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Parent-child shared experiences has an important influence on social development in children although contributions of mothers and fathers may differ. Neural synchronicity occurs between mothers and fathers and their children during social interactions but it is unclear whether they differ in this respect. We used data from simultaneous fNIRS hyperscanning in mothers (n = 33) and fathers (n = 29) and their children (3–4 years) to determine different patterns and strengths of neural synchronization in the frontal cortex during co-viewing of videos or free-play. Mothers showed greater synchrony with child than fathers during passive viewing of videos and the synchronization was positively associated with video complexity and negatively associated with parental stress. During play interactions, mothers showed more controlling behaviors over their child and greater evidence for joint gaze and joint imitation play with child whereas fathers spent more time gazing at other things. In addition, different aspects of child communication promoted neural synchrony between mothers and fathers and child during active play interactions. Overall, our findings indicate greater neural and behavioral synchrony between mothers than fathers and young children during passive or active shared experiences, although for both it was weakened by parental distress and child difficulty.

Background: Numerous studies showed that electroacupuncture at Shenting (GV24) and Baihui (GV20) could improve cognitive function in MCAO rats. However, the underlying molecular protein mechanisms need to be further investigated, including the effects of electroacupuncture at Shenting and Baihui points on MCAO-related gene and protein expression. Methods: Sprague-Dawley (SD) adult male rats (n = 40) were randomly divided into the following four groups: sham group (SHAM/S), Middle cerebral artery occlusion (MCAO/M) group, electroacupuncture at Shenting and Baihui group (EA/E) and acupuncture at non-meridian and non-acupuncture points (NON/N) (n = 10 per group). After one week of electroacupuncture treatment, the protein expression of hippocampus-related genes in the brain regions of rats in all was measured. Three samples from each groups were used to identify potential biomarkers in the hippocampus of the rat brain region using tandem mass labeling (TMT), liquid chromatography and functional enrichment clustering analysis of differentially expressed proteins (DEPs). The protein interactions network was analysed by enrichment clustering to explore the major and potential protein targets of electroacupuncture at Shenting and Baihui for the treatment of MCAO rats. Results: (1) Protein functional annotation and repeated quantitative analysis showed that protein expression in the E groups was closer to that in the S group, while the N group similarly to the M group. These demonstrated that electroacupuncture could regulate protein expression in the hippocampal region of MCAO rats to normalize the expression. (2) The difference in protein expression between groups quantified by the specific peptide could be hypothesized that the improvement of learning memory in MCAO rats after electroacupuncture of Shenting and Baihui was achieved by the downregulation of a class or a specific protein in hippocampus. (3) It was observed that the inter-synaptic regulatory proteins were the structural basis for the improvement of protein expression in MCAO rats by electroacupuncture, which could provide a new idea for the localization and characterization of specific proteins. Conclusions: Our findings provided valuable protein biomarkers and new ideas for future mechanistic studies on improving cognitive function in post-stroke cognitive impairment.

Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

Abstract Background Epstein–Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (EBV‐posDLBCL) is an aggressive B‐cell lymphoma that often presents similar morphological and immune phenotype features to that of EBV‐negative DLBCL (EBV‐negDLBCL). Aims and Methods To better understand their difference in genomic landscape, we performed whole‐exome sequencing (WES) of EBV‐posDLBCL and EBV‐negDLBCL. Results This analysis revealed a new mutational signature 17 (unknown) and signature 29 (smoking) in EBV‐posDLBCL as well as a specific mutational signature 24 (associated with aflatoxin) in EBV‐negDLBCL. Compared with EBV‐negDLBCL, more somatic copy number alterations (CNAs) and deletions were detected in EBV‐posDLBCL (p = 0.01). The most frequent CNAs specifically detected in EBV‐posDLBCL were gains at 9p24.1 (PDL1 and JAK2), 8q22.2‐q24.23 (DEPTOR and MYC), and 7q31.31‐q32.2 (MET), which were validated in additional EBV‐posDLBCL cases. Overall, 53.7% (22/41) and 62.9% (22/35) of the cases expressed PD‐L1 and c‐MET, respectively, in neoplastic cells, whereas only 15.4% (4/26) expressed c‐MYC. Neoplastic c‐MET expression was positively correlated with PD‐L1 (p

Objectives The association between sarcopenia severity and fall history remains under-researched at present. Accordingly, this study was developed to evaluate the relationship between sarcopenic status and prior fall events in a multiethnic group of older community-dwelling adults in Western China.Design A retrospective survey study, the data comes from the West China Health and Aging Trend study.Setting The study was based in Western China.Participants In total, this retrospective analysis incorporated data from 2719 older adults (59.2% women).Primary and secondary outcome measures Grip strength, gait speed and skeletal muscle mass index values were analysed for all participants, and the Asian Working Group for Sarcopenia (AWGS) 2014 and 2019 consensus criteria were leveraged to assess sarcopenia status in these individuals. Prior fall history was defined by any incidents in which an individual unintentionally came to rest on the floor within the past year. The association between sarcopenia status and fall history was examined through a binary logistic regression approach, with p

Primary pericardial angiosarcoma is a rare malignancy of the pericardium with variable clinical features and imaging characteristics. Herein, we report a case of histopathologically confirmed pericardial angiosarcoma in a 66-year-old man. The patient developed cardiac tamponade in a short time period. The transthoracic echocardiography showed the presence of multiple irregular echodensities, heterogeneous in echogenicity, encasing the apex of both ventricles in the pericardial space, initially misinterpreted as pericardial effusion. The patient died of cardiogenic shock despite undergoing a surgical pericardiectomy. Pericardial angiosarcoma can manifest as a mass obliterating the pericardial sac, rather than the typical pericardial effusion observed on echocardiography. Multimodality imaging studies aid in diagnosing primary pericardial angiosarcoma, but the final diagnosis relies on tissue histopathology.

Purpose: To investigate the rate of vault changes after implantation of ICL V4c and the correlation with anterior segment parameters. Methods: A total of 64 eyes were studied from the 37 myopic subjects recruited. CASIA2 was used to record the vault at 1 week, 1 month, 3 months and 6 months after the operation as well as the preoperative anterior segment parameters including pupil diameter, lens vault, anterior chamber depth, anterior chamber width, iris area (IA), iris thickness, angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle. The rates of vault change in different time intervals were compared and the correlations between the rates and anterior segment parameters were analyzed. P 0.05). Conclusion: The rate of decreasing vault significantly slowed down from 3 months post-operation. A larger IA may imply a lower decreasing rate of vault change.

Obesity has a significant impact on endocrine function, which leads to metabolic diseases including diabetes, insulin resistance, and other complications associated with obesity. Development of effective and safe anti-obesity drugs is imperative and necessary. Equisetin (EQST), a tetramate-containing marine fungal product, was reported to inhibit bacterial fatty acid synthesis and affect mitochondrial metabolism. It is tempting to speculate that EQST might have anti-obesity effects. This study was designed to explore anti-obesity effects and underlying mechanism of EQST on 3T3-L1 adipocytes differentiated from 3T3-L1 cells. Oil Red O staining showed that EQST reduced lipid accumulation in 3T3-L1 adipocytes. Quantitative real-time polymerase chain reaction and Western blot analysis revealed that EQST significantly inhibited expression of adipogenesis/lipogenesis-related genes C/ebp-α, Ppar-γ, Srebp1c, Fas, and reduced protein levels. There was also increased expression of key genes and protein levels involved in lipolysis (Perilipin, Atgl, Hsl), brown adipocyte differentiation (Prdm16, Ucp1), mitochondrial biogenesis (Pgc1α, Tfam) and β-oxidation Acsl1, Cpt1. Moreover, mitochondrial content, their membrane potential ΔΨM, and respiratory chain genes Mt-Co1, Cox7a1, Cox8b, and Cox4 (and protein) exhibited marked increase in expression upon EQST treatment, along with increased protein levels. Importantly, EQST induced expression and activation of AMPK, which was compromised by the AMPK inhibitor dorsomorphin, leading to rescue of EQST-downregulated Fas expression and a reduction of the EQST-increased expression of Pgc1α, Ucp1, and Cox4. Together, EQST robustly promotes fat clearance through the AMPK pathway, these results supporting EQST as a strong candidate for the development into an anti-obesity therapeutic agent.

