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Abstract Vestibular hair cells are mechanoreceptors critical for detecting head position and motion. In mammals, hair cell loss causes vestibular dysfunction as spontaneous regeneration is nearly absent. Constitutive expression of exogenous ATOH1, a hair cell transcription factor, increases hair cell regeneration, however, these cells fail to fully mature. Here, we profiled mouse utricles at 14 time points, and defined transcriptomes of developing and mature vestibular hair cells. To mimic native hair cells which downregulate endogenous ATOH1 as they mature, we engineered viral vectors carrying the supporting cell promoters GFAP and RLBP1. In utricles damaged ex vivo, both CMV-ATOH1 and GFAP-ATOH1 increased regeneration more effectively than RLBP1-ATOH1, while GFAP-ATOH1 and RLBP1-ATOH1 induced hair cells with more mature transcriptomes. In utricles damaged in vivo, GFAP-ATOH1 induced regeneration of hair cells expressing genes indicative of maturing type II hair cells, and more hair cells with bundles and synapses than untreated organs. Together our results demonstrate the efficacy of spatiotemporal control of ATOH1 overexpression in inner ear hair cell regeneration.

This study aims to elucidate the mechanism of lipid metabolism disorder in intrauterine growth retardation (IUGR) pigs and the potential alleviating effects of dimethylglycine sodium salt (DMG-Na). A total of 60 male newborn piglets were selected for this study. Within each litter, one normal birth weight (NBW) male piglet (1.53 ± 0.04 kg) and two IUGR male piglets (0.76 ± 0.06 kg) were chosen based on their birth weight. The piglets were divided into three groups for the study: NBW pigs received a PBS gavage and a common basal diet (NBW-C group), IUGR pigs received the same PBS gavage and common basal diet (IUGR-C group), and IUGR pigs received a 70-mg DMG-Na gavage along with a common basal diet supplemented with 0.1% DMG-Na (IUGR-D group). At 150 d of age, all piglets underwent euthanasia by exsanguination following electrical stunning, after which plasma, liver, and longissimus dorsi (LM) samples were promptly collected. The IUGR-D group demonstrated improvements in plasma parameters (P < 0.05), with lower triglyceride and free fatty acid (FFA) values, and hormone levels (P < 0.05), with lower growth hormone, insulin, and homeostasis model assessment of insulin resistance values. Restoration of lipid metabolism was observed (P < 0.05), with lower triglyceride and FFA, and higher hepatic lipase and total lipase values in the liver, and lower triglyceride and FFA values in the LM. Mitochondrial ETC complexes showed increased levels (P < 0.05), including higher complex III values in the liver, and higher complex I, complex III, and complex V values in the LM. Enhanced levels of energy metabolites were noted (P < 0.05), with higher NAD+, NAD+/NADH, adenosine triphosphate, and mtDNA values, and lower NADH values in the liver and LM. Additionally, meat quality parameters showed improvement (P < 0.05), with higher pH 24 h and a∗ values, and lower drip loss 48 h, L∗, and b∗ values. The expressions of lipid metabolism and mitochondrial function-related genes and proteins were upregulated (P < 0.05) compared to the IUGR-C group. In conclusion, it was indicated that IUGR pigs experienced lipid metabolism disorders and diminished performance. However, supplementation with DMG-Na showed promise in mitigating these adverse physiological effects by safeguarding body tissues and modulating energy metabolism.

Abstract Alpine natural heritage sites hold significant value due to their unique global resources. Studying land cover changes in these areas is crucial for maintaining and preserving multiple their values. This study takes Kalajun-Kuerdening, one of the components of Xinjiang Tianshan World Natural Heritage Site, as an example to analyze land cover changes and their driving factors in alpine heritage sites. Highlights include: (1) Between 1994 and 2023, Forest and Grassland increased by 55.96 km2 and 18.16 km2, with notable forest growth from 2007 to 2017. Trends in Forest changes align with forest protection policies, and a substantial amount of Bareland converted to Grassland indicates an increase in vegetation cover. (2) Elevation, precipitation, temperature, and evapotranspiration are key drivers of land cover changes, as validated by Random Forest algorithm and Geodetector model. (3) Favorable conditions for Grassland to Forest transition include annual precipitation between 275 and 375 mm, annual temperature between −2 and 3 °C, annual evapotranspiration between 580 and 750 mm, elevation between 1800 and 2600 m, and aspect between 0 to 110° and 220 to 259.9°. Continuous monitoring of land cover changes and their driving factors in mountain heritage sites contributes to the protection of the ecological environment and provides data and information support for addressing climate change, resource management, and policy making.

