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Abstract Promoters play a crucial role in regulating gene transcription. However, our understanding of how genetic variants influence alternative promoter selection is still incomplete. In this study, we implement a framework to identify genetic variants that affect the relative usage of alternative promoters, known as promoter usage quantitative trait loci (puQTLs). By constructing an atlas of human puQTLs across 49 different tissues from 838 individuals, we have identified approximately 76,856 independent loci associated with promoter usage, encompassing 602,009 genetic variants. Our study demonstrates that puQTLs represent a distinct type of molecular quantitative trait loci, effectively uncovering regulatory targets and patterns. Furthermore, puQTLs are regulating in a tissue-specific manner and are enriched with binding sites of epigenetic marks and transcription factors, especially those involved in chromatin architecture formation. Notably, we have also found that puQTLs colocalize with complex traits or diseases and contribute to their heritability. Collectively, our findings underscore the significant role of puQTLs in elucidating the molecular mechanisms underlying tissue development and complex diseases.

Abstract Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.

Intronic polyadenylation (IPA) refers to a particular type of alternative polyadenylation where a gene makes use of a polyadenylation site located within its introns. Aberrant IPA events have been observed in various types of cancer. IPA can produce noncoding transcripts or truncated protein-coding transcripts with altered coding sequences in the resulting protein product. Therefore, IPA events hold the potential to act as a reservoir of tumor neoantigens. Here, we developed a computational method termed DIPAN, which incorporates IPA detection, protein fragmentation, and MHC binding prediction to predict IPA-derived neoantigens. Utilizing RNA-seq from breast cancer cell lines and ovarian cancer clinical samples, we demonstrated the significant contribution of IPA events to the neoantigen repertoire. Through mass spectrometry immunopeptidome analysis, we further illustrated the processing and presentation of IPA-derived neoantigens on the surface of cancer cells. While most IPA-derived neoantigens are sample-specific, shared neoantigens were identified in both cancer cell lines and clinical samples. Furthermore, we demonstrated an association between IPA-derived neoantigen burden and overall survival in cancer patients.

Background Low energy availability (LEA) occurs when athletes’ energy intake fails to match the energy expended during exercise, resulting in insufficient energy to support essential functions for optimal health, a condition known as relative energy deficiency in sports (REDs).Objective This study aims to explore the prevalence of LEA among Malaysian national athletes and its associations with health-related outcomes.Methods A total of 43 athletes (51.2% males, aged 18–40) identified previously as having moderate or high risk of REDs through a questionnaire underwent comprehensive clinical assessments. Resting metabolic rate (RMR) was measured using indirect calorimetry, with an RMR ratio of

Different sampling strategies produce varying sample data, serve as the primary input data and directly affect the accuracy of predictions in data-driven grid-based susceptibility models. This study analyzes the accuracy and variation of debris flow susceptibility maps (DFSMs) generated by various sampling strategies. The study area is the Yingxiu region in China, where six sampling strategies were applied, including three sampling locations (deposition area, runout area, and source area) and two sampling types (centroid and polygon) for the debris flow inventory. The effectiveness of 10 conditioning factors used to build the model was assessed by using Pearson correlation coefficient, variance inflation factor, and information gain ratio (IGR) techniques. We then used Weight of Evidence (WofE), Logistic Regression (LR), and Deep Neural Network (DNN) models to produce DFSMs and quantify their performance using the receiver operating characteristic curve (ROC), Accuracy (ACC), Precision, F1 score, and Recall. The results show that the WofE (AUC: 0.754–0.960), LR (AUC: 0.761–0.965), and DNN (AUC: 0.786–0.976) models all perform well, but the DFSMs and dominant factors depend strongly on sampling strategies, especially on sampling location. If the sample areas are excessively large and span across different factor class labels, or if there is a concentration of either large or small sample areas within a specific region, the results of centroid and polygon sampling strategies may differ or even be contradictory.We recommend: (1) determining sampling locations based on the research objectives to provide more accurate evaluation results; (2) selecting the sampling type by first considering the sample size. If the aforementioned conditions are not present, the quicker and more convenient centroid sampling strategy can be chosen; and (3) determining an appropriate sampling strategy and ensuring the accuracy of initial samples are paramount before producing DFSMs.

Advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), acrylamide (AA), 5-hydroxymethylfurfural (5-HMF), and polycyclic aromatic hydrocarbons (PAHs) are toxic substances that are produced in certain foods during thermal processing by using common high-temperature unit operations such as frying, baking, roasting, grill cooking, extrusion, among others. Understanding the formation pathways of these potential risk factors, which can cause cancer or contribute to the development of many chronic diseases in humans, is crucial for reducing their occurrence in thermally processed foods. During thermal processing, food rich in carbohydrates, proteins, and lipids undergoes a crucial Maillard reaction, leading to the production of highly active carbonyl compounds. These compounds then react with other substances to form harmful substances, which ultimately affect negatively the health of the human body. Although these toxic compounds differ in various forms of formation, they all partake in the common Maillard pathway. This review primarily summarizes the occurrence, formation pathways, and reduction measures of common toxic compounds during the thermal processing of food, based on independent studies for each specific contaminant in its corresponding food matrix. Finally, it provides several approaches for the simultaneous reduction of multiple toxic compounds.

