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Summary: Background: Finding the oncogene, which was able to inhibit tumor cells intrinsically and improve the immune answers, will be the future direction for renal cancer combined treatment. Following patient sample analysis and signaling pathway examination, we propose p21-activated kinase 4 (PAK4) as a potential target drug for kidney cancer. PAK4 exhibits high expression levels in patient samples and plays a regulatory role in the immune microenvironment. Methods: Utilizing AI software for peptide drug design, we have engineered a specialized peptide proteolysis targeting chimera (PROTAC) drug with selectivity for PAK4. To address challenges related to drug delivery, we developed a nano-selenium delivery system for efficient transport of the peptide PROTAC drug, termed PpD (PAK4 peptide degrader). Findings: We successfully designed a peptide PROTAC drug targeting PAK4. PpD effectively degraded PAK4 with high selectivity, avoiding interference with other homologous proteins. PpD significantly attenuated renal carcinoma proliferation in vitro and in vivo. Notably, PpD demonstrated a significant inhibitory effect on tumor proliferation in a fully immunocompetent mouse model, concomitantly enhancing the immune cell response. Moreover, PpD demonstrated promising tumor growth inhibitory effects in mini-PDX and PDO models, further underscoring its potential for clinical application. Interpretation: This PAK4-targeting peptide PROTAC drug not only curtails renal cancer cell proliferation but also improves the immune microenvironment and enhances immune response. Our study paves the way for innovative targeted therapies in the management of renal cancer. Funding: This work is supported by Research grants from non-profit organizations, as stated in the Acknowledgments.

There is a growing amount of research that highlights the significant connection between the development of colitis and both metabolic imbalance and the inflammatory response. Tagatose, an inherent sweetening agent and alternative to sugar, plays a crucial role in the biosynthesis of several chemicals and metabolic pathways in living organisms. However, the specific biochemical mechanism via which tagatose hinders colitis is still not understood. According to recent study, tagatose plays a crucial role in safeguarding the integrity of tight junctions inside the intestinal mucosal barrier. Furthermore, it is crucial to acknowledge the presence of a correlation between the severity of inflammatory bowel disease (IBD) and the occurrence of colorectal cancer (CRC), chemically-induced colitis in rodents, and reduced blood levels of tagatose. The treatment of tagatose resulted in a decrease in intestinal mucosal injury in mice with colitis, regardless of whether it was caused by dextran sodium sulfate (DSS) or spontaneous colitis in IL-10-/- mice and C3H/HeJBir mice. The introduction of tagatose in a colitis model triggers a cascade of events, wherein it hinders the expulsion of cathepsin B and enhances lysosomal cohesiveness. The aforementioned method successfully inhibits the activity of myosin light chain kinase (MLCK) in the context of intestinal epithelial damage, hence impeding the deterioration of tight junction integrity and the initiation of mitochondrial dysfunction. In summary, the outcomes of the study have provided empirical evidence that substantiates the beneficial effects of tagatose in mitigating the progression of colitis. The ability to prevent the disruption of the intestinal barrier is responsible for this achievement. Hence, tagatose has promise as a therapeutic adjunct for the management of colitis.

This conceptual paper examines the use of odours and scents in books to enhance storytelling and engage readers. While books often possess a distinctive smell linked to their material production, the intentional use of scents in books is rare. Our study focuses on scratch-and-sniff books, examining their narrative purposes and contributions to young children's literature. We conduct a narrative historical review, supplemented by a systematic search of databases, online catalogues and lists, to identify a collection of these scented books. Through this review, we explore the extent to which these books represent a unique category of children's picture books, investigating how their features align with theoretical understandings of quality characteristics in children's literature and the role of olfactory cues in storytelling. We address why most scented books target younger readers and discuss possible reasons for the absence of scented books for an adult readership. This intriguing asymmetry contrasts the use of scent in other media (such as film, theatre or virtual reality), often directed toward adults. In addition, this review sheds light on the innovative use of scents in books and their impact on reader immersion and narrative experience. Finally, we consider possible future uses of scent in the context of digital books (ebooks).

Alfalfa (Medicago sativa L.) is one of the most important forage crops in the world. Drought is recognized as a major challenge limiting alfalfa production and threatening food security. Although some literature reviews have been conducted in this area, bibliometric reviews based on large amounts of published data are still lacking. In this paper, a bibliometric analysis of alfalfa drought stress from 1998–2023 was conducted using the Web of Science Core Collection database in order to assess global trends in alfalfa drought stress research and to provide new directions for future research. The results showed that the annual publication output maintained an increase in most years, with China and the United States contributing significantly to the field. Most of the journals published are specialized journals in botany, environmental science, soil science and crop science, as well as related agribusiness journals. “plant growth” and “yield” were the most frequently used keywords, reflecting the important purpose of research in this field. And two main research directions were identified: research on drought response mechanism of alfalfa and exploration of drought-resistant technology. In addition, physiological, biochemical, and molecular responses of drought tolerance and high yield in alfalfa, transgenics, and microbial fertilizer research have been hot research topics in recent years and may continue in the future. The ultimate goal of this paper is to provide a foundational reference for future research on alfalfa’s drought resistance and yield optimization mechanisms, thereby enhancing the crop’s application in agricultural production.

Abstract Background Kawasaki disease (KD) is an autoimmune disease with cardiovascular disease as its main complication, mainly affecting children under 5 years old. KD treatment has made tremendous progress in recent years, but intravenous immunoglobulin (IVIG) resistance remains a major dilemma. Bibliometric analysis had not been used previously to summarize and analyze publications related to IVIG resistance in KD. This study aimed to provide an overview of the knowledge framework and research hotspots in this field through bibliometrics, and provide references for future basic and clinical research. Methods Through bibliometric analysis of relevant literature published on the Web of Science Core Collection (WoSCC) database between 1997 and 2023, we investigated the cooccurrence and collaboration relationships among countries, institutions, journals, and authors and summarized key research topics and hotspots. Results Following screening, a total of 364 publications were downloaded, comprising 328 articles and 36 reviews. The number of articles on IVIG resistance increased year on year and the top three most productive countries were China, Japan, and the United States. Frontiers in Pediatrics had the most published articles, and the Journal of Pediatrics had the most citations. IVIG resistance had been studied by 1889 authors, of whom Kuo Ho Chang had published the most papers. Conclusion Research in the field was focused on risk factors, therapy (atorvastatin, tumor necrosis factor‐alpha inhibitors), pathogenesis (gene expression), and similar diseases (multisystem inflammatory syndrome in children, MIS‐C). “Treatment,” “risk factor,” and “prediction” were important keywords, providing a valuable reference for scholars studying this field. We suggest that, in the future, more active international collaborations are carried out to study the pathogenesis of IVIG insensitivity, using high‐throughput sequencing technology. We also recommend that machine learning techniques are applied to explore the predictive variables of IVIG resistance.