Abstract Objective Explore the efficacy and safety of involved-field irradiation (IFI) combined with S-1 as definitive concurrent chemoradiotherapy (dCRT) for locally advanced elderly esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT). Methods We designed a prospective single-arm phase II study. The study enrolled 91 patients aged 75 to 92 years. Eligible participants had histologically confirmed squamous cell carcinoma, stage II to IV disease based on the 8th edition of the American Joint Committee on Cancer (AJCC). All elderly patients (EPs) received dCRT with S-1. which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions or 50.4 Gy delivered in 28 fractions. The primary endpoint was 2-year overall survival (OS), and the secondary endpoints were progression-free survival (PFS), local control rate (LCR), and safety. Results From July 2017 to July 2021, we enrolled EPs with ESCC who were treated at the Jiangsu Cancer hospital. As of August 1, 2023, the median follow-up of surviving EPs was 31.4 months (IQR: 25.2 to 72.6 months). 83 patients (91.2%) completed the whole course of treatment. The 2-year OS rate was 59.2%, and the PFS rate was 43.7%. The most common grade 1 to 2 adverse effects (AEs) were radiation esophagitis (79.1%), and then were radiation pneumonia (46.2%). Anemia (41.8%) was the most common of grade 1 to 2 hematologic toxicity. The incidence of grade 3 or above AEs was 24.2%, and the incidence of leukopenia was the highest (11.0%). There was not one death due to treatment-related toxicity. In a subgroup analysis of radiotherapy doses, we found no statistically significant differences in PFS (P = 0.465) and OS (P = 0.345) in EPs with ESCC who received 50.4 Gy and 61.2 Gy, and that patients in the 50.4 Gy group had lower dermatitis (P = 0.045) and anemia (P = 0.004). Conclusions IF-IMRT combined with S-1 is a promising regimen for elderly ESCC. And the radiotherapy dose of 50.4 Gy remains the standard dose for EPs with ESCC undergoing CCRT.

Abstract Background Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type 2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to identify the metabolic changes that are associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and subsequently assess their link to disease. Methods NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases. Results Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2–0.3 SD, p

Abstract The COVID-19 pandemic has significantly impacted the mental health of children and adolescents worldwide. While various factors contributing to this phenomenon have been explored, the role of learning style preferences remains underexamined. This cross-sectional study, conducted between October and November 2020, involved over 20,000 participants, including students from junior high school, senior high school, and undergraduate levels. Significant differences in depressive mood levels were observed among individuals with different learning modality preferences upon the return to traditional, in-person learning. Students with in-person learning preferences exhibited lower depression levels, while students with no preference for either learning style outperformed devotees of remote learning. The highest depression occurred among those endorsing neither learning mode. Importantly, the impact of these preferences on depressive moods was found to be moderated by COVID-19 infection experiences. The findings highlight the nuanced relationship between learning style preferences, COVID-19 infection experiences, and mental health outcomes among students. Acknowledging the moderating effect of infection experiences is crucial for developing targeted interventions and adapting pedagogical approaches post-pandemic. This study contributes valuable insights into the complex relationships shaping the mental well-being of students amidst educational disruptions caused by the pandemic.

Abstract Understanding the fluorescence resonance energy transfer (FRET) of metal nanoparticles at the atomic level has long been a challenge due to the lack of accurate systems with definite distance and orientation of molecules. Here we present the realization of achieving FRET between two atomically precise copper nanoclusters through cocrystallization-induced spatial confinement. In this study, we demonstrate the establishment of FRET in a cocrystallized Cu8(p-MBT)8(PPh3)4@Cu10(p-MBT)10(PPh3)4 system by exploiting the overlapping spectra between the excitation of the Cu10(p-MBT)10(PPh3)4 cluster and the emission of the Cu8(p-MBT)8(PPh3)4 cluster, combined with accurate control over the confined space between the two nanoclusters. Density functional theory is employed to provide deeper insights into the role of the distance and dipole orientations of molecules to illustrate the FRET procedure between two cluster molecules at the electronic structure level.

Abstract Background B3GNT7, a glycosyltransferase of significant importance that is highly expressed in intestinal epithelial cells, plays a pivotal role in intestinal physiological processes. This study elucidates novel insights into the potential role and underlying mechanisms of B3GNT7 in ulcerative colitis (UC). Methods An experimental colitis model was induced using DSS in mice to investigate B3GNT7 expression in the colon via transcriptomics and immunohistochemistry. Bioinformatics analysis was employed to delineate the biological functions of B3GNT7. Additionally, the correlation between the transcription levels of B3GNT7 in colonic tissues from patients with UC, sourced from the IBDMDB database, and the severity of colonic inflammation was analyzed to elucidate potential mechanisms. Results The DSS-induced colitis model was successfully established, and transcriptomic analysis identified a marked downregulation of B3GNT7 expression in the colonic tissues compared to the controls. Functional enrichment analysis indicated B3GNT7’s predominant role in mucin O-glycosylation. Protein interaction analysis revealed that B3GNT7 predominantly interacts with members of the mucin MUC family, including MUC2, MUC3, and MUC6. In patients with UC, B3GNT7 transcription levels were significantly reduced, particularly in those with moderate to severe disease activity. The expression level of B3GNT7 exhibited a negative correlation with the endoscopic severity of UC. Gene set enrichment analysis (GSEA) further demonstrated significant enrichment of B3GNT7 in the mucin O-glycosylation synthesis pathway. Conclusion The downregulation of B3GNT7 expression in the colonic tissues of UC patients may contribute to the compromised mucin barrier function and the exacerbation of colitis.

Abstract This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

Highlights MXene sediments is innovatively used as photothermal material for seawater desalination. Inspired by the natural wood transpiration process, a 3D MXene sediment-based aerogel with vertically aligned channels is innovatively prepared as solar evaporator. With unique structure and composition, excellent photothermal conversion efficiency, evaporation rate, salt resistance, and resistance to biological/oil/special environments are achieved in practical desalination.

Abstract Background Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method. Methods A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 ∼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively. Results Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 ∼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method. Conclusions The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment.