Objectives: To update recent information on contamination levels of mycotoxins in South Korea. Materials and methods: A total of 208 samples sourced from the feeds of swine farms were collected. The contamination levels of mycotoxins, which are aflatoxin (Afla), ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEN), fumonisin (FUM), and T-2 toxin, were investigated by enzyme-linked immunosorbent assays (ELISAs). Results: The detection levels of the total samples were 78.91% for DON, 75.24% for Afla, 47.02% for ZEN, 68.31% for FUM, and 5.94% for OTA and T-2, which were not detected at all. Most of the analyzed mycotoxins showed significant high occurrences in 47.02%–78.91% of the swine feed samples. 11 of the 152 alfa-positive samples exceeded the maximum residue limit (MRL) of Afla proposed by the Korean regulation. In the analysis of mycotoxin detection levels by growth stage, ZEN was found in the nursery stage at a remarkably high concentration level (126.46 ± 63.76 ppb), exceeding the MRL of ZEN for piglets proposed by the European Commission. This mycotoxin was also found in the samples from the gestation barn (89.04 ± 46.05 ppb) and the farrowing house (105.58 ± 94.12) at a high concentration level. Afla was found in the nursery stage at a high concentration (8.00 ± 2.22 ppb), approaching the MRL (10 ppb) of Afla proposed by the Korean regulation. Conclusion: These results indicate that many swine farms in South Korea are still exposed to mycotoxin risk, and special attention and surveillance are necessary for these mycotoxin risks in swine farms. [J Adv Vet Anim Res 2024; 11(1.000): 125-131]

Abstract Alternative polyadenylation can occur in introns, termed intronic polyadenylation (IPA), has been implicated in diverse biological processes and diseases, as it can produce noncoding transcripts or transcripts with truncated coding regions. However, a reliable method is required to accurately characterize IPA. Here, we propose a computational method called InPACT, which allows for the precise characterization of IPA from conventional RNA-seq data. InPACT successfully identifies numerous previously unannotated IPA transcripts in human cells, many of which are translated, as evidenced by ribosome profiling data. We have demonstrated that InPACT outperforms other methods in terms of IPA identification and quantification. Moreover, InPACT applied to monocyte activation reveals temporally coordinated IPA events. Further application on single-cell RNA-seq data of human fetal bone marrow reveals the expression of several IPA isoforms in a context-specific manner. Therefore, InPACT represents a powerful tool for the accurate characterization of IPA from RNA-seq data.

Fungal diseases form perforated disease spots in tobacco plants, resulting in a decline in tobacco yield and quality. The present study investigated the antagonistic effect of Bacillus subtilis CTXW 7-6-2 against Rhizoctonia solani, its ability to promote the growth of tobacco seedlings, and the expression of disease resistance-related genes for efficient and eco-friendly plant disease control. Our results showed that CTXW 7-6-2 had the most vigorous growth after being cultured for 96 h, and its rate of inhibition of R. solani growth in vitro was 94.02%. The volatile compounds produced by CTXW 7-6-2 inhibited the growth of R. solani significantly (by 96.62%). The fungal growthinhibition rate of the B. subtilis CTXW 7-6-2 broth obtained after high-temperature and no-high-temperature sterile fermentation was low, at 50.88% and 54.63%, respectively. The lipopeptides extracted from the B. subtilis CTXW 7-6-2 fermentation broth showed a 74.88% fungal growth inhibition rate at a concentration of 100 mg/l. Scanning and transmission electron microscopy showed some organelle structural abnormalities, collapse, shrinkage, blurring, and dissolution in the R. solani mycelia. In addition, CTXW 7-6-2 increased tobacco seedling growth and improved leaf and root weight compared to the control. After CTXW 7-6-2 inoculation, tobacco leaves showed the upregulation of the PDF1.2, PPO, and PAL genes, which are closely related to target spot disease resistance. In conclusion, B. subtilis CTXW 7-6-2 may be an efficient biological control agent in tobacco agriculture and enhance plant growth potential.

Abstract The chromosome 20 long arm (20q) is one of the genomic hotspots where copy number alterations frequently occur in multiple types of tumors. However, it remains elusive which genes are implicated in 20q-related tumorigenesis. Here, by querying TCGA and GEO databases, we observed frequent copy number amplification at 20q and the chromosome subband 20q13.33 was amplificated in multiple cancers. Among those genes at 20q13.33, PSMA7 was found with the strongest correlation with cancers. Further analysis revealed that PSMA7 amplification was the most frequent genetic alteration event conferring adverse prognosis in various cancers. Consistent with the strong positive correlation between PSMA7 amplification and gene expression, elevated PSMA7 expression was observed in 20 of 33 types of cancers with a close link to adverse outcomes in certain tumors. In addition, PSMA7 was essential for the growth of almost 1095 cancer lines. Mechanistically, aberrant PSMA7 most probably influenced the proteasome and protease-related pathways to promote tumorigenesis and might be antagonized by several compounds, e.g., Docetaxel in relevant cancers. The current in-depth pan-cancer analysis refines our understanding of the crucial oncogenic role of copy number amplifications at PSMA7 loci at the novel chromosome amplicon 20q13.33 across different tumors.