Background: Bladder cancer (BLCA) is a common malignant tumor of urinary system and prognostic biomarkers are needed for better clinical decision-making and patient management. Cancer stem cells (CSCs) are involved in carcinogenesis, development, metastasis and recurrence of BLCA. This study explored the prognostic and predictive value of CSCs-related genes and laid the groundwork for precision treatment development in BLCA. Methods: The mRNA data and corresponding clinical information obtained from TCGA-BLCA cohort was used to discover biomarkers and develop CSCs-related prognostic model, which was further validated in GSE32548 and GSE32894 datasets. In addition, the association between CSCs-related risk score and therapeutic efficacy was analyzed to explore the potential predictive value of the prognostic model. Results: We identified four CSCs-related subtypes and 900 differentially expressed genes (DEGs) among subtypes. Then the CSCs-related prognostic model was built based on 16 CSCs-related DEGs with the most significant prognostic value. Patients in the low-risk group had better overall survival than those in high-risk group (P

IntroductionThere are no standardized assessment criteria for selecting nutritional risk screening tools or indicators to assess reduced muscle mass (RMM) in the Global Leadership Initiative on Malnutrition (GLIM) criteria. We aimed to compare the consistency of different GLIM criteria with Subjective Global Assessment (SGA) and protein-energy wasting (PEW).MethodsIn this study, nutritional risk screening 2002 first four questions (NRS-2002-4Q), Nutritional Risk Screening 2002 (NRS-2002), Malnutrition Universal Screening Tool (MUST), and Mini-Nutritional Assessment Short-Form (MNA-SF) tools were used as the first step of nutritional risk screening for the GLIM. The RMM is expressed using different metrics. The SGA and PEW were used to diagnose patients and classify them as malnourished and non-malnourished. Kappa (κ) tests were used to compare the concordance between the SGA, PEW, and GLIM of each combination of screening tools.ResultsA total of 157 patients were included. Patients with Chronic kidney disease (CKD) stage 1–3 accounted for a large proportion (79.0%). The prevalence rates of malnutrition diagnosed using the SGA and PEW were 18.5% and 19.7%, respectively. The prevalence of GLIM-diagnosed malnutrition ranges from 5.1% to 37.6%, depending on the different screening methods for nutritional risk and the different indicators denoting RMM. The SGA was moderately consistent with the PEW (κ = 0.423, p

Deep learning relies on learning from extensive data to generate prediction results. This approach may inadvertently capture spurious correlations within the data, leading to models that lack interpretability and robustness. Researchers have developed more profound and stable causal inference methods based on cognitive neuroscience. By replacing the correlation model with a stable and interpretable causal model, it is possible to mitigate the misleading nature of spurious correlations and overcome the limitations of model calculations. In this survey, we provide a comprehensive and structured review of causal inference methods in deep learning. Brain-like inference ideas are discussed from a brain-inspired perspective, and the basic concepts of causal learning are introduced. The article describes the integration of causal inference with traditional deep learning algorithms and illustrates its application to large model tasks as well as specific modalities in deep learning. The current limitations of causal inference and future research directions are discussed. Moreover, the commonly used benchmark datasets and the corresponding download links are summarized.

Nature, with its numerous surprising rules, serves as a rich source of creativity for the development of artificial intelligence, inspiring researchers to create several nature-inspired intelligent computing paradigms based on natural mechanisms. Over the past decades, these paradigms have revealed effective and flexible solutions to practical and complex problems. This paper summarizes the natural mechanisms of diverse advanced nature-inspired intelligent computing paradigms, which provide valuable lessons for building general-purpose machines capable of adapting to the environment autonomously. According to the natural mechanisms, we classify nature-inspired intelligent computing paradigms into 4 types: evolutionary-based, biological-based, social-cultural-based, and science-based. Moreover, this paper also illustrates the interrelationship between these paradigms and natural mechanisms, as well as their real-world applications, offering a comprehensive algorithmic foundation for mitigating unreasonable metaphors. Finally, based on the detailed analysis of natural mechanisms, the challenges of current nature-inspired paradigms and promising future research directions are presented.

Type II crustacean hyperglycemic hormone (CHH) neuropeptides play diverse roles in crustaceans. In the hermaphrodite shrimp Lysmata vittata, two transcripts of type II CHHs (molt-inhibiting hormone/gonad-inhibiting hormone, MIH/GIH1 and MIH/GIH2) were identified by transcriptome sequencing, and MIH/GIH1 was later named Lvit-GIH1 for its inhibitory effect on ovarian development. Based on the high similarity of MIH/GIH2 to Lvit-GIH1, we named tentatively MIH/GIH2 as Lvit-GIH2 and explored the role of Lvit-GIH2 in ovarian development. The open reading frame (ORF) of Lvit-GIH2 was 333 bp in length, encoding a precursor consisted of a 32-aa signal peptide and a 78-aa mature peptide, which shared high sequence similarity with the type II subfamily peptides in crustaceans. Notably, Lvit-GIH2 was widely expressed in multiple tissues. The qRT-PCR findings indicated a rising trend in the expression of Lvit-GIH2 from the male phase to the euhermaphrodite phase. Both RNA interference and addition of GIH2 recombinant proteins (rGIH2) experiments showed that Lvit-GIH2 suppressed Lvit-Vg expression in hepatopancreas and Lvit-VgR expression in ovary. To further investigate the role of Lvit-GIH2 in ovarian development, the RNA-sequence analysis was performed to examine the changes in ovary after addition of rGIH2. The results showed that the pathways (Cysteine and methionine metabolism, Apoptosis-multiple species, etc.) and the genes (17bHSD8, IGFR, CHH, etc.) related to ovarian development were negatively regulated by rGIH2. In brief, Lvit-GIH2 might inhibit the ovarian development in L. vittata.

It has been reported that Ywhah (14-3-3η) reduces glycolysis. However, it remains unclear about the downstream mechanism by which glycolysis is regulated by 14-3-3η in cardiac hypertrophy. As an important regulator, Yes-associated protein (YAP) interacts with 14-3-3η to participate in the initiation and progression of various diseases in vivo. In this study, the model of H9C2 cardiomyocyte hypertrophy was established by triiodothyronine (T3) or rotenone stimulation to probe into the action mechanism of 14-3-3η. Interestingly, the overexpression of 14-3-3η attenuated T3 or rotenone induced cardiomyocyte hypertrophy and decreased glycolysis in H9C2 cardiomyocytes, whereas the knockdown of 14-3-3η had an opposite effect. Mechanistically, 14-3-3η can reduce the expression level of YAP and bind to it to reduce its nuclear translocation. In addition, changing YAP may affect the expression of lactate dehydrogenase A (LDHA), a glycolysis-related protein. Meanwhile, LDHA is also a possible target for 14-3-3η to mediate glycolysis based on changes in pyruvate, a substrate of LDHA. Collectively, 14-3-3η can suppress cardiomyocyte hypertrophy via decreasing the nucleus translocation of YAP and glycolysis, which indicates that 14-3-3η could be a promising target for inhibiting cardiac hypertrophy.

