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Abstract Sustainable photoactivated room temperature phosphorescent materials exhibit great potential but are difficult to obtain. Here, we develop photoactivated room temperature phosphorescent materials by covalently attaching lignin to polylactic acid, where lignin and polylactic acid are the chromophore and matrix, respectively. Initially the phosphorescence of the lignin is quenched by residual O2. However, the phosphorescence is switched on when the residual oxygen is consumed by the triplet excitons of lignin under continuous UV light irradiation. As such, the lifetime increases from 3.0 ms to 221.1 ms after 20 s of UV activation. Interestingly, the phosphorescence is quenched again after being kept under an atmosphere of air for 2 h in the absence of UV irradiation due to the diffusion of oxygen into the materials. Using these properties, as-developed material is successfully used as a smart anti-counterfeiting logo for a medicine bottle and for information recording.

Abstract Artificial intelligence transforms drug discovery, with phenotype-based approaches emerging as a promising alternative to target-based methods, overcoming limitations like lack of well-defined targets. While chemical-induced transcriptional profiles offer a comprehensive view of drug mechanisms, inherent noise often obscures the true signal, hindering their potential for meaningful insights. Here, we highlight the development of TranSiGen, a deep generative model employing self-supervised representation learning. TranSiGen analyzes basal cell gene expression and molecular structures to reconstruct chemical-induced transcriptional profiles with high accuracy. By capturing both cellular and compound information, TranSiGen-derived representations demonstrate efficacy in diverse downstream tasks like ligand-based virtual screening, drug response prediction, and phenotype-based drug repurposing. Notably, in vitro validation of TranSiGen’s application in pancreatic cancer drug discovery highlights its potential for identifying effective compounds. We envisage that integrating TranSiGen into the drug discovery and mechanism research holds significant promise for advancing biomedicine.

Abstract Proton cyclotron waves (PCWs) upstream of Mars are thought to be associated with the instabilities of pickup ions. The instabilities of pickup ions of ring distributions have larger maximum growth rates compared with beam distributions. However, observations revealed a notably‐reduced occurrence rate of PCWs for pickup ions of ring distributions. Linear instability analysis and a corresponding two‐dimensional particle‐in‐cell (PIC) simulation are performed to investigate the instabilities of pickup ion ring distributions upstream of Mars. Linear instability analysis indicates that a pickup ion ring distribution is unstable to the ion cyclotron, ion Bernstein, and mirror instabilities. The corresponding PIC simulation confirms the linear analysis results and further demonstrates that the pickup ions are scattered toward an isotropic shell distribution by the waves excited. Interestingly, the saturation energy of the waves is much lower than that driven by a corresponding pickup ion beam distribution, and mirror waves eventually dominate the system.

The onset of drug resistance in advanced cancer patients markedly diminishes their prognosis. Recently, disulfidptosis, a novel form of cell death, has been identified, triggered by excessive disulfide formation leading to cell shrinkage and F-actin contraction. Previous studies have identified 15 essential genes (FLNA, FLNB, MYH9, TLN1, ACTB, MYL6, MYH10, CAPZB, DSTN, IQGAP1, ACTN4, PDLIM1, CD2AP, INF2, SLC7A11) associated with disulfidptosis. This study sourced pan-cancer mRNA expression data from Xena to thoroughly evaluate the molecular and clinical characteristics of disulfidptosis-related genes. Through unsupervised clustering, mRNA expression data identified the expression levels of disulfidptosis-related genes and potential clusters related to this form of cell death. Kaplan-Meier survival curves illustrated the correlation between different clusters and overall survival. The findings reveal that high expression of disulfidptosis-related genes is linked to poor survival in liver cancer. The GDSC database was utilized to analyze the relationship between disulfidptosis-related genes and the AUC of 198 drugs. The results demonstrate that 12 disulfidptosis-related genes influence sorafenib resistance, as revealed by the intersection of differential genes related to sorafenib resistance from the GSE109211 dataset. Among them, the MYH9 gene was found to play a crucial role in both. Finally, experimental evidence confirmed that MYH9 mitigates sorafenib resistance in hepatocellular carcinoma through disulfidptosis-like changes. This study identifies disulfidptosis as a promising avenue for enhancing the sensitivity of tumor cells to drugs, offering new therapeutic perspectives for future research on disulfidptosis and drug resistance in cancer patients.

Soy milk, rich in vitamin D and calcium, is a common alternative to dairy milk. However, its distinct 'beany off-flavor' has limited its acceptance, particularly in Western countries. A new technique employing preformed 'empty' V-type starch has been introduced to scavenge this off-flavor, aiming to promote soy milk consumption. The purpose of this study was to identify predictors of consumers' purchase intention of 'empty' V-type starch deodorized soy milk, particularly among college students. In this cross-sectional study, 105 college students were surveyed by a validated survey instrument that measures their perceptions of sensory quality, healthiness, price, environmental friendliness, food safety, and purchase intention of a novel product – 'empty' V-type starch deodorized soy milk. Additionally, demographic data were gathered to understand any correlations between these factors and the students' willingness-to-purchase of the deodorized soy milk. From the results, more than 80% of the participants expressed a positive attitude toward the 'empty' V-type starch-deodorized soy milk. The two dominant drivers behind their purchasing decision were Sensory Quality and Environmental Concern. Accordingly, it is crucial to highlight the improved sensory profile and the environmental friendliness of this soy milk product in order to achieve marketing success.

Objective: To study the relation between adult vertebral bone mineral density (BMD) and gender and age in Foshan, to explore the average BMD of each age group and osteoporosis (OP) incidence distribution in the region. Methods: Quantitative computed tomography (QCT) was used to examine and record the vertebral BMD of 1065 (male 648, female 417) healthy adults who underwent physical examination in Foshan Hospital of TCM from October 2021 to March 2023, and grouped according to age, T test and variance analysis were used on BMD in different sex and age group. Chi square analysis and correlation analysis were used on the incidence of OP in different sex and age group. Results: There was significant difference in the BMD between male and female of 20~29, 30~39, 40~49 and 60~69, 70~79 years old, women had higher peak BMD than man in young to middle age. In the male groups of 40~49、50~59, 60~69, 70~79 and female groups of 30~39, 40~49, 50~59, 60~69 years old, there were also significant differences in BMD in different age groups of the same sex, and decreased with age. There was significant difference in the incidence of OP between different age groups in the male and female groups. Age was positively related to the incidence of OP (r=0.517 for male and r=0.636 for female). Conclusion: The vertebral BMD derived from QCT for healthy adults in Foshan are associated with sex and age, peaked at 20~29 years old, and decreased with age. The incidence of OP for male and female increased with age from 40~49 years old.