ObjectiveThe aim of this study is to examine the role of activities of daily living performance (ADLs) and psychological distress in mediating the process by which health behaviors affect QOL.MethodsA non-probabilistic study was conducted among 1,065 older adult people older than 60 years. Participants were assessed using the Barthel Index, Functional Activities Questionnaire (FAQ), Kessler Psychological Distress Scale (K10), Australian Active Survey, and EQ-VAS score. The SPSS22.0 software was used to analyze the differences in QOL scores among older adults with different demographic characteristics. Pearson correlation analysis was used to analyze the correlation between health behaviors, psychological distress, ADLs, and QOL. Amos23.0 software was used to construct structural equation model (SEM) to analyze the path of health behavior affecting QOL and the mediating role of BADLs, IADLs and psychological distress.Results(1) The direct effect of health behaviors on QOL was not significant in the model; (2) ADLs had multiple mediating effects on the relationship between health behaviors and QOL, and the incidence of ADL limitation was negatively correlated with the reported QOL in the older adult; (3) Psychological distress had a significant mediating effect on the relationship between health behaviors and QOL.ConclusionThe results of this study elucidated the mechanisms of the correlation between health behaviors and QOL, and added to the existing literature. In addition, these mediating factors and indirect pathways have been identified as targets for intervention to improve the QOL of older adult individuals, which is important for achieving healthy aging.

Background Persistent infection with high-risk human papillomavirus (HPV) is closely related to cervical cancer. The epidemiologic characteristics of cervical HPV have regional differences. Therefore, it is necessary to develop the most favorable policies according to the actual situation of each region to prevent and reduce the prevalence of cervical cancer. This retrospective cross-sectional study investigated the prevalence, gene subtypes, and temporal trends of HPV in women undergoing physical examination in Wenzhou, to provide a decision-making basis for further prevention and control of HPV. Methods A total of 31 131 cervical exfoliated cell specimens obtained from physical examinations in Wenzhou, a coastal city of China, from 2015 to 2020 were collected. The age distribution was analyzed using the chi-squared test, and the time change trend was analyzed using the Mann–Kendall trend test. On this basis, the distribution characteristics of the HPV subtypes were analyzed. Results The total prevalence rate was 9.55%, and the prevalence rate in different age groups ranged from 7.77% to 14.16%. The prevalence rate in different years was 8.84%-11.83%. The prevalence rate was bimodal; it was highest in the group 25 years old, followed by the group >61 years old. The top five high-risk gene subtypes were HPV52, HPV58, HPV53, HPV16, and HPV39, whereas the low-risk subtypes were HPV61, HPV81, HPV44, HPV43, and HPV55. Of all the positive samples, 76.03% were infected with a high-risk subtype. Conclusion Most female HPV patients in Wenzhou are infected with high-risk gene subtypes. Therefore, physical examination and screening for HPV should be further strengthened, and the corresponding vaccination policy should focus on high-risk gene subtypes.

Acanthopanax senticosus (AS) is a geo-authentic crude medicinal plant that grows in China, Korea, Russia, and Japan. AS contains bioactive compounds such as eleutherosides, polysaccharides, and flavonoids. It is also a key traditional herb in the Red List of Chinese Species. AS is mainly distributed in Northeast China, specifically in Heilongjiang, Jilin, and Liaoning provinces. Its active compounds contribute to significant biological activities, including neuroprotective, antioxidant, anti-fatigue, and antitumor effects. However, the extraction methods of active compounds are complex, the extraction efficiency is poor, and the structure–activity relationship is unclear. This study focused on the nutrients in AS, including protein, carbohydrates, and lipids. Particularly, the active ingredients (eleutherosides, polysaccharides, and flavonoids) in AS and their extraction and purification methods were analyzed and summarized. The biological activities of extracts have been reviewed, and the mechanisms of anti-oxidation, antitumor, anti-inflammation, and other activities are introduced in detail. The applications of AS in various domains, such as health foods, medicines, and animal dietary supplements, are then reported. Compared with other extraction methods, ultrasonic or microwave extraction improves efficiency, yet they can damage structures. Challenges arise in the recovery of solvents and in achieving extraction efficiency when using green solvents, such as deep eutectic solvents. Improvements can be made by combining extraction methods and controlling conditions (power, temperature, and time). Bioactive molecules and related activities are exposited clearly. The applications of AS have not been widely popularized, and the corresponding functions require further development.

IntroductionHIV molecular network based on genetic distance (GD) has been extensively utilized. However, the GD threshold for the non-B subtype differs from that of subtype B. This study aimed to optimize the GD threshold for inferring the CRF01_AE molecular network.MethodsNext-generation sequencing data of partial CRF01_AE pol sequences were obtained for 59 samples from 12 transmission pairs enrolled from a high-risk cohort during 2009 and 2014. The paired GD was calculated using the Tamura-Nei 93 model to infer a GD threshold range for HIV molecular networks.Results2,019 CRF01_AE pol sequences and information on recent HIV infection (RHI) from newly diagnosed individuals in Shenyang from 2016 to 2019 were collected to construct molecular networks to assess the ability of the inferred GD thresholds to predict recent transmission events. When HIV transmission occurs within a span of 1-4 years, the mean paired GD between the sequences of the donor and recipient within the same transmission pair were as follow: 0.008, 0.011, 0.013, and 0.023 substitutions/site. Using these four GD thresholds, it was found that 98.9%, 96.0%, 88.2%, and 40.4% of all randomly paired GD values from 12 transmission pairs were correctly identified as originating from the same transmission pairs. In the real world, as the GD threshold increased from 0.001 to 0.02 substitutions/site, the proportion of RHI within the molecular network gradually increased from 16.6% to 92.3%. Meanwhile, the proportion of links with RHI gradually decreased from 87.0% to 48.2%. The two curves intersected at a GD of 0.008 substitutions/site.DiscussionA suitable range of GD thresholds, 0.008-0.013 substitutions/site, was identified to infer the CRF01_AE molecular transmission network and identify HIV transmission events that occurred within the past three years. This finding provides valuable data for selecting an appropriate GD thresholds in constructing molecular networks for non-B subtypes.