The scientific determination of crucial regions for ecological land restoration and reasonable early warnings for ecologically weak areas are vital for implementing land ecological restoration. Five major plateau lake basins in central Yunnan (China) are selected as the study area in this research. An ecological security pattern (ESP) is constructed using the source-resistance surface-corridor-pinch point framework to effectively identify crucial areas for ecological restoration. Finally, the land use/cover change (LUCC) in the study region in 2030 is simulated in terms of the natural development prospect (NDP), with priority given to urban development (PUD) and priority given to ecological protection (PEP) scenarios, and identify areas where future urban expansion poses a threat to current ecological source areas and corridors as early warning regions. The results indicate the following: (1) There are 15 ecological source regions in the Five Lakes Basin, mainly forestland and waters, with a total area of 787.54 km2. The ecological corridor spans 245.72 km, with a total area of 439.90 km2. (2) The key ecological restoration areas include 72.87 km2 of ecological pinch points, 70.46 km2 of barrier points of ecological, and 71 breakpoints. (3) The ecological land under the NDP scenario and the PUD scenario were damaged to varying degrees. The ecological land dominated by forestland and water area under the PEP scenario is effectively protected. (4) The seven ecological protection space early warning points are mainly distributed in the eastern part of Dianchi Lake and the northern part of Fuxian Lake, which have good economic development and better habitat quality. The comprehensive analysis identified key ecological restoration areas and identified future ecological stresses due to land use change in the Five-Lakes Basin. Restoration strategies are proposed based on current land use and future scenarios to enhance the ESP in central Yunnan's Five Lakes Basin.

Summary: The 5′-deoxyadenosine deaminase (DADD), a member of the amidohydrolase family regulates biological purine metabolism. In this study, bioinformatic analysis, overexpression and knockdown of GhdadD gene were detected to identify its potential role in drought and salt stress tolerance. The results revealed that GhdadD was induced by ABA, Auxin, MBS and light responsive elements. In transgenic Arabidopsis, seed germination rate and root length were increased under drought or salt stress. GhdadD overexpressed seedlings resulted in higher plant height, less leaf damage and lower ion permeability. The expression of osmotic stress and ABA-responsive genes were up regulated. While in GhdadD-silenced cotton seedlings, CAT, SOD activity and soluble sugar content were reduced, MDA content was increased, and the stoma opening was depressed under drought or salt stress. Some osmics stress marker genes were also up regulated. These data indicating that GhdadD enhanced plant resistance to drought and salt stress through ABA pathways.

Campylobacter concisus is an oral bacterium. Recent studies suggest that C. concisus may be involved in human gastric diseases. The mechanisms, however, by which C. concisus causes human gastric diseases have not been investigated. Here we examined the gastric epithelial pathogenicity of C. concisus using a cell culture model. Six C. concisus strains and the human gastric epithelial cell line AGS cells were used. IL-8 produced by AGS cells after incubation with C. concisus was measured using enzyme-linked immunosorbent assay (ELISA), and AGS cell apoptosis was determined by caspase 3/7 activities. The effects of C. concisus on actin arrangement in AGS cells was determined using fluorescence staining. The effects of C. concisus on global gene expression in AGS cells was determined by transcriptomic analysis and quantitative real-time PCR (qRT-PCR). The role of the upregulated CYP1A1 gene in gastric cancer survival was assessed using the Kaplan-Meier method. C. concisus induced production of IL-8 by AGS cells with strain variation. Significantly increased caspase 3/7 activities were observed in AGS cells incubated with C. concisus strains when compared to AGS cells without bacteria. C. concisus induced actin re-arrangement in AGS cells. C. concisus upregulated 30 genes in AGS cells and the upregulation of CYP1A1 gene was confirmed by qRT-PCR. The Kaplan-Meier analysis showed that upregulation of CYP1A1 gene is associated with worse survival in gastric cancer patients. Our findings suggest that C. concisus may play a role in gastric inflammation and the progression of gastric cancer. Further investigation in clinical studies is warranted.

One patient with rifampin-resistant tuberculosis underwent emergency left pneumonectomy and thoracic gauze packing for hemoptysis due to recurrent hemoptysis after transcatheter arterial embolization. Vital signs were maintained by mechanical ventilation and medication. Tracheotomy and anti-tuberculosis treatment were performed. After half a year of follow-up, the patient's condition was stable.

Various psychosocial and psychological interventions have been developed to reduce schizophrenia relapse prevention. A better understanding of these active interventions is important for clinical practice and for meaningful allocation of resources. However, no bibliometric analysis of this area has been conducted. Studies were retrieved from the Web of Science Core Collection database. The publication outputs and cooperation of institutions were visualized with Origin 2021. Global cooperation was visualized using ArcGIS Pro3.0. VOSviewer was used to generate visualizations of network of authors and keywords. The number of annual publications generally showed a fluctuating upward trend over the past 20 years. Germany published the most relevant articles (361, 26.76%). The Technical University of Munich was the most productive institution (70, 9.86%). Leucht Stefan published the most articles (46, 6.48%) and had the highest number of citations (4,375 citations). Schizophrenia Research published the most studies (39, 5.49%). Keywords were roughly classified into three clusters: cognitive behavioral therapy (CBT), family interventions and family psychoeducation and other factors related to interventions. The findings provided the current status of research on psychosocial and psychological interventions for schizophrenia relapse prevention from a bibliometric perspective. Recent research has mainly focused on CBT, family interventions and family psychoeducation.

We explored the nonlinear characteristics of energy resolution (ER) for the sealed NaI (Tl) scintillator detector by using a gamma-ray spectroscopy system and Monte Carlo simulation. Our research focused on the two primary factors of energy resolution including the photomultiplier tube (PMT) voltage and the distance between the gamma-ray sources (137Cs and 60Co) and the scintillator detector. The experimental results showed that energy resolution decreased when the PMT voltage increased, and the energy resolution of NaI (Tl) detectors reached a smaller value (6.92%, 6.76%, and 6.56%), especially with the PMT voltage in the range of 575–595 V. In addition, a suitable distance between the gamma-ray source and the scintillator (5 cm) can also effectively reduce the energy resolution. We established the simulation models of the experimental NaI (Tl) detectors and simulated their energy spectra. The simulation results in the peak area agreed with the experimental results. A possible better PMT voltage choice has been proposed to obtain a smaller energy resolution.

BackgroundAs the impact of the COVID-19 pandemic winds down, both individuals and society are gradually returning to life and activities before the pandemic. This study aims to explore how people's emotions have changed from the pre-pandemic period during the pandemic to this post-emergency period and whether the sentiment level nowadays has returned to the pre-pandemic level.MethodWe collected Reddit social media data in 2019 (pre-pandemic), 2020 (peak period of the pandemic), 2021, and 2022 (late stages of the pandemic, transitioning period to the post-emergency period) from the subreddits communities in 128 universities/colleges in the U.S., and a set of school-level baseline characteristics such as location, enrollment, graduation rate, selectivity, etc. We predicted two sets of sentiments from a pre-trained Robustly Optimized BERT pre-training approach (RoBERTa) and a graph attention network (GAT) that leverages both the rich semantic information and the relational information among posted messages and then applied model stacking to obtain the final sentiment classification. After obtaining the sentiment label for each message, we employed a generalized linear mixed-effects model to estimate the temporal trend in sentiment from 2019 to 2022 and how the school-level factors may affect the sentiment.ResultsCompared to the year 2019, the odds of negative sentiment in years 2020, 2021, and 2022 are 25%. 7.3%, and 6.3% higher, respectively, which are all statistically significant at the 5% significance level based on the multiplicity-adjusted p-values.ConclusionsOur study findings suggest a partial recovery in the sentiment composition (negative vs. non-negative) in the post-pandemic-emergency era. The results align with common expectations and provide a detailed quantification of how sentiments have evolved from 2019 to 2022 in the sub-population represented by the sample examined in this study.

