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Abstract Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management, such as pig, sheep, bovine and other species. It helps synchronize ovulation or stimulate multiple ovulations. However, a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation. This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy. Results Compared with those in the control group, gilts that underwent ovarian stimulation showed a decrease in pregnancy rate, farrowing rate, and total number of piglets born. Stimulated gilts also showed an increase in estradiol (E2) levels. The supraphysiological E2 level was correlated with the decrease in the number of piglets born. Furthermore, we found that high levels of E2 impair uterine receptivity, as shown by the overproliferation of endometrial epithelial cells. In vitro mechanistic studies demonstrated that high levels of E2 hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium, and in turn induces overproliferation of endometrial epithelial cells. Of note, N-acetyl-L-cysteine (NAC) supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation. Importantly, in vivo experiments indicated that dietary NAC supplementation, compared with ovarian stimulation group, improves the uterine receptivity in gilts, and significantly increases the pregnancy rate and total number of piglets born. Conclusions Ovarian stimulation-induced supraphysiological levels of E2 impairs uterine receptivity by hyperactivating FGF-FGFR-ERK signaling cascade, thereby reducing pregnancy rate and litter size. Supplementing NAC to a conventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity, thus rescuing adverse pregnancy outcomes following ovarian stimulation. Graphical Abstract

Layered MAX phases possess distinctive chemical, physical, electrical, and mechanical properties due to their amalgamation of metallic and ceramic characteristics. Understanding the corrosion mechanisms of MAX phases in various extreme environments is crucial. This paper commenced by scrutinizing synthesis techniques for MAX phase powders, thin films, and bulk materials, with a focus on fabrication processes and formation mechanisms. Subsequently, it delved into corrosion & oxidation mechanisms in diverse environments, emphasized their unique self-healing properties, and outlined future research directions. This comprehensive and systematic review aims to furnish researchers with effective guidance for selecting MAX phases based on different application environments.

Abstract The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Abstract Colorectal cancer is a common malignant tumor of the digestive system. Its morbidity and mortality rank among the highest in the world. Cancer development is associated with aberrant signaling pathways. Autophagy is a process of cell self-digestion that maintains the intracellular environment and has a bidirectional regulatory role in cancer. Apoptosis is one of the important death programs in cancer cells and is able to inhibit cancer development. Studies have shown that a variety of substances can regulate autophagy and apoptosis in colorectal cancer cells through signaling pathways, and participate in the regulation of autophagy on apoptosis. In this paper, we focus on the relevant research on autophagy in colorectal cancer cells based on the involvement of related signaling pathways in the regulation of apoptosis in order to provide new research ideas and therapeutic directions for the treatment of colorectal cancer.

This is an article in the field of mining engineering. The deep sand gravel type pore brine in Qaidam Basin belongs to the unsaturated chloride type brine with high calcium, high sodium and low potassium. 480 kg of gravel-type pore brine at 1000～2000 meters underground in Dalangtan mining area was selected for the test, and evaporated and crysta-llized in the natural state in summer. The distribution law of ions in the solid and liquid phases, the salt crystallization law and crystal morphology were analyzed, and the main precipitation characteristics of potassium were studied. The results show when evaporating in the outdoor natural state, the salt precipitation process is mainly divided into four stages: halite→carnallite→bischofite→tachyhydrite. The salt evolution law in the halite stage conforms to the phase diagram of Na+, K+, Mg2+//Cl-—H2O at 25 ℃, and that in carnallite and bischofite stages conforms to the phase diagram of K+, Ca2+, Mg2+//Cl-—H2O system at 25 ℃. There is a separate precipitation stage of potassium, at which potassium is mainly precipitated in the form of carnallite, and the recovery rate of potassium is 85.76%. The K+content in the potassium mixed salt can reach 9.27%, which is a high quality raw material for the production of potassium fertilizer. Calcium precipitates after the brucite stage. The experimental results can provide references for the development and utilization of this type of brine.

Background and objective Neoantigen reactive T cell (NRT) has the ability to inhibit the growth of tumors expressing specific neoantigens. However, due to the difficult immune infiltration and the inhibition of tumor microenvironment, the therapeutic effect of NRT in solid tumors is limited. In this study, we designed NRT cells (7×19 NRT) that can express both interleukin-7 (IL-7) and chemokine C-C motif ligand 19 (CCL19) in mouse lung cancer cells, and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells. Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma (LLC), prepared RNA vaccine, cultured NRT cells, constructed retroviral vectors encoding IL-7 and CCL19, transduced NRT cells and IL-7 and CCL19 were successfully expressed, and 7×19 NRT was successfully obtained. The anti-tumor effect was evaluated in vivo and in vitro in mice. Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19, achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice. The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment. In addition, both 7×19 NRT treatment and conventional NRT treatment were safe. Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19, which is a safe and effective genetic modification of NRT.

Abstract [11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained

Abstract The loss of dopaminergic neurons in the substantia nigra is a hallmark of pathology in Parkinson’s disease (PD). Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) is the critical enzyme responsible for the degradation of asymmetric dimethylarginine (ADMA) which inhibits nitric oxide (NO) synthase and has been implicated in neurodegeneration. Mitochondrial dysfunction, particularly in the mitochondria-associated endoplasmic reticulum membrane (MAM), plays a critical role in this process, although the specific molecular target has not yet been determined. This study aims to examine the involvement of DDAH-1 in the nigrostriatal dopaminergic pathway and PD pathogenesis. The distribution of DDAH-1 in the brain and its colocalization with dopaminergic neurons were observed. The loss of dopaminergic neurons and aggravated locomotor disability after rotenone (ROT) injection were showed in the DDAH-1 knockout rat. l-arginine (ARG) and NO donors were employed to elucidate the role of NO respectively. In vitro, we investigated the effects of DDAH-1 knockdown or overexpression on cell viability and mitochondrial functions, as well as modulation of ADMA/NO levels using ADMA or ARG. MAM formation was assessed by the Mitofusin2 oligomerization and the mitochondrial ubiquitin ligase (MITOL) phosphorylation. We found that DDAH-1 downregulation resulted in enhanced cell death and mitochondrial dysfunctions, accompanied by elevated ADMA and reduced NO levels. However, the recovered NO level after the ARG supplement failed to exhibit a protective effect on mitochondrial functions and partially restored cell viability. DDAH-1 overexpression prevented ROT toxicity, while ADMA treatment attenuated these protective effects. The declines of MAM formation in ROT-treated cells were exacerbated by DDAH-1 downregulation via reduced MITOL phosphorylation, which was reversed by DDAH-1 overexpression. Together, the abundant expression of DDAH-1 in nigral dopaminergic neurons may exert neuroprotective effects by maintaining MAM formation and mitochondrial function probably via ADMA, indicating the therapeutic potential of targeting DDAH-1 for PD.