Abstract Background Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non‐coding RNAs (lncRNAs) play essential roles in cervical cancer occurrence and progression, but their specific functions and mechanisms remain to be further explored. Methods The RT‐qPCR assay was used to detect the expression of NEAT1 in cervical cancer tissues and cell lines. CCK‐8, colony formation, flow cytometry, western blotting, and Transwell assays were used to evaluate the impact of NEAT1 on the malignant behavior of cervical cancer cells. Glucose consumption, lactate production, ATP levels, ROS levels, MMP levels, and the mRNA expressions of glycolysis‐related genes and tricarboxylic acid cycle‐related genes were detected to analyze the effect of NEAT1 on metabolism reprograming in cervical cancer cells. The expressions of PDK1, β‐catenin and downstream molecules of the WNT/β‐catenin signaling pathway in cervical cancer cells and tissues were detected by western blotting, RT‐qPCR, immunofluorescence and immunohistochemistry assays. Results This study investigated the role and possible molecular mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in cervical cancer. Our results showed that NEAT1 was highly expressed in cervical cancer tissues and cell lines. Downregulation of NEAT1 inhibited the proliferation, migration, invasion and glycolysis of cervical cancer cells, while overexpression of NEAT1 led to the opposite effects. Mechanistically, NEAT1 upregulated pyruvate dehydrogenase kinase (PDK1) through the WNT/β‐catenin signaling pathway, which enhanced glycolysis and then facilitated cervical cancer metastasis. Furthermore, NEAT1 maintained the protein stability of β‐catenin but did not affect its mRNA level. We also excluded the direct binding of NEAT1 to the β‐catenin protein via RNA pull‐down assay. The suppressive impact of NEAT1 knockdown on cell proliferation, invasion, and migration was rescued by β‐catenin overexpression. The WNT inhibitor iCRT3 attenuated the carcinogenic effect induced by NEAT1 overexpression. Conclusion In summary, these findings indicated that NEAT1 may contribute to the progression of cervical cancer by activating the WNT/β‐catenin/PDK1 signaling axis.

Objective To examine the current prevalence and cost of paediatric off-label drug prescriptions in Gansu, China, and the potential influencing factors.Design The prevalence of off-label prescriptions in paediatrics was evaluated according to the National Medical Products Administration drug instructions in the China Pharmaceutical Reference (China Pharmaceutical Reference, MCDEX) database. The evidence of the prescription was determined by existing clinical practice guidelines and the Thomson Grade in the Micromedex 2021 compendium. We used logistic regression to investigate the characteristics that influence paediatric off-label drug use after single-factor regression analysis.Setting A multicentre cross-sectional study of outpatient paediatric prescriptions in 196 secondary and tertiary hospitals in Gansu Province, China, in March and September 2020.Results We retrieved 104 029 paediatric prescriptions, of which 39 480 (38.0%) contained off-label use. The most common diseases treated by off-label drugs were respiratory system diseases (n=15 831, 40.1%). A quarter of off-label prescriptions had adequate evidence basis (n=10 130, 25.6%). Unapproved indications were the most common type of off-label drug use (n=25 891, 65.6%). A total of 1177 different drugs were prescribed off-label, with multienzyme tablets being the most common drug (n=1790, 3.5%). The total cost of the prescribed off-label drugs was ¥106 116/day. Off-label prescriptions were less frequent in tertiary than in secondary hospitals. Topical preparations were more commonly prescribed off-label than other types of drugs. Senior-level clinicians prescribed drugs off-label more often than intermediate and junior clinicians.Conclusion Off-label drug use is widespread in paediatric practice in China. Three-quarters of the prescriptions may potentially include inappropriate medication use, resulting in a daily economic burden of about ¥81 000 in 2020 in Gansu Province with 25 million inhabitants. The management of off-label drug use in paediatrics in China needs improvement.

The E2F family of transcription factors plays a crucial role in the regulation of cell cycle progression and cell proliferation. Accumulative evidence indicates that aberrant expression or activation of E2F2 is a common phenomenon in malignances. E2F2 has emerged as a key player in the development and progression of various types of tumors. A wealth of research has substantiated that E2F2 could contribute to the enhancement of tumor cell proliferation, angiogenesis, and invasiveness. Moreover, E2F2 exerts its influence on a myriad of cellular processes by engaging with a spectrum of auxiliary factors and downstream targets, including apoptosis and DNA repair. The dysregulation of E2F2 in the context of carcinogenesis may be attributable to a multitude of mechanisms, which encompass modifications in upstream regulatory elements or epigenetic alterations. This review explores the function of E2F2 in cancer progression and both established and emerging therapeutic strategies aiming at targeting this oncogenic pathway, while also providing a strong basis for further research on the biological function and clinical applications of E2F2.

BackgroundCommunity engagement plays a vital role in global immunization strategies, offering the potential to overcome vaccination hesitancy and enhance vaccination confidence. Although there is significant backing for community engagement in health promotion, the evidence supporting its effectiveness in vaccination promotion is fragmented and of uncertain quality. ObjectiveThis review aims to systematically examine the effectiveness of different contents and extent of community engagement for promoting vaccination rates. MethodsThis study was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive and exhaustive literature search was performed in 4 English databases (PubMed, Embase, Web of Science, and Cochrane Library) and 2 Chinese databases (CNKI and Wan Fang) to identify all possible articles. Original research articles applying an experimental study design that investigated the effectiveness of community engagement in vaccination promotion were eligible for inclusion. Two reviewers independently performed the literature search, study selection, quality assessment, and data extraction. Discrepancies were resolved through discussion, with the arbitration of a third reviewer where necessary. ResultsA total of 20 articles out of 11,404 records from 2006 to 2021 were retrieved. The studies used various designs: 12 applied single-group pre-post study designs, 5 were cluster randomized controlled trials (RCTs), and 3 were non-RCTs. These studies targeted multiple vaccines, with 8 focusing on children’s immunization, 8 on human papillomavirus vaccine, 3 on hepatitis B virus vaccine, and 1 on COVID-19 vaccine. The meta-analysis revealed significant increases in vaccination rates both in pre-post comparison (rate difference [RD] 0.34, 95% CI 0.21-0.47, I2=99.9%, P

BackgroundInborn errors of metabolism (IEMs) are rare diseases caused by inherited defects in various biochemical pathways that strongly correlate with early neonatal mortality and stunting. Currently, no studies have reported on the incidence of IEMs of multi-ethnic groups in Huaihua, China.MethodsA total of 206,977 neonates with self-reported ethnicity who underwent IEM screening at Huaihua from 2015 to 2021 were selected for observation. Among them, 69 suspected IEM-positive neonates were referred for urine gas chromatography-mass spectrometry analysis, biochemical detection, next-generation sequencing, and Sanger sequencing.ResultsSixty-nine newborns were diagnosed with IEMs, with an overall incidence of 1:3,000. The two most common disorders were 2-methylbutyryl glycinuria (1:7,137) and phenylalanine hydroxylase deficiency (1:22,997). Moreover, the incidence of IEMs in the minority ethnic group (Miao, Dong, Tujia and Yao) (1:1,852) was markedly higher than in the Han ethnic group (1:4,741). Some ethnic features variants were identified; NM_001609.4:c.1165A>G in the ACADSB gene for Miao and Dong ethnic groups, NM_014251.2:c.852_855del in the SLC25A13 gene for Miao ethnic groups.ConclusionThis study revealed the IEM incidence within the minority ethnic groups is markedly higher than among the Han nationality and the gene variant spectrum is dramatically different in Huaihua, China. Hence, It serves as a theoretical reference for the screening and diagnosing of neonatal IEMs of multi-ethnic groups in the Huaihua area, and across China.