Drug repurposing is a strategy for identifying new uses of approved or investigational drugs that are outside the scope of the original medical indication. Even though many repurposed drugs have been found serendipitously in the past, the increasing availability of large volumes of biomedical data has enabled more systemic, data-driven approaches for drug candidate identification. At National Center of Advancing Translational Sciences (NCATS), we invent new methods to generate new data and information publicly available to spur innovation and scientific discovery. In this study, we aimed to explore and demonstrate biomedical data generated and collected via two NCATS research programs, the Toxicology in the 21st Century program (Tox21) and the Biomedical Data Translator (Translator) for the application of drug repurposing. These two programs provide complementary types of biomedical data from uncovering underlying biological mechanisms with bioassay screening data from Tox21 for chemical clustering, to enrich clustered chemicals with scientific evidence mined from the Translator towards drug repurposing. 129 chemical clusters have been generated and three of them have been further investigated for drug repurposing candidate identification, which is detailed as case studies.

With the increasingly widespread application of CMOS image sensors (CIS) in radiation environments, such as aerospace, their radiation effects have gained attention. This paper investigates single-event transient (SET) caused by the proton direct ionization on CIS, combining both experimental and simulation methods. The proton beam energy used in the experiment is 12 MeV, with a flux up to 3.5 × 108 p/(cm2 s). Due to the periodicity of the proton beam, the CIS output displays a phenomenon of alternating brightness and darkness. When the proton beam flux is low, numerous SET bright spots with different outputs are observed. To comprehensively analyze these experimental phenomena, a typical three-dimensional 4T pinned photodiode model is constructed in TCAD, and relevant SET simulation is carried out. The results indicate that incident position, incident time, and the number of incident protons significantly affect the output of SET-generated bright spots, which are key factors contributing to the different bright spots observed in the experiment.

Pan-entertainment live streaming combines video with two-way communication and real-time viewer participation, allowing viewers to send virtual gifts to their favorite streamers. Drawing on social exchange theory, this study investigates the factors that influence viewers' gift-giving intentions in live streaming from the perspectives of both viewers and streamers. It also explores the moderating role of streamers' deceptive self-presentation. The theoretical framework is tested using AMOS and PROCESS Macro based on survey responses collected from 331 TikTok users in China. The results suggest that streamers' attractiveness, expertise, parasocial interaction, and the viewers' deceptive self-presentation significantly affect viewers' gift-giving intention, and that streamers' deceptive self-representation moderates the relationship between attractiveness, expertise, parasocial inter-action and the viewer's consumer intention. These findings contribute to social exchange theory by highlighting the importance of streamers' deceptive self-presentation in moderating the effects of attractiveness, expertise, parasocial interaction, and the viewer's deceptive self-presentation on the viewer's gift-giving intention.

Objective: To analyze the efficacy of noninvasive prenatal genetic testing (NIPT) in detecting fetal sex chromosome abnormalities and copy number variation (CNV), compare the efficacy between NIPT and serological screening alone, and further analyze the fetal sex chromosome abnormalities and CNV differentiation in pregnant women of different ages, so as to provide a reference for the prevention and control of fetal birth defects. Methods: Clinical data from 22,692 pregnant women admitted to our hospital from January 2013 to December 2022 were retrospectively analyzed. All participants underwent serological screening and NIPT screening to compare fetal chromosomal abnormalities between the two screening modalities. 145 women whose fetus were diagnosed as sex chromosome abnormalities and 36 women whose fetus were diagnosed as CNV abnormalities based on NIPT screening were selected for prenatal diagnosis by amniocentesis or karyotyping. Taking prenatal diagnosis as the standard, the four-grid table method was used to detect the positive predictive value of NIPT screening for fetal sex chromosomal abnormalities and CNV. According to the age, pregnant women were divided into 18–30 years old (n = 9844), 31–35 years old (n = 7612), >35 years old (n = 5236), and then the detection rates of sexual fetal chromosomal abnormalities, CNV and total chromosomal abnormalities were compared in pregnant women. Results: Among the 22,692 pregnant women in this study, the high-risk proportion of serologic screening with 4.38% was higher than that of NIPT screening with 1.93% (P 10 Mb were 33.33% and 66.67%, respectively. There were 12 cases of prenatal diagnosis of fetal CNV, among which the NIPT-screened positive predictive values of fetal copy number deletion, duplicate, deletion and duplicate were 50.00%, 57.14% and 100.00%, respectively, with an overall predictive value of 58.33%. The positive predictive value of CNV in NIPT screening was higher than that of serological screening without statistically significant difference (P > 0.05). The results of NIPT screening showed that the detection rate of fetal sex chromosome abnormalities and total abnormalities of pregnant women over 35 years of age was significantly higher than that of pregnant women aged 18–30 and 31–35 years (P

Background: Anti-Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) have shown significant efficacy in preventing migraine. However, there have been limited reports of adverse events (AEs) after marketing, particularly for eptinezumab launched in 2020. The study aimed to mine and analyze the AE signals with four anti-CGRP mAbs from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insights into the safety profile of these medications post-marketing.Methods: All AE reports on the four anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab, and eptinezumab) were retrieved from the FAERS database from the first quarter (Q1) of 2018 to Q1 of 2023. Disproportionality analysis was measured by reporting odd ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) to identify potential AE signals. Comparisons were made between the four drugs in terms of AEs.Results: A total of 38,515 reports of erenumab, 19,485 reports of galcanezumab, 5,332 reports of fremanezumab, and 2,460 reports of eptinezumab were obtained, mostly reported in the second to third year after launch in the market. The common AEs to erenumab included constipation (17.93%), injection site pain (14.08%), and alopecia (7.23%). The AEs that occurred more frequently with galcanezumab included injection site pain (24.37%), injection site erythema (5.35%), and injection site haemorrhage (4.97%). Common AEs related to fremanezumab were injection site pain (13.10%), injection site erythema (7.02%), and injection site pruritus (5.47%). Fatigue (13.54%), throat irritation (9.02%), and pruritus (8.20%) were the most common AEs with eptinezumab. In addition, there are new AEs that were not listed in the drug instructions but occurred concurrently with multiple drugs, such as Raynaud’s phenomenon, weight increase, menstrual disorders, throat tightness, and paraesthesia oral.Conclusion: Common AE signals of the four anti-CGRP mAbs and new AE signals were found to provide a reference for clinical drug selection in clinical practice.

BackgroundHepatocellular carcinoma (HCC) is a malignant tumor with a high rate of recurrence and m metastasis that does not respond well to current therapies and has a very poor prognosis. Disulfidptosis is a novel mode of cell death that has been analyzed as a novel therapeutic target for HCC cells.MethodsThis study integrated bulk ribonucleic acid (RNA) sequencing datasets, spatial transcriptomics (ST), and single-cell RNA sequencing to explore the landscape of disulfidptosis and the immune microenvironment of HCC cells.ResultsWe developed a novel model to predict the prognosis of patients with HCC based on disulfidptosis. The model has good stability, applicability, and prognostic and immune response prediction abilities. N-myc downregulated gene1 (NDRG1) may contribute to poor prognosis by affecting macrophage differentiation, thus allowing HCC cells to evade the immune system.ConclusionOur study explores the disulfidptosis of HCC cells through multi-omics and establishes a new putative model that explores possible targets for HCC treatment.