Abstract Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

BackgroundThe low positive rate of blood cultures often leads to downstream consequences. We present a summary of multidisciplinary interventions implemented by a tertiary referral hospital to improve blood culture efficiency and optimize antimicrobial usage.MethodsWe evaluated the knowledge, attitude, and practice (KAP) of healthcare workers in a tertiary care hospital before and after intervention using a questionnaire. A multidisciplinary team was formed to implement the intervention, defining roles, standardizing procedures, continually improving education and feedback, and establishing incentive mechanisms. Regular quality control assessments are conducted on the responsible departments.ResultsFollowing the intervention, the median submission time for blood culture specimens was reduced from 2.2 h to 1.3 h (p

Postoperative cognitive dysfunction (POCD) poses a significant threat to patients undergoing anesthesia and surgery, particularly elderly patients. It is characterized by diminished cognitive functions post surgery, such as impaired memory and decreased concentration. The potential risk factors for POCD include age, surgical trauma, anesthetic type, and overall health condition; however, the precise mechanisms underlying POCD remain elusive. Recent studies suggest that neuroinflammation might be a primary pathogenic factor. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes are implicated in exacerbating POCD by promoting the release of inflammatory factors and proteins that initiate pyroptosis, further influencing the disease process. The regulation of NLRP3 inflammasome activity, including its activation and degradation, is tightly controlled through multiple pathways and mechanisms. In addition, autophagy, a protective mechanism, regulates the NLRP3 inflammasome to control the progression of POCD. This review reviews recent findings on the role of the NLRP3 inflammasome in POCD pathogenesis and discusses therapeutic strategies aimed at reducing NLRP3 sources, inhibiting cellular pyroptosis, and enhancing autophagy.

Abstract The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Abstract Background Gonadotropin precisely controls mammalian reproductive activities. Systematic analysis of the mechanisms by which epigenetic modifications regulate the synthesis and secretion of gonadotropin can be useful for more precise regulation of the animal reproductive process. Previous studies have identified many differential m6A modifications in the GnRH-treated adenohypophysis. However, the molecular mechanism by which m6A modification regulates gonadotropin synthesis and secretion remains unclear. Results Herein, it was found that GnRH can promote gonadotropin synthesis and secretion by promoting the expression of FTO. Highly expressed FTO binds to Foxp2 mRNA in the nucleus, exerting a demethylation function and reducing m6A modification. After Foxp2 mRNA exits the nucleus, the lack of m6A modification prevents YTHDF3 from binding to it, resulting in increased stability and upregulation of Foxp2 mRNA expression, which activates the cAMP/PKA signaling pathway to promote gonadotropin synthesis and secretion. Conclusions Overall, the study reveals the molecular mechanism of GnRH regulating the gonadotropin synthesis and secretion through FTO-mediated m6A modification. The results of this study allow systematic interpretation of the regulatory mechanism of gonadotropin synthesis and secretion in the pituitary at the epigenetic level and provide a theoretical basis for the application of reproductive hormones in the regulation of animal artificial reproduction.

Glass properties play crucial roles in ensuring the safety and reliability of electronic packaging. However, challenges, such as thermal expansion and resistance to acid corrosion, pose long-term service difficulties. This study investigated the impact of the microstructure on acid resistance by adjusting the glass composition. A glass material with excellent acid resistance was obtained by achieving a similar coefficient of thermal expansion to tantalum; it exhibited a weight loss rate of less than 0.03% when submerged in 38% sulfuric acid at 85 °C for 200 h. Theoretically, this glass can be used to seal wet Ta electrolytic capacitors. Differential scanning calorimetry (DSC) was used to analyze the glass transition temperature and thermal stability of borosilicate glasses. X-ray diffractometry (XRD), scanning electron microscopy (SEM), and Raman spectroscopy were used to study the microstructure of the amorphous phase of the borosilicate glass, which revealed a close relationship between the degree of network phase separation in the borosilicate glass and the degree of polymerization (isomorphic polyhedron value, IP) of the glass matrix. The IP value decreased from 3.82 to 1.98 with an increasing degree of phase separation. Boron transitions from [BO4] to [BO3] within the glass network structure with increasing boron oxide content, which diminishes the availability of free oxygen provided by alkaline oxide, resulting in a lower acid resistance. Notably, the glass exhibited optimal acid resistance at boron trioxide and mixed alkaline oxide contents of 15% and 6%, respectively. Raman experiments revealed how the distributions of various bridging oxygen atoms (Qn) affect the structural phase separation of the glass network. Additionally, Raman spectroscopy revealed the depolymerization of Q4 into Q3, thereby promoting high-temperature phase separation and highlighting the unique advantages of Raman spectroscopy for phase recognition.

Abstract Electrochemical carbon dioxide/carbon monoxide reduction reaction offers a promising route to synthesize fuels and value-added chemicals, unfortunately their activities and selectivities remain unsatisfactory. Here, we present a general surface molecular tuning strategy by modifying Cu2O with a molecular pyridine-derivative. The surface modified Cu2O nanocubes by 4-mercaptopyridine display a high Faradaic efficiency of greater than 60% in electrochemical carbon monoxide reduction reaction to acetate with a current density as large as 380 mA/cm2 in a liquid electrolyte flow cell. In-situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy reveals stronger *CO signal with bridge configuration and stronger *OCCHO signal over modified Cu2O nanocubes by 4-mercaptopyridine than unmodified Cu2O nanocubes during electrochemical CO reduction. Density function theory calculations disclose that local molecular tuning can effectively regulate the electronic structure of copper catalyst, enhancing *CO and *CHO intermediates adsorption by the stabilization effect through hydrogen bonding, which can greatly promote asymmetric *CO-*CHO coupling in electrochemical carbon monoxide reduction reaction.