In the context of the digital era, e-learning has become an innovative and indispensable component of the educational sector. With the continuous advancement of technology and the widespread adoption of the internet, e-learning has demonstrated its key role in maintaining educational continuity and supporting remote teaching. However, despite the extensive applications and significant advantages of e-learning, the willingness of college students to continue using e-learning platforms is not always high, presenting a challenge for educators and technology developers. Based on the Expectation Confirmation Model, this study examines the influence of perceived educational and emotional support on the continuance intention of e-learning among college students. The researchers conducted a survey using a structured questionnaire randomly among 379 university students from three universities in Henan Province to measure their self-reported responses on six constructs: perceived educational support, perceived emotional support, perceived usefulness, confirmation, satisfaction, and continuance intention. The study uses the Structural Equation Modeling—Artificial Neural Network (SEM-ANN) method to elucidate the non-compensatory and non-linear relationships between predictive factors and e-learning continuance intention. Except for the direct effects of perceived educational support and perceived emotional support on perceived usefulness, which were not significant, all other hypotheses were confirmed. Moreover, according to the normalized importance obtained from the multilayer perceptron, satisfaction (100%) was found to be the most critical predictive factor, followed by confirmation (29.8%), perceived usefulness (28.2%), perceived educational support (22.7%), and perceived emotional support (21.8%). All constructs together accounted for 62.0% of the total variance in college students’ e-learning continuance intention. This study’s adoption of a two-stage analysis approach improved the depth and accuracy of data processing and expanded the methodological scope of educational technology research. It provides direction for future in-depth studies in various environments and cultural contexts.

ObjectivesWe aim to investigate the prevalence of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) among pediatric patients with acute respiratory tract illness (ARTI) in southern China both pre- and post-COVID-19 pandemic, as well as identify associated risk factors for severe infections.MethodsThe study conducted a real-time PCR analysis on hospitalized children with ARTI from 2012 to 2023, specifically targeting RSV, hMPV, and other respiratory pathogens. Additionally, demographic data was collected during this analysis.ResultsThe prevalence of RSV occurs triennially, and likewise, the temporal pattern of hMPV outbreaks mirrors that of RSV. The peak infection rates of RSV and hMPV occurred during and following the implementation of COVID-19 epidemic prevention and control measures. The incidence of RSV infection exhibited bimodal peaks in 2022, while hMPV demonstrated seasonal peaks during the spring, fall, and winter periods post-COVID-19 pandemic. After the COVID-19 outbreak, there has been an upward trend in the proportion of female patients and patients aged one year and older presenting with ARTI, RSV infections, and hMPV infections. Infant (OR = 4.767, 95%CI: [3.888–5.846], p < 0.0001), presence of co-infection (OR = 0.540, 95%CI: [0.404–0.722], p < 0.0001), and existence of comorbidities (OR = 1.582, 95%CI: [1.285–1.949], p < 0.0001) was the risk ratio for the severity of RSV infection. Children infected with hMPV under the age of 1 year (OR = 0.322, 95%CI: [0.180 – 0.575], p < 0.0001), as well as those with comorbidities (OR = 8.809, 95%CI: [4.493 – 17.272], p < 0.0001), have a higher risk of developing severe illness.ConclusionThe changing epidemiological patterns have the potential to lead to widespread severe outbreaks among children, particularly those with underlying medical conditions who may experience more severe symptoms. Conducting surveillance for pneumoviridae viruses in children is an imperative measure to establish a robust foundation for future epidemic prevention and treatment strategies.

Objective To study the changes in related parameters after secondary preparation of blood components, in order to further improve the quality of blood components. Methods Different centrifugation conditions were selected for the preparation of primary blood component red blood cells in additive solution leukocytes reduced, and the quality was tested. Then, using the red blood cells in additive solution leukocytes reduced as the initial blood for secondary preparation, and the red blood cells were washed through the Haemonetics ACP 215 device, and the quality was tested. The preparation parameters of blood components were observed, compared and optimized. Results Under comparable centrifugation effects of different centrifugation conditions, the quality control items, which of primary blood components of red blood cells in additive solution leukocytes reduced and frozen plasma prepared by the separation, such as volume, hemoglobin, hematocrit and residual white blood cells met the relevant national standards. And the quality control items of secondary blood components of washed red blood cells such as the hemoglobin and superalbumin content both met the relevant national standards, while volume exceeded the standard by 7-14 mL, which can be operated to the standard range. In addition, the recovery rate of red blood cells and the clearance rate of plasma protein could reach 75% and 99% respectively. Conclusion There is a certain correlation between primary and secondary preparation of blood components, but the relevant parameters of secondary preparation of blood components can be flexibly adjusted according to the actual situation to ensure that the quality of prepared blood component products meet the national standards, thus ensuring clinical treatment effect and safety.

【Objective】Auxin response factors (ARF) are key transcription factors engaged in the auxin signaling system and play significant roles in plant flower and fruit development, organ morphogenesis, hormone control, and stress responses. The study aims to investigate the biological functions of AsARF gene in Aquilaria sinensis (Lour.) Gilg during the aroma formation process.【Method】The AsARF genes in A. sinensis at genome-wide level were identified and analyzed by bioinformatics approaches. The expression patterns of ARF family members in response to mechanical damage in A. sinensis were revealed through transcriptome data analysis.【Result】Twenty-one AsARF genes were identified at the genome-wide level, and the systematic bioinformatics analysis results showed that these 21 AsARF genes were divided into five groups, with gene sequences within the same group sharing similar gene structures and conserved protein domains, while different groups of AsARF genes exhibited significant variations in the number of exons and introns. Furthermore, cis-acting element analysis revealed that the promoter regions of ARF genes in A. sinensis contained numerous sequences associated with sunlight, anaerobic conditions, gibberellin and other response elements. Gene duplication and collinearity analysis indicated that fragment duplication events played a crucial role in the evolution and expansion of the A. sinensis ARF gene family. Comparing with rice ARF genes, it revealed there was a closer relationship between A. sinensis and Arabidopsis thaliana ARF genes. Additionally, transcriptome data analysis demonstrated a significant decrease in expression levels of AsARF5, AsARF6, AsARF19, AsARF20, and AsARF21 genes in response to mechanical damage in A. sinensis.【Conclusion】The study conducted the first genome-wide identification of the AsARF gene family and offered a comprehensive analysis on their physicochemical properties, systematic evolution, gene structure, conserved protein domains, promoter cis-acting elements, gene duplication, and collinearity. Furthermore, the potential mechanisms of AsARF genes in the aroma formation process of A. sinensis were explored through RNA-seq analysis. The results suggested that some AsARF genes may be involved in the defense and dynamic balance of aroma formation in A. sinensis. These findings provided important theoretical basis for a deeper understanding of the aroma formation mechanism in A. sinensis.

