagnetic VBi2Te4 and ferroelectric In2Se3 monolayers. By manipulating the polarized states of In2Se3, the VBi2Te4 can be reversibly transformed between 2D XY and Heisenberg ferromagnets, characterized by the switching of easy magnetization axis between in-plane and out-of-plane directions. More interestingly, accompanied by the changes in magnetic anisotropy, the VBi2Te4 also demonstrates a phase transition from a semiconductor to a half-metal state, which can be ascribed to the band alignment and interfacial charge transfer. The switchable magnetic and electronic properties enable the heterostructure to be utilized in nonvolatile memory and logic devices. Additionally, the half-metallicity and magnetocrystalline anisotropy energy of the heterostructure can be effectively tuned by biaxial strain. These findings not only pave the way for electrically nonvolatile control of 2D XY ferromagnet, but also facilitate the development of interfacial magnetoelectric physics and applications.

AbstractContext 5-Fluorouracil (5-FU)-injured stromal cells may cause chronic bone marrow suppression; however, the underlying mechanism remains unclear. Angelica sinensis polysaccharide (ASP), the main biologically active ingredient of the Chinese herb, Angelica sinensis (Oliv.) Diels (Apiaceae), may enrich the blood and promote antioxidation.Objective This study investigated the protective antioxidative effects of ASP on perivascular mesenchymal progenitors (PMPs) and their interactions with hematopoietic cells.Materials and methods PMPs were dissociated from C57BL/6 mouse femur and tibia and were subsequently divided into the control, ASP (0.1 g/L), 5-FU (0.025 g/L), and 5-FU + ASP (pre-treatment with 0.1 g/L ASP for 6 h, together with 0.025 g/L 5-FU) then cultured for 48 h. Hematopoietic cells were co-cultured on these feeder layers for 24 h. Cell proliferation, senescence, apoptosis, and oxidative indices were detected, along with stromal osteogenic and adipogenic differentiation potentials. Intercellular and intracellular signaling was analyzed by real-time quantitative reverse transcription polymerase chain reaction and Western blotting.Results ASP ameliorated the reactive oxygen species production/scavenge balance in PMPs; improved osteogenic differentiation; increased SCF, CXCL12, VLA-4/VCAM-1, ICAM-1/LFA1, and TPO/MPL, Ang-1/Tie-2 gene expression. Further, the ASP-treated feeder layer alleviated hematopoietic cells senescence (from 21.9 ± 1.47 to 12.1 ± 1.13); decreased P53, P21, p-GSK-3β, β-catenin and cyclin-D1 protein expression, and increased glycogen synthase kinase (GSK)-3β protein expression in co-cultured hematopoietic cells.Discussion and conclusions ASP delayed oxidative stress-induced premature senescence of 5-FU-treated feeder co-cultured hematopoietic cells via down-regulation of overactivated Wnt/β-catenin signaling. These findings provide a new strategy for alleviating myelosuppressive stress.