Abstract Background Cyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer. Methods This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations. Results The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057–2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029–3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428–90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276–8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025–1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088–3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015–2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017–4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083–6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism. Conclusion This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.

Abstract Introduction ABP 938 is being developed as a biosimilar candidate to aflibercept reference product (RP), a biologic used for certain angiogenic eye disorders. This study was designed to provide a comparative analytical assessment of the structural and functional attributes of ABP 938 and aflibercept RP sourced from the United States (US) and the European Union (EU). Methods Structural and functional characterization studies were performed using state-of-the-art analytical techniques that were appropriate to assess relevant quality attributes and capable of detecting qualitative and quantitative differences in primary structure, higher-order structure and biophysical properties, product-related substances and impurities, general properties, and biological activities. Results ABP 938 had the same amino acid sequence and exhibited similar secondary and tertiary structures, and biological activity as aflibercept RP. There were minor differences in a small number of biochemical attributes which are not expected to impact clinical performance. In addition, aflibercept RP sourced from the US and EU were analytically similar. Conclusions ABP 938 was structurally and functionally similar to aflibercept RP. Since aflibercept RP sourced from the US and EU were analytically similar, this allows for the development of a scientific bridge such that a single-source RP can be used in nonclinical and clinical studies.

Crystallization is an important process that affects the properties of final products and is essential in nearly all chemical processing industries. In recent years, ultrasonic technology has received widespread attention due to its ability to enhance crystallization yield, improve crystal morphology and shape, and regulate the particle size and distribution of crystal products. It holds promising prospects for industrial crystallization. In this work, the ultrasonic cavitation effect and ultrasonic crystallization mechanism are described, and the influence of ultrasound on the crystallization effect of products is analysed and discussed. In addition, the application status of ultrasonic reactors and ultrasonic crystallization processes is introduced in detail, and the change trend from laboratory to industrialization is analyzed. Finally, the challenges and opportunities facing the industrialization of ultrasonic crystallization in future developments are discussed. The purpose of this work is to make the selective promotion or inhibition of ultrasound more helpful for industrial crystallization.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with dismal prognosis. Vascular abnormality is a hallmark of GBM, and aggravates diseases progression by increasing hypoxia, inducing life-threaten edema and hindering drug delivery. Nonetheless, the intricate mechanism underlying vascular abnormality remains inadequately understood. Here, we revealed a key role of SOX4 on vascular abnormality in GBM. SOX4 expression was increased in endothelial cells (ECs) from human brain tumors compared with ECs from paired normal brain tissue. Knockdown of SOX4 in mouse brain ECs restrained cell migration and proliferation. Furthermore, in vitro suppression of SOX4 in brain ECs and in vivo conditional knockout of SOX4 in tumor ECs led to the downregulation of genes linked with vascular abnormality. Notably, specific depletion of SOX4 in ECs enhanced drug delivery and sensitive tumor to chemotherapeutic drugs in GBM. Taken together, these results demonstrated that SOX4 is a novel regulator for tumor angiogenesis and vascular abnormality in GBM. Our findings identify SOX4 as a potential vascular therapeutic target to improve drug delivery for GBM treatment.

Background: Elderly patients with esophageal cancer can benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen remains undetermined. We aimed to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma (ESCC). Methods: From January 2016 to November 2022, a total of 349 patients aged 70 and above with ESCC were included. The patient population was divided into two treatment groups: patients receiving paclitaxel-based CCRT were allocated to the TP group, and those receiving S-1 regimen CCRT were allocated to the S-1 group. Propensity score matching (PSM) was used to balance potential biases. Survival outcomes, overall response rate, and treatment-related toxicities were assessed. Results: After PSM, there were 82 patients in each group. The median follow up of the surviving patients was 42.6 months (IQR 28.0–58.8 months). The 2-year overall survival (OS) rate (71.4% vs 65.4%; log-rank P = 0.010) and progression-free survival (PFS) rate (64.4% vs 58.0%; log-rank P = 0.048) were significantly higher in the TP group. Compared with the S-1 group, the TP group experienced a higher rate of grade 3 and above hematologic toxicities, such as leukopenia (47.6% vs 15.9%, P < 0.001) and neutropenia (35.4% vs 6.1%, P < 0.001). One patient in the TP group and two patients in the S-1 group had grade 5 toxic effects. Conclusions: Our findings suggest that paclitaxel-based CCRT was well tolerated in elderly patients with ESCC and provided significant survival benefits over S-1 regimen.

ABSTRACT: This study aimed to explore the impact of dietary Bacillus subtilis fmbj (BS) supplementation on acute intestinal dysfunction induced by lipopolysaccharide (LPS) in broilers. One hundred and eighty 1-day-old male Arbor Acres broilers were randomly divided into three treatment groups, each comprising ten replicates of 6 birds. On d 20, LPS-challenged (LPS group and LPS-BS group) and LPS-unchallenged (CON group) broilers received intraperitoneal injections of 1 mg/kg body weight LPS solution and an equivalent volume of sterile saline, respectively. Compared to the CON group, LPS disrupted (P < 0.05) the morphology of the small intestine (jejunum or ileum), exacerbated (P < 0.05) serum, small intestinal, and small intestinal mitochondrial antioxidant capacity, induced (P < 0.05) small intestinal oxidative damage, and altered (P < 0.05) the expression of genes and proteins related to antioxidants, cell adhesion, and mitochondrial function in the jejunum. The LPS-BS group exhibited a tendency towards improvement in small intestinal morphology, serum, small intestinal, and small intestinal mitochondrial antioxidant capacity, small intestinal oxidative damage, and the expression of genes and proteins related to antioxidants, cell adhesion, and mitochondrial function in the jejunum when compared to the LPS group. In conclusion, BS supplementation may confer protection against LPS-induced acute intestinal dysfunction in broilers by enhancing the activation of SIRT1/PGC1α, suggesting its potential as a valuable additive for the poultry industry.

