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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 Background Winter rapeseed, the sole overwintering oilseed crop in northern China, emphasizes winter resilience, yet epigenetic regulatory mechanisms governing overwintering memory remain poorly understood. Results In this study, the root collar tissues from the robust cold-resistant variety Longyou-7 were sampled during the pre-winter period (S1), overwintering periods (S2–S5), and re-greening period (S6), to analyze overall genomic DNA methylation levels using high-performance liquid chromatography (HPLC). The result showed that DNA methylation level exceeded 80% in the S1 stage. Throughout the overwintering periods, methylation levels displayed a decreasing trend in S3, followed by an increase in S5, and a pronounced decrease in S6. Consequently, S1, S3, S5, and S6 periods were chosen for whole-genome bisulfite sequencing analyses to elucidate the overwintering memory mechanisms of Longyou-7. The result revealed that DNA methylation primarily occurs in the CG context in Longyou-7. However, methylation of mC sites is most prevalent in the CHH type, gradually decreasing during overwintering periods. Analysis of methylation patterns in specific genomic regions of Longyou-7 showed that the highest methylation levels in the intergenic region. Moreover, mC sites in repeats and transposon elements are distributed differently across the three contexts. Subsequently, differentially methylated regions and promoters of Longyou-7 were identified during various periods compared to the S1 stage, followed by joint analysis with transcriptome sequencing. Functional enrichment analysis highlighted the involvement of most overlapping genes in the MAPK signaling pathway, plant hormone signal transduction, and starch and sucrose metabolism pathways. Changes in candidate gene expression within these three pathways correlated closely with DNA methylation levels. Conclusions Our findings underscored the critical role of DNA methylation in regulating the expression of overwintering memory genes in winter rapeseed. These results offer a comprehensive insights into the epigenetic regulatory mechanisms governing winter rapeseed's overwintering memory, while identified overwintering memory genes served as crucial genetic resources for multifaceted breeding of winter-resistant varieties. Graphical Abstract

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 Machine learning potential (MLP) has been a popular topic in recent years for its capability to replace expensive first-principles calculations in some large systems. Meanwhile, message passing networks have gained significant attention due to their remarkable accuracy, and a wave of message passing networks based on Cartesian coordinates has emerged. However, the information of the node in these models is usually limited to scalars, and vectors. In this work, we propose High-order Tensor message Passing interatomic Potential (HotPP), an E(n) equivariant message passing neural network that extends the node embedding and message to an arbitrary order tensor. By performing some basic equivariant operations, high order tensors can be coupled very simply and thus the model can make direct predictions of high-order tensors such as dipole moments and polarizabilities without any modifications. The tests in several datasets show that HotPP not only achieves high accuracy in predicting target properties, but also successfully performs tasks such as calculating phonon spectra, infrared spectra, and Raman spectra, demonstrating its potential as a tool for future research.

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.

Objective: Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss. Methods: To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed in vitro. Results: CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68+ macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163. Conclusion: Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.

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 Background Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. Methods db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein–protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. Results In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P

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.

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.

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

Diminished testosterone levels have been documented as a key factor in numerous male health disorders. Both human and animal studies have consistently demonstrated that cadmium (Cd), a pervasive environmental heavy metal, results in decreased testosterone levels. However, the exact mechanism through which Cd interferes with testosterone synthesis remains incompletely elucidated. This research sought to examine the impact of cellular senescence on Cd-suppressed testosterone synthesis. We also investigated the related m6A modification mechanism. The results demonstrated that Cd (100 mg/L) led to a decrease in testosterone levels, along with downregulated expression of testosterone synthase in C57BL/6 N male mice. Furthermore, Cd significantly increased β-galactosidase staining intensity, senescence-related proteins, and senescence-related secretory phenotypes in mouse testicular Leydig cells. Subsequent investigations revealed that Cd decreased the mRNA and protein levels of NAD-dependent deacetylase Sirtuin-1 (SIRT1) in Leydig cells. Mechanistically, mice treated with resveratrol (50 mg/kg), a specific SIRT1 activator, mitigated Leydig cell senescence and reversed Cd-reduced testosterone levels in mouse testes. These effects were also restored by SIRT1 overexpression in Leydig cells. Additionally, we found that Cd increased the level of methyltransferase enzyme METTL3 and Sirt1 m6A modification in Leydig cells. Mettl3 siRNA effectively restored Cd-enhanced Sirt1 m6A level and reversed Cd-downregulated Sirt1 mRNA expression in Leydig cells. Overall, our findings suggest that Cd exposure inhibits testosterone synthesis via Sirt1 m6A modification-mediated senescence in mouse testes. These results offer an experimental basis for investigating the causes and potential treatments of hypotestosteronemia induced by environmental factors.