Abstract Acute promyelocytic leukemia (APL) represents a paradigm for targeted differentiation therapy, with a minority of patients experiencing treatment failure and even early death. We here report a comprehensive single-cell analysis of 16 APL patients, uncovering cellular compositions and their impact on all-trans retinoic acid (ATRA) response in vivo and early death. We unveil a cellular differentiation hierarchy within APL blasts, rooted in leukemic stem-like cells. The oncogenic PML/RARα fusion protein exerts branch-specific regulation in the APL trajectory, including stem-like cells. APL cohort analysis establishes an association of leukemic stemness with elevated white blood cell counts and FLT3-ITD mutations. Furthermore, we construct an APL-specific stemness score, which proves effective in assessing early death risk. Finally, we show that ATRA induces differentiation of primitive blasts and patients with early death exhibit distinct stemness-associated transcriptional programs. Our work provides a thorough survey of APL cellular hierarchies, offering insights into cellular dynamics during targeted therapy.

Abstract Background Biological processes are controlled by groups of genes acting in concert. Investigating gene–gene interactions within different cell types can help researchers understand the regulatory mechanisms behind human complex diseases, such as tumors. Methods We collected extensive single-cell RNA-seq data from tumors, involving 563 patients with 44 different tumor types. Through our analysis, we identified various cell types in tumors and created an atlas of different immune cell subsets across different tumor types. Using the SCINET method, we reconstructed interactome networks specific to different cell types. Diverse functional data was then integrated to gain biological insights into the networks, including somatic mutation patterns and gene functional annotation. Additionally, genes with prognostic relevance within the networks were also identified. We also examined cell–cell communications to investigate how gene interactions modulate cell–cell interactions. Results We developed a data portal called CellNetdb for researchers to study cell-type-specific interactome networks. Our findings indicate that these networks can be used to identify genes with topological specificity in different cell types. We also found that prognostic genes can deconvolved into cell types through analyzing network connectivity. Additionally, we identified commonalities and differences in cell-type-specific networks across different tumor types. Our results suggest that these networks can be used to prioritize risk genes. Conclusions This study presented CellNetdb, a comprehensive repository featuring an atlas of cell-type-specific interactome networks across 44 human tumor types. The findings underscore the utility of these networks in delineating the intricacies of tumor microenvironments and advancing the understanding of molecular mechanisms underpinning human tumors.

Bispecific T-cell-engaging antibodies are a growing class of therapeutics with numerous molecules being tested in clinical trials and, currently, seven of them have received market approval. They are structurally complex and function as adaptors to redirect the cytotoxicity of T cells to kill tumor cells. T-cell-engaging bispecific antibodies can be generally divided into two categories: IgG/IgG-like and non-IgG-like formats. Different formats may have different intrinsic potencies and physiochemical properties, and comprehensive studies are needed to gain a better understanding of how the differences in formats impact on structural and functional characteristics. In this study, we designed and generated bispecific T-cell-engaging antibodies with IgG-like (DVD-Ig) and non-IgG (BiTE) formats. Both target the same pair of antigens (EGFR and CD3) to minimize the possible influence of targets on functional characterization. We performed a side-by-side comparison to assess differences in the physiochemical and biological properties of these two bispecific T-cell-engaging antibodies using a variety of breast and ovarian cancer cell-based functional assays to delineate the structural–functional relationships and anti-tumor activities/potency. We found that the Fc portion of T-cell-engaging bispecific antibodies can significantly impact antigen binding activity, potency, and stability in addition to eliciting different mechanisms of action that contribute the killing of cancer cells.

Background There is limited evidence suggesting that osteoporosis might exacerbate depressive symptoms, while more studies demonstrate that depression negatively affects bone density and increases fracture risk.Aims To explore the relationship between major depressive disorder (MDD) and fracture risk.Methods We conducted a nested case-control analysis (32 670 patients with fracture and 397 017 individuals without fracture) and a matched cohort analysis (16 496 patients with MDD and 435 492 individuals without MDD) in the same prospective UK Biobank data set. Further, we investigated the shared genetic architecture between MDD and fracture with linkage disequilibrium score regression and the MiXeR statistical tools. We used the conditional/conjunctional false discovery rate approach to identify the specific shared loci. We calculated the weighted genetic risk score for individuals in the UK Biobank and logistic regression was used to confirm the association observed in the prospective study.Results We found that MDD was associated with a 14% increase in fracture risk (hazard ratio (HR) 1.14, 95% CI 1.14 to 1.15, p