Abstract Introduction This study assessed the cost-effectiveness of secukinumab compared with other biologics (adalimumab, infliximab, ustekinumab, ixekizumab, guselkumab, and Yisaipu [etanercept biosimilar]) for moderate-to-severe plaque psoriasis from the Chinese healthcare system perspective. Methods A decision-tree (first year)/Markov model (subsequent years), with an annual cycle, was implemented over a lifetime horizon. The Psoriasis Area and Severity Index (PASI) response rate at week 16 was used for treatment response. Efficacy inputs were obtained from a mixed-treatment comparison conducted using data from randomized controlled trials. Other clinical inputs (adverse events, dropout, and mortality rates), utility weights, and costs were derived from published literature and local Chinese sources. Both costs and outcomes were discounted at 5% per annum. Model outcomes included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to test the robustness of results. Results For patients with moderate-to-severe psoriasis, secukinumab generated the highest QALYs (12.334) against all comparators at a lifetime cost of ¥231,477. Secukinumab dominated (higher QALYs at lower costs) all other biologics except ixekizumab in this population. Compared with secukinumab, ixekizumab incurred slightly lower costs (¥228,320) but gained lesser QALYs (12.284). Thus, secukinumab was a cost-effective treatment than ixekizumab at a willingness-to-pay (WTP) threshold of ¥257,094 per QALY gained. In the one-way sensitivity analysis, base-case results were most sensitive to changes in the PASI response at 16 weeks and year 2+ dropout rates. Conclusion Secukinumab is the most cost-effective treatment option for patients with moderate-to-severe psoriasis compared with other commonly used biologics from the Chinese healthcare system perspective.

Abstract Based on 4.5 fb −1 data taken at seven center-of-mass energies ranging from 4.600 to 4.699 GeV with the BESIII detector at the BEPCII collider, we measure the branching fractions of Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ + hadrons relative to Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ π + π − . Combining with the world average branching fraction of Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ π + π − , their branching fractions are measured to be (0.377 ± 0.042 ± 0.020 ± 0.021)% for Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ K + K − , (0.200 ± 0.023 ± 0.011 ± 0.011)% for Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ K + π − , (0.414 ± 0.080 ± 0.030 ± 0.023)% for Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ ϕ and (0.197 ± 0.036 ± 0.009 ± 0.011)% for Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ K + K − (non-ϕ). In all the above results, the first uncertainties are statistical, the second are systematic and the third are from external input of the branching fraction of Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ π + π − . Since no signal for Λ c + $$ {\Lambda}_c^{+} $$ → Σ+ K + π − π 0 is observed, the upper limit of its branching fraction is determined to be 0.13% at the 90% confidence level.

Abstract Utilizing 7.33 fb −1 of e + e − collision data taken at the center-of-mass energies of 4.128, 4.157, 4.178, 4.189, 4.199, 4.209, 4.219, and 4.226 GeV with the BESIII detector, the branching fraction of the leptonic decay D s + $$ {D}_s^{+} $$ → τ + ν τ via τ + → μ + ν μ ν ¯ $$ \overline{\nu} $$ τ is measured to be B D s + → τ + ν τ $$ {\mathcal{B}}_{D_s^{+}\to {\tau}^{+}{\nu}_{\tau }} $$ = (5.37 ± 0.17stat ± 0.15syst)%. Combining this branching fraction with the world averages of the measurements of the masses of τ + and D s + $$ {D}_s^{+} $$ as well as the lifetime of D s + $$ {D}_s^{+} $$ , we extract the product of the decay constant of D s + $$ {D}_s^{+} $$ and the c → s Cabibbo-Kobayashi-Maskawa matrix element to be f D s + $$ {f}_{D_s^{+}} $$ |V cs | = (246.7 ± 3.9stat ± 3.6syst) MeV. Taking |V cs | from a global fit in the standard model we obtain f D s + $$ {f}_{D_s^{+}} $$ = (253.4 ± 4.0stat ± 3.7syst) MeV. Conversely, taking f D s + $$ {f}_{D_s^{+}} $$ from lattice quantum chromodynamics calculations, we obtain |V cs | = 0.987 ± 0.016stat ± 0.014syst.

Abstract Background There are few studies on acute-on-chronic liver failure (ACLF) in patients with recompensated cirrhosis. This study was aimed to investigate the clinical features of ACLF patients with recompensated cirrhosis. Methods A total of 461 ACLF patients were enrolled and divided into three groups: compensated, recompensated, and decompensated cirrhosis with ACLF. The baseline clinical data and 1-year survival rates were compared among the three groups. Results Compared with the decompensated group, in the recompensated group, the levels of hemoglobin, albumin, and serum sodium were significantly higher and the white blood cell count, international normalized ratio, and incidence of respiratory failure were significantly lower; there were no evident differences in other organ failures. The proportion of patients with ACLF grade 3 and 1-year survival rates significantly differed between the two groups. Conversely, compared with the compensated group, in the recompensated group, the platelet and total bilirubin levels were significantly lower and the proportion of patients with ACLF grade 1 was significantly higher. However, other clinical indicators or 1-year survival rates did not significantly differ between the two groups. Conclusions Compared with patients who developed ACLF with decompensated cirrhosis, those who developed ACLF with recompensated cirrhosis had a less severe condition, lower incidence of respiratory failure, and better 1-year prognosis. However, the baseline clinical features and prognosis were similar between ACLF patients with recompensated and compensated cirrhosis. Trial registration Chinese clinical trials registry: ChiCTR1900021539.

Abstract Using 2.93 fb −1 of e + e − collision data collected with the BESIII detector at the center-of-mass energy 3.773 GeV, we perform the first amplitude analysis of the decay D + → K S 0 $$ {K}_S^0 $$ π + π 0 π 0 and determine the relative magnitudes and phases of different intermediate processes. The absolute branching fraction of D + → K S 0 $$ {K}_S^0 $$ π + π 0 π 0 is measured to be (2.888 ± 0.058stat. ± 0.069syst. )%. The dominant intermediate processes are D + → K S 0 $$ {K}_S^0 $$ a 1(1260)+(→ ρ + π 0) and D + → K ¯ $$ \overline{K} $$ *0 ρ +, with branching fractions of (8.66 ± 1.04stat. ± 1.39syst. ) × 10 −3 and (9.70 ± 0.81stat. ± 0.53syst. ) × 10 −3, respectively.