Fast homogenization without incipient melting is the key to designing solution heat treatment (SHT) process for single crystal superalloys. In this paper, a multicomponent phase-field model coupled with solidus temperature is developed for dynamically tracking incipient melting temperature, TIM, of alloy during SHT. The simulation process runs completely automatically only by inputting the composition information of as-cast specimen. Based on the obtained TIM-time profile, the holding temperature and the time of SHT are determined. Applying this approach to Co–30Ni–11Al–4W–1Ta–4Ti–5Cr single crystal specimen, a gradual increased TIM from 1247 °C to 1293 °C within 72,000 s is obtained, and thus a stepwise SHT process with a short time of less than 20 h is designed. The experimental verification shows that after SHT, the segregation coefficient of the slowest diffusing element W decreased from more than 2 to 1.065, the content of harmful secondary phase has decreased to below 0.1%, and no incipient melting occurs.

Abstract Background Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se. Methods VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis. Results VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis. Conclusions VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.

Abstract Pure self-management model, pure aggregation business model and Self-support + aggregation model are three commonly used business modes on ride-hailing platforms. We use an analytical model to study these three business models and give the optimal business model decision of the platform. The research shows that the heterogeneity ratio of drivers, the cost of the platform under the Self-support model, the franchise fee received by the platform under the aggregation model and the dissatisfaction of the original users on the platform play a key role in the selection of the platform’s business model. When the difference between the franchise fee under the aggregation mode and the platform cost under the Self-support mode fails to generate positive feedback on the platform profit, the platform should choose the pure Self-support mode. When riders are more sensitive to the heterogeneity of service quality of the platform and user stickiness can be ensured, the platform should choose the pure aggregation business model. When user stickiness can be guaranteed and the cost of the platform under the self-run model is controllable, the platform should choose the Self-support + aggregation business model.

Abstract Background Small intestinal monomorphic–epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. Methods The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein–Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. Results Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. Conclusions Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

Background: Colorectal cancer is a major cause of mortality among the prevalent malignant tumors of the gastrointestinal tract. Although chemotherapy is a standard treatment for colorectal cancer, its efficacy is limited by chemoresistance. Recent studies have investigated targeting tumor stem cells as a potential new therapeutic approach for addressing chemoresistance in colorectal cancer. Colorectal cancer frequently relapses, with tumor stem cells often representing one of the leading causes of treatment failure. Purpose: Understanding drug resistance in colorectal cancer stem cells is crucial for improving treatment outcomes. By focusing on developing targeted therapies that specifically address drug resistance in colorectal cancer stem cells, there is potential to make significant advancements in the treatment of colorectal cancer.This approach may lead to more effective and lasting outcomes in patients battling colorectal cancer. Research Design: In this review, a comprehensive overview of recent research on colorectal cancer stem cell treatment resistance is presented.Results: Elucidating the key underlying mechanisms. This review also highlights the potential benefits of targeted therapies in overcoming colorectal cancer resistance to treatment. Conclusions: CCSCs are key players in drug resistance of CRC, indicating their potential as targets for effective therapy. Elucidating their role in this process could aid in discovering tailored treatment strategies.The significance of signaling pathways, TME, and miRNA in regulating drug resistance in CCSCs is been highlighted.

Leukemia is a malignant tumor with high heterogeneity and a complex evolutionary process. It is difficult to resolve the heterogeneity and clonal evolution of leukemia cells by applying traditional bulk sequencing techniques, thus preventing a deep understanding of the mechanisms of leukemia development and the identification of potential therapeutic targets. However, with the development and application of single-cell sequencing technology, it is now possible to investigate the gene expression profile, mutations, and epigenetic features of leukemia at the single-cell level, thus providing a new perspective for leukemia research. In this article, we review the recent applications and advances of single-cell sequencing technology in leukemia research, discuss its potential for enhancing our understanding of the mechanisms of leukemia development, discovering therapeutic targets and personalized treatment, and provide reference guidelines for the significance of this technology in clinical research.

Objective and rationale: Hospital-acquired falls are common and serious adverse events in medical institutions, with high incidence and injury rates. Studying the occurrence patterns of hospital-acquired falls is important for preventing falls in hospitalized patients. However, the effect of meteorological factors on hospital-acquired falls has not been elucidated. Therefore, this study explored the impact of meteorological parameters on hospital-acquired falls in Chongqing, China, and provided new ideas for the clinical prevention of falls in patients. Methods: Correlation analysis and distributed lag nonlinear models were employed to analyze the relationship between 3890 cases of hospital-acquired falls and meteorological data in 13 hospitals in 11 districts and counties in Chongqing from January 2013 to April 2023. Results: The number of hospital-acquired falls demonstrated a nonlinear correlation with the daily average relative humidity and negatively correlated with sunshine duration; however, temperature, air pressure, and wind speed were not correlated. Compared to the reference humidity (87 %), the immediate effects of daily average relative humidity (65–68 % and 90–97 %) increased the risk of hospital-acquired falls on the same day (relative risk [RR]:1.027–1.243). When the daily average relative humidity was 95–97 %, lags of 0–1 d and 8–12 d had greater effects on falls (RR:1.073–1.243). The daily average relative humidities of 62–74 % and 91–97 % were statistically significant at cumulative relative risk (CRR)of 4, 7, 10, and 14 d with a cumulative lag (CRR: 1.111–4.277). On sex and age stratification, the lag and cumulative effects of relative humidity more significantly impacted falls in women and patients aged ≥65 years. Conclusion: Daily average relative humidity had a nonlinear correlation and lag effect on hospital-acquired falls; therefore, medical institutions should pay attention to the effect of relative humidity on hospital-acquired falls in patients, especially old and female patients.

Abstract Background Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. Methods The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. Conclusions The MOYAOMICS project represents a significant step toward comprehending MMD’s molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

Volcanic activity is often associated with the development of faulted lacustrine basins. Organic-rich shale in such basins usually contains abundant volcanic material. The influence of volcanic input on organic-rich shale deposition in the basin studied has not been discussed in detail. Based on the ten shale samples from three wells, this study analyzed the depositional environment of the Yingcheng Formation shale in the Lishu Fault Depression area of the Songliao Basin by using interpretation of logging, total organic carbon analysis, gas chromatography mass spectrometry analysis, and trace element analysis. The impact of fault break to basement and volcanic materials on the organic matter enrichment was evaluated. The results show that the organic matter of Ying 1 (Y1), the First Member of the Yingcheng Formation, in the Lishu Fault Depression is characterized mainly by type I kerogen. The shale of the Y1 Member, having high total organic carbon content, is laterally continuous and could be considered as a potential target for shale oil exploration. The shale with high total organic carbon was deposited in a freshwater deep lake under an anoxic environment. There is a significant input of volcanic material, especially around the Su2 well near the Sangshutai Fault. This study has established a sedimentary model of organic-rich shale in the faulted lacustrine basin affected by volcanic activity, which has significance for the exploration of shale oil in faulted lacustrine basins.