IntroductionWith the boom in social media, many people spend a lot of time on these platforms. Among them, some developed negative emotions, such as fatigue, depression, or disinterest in communicating, and used social media temporarily or permanently. Therefore, this study aims to explore the antecedents of social media fatigue, including social media helpfulness, social media self-efficacy, online subjective well-being, social comparison, compulsive social media use, privacy concerns, fear of missing out, and information overload, and to further discuss the determinants of social media fatigue on social anxiety and lurking.MethodsAn online questionnaire was distributed to social media users, and 659 valid samples were obtained with the help of a purposive sampling strategy. The data was analyzed by the partial least square (PLS) method.ResultsThe study found that social media self-efficacy had a significant negative effect on social media fatigue; compulsive social media use, fear of missing out, and information overload had a significant positive effect on social media fatigue; and social media fatigue had a significant positive effect on social anxiety and lurking.DiscussionThe research results can be used as a reference for social media marketers and internet service providers in developing business strategies.

Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in ‘fresh’ human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients’ brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.

Summary: This study aims to establish a scientific foundation for early detection and diagnosis of silicosis by conducting meta-analysis on the role of single biomarkers in independent diagnosis. The combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, and diagnostic odds ratio (DOR) were 0.84 (95% confidence interval (CI): 0.77–0.90), 0.83 (95% CI: 0.78–0.88), 5.08 (95% CI: 3.92–6.59), 0.19 (95% CI: 0.13–0.27), 3.31 (95% CI: 2.88–3.74) and 27.29 (95% CI: 17.77–41.91), respectively. The area under the curve (AUC) was 0.90 (95% CI: 0.88–0.93). The Fagan plot shows a positive posterior probability of 82% and a negative posterior probability of 15%. This study establishes an academic basis for the swift identification, mitigation, and control of silicosis through scientific approaches. The assessed biomarkers offer precision and dependability in silicosis diagnosis, opening novel paths for early detection and intervention, thereby mitigating the disease burden associated with silicosis.

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation. The expression of Atox1 was significantly diminished following TBI, while mice with overexpressed Atox1 exhibited a more preserved hippocampal structure and reduced levels of oxidative stress post-TBI. Furthermore, the mice displayed notable impairments in learning and memory functions after TBI, which were ameliorated by the overexpression of Atox1. In the stretch injury model of HT-22 cells, overexpression of Atox1 mitigated oxidative stress by preserving the normal morphology and network connectivity of mitochondria, as well as facilitating the elimination of damaged mitochondria. Mechanistically, co-immunoprecipitation and mass spectrometry revealed the binding of Atox1 to DJ-1. Knockdown of DJ-1 in HT-22 cells significantly impaired the antioxidant capacity of Atox1. Mutations in the copper-binding motif or sequestration of free copper led to a substantial decrease in the interaction between Atox1 and DJ-1, with overexpression of DJ-1 failing to restore the antioxidant capacity of Atox1 mutants. The findings suggest that DJ-1 mediates the ability of Atox1 to withstand oxidative stress. And targeting Atox1 could be a potential therapeutic approach for addressing post-traumatic neurological dysfunction.

The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.

Mutations in CHCHD2 have been reported to be associated with familial Parkinson’s disease (PD). We generated a human induced pluripotent stem cell (hiPSC) line by reprogramming dermal fibroblasts from a PD patient harboring a novel CHCHD2 mutation (c.434G > A, p.R145Q). This line exhibited human embryonic stem cell (hESC)-like clonal morphology, expression of undifferentiated stem cell markers, a normal karyotype and trilineage differentiation capacity and thus the potential to serve as a model for further investigating the underlying molecular mechanisms of CHCHD2 function in PD.

Due to their simple hardware, sensor nodes in IoT are vulnerable to attack, leading to data routing blockages or malicious tampering, which significantly disrupts secure data collection. An Intelligent Active Probing and Trace-back Scheme for IoT Anomaly Detection (APTAD) is proposed to collect integrated IoT data by recruiting Mobile Edge Users (MEUs). (a) An intelligent unsupervised learning approach is used to identify anomalous data from the collected data by MEUs and help to identify anomalous nodes. (b) Recruit MEUs to trace back and propose a series of trust calculation methods to determine the trust of nodes. (c) The last, the number of active detection packets and detection paths are designed, so as to accurately identify the trust of nodes in IoT at the minimum cost of the network. A large number of experimental results show that the recruiting cost and average anomaly detection time are reduced by 6.5 times and 34.33% respectively, while the accuracy of trust identification is improved by 20%.