ObjectiveThe primary objective of this study was to assess the impact of high-intensity deep squat training integrated with various blood flow restriction (BFR) modalities on the activation of lower limb and core muscles.MethodsA randomized, self-controlled crossover experimental design was employed with 12 participants. The exercise protocol consisted of squat training at 75% of one-repetition maximum (1RM), performed in 3 sets of 8 repetitions with a 2-min inter-set rest period. This was conducted under four distinct BFR conditions: continuous low BFR (T1), intermittent medium BFR (T2), intermittent high BFR (T3), and a non-restricted control (C). Surface electromyography (EMG) was utilized to collect EMG signals from the target muscles during the BFR and squat training sessions. The root mean square (RMS) amplitude standard values were calculated for each squat set to quantify muscle activation levels, with these values expressed as a percentage of the maximum voluntary contraction (%MVC). Rating of Perceived Exertion was evaluated after each squat set, and leg circumference measurements were taken.Results1) During the first two sets of deep squats, the %MVC of the vastus lateralis and vastus medialis in all compression groups was significantly higher than that in the control group (p < 0.05). Furthermore, in the first set, the %MVC of the vastus lateralis in Group T3 was significantly higher than in Group T2 (p < 0.05). In the third set, the %MVC of the vastus medialis in Groups T1 and T3 was significantly lower than in the first two sets (p < 0.05). 2) Group T1 showed an increased activation of the biceps femoris and semitendinosus muscles in the second and third sets, with %MVC values significantly greater than in the first set (p < 0.05). Group T2 only showed an increase in biceps femoris activation in the third set (p < 0.05). Group T3 significantly increased the activation of the biceps femoris and semitendinosus muscles only in the first set (p < 0.05). 3) No significant differences were observed in the changes of rectus abdominis %MVC among the groups (p > 0.05). In the first set, Group T3’s erector spinae %MVC was significantly higher than the control group’s; in the second set, it was significantly higher than both Group T2 and the control group’s (p < 0.05). 4) After training, a significant increase in thigh circumference was observed in all groups compared to before training (p < 0.05). 5) For RPE values, Group T2’s post-squat values were significantly higher than the control group’s after all three sets (p < 0.05). Group T1’s RPE values were also significantly higher than the control group’s after the third set (p < 0.05). Groups T1, T2, and C all had significantly higher RPE values in the second and third sets compared to the first set (p < 0.05).ConclusionAll BFR modalities significantly enhanced the activation level of the anterior thigh muscles, with the continuous low BFR mode demonstrating a more stable effect. No significant differences were found in the activation level of the rectus abdominis among the groups. However, the intermittent high BFR mode was the most effective in increasing the activation level of the erector spinae muscles. While BFR did not further augment leg circumference changes, it did elevate subjective fatigue levels. The RPE was lowest during squatting under the intermittent high BFR condition.

Introduction: Inflammatory bowel disease (IBD) is a global health concern. Aloe-emodin (AE) has diverse pharmacological benefits, including anti-inflammatory effects. However, its role in IBD remains unclear, prompting our investigation of its regulatory effects and mechanisms in an IBD mouse model. Methods: We studied the therapeutic efficacy of AE in alleviating symptoms and modulating cytokine secretion in a murine model of dextran sulfate sodium (DSS)-induced colitis. BALB/c mice were administered DSS to induce colitis and were subsequently treated with varying doses of AE. Changes in body weight, fecal lipocalin-2 (LCN2) levels, colon tissue histology, and serum cytokine concentrations were evaluated to assess the effects of AE treatment. Additionally, 16 S rRNA sequencing was used to analyze alterations in the composition of the gut microbiota following AE intervention. Finally, the database was used to analyze the signaling pathways associated with IBD in AE and to detect the expression levels of interleukin (IL)-4 pathway using real-time quantitative reverse transcription PCR. Exogenous IL-4 was used in rescue experiments to observe its effects on the disease process of IBD under AE regulation. Results: AE treatment resulted in a dose-dependent mitigation of weight loss, reduction in fecal LCN2 levels, and amelioration of histological damage in DSS-induced colitis in mice. The levels of superoxide dismutase and catalase increased, whereas malondialdehyde decreased following AE treatment, indicating a dose-dependent alleviation of colitis symptoms. Furthermore, AE administration attenuated the secretion of pro-inflammatory cytokines, including IL-17, tumor necrosis factor-alpha (TNF-α), and chemokine ligand 1, while promoting the expression of anti-inflammatory cytokines IL-4 and IL-13. Analysis of the gut microbiota revealed that AE effectively suppressed the overgrowth of colitis-associated bacterial species and restored microbial homeostasis. Finally, we found that overexpression of IL-4 was able to reverse the therapeutic effect of AE for DSS-induced IBD. Conclusion: AE shows promise in alleviating colitis severity, influencing inflammatory cytokines, and modulating the gut microbiota in an IBD mouse model via the IL-4/IL-13 pathway, suggesting its potential as a natural IBD remedy.

Background The Yunnan section of the Nujiang River (YNR) Basin in the alpine-valley area is one of the most critical areas of debris flow in China. Methods We analyzed the applicability of three machine learning algorithms to model of susceptibility to debris flow—Random Forest (RF), the linear kernel support vector machine (Linear SVM), and the radial basis function support vector machine (RBFSVM)—and compared 20 factors to determine the dominant controlling in debris flow occurrence in the region. Results We found that (1) RF outperformed RBFSVM and Linear SVM in terms of accuracy, (2) topographic conditions were prerequisites, and geology, precipitation, vegetation, and anthropogenic influence were critical to forming debris flows. Also, the relative elevation difference was the most prominent evaluation factor of debris flow susceptibility, and (3) susceptibility maps based on RF’s debris flow susceptibility (DFS) showed that zones with very high susceptibility were distributed along the mainstream of the Nujiang River. These findings provide methodological guidance and reference for improvement of DFS assessment. It enriches the content of DFS studies in the alpine-valley areas.

Unopposed oestrogen is recognised as an inducer of endometrial cancer. Over the past 50 years, the effects of oestrogen on the endometrium and endometrial cancer have been a hot topic in the field of gynaecological oncology. In recent years, a series of studies by our team revealed that the non-genomic transcriptional effects of oestrogen can influence the progression of endometrial carcinoma by regulating calcium ions, suggesting that inhibiting calcium ion channel proteins could serve as an adjuvant therapy for endometrial cancer. In this review, we retrospectively summarise the sources of oestrogen in vivo, the effects of oestrogens on the uterus and endometrium, oestrogen signalling and the clinical application of oestrogen-related compounds, emphasising the significant role of oestrogen–calcium axis inhibition in adjuvant therapy for endometrial cancer.

Abstract. Background:. Steroid receptor-associated and regulated protein (SRARP) suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer. In endometrial cancer (EC), progesterone receptor (PR) signaling is crucial for responsiveness to progestin therapy. The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC. Methods:. Ribonucleic acid sequencing data from the Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium, and Gene Expression Omnibus were used to analyze the clinical significance of SRARP and its correlation with PR expression in EC. The correlation between SRARP and PR expression was validated in EC samples obtained from Peking University People's Hospital. SRARP function was investigated by lentivirus-mediated overexpression in Ishikawa and HEC-50B cells. Cell Counting Kit-8 assays, cell cycle analyses, wound healing assays, and Transwell assays were used to evaluate cell proliferation, migration, and invasion. Western blotting and quantitative real-time polymerase chain reaction were used to evaluate gene expression. The effects of SRARP on the regulation of PR signaling were determined by co-immunoprecipitation, PR response element (PRE) luciferase reporter assay, and PR downstream gene detection. Results:. Higher SRARP expression was significantly associated with better overall survival and disease-free survival and less aggressive EC types. SRARP overexpression suppressed growth, migration, and invasion in EC cells, increased E-cadherin expression, and decreased N-cadherin and Wnt family member 7A (WNT7A) expression. SRARP expression was positively correlated with PR expression in EC tissues. In SRARP-overexpressing cells, PR isoform B (PRB) was upregulated and SRARP bound to PRB. Significant increases in PRE-based luciferase activity and expression levels of PR target genes were observed in response to medroxyprogesterone acetate. Conclusions:. This study illustrates that SRARP exerts a tumor-suppressive effect by inhibiting the epithelial-mesenchymal transition via Wnt signaling in EC. In addition, SRARP positively modulates PR expression and interacts with PR to regulate PR downstream target genes.