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.

Delirium is an acute, global cognitive disorder syndrome, also known as acute brain syndrome, characterized by disturbance of attention and awareness and fluctuation of symptoms. Its incidence is high among critically ill patients. Once patients develop delirium, it increases the risk of unplanned extubation, prolongs hospital stay, increases the risk of nosocomial infection, post-intensive care syndrome-cognitive impairment, and even death. Therefore, it is of great importance to understand how delirium occurs and to reduce the incidence of delirium in critically ill patients. This paper reviews the potential pathophysiological mechanisms of delirium in critically ill patients, with the aim of better understanding its pathophysiological processes, guiding the formulation of effective prevention and treatment strategies, providing a basis for clinical medication.

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.

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.

ABSTRACTLaser surface texturing (LST) with different patterns was performed on silicon nitride (Si3N4) ceramic. Effect of patterns created by LST on coefficient of friction (COF) and surface damage under dry friction was investigated. Results indicated that fluctuation of COF decreased with the increasing loading force for both un-textured and textured samples. Under the same loading force, COF of Si3N4 ceramic with textured patterns was more stable than the samples with smoothly finished surface. The COF of textured samples was not always lower than that of un-textured samples. This may be caused by differences in the distribution of debris and the continuity of surface contact. The worn surface existed damages of plow and crack. However, peeling was observed on un-textured samples only. The surface damage of textured samples was slighter than un-textured samples. Especially under the high loading force, catastrophic damage appeared on the smooth surface. The worn surface of textured samples still maintained the similar state. This could be mainly due to the more complex friction process on the surface of textured sample. The wear rate of the frictional pair was also studied. The mechanisms of friction process for smooth and textured surface were analyzed.

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.

Triterpenoids widely exist in nature, displaying a variety of pharmacological activities. Determining triterpenoids in different matrices, especially in biological samples holds great significance. High-performance liquid chromatography (HPLC) has become the predominant method for triterpenoids analysis due to its exceptional analytical performance. However, due to the structural similarities among botanical samples, achieving effective separation of each triterpenoid proves challenging, necessitating significant improvements in analytical methods. Additionally, triterpenoids are characterized by a lack of ultraviolet (UV) absorption groups and chromophores, along with low ionization efficiency in mass spectrometry. Consequently, routine HPLC analysis suffers from poor sensitivity. Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance. Considering the structural characteristics of triterpenoids, various derivatization reagents such as acid chlorides, rhodamines, isocyanates, sulfonic esters, and amines have been employed for the derivatization analysis of triterpenoids. This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids. Moreover, the limitations and challenges encountered in previous studies are discussed, and future research directions are proposed to develop more effective derivatization methods.

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.

Dihydrotanshinone I (DHT), a lipophilic compound extracted from Salvia miltiorrhiza, has cardiovascular protective effects, but the underlying molecular mechanisms of action have rarely been reported. Based on this, whether DHT affects cholesterol metabolism by regulating LDLR is investigated in this work. The results revealed that DHT can increase LDLR expression and promote LDL uptake by HepG2 cells. Meanwhile, DHT stabilizes LDLR mRNA expression by activating the epidermal growth factor receptor/extracellular signal-regulated kinase 1/2 (EGFR/erk1/2) signaling pathway. In addition, DHT inhibits the expression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) by down-regulating the liver nuclear transcription factor 1 A (HNF1A) and up-regulating the forkhead box O3 (FOXO3). All of these indicate that DHT increases LDLR expression at the post-transcriptional and post-translational levels thereby promoting LDL-C metabolism. The potential mechanism of DHT to improve lipid metabolism has been revealed as a promising drug against AS.

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.

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.

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. The progressive damage to glomeruli, tubules, and interstitium in the kidneys can lead to the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Most of the energy we need comes from mitochondria. Mitochondria are best known as the sites for production of respiratory ATP and are essential for eukaryotic life. The pathogenesis of DN involves a variety of factors, such as altered haemodynamics, oxidative stress, and inflammation, and studies from animal models suggest that mitochondrial dysfunction plays an important role in the development of DN. Traditional Chinese medicine (TCM) has a history of more than 2,500 years and has rich experience and remarkable efficacy in the treatment of DN. Recent studies have found that TCM may have great potential in regulating mitochondrial dysfunction in the treatment of DN. This review will elucidate the main causes of mitochondrial dysfunction and the relationship with DN, and explore in depth the potential mechanisms of TCM to protect the kidney by improving mitochondrial dysfunction. Current pharmacological treatments for patients with DN do not prevent the inevitable progression to ESRD. With the rich variety of Chinese herbs, TCM is expected to be the most promising candidate for the treatment of DN as we continue to learn more about the mechanisms of DN and incorporate the current advances in extraction techniques.