To mitigate the shrinkage of high-strength alkali-activated slag concrete (AASC), this paper introduces emulsified cooking oil (ECO) and emulsified waste cooking oil (EWCO) into the AASC system. The effects of admixing ECO and EWCO on the compressive strength, drying shrinkage, autogenous shrinkage, carbonation, and sulfuric acid resistance of the AASC are systematically explored. The optimization mechanism is also proposed based on the surface tension and microstructural analysis. The experimental results show that the admixing ECO and EWCO slightly reduce the compressive strength of the AASC by 7.8%. Interestingly, the admixing ECO and EWCO significantly reduce the drying shrinkage and autogenous shrinkage, simultaneously improving the resistance to carbonation and sulfuric acid of the AASC. Specifically, the introduction of 2 wt.% ECO and EWCO can reduce the autogenous shrinkage of the AASC by 66.7% and 41.0%, respectively. Microstructural observations reveal that the addition of ECO and EWCO can reduce the internal surface tension of the AASC, improve the transport and diffusion of the pore solution, and increase the absorbable free water of the slag, which in turn reduces the shrinkage of the composites. It also increases the ionic concentration in the pore solution, resulting in a more complete reaction of the AASC, which can optimize the pore structure and thus improve the durability of the AASC. This study proposes a promising way to develop sustainable alkali-activated slag concrete achieved by recycling waste materials.

A massless particle beyond the Standard Model is searched for in the two-body decay Σ+→p+invisible using (1.0087±0.0044)×1010 J/ψ events collected at a center-of-mass energy of s=3.097GeV with the BESIII detector at the BEPCII collider. No significant signal is observed, and the upper limit on the branching fraction B(Σ+→p+invisible) is determined to be 3.2×10−5 at the 90% confidence level. This is the first search for a flavor-changing neutral current process with missing energy in hyperon decays which plays an important role in constraining new physics models.

The data-driven approach of supervised learning methods has limited applicability in solving dipole inversion in Quantitative Susceptibility Mapping (QSM) with varying scan parameters across different objects. To address this generalization issue in supervised QSM methods, we propose a novel training-free model-based unsupervised method called MoDIP (Model-based Deep Image Prior). MoDIP comprises a small, untrained network and a Data Fidelity Optimization (DFO) module. The network converges to an interim state, acting as an implicit prior for image regularization, while the optimization process enforces the physical model of QSM dipole inversion. Experimental results demonstrate MoDIP's excellent generalizability in solving QSM dipole inversion across different scan parameters. It exhibits robustness against pathological brain QSM, achieving over 32 % accuracy improvement than supervised deep learning methods. It is also 33 % more computationally efficient and runs 4 times faster than conventional DIP-based approaches, enabling 3D high-resolution image reconstruction in under 4.5 min.

Abstract Background Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch‐to‐batch variations, lack of the native microenvironment and clinical applicability. Main body The concept of organoids has derived patient‐derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, ‘tumour assembloids’ inspired by cell‐coculture technology have attracted attention to complement the current PDTO technology. High‐quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour‐infiltrating lymphocyte, T cell receptor‐engineered T cell and chimeric antigen receptor‐T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. Conclusion Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre‐clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. Key Points The current PDTO models have not yet constructed key cellular and non‐cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

This study aims to further enhance the oil recovery of reservoirs in the Zhong-2 Block of the Gudao Oilfield by identifying the most effective microbial-flooding activator systems and applying them in the field. We began by analyzing the structure of the reservoirs' endogenous microbial communities to understand the potential impact of microbial flooding. This was followed by determining commonly used activator systems based on their abilities to stimulate oil-displacement functional bacteria. Through laboratory experiments on oil displacement efficiency and sweep characteristics, we determined the optimal activator injection method (injection ratio) and the requisite bacterial concentration for maximal microbial-flooding efficacy. Finally, we selected the optimal activator systems and applied them to field tests. Our findings suggest the target block is highly receptive to microbial-flooding. In terms of performance, the activator systems ranked as No. 3 > No. 4 > No. 1 > No. 2. Interestingly, a deep activator system, when compared to the top-performing No. 3 system, exhibited a higher bacterial concentration peak and longer peaking duration. Optimal oil displacement effects were observed at a 1:4 vol ratio between the No. 3 activator and deep activator systems, with bacterial concentrations of up to 106 cells/mL or above. Field tests with the selected activator systems, following a specific injection protocol, demonstrated a notable increase in oil production and a reduction in water cut.

In mammals, gonadal somatic cell lineage differentiation determines the development of the bipotential gonad into either the ovary or testis. Sertoli cells, the only somatic cells in the spermatogenic tubules, support spermatogenesis during gonadal development. During embryonic Sertoli cell lineage differentiation, relevant genes, including WT1, GATA4, SRY, SOX9, AMH, PTGDS, SF1, and DMRT1, are expressed at specific times and in specific locations to ensure the correct differentiation of the embryo toward the male phenotype. The dysregulated development of Sertoli cells leads to gonadal malformations and male fertility disorders. Nevertheless, the molecular pathways underlying the embryonic origin of Sertoli cells remain elusive. By reviewing recent advances in research on embryonic Sertoli cell genesis and its key regulators, this review provides novel insights into sex determination in male mammals as well as the molecular mechanisms underlying the genealogical differentiation of Sertoli cells in the male reproductive ridge.

Objective We explored whether changes in clinical parameters and inflammatory markers can facilitate early identification of positive blood culture in adult patients with COVID-19 and clinically suspected bloodstream infection (BSI). Methods This single-center retrospective study enrolled 20 adult patients with COVID-19 admitted to the intensive care unit who underwent blood culture for clinically suspected BSI (February 2020–November 2021). We divided patients into positive (Pos) and negative blood culture groups. Clinical parameters and inflammatory markers were obtained from medical records between blood culture collection and the first positive or negative result and compared between groups on different days. Results Patients in the positive culture group had significantly older age and higher D-dimer, immunoglobulin 6 (IL-6), and Sequential Organ Failure Assessment score as well as lower albumin (ALB). The area under the receiver operating characteristic curve (AUC) was 0.865 for IL-6, D-dimer and ALB on the first day after blood culture collection; the AUC was 0.979 for IL-6, IL-10, D-dimer, and C-reactive protein on the second day after blood culture collection. Conclusion Changes in clinical parameters and inflammatory markers after blood culture collection may facilitate early identification of positive culture in adult patients with COVID-19 and clinically suspected BSI.