Abstract Starch, especially its amylose component can form inclusion complex (IC) with various small molecules, such as flavor and aroma compounds. Complexation of flavor compounds using starch matrices is driven by the hydrophobic interaction and the successful complexation may increase the retention of flavor compounds. In the present study, thymol (2‐isopropyl‐5‐methylphenol) at two different concentrations was introduced into three types of V‐type crystalline starches that have different inner helical cavity size, namely V6h, V7, and V8, and the formed ICs were characterized by X‐ray diffraction (XRD) and differential scanning calorimetry (DSC). The encapsulation efficiency (EE), loading efficiency (LE), and retention profile were determined by gas chromatography‐mass spectrometry (GC‐MS). The results indicated that when preparing ICs using V6h high amylose maize starch (HAMS) at a starch/thymol mass ratio of 2:1, the helical cavity of V6h helices was expanded and resulted in the formation of V7 crystals. Such circumstance could be owing to the cyclic structure of thymol and caused the minor phase transition at T2 of around 110°C observed in DSC. While in other conditions, the complexation with thymol did not alter the structure of starch. The EE and LE results suggested that V6h‐type HAMS exhibits higher capability to encapsulate thymol compared to V7 and V8 HAMS. All ICs demonstrated potent flavor retention ability and retained more than 70% of thymol after 8 h treatment. This study suggested that preformed “empty” V‐type starch could act as a potential matrix to encapsulate thymol, and this encapsulation technology should enable targeted applications of thymol for food processing and formulation applications.

Abstract Multi‐layered plasmonic nanostructures are able to highly promote the near‐field confinement and effectively activate analytes, which are of predominate significance but are extremely challenging. Herein, the semi‐open Au core@carved AuAg multi‐shell superstructure nanoparticles (multi‐Au@Ag‐Au NPs, multi = mono, bi, tri, tetra, and penta) are reported with a high designability on electromagnetic field and capability of effectively capturing analytes. By controlling synthetic parameters such as the number of galvanic exchange and Ag growth, multi‐Au@Ag‐Au NPs are successfully obtained, with tunable layer numbers and asymmetric nanoholes. Due to collective plasmon oscillations of multi‐layered built‐in nanogaps, the electromagnetic field strength of a single penta‐Au@Ag‐Au entity reach 48841. More importantly, the penta‐Au@Ag‐Au NPs show a remarkable light‐harvesting capability, which is adaptive to different Raman lasers, supporting high‐diversity detection. Additionally, the structural specificity allows analytes to be sufficiently captured into interior hotspots, and further achieve highly sensitive detection with limit of detection down to 3.22 × 10−12 M. This study not only provides an effective pathway for integrating abundant hotspots and activating target molecules in single plasmonic superstructure, but stimulates advancements in SERS substrates for various applications.

Among the directional angle calculation models of Bluetooth 5.1, the rectangular hollow array offers the advantage of shorter sampling time due to its fewer elements compared to traditional planar arrays. However, the antimultipath algorithms suitable for traditional planar arrays cannot be applied to rectangular hollow arrays. Therefore, this study proposes a virtual array filling algorithm, wherein four virtual matrices are inserted into the hollow matrix to transform the array into a uniform rectangular array. This algorithm ensures translation invariance of the rectangular array, enabling the application of the antimultipath coherent source algorithm to a rectangular hollow array. An algorithm for reconstructing Toeplitz matrices in two-dimensional uniform planar arrays is also proposed. Through the analysis of the spatial spectrum and angle estimation results of various algorithms, the effectiveness of the signal angle of arrival estimation theory is verified.

Background: Acute intermittent porphyria (AIP) is a rare metabolic disorder that results from mutations in the gene encoding hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP follows an autosomal dominant inheritance pattern, but most carriers are asymptomatic. The clinical manifestations of AIP include acute attacks of abdominal pain and neuropsychiatric disturbances. The pathogenicity of novel HMBS variants identified in Chinese patients has not been well established.Objective: The article aims to identify the pathogenic mutation in an AIP patient and prove its pathogenicity through in vitro experiments.Methods: A 22-year-old female diagnosed with AIP participated in the study. Variant screening of her HMBS gene was carried out through Sanger sequencing. To ascertain the consequences of the newly discovered variant, we conducted in vitro experimentation targeting HMBS gene expression and enzymatic function. Additionally, protein structure analysis was performed. Cycloheximide treatment and UPF1-specific siRNA knockdown were employed to assess the impact of the mutation on the mechanism of non-sense-mediated mRNA decay (NMD).Results: A novel splice site variant in the HMBS gene (c.648_651+1delCCAGG) was detected in the patient, which caused aberrant mRNA splicing. In vitro experiments demonstrated that this variant significantly decreased the expression of HMBS. Further investigation confirmed that this decrease was due to NMD. Additionally, structural analysis indicated that this variant would destabilize the HMBS protein and impair its catalytic activity. To gain a comprehensive understanding of HMBS mutations in the context of AIP, we conducted a literature search on PubMed using the keywords ‘HMBS’ and ‘Acute intermittent porphyria’ from 2013 to 2023. This search yielded 19 clinical case reports written in English, which collectively described 220 HMBS gene mutations worldwide.Conclusion: The study identified and proved the pathogenicity of a novel splice site HMBS variant for the first time. Our results elucidated the pathological mechanism by which this mutation causes AIP through reducing HMBS expression and activity. These findings provide theoretical guidance for the diagnosis, treatment and genetic counseling of AIP patients.

One of the key properties of the kinetic energy penetrator is self-sharpening ability during penetration. In this work, twisted tungsten-fiber-reinforced Cu–Zn composites with varying volume fraction of twisting fibers are designed to optimize self-sharpening capacity. The high-strain-rate compression and penetration behavior of the composites are systematically investigated. It was shown that the penetrator made of partially twisted-tungsten -fiber has the best penetration properties, which is marked by a 57% increased penetration depth compared with the untwisted penetrator. This is attributed to the excellent self-sharpening capability, rendering the head of remnant acute. The self-sharpening capability of the partially-twisted composite originates from the mismatch of the mechanical behavior between the edge and center part of the material. In specific, the tungsten fibers of the edge part are prone to fracture under shear deformation. The different macro-structure and microstructure between center and edge of the composite is favored for excellent penetration performance.

Aroma compounds are low-molecular-weight organic volatile molecules and are broadly utilized in the food industry. However, due to their high volatility and evaporative losses during processing and storage, the stabilization of these volatile ingredients using encapsulation is a commonly investigated practice. Complexation of aroma compounds using starch inclusion complex could be a potential approach due to the hydrophobicity of the left-handed single helical structure. In the present study, we used starch of three different V-type structures, namely V6h, V7, and V8, to encapsulate six different aroma compounds, including 1-decanol (DN), cis-3-hexen-1-ol (HN), 4-allylanisole (AN), γ-decalactone (DA), trans-cinnamaldehyde (CA), and citral (CT). The formed inclusion complexes samples were characterized using complementary techniques, including X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The results showed that upon complexation with aroma compounds, all V-subtypes retained their original crystalline structures. However, different trends of crystallinity were observed for each type of the prepared inclusion complexes. Additionally, among three V-type starches, V6h-type starch formed inclusion complexes with aroma compounds most efficiently and promoted the formation of Form II complex. This study suggested that the structure of aroma compounds and the type of V starch could both affect the complexation properties.

Microbiologically influenced corrosion (MIC) caused by sulfate reducing bacteria (SRB) is a serious challenge in many industries, but biofilm greatly decreases the toxicity of bactericides to cell inside. d-amino acids are potential enhancers for bactericides due to their excellent performance on biofilm inhibition. However, the mechanism of d-amino acid cooperating with bactericides for MIC inhibition is still unknown. In this study, d-tyrosine（D-Tyr）and disoctyl dimethyl ammonium chloride (DDAC) were selected as the typical d-amino acid and bactericide, respectively, to evaluate their synergetic inhibition on the corrosion caused by Desulfovibrio vulgaris. D-Tyr obviously enhanced the role of DDAC in inhibiting corrosion with high corrosion inhibition efficiency at 77.23 %. The attachment of EPS and live cells on the coupon surface decreased in the presence of D-Try, leading to more cells directly exposed to DDAC. Besides, D-Try decreased the amount of live cells on the surface and thus reduced the utilization of Fe by SRB and corrosion current. Moreover, dead cells settling to the coupon surface may form a protective lay to retard the contact between live SRB and Fe, leading to slow cathode reaction and less corrosion. Therefore, D-Tyr can reduce the coverage of biofilm, thereby reducing its protective effect on SRB and achieving better corrosion inhibition effect. This work provides a new strategy for improving bactericides and inhibiting MIC.