Background: The accumulation of diverse molecular and cytogenetic variations contributes to the heterogeneity of acute myeloid leukemia (AML), a cluster of hematologic malignancies that necessitates enhanced risk evaluation for prognostic prediction and therapeutic guidance. The ubiquitin–proteasome system plays a crucial role in AML; however, the specific contributions of 49 core proteasome family members (PSMs) in this context remain largely unexplored. Methods: The expression and survival significance of 49 PSMs in AML were evaluated using the data from BeatAML2.0, TCGA, and the GEO database, mainly through the K-M plots, differential genes enrichment analysis, and candidate compounds screening via R language and statistical software. Results: we employed LASSO and Cox regression analyses and developed a model comprising three PSMs (PSMB8, PSMG1, and PSMG4) aimed at predicting OS in adult AML patients, utilizing expression profiles from the BeatAML2.0 training datasets. Patients with higher risk scores were predominantly found in the AML–M2 subtype, exhibited poorer ELN stratification, showed no complete remission following induction therapies, and had a higher mortality status. Consistently, significantly worse OS was observed in high-risk patients across both the training and three validation datasets, underscoring the robust predictive capability of the three-PSMs model for AML outcomes. This model elucidated the distinct genetic abnormalities landscape between high- and low-risk groups and enhanced the ELN risk stratification system. Ultimately, the three-PSMs risk score captured AML-specific gene expression signatures, providing a molecular basis for selecting potential therapeutic agents. Conclusions: In summary, these findings manifested the significant potential of the PSM model for predicting AML survival and informed treatment strategies.

Strong earthquakes often bring amounts of loose material, disrupting the balance of material transportation within a watershed and severely impacting the restoration of the ecological environment and human safety downstream. Therefore, it is crucial to identify the frequency and scale of these debris flow events, as well as to explore their long-term development and impact on internal and external channels. Using multi-source remote sensing images from four perspectives, hillslope, channel, accumulation fan, and their relationship with the mainstream, we reconstructed a debris flow event dataset from 2008 to 2020, explored a method for identifying these events, and analyzed their impacts on channels and accumulation fans in Mozi Gully affected by the Wenchuan earthquake. Loose matter was predominantly found in areas proximate to the channel and at lower elevations during debris flow events. Alterations in channel width, accumulation fans downstream, and their potential to obstruct rivers proved to be vital for identifying the large scale of debris flow event. Finally, we encapsulated the evolution patterns and constraints of post-earthquake debris flows. Determination in frequency and scale could offer valuable supplementary data for scenario hypothesis parameters in post-earthquake disaster engineering prevention and control.

Al₂TiO₅ based ceramics with high mechanical strength and good thermal shock resistance were successfully prepared by adding 1 % -7 % CaO to the alumina titanium dioxide mixtures at 1280-1380 °C for 0.5 h, and the effects of the CaO additive and firing temperature on the phase composition and thermo-mechanical properties of the Al₂TiO₅ ceramics were investigated in the present work. The results show that CaO could promote the formation of the Al₂TiO₅ solid solution, showed a significant impact on the development of the phase composition. The aluminium titanate ceramics sintered with 3% CaO at 1350 °C for 30 min gave an average thermal expansion coefficient of (20-600 °C) 0.83×10-6 K-1, and a bending strength before and after three thermal shock cycles in water from 600 °C to room temperature of 40.59 MPa and 42.23 MPa, respectively.

Objective To exploratively analyze the efficacy and safety of combined laparoscopy and cystoscopy in the treatment of bladder diverticula. Methods Clinical data of patients who received bladder diverticulectomy in Peking Union Medical College Hospital from March 2007 to September 2022 were retrospectively collected.The patients were divided into open/laparoscopy alone group and combined laparoscopy and cystoscopy group based on surgical approach.Surgery-related outcomes and complication rates were compared. Results A total of 11 patients with bladder diverticula who met the inclusion and exclusion criteria were enrolled in thestudy, including 6 patients in the open/laparoscopy alone group and 5 patients in the combined laparoscopy and cystoscopy group.The median maximum diameter of diverticula in the open/laparoscopy alone group and combined laparoscopy and cystoscopy group were 7.5(4.5, 11.5) cm and 5.2(5.0, 7.9) cm, respectively, and the median diameter of diverticula neck were 1.1(1.0, 1.6) cm and 1.5(1.1, 1.8) cm, respectively.Operations were successfully performed in both two groups and the patients had normal urination after drawing the catheter.No recurrence of bladder diverticulum at 6 to 60 months of follow-up.The median operative time[150.0(142.5, 180.0) min vs. 160.0(108.8, 300.0) min], blood loss[50.0(35.0, 50.0) mL vs. 50.0(45.0, 62.5) mL]and indwelling time of drainage tube[5.0(3.5, 5.5) d vs. 4.5(4.0, 6.8) d]were similar between the two group.Compared to the open/laparoscopy alone group, the combined laparoscopy and cystoscopy group had a shorter postoperative hospital stay[6.0(6.0, 8.5) d vs. 9.5(7.0, 16.0) d]and longer indwelling time of urinary catheter[14.0(10.5, 14.0) d vs. 11.5(6.5, 13.3) d].No complications occurred in the combined laparoscopy and cystoscopy group.In the open/laparoscopy alone group, 2 patients underwent postoperative complications, including 1 patient with deep vein thrombosis of the lower extremities and 1 patient with hyperpyrexia. Conclusion Preliminary results show that cystoscopy combined with laparoscopic resection for bladder diverticula can achieve similar outcomes as open surgery alone or laparoscopic surgery, and with greater safety and faster postoperative patient recovery.