With the increasing frequency of extreme convective weather, the spatial–temporal variability of rainfall becomes more diversified. As a result of the insufficient quality of rainfall monitoring data in mountainous areas, the flash flood simulation usually does not consider the effect of the rainfall center location. In this work, the GPU Accelerated Surface Water Flow and Associated Transport hydrodynamic model is used to simulate the flash flood discharge process. The effect of the rainfall center location and the basin scale on the discharge process were analyzed based on simulated data. The results show that when the rainfall center is in the upstream and midstream basins, because of gravitational potential energy conversion, the total flood volume and the flood peak discharge increase to 2–10 times, and the peak time of flash flood caused by 100 mm rainfall amount can be advanced by up to 3,000 s compared to the 20 mm rainfall amount condition. The peak discharge and the delay of peak time increase with the increase of rain peak coefficient. In addition, the increase of the basin area enhances the effect of the rainfall center location. This work is helpful to quantify the effect of the rainfall center location, which can clarify the uncertainty of flash flood simulation caused by not considering the rainfall center factor. HIGHLIGHTS When the rainfall center is in the upstream and midstream basins, the total flood volume and the peak discharge increase to about 2–10 times, the flood peak time can be advanced by 3,000 s.; The flood peak discharge increases with the increase of the rain peak coefficient, while the delay of the flood peak time is longer.; The increase of the basin area enhances the effect of the rainfall center location on flash flood.;

Highlights A stable Zn anode was obtained by patterning Zn foil surfaces and endowing a zincphilic interface in microchannels. The accumulation of electrons in the microchannel and the zincphilic interface promoted preferential heteroepitaxial Zn deposition in the microchannel region and subsequent homoepitaxial Zn deposition on the array surface. The Zn symmetrical cells could undergo repeated plating/stripping for more than 25,000 cycles at the current densities of 10 and 20 mA cm−2.

Abstract The coding privilege of end-spectral hues (red and blue) in the early visual cortex has been reported in primates. However, the origin of such bias remains unclear. Here, we provide a complete picture of the end-spectral bias in visual system by measuring fMRI signals and spiking activities in macaques. The correlated end-spectral biases between the LGN and V1 suggest a subcortical source for asymmetric coding. Along the ventral pathway from V1 to V4, red bias against green peaked in V1 and then declined, whereas blue bias against yellow showed an increasing trend. The feedforward and recurrent modifications of end-spectral bias were further revealed by dynamic causal modeling analysis. Moreover, we found that the strongest end-spectral bias in V1 was in layer 4C $$\beta$$ β . Our results suggest that end-spectral bias already exists in the LGN and is transmitted to V1 mainly through the parvocellular pathway, then embellished by cortical processing.

Abstract Transdermal drug delivery is of vital importance for medical treatments. However, user adherence to long-term repetitive drug delivery poses a grand challenge. Furthermore, the dynamic and unpredictable disease progression demands a pharmaceutical treatment that can be actively controlled in real-time to ensure medical precision and personalization. Here, we report a spatiotemporal on-demand patch (SOP) that integrates drug-loaded microneedles with biocompatible metallic membranes to enable electrically triggered active control of drug release. Precise control of drug release to targeted locations (

Regular exercise is known to confer various health benefits, but the specific impact of exercise intensity on antioxidant capacity and immune function remains complex and incompletely understood. Our study investigates the impact of exercise intensity on antioxidant capacity and immune function in mice. Mice were subjected to various exercise intensities (low, moderate, high) on a treadmill. Antioxidant enzyme activity, oxidative stress markers, ROS production, hemoglobin, hematocrit, leukocyte counts, lymphocyte subsets, and phagocytic activities were assessed. Exercise intensity influenced antioxidant enzyme activity, with low and high intensities showing significant effects. High-intensity exercise led to increased lipid peroxidation but improved the glutathione redox ratio. Exercise, irrespective of intensity, significantly affected immune function, notably increasing leukocyte counts, T-cell and B lymphocyte subsets, and phagocytic activities. Even at lower intensities, exercise profoundly impacts antioxidant capacity and immune function. These findings highlight the relationship between exercise, oxidative stress, and immune modulation.

Abstract Retinitis pigmentosa is an inherited photoreceptor degeneration that begins with rod loss followed by cone loss. This cell loss greatly diminishes vision, with most patients becoming legally blind. Gene therapies are being developed, but it is unknown how retinal function depends on the time of intervention. To uncover this dependence, we utilize a mouse model of retinitis pigmentosa capable of artificial genetic rescue. This model enables a benchmark of best-case gene therapy by removing variables that complicate answering this question. Complete genetic rescue was performed at 25%, 50%, and 70% rod loss (early, mid and late, respectively). Early and mid treatment restore retinal output to near wild-type levels. Late treatment retinas exhibit continued, albeit slowed, loss of sensitivity and signal fidelity among retinal ganglion cells, as well as persistent gliosis. We conclude that gene replacement therapies delivered after 50% rod loss are unlikely to restore visual function to normal. This is critical information for administering gene therapies to rescue vision.

Large-scale urban water distribution network simulation plays a critical role in the construction, monitoring, and maintenance of urban water distribution systems. However, during the simulation process, matrix inversion calculations generate a large amount of computational data and consume significant amounts of time, posing challenges for practical applications. To address this issue, this paper proposes a parallel gradient calculation algorithm based on GPU hardware and the CUDA Toolkit library and compares it with the EPANET model and a model based on CPU hardware and the Armadillo library. The results show that the GPU-based model not only achieves a precision level very close to the EPANET model, reaching 99% accuracy, but also significantly outperforms the CPU-based model. Furthermore, during the simulation, the GPU architecture is able to efficiently handle large-scale data and achieve faster convergence, significantly reducing the overall simulation time. Particularly in handling larger-scale water distribution networks, the GPU architecture can improve computational efficiency by up to 13 times. Further analysis reveals that different GPU models exhibit significant differences in computational efficiency, with memory capacity being a key factor affecting performance. GPU devices with larger memory capacity demonstrate higher computational efficiency when processing large-scale water distribution networks. This study demonstrates the advantages of GPU acceleration technology in the simulation of large-scale urban water distribution networks and provides important theoretical and technical support for practical applications in this field. By carefully selecting and configuring GPU devices, the computational efficiency of large-scale water distribution networks can be significantly improved, providing more efficient solutions for future urban water resource management and planning.