Abstract Against the backdrop of accelerated global climate change and urbanization, the frequency and severity of flood disasters have been increasing. In recent years, influenced by climate change, the Hai-River Basin (HRB) has experienced multiple large-scale flood disasters. During the widespread extraordinary flood event from July 28th to August 1st, 2023, eight rivers witnessed their largest floods on record. These events caused significant damage and impact on economic and social development. The development of hydrological models with better performance can help researchers understand the impacts of climate change, provide risk information on different disaster events within watersheds, support decision-makers in formulating adaptive measures, urban planning, and improve flood defense mechanisms to address the ever-changing climate environment. This study examines the potential for enhancing streamflow simulation accuracy in the HRB located in Northeast China by combining the physically-based hydrological model with the data-driven model. Three hybrid models, SWAT-D-BiLSTM, SWAT-C-BiLSTM and SWAT-C-BiLSTM with SinoLC-1, were constructed in this study, in which SWAT was used as a transfer function to simulate the base flow and quick flow generation process based on weather data and spatial features, and BiLSTM was used to directly predict the streamflow according to the base flow and quick flow. In the SWAT-C-BiLSTM model, SWAT parameters with P values less than 0.4 in each hydrological station-controlled watershed were calibrated, while the SWAT-D-BiLSTM model did not undergo calibration. Additionally, this study utilizes both 30 m resolution land use and land cover (LULC) map and the first 1 m resolution LULC map SinoLC-1 as input data for the models to explore the impact on streamflow simulation performance. Among five models, the NSE of SWAT-C-BiLSTM with SinoLC-1 reached 0.93 and the R2 reached 0.95 during the calibration period, and both of them stayed at 0.92 even in the validation period, while the NSE and R2 of the other four models were all below 0.90 in the validation period. The potential impact of climate change on streamflow in the HRB was evaluated by using predicted data from five global climate models from CMIP6 as input for the best-performing SWAT-C-BiLSTM with SinoLC-1. The results indicate that climate change exacerbates the uneven distribution of streamflow in the HRB, particularly during the concentrated heavy rainfall months of July and August. It is projected that the monthly streamflow in these two months will increase by 34% and 49% respectively in the middle of this century. Furthermore, it is expected that the annual streamflow will increase by 5.6% to 9.1% during the mid-century and by 6.7% to 9.3% by the end of the century. Both average streamflow and peak streamflow are likely to significantly increase, raising concerns about more frequent urban flooding in the capital economic region within the HRB.

Abstract Anti-Stokes photoluminescence (PL) is light emission at a higher photon energy than the excitation, with applications in optical cooling, bioimaging, lasing, and quantum optics. Here, we show how plasmonic nano-cavities activate anti-Stokes PL in WSe2 monolayers through resonant excitation of a dark exciton at room temperature. The optical near-fields of the plasmonic cavities excite the out-of-plane transition dipole of the dark exciton, leading to light emission from the bright exciton at higher energy. Through statistical measurements on hundreds of plasmonic cavities, we show that coupling to the dark exciton leads to a near hundred-fold enhancement of the upconverted PL intensity. This is further corroborated by experiments in which the laser excitation wavelength is tuned across the dark exciton. We show that a precise nanoparticle geometry is key for a consistent enhancement, with decahedral nanoparticle shapes providing an efficient PL upconversion. Finally, we demonstrate a selective and reversible switching of the upconverted PL via electrochemical gating. Our work introduces the dark exciton as an excitation channel for anti-Stokes PL in WSe2 and paves the way for large-area substrates providing nanoscale optical cooling, anti-Stokes lasing, and radiative engineering of excitons.

Abstract Objectives This study aims to investigate molecular epidemiology and clinical characteristics of enterovirus associated hand-foot-mouth disease (HFMD) in Chengdu, China, 2013–2022. Monitoring the molecular epidemiology and clinical features of HFMD for up to 10 years may provide some ideas for future protection and control measures. Methods We conducted a retrospective analysis of the medical records of all patients with laboratory-confirmed HFMD-related enterovirus infection at the West China Second University Hospital from January 2013 to December 2022. We described the characteristics in serotype, age, sex distribution and hospitalization of enterovirus infection cases using data analysis and graphic description. Results A total of 29,861 laboratory-confirmed cases of HFMD-related enterovirus infection were reported from 2013 to 2022. There was a significant reduction in the number and proportion of EV-A71 cases after 2016, from 1713 cases (13.60%) in 2013–2015 to 150 cases (1.83%) in 2017–2019. During the COVID-19 pandemic, EV-A71 cases even disappeared. The proportion of CV-A16 cases decreased from 13.96% in 2013–2015 to 10.84% in 2017–2019 and then to 4.54% in 2020–2022. Other (non-EV-A71 and non-CV-A16) serotypes accounted for 95.45% during 2020–2022, with CV-A6 accounting for 50.39% and CV-A10 accounting for 10.81%. Thus, CV-A6 and CV-A10 became the main prevalent serotypes. Furthermore, There was no significant difference in the enterovirus prevalence rate between males and females. The hospitalization rate of EV-A71 patients was higher that of other serotypes. In general, the proportion of HFMD hospitalizations caused by other pathogens except for EV-A71, CV-A16, CV-A10 and CV-A16 was second only to that caused by EV-A71. The proportion of children over 4 years old infected with enterovirus increased. Conclusion The incidence of HFMD associated with enterovirus infection has decreased significantly and CV-A6 has been the main pathogen of HFMD in Chengdu area in recent years. The potential for additional hospitalizations for other untested enterovirus serotypes suggested that attention should also be paid to the harms of infections with unknown enterovirus serotypes. Children with HFMD were older. The development of new diagnostic reagents and vaccines may play an important role in the prevention and control of enterovirus infection.

Abstract Background Long term care (LTC) services for functionally impaired senior citizens are crucial for addressing the challenges of aging. However, research on eligibility criteria and coverage of LTC in China is lacking. Our objective is to assess the current status of LTC and explore eligibility criteria and coverage for the elderly. Methods This is a cross-sectional study conducted in two first-tier cities in China. Residents aged 65 or over were recruited from a nursing home and four primary hospitals. Participants were divided into three groups (bedridden, domestic, and community), then six grades (grade one to six) according to the Longshi Scale, and their functional ability was assessed using the Modified Barthel Index. Information such as diseases, complications, and daily care needs were collected. Nursing staff were invited to indicate patients’ needs for care. A one-way ANOVA test, Kruskal Wallis H test and Mann–Whitney U test were used to explore the differences of variables in three Longshi groups or Longshi grades. Results Among all 1157 participants, with an average age of 80.54, 69.3% were in the bedridden group. The most common diagnosis was stroke (71.4%), with the most prevalent complication being pulmonary infection (25.2%). In the nursing assessment, basic health care, disease care, activity care, complication prevention care and psychosocial care were summarized as the five main aspects of LTC for the elderly. Feeding, bathing, drinking, bowel management and bladder management were identified as the basic care which fulfills participants’ basic physical needs in each Longshi group. Mouth care, artificial airway management, and body reposition, which can prevent immobility complications, were highly demanded by bedridden elderly. Conclusions The elderly in grade one to three are the ones in need of LTC most. The content of LTC for elderly should include basic care which fulfills their basic physical needs and complication care which can prevent immobility complications. The evidence of this research may contribute to the design of LTC in China. Trial registration The study design was registered in the Chinese Clinical Trial Registry (ChiCTR-2000034067, Registered 22 Jun 2020, http://www.chictr.org.cn/showproj.aspx?proj=54770 ).

Hepatocellular carcinoma (HCC) has a very high incidence and fatality rate, and in most cases, it is already at an advanced stage when diagnosed. Therefore, early prevention and detection of HCC are two of the most effective strategies. However, the methods recommended in the practice guidelines for the detection of HCC cannot guarantee high sensitivity and specificity except for the liver biopsy, which is known as the “gold standard”. In this review, we divided the detection of HCC into pre-treatment diagnosis and post-treatment monitoring, and found that in addition to the traditional imaging detection and liver biopsy, alpha fetoprotein (AFP), lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), protein induced by vitamin K absence or antagonist-II (PIVKA-II) and other biomarkers are excellent biomarkers for HCC, especially when they are combined together. Most notably, the emerging liquid biopsy shows great promise in detecting HCC. In addition, lactic dehydrogenase (LDH), suppressor of cytokine signaling (SOCS) and other relevant biomarkers may become promising biomarkers for HCC post-treatment monitoring. Through the detailed introduction of the diagnostic technology of HCC, we can have a detailed understanding of its development process and then obtain some enlightenment from the diagnosis, to improve the diagnostic rate of HCC and reduce its mortality.