Introduction: N6-methyladenosine (m6A) is an emerging epigenetic modification, which plays a crucial role in the development of cancer. Nevertheless, the underlying mechanism of m6A-associated proteins and m6A modification in gallbladder cancer remains largely unknown. Materials and methods: The Gene Expression Omnibus database and tissue microarray were used to identify the key m6A-related gene in gallbladder cancer. The function and mechanism of IGF2BP3 were further investigated by knockdown and overexpression techniques in vitro and in vivo. Results: We found that IGF2BP3 was elevated and correlated with poor prognosis in gallbladder cancer, which can be used as an independent prognostic factor for gallbladder cancer. IGF2BP3 accelerated the proliferation, invasion and migration of gallbladder cancer cells in vitro and in vivo. Mechanistically, IGF2BP3 interacted with and augmented the stability of CLDN4 mRNA by m6A modification. Enhancement of CLDN4 reversed the inhibitory effect of IGF2BP3 deficiency on gallbladder cancer. Furthermore, we demonstrated that IGF2BP3 promotes the activation of NF-κB signaling pathway by up-regulation of CLDN4. Overexpression of IGF2BP3 in gallbladder cancer cells obviously promoted the polarization of immunosuppressive phenotype in macrophages. Besides, Gallbladder cancer cells-derived IGF2BP3 up-regulated the levels of STAT3 in M2 macrophages, and promoted M2 polarization. Conclusions: We manifested IGF2BP3 promotes the aggressive phenotype of gallbladder cancer by stabilizing CLDN4 mRNA in an m6A-dependent manner and induces macrophage immunosuppressive polarization, which might offer a new theoretical basis for against gallbladder cancer.

Abstract Background Increasing research indicates that circular RNAs (circRNAs) play critical roles in the development of ulcerative colitis (UC). This study aimed to determine the role of circRNA CCND1 in UC bio-progression, which has been shown to be downregulated in UC tissues. Methods Reverse transcription quantitative polymerase chain reaction was used to determine the levels of circRNA CCND1, miR-142-5p, and nuclear receptor coactivator-3 (NCOA3) in UC tissues and in lipopolysaccharide (LPS)-induced Caco-2 cells. Target sites of circRNA CCND1 and miR-142-5p were predicted using StarBase, and TargetScan to forecast potential linkage points of NCOA3 and miR-142-5p, which were confirmed by a double luciferase reporter-gene assay. Cell Counting Kit 8 and flow cytometry assays were performed to assess Caco-2 cell viability and apoptosis. TNF-α, IL-1β, IL-6, and IL-8 were detected using Enzyme-Linked Immunosorbent Assay kits. Results CircRNA CCND1 was downregulated in UC clinical samples and LPS-induced Caco-2 cells. In addition, circRNA CCND1 overexpression suppressed LPS-induced apoptosis and inflammatory responses in Caco-2 cells. Dual-luciferase reporter-gene assays showed that miR-142-5p could be linked to circRNA CCND1. Moreover, miR-142-5p was found to be highly expressed in UC, and its silencing inhibited LPS-stimulated Caco-2 cell apoptosis and inflammatory responses. Importantly, NCOA3 was found downstream of miR-142-5p. Overexpression of miR-142-5p reversed the inhibitory effect of circRNA CCND1-plasmid on LPS-stimulated Caco-2 cells, and the effects of miR-142-5p inhibitor were reversed by si-NCOA3. Conclusion CircRNA CCND1 is involved in UC development by dampening miR-142-5p function, and may represent a novel approach for treating UC patients.

Abstract Background Metabolic disorder is considered a well-established risk factor for endometrial carcinoma (EC). However, the mechanism remains unclear. Insulin resistance and excessive flux of free fatty acids serve as fundamental pathogenic factors in metabolic disorders, including obesity and type 2 diabetes. The aim of this study was to test the correlation between insulin resistance and dyslipidaemia in EC and to determine the effect of insulin and saturated fatty acids on EC cells. Methods A retrospective study on the medical records of patients with EC and RNA-seq from the TCGA database analysed with edgR and Gene Ontology (GO) were used to assess the correlation of dyslipidaemia and diabetes as well as obesity. Crystal violet assays and CCK-8 assays were used to detect the proliferation of EC cells, and Annexin V-PI was used to examine apoptosis. Transient changes in mitochondrial Ca2+ and reactive oxygen species (ROS) were monitored via confocal microscopy. DNA damage was assessed by comet assays. Changes in signalling pathways were detected via phospho-kinase array. western blotting was used to assess the molecular changes in endoplasmic reticulum (ER) stress and DNA damage. Results We found that glucose metabolism disorders accompanied dyslipidaemia in patients with EC. As a key regulator of glucose metabolism disorders, insulin promoted DNA damage, ROS and Ca2+ homoeostasis imbalance in a panel of established EC cell lines. Interestingly, excessive insulin boosted saturated fatty acid-induced pro-apoptotic effects in EC cells. Furthermore, our data showed that insulin synergised with saturated fatty acids to activate the mechanistic target of rapamycin kinase/70 kDa ribosomal protein S6 kinase (mTOR/p70S6K) pathway and ER stress, resulting in Ca2+ release from ER and unfolded protein response (UPR) activation, which contributed to combined insulin and saturated fatty acid treatment-induced apoptosis and tumour progression. Conclusions Our data are the first to illustrate that impaired glucose metabolism accelerates dyslipidaemia-promoted EC progression, which is attributed to hyperinsulinaemia and saturated fatty acid-induced Ca2+ dyshomoeostasis and UPR activation in EC cells via ER stress.

Abstract Objective N6-methyladenosine (m6A) RNA methylation is involved in governing the mechanism of tumor progression. We aimed to excavate the biological role and mechanism of the m6A methyltransferase METTL3 in cholangiocarcinoma (CCA). Methods METTL3 expression was determined by database and tissue microarray analyses. The role of METTL3 in CCA was explored by loss- and gain-of-function experiments. The m6A target of METTL3 was detected by RNA sequencing. The role of AKR1B10 in CCA was explored, and the association between METTL3 and AKR1B10 was confirmed by rescue experiments. Result METTL3 expression was upregulated in CCA tissue, and higher METTL3 expression was implicated in poor prognoses in CCA patients. Overexpression of METTL3 facilitated proliferation, migration, invasion, glucose uptake, and lactate production in CCA cells, whereas knockdown of METTL3 had the opposite effects. We further found that METTL3 deficiency inhibited CCA tumor growth in vivo. RNA sequencing and MeRIP-qPCR confirmed that METTL3 enhanced AKR1B10 expression and m6A modification levels. Furthermore, METTL3 directly binds with AKR1B10 at an m6A modification site. A CCA tissue microarray showed that AKR1B10 expression was upregulated in CCA tissue and that silencing AKR1B10 suppressed the malignant phenotype mentioned above in CCA. Notably, knockdown of AKR1B10 rescued the tumor-promoting effects induced by METTL3 overexpression. Conclusion Elevated METTL3 expression promotes tumor growth and glycolysis in CCA through m6A modification of AKR1B10, indicating that METTL3 is a potential target for blocking glycolysis for application in CCA therapy.