This paper aimed to explore the correlation between the physical and chemical indicators of sauce-flavor Daqu with different sensory characteristics and the community of molds, six physical and chemical indicators of WQ, YQ and BQ were tested, the mold of Daqu were separated and identified, the correlation between the physical and chemical indicators and mold community in three kinds of Daqu were analyzed by redundancy analysis. The results showed that the liquefaction power of YQ was higher, and YQ and BQ showed the higher fermentation power and esterification power, respectively: 1.56 U, 22.63 U and 1.51 U, 22.48 U. A total of 78 strains of 13 species of molds belonging to 6 genera were isolated and identified from three kinds of Daqu, including 7 species in WQ, namely Paecilomyces subglobosus, Paecilomyces variotii, Lichtheimia corymbifera, Lichtheimia ornata, Penicillium tardochrysogenum, Penicillium chrysogenum, Epicoccum endophytica. 6 Species were isolated from YQ, namely Lichtheimia ramosa, Lichtheimia corymbifera, Paecilomyces variotii, Lichtheimia hongkongensis, Lichtheimia ornata, Aspergillus intermedius. 7 Species were isolated from BQ, namely Paecilomyces variotii, Paecilomyces subglobosus, Lichtheimia ramosa, Scopulariopsis brevicaulis, Lichtheimia corymbifera, Aspergillus sydowii, Aspergillus quadrilineatus. Through redundancy analysis, it was concluded that Lichtheimia was the main strain affecting the saccharification and esterification of Daqu. This study provides a basis for the research and application of molds in sauce-flavored Daqu and provides data support for improving the fermentation performance of sauce-flavored Daqu.

Abstract The mechanisms by which animals respond to rapid changes in temperature are largely unknown. Here, we found that polymodal ASH sensory neurons mediate rapid cooling-evoked avoidance behavior within the physiological temperature range in C. elegans. ASH employs multiple parallel circuits that consist of stimulatory circuits (AIZ, RIA, AVA) and disinhibitory circuits (AIB, RIM) to respond to rapid cooling. In the stimulatory circuit, AIZ, which is activated by ASH, releases glutamate to act on both GLR-3 and GLR-6 receptors in RIA neurons to promote reversal, and ASH also directly or indirectly stimulates AVA to promote reversal. In the disinhibitory circuit, AIB is stimulated by ASH through the GLR-1 receptor, releasing glutamate to act on AVR-14 to suppress RIM activity. RIM, an inter/motor neuron, inhibits rapid cooling-evoked reversal, and the loop activities thus equally stimulate reversal. Our findings elucidate the molecular and circuit mechanisms underlying the acute temperature stimuli-evoked avoidance behavior.

A novel method is proposed for reconstructing high-fall scenes in complex urban environments based on prominence maximization, addressing the limitations of traditional UAV tilt photogrammetry. Initially, UAV’s initial acquisition data is used to generate a Digital Surface Model (DSM). An algorithm is designed to identify local wave peaks and calculate their saliency values, which, combined with linear interpolation, results in a smoother surface elevation model(SDSM). This provides new planning points for the camera’s position, overcoming issues like mismatching shadows in the DSM model. The method was tested in Boston, USA, covering various functional types and traffic scenarios. Results indicate that compared to traditional tilt photogrammetry, UAV tilt photogrammetry based on saliency maximization achieves higher accuracy, effectively capturing local details in the surveyed area while ensuring flight safety. Furthermore, the actual 3D model’s texture information and geometric structure are expressed with high quality.

Abstract Background Numerous studies have demonstrated a positive correlation between diet quality and cognitive performance, indicating that improving diet quality may be beneficial in preventing cognitive decline in older adults. However, few study has investigated the causal relationship between diet quality and cognitive performance. The purpose of this study is to evaluate the causal effects of diet quality on cognitive performance in Chinese adults aged 55 years and older. Particularly, we utilize the Chinese Diet Quality Index (CHEI), a dietary assessment tool tailored for Chinese populations, as a proxy for older adults’ diet quality. Methods Data were obtained from the China Health and Nutrition Survey (CHNS) ( $$N = 2337$$ N = 2337 , $$\ge$$ ≥ 55 years old) conducted in 2004 and 2006. Cognitive function was tested by a subset of items from the Telephone Interview for Cognitive Status-Modified (TICS-m). Data on dietary intake was retrieved from three consecutive 24 hour recalls by participants and its quality was assessed by the 17-items Chinese Healthy Eating Index (CHEI). An Instrumental Variable technique was used to deal with the potential endogeneity of dietary quality. The instrumental variable used in our study is the community mean of CHEI. Results After adjusting for socio-demographic factors (age, gender, education, per capita household income), lifestyle habits (smoking, alcohol consumption, physical activity, BMI), and chronic diseases (hypertension, diabetes), our findings revealed that improving diet quality had a significant positive effect on cognitive performance ( $$P = 0.020$$ P = 0.020 ), particularly in females aged 55-65 years ( $$P = 0.003$$ P = 0.003 ) and females with primary education and below ( $$P < 0.001$$ P < 0.001 ). Conclusion Our study suggests that improving diet quality and adhering to the Dietary Guidelines for Chinese may enhance cognitive performance in Chinese adults aged 55 years and older.

【Objective】Aroma is one of the important quality traits of rice, which directly affects consumers' evaluation on cooking and eating quality of rice. The selection of aromatic rice resources and the identification and utilization of aroma genes has practical significance for the genetic breeding and the development of aromatic rice. The aroma gene, Badh2, is a major gene that has been cloned to control the aroma of rice. Clarifying the distribution and utilization frequency of different alleles of Badh2 in main aromatic rice varieties planted in South China will better serve the breeding practice of aromatic rice in this area.【Method】Genotypic analysis was conducted on Badh2 in 30 rice cultivars collected from different areas in South China with the KASP functional molecular marker. The aroma of all the cultivars were tested with different evaluation methods including chewing method, KOH soaking method and HS-SPME/GC-MS. Meanwhile, the aroma ancestries of the above aromatic rice cultivars were traced, and their genetic backgrounds of aroma origins were analysed.【Result】KASP molecular markers could accurately genotype the aroma gene Badh2. The Badh2 allele variations of 30 aromatic rice varieties planted in South China were all Badh2-E7 type. The results of the aroma test showed that all Badh2-E7 type varieties possessed aroma. The aroma source parent tracing analysis of the aromatic rice varieties revealed that the aroma source parents of aromatic rice varieties were relatively simple and mainly included Xiangyaxiangzhan, Basmati 370, and etc. Xiangyaxiangzhan accounted for about 30% of the aroma source parents, and Basmati 370 accounted for about 13% of the aroma source parents.【Conclusion】Large scale and rapid identification of aromatic rice can be achieved through KASP genotyping technology. The Badh2 alleles of 30 aromatic rice varieties collected in South China are all the genotype of Badh2-E7, and the simplicity of the genetic background of the aroma gene may result from the single source of the aroma parent. In future aromatic rice breeding, new aroma genes can be introduced to enrich the genetic background of rice aroma.