A transparent ceramic glaze with good apparent quality and water wettability was successfully prepared by adjusting the mass fraction ratio of Na₂O/K₂O and R₂O/Al₂O₃ at 1280 °c. The effects of the Na₂O/K₂O and R₂O/Al₂O₃ ratios on the surface energy and glossiness of the ceramic glaze were studied in the present work. The results show that the mass fraction ratio of Na₂O/K₂O and R₂O/Al₂O₃ showed an obvious effect on the high temperature viscosity and melting temperature of the glaze, the density of the glaze network structure and the number of broken bonds on the glaze. When Na₂O/K₂O=0.8-1.6, R₂O/Al₂O₃=0.8-1.2, the glaze showed a glossiness of 88.3-108.3 with a 0.11%-12% increase, and the surface energy of 70.17-78.5 mJ · m-2 with a 5.62%-29.55% increase, being obviously higher than those of the basic glaze. The greater the surface energy of the glaze was, the greater the polarity component was, and the better the wettability of the water on the glaze was, which would be conducive to improving the antifouling and easy cleaning of ceramic products.

Strontium-doped hydroxyapatite ceramics with good ferroelectric properties were prepared using 5% bioactive phosphate glass as an additive at 700 °C in this paper. XRD, FTIR, SEM analyses and a ferroelectric tester were used to analyse the crystal structure, phase composition, microstructure and ferroelectric properties of the prepared ceramics. The results revealed that substitution of Ca2+ by Sr2+ in the HA lattice would lead to an increase in its lattice parameters and a decrease in crystallinity. Moreover, the lattice distortion and the increase in the electric dipole moment caused by the Sr2+ doping enhanced the ferroelectric properties of the Sr-HA ceramics. Increasing the density of the samples could enhance their ferroelectric properties. The remnant polarisation intensity increased from 0.0156 μC/cm² to 0.0728 μC/cm², the maximum polarisation intensity increased from 0.1210 μC/cm² to 0.1628 μC/cm².

Abstract Background: Diverticular disease has been inconsistently associated with colorectal cancer risk. We conducted a bidirectional Mendelian randomization study to assess this association. Methods: Forty-three and seventy single-nucleotide polymorphisms associated with diverticular disease and colorectal cancer at the genome-wide significance level (p

ObjectCognitive decline and obesity are major global public health issues, and their association has been widely acknowledged. The link between the visceral adiposity index (VAI) and cognitive function in the Chinese population remains uncertain. This study aims to investigate the effects of VAI levels on cognitive function in the Chinese middle-aged and elderly population.MethodsWe analyzed longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) collected in 2011, 2013, 2015, and 2018. VAI levels were divided into three tertiles. Generalized estimating equation (GEE) models were used to explore the relationships between VAI levels and cognitive function, including overall cognitive scores, episodic memory, and mental status. Adjustments were made for potential confounders.ResultsThe study consisted of 2,677 participants. Contrary to expectations, higher VAI levels were associated with higher overall cognitive scores and improved episodic memory scores, while no significant effect was observed on mental status. The GEE models consistently indicated that higher VAI levels were associated with higher overall cognitive scores, primarily due to their association with episodic memory. Stratified analyses revealed that the VAI was associated with better cognitive function primarily in males, individuals under 60 years old, those with lower education levels, rural residents, and married individuals, mainly in relation to episodic memory. No significant interactions were observed between VAI and demographic factors.ConclusionOur findings suggest that higher visceral adiposity is associated with slower cognitive decline in the Chinese middle-aged and elderly population, especially in its association with episodic memory. These results underline the need to further investigate the potential protective role of visceral fat in cognitive function, potentially offering new insights for interventions to enhance cognitive function and prevent dementia in this population.

Abstract Ferroptosis, a newly discovered irondependent form of regulated cell death caused by excessive accumulation of lipid peroxides, is linked to the development and treatment response of various types of cancer, including gastric cancer (GC). Noncoding RNAs (ncRNAs), as key regulators in cancer, have both oncogenic and tumor suppressive roles. However, studies on ferroptosis-related ncRNA networks in GC are still lacking. Here, we first identified 61 differentially expressed genes associated with ferroptosis in GC by computing and analyzing gene expression profile of tumor and normal tissues for GC. Then, upstream lncRNAs and miRNAs interacting with them were found through miRNet and miRBase databases, and hub lncRNAs and miRNAs were obtained through topological analysis. Finally, the ceRNA regulatory network linked to ferroptosis in GC was established, which includes two ferroptosis marker genes (TXNIP and TSC22D3), one driver gene (GABARAPL1), and one suppressor gene (CAV1). Kaplan-Meier survival analysis showed that changes in the expression of these genes were associated with the survival of GC patients. Furthermore, our study revealed that this ceRNA network may influence the progression of GC by regulating ferroptosis process. These results will help experimental researchers to design an experiment study to further explore the roles of this regulatory network in GC ferroptosis.