Abstract Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke with high mortality and disability rate. Meningeal lymphatic vessels (mLVs) are a newly discovered intracranial fluid transport system and are proven to drain extravasated erythrocytes from cerebrospinal fluid into deep cervical lymph nodes after SAH. However, many studies have reported that the structure and function of mLVs are injured in several central nervous system diseases. Whether SAH can cause mLVs injury and the underlying mechanism remain unclear. Herein, single‐cell RNA sequencing and spatial transcriptomics are applied, along with in vivo/vitro experiments, to investigate the alteration of the cellular, molecular, and spatial pattern of mLVs after SAH. First, it is demonstrated that SAH induces mLVs impairment. Then, through bioinformatic analysis of sequencing data, it is discovered that thrombospondin 1 (THBS1) and S100A6 are strongly associated with SAH outcome. Furthermore, the THBS1‐CD47 ligand‐receptor pair is found to function as a key role in meningeal lymphatic endothelial cell apoptosis via regulating STAT3/Bcl‐2 signaling. The results illustrate a landscape of injured mLVs after SAH for the first time and provide a potential therapeutic strategy for SAH based on mLVs protection by disrupting THBS1 and CD47 interaction.

Abstract Linear instability analysis as well as a corresponding two‐dimensional hybrid simulation are performed to examine the excitation of the proton cyclotron waves observed upstream of Mars. The waves are believed to be excited by the pickup ions produced from the ionization of the Martian hydrogen exosphere. And previous statistical analysis of wave observations suggested that the waves are mostly related to pickup ion beam velocity distributions. While earlier linear instability analysis of pickup ion beam distributions has mainly been focused on the parallel unstable modes, our analysis reveals that the maximum growth rate occurs at very oblique propagation. The corresponding hybrid simulation confirms the linear analysis results and further demonstrates that the pickup ions are scattered toward an isotropic shell velocity distribution by the waves excited. Interestingly, the waves at oblique propagation gradually damp out and the system is eventually dominated by waves of quasi‐parallel propagation.

Three-dimensional global hybrid simulations are performed to explore how the interplanetary magnetic field (IMF), the Martian crustal fields, and planetary pickup ions affect the twisting of the Martian magnetotail. The results agree with previous studies that the crustal magnetic fields cause the Martian magnetotail to twist counterclockwise or clockwise depending on the sign of the IMF Y -component in the Mars solar orbital coordinates. However, the twist is more pronounced when the crustal fields are on the nightside, contradicting the early explanation that the crustal fields affect the twist through dayside magnetic reconnection between the crustal fields and the draped IMF. Additionally, planetary pickup ions also contribute to the twist because their mass loading slows down the plasma flow and leads to the bending of the magnetic field lines in the magnetotail. It is demonstrated that the twist inside Mars’ shadow in the near magnetotail region (at X = −1.5 R _M , where R _M is Mars’ radius) is mainly attributable to the crustal fields, while the influence of planetary pickup ions starts to dominate outside Mars’ shadow and in regions further away from Mars.

The solar wind deceleration upstream of the Martian bow shock is examined using particle and magnetic field measurements obtained by the Mars Atmosphere and Volatile EvolutioN (MAVEN). Mars lacks a strong intrinsic magnetic field so its upper atmosphere extends beyond the Martian bow shock and interacts directly with the solar wind. Neutral atoms in the Martian upper atmosphere can be ionized through several physical processes and then start to move with the solar wind flow to form pickup ions. In return, the solar wind is expected to slow down due to the momentum transfer to the pickup ions. The present study surveys the MAVEN solar wind measurements between 2015 and 2019 to evaluate the solar wind deceleration upstream of the Martian bow shock. Different from previous studies of solar wind deceleration, our analysis carefully excludes the solar wind deceleration in the shock foot region. The average solar wind deceleration obtained is about 0.7% of the initial solar wind speed, much smaller than the values given by previous studies. Further calculation using several reasonable Martian upper atmosphere density profiles demonstrates that the deceleration observed is consistent with the pickup ion mass-loading scenario.

Combining Terahertz (THz) and Orbital Angular Momentum (OAM) technologies has great potential in high-speed wireless communication. Theoretically, OAM with different modes has strict orthogonality. The communication capacity of the system will improve significantly if OAM technology is applied to the THz communication system. Thus, the manner to generate a high-quality and dynamically controllable THz-OAM beam has been of significant interest to researchers in related fields. In this study, a double-layer transmissive metasurface that uses 3D printing as the processing method with a low cost and processing difficulty is designed. Note that the height of the unit cell for constructing the metasurface is configurable. As the height changes continuously, the phase of the transmitted wave covers 0～2\begin{document}${\pi }$\end{document} within 90~110 GHz, while the transmittance of the units is always higher than 88%. At 100 GHz, which is fed by a WR-10 standard waveguide horn antenna, OAM beams with different modes are generated by changing the relative rotation angle between the double-layer metasurface. The simulation results show that the metasurface antenna designed in this study can achieve OAM beams of \begin{document}$ l=1, \mathrm{2,3} $\end{document}, and the two-dimensional amplitude and phase results correspond with the characteristics of the corresponding modes. When \begin{document}$ l=1,\mathrm{ }2,\mathrm{ }3 $\end{document}, the OAM beam’s modal purity is 85.4%, 84.9%, and 83.4%, respectively. The measurement results include the results at frequency points of 90, 100, and 110 GHz. The results show that the OAM beam has a high-quality bandwidth of 20 GHz, which indicates that the metasurface antenna designed in this study has a wide working bandwidth at a high frequency and can be applied to high-frequency OAM communication.

Natural cellulosic materials are attractive biopolymers for their naturally abundant source, mechanical toughness, bioactivity, etc. However, porosity and flexibility remain challenges for the preparation of aerogels from natural cellulose. To maintain the characteristics of cellulose aerogels possessing the toughness of fibers and high porosity of aerogels, cellulose aerogels with three-dimensional void structures and high compressive resilience were prepared by mixing cellulose fiber suspension and polyvinyl alcohol (PVA). The PM 2.5 removal rate and thermal conductivity of cellulose aerogel reached 92.4% and 0.028 W/mK, respectively, when a PVA content of 0.7% was added, and the radiation cooling temperature was about 10.0°C lower than that of PE foam. The three-dimensional void structure and surface morphology of the cellulose aerogels were investigated by scanning electron microscopy (SEM). The cellulose aerogel porosity and pore size distribution were evaluated by a mercury intrusion meter. The crystal structure of cellulose was analyzed by X-ray diffraction (XRD). UV-Vis-NIR spectroscopy was used to investigate the infrared reflectance of cellulose aerogels. Then the air purification efficiency and radiation cooling effect of porous cellulose aerogels were evaluated in a homemade device, respectively.