The composition and distribution of storage substances in rice endosperm directly affect grain quality. A floury endosperm mutant, wcr (white-core rice), was identified, exhibiting a loose arrangement of starch granules with a floury opaque appearance in the inner layer of mature grains, resulting in reduced grain weight. The total starch and amylose content remained unchanged, but the levels of the four component proteins in the mutant brown rice significantly decreased. Additionally, the milled rice (inner endosperm) showed a significant decrease in total starch and amylose content, accompanied by a nearly threefold increase in albumin content. The swelling capacity of mutant starch was reduced, and its chain length distribution was altered. The target gene was mapped on chromosome 5 within a 65 kb region. A frameshift mutation occurred due to an insertion of an extra C base in the second exon of the cyOsPPDKB gene, which encodes pyruvate phosphate dikinase. Expression analysis revealed that wcr not only affected genes involved in starch metabolism but also downregulated expression levels of genes associated with storage protein synthesis. Overall, wcr plays a crucial role as a regulator factor influencing protein synthesis and starch metabolism in rice grains.

When analyzing GPS time series, common mode errors (CME) often obscure the actual crustal movement signals, leading to deviations in the velocity estimates of station coordinates. Therefore, mitigating the impact of CME on station positioning accuracy is crucial to ensuring the precision and reliability of GNSS time series. The current approach to separating CME mainly uses signal filtering methods to decompose the residuals of the observation network into multiple signals, from which the signals corresponding to CME are identified and separated. However, this method overlooks the spatial correlation of the stations. In this paper, we improved the Independent Component Analysis (ICA) method by introducing correlation coefficients as weighting factors, allowing for more accurate emphasis or attenuation of the contributions of the GNSS network’s spatial distribution during the ICA process. The results show that the improved Weighted Independent Component Analysis (WICA) method can reduce the root mean square (RMS) of the coordinate time series by an average of 27.96%, 15.23%, and 28.33% in the E, N, and U components, respectively. Compared to the ICA method, considering the spatial distribution correlation of stations, the improved WICA method shows enhancements of 12.53%, 3.70%, and 8.97% in the E, N, and U directions, respectively. This demonstrates the effectiveness of the WICA method in separating CMEs and provides a new algorithmic approach for CME separation methods.

Abstract Hereditary deafness is a common neurosensory disorder, and 148 non‐syndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre‐clinical research, patient selection criteria, pre‐clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

Abstract The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine‐induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD.

To address the challenges posed by the fast-charging demand of electric vehicles, causing feeder load and voltage imbalances during operation, this paper introduces a spatio-temporal pricing strategy tailored to enhance feeder operation equilibrium. This approach facilitates the spatio-temporal guidance of fast-charging loads for electric vehicles in operation. This paper begins by formulating a spatio-temporal distribution model for electric vehicle fast-charging loads, considering owners’ preferences. It further develops a behavioral model for the travel choices of electric vehicles, illustrating the impact of spatio-temporal electricity pricing at fast-charging stations on load distribution. Next, it proposes a multi-objective spatio-temporal pricing model and its solution method specifically designed for feeder-balance-oriented fast-charging stations. This model targets the minimization of the spatio-temporal imbalance in feeder voltage and load. It takes a comprehensive approach, considering the constraints of the spatio-temporal load distribution model and optimal power flow model. The resulting spatio-temporal pricing model for fast-charging stations is effectively solved using the extended Pareto evolutionary algorithm. To validate the effectiveness of the proposed method in achieving feeder balancing, this paper analyzes two examples: a self-built 29-node road network and a 9-node distribution network, as well as a 66-node road network and a 33-node distribution network in the Xinjiang region. The results show that the proposed method can effectively guide the charging of electric vehicles and make the load distribution more balanced.

Salt lakes are significant components of global inland waters. Salt lake (SL) water can provide precious mineral resource for microbial growth. The prospect of utilizing diluted SL water for cultivation of a terrestrial oil-producing microalga Vischeria sp. WL1 was evaluated under laboratory conditions. Based on the detected mineral element composition, the water from Gouchi Salt Lake was diluted 2, 4, 6 and 8 folds and used with supplementation of additional nitrogen, phosphorus and iron (SL+ water). It was found that 4 folds diluted SL+ water was most favorable for biomass and oil production. When cultivated in this condition, Vischeria sp. WL1 gained a biomass yield of 0.82 g L−1 and an oil yield of 0.56 g L−1 after 24 days of cultivation, which is comparable to the optimum productivity we previously established. In addition, total monounsaturated fatty acid contents (64.4∼68.1 %) of the oils resulted from cultures in diluted SL+waters were higher than that in the control (55.5 %). It was also noteworthy that in all these cultures the oil contents (652.0∼681.0 mg g−1) accounted for the most of the biomass, which are far more than the protein and starch contents. This study demonstrates the feasibility of using SL water as a cost-effective mineral resource to cultivate microalgae for biomass and oil production.

Objective To investigate the preparation quality and clinical application effect of pooled platelets with leukocytes reduced. Methods The quality and clinical effect of the buffy-coated method prepared pooled platelets leukocytes reduced (experimental group, n=40) and apheresis platelets leukocytes reduced (control group, n=40) were compared. Results The platelet volume (mL), platelet count (×1011), red blood cell contamination (×108) and residual white blood cell (×106) of the experimental group and control group were 278.90±7.92 vs 276.52±8.01, 2.66±0.09 vs 2.66±0.83, 0.54±0.42 vs 0.83±0.84, 0.29±0.54 vs 0.27±0.51, respectively, with no significant difference. The results of bacterial culture were negative, all met the requirements of relevant national standards. In addition, the CCI (×103, 24 h) and PPR (%) were 15.11±9.86 vs 14.61±12.55 and 54.23±18.70 vs 61.41±19.09 respectively, with no significant difference, indicating a certain degree of therapeutic effect. Conclusion The quality and clinical therapeutic effect of pooled platelets leukocytes reduced were consistent with that of apheresis platelets leukocytes reduced.