Abstract Senile plaque, composed of amyloid β protein (Aβ) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aβ aggregates exert age‐dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age‐gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of β‐amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age‐dependent Aβ deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age‐dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age‐dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age‐gradient changes in the autophagy–lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

Abstract Photodynamic therapy (PDT) is a minimally invasive and controllable local cancer treatment for cholangiocarcinoma (CCA). However, the efficacy of PDT is hindered by intratumoral hypoxia and the presence of an antioxidant microenvironment. To address these limitations, combining PDT with gas therapy may be a promising strategy to enhance tumor oxygenation. Moreover, the augmentation of oxidative damage induced by PDT and gas therapy can be achieved by inhibiting NRF2, a core regulatory molecule involved in the antioxidant response. In this study, an integrated nanotherapeutic platform called CMArg@Lip, incorporating PDT and gas therapies using ROS‐responsive liposomes encapsulating the photosensitizer Ce6, the NO gas‐generating agent L‐arginine, and the NRF2 inhibitor ML385, is successfully developed. The utilization of CMArg@Lip effectively deals with challenges posed by tumor hypoxia and antioxidant microenvironment, resulting in elevated levels of oxidative damage and subsequent induction of ferroptosis in CCA. Additionally, these findings suggest that CMArg@Lip exhibits notable immunomodulatory effects, including the promotion of immunogenic cell death and facilitation of dendritic cell maturation. Furthermore, it contributes to the anti‐tumor function of cytotoxic T lymphocytes through the downregulation of PD‐L1 expression in tumor cells and the activation of the STING signaling pathway in myeloid‐derived suppressor cells, thereby reprogramming the immunosuppressive microenvironment via various mechanisms.

Random-pattern skin flaps play a vital role in repairing and reconstructing soft tissue defects. Clinical utilization of skin flaps is limited due to distal necrosis. Calycosin (CAL) is an effective ingredient present in Astragalus, and is reported to possess diverse pharmacological properties. Our study aims to assess the potential benefits of CAL on random flap survival and reveal the underlying mechanisms. Our study revealed that CAL promoted the survival area of the skin flap and improved flap blood flow. CAL treatment exerted anti-apoptosis and anti-ferroptosis effects in the flap model. In our mechanistic investigation, we demonstrated that CAL could activate the AMPK-mTOR signaling pathway and increase transcription factor EB (TFEB) nucleus translocation, thereby suppressing ferroptosis and apoptosis as a result of decreased reactive oxygen species (ROS) which was triggered by increasing superoxide dismutase 1(SOD1). In summary, our findings revealed CAL may protect against flap necrosis by inhibiting ferroptosis and apoptosis via AMPK-mTOR signaling pathway modulation.

The etiology of intervertebral disc degeneration (IDD) and osteoarthritis (OA) is complex and multifactorial. Both predisposing genes and environmental factors are involved in the pathogenesis of IDD and OA. Moreover, epigenetic modifications affect the development of IDD and OA. Dysregulated phenotypes of nucleus pulposus (NP) cells and OA chondrocytes, including apoptosis, extracellular matrix disruption, inflammation, and angiogenesis, are involved at all developmental stages of IDD and OA. RNA binding proteins (RBPs) have recently been recognized as essential post‐transcriptional regulators of gene expression. RBPs are implicated in many cellular processes, such as proliferation, differentiation, and apoptosis. Recently, several RBPs have been reported to be associated with the pathogenesis of IDD and OA. This review briefly summarizes the current knowledge on the RNA‐regulatory networks controlled by RBPs and their potential roles in the pathogenesis of IDD and OA. These initial findings support the idea that specific modulation of RBPs represents a promising approach for managing IDD and OA.

Abstract Background Pemphigus and pemphigoid are rare autoimmune skin disorders caused by autoantibodies against structural proteins and characterized by blistering of the skin and/or mucous membranes. Associations have been noted between skin diseases and Alzheimer’s dementia (AD). Dementia is a neurological disorder of progressive cognitive impairment with increasing incidence among older adults. This study aimed to assess the potential associations between pemphigus, pemphigoid and AD in a large, nationally representative US cohort. Methods All data of hospitalized patients aged 60 years or older were extracted from the US Nationwide Inpatient Sample (NIS) database 2016–2018. Patients with a history of head trauma, diagnosis of vascular dementia, history of cerebrovascular disease, or malformation of cerebral vessels were excluded. The study population was divided into those with and without pemphigus (cohort 1) and with and without pemphigoid (cohort 2). Results Pemphigus was independently associated with a 69% increased risk of AD. Adults ≥80 years old with pemphigus were 72% more likely to develop AD than adults without pemphigus. Women with pemphigus were 78% more likely to develop AD than women without pemphigus. On the other hand, pemphigoid was independently associated with a 39% increased risk for AD and subjects ≥80 years with pemphigoid were 40% more likely to have AD than those without pemphigoid. Females with pemphigoid were 63% more likely to have AD than those without pemphigoid. Moreover, Hispanic older adults with pemphigus were 3-times more likely to have AD than those without pemphigoid. Conclusions Pemphigus and pemphigoid were both independently associated with AD in older adults, especially among females and octogenarians. Further studies addressing the etiology and mechanisms underlying these associations are highly warranted.

Abstract The D s + → K + K − μ + ν μ $$ {D}_s^{+}\to {K}^{+}{K}^{-}{\mu}^{+}{\nu}_{\mu } $$ decay is studied based on 7.33 fb −1 of e + e − collision data collected with the BESIII detector at center-of-mass energies in the range from 4.128 to 4.226 GeV. The absolute branching fraction is measured as B D s + → ϕ μ + ν μ = 2.25 ± 0.09 ± 0.07 × 10 − 2 $$ \mathcal{B}\left({D}_s^{+}\to \phi {\mu}^{+}{\nu}_{\mu}\right)=\left(2.25\pm 0.09\pm 0.07\right)\times {10}^{-2} $$ , the most precise measurement to date. Combining with the world average of B D s + → ϕ e + ν e $$ \mathcal{B}\left({D}_s^{+}\to \phi {e}^{+}{\nu}_e\right) $$ , the ratio of the branching fractions obtained is B D s + → ϕ μ + ν μ B D s + → ϕ e + ν e = 0.94 ± 0.08 $$ \frac{\mathcal{B}\left({D}_s^{+}\to \phi {\mu}^{+}{\nu}_{\mu}\right)}{\mathcal{B}\left({D}_s^{+}\to \phi {e}^{+}{\nu}_e\right)}=0.94\pm 0.08 $$ , in agreement with lepton universality. By performing a partial wave analysis, the hadronic form factor ratios at q 2 = 0 are extracted, finding r V = V 0 A 1 0 = 1.58 ± 0.17 ± 0.02 $$ {r}_V=\frac{V(0)}{A_1(0)}=1.58\pm 0.17\pm 0.02 $$ and r 2 = A 2 0 A 1 0 = 0.71 ± 0.14 ± 0.02 $$ {r}_2=\frac{A_2(0)}{A_1(0)}=0.71\pm 0.14\pm 0.02 $$ , where the first uncertainties are statistical and the second are systematic. No significant S-wave contribution from f 0(980) → K + K − is found. The upper limit B D s + → f 0 980 μ + ν μ ⋅ B f 0 980 → K + K − < 5.45 × 10 − 4 $$ \mathcal{B}\left({D}_s^{+}\to {f}_0(980){\mu}^{+}{\nu}_{\mu}\right)\cdot \mathcal{B}\left({f}_0(980)\to {K}^{+}{K}^{-}\right)