BackgroundPhysical exercise has been recommended as an important nonpharmacological therapeutic strategy for managing attention deficit hyperactivity disorder (ADHD). We conducted a network meta-analysis (NMA) to assess the comparative impact of different physical exercise modalities on enhancing executive functions (EFs) and alleviating symptoms in children and adolescents with ADHD.MethodsWe searched Web of Science, PubMed, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, PsycINFO, CNKI, and clinical trials databases from inception to October 20, 2022. Randomized controlled trials (RCTs) and quasi-experimental studies investigating physical exercise for ADHD-related symptoms of hyperactivity/impulsivity and inattention, and executive functions were included. The frequentist random-effect NMA method was applied to pool the results.ResultsA total of 59 studies (including 39 RCTs, 5 quasi-RCTs, and 15 self-controlled trials) published between 1983 and 2022 were incorporated into the systematic review, of which 44 studies with 1757 participants were eligible for meta-analysis. All types of physical exercise were effective in improving EFs (SMD = 1.15, 95% CI: 0.83 to 1.46), and open-skill activities which require participants to react in a dynamically changing and externally paced environment induced the most incredible benefits for executive functions (SUCRA = 98.0%, SMD = 1.96, and 95% CI: 1.15 to 2.77). Subgroup analyses for EFs revealed varied findings that open-skill activities were the most promising physical exercise type for improving inhibitory control (SUCRA = 99.1%, SMD = 1.94, and 95% CI: 1.24 to 2.64), and closed-skill activities dominated by aerobic exercises had a slightly higher probability of being the most promising physical exercise intervention for working memory (SUCRA = 75.9%, SMD = 1.21, and 95% CI: −0.22 to 2.65), and multicomponent physical exercise tended to be the most effective in cognitive flexibility (SUCRA = 70.3%, SMD = 1.44, and 95% CI: −0.19 to 3.07). Regarding ADHD-related symptoms, closed-skill activities dominated by aerobic exercises might be more advantageous for hyperactivity/impulsivity (SUCRA = 72.5%, SMD = -1.60, and 95% CI: −3.02 to −0.19) and inattention (SUCRA = 96.3%, SMD = -1.51, and 95% CI: −2.33 to −0.69) improvement.ConclusionPhysical exercise can significantly help to alleviate the symptoms of ADHD and improve executive functions in children and adolescents with ADHD. Most of all, to promote adherence to treatment, they should be encouraged to perform the physical exercises that they enjoy most.

Abstract Recombination plays important roles in the genetic diversity and evolution of Enterovirus A71 (EV-A71). The phylogenetics of EV-A71 in mainland China found that one strain DL71 formed a new subgenotype C6 with unknown origin. This study investigated the detailed genetic characteristics of the new variant. DL71 formed a distinct cluster within genotype C based on the genome and individual genes (5′UTR, VP4, VP1, 2A, 2B, 2C, 3D, and 3′UTR). The average genetic distances of the genome and individual genes (VP3, 2A, 2B, 2C, 3A, 3C, and 3D) between DL71 and reference strains were greater than 0.1. Nine recombination events involving smaller fragments along DL71 genome were detected. The strains Fuyang-0805a (C4) and Tainan/5746/98 (C2) were identified as the parental strains of DL71. In the non-recombination regions, DL71 had higher identities with Fuyang-0805a than Tainan/5746/98, and located in the cluster with C4 strains. However, in the recombination regions, DL71 had higher identities with Tainan/5746/98 than Fuyang-0805a, and located in the cluster with C2 strains. Thus, DL71 was a novel multiple inter-subgenotype recombinant derived from the dominant subgenotype C4 and the sporadic subgenotype C2 strains. Monitoring the emergence of new variants by the whole-genome sequencing remains essential for preventing disease outbreaks and developing new vaccines.

ObjectivesPrimary brainstem hemorrhage (PBSH) is one of the most catastrophic spontaneous intracerebral hemorrhage diseases, with a mortality rate of 70–80%. We explored the predictive factors for survival and consciousness in patients with PBSH (ClinicalTrials.gov ID: NCT04910490).MethodsWe retrospectively reviewed 211 patients with PBSH admitted to our institution between January 2014 and October 2020. Clinical outcomes included the 30-day survival rate and the 90-day consciousness rate as evaluated by the National Institutes of Health Stroke Scale score. Multiple logistic regression analysis was performed.ResultsThe overall 30-day survival rate of 211 patients with PBSH was 70%. Several predictive factors including hematoma volume, hematoma location, activated partial thromboplastin time (APTT) upon admission, and therapeutic strategy were significantly related to 30-day survival. Compared with conservative treatment, stereotactic aspiration in our prediction model is strongly associated with improved 30-day survival (odds ratio, 6.67; 95% confidence interval, 3.13–14.29; P < 0.001). The prognosis prediction model of 90-day consciousness including factors such as mydriasis, APTT value, hematoma location, and hematoma volume upon admission has a good predictive effect (AUC, 0.835; 95% confidence interval, 0.78–0.89; P < 0.001).ConclusionIn patients with PBSH, conscious state upon admission, coagulation function, hematoma volume, hematoma location, and therapeutic strategy were significantly associated with prognosis. Stereotactic aspiration could significantly reduce the 30-day mortality rate.

Abstract As electromagnetic environments are increasingly complex, there are more kinds of radar jamming signals. Active jamming recognition has problems of the low recognition accuracy and the high computational complexity, especially under a low jamming‐to‐noise ratio (JNR). Herein, a deep learning network based on bilinear EfficientNet and attention mechanism is proposed to recognise and classify eight kinds of jamming signals automatically. Firstly, the one‐dimensional interference signal is transformed into a two‐dimensional time–frequency image by the time–frequency analysis. Based on the transfer learning of EfficientNet‐B3, the effective features of the time–frequency image are automatically extracted by the two‐way network with attention mechanism, and the active interference classification is realised. The experimental results show that the method's overall recognition rate for eight kinds of interference signals is more than 97.5% when the JNR is −8 dB and is close to 100% at −2 dB.

Objective: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. Methods: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. Results: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. Conclusions: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis.

Colorectal cancer (CRC), one of the cancers with highest mortality, involves complicated molecular mechanisms leading to the onset of malignant phenotypes. ZNF280A, a member of the zinc-finger protein family, was shown to be a promotor of oncogenesis in CRC in this study. ZNF280A was remarkably upregulated in CRC tissues, which was meaningfully associated with tumor progression and poor prognosis in patients with CRC. Loss-of-function studies revealed that ZNF280A knockdown inhibited the development and progression of CRC as evident by the inhibition of cell proliferation, colony formation, cell apoptosis, cell cycle distribution, and cell migration in vitro and the repressed tumorigenesis of CRC cells in vivo. Next, we showed that RPS14 was the downstream target of ZNF280A and ZNF280A knockdown promoted the ubiquitination as well as degradation of RPS14 in CRC. Additionally, we demonstrated that RPS14 regulated the development of CRC via PI3K-Akt signaling pathway. Taken together, our findings provide a novel clear insight into ZNF280A/RPS14/PI3K-Akt axis in CRC for the first time, offering a potential target for early detection, diagnosis and treatment of CRC in future clinical applications.

After the first attempt to induce operational tolerance, it has taken decades to implement it in clinical practice. Recipients with Human leukocyte antigen (HLA) identical sibling donors were enrolled. Hematopoietic stem cells (HSCs) infusion was done after HLA identical sibling kidney transplantation (KTx). Three cases included were followed up for over 8 years. The perioperative conditioning protocol included anti-CD20, rabbit anti-thymocyte globulin (ATG), total lymphoid irradiation (TLI), and cyclophosphamide. Infusion of CD3+ cells and CD34+ cells was conducted. The withdrawal of immunosuppression was determined by mixed lymphocyte reaction (MLR) and graft biopsy. Case 1 and Case 2 showed persistent chimerism, while chimerism was not detected in Case 3. All three recipients showed a low-level response to donor-specific stimulation. Case 1 and Case 3 met the withdrawal rules at 16 and 32 months after transplantation, respectively. Graft function was stable, and no rejection signs were observed in routine biopsies until 94 and 61 months after transplantation. Case 2 was diagnosed with graft-versus-host disease (GVHD) 9 months after transplantation and recovered after an enhanced immunosuppression therapy. Steroids were withdrawn after 1 year, and 0.5 mg tacrolimus twice a day is currently the only immunosuppression at 8 years and 8 months. In conclusion, our clinical experience indicated the efficacy of non-myeloablative conditioning protocol for tolerance induction in HLA identical patients. Complete chimerism might be a risk factor for GVHD.