Highly accurate rainfall prediction can provide a reliable scientific basis for human production and life. For the characteristics of occasional and sudden changes of rainfall in coastal hilly areas, this article chooses four cities in the eastern Zhejiang province as the object of the study and establishes a rainfall prediction model based on variational mode decomposition (VMD), reptile search algorithm (RSA), and differentiable neural computer (DNC). The VMD algorithm reduces the complexity of the sequence data; RSA is used to find the best-fit function; and DNC combines the advantages of the recurrent neural network and computational processing to improve the problem of memory forgetting of long short-term memory. To verify the prediction accuracy of the model, the prediction results are compared with the other three models, and the results show that the VMD–RSA–DNC model has the best prediction with the maximum and minimum relative errors of 9.62 and 0.17%, respectively, the average root-mean-square error of 5.43, the average mean absolute percentage error of 3.59%, and the average Nash–Sutcliffe efficiency of 0.95 for predicting four cities in the coastal hilly area. This study provides a new reference method for the construction of rainfall prediction models. HIGHLIGHTS Optimization of the differentiable neural computer (DNC) controller with reptile search algorithm (RSA) has a solid theoretical basis.; The coastal hilly area where plum rains and typhoons exist is selected for the study, and the prediction effect is better.; The coupled variational mode decomposition (VMD)–RSA–DNC model has higher prediction accuracy compared with other models.;

Abstract Using 15.6 fb −1 of e + e − collision data collected at twenty-four center-of-mass energies from 4.0 to 4.6 GeV with the BESIII detector, the helicity amplitudes of the process e + e − → π + π − ω are analyzed for the first time. Born cross section measurements of two-body intermediate resonance states with statistical significance greater than 5σ are presented, such as f 0(500), f 0(980), f 2(1270), f 0(1370), b 1(1235) ± , and ρ(1450) ± . In addition, evidence of a resonance state in e + e − → π + π − ω production is found. The mass of this state obtained by line shape fitting is about 4.2 GeV/c 2, which is consistent with the production of ψ(4160) or Y(4220).

Abstract Background Immunotoxins are antibody-toxin conjugates that bind to surface antigens and exert effective cytotoxic activity after internalization into tumor cells. Immunotoxins exhibit effective cytotoxicity and have been approved by the FDA to treat multiple hematological malignancies, such as hairy cell leukemia and cutaneous T-cell lymphoma. However, most of the internalized immunotoxin is degraded in lysosomes, and only approximately 5% of free toxin escapes into the cytosol to exert cytotoxicity. Many studies have improved immunotoxins by engineering the toxin fragment to reduce immunogenicity or increase stability, but how the antibody fragment contributes to the activity of immunotoxins has not been well demonstrated. Methods In the current study, we used 32A9 and 42A1, two anti-GPC3 antibodies with similar antigen-binding capabilities and internalization rates, to construct scFv-mPE24 immunotoxins and evaluated their in vitro and in vivo antitumor activities. Next, the antigen-binding capacity, trafficking, intracellular protein stability and release of free toxin of 32A9 scFv-mPE24 and 42A1 scFv-mPE24 were compared to elucidate their different antitumor activities. Furthermore, we used a lysosome inhibitor to evaluate the degradation behavior of 32A9 scFv-mPE24 and 42A1 scFv-mPE24. Finally, the antigen-binding patterns of 32A9 and 42A1 were compared under neutral and acidic pH conditions. Results Although 32A9 and 42A1 had similar antigen binding capacities and internalization rates, 32A9 scFv-mPE24 had superior antitumor activity compared to 42A1 scFv-mPE24. We found that 32A9 scFv-mPE24 exhibited faster degradation and drove efficient free toxin release compared to 42A1 scFv-mPE24. These phenomena were determined by the different degradation behaviors of 32A9 scFv-mPE24 and 42A1 scFv-mPE24 in lysosomes. Moreover, 32A9 was sensitive to the low-pH environment, which made the 32A9 conjugate easily lose antigen binding and undergo degradation in lysosomes, and the free toxin was then efficiently produced to exert cytotoxicity, whereas 42A1 was resistant to the acidic environment, which kept the 42A1 conjugate relatively stable in lysosomes and delayed the release of free toxin. Conclusions These results showed that a low pH-sensitive antibody-based immunotoxin degraded faster in lysosomes, caused effective free toxin release, and led to improved cytotoxicity compared to an immunotoxin based on a normal antibody. Our findings suggested that a low pH-sensitive antibody might have an advantage in the design of immunotoxins and other lysosomal degradation-dependent antibody conjugate drugs.

Abstract Nonlinear optical materials possess wide applications, ranging from terahertz and mid-infrared detection to energy harvesting. Recently, the correlations between nonlinear optical responses and certain topological properties, such as the Berry curvature and the quantum metric tensor, have attracted considerable interest. Here, we report giant room-temperature nonlinearities in non-centrosymmetric two-dimensional topological materials—the Janus transition metal dichalcogenides in the 1 T’ phase, synthesized by an advanced atomic-layer substitution method. High harmonic generation, terahertz emission spectroscopy, and second harmonic generation measurements consistently show orders-of-the-magnitude enhancement in terahertz-frequency nonlinearities in 1 T’ MoSSe (e.g., > 50 times higher than 2H MoS2 for 18th order harmonic generation; > 20 times higher than 2H MoS2 for terahertz emission). We link this giant nonlinear optical response to topological band mixing and strong inversion symmetry breaking due to the Janus structure. Our work defines general protocols for designing materials with large nonlinearities and heralds the applications of topological materials in optoelectronics down to the monolayer limit.

Abstract Background Lotus corniculatus is a widely distributed perennial legume whose great adaptability to different environments and resistance to barrenness make it an excellent forage and ecological restoration plant. However, its molecular genetics and genomic relationships among populations are yet to be uncovered. Result Here we report on a genomic variation map from worldwide 272 L. corniculatus accessions by genome resequencing. Our analysis suggests that L. corniculatus accessions have high genetic diversity and could be further divided into three subgroups, with the genetic diversity centers were located in Transcaucasia. Several candidate genes and SNP site associated with CNglcs content and growth traits were identified by genome-wide associated study (GWAS). A non-synonymous in LjMTR was responsible for the decreased expression of CNglcs synthesis genes and LjZCD was verified to positively regulate CNglcs synthesis gene CYP79D3. The LjZCB and an SNP in LjZCA promoter were confirmed to be involved in plant growth. Conclusion This study provided a large number of genomic resources and described genetic relationship and population structure among different accessions. Moreover, we attempt to provide insights into the molecular studies and breeding of CNglcs and growth traits in L. corniculatus.

Abstract The accurate prediction of monthly runoff in the lower reaches of the Yellow River is crucial for the rational utilization of regional water resources, optimal allocation, and flood prevention. This study proposes a VMD-SSA-BiLSTM coupled model for monthly runoff volume prediction, which combines the advantages of Variational Modal Decomposition (VMD) for signal decomposition and preprocessing, Sparrow Search Algorithm (SSA) for BiLSTM model parameter optimization, and Bi-directional Long and Short-Term Memory Neural Network (BiLSTM) for exploiting the bi-directional linkage and advanced characteristics of the runoff process. The proposed model was applied to predict monthly runoff at GaoCun hydrological station in the lower Yellow River. The results demonstrate that the VMD-SSA-BiLSTM model outperforms both the BiLSTM model and the VMD-BiLSTM model in terms of prediction accuracy during both the training and validation periods. The Root-mean-square deviation of VMD-SSA-BiLSTM model is 30.6601, which is 242.5124 and 39.9835 lower compared to the BiLSTM model and the VMD-BiLSTM model respectively; the mean absolute percentage error is 5.6832%, which is 35.5937% and 6.3856% lower compared to the other two models, respectively; the mean absolute error was 19.8992, which decreased by 136.7288 and 25.7274 respectively; the square of the correlation coefficient (R 2 ) is 0.93775, which increases by 0.53059 and 0.14739 respectively; the Nash–Sutcliffe efficiency coefficient was 0.9886, which increased by 0.4994 and 0.1122 respectively. In conclusion, the proposed VMD-SSA-BiLSTM model, utilizing the sparrow search algorithm and bidirectional long and short-term memory neural network, enhances the smoothness of the monthly runoff series and improves the accuracy of point predictions. This model holds promise for the effective prediction of monthly runoff in the lower Yellow River.