Abstract Using e + e − collision datasets corresponding to a total integrated luminosity of 21.7 fb −1 collected with the BESIII detector at the BEPCII collider at center-of-mass energies ranging from 4.009 GeV to 4.951 GeV, the energy-dependent cross sections of e + e − → p K − Λ ¯ + c . c . $$ {e}^{+}{e}^{-}\to p{K}^{-}\overline{\Lambda}+c.c. $$ are measured for the first time. By fitting these energy-dependent cross sections, we search for the excited ψ states ψ(4160) and ψ(4415), and the vector charmonium-like states ψ(4230), ψ(4360), and ψ(4660). No evidence for these is observed and the upper limits on the branching fractions of these states decaying into p K − Λ ¯ + c . c . $$ p{K}^{-}\overline{\Lambda}+c.c. $$ are set at the 90% confidence level.

Abstract Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin’s model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin’s model was free with open access at http://jinmodel.com:3000/ . Jin’s model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.

Abstract Background Intraneuronal accumulation of hyperphosphorylated tau is a defining hallmark of Alzheimer’s disease (AD). However, mouse models imitating AD-exclusive neuronal tau pathologies are lacking. Methods We generated a new tet-on transgenic mouse model expressing truncated human tau N1-368 (termed hTau368), a tau fragment increased in the brains of AD patients and aged mouse brains. Doxycycline (dox) was administered in drinking water to induce hTau368 expression. Immunostaining and Western blotting were performed to measure the tau level. RNA sequencing was performed to evaluate gene expression, and several behavioral tests were conducted to evaluate mouse cognitive functions, emotion and locomotion. Results Dox treatment for 1–2 months at a young age induced overt and reversible human tau accumulation in the brains of hTau368 transgenic mice, predominantly in the hippocampus. Meanwhile, the transgenic mice exhibited AD-like high level of tau phosphorylation, glial activation, loss of mature neurons, impaired hippocampal neurogenesis, synaptic degeneration and cognitive deficits. Conclusions This study developed a well-characterized and easy-to-use tool for the investigations and drug development for AD and other tauopathies.

Introduction: Background field removal (BFR) is a critical step required for successful quantitative susceptibility mapping (QSM). However, eliminating the background field in brains containing significant susceptibility sources, such as intracranial hemorrhages, is challenging due to the relatively large scale of the field induced by these pathological susceptibility sources. Method: This study proposes a new deep learning-based method, BFRnet, to remove the background field in healthy and hemorrhagic subjects. The network is built with the dual-frequency octave convolutions on the U-net architecture, trained with synthetic field maps containing significant susceptibility sources. The BFRnet method is compared with three conventional BFR methods and one previous deep learning method using simulated and in vivo brains from 4 healthy and 2 hemorrhagic subjects. Robustness against acquisition field-of-view (FOV) orientation and brain masking are also investigated. Results: For both simulation and in vivo experiments, BFRnet led to the best visually appealing results in the local field and QSM results with the minimum contrast loss and the most accurate hemorrhage susceptibility measurements among all five methods. In addition, BFRnet produced the most consistent local field and susceptibility maps between different sizes of brain masks, while conventional methods depend drastically on precise brain extraction and further brain edge erosions. It is also observed that BFRnet performed the best among all BFR methods for acquisition FOVs oblique to the main magnetic field. Conclusion: The proposed BFRnet improved the accuracy of local field reconstruction in the hemorrhagic subjects compared with conventional BFR algorithms. The BFRnet method was effective for acquisitions of tilted orientations and retained whole brains without edge erosion as often required by traditional BFR methods.

Abstract Using e + e − collision data corresponding to a total integrated luminosity of 12.9 fb −1 collected with the BESIII detector at the BEPCII collider, the exclusive Born cross sections and the effective form factors of the reaction e + e − → Ξ − Ξ ¯ + $$ {e}^{+}{e}^{-}\to {\Xi}^{-}{\overline{\Xi}}^{+} $$ are measured via the single baryon-tag method at 23 center-of-mass energies between 3.510 and 4.843 GeV. Evidence for the decay ψ 3770 → Ξ − Ξ ¯ + $$ \psi (3770)\to {\Xi}^{-}{\overline{\Xi}}^{+} $$ is observed with a significance of 4.5σ by analyzing the measured cross sections together with earlier BESIII results. For the other charmonium(-like) states ψ(4040), ψ(4160), Y(4230), Y(4360), ψ(4415), and Y(4660), no significant signal of their decay to Ξ − Ξ ¯ + $$ {\Xi}^{-}{\overline{\Xi}}^{+} $$ is found. For these states, upper limits of the products of the branching fraction and the electronic partial width at the 90% confidence level are provided.

Abstract Based on 4.5 fb −1 e + e − collision data collected with BESIII detector at seven energy points between 4.600 and 4.699 GeV, the branching fractions for Λ c + → pη $$ {\Lambda}_c^{+}\to p\eta $$ and Λ c + → pω $$ {\Lambda}_c^{+}\to p\omega $$ were measured by means of single-tag method. The branching fractions of Λ c + → pη $$ {\Lambda}_c^{+}\to p\eta $$ and Λ c + → pω $$ {\Lambda}_c^{+}\to p\omega $$ are determined to be (1.57 ± 0.11stat ± 0.04syst) × 10 −3 and (1.11 ± 0.20stat ± 0.07syst) × 10 −3, with a statistical significance of greater than 10σ and 5.7σ, respectively. These results are consistent with the previous measurements by BESIII, LHCb and Belle, and the result of Λ c + → pη $$ {\Lambda}_c^{+}\to p\eta $$ is the most precise to date.