BackgroundOnline pharmacies have gradually penetrated the market, but pose risks to patients' health. Failure Mode and Effect Analysis (FMEA) is an effective and reliable method for reducing pharmacy and medication risks. The purpose of this study was to conduct a prospective risk analysis of the process of purchasing prescription drugs from online pharmacies in China to guarantee drug quality and patient safety.MethodsThe FMEA was performed at Sichuan University, China. A multidisciplinary team was assembled comprising a leader, four regulators, four pharmacists, two experts, etc. The process was composed of eight subprocesses: searching for prescription drugs, submitting medication requirements, completing patient information forms, dispensing, delivering, etc. Brainstorming was used to identify and prioritize failure modes, propose corrective actions, and reduce risks. Risk priority numbers were the main criterion and were obtained by multiplying three scores: severity, occurrence and detectability, which were scored by the team The team proposed corrective actions for each selected failure mode.ResultsA total of forty-one potential failure modes were identified, and the causes, effects, and corrective actions of the 30 top failure modes were analyzed. The highest risk value was assigned to “photocopies of paper prescriptions uploaded were reused by patients.” Three failure modes for the S value of 5 were: “drugs are eroded and polluted by moisture or insects in the process of transportation,” “the qualification information of the pharmacies were absent or fake,” and “pharmacists fail to check prescriptions in accordance with Prescription Administrative Regulation.” Of the top failure modes, 36.67% were from Step 5, delivering the drug. After taking corrective measures to control risks, the risks reduced by 69.26%.ConclusionThe results of this study proves that the FMEA is a valuable tool for identifying and prioritizing the risks inherent in online pharmacies. This study shows that there are many potential risks in the process of purchasing prescription drugs from online pharmacies, especially in the drug delivery stage. Enhanced training and the introduction of smart devices may minimize risks. Online pharmacies and Chinese regulators should consider these findings for risk mitigation and the improvement of regulations pertaining to online pharmacies.

The fungal decay of fresh fruits and vegetables annually generates substantial global economic losses. The utilization of conventional synthetic fungicides is damaging to the environment and human health. Recently, the biological control of post-harvest fruit and vegetable diseases via antagonistic microorganisms has become an attractive possible substitution for synthetic fungicides. Numerous studies have confirmed the potential of volatile organic compounds (VOCs) for post-harvest disease management. Moreover, VOC emission is a predominant antifungal mechanism of antagonistic microorganisms. As such, it is of great significance to discuss and explore the antifungal mechanisms of microbial VOCs for commercial application. This review summarizes the main sources of microbial VOCs in the post-harvest treatment and control of fruit and vegetable diseases. Recent advances in the elucidation of antifungal VOC mechanisms are emphasized, and the applications of VOCs produced from antagonistic microorganisms are described. Finally, the current prospects and challenges associated with microbial VOCs are considered.

Glioma is the most common intracranial malignant tumor in adults and the 5-year survival rate of glioma patients is extremely poor, even in patients who received Stupp treatment after diagnosis and this forces us to explore more efficient clinical strategies. At this time, immunotherapy shows great potential in a variety of tumor clinical treatments, however, its clinical effect in glioma is limited because of tumor immune privilege which was induced by the glioma immunosuppressive microenvironment, so remodeling the immunosuppressive microenvironment is a practical way to eliminate glioma immunotherapy resistance. Recently, increasing studies have confirmed that ferroptosis, a new form of cell death, plays an important role in tumor progression and immune microenvironment and the crosstalk between ferroptosis and tumor immune microenvironment attracts much attention. This work summarizes the progress studies of ferroptosis in the glioma immune microenvironment.

We obtained sixteen clear-sky remote sensing images of Landsat series data from 1973 to 2021 and extracted continental and island coastlines of the Salween River Delta based on the Modified Normalized Difference Water Index (MNDWI) and visual interpretation correction. We determined the overall evolution of coastlines with statistical and superposition analysis and applied the Digital Shoreline Analysis System (DSAS) to summarize the spatial and temporal evolution process and characteristics in the past 50 years. Experimental results show that (1) the overall change of the coastline was more rapid on the island than on the continent, and on the Indian Ocean side than on the continental side, (2) the total area of the island increased by 91.16 km2 from 1973 to 2021, the area of Bilu Island increased by 50.38 km2, the length of the continental coastline decreased by 0.39 km, and the length of the coastline of the Bilu Island increased by 6.43 km, (3) the Linear Regression Rate (LRR) were: 4.69 m/yr for the total coastline, 1.06 and −2.07 m/yr, respectively, for the western and southern branches of the continental coastline, and 0.83 and 21.52 m/yr, respectively, for the continental and Indian Ocean sides of Bilu Island, and (4) the dominant process in the Salween River Delta was accretion, with an overall accretion area of about 10 km2, and an unstable accretion rate.

To analyze and improve ZJUSAH classification for primary brainstem hematoma, we retrospectively reviewed 211 patients with primary brainstem hemorrhage who were admitted to our institution between January 2014 and October 2020. The primary clinical outcomes were the 30-day survival rate and 90-day consciousness recovery rate, which were evaluated using the National Institutes of Health Stroke Scale score. Univariate logistic regression and multivariate Cox regression analyses were performed to evaluate the prognostic model. The overall 30-day survival rate of the 211 patients was 69.7%. The 30-day survival rate was 95% among Type 1 patients, 77.8% among Type 2 patients, and 63.2% among Type 3 patients. The 90-day consciousness recovery rate was 63.2% among Type 1 patients, 61.9% among Type 2 patients, and 30.2% among Type 3 patients. Our findings suggest that ZJUSAH classification can be optimized according to hematoma volume, with Type 3 patients with a hematoma larger than 12.4 mL tending to have a worse state of consciousness. Additionally, we discovered that ZJUSAH classification is valuable in predicting 30-day survival rates in conservative treatment patients. In conclusion, our study established and optimized a new CT-based hematoma classification system for primary brainstem hematoma, which facilitates treatment selection and prognostic prediction.

Abstract In hepatocellular carcinoma patients, due to the microenvironmental specificity of liver, the tumor microenvironment exhibits high immunosuppression and drug resistance, resulting in excessive or insufficient responses to immunotherapy. The dynamic interactions between tumor cells and immune modulators in the TME significantly impact the occurrence and development of tumors, efficacy, and drug resistance, which can create a much more positive response to immunotherapy. Moreover, with the wide application of single-cell sequencing technology in the TME, increasing evidence shows an interaction network among cells. Sequencing results suggest that specific tumor-associated macrophages are a hub node, connecting different cell populations in the cell interaction network, and can could regulate tumor generation and antitumor immunity. This review focused on therapeutic targets that could be targeted to remodel the tumor microenvironment and reprogram the tumor-associated macrophage phenotype in hepatocellular carcinoma patients, thereby improving immunotherapeutic efficacy.