Aluminium titanate (Al₂TiO₅) based ceramic materials were successfully processed through the addition of porcelain clay and different amounts of CaO to the stoichiometric alumina - titania mixtures that contain commonly used MgO and Fe₂O₃ additives at 1350-1400 ̊C for 1 h. The effect of the addition of CaO and sintering temperatures on the formation of the Al₂TiO₅ ceramics and thermal-mechanical performances were investigated. The results revealed that CaO promoted the formation of a long columnar Al₂TiO₅ solid solution and anorthite as well as gahnite phases. Due to the mismatch of the thermal expansion coefficient between the Al₂TiO₅ solid solution crystals and the anorthite and gahnite phases, a compressive residual stress developed on the surface of the Al₂TiO₅ solid solution particulates, effectively improving the mechanical properties and inhibiting the thermal decomposition of the Al₂TiO₅ solid solution and the microcrack propagation. The average thermal expansion coefficient (20-800 ̊C) of the sample with 3 wt% CaO sintered at 1400 ̊C for 60 min was 0.80×10-6 ̊C-1, and the flexural strength of the sample with 5 wt% CaO sintered at 1380 ̊C was as high as 58.59 MPa, with a 12.43 % increase in the strength after the thermal shock test.

Abstract Background Globally, gastric cancer is the third most common cancer and the third leading cause of cancer death. Proximal and distal gastric cancers have distinct clinical and biological behaviors. The microbial composition and metabolic differences in proximal and distal gastric cancers have not been fully studied and discussed. Methods In this study, the gastric microbiome of 13 proximal gastric cancer tissues, 16 distal gastric cancer tissues, and their matched non-tumor tissues were characterized using 16S rRNA amplicon sequencing. Additionally, 10 proximal gastric cancer tissues, 11 distal gastric cancer tissues, and their matched non-tumor tissues were assessed by untargeted metabolomics. Results There was no significant difference in microbial diversity and richness between the proximal and distal gastric cancer tissues. At the genus level, the abundance of Rikenellaceae_RC9_gut_group, Porphyromonas, Catonella, Proteus, Oribacterium, and Moraxella were significantly increased in Proximal T, whereas that of Methylobacterium_Methylorubrum was significantly increased in Distal T. The untargeted metabolomics analysis revealed 30 discriminative metabolites between Distal T and Distal N. In contrast, there were only 4 discriminative metabolites between Proximal T and Proximal N. In distal gastric cancer, different metabolites were scattered through multiple pathway, including the sphingolipid signaling pathway, arginine biosynthesis, protein digestion and absorption, alanine, aspartate and, glutamate metabolism, etc.In proximal gastric cancer, differential microbial metabolites were mainly related to hormone metabolism. Conclusion Methylobacterium-Methylorubrum was significantly increased in Distal T, positively correlated with cancer-promoting metabolites, and negatively correlated with cancer-inhibiting metabolites. Rikenellaceae_RC_gut_group was significantly increased in Proximal T and positively correlated with cancer-promoting metabolites. Further studies regarding the functions of the above-mentioned microorganisms and metabolites were warranted as the results may reveal the different mechanisms underlying the occurrence and development of proximal and distal gastric cancers and provide a basis for future treatments. Importance First, the differences in microbial composition and metabolites between the proximal and distal gastric cancers were described; then, the correlation between microbiota and metabolites was preliminarily discussed. These microbes and metabolites deserve further investigations as they may reveal the different mechanisms involved in the occurrence and development of proximal and distal gastric cancers and provide a basis for future treatments.

Abstract Stigmasterol (ST) has been shown to improve both lipid and bile acid (BA) metabolism. However, the mechanism(s) by which ST prevents dyslipidemia via BA metabolism, and the potential involvement of other regulatory mechanisms, remains unclear. Here, we found that ST treatment effectively alleviates lipid metabolism disorder induced by a high-fat diet (HFD). Moreover, we also show that fecal microbiota transplantation from ST-treated rats displays similar protective effects in rats fed on an HFD. Our data confirm that the gut microbiota plays a key role in attenuating HFD-induced fat deposition and metabolic disorders. In particular, ST reverses HFD-induced gut microbiota dysbiosis in rats by reducing the relative abundance of Erysipelotrichaceae and Allobaculum bacteria in the gut. In addition, ST treatment also modifies the serum and fecal BA metabolome profiles in rats, especially in CYP7A1 mediated BA metabolic pathways. Furthermore, chenodeoxycholic acid combined with ST improves the therapeutic effects in HFD-induced dyslipidemia and hepatic steatosis. In addition, this treatment strategy also alters BA metabolism profiles via the CYP7A1 pathway and gut microbiota. Taken together, ST exerts beneficial effects against HFD-induced hyperlipidemia and obesity with the underlying mechanism being partially related to both the reprogramming of the intestinal microbiota and metabolism of BAs in enterohepatic circulation. This study provides a theoretical basis for further study of the anti-obesity effects of ST and consideration of the gut microbiota as a potential target for the treatment of HFD-induced dyslipidemia.