Pelvic organ prolapse (POP) is a benign disease characterized by the descent of pelvic organs due to weakened pelvic floor muscles and fascial tissues. Primarily affecting elderly women, POP can lead to various urinary and gastrointestinal tract symptoms, significantly impacting their quality of life. The pathogenesis of POP predominantly involves nerve–muscle damage and disorders in the extracellular matrix metabolism within the pelvic floor. Recent studies have indicated that genetic factors may play a crucial role in this condition. Focusing on linkage analyses, single-nucleotide polymorphisms, genome-wide association studies, and whole exome sequencing studies, this review consolidates current research on the genetic predisposition to POP. Advances in epigenetics are also summarized and highlighted, aiming to provide theoretical recommendations for risk assessments, diagnoses, and the personalized treatment for patients with POP.

The Epichloë genus represents a significant group of above-ground endophytes extensively researched for their potential applications in agriculture and ecology. Additionally, Epichloë species synthesize bioactive alkaloids, which generally cause health problems in livestock and have detrimental effects on the performance of insect herbivores. Psathyrostachys lanuginosa serves as a valuable forage grass for livestock owing to its high nutritional value and resilience in adverse environmental conditions. Nevertheless, to date, no reports have documented Epichloë as endophytes of P. lanuginosa. In this study, four strains (PF5, PF9, QG2, and QG4) were isolated and identified through morphological, molecular, and phylogenetic analyses as endophytes of P. lanuginosa. Morphological analysis indicated colony characteristics and conidia features consistent with symbiotic Epichloë, with no significant differences observed in growth rates or conidia dimensions among the four strains. Phylogenetic analysis confirmed all strains as E. bromicola. Additionally, alkaloid biosynthetic genes were detected, revealing differences in the potential synthesis of peramine and indole diterpenoid alkaloids among strains from different geographic origins. However, all four E. bromicola strains exhibited similar potential for synthesizing ergot alkaloids, but not loline alkaloids. Overall, this study identified P. lanuginosa as a novel host for E. bromicola and provided insights into the alkaloid profiles of these strains, laying a solid foundation for the scientific and rational utilization of Epichloë resources.

Abstract Vascular calcification is a strong predictor of cardiovascular events. Essential metals play critical roles in maintaining human health. However, the association of essential metal levels with risk of aortic arch calcification (AoAC) remains unclear. We measured the plasma concentrations of nine essential metals in a cross‐sectional population and evaluated their individual and combined effects on AoAC risk using multiple statistical methods. We also explored the mediating role of fasting glucose. In the logistic regression model, higher quartiles of magnesium and copper were associated with the decreased AoAC risk, while higher quartile of manganese was associated with higher AoAC risk. The least absolute shrinkage and selection operator penalized regression analysis identified magnesium, manganese, calcium, cobalt, and copper as key metals associated with AoAC risk. The weighted quantile sum regression suggested a combined effect of metal mixture. A linear and positive dose–response relationship was found between manganese and AoAC in males. Moreover, blood glucose might mediate a proportion of 9.38% of the association between manganese exposure and AoAC risk. In summary, five essential metal levels were associated with AoAC and showed combined effect. Fasting glucose might play a significant role in mediating manganese exposure‐associated AoAC risk.

IntroductionThis study used Bacillus amyloliquefaciens DGL1 isolated from the arid sandy land of the Qinghai–Tibetan Plateau as the research strain and investigated the effects of DGL1 on the biomass, physiology, and metabolites of Medicago sativa under different intensities of drought stress to provide a high-quality bacterial source and a theoretical basis for the research and development of biological fertilizer suitable for arid areas.MethodsThe exopolysaccharides (EPS), 1-Aminocyclopropane-1-carboxylate deaminase (ACC), and phosphorus solubilizing capacity of DGL1 were determined. The effects of a DGL1 suspension on alfalfa biomass, physiological indexes, degree of peroxidation of cell membranes, and activity of antioxidant enzymes were determined after irrigating roots under drought stress. The effects on soil physicochemical properties were also evaluated, and metabolomics analysis was performed to explore the effect of DGL1 on the metabolites of alfalfa under drought stress.ResultsStrain DGL1 produced extracellular polysaccharide EPS and ACC deaminase and was capable of phosphorus solubilization. Treatment with DGL1 increased the biomass of alfalfa under different degrees of drought stress, significantly increased the activities of alfalfa antioxidant enzymes Super Oxide Dismutase (SOD), Peroxidase (POD), and catalase (CAT), reduced the content of MDA and H2O2, and increased the content of quick-acting phosphorus, quick-acting potassium, ammonium nitrogen, and nitrate nitrogen in the soil, thus improving soil fertility. Through metabolomics analysis, DGL1 was shown to affect amino acid metabolic pathways, such as arginine, leucine, glutamate, and tyrosine, as well as the levels of energy-providing polysaccharides and lipids, in alfalfa under 15% PEG-6000 drought stress, enhancing alfalfa’s capacity to resist drought stress.DiscussionStrain DGL1 enhances the drought suitability of alfalfa and has the potential for dryland development as a biological agent.