Abstract Background Perfluoroalkyl and polyfluoroalkyl substances (PFAS) represent a category of pervasive and enduring environmental pollutants that present a risk to human health. Although growing evidence suggests that probiotics can potentially alleviate the adverse effects of PFAS, large cross-sectional studies on the relationship between probiotic consumption and PFAS remain lacking. Objective The objective of this study is to assess the association between the exposure of probiotics and serum levels of PFAS. Methods This analysis included individuals aged 20 and above who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2018. Probiotic consumption was considered when a participant reported consuming yogurt during the two 24-h dietary recall or using a probiotic supplement in dietary supplement questionnaires over the past 30 days. Results This study involved 9469 adults, out of which 1333 had been exposed to probiotics. We found negative associations between probiotic consumption and serum concentrations of perfluorooctanoic acid (PFOA) (β: − 0.19, 95% CI − 0.35 to − 0.02; P = 0.027), and perfluorooctane sulfonic acid (PFOS) (β: − 0.1.27, 95% CI − 2.23 to − 0.32; P = 0.010). The consumption of probiotic supplements alone was associated with reduced perfluorononanoic acid (PFNA) (β: − 0.19, 95% CI − 0.28 to − 0.10; P

Abstract Background Ankyrin repeat domain 49 (ANKRD49) has been found to be highly expressed in multiple cancer including lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). However, the function of ANKRD49 in the pathogenesis of NSCLC still remains elusive. Previously, ANKRD49 has been demonstrated to promote the invasion and metastasis of A549 cells, a LUAD cell line, via activating the p38-ATF-2-MMP2/MMP9 pathways. Considering the heterogeneity of tumor cells, the function and mechanism of ANKRD49 in NSCLC need more NSCLC-originated cells to clarify. Methods Real-time qPCR was employed to test ANKRD49 expression levels in nine pairs of fresh NSCLC tissues and the corresponding adjacent normal tissues. The function of ANKRD49 was investigated using overexpression and RNA interference assays in lung adenocarcinoma cell line (NCI-H1299) and lung squamous carcinoma cell line (NCI-H1703) through gelatin zymography, cell counting kit-8, colony formation, wound healing, migration and invasion assays mmunoprecipitation was performed to in vitro. Immunoprecipitation was performed to test the interaction of c-Jun and ATF2. Chromatin immunoprecipitation was conducted to assess the transcriptional regulation of ATF2/c-Jun on MMP-2/9. Moreover, the tumorigenicity of ANKRD49 was evaluated in nude mice models and the involved signal molecular was also measured by immunohistochemical method. Results We found that the levels of ANKRD49 in cancerous tissues were higher than those in adjacent normal tissues. in vitro assay showed that ANKRD49 promoted the migration and invasion of NCI-H1299 and NCI-H1703 cells via enhancing the levels of MMP-2 and MMP-9. Furthermore, ANKRD49 elevated phosphorylation of JNK and then activated c-Jun and ATF2 which interact in nucleus to promote the binding of ATF2:c-Jun with the promoter MMP-2 or MMP-9. In vivo assay showed that ANKRD49 promoted lung metastasis of injected-NSCLC cells and the high metastatic rate was positively correlated with the high expression of ANKRD49, MMP-2, MMP-9, p-JNK, p-c-Jun and p-ATF2. Conclusion The present study indicated that ANKRD49 accelerated the invasion and metastasis of NSCLC cells via JNK-mediated transcription activation of c-Jun and ATF2 which regulated the expression of MMP-2/MMP-9. The molecular mechanisms of ANKRD49’s function is different from those found in A549 cells. The current study is a supplement and improvement to the previous research.

Abstract Background Physical activity (PA) is known to positively affect individuals’ mental and physical health, especially those who experience high levels of stress, such as teachers. Previous studies have examined the relationship between teachers’ PA, mental health, and well-being. Still, there is a lack of research on the direct and indirect effects of PA and self-efficacy. Purpose This study aimed to investigate the structural relationship between teachers’ PA, mental health, well-being, and self-efficacy among ESL/EFL teachers. A total of 364 Chinese English language teachers were selected through convenience sampling. Mental health, physical activity, psychological well-being, and self-efficacy instruments were used. Methodology The data was analyzed using Smart PLS software, and the hypothesized model was evaluated. The results indicated an acceptable level of divergent and convergent validity and goodness of fit. Results The findings revealed that PA directly predicts teachers’ mental health and well-being, but the direct structural relationship between teachers’ PA and self-efficacy was not confirmed. However, the results showed that teachers’ PA contributes to their self-efficacy by enhancing their mental and psychological well-being. The total effect of teachers’ PA on their self-efficacy was significant. Additionally, mental health and psychological well-being strongly influenced teachers’ self-efficacy. Conclusion In conclusion, regular weekly physical activity can help EFL/ESL teachers foster their mental health, psychological well-being, and self-efficacy. These findings have theoretical and practical significance for teachers, trainers, and educational psychologists.

This paper presents a charge pump circuit with a wide output range and low current mismatch applied to phase-locked loops. In this designed structure, T-shaped analog switches are adopted to suppress the non-ideal effects of clock feedthrough, switching time mismatch, and charge injection. A source follower and current splitting circuits are proposed to improve the matching accuracy of the charging and discharging currents and reduce the current mismatch rate. A rail-to-rail high-gain amplifier with a negative feedback connection is introduced to suppress the charge-sharing effect of the charge pump. A cascode current mirror with a high output impedance is used to provide the charge and discharge currents for the charge pump, which not only improves the current accuracy of the charge pump but also increases the output voltage range. The proposed charge pump is designed and simulated based on a 65 nm CMOS process. The results show that when the power supply voltage is 1.2 V, the output current of the charge pump is 100 μA, the output voltage is in the range of 0.2~1 V, and the maximum current mismatch rate and current variation rate are only 0.21% and 1.4%, respectively.

The accurate perception of external environment information through the robot foot is crucial for the mobile robot to evaluate its ability to traverse terrain. Adequate foot-end contact signals can provide robust support for robot motion control and decision-making processes. The shape and uncertain rotation of the wheel-legged robot foot end represent a significant challenge to sensing the robot foot-end contact state, which current foot-end sensing schemes cannot solve. This paper presents a sensing method for the tire stress field of wheel-legged robots. A finite element analysis was conducted to study the deformation characteristics of the foot-end tire under force. Based on this analysis, a heuristic contact position estimator was designed that utilizes symmetrical deformation characteristics. Strain sensors, arranged in an array, extract the deformation information on the inner surface of the tire at a frequency of 200 Hz. The contact position estimator reduces the dimensionality of the data and fits the eigenvalues to the estimated contact position. Using support vector regression, the force estimator utilizes the estimated contact position and sensor signal to estimate the normal reaction force, designated as FZ. The sensing system is capable of detecting the contact position on the wheel circumference (with a root mean square error of 1.150°), as well as the normal force of 160 N on the Z axis (with a root mean square error of 6.04%). To validate the efficacy of the sensor detection method, a series of randomized and repeated experiments were conducted on a self-constructed test platform. This novel approach offers a promising avenue for perceiving contact states in wheel-legged robots.