In isotropic two dimensional systems, long range ferromagnetic order is supressed by thermal fluctuations, and it is due to magnetic anisotropy that van der Waals magnetic materials can have ferromagnetic ordering at finite temperatures. Usually this magnetic anisotropy is relatively small, but in this manuscript Zhang et al make a two dimensional van der Waals material with exceptionally large perpendicular magnetic anisotropy and ferromagnetic ordering that exits up to 350 K.

Objective To explore the expression of insulin-like growth factor 2 (IGF2) in urinary exosomes of patients with bladder urothelial carcinoma, and to evaluate its clinical value in the diagnosis of bladder urothelial carcinoma. Methods Patients with bladder urothelial carcinoma or non-urothelial carcinoma diagnosed and treated by Peking Union Medical College Hospital from September to December 2020 were prospectively selected as the research subjects. Fluorescence quantitative reverse transcription PCR was used to detect the expression levels of IGF2 in the urine exosomes of the two groups. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of IGF2 in urinary exosomes for diagnosing bladder urothelial carcinoma were calculated, using pathological results as the gold standard. Results A total of 35 patients with bladder urothelial carcinoma and 60 non-urothelial carcinoma patients who met the inclusion and exclusion criteria were selected. The positive expression rate of IGF2 in urinary exosomes in patients with bladder urothelial carcinoma was significantly higher than that in patients with non-urothelial carcinoma (71.4% vs. 10.0%, P=0.000). The sensitivity of IGF2 in urinary exosomes for diagnosing bladder urothelial carcinoma was 71.43% (95% CI: 53.48%-84.76%), the specificity was 90.00% (95% CI: 78.83%-95.87%), the positive likelihood ratio was 7.14 (95% CI: 3.25-15.70), the negative likelihood ratio was 0.32 (95% CI: 0.19-0.54). Conclusions IGF2 is highly expressed in urinary exosomes of patients with bladder urothelial carcinoma, which has high diagnostic specificity for bladder urothelial carcinoma, but a slightly lower sensitivity. IGF2 is expected to be used as a primary screening index for bladder urothelial carcinoma.

Prostate cancer (PCa) is currently the second most common cancer in men worldwide.The current gold standard for diagnosing PCa relies on ultrasound-guided systematic core needle biopsy after detection changes in a digital rectal examination and elevated prostate-specific antigen(PSA) level in the blood serum. Yet, serum PSA cannot reliably discriminate between benign pathologies and clinically significant forms of PCa. A common problem caused by the low specificity of this marker is over diagnosis, which leads to unnecessary biopsies and over treatment. This may be associated with various treatment complications (such as bleeding or infection) and generate unnecessary costs. Therefore, there is an urgent need for more specific and predictive biomarkers to effectively discriminate between aggressive and nonaggressive tumors and to avoid unnecessary prostate biopsies. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with PCa biomarkers, including prostate cancer cells, DNAs, RNAs, proteins and other small molecules. In recent years, several non-invasive, cost-effective, high-accuracy urinary diagnostic biomarkers such as PSA, PCA3, MALAT1 and microRNA have been developed. This article reviews the biomarkers for the non-invasive testing of PCa in urine.

Colorectal neoplasia differentially expressed (CRNDE) is an oncogenic long noncoding RNA (lncRNA). Increased CRNDE expression was initially discovered in colorectal cancer and then in a variety of solid tumors and hematological malignancies. CRNDE participates in multiple biological processes, such as cell proliferation, differentiation, migration, and apoptosis. CRNDE has been shown to modulate target gene expression through multiple mechanisms, including transcriptional regulation, post-transcriptional regulation, and competition for microRNA (miRNA) binding. In this review, we summarize the evidence that supports CRNDE in the diagnosis and prognosis predicting of cancers. The functional roles and molecular mechanisms of CRNDE are further described for major types of solid tumors and hematological malignancies. The therapeutic potential of CRNDE as a target for research and development is also discussed.

Immune cells play an important role in the inflammatory and proliferative stages of diabetes skin defect. How to regulate immune response is the key to skin regeneration. To address this challenge, we developed chitosan polymer membrane (CM) to directly deliver solamarine (Sol) for targeting reactive oxygen species (ROS)-enriched microenvironment. The Sol-loaded CM (Sol-CM) inhibits the excessive recruitment of inflammatory cells, and polarizes macrophages into an anti-inflammatory phenotype “M2″ to inhibit excessive inflammatory response. Therefore, the Sol-CM can help maintain immune homoeostasis, which contributes to the pathogenesis of wound. The Sol-CM demonstrated excellent therapeutic efficacy in treating wound. In addition, Sol-CM significantly attenuates focal inflammation and fibrosis level, thus potentially leading to a highly innovative and translational approach to treat diabetic wound efficiently and safely.