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. In the brain, no detectable viral RNA and minimal residential immune cell activation was observed in the surviving mice post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and gene expression levels associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent systemic T helper 1 prone cellular immune responses and strong sera neutralizing antibodies against Delta and Omicron variants months post-acute infection. Overall, our findings suggest that infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long-COVID patients and provides new insights into the role of systemic and brain residential immune factors in PASC pathogenesis.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease, with a complex pathogenesis and an irreversible course. Therefore, the early diagnosis of AD is particularly important for the intervention, prevention, and treatment of the disease. Based on the different pathophysiological mechanisms of AD, the research progress of biofluid biomarkers are classified and reviewed. In the end, the challenges and perspectives of future research are proposed.

IntroductionBacillus amyloliquefaciens DGL1, isolated from the arid sandy areas in Dagler, Qinghai Province, China, promotes the growth of Avena sativa variety “Qing Yan 1”.MethodsTo elucidate the transcriptomic changes in the oat root system following interaction with DGL1 and to reveal the molecular mechanism by which DGL1 promotes oat growth, treatment and control groups of oat roots at 2, 4, 8, and 12 h after inoculation with a suspension of strain DGL1 were analyzed using Illumina high-throughput transcriptome sequencing technology. The differentially expressed genes were determined through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the metabolic pathways and key genes were analyzed.ResultsThe results showed that 7874, 13,392, 13,169, and 19,026 differentially expressed genes were significantly enriched in the glycolysis/gluconeogenesis pathway, amino acid metabolism, nitrogen metabolism, plant hormone signal transduction, and other related metabolic pathways in the oat roots at 2, 4, 8, and 12 h after inoculation with a DGL1 suspension. The GO and KEGG enrichment analyses revealed that the genes encoding plasma membrane ATPase, phosphoglycerate kinase gene PGK, ammonium transporter protein gene AMT, cellulose synthase gene CSLF6, and growth hormone response family gene IAA18 were significantly upregulated.DiscussionIt is hypothesized that the pro-growth mechanism of strain DGL1 in oats is the result of the coordination of multiple pathways through the promotion of oat energy metabolism, phytohormone signaling, secondary metabolite synthesis, and amino acid metabolism.

ABSTRACTIdentification and the time since deposition (TsD) estimation of body fluid stains from a crime scene could provide valuable information for solving the cases and are always difficult for forensics. Microbial characteristics were considered as a promising biomarker to address the issues. However, changes in the microbiota may damage the specific characteristics of body fluids. Correspondingly, incorrect body fluid identification may result in inaccurate TsD estimation. The mutual influence is not well understood and limited the codetection. In the current study, saliva, semen, vaginal secretion, and menstrual blood samples were exposed to indoor conditions and collected at eight time points (from fresh to 30 days). High-throughput sequencing based on the 16S rRNA gene was performed to characterize the microbial communities. The results showed that a longer TsD could decrease the discrimination of different body fluid stains. However, the accuracies of identification still reached a quite high value even without knowing the TsD. Correspondingly, the mean absolute error (MAE) of TsD estimation significantly increased without distinguishing the types of body fluids. The predictive TsD of menstrual blood reached a quite low MAE (1.54 ± 0.39 d). In comparison, those of saliva (6.57 ± 1.17 d), semen (6.48 ± 1.33 d), and vaginal secretion (5.35 ± 1.11 d) needed to be further improved. The great effect of individual differences on these stains limited the TsD estimation accuracy. Overall, microbial characteristics allow for codetection of body fluid identification and TsD estimation, and body fluids should be identified before estimating TsD in microbiome-based stain analyses.IMPORTANCEEmerged evidences suggest microbial characteristics could be considered a promising tool for identification and time since deposition (TsD) estimation of body fluid stains. However, the two issues should be studied together due to a potential mutual influence. The current study provides the first evidence to understand the mutual influence and determines an optimal process for codetection of identification and TsD estimation for unknown stains for forensics. In addition, we involved aged stains into our study for identification of body fluid stains, rather than only using fresh stains like previous studies. This increased the predictive accuracy. We have preliminary verified that individual differences in microbiotas limited the predictive accuracy of TsD estimation for saliva, semen, and vaginal secretion. Microbial characteristics could provide an accurate TsD estimation for menstrual blood. Our study benefits the comprehensive understanding of microbiome-based stain analyses as an essential addition to previous studies.

Human–robot interaction (HRI) has escalated in notability in recent years, and multimodal communication and control strategies are necessitated to guarantee a secure, efficient, and intelligent HRI experience. In spite of the considerable focus on multimodal HRI, comprehensive disquisitions delineating various modalities and intricately analyzing their combinations remain elusive, consequently limiting holistic understanding and future advancements. This article aspires to bridge this inadequacy by conducting a profound exploration of multimodal HRI, predominantly concentrating on four principal modalities: vision, auditory and language, haptics, and physiological sensing. An extensive review encapsulating algorithmic dissection, interface devices, and applicative dimensions forms part of this discourse. This manuscript distinctively combines multimodal HRI with cognitive science, deeply probing into the three dimensions, perception, cognition, and action, thereby demystifying algorithms intrinsic to multimodal HRI. Finally, it accentuates the empirical challenges and contours preemptive trajectories for multimodal HRI in human‐centric smart manufacturing.