Abstract Background This study aimed to explore the prognostic role of DNA methylation pattern in endometrial cancer (EC) patients. Methods Differentially methylated genes (DMGs) of EC patients with distinct survival from The Cancer Genome Atlas (TCGA) database were analyzed to identify methylated genes as biomarkers for EC prognosis. The Least Absolute Shrinkage and Selection Operator (LASSO) analysis was used to construct a risk score model. A nomogram was built based on analysis combining the risk score model with clinicopathological signatures together, and then verified in the validation cohort and patients in our own center. Results In total, 157 DMGs were identified between different prognostic groups. Based on the LASSO analysis, five genes (GBP4, OR8K3, GABRA2, RIPPLY2, and TRBV5‐7) were screened for the establishment of risk score model. The model outperformed in prognostic accuracy at varying follow‐up times (AUC for 3 years: 0.824, 5 years: 0.926, and 7 years: 0.853). Multivariate analysis identified four independent risk factors including menopausal status (HR = 3.006, 95%CI: 1.062–8.511, p = 0.038), recurrence (HR = 2.116, 95%CI: 1.061–4.379, p = 0.046), lymph node metastasis (LNM, HR = 3.465, 95%CI: 1.225–9.807, p = 0.019), and five‐DNA methylation risk model (HR = 3.654, 95%CI: 1.458–9.161, p = 0.006) in training cohort. The performance of the nomogram was good in the training (AUC = 0.828), validation (AUC = 0.866) and the whole cohorts (AUC = 0.843). Furthermore, we verified the nomogram with 24 patients in our center and the Kaplan–Meier survival curve also proved to be significantly different (p

In the field chemical flooding test of the Qizhong District of Xinjiang Oilfield, emulsion with high apparentviscosity (4 000 mPa·s) was found in some well, without demulsification and viscosity reduction after placement inseveral days, which affected the oil production and transportation seriously. In order to reduce the apparent viscosity of theemulsion, the effects of demulsifier, heating, ultrasound and salt on the apparent viscosity of the emulsion were studied tosummarize the optimal method for viscosity reduction. According to the study results, quaternary ammonium salt demulsifierhas very poor effect on viscosity reduction of the emulsion. Temperature has a great effect on rheological property ofthe emulsion. With same shear rate, the higher the temperature, the lower the apparent viscosity of the emulsion is. Theultrasound can reduce the apparent viscosity of the emulsion significantly, and the viscosity reduction effect is best in thecondition that the salt content is 10 000 mg/L and the volume ratio of the emulsion and the wastewater is 5:5. Generally, theabove research results are of important guiding significance to the gathering and transportation of chemical flooding highviscosityproduced fluid and its subsequent treatment.

Objective To investigated the clinical efficacy of Soluble thrombomodulin (sTM), tissue plasminogen activator inhibitor complex (t-PAI·C),thrombin-antithrombin complex (TAT),α2-plasmininhibitor-plasmin complex (PIC) in pediatric sepsis and pediatrics sepsis-induced coagulopathy (pSIC). Methods We prospectively collected patient data with sepsis diagnosed in the PICU of Shanghai Children's Medical Center from June 2019 to June 2021. sTM,t-PAI·C, TAT,PIC and classical coagulation laboratory tests (CCTs) were evaluated on the day of sepsis diagnosis. Results Fifty-nine children were enrolled, There were significant differences in t-PAI·C (P = 0.001), Plt (P < 0.001), PT (P < 0.001), INR (P < 0.001), aPTT (P < 0.001), and TT (P = 0.048) between the pSIC and non-pSIC groups, logistic regression analysis showed that Plt (P = 0.032) was an independent risk factor for pSIC. Logistic regression analysis showed that sTM (P = 0.007) and Plt (P = 0.016) were independent risk factors for the outcome in pediatrics sepsis following discharge. The AUC of sTM combined with Plt on the mortality outcome of children with sepsis at discharge was 0.889 (95%CI: 0.781,0.956). which was better than that for PRISM III (AUC, 0.723), pSOFA (AUC, 0.764), and blood Lac (AUC, 0.717) when sepsis was diagnosed in the PICU. Conclusions The t-PAI·C increased in children with pSIC. The prediction of sepsis outcome using sTM combined with Plt was better than with PRISM III, pSOFA, or Lac.Further research is still needed in the future to explore the clinical value of sTM, TAT, PIC, and t-PAI·C in diagnosis and outcome of pediatrics sepsis and pSIC.

Abstract Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable cation channel that has been associated with several types of cancer. However, its biological significance, as well as its related mechanism in endometrial cancer (EC) still remains elusive. In this study, we examined the function of calcium in EC, with a specific focus on TRPV4 and its downstream pathway. We reported here on the findings that a high level of serum ionized calcium was significantly correlated with advanced EC progression, and among all the calcium channels, TRPV4 played an essential role, with high levels of TRPV4 expression associated with cancer progression both in vitro and in vivo. Proteomic and bioinformatics analysis revealed that TRPV4 was involved in cytoskeleton regulation and Rho protein pathway, which regulated EC cell migration. Mechanistic investigation demonstrated that TRPV4 and calcium influx acted on the cytoskeleton via the RhoA/ROCK1 pathway, ending with LIMK/cofilin activation, which had an impact on F-actin and paxillin (PXN) levels. Overall, our findings indicated that ionized serum calcium level was significantly associated with poor outcomes and calcium channel TRPV4 should be targeted to improve therapeutic and preventive strategies in EC.

Abstract Background This study aimed to understand the mechanistic role of N-methyl-D-aspartate receptor (NMDAR) in acute fibrogenesis using models of in vivo ureter obstruction and in vitro TGF-β administration. Methods Acute renal fibrosis (RF) was induced in mice by unilateral ureteral obstruction (UUO). Histological changes were observed using Masson’s trichrome staining. The expression levels of NR1, which is the functional subunit of NMDAR, and fibrotic and epithelial-to-mesenchymal transition markers were measured by immunohistochemical and Western blot analysis. HK-2 cells were incubated with TGF-β, and NMDAR antagonist MK-801 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 were administered for pathway determination. Chronic RF was introduced by sublethal ischemia–reperfusion injury in mice, and NMDAR inhibitor dextromethorphan hydrobromide (DXM) was administered orally. Results The expression of NR1 was upregulated in obstructed kidneys, while NR1 knockdown significantly reduced both interstitial volume expansion and the changes in the expression of α-smooth muscle actin, S100A4, fibronectin, COL1A1, Snail, and E-cadherin in acute RF. TGF-β1 treatment increased the elongation phenotype of HK-2 cells and the expression of membrane-located NR1 and phosphorylated CaMKII and extracellular signal–regulated kinase (ERK). MK801 and KN93 reduced CaMKII and ERK phosphorylation levels, while MK801, but not KN93, reduced the membrane NR1 signal. The levels of phosphorylated CaMKII and ERK also increased in kidneys with obstruction but were decreased by NR1 knockdown. The 4-week administration of DXM preserved renal cortex volume in kidneys with moderate ischemic–reperfusion injury. Conclusions NMDAR participates in both acute and chronic renal fibrogenesis potentially via CaMKII-induced ERK activation.

Peach gummosis is one of the most widespread and destructive diseases. It causes growth stunting, yield loss, branch, trunk, and tree death, and is becoming a restrictive factor in healthy and sustainable development of peach production. Although a locus has been identified based on bi-parental quantitative trait locus (QTL) mapping, selection of gummosis-resistant cultivars remains challenging due to the lack of resistant parents and of the complexity of an inducing factor. In this study, an integrated approach of genome-wide association study (GWAS) and comparative transcriptome was used to elucidate the genetic architecture associated with the disease using 195 accessions and 145,456 genome-wide single nucleotide polymorphisms (SNPs). The broad-sense and narrow-sense heritabilities were estimated using 2-year phenotypic data and genotypic data, which gave high values of 70 and 73%, respectively. Evaluation of population structure by neighbor-joining and principal components analysis (PCA) clustered all accessions into three major groups and six subgroups, mainly according to fruit shape, hairy vs. glabrous fruit skin, pedigree, geographic origin, and domestication history. Five SNPs were found to be significantly associated with gummosis disease resistance, of which SNPrs285957, located on chromosome6 across 28 Mb, was detected by both the BLINK and the FarmCPU model. Six candidate genes flanked by or harboring the significant SNPs, previously implicated in biotic stress tolerance, were significantly associated with this resistance. Two highly resistant accessions were identified with low disease severity, which could be potential sources of resistance genes for breeding. Our results provide a fresh insight into the genetic control of peach gummosis disease.