Abstract Background Programmed death ligand 1 (PD‐L1) has been demonstrated to facilitate tumor progression and therapeutic resistance in an immune‐independent manner. Nevertheless, the function and underlying signaling network(s) of cancer cell‐intrinsic PD‐L1 action remain largely unknown. Herein, we sought to better understand how ubiquitin‐specific peptidase 51 (USP51)/PD‐L1/integrin beta‐1 (ITGB1) signaling performs a cell‐intrinsic role in mediating chemotherapeutic resistance in non‐small cell lung cancer (NSCLC). Methods Western blotting and flow cytometry were employed for PD‐L1 detection in NSCLC cell lines. Coimmunoprecipitation and pulldown analyses, protein deubiquitination assay, tissue microarray, bioinformatic analysis and molecular biology methods were then used to determine the significance of PD‐L1 in NSCLC chemoresistance and associated signaling pathways in several different cell lines, mouse models and patient tissue samples. Ubiquitin‐7‐amido‐4‐methylcoumarin (Ub‐AMC)‐based deubiquitinase activity, cellular thermal shift and surface plasmon resonance (SPR) analyses were performed to investigate the activity of USP51 inhibitors. Results We provided evidence that cancer cell‐intrinsic PD‐L1 conferred the development of chemoresistance by directly binding to its membrane‐bound receptor ITGB1 in NSCLC. At the molecular level, PD‐L1/ITGB1 interaction subsequently activated the nuclear factor‐kappa B (NF‐κB) axis to elicit poor response to chemotherapy. We further determined USP51 as a bona fide deubiquitinase that targeted the deubiquitination and stabilization of the PD‐L1 protein in chemoresistant NSCLC cells. Clinically, we found a significant direct relationship between the USP51, PD‐L1 and ITGB1 contents in NSCLC patients with chemoresistant potency. The elevated USP51, PD‐L1 and ITGB1 levels were strongly associated with worse patient prognosis. Of note, we identified that a flavonoid compound dihydromyricetin (DHM) acted as a potential USP51 inhibitor and rendered NSCLC cells more sensitive to chemotherapy by targeting USP51‐dependent PD‐L1 ubiquitination and degradation in vitro and in vivo. Conclusions Together, our results demonstrated that the USP51/PD‐L1/ITGB1 network potentially contributes to the malignant progression and therapeutic resistance in NSCLC. This knowledge is beneficial to the future design of advanced cancer therapy.

Abstract Background Modular tissue engineering (MTE) is a novel “bottom-up” approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue. Results Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis. Conclusions The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair.

Oil spill pollution seriously endangers human and ecosystem health. Therefore, it is urgent to develop oil-absorbing materials to effectively remove oil spill pollution. Among the traditional oil-absorbing materials, natural organic adsorption material has low oil absorption capacity and hydrophilicity; inorganic adsorption materials are difficult to recover and have low oil absorption efficiency and high price; and although the synthetic organic adsorbent has outstanding oil absorption capacity, its biodegradation is poor. Silica aerogel (SA) has the characteristics of high porosity, low density, and high specific surface area, which make it an excellent oil-absorbing material. However, the hydrophilic surface and pearl necklace structure of SA limit its wide applications in the oil absorption field. Hydrophobically modified hydrophobic silica aerogel (HSA) has not only excellent SA characteristics but also good hydrophobic/lipophilic properties. In this paper, focusing on HSA preparation by surface posttreatment modification and coprecursor modification, the research progress on these two methods combined with supercritical drying and ambient pressure drying is systematically introduced, and the advantages and disadvantages of the two methods are analyzed and summarized. The coprecursor modification is mainly combined with a supercritical drying process to prepare HSA, while the surface posttreatment modification is often combined with an ambient pressure drying process. Both methods normally use silylating agents as hydrophobic modifiers. The surface posttreatment modification does not change the formed pore structure, and the pore size and particle size of HSA are relatively uniform. However, the modification process of surface posttreatment is long, the solvent consumption is large, and the cost is high. In addition, incomplete internal modification may be a problem. In the coprecursor modification method, wet gel is formed and modified simultaneously, shortening the modification time and saving costs. The prepared HSA of coprecursor modification has a larger specific surface area and better hydrophobicity, but its pore size is uneven, and the introduced hydrophobic groups are limited. Excessive silylating agents affect the sol–gel process of HSA. In addition, the current methods for strengthening HSA mechanical properties and the research progress on HSA oil absorption properties are reviewed. Finally, based on the current development of HSA as oil-absorbing materials, the development direction of these materials is discussed, for example, developing low-cost and eco-friendly raw materials, shortening the hydrophobic modification process, preparing bulk HSA, strengthening the mechanical properties, and improving the oil-absorbing properties of HSA.

Introduction: An ideal bone repair scaffold should have dual functions of osteoinductive ability and in vivo imaging. In this study, the simultaneous substitution of silicon (Si) and gadolinium (Gd) in hydroxyapatite (HA) as potential multifunctional bone graft materials has been successfully developed.Methods: A series of HA nanoparticles (HA NPs) doped with different proportions of Si and Gd were prepared. The chemical structure and phase composition of the materials were analyzed using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The microstructure, magnetic properties, surface potential, and cytotoxicity of the materials were also analyzed. The magnetic resonance imaging (MRI) effect of Gd&Si-HA/poly(lactic-co-glycolic acid) (Gd&Si-HA/PLGA) composite materials was evaluated. Osteogenic-related gene expression, alkaline phosphatase (ALP) level, and mineralization capacity of MC3T3-E1 cultured on Gd&Si-HA/PLGA composite materials were also detected.Results and Discussion: The 1.5Gd&Si-HA@PLGA group showed good ability to promote osteogenic differentiation of cells. The MRI effect of the 1.5Gd&Si-HA@PLGA scaffold was observable. This HA material containing Si and Gd co-doping has a broad application prospect in the field of bone tissue engineering owing to its ability to enhance osteoinductive property and improve MRI effect.

Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) has been reported to be linked to a series of adverse health outcomes in mothers and their children. As the gut microbiota is a sensitive biomarker for assessing the toxicity of environmental contaminants, this study attempted to investigate whether prenatal PFASs exposure was associated with the gut microbiota of infants. Based on the Shanghai-Minhang Birth Cohort Study, this prospective cohort study included 69 mother-infant pairs. Fasting blood samples were collected from pregnant women for the PFASs assay. We collected fecal samples of infants at 1 year of age and analyzed the V3-V4 hypervariable region of the bacterial 16 S rRNA gene by high-throughput sequencing. Among the detected 11 PFASs, the concentration of perfluorooctanoic acid (22.19 ng/mL) was the highest, followed by perfluorooctane sulfonic acid (12.08 ng/mL). Compared with infants whose mothers’ total PFASs concentrations during pregnancy were at the 40th percentile or lower (reference group), the species richness and diversity of microbiota were lower in infants prenatally exposed to a high level of PFASs (the sum of PFASs concentrations above the 60th percentile). Prenatal exposure to PFASs was associated with a higher proportion of Acidaminococcaceae, Acidaminococcus, Megamonas, Megasphaera micronuciformis and Megamonas funiformis in infants. The changes of the species have been suggested to be associated with immune and metabolic dysfunction in humans. Functional alterations of gut microbiota due to PFASs exposure were dominated by an enrichment of butanoate metabolism. Our preliminary findings may shed light on the potential role of the microbiota underlying the well-known impact of prenatal PFASs exposure on health outcomes of humans in later life.