The study describes large strain high-speed asynchronous rolling process to process AZ91 magnesium alloy sheets with an overall thickness reduction of 84 % via two-pass rolling at 350 °C. Rolling speed ratios of 1.0, 1.1, 1.2, and 1.3 were used to obtain bimodal grain structure with different organizational states. Microstructural analysis unraveled that the formation of the bimodal structure was a consequence of combined effect of precipitation-strengthening and the Zener pinning effect. The R3 exhibiting an asynchronous ratio of 1.2 exhibited an optimized bimodal grain structure characterized by smaller recrystallized grains and a more homogeneous distribution. This phenomenon underscored the beneficial impact on enhancing strength and alleviating the anisotropic behavior.

Abstract Robotic 3D bin packing (R‐3dBPP), aiming to place deformed cases in various sizes in the container without fences, is a comprehensive application that includes perception, planning, execution, and hardware design. Traditional studies assume that the context of the real space must be accurately perceived and represented. However, disjunctions between the planner and reality are unavoidable in R‐3dBPP, especially with low‐cost sensors. As far as the author knows, there is no practical solution. In this paper, the above assumption is discarded and the typical types of uncertainties prevalent to guide the design of the algorithms are formulated. A new online bin‐packing algorithm is proposed, keeping deformed boxes stacked in close contact with each other, so that the whole pallet is kept stable by friction between the boxes and the container. In order to meet the requirement of close contact under the non‐negligible errors from sensors and planners, a compliant‐based motion planning system is introduced. It replaces the precision‐based feedback with a compliant end‐effector and accompanying motion strategies. Last but not least, a complete online bin‐packing robot system is developed and the system's performance under the influence of the uncertainties mentioned above through simulation and physical experiments is evaluated.

Objective Exploration of recombinant Newcastle disease virus with stable expression of rabies virus glycoprotein(rL-RVG) to inhibit the proliferation of human lung adenocarcinoma cell lines A549 and PC9. Methods Human lung adenocarcinoma cell lines A549 and PC9 were cultured in vitro, and cells in logarithmic proliferation phase were collected and divided into control group, Newcastle disease virus infection group (NDV), recombinant Newcastle disease virus infection group(rL-RVG),ferroptosis group (Erastin) and recombinant Newcastle disease virus combined with ferroptosis inducer group (rL-RVG+Erastin). After 24 h of incubation, cell morphology was observed by microscope and cell proliferation was detected by CCK-8 method, cell migration was detected by scratch test, lactate dehydrogenase (LDH) release was measured by cytotoxicity assay kit, intracellular reactive oxygen species (ROS) content was detected by flow cytometry, and the expression of ferroptosis related proteins (p53, SLC7A11, GPX4) was detected by Western blot. Results Compared with the control group, the cell counting, cell proliferation and distance of migration were significantly reduced in the NDV group, rL-RVG group and Erastin group(P＜0.001). LDH release and total ROS level were significantly increased (P＜0.01), p53 protein expression was significantly increased(P＜0.001), while SLC7A11 and GPX4 protein expression were significantly decreased (P＜0.001). rL-RVG group had a more pronounced effect as compared with NDV group. rL-RVG+Erastin group had significantly decreased cell number, cell proliferation capacity and distance of migration compared with rl-RVG and Erastin groups(P＜0.05), and LDH release and total ROS level were significantly increased(P＜0.05), p53 protein expression was significantly increased (P＜0.001), while SLC7A11 and GPX4 protein expression were significantly decreased (P＜0.001). Conclusions rL-RVG can exert a similar effect to Erastin to inhibit tumor cell proliferation, and its effect is much stronger than that of NDV. This provides new insights into rL-RVG-induced cell death and highlights the critical role of oncolytic viruses in the treatment of tumors.

Abstract Background Nuclear respiratory factor 1 (NRF1) is a transcription factor that participates in several kinds of tumor, but its role in hepatocellular carcinoma (HCC) remains elusive. This study aims to explore the role of NRF1 in HCC progression and investigate the underlying mechanisms. Results NRF1 was overexpressed and hyperactive in HCC tissue and cell lines and high expression of NRF1 indicated unfavorable prognosis of HCC patients. NRF1 promoted proliferation, migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NRF1 activated ERK1/2-CREB signaling pathway by transactivating lysophosphatidylcholine acyltransferase 1 (LPCAT1), thus promoting cell cycle progression and epithelial mesenchymal transition (EMT) of HCC cells. Meanwhile, LPCAT1 upregulated the expression of NRF1 by activating ERK1/2-CREB signaling pathway, forming a positive feedback loop. Conclusions NRF1 is overexpressed in HCC and promotes HCC progression by activating LPCAT1-ERK1/2-CREB axis. NRF1 is a promising therapeutic target for HCC patients.

Abstract Background Silicon nanoparticles (SiO2-NPs) play a crucial role in plants mitigating abiotic stress. However, the regulatory mechanism of SiO2-NPs in response to multiple stress remains unclear. The objectives of this study were to reveal the regulatory mechanism of SiO2-NPs on the growth and photosynthesis in cotton seedlings under salt and low-temperature dual stress. It will provide a theoretical basis for perfecting the mechanism of crop resistance and developing the technology of cotton seedling preservation and stable yield in arid and high salt areas. Results The results showed that the salt and low-temperature dual stress markedly decreased the plant height, leaf area, and aboveground biomass of cotton seedlings by 9.58%, 15.76%, and 39.80%, respectively. While SiO2-NPs alleviated the damage of the dual stress to cotton seedling growth. In addition to reduced intercellular CO2 concentration, SiO2-NPs significantly improved the photosynthetic rate, stomatal conductance, and transpiration rate of cotton seedling leaves. Additionally, stomatal length, stomatal width, and stomatal density increased with the increase in SiO2-NPs concentration. Notably, SiO2-NPs not only enhanced chlorophyll a, chlorophyll b, and total chlorophyll content, but also slowed the decrease of maximum photochemical efficiency, actual photochemical efficiency, photochemical quenching of variable chlorophyll, and the increase in non-photochemical quenching. Moreover, SiO2-NPs enhanced the activities of ribulose-1,5-bisphosphate carboxylase/oxygenase and phosphoenolpyruvate carboxylase, improved leaf water potential, and decreased abscisic acid and malondialdehyde content. All the parameters obtained the optimal effects at a SiO2-NPs concentration of 100 mg L− 1, and significantly increased the plant height, leaf area, and aboveground biomass by 7.68%, 5.37%, and 43.00%, respectively. Furthermore, significant correlation relationships were observed between photosynthetic rate and stomatal conductance, stomatal length, stomatal width, stomatal density, chlorophyll content, maximum photochemical efficiency, actual photochemical efficiency, photochemical quenching of variable chlorophyll, and Rubisco activity. Conclusion The results suggested that the SiO2-NPs improved the growth and photosynthesis of cotton seedlings might mainly result from regulating the stomatal state, improving the light energy utilization efficiency and electron transport activity of PSII reaction center, and inducing the increase of Rubisco activity to enhance carbon assimilation under the salt and low-temperature dual stress.