Abstract The relationship between muscle wasting and mortality risk in the general population remains unclear. Our study was conducted to examine and quantify the associations between muscle wasting and all‐cause and cause‐specific mortality risks. PubMed, Web of Science and Cochrane Library were searched until 22 March 2023 for main data sources and references of retrieved relevant articles. Prospective studies investigating the associations of muscle wasting with risks of all‐cause and cause‐specific mortality in the general population were eligible. A random‐effect model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the lowest versus normal categories of muscle mass. Subgroup analyses and meta‐regression were performed to investigate the potential sources of heterogeneities among studies. Dose–response analyses were conducted to evaluate the relationship between muscle mass and mortality risk. Forty‐nine prospective studies were included in the meta‐analysis. A total of 61 055 deaths were ascertained among 878 349 participants during the 2.5‐ to 32‐year follow‐up. Muscle wasting was associated with higher mortality risks of all causes (RR = 1.36, 95% CI, 1.28 to 1.44, I2 = 94.9%, 49 studies), cardiovascular disease (CVD) (RR = 1.29, 95% CI, 1.05 to 1.58, I2 = 88.1%, 8 studies), cancer (RR = 1.14, 95% CI, 1.02 to 1.27, I2 = 38.7%, 3 studies) and respiratory disease (RR = 1.36, 95% CI, 1.11 to 1.67, I2 = 62.8%, 3 studies). Subgroup analyses revealed that muscle wasting, regardless of muscle strength, was significantly associated with a higher all‐cause mortality risk. Meta‐regression showed that risks of muscle wasting‐related all‐cause mortality (P = 0.06) and CVD mortality (P = 0.09) were lower in studies with longer follow‐ups. An approximately inverse linear dose–response relationship was observed between mid‐arm muscle circumference and all‐cause mortality risk (P

Abstract Inhibin subunit beta A (INHBA) is a member of the transforming growth factor-beta (TGF-β) superfamily that plays a fundamental role in various cancers. However, a systematic analysis of the exact role of INHBA in patients with gastric cancer (GC) has not yet been conducted. We evaluated the expression levels of INHBA and the correlation between INHBA and GC prognosis in GC. The relationship between INHBA expression, immune infiltration levels, and type markers of immune cells in GC was also explored. In addition, we studied INHBA mutations, promoter methylation, and functional enrichment analysis. Besides, high expression levels of INHBA in GC were significantly related to unfavorable prognosis. INHBA was negatively correlated with B cell infiltration, but positively correlated with macrophage and most anticancer immunity steps. INHBA expression was positively correlated with the type markers of CD8+ T cells, neutrophils, macrophages, and dendritic cells. INHBA has a weak significant methylation level change between tumor and normal tissues and mainly enriched in cancer-related signaling pathways. The present study implies that INHBA may serve as a potential biomarker for predicting the prognosis of patients with GC. INHBA is a promising predictor of immunotherapy response, with higher levels of INHBA indicating greater sensitivity.

To investigate the effects of different packaging methods on microbial composition of chilled chicken during storage, the microbial diversity was analyzed by Illumina MiSeq high-throughput sequencing. The results showed that the modified atmosphere packaging (MAP), the vacuum packaging (VP) and the nitrogen-filled packaging (N2) could significantly reduce the number of microorganisms and volatile base nitrogen during refrigeration at 4 °C compared with the pallet packed (PP) group. High-throughput sequencing showed that the bacterial species richness of chilled chicken was high in the early stage of storage. The dominant bacteria of chilled chickens in PP group at the later stage of storage were Pseudomonas, Brochothrix, Acinetobacter and Shewanella. It indicated that they could tolerate lower temperatures. Compared with the PP group, the abundance of Pseudomonas and Acinetobacter in MAP group decreased by 14.8% and 9.2%, respectively, while nitrogen-filled packaging reduced the abundance of Acinetobacter and Shewanella. by 9.6% and 7.4%, respectively. The abundance of Acinetobacter and Brochothrix decreased significantly by 8% and 5.6% after vacuum packaging. Different packaging methods could have a greater impact on the flora in chilled chicken meat. All three types of packaging could inhibit the growth of Acinetobacter and MAP had a better inhibitory effect on Pseudomonas, while nitrogen-filled packaging and vacuum packaging had a better inhibitory effect on Shewanella and Brochothrix. This study also provides a theoretical basis for the future packaging methods used in chilled chicken meat.

Abstract Background The development of cotton fiber is regulated by the orchestrated binding of regulatory proteins to cis-regulatory elements associated with developmental genes. The cis–trans regulatory dynamics occurred throughout the course of cotton fiber development are elusive. Here we generated genome-wide high-resolution DNase I hypersensitive sites (DHSs) maps to understand the regulatory mechanisms of cotton ovule and fiber development. Results We generated DNase I hypersensitive site (DHS) profiles from cotton ovules at 0 and 3 days post anthesis (DPA) and fibers at 8, 12, 15, and 18 DPA. We obtained a total of 1185 million reads and identified a total of 199,351 DHSs through ~ 30% unique mapping reads. It should be noted that more than half of DNase-seq reads mapped multiple genome locations and were not analyzed in order to achieve a high specificity of peak profile and to avoid bias from repetitive genomic regions. Distinct chromatin accessibilities were observed in the ovules (0 and 3 DPA) compared to the fiber elongation stages (8, 12, 15, and 18 DPA). Besides, the chromatin accessibility during ovules was particularly elevated in genomic regions enriched with transposable elements (TEs) and genes in TE-enriched regions were involved in ovule cell division. We analyzed cis-regulatory modules and revealed the influence of hormones on fiber development from the regulatory divergence of transcription factor (TF) motifs. Finally, we constructed a reliable regulatory network of TFs related to ovule and fiber development based on chromatin accessibility and gene co-expression network. From this network, we discovered a novel TF, WRKY46, which may shape fiber development by regulating the lignin content. Conclusions Our results not only reveal the contribution of TEs in fiber development, but also predict and validate the TFs related to fiber development, which will benefit the research of cotton fiber molecular breeding.

Abstract Background It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. Methods This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a

Abstract Background work alienation is receiving increasing attention as a psychological risk at work, and little is known about the mechanisms of role ambiguity and work alienation in nurses in the context of the COVID-19 pandemic. This article aims to examine how role ambiguity affects work alienation among Chinese nurses during the two years after COVID-19 pandemic and verify emotional exhaustion as mediators. Methods A cross-sectional study design was used to recruit 281 Chinese nurses. Nurses completed online questionnaires containing demographic characteristics, role ambiguity, emotional exhaustion, and work alienation, and SPSS 26.0 and AMOS 24.0 were used for data analysis and structural equation modelling. Results work alienation scores were (34.64 ± 10.09), work alienation was correlated with role ambiguity and emotional exhaustion (r1 = 0.521, r2 = 0.755; p