Epimedium koreanum Nakai, a well-known traditional Chinese medicinal herb, has been widely used to treat osteoporosis and sexual dysfunction for thousands of years. However, due to the decreasing population of East Asian natural resources, yearly output of Epimedium crude herb has been in low supply year by year. In this study, an unusual variety of E. koreanum was discovered in Dunhua, Jilin Province, the northernmost area where this variety was found containing 6 individuals, with three branches that had 27 leaflets, which is much more than the typical leaflet number of 9. Firstly, the novel E. koreanum varety was identified using DNA barcodes. Then, 1171 differentially expressed genes (DEGs) were discovered through parallel RNA-seq analysis between the newly discovered variety and wild type (WT) E. koreanum plant. Furthermore, the results of bioinformatics investigation revealed that 914 positively and 619 negatively correlated genes associated with the number of leaflets. Additionally, based on RNA-Seq and qRT-PCR analysis, two homologous hub TCP genes, which were commonly implicated in plant leaf development, and shown to be up regulated and down regulated in the discovered newly variety, respectively. Thus, our study discovered a novel wild resource for leaf yield rewarding medicinal Epimedium plant breeding, provided insights into the relationship between plant compound leaf formation and gene expression of TCPs transcription factors and other gene candidates, providing bases for creating high yield cultivated Epimedium variety by using further molecular selection and breeding techniques in the future.

ABSTRACT Fusobacterium nucleatum is a harmful bacterium that produces hydrogen sulfide by metabolizing sulfur-containing amino acids, both of which have been shown to promote/initiate the development of various cancers, such as colorectal cancer, liver cancer, as well as lung cancer. However, few studies have reported how F. nucleatum acts on gut microbiota, influences the autophagy process, and promotes the development of colorectal cancer through the metabolite hydrogen sulfide. It was found that HCT116 cells secreted more inflammatory factors and showed higher survival as well as migration rate when given a pathological concentration of hydrogen sulfide. Using cellular transcriptome sequencing, it could be seen that after giving HCT116 cells F. nucleatum or F. nucleatum with L-cysteine, many inflammation-related signaling pathways, including autophagic pathways, were elevated compared to the control group. In vivo, the mice in the model groups displayed cancer progression, and the expression of some of the autophagy-related genes, DRAM1, NBR1, ATG7, MAP1LC3A were also increased in mice given F. nucleatum or F. nucleatum with L-cysteine when compared to the untreated control mice. The number of certain probiotic bacteria and fungi in the mice given F. nucleatum or F. nucleatum and L-cysteine decreased significantly; in contrast, the number of potentially pathogenic bacteria and fungi increased. These findings suggest that F. nucleatum and its metabolite hydrogen sulfide can modulate intestinal microbiota and autophagy as well as promote the development and progression of colorectal cancer. IMPORTANCE Colorectal cancer (CRC) is the second most common cancer in the world; the main treatment for CRC is immunosuppressive therapy, but this therapy is only effective for a small percentage of CRC patients, so there is an urgent need for a treatment with fewer side effects and higher efficacy. This study demonstrated that Fusobacterium nucleatum with increased abundance in CRC can regulate the autophagy process and disrupt normal intestinal microbiota by producing hydrogen sulfide, factors that may be involved in the development and progression of CRC. This study may provide a reference for future CRC treatment options that are efficient and have fewer side effects.

Background and aimHigh-grade fetal adenocarcinoma of the lung (HG-FLAC) is a specific subtype of lung adenocarcinoma with a poor prognosis. A lack of understanding exists because of the rarity of this disease. This study aimed to present a case of HG-FLAC with multiple metastases misdiagnosed as male breast carcinoma at the initial diagnosis.Case presentationThe patient visited our hospital due to a month-long cough. The chest computed tomography (CT) scan revealed a mass in the left lung and chest wall, accompanied by enlargement of mediastinal lymph nodes. The magnetic resonance imaging indicated potential metastatic lesions in the brain and adrenal glands. The patient underwent a biopsy of the lesion in the right chest wall. The pathological and immunohistochemical findings indicated a high possibility of male breast cancer. However, the clinical features did not support this diagnosis. Therefore, a CT-guided percutaneous lung biopsy was performed, and the pathological examination finally indicated HG-FLAC.ConclusionsWe presented a complex yet interesting case in which HG-FLAC was misdiagnosed as male breast cancer. Our interesting case may stimulate discussions about the methods to manage patients with HG-FLAC.

Citrus aurantium L. fruit is a commonly used Chinese medicine whose therapeutic effects tends to be affected by growing conditions. In order to gain insights into the effects of growing location on the cuticular wax composition of C. aurantium L. fruit, we analyzed the differences in the wax composition of its fruits collected from different regions. The findings showed that the cuticular waxes in the fruit peels were mainly composed of fatty acids, which differed quantitatively in the chemical profiles of C. aurantium L. samples from different geographical conditions. Particularly, the concentrations of linoleic acid and stearic acid in the total component content of the fruit peel were above 1%, with a greater level in the geo-authentic samples. Thus, GC–MS-based wax analysis was first used for the chemical characterization and quantification of cuticular waxes, which could be considered as a rapid way for evaluating the quality of medicinal fruits.

Cyclic olefin copolymer is a type of high-performance polyolefin material, which is prepared by using a single-site catalyst in solution polymerization. The common activator of this system is alkyl aluminoxane or organic boron/aluminum system. Among them, organic boron is mostly triphenylcarbenium tetrakis(pentafluorophenyl)borate or dimethylanilinium tetrakis(pentafluorophenyl)borate. In this study, ethylene and norbornene were copolymerized with metallocene catalyst activated with the combination of tris(pentafluorophenyl)boron and triisobutylaluminium. Compared with homopolymerization of ethylene, copolymerization shows high activity. The molecular weight of the polymer increased significantly with the increase of the insertion rate of norbornene. Fineman-Ross method was used to calculate the reactivity ratio, which showed that the reactivity ratio of norbornene was much lower than that of ethylene. The high copolymerization activity may indicate that, although norbornene has a lower coordination probability, its insertion rate is higher than ethylene. The copolymer with higher norbornene incorporation has a higher glass transition temperature, and the relationship between them is linear.

The existence of Himalayan long-eared bats, Plecotus homochrous (Chiroptera, Vespertilionidae), in China has not been previously confirmed. In this study, four bats captured with harp traps from two sites in the Maoershan National Nature Reserve in Guangxi, China were investigated. These bats have long, wide auricles, each with a prominent tragus. The length of each auricle is about the same as that of a forearm. Hairs on the ventral fur have a dark base with mixed grey and yellowish tips; those on the dorsal fur also have a dark base and are bicolored with brown tips. The thumbs are very short. A concavity is present in the front of the dorsal side of the cranium. Based on morphological characteristics and phylogeny using Cyt b gene sequences, these bats were identified as P. homochrous, thus confirming the existence of Himalayan long-eared bats in China.