Abstract With data samples collected with the BESIII detector at seven energy points at s $$ \sqrt{s} $$ = 3.68 − 3.71 GeV, corresponding to an integrated luminosity of 333 pb −1, we present a study of the Λ transverse polarization in the e + e − → Λ Λ ¯ $$ \Lambda \overline{\Lambda} $$ reaction. The significance of polarization by combining the seven energy points is found to be 2.6σ including the systematic uncertainty, which implies a non-zero phase between the transition amplitudes of the Λ Λ ¯ $$ \Lambda \overline{\Lambda} $$ helicity states. The modulus ratio and the relative phase of EM-psionic form factors combined with all energy points are measured to be R Ψ = 0.71 − 0.10 + 0.10 $$ {0.71}_{-0.10}^{+0.10} $$ ± 0.03 and ∆ΦΨ = 23 − 8.0 + 8.8 $$ {23}_{-8.0}^{+8.8} $$ ± 1.6°, where the first uncertainties are statistical and the second systematic.

Abstract Background Despite improvements in prognosis due to advances in treatment, including surgery, genetic screening, and molecular targeted therapy, the outcomes of ovarian cancer (OC) remain unsatisfactory. Internal mRNA modifications are extremely common in eukaryotes; N6-methyladenosine (m6A) alteration has significant effects on mRNA stability and translation, and it is involved in the pathophysiology of numerous diseases related to cancer. Methods Bioinformatics analysis, quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of vir-like m6A methyltransferase associated (KIAA1429) in OC tissues and cell lines. Several different cell models and animal models were established to determine the role of KIAA1429 in glucose metabolism reprogramming and the underlying molecular mechanism of OC. The mechanism of oncology functional assays, co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how KIAA1429 interacts with important molecular targets. Results We reported that KIAA1429 was overexpressed in OC and predicted a poor prognosis. Functionally, KIAA1429 promoted cell growth by inducing proliferation and inhibiting necrosis. Mechanistically, KIAA1429 promoted tumor progression and glycolysis via stabilizing ENO1 mRNA in a way dependent on m6A. Furthermore, we investigated that the SPI1 transcription factor is the main transcription factor that regulates KIAA1429 transcription in OC. Conclusion Our findings revealed that SPI1/KIAA1429/ENO1 signaling is a novel molecular axis and raises awareness of the vital functions of the changes in KIAA1429 and m6A changes in the metabolic reprogramming of OC. These results identified new potential biomarkers and treatment targets for OC.

Abstract Background Conus, a highly diverse species of venomous predators, has attracted significant attention in neuroscience and new drug development due to their rich collection of neuroactive peptides called conotoxins. Recent advancements in transcriptome, proteome, and genome analyses have facilitated the identification of conotoxins within Conus’ venom glands, providing insights into the genetic features and evolutionary patterns of conotoxin genes. However, the underlying mechanism behind the extraordinary hypervariability of conotoxins remains largely unknown. Results We analyzed the transcriptomes of 34 Conus species, examining various tissues such as the venom duct, venom bulb, and salivary gland, leading to the identification of conotoxin genes. Genetic variation analysis revealed that a subset of these genes (15.78% of the total) in Conus species underwent positive selection (Ka/Ks > 1, p

Abstract Aims Previous studies have shown a significant reduction in skeletal muscle content in patients with chronic heart failure (CHF). The present study focused on the erector spinae muscle (ESM) to determine whether ESM content is associated with the development and severity of CHF. Methods and results A total of 652 patients were included in this trial for the study. According to the diagnostic criteria of CHF, 652 patients were divided into two groups, namely, the control group (268 patients) and the CHF group (384 patients). Meanwhile, to assess whether the ESM is associated with the severity of CHF, patients in the CHF group were divided into two groups according to left ventricular ejection fraction (LVEF) values: heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%, 256 patients) and heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%, 68 patients). Receiver operating curve analysis was performed to assess whether ESM content could predict CHF and determine its severity. Compared with the control group, the patients in the CHF group were older, the prevalence of coronary heart disease (CHD) and atrial fibrillation was higher, the colour ultrasound results showed that LVEF decreased significantly, and the left ventricular end‐diastolic internal diameter and left ventricular end‐systolic internal diameter increased significantly. Besides, patients in the CHF group had significantly lower ESM content, and ESM is an independent predictor of heart failure, with an odds ratio of 0.713 (CHF group vs. control group, 95% confidence interval 0.626–0.811, P

Abstract Background EEG monitoring techniques are receiving increasing clinical attention as a common method of reflecting the depth of sedation in the perioperative period. The influence of depth of sedation indices such as the bispectral index (BIS) generated by the processed electroencephalogram (pEEG) machine to guide the management of anesthetic depth of sedation on postoperative outcome remains controversial. This research was designed to decide whether an anesthetic agent exposure determined by raw electroencephalogram (rEEG) can influence anesthetic management and cause different EEG patterns and affect various patient outcomes. Methods A total of 141 participants aged ≥ 60 years undergoing abdominal major surgery were randomized to rEEG-guided anesthesia or routine care group. The rEEG-guided anesthesia group had propofol titrated to keep the rEEG waveform at the C-D sedation depth during surgery, while in the routine care group the anesthetist was masked to the patient’s rEEG waveform and guided the anesthetic management only through clinical experience. The primary outcome was the presence of postoperative complications, the secondary outcomes included intraoperative anesthetic management and different EEG patterns. Results There were no statistically significant differences in the occurrence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. Further EEG analysis revealed that lower frontal alpha power was significantly associated with a higher incidence of POD, and that rEEG-guidance not only reduced the duration of deeper anesthesia in patients with lower frontal alpha power, but also allowed patients with higher frontal alpha power to receive deeper and more appropriate depths of anesthesia than in the routine care group. Conclusions In elderly patients undergoing major abdominal surgery, rEEG-guided anesthesia did not reduce the incidence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. rEEG-guided anesthesia management reduced the duration of intraoperative BS in patients and the duration of over-deep sedation in patients with lower frontal alpha waves under anesthesia, and there was a strong association between lower frontal alpha power under anesthesia and the development of POD. rEEG-guided anesthesia may improve the prognosis of patients with vulnerable brains by improving the early identification of frail elderly patients and providing them with a more effective individualized anesthetic managements.