BackgroundSince severe fever with thrombocytopenia syndrome virus (SFTSV) was first reported in 2009, a large number of relevant studies have been published. However, no bibliometrics analysis has been conducted on the literature focusing on SFTSV. This study aims to evaluate the research hotspots and future development trends of SFTSV research through bibliometric analysis, and to provide a new perspective and reference for future SFTSV research and the prevention of SFTSV.MethodsWe retrieved global publications on SFTSV from the Web of Science Core Collection (WoSCC) and Scopus databases from inception of the database until 2022 using VOSviewer software and CiteSpace was used for bibliometric analysis.ResultsThe number of SFTSV-related publications has increased rapidly since 2011, peaking in 2021. A total of 45 countries/regions have published relevant publications, with China topping the list with 359. The Viruses-Basel has published the most papers on SFTSV. In addition, Yu et al. have made the greatest contribution to SFTSV research, with their published paper being the most frequently cited. The most popular SFTSV study topics included: (1) pathogenesis and symptoms, (2) characteristics of the virus and infected patients, and (3) transmission mechanism and risk factors for SFTSV.ConclusionsIn this study, we provide a detailed description of the research developments in SFTSV since its discovery and summarize the SFTSV research trends. SFTSV research is in a phase of explosive development, and a large number of publications have been published in the past decade. There is a lack of collaboration between countries and institutions, and international collaboration and exchanges should be strengthened in the future. The current research hotpots of SFTSV is antiviral therapy, immunotherapy, virus transmission mechanism and immune response.

Abstract Background Breast cancer is the malignant tumor with the highest incidence in women. DNA methylation has an important effect on breast cancer, but the effect of abnormal DNA methylation on gene expression in breast cancer is still unclear. Therefore, it is very important to find therapeutic targets related to DNA methylation. Results In this work, we calculated the DNA methylation distribution and gene expression level in cancer and para-cancerous tissues for breast cancer samples. We found that DNA methylation in key regions is closely related to gene expression by analyzing the relationship between the distribution characteristics of DNA methylation in different regions and the change of gene expression level. Finally, the 18 key genes (17 tumor suppressor genes and 1 oncogene) related to prognosis were confirmed by the survival analysis of clinical data. Some important DNA methylation regions in these genes that result in breast cancer were found. Conclusions We believe that 17 TSGs and 1 oncogene may be breast cancer biomarkers regulated by DNA methylation in key regions. These results will help to explore DNA methylation biomarkers as potential therapeutic targets for breast cancer.

As regression testing size and cost increase,test suite reduction becomes more important to promote its efficiency.Du-ring the selection of test suite subset,we are supposed to consider the representativeness and diversity of subset,and apply an effective algorithm to solve it.Aimed at test suite reduction,a submodular function maximization based algorithm,SubTSR,is proposed in this paper.Although the introduced discrete optimization problem is an NP-hard problem,the heuristic greedy search is used in this paper to find the suboptimal solution with approximation guarantee by exploiting the submodularity of the objective function.To validate the effectiveness of the SubTSR algorithm,the SubTSR algorithm is experimented on fifteen datasets with changes of topic count in LDA and distance for similarity measurement,and compared with other test suite reduction algorithms about the average percentage of fault-detection,fault detection loss rate,first faulty test's index and other metrics.The experiment results show that the SubTSR algorithm has significant improvement in fault detection performance compared with other algorithms,and its performance remains relatively stable on different datasets.Under the text representation change due to topic count change,the SubTSR combined with Manhattan distance keeps relatively stable compared with other algorithms.

SiC-TiC composite powders were synthesised through carbothermal reduction under an argon atmosphere by using silica sol, starch, and TiO₂ as the raw materials. The influences of the starch dosage and holding time on the synthesis of SiC-TiC composite powder are discussed in detail. The samples were characterised using an X-ray diffractometer (XRD), an integrated thermal analyser (TG-DTA), a scanning electron microscope (SEM), and an energy spectrometer (EDS). The results showed that the SiC-TiC composite powders were completely synthesised after holding at 1550 °C for 3 h when the amount of excess starch was 5 wt% and after holding at 1550 °C for 2 h when the amount of excess starch was 10 wt%-20 wt%. The morphological characteristics of the powder samples with 5 wt%-15 wt% excess starch calcined at 1550 °C for 2 h were mainly flake particles, spherical particles, irregularly shaped particles and elongated whiskers. Conversely, no whiskers were found in the powder samples calcined at 1550 °C for 2 h when the amount of excess starch was 20 wt%.

This patient was an elderly man with left carotid body tumor, cardiac paraganglioma and right adrenal pheochromocytoma at the same time. It was a rare case with a complex condition, and the diagnosis and treatment were difficult. After two rounds of discussion in the multidisciplinary team, our hospital successively removed the lesions of the heart and the right adrenal, and the patient was discharged smoothly after the operations. The diagnosis and treatment of this patient reflects the significance of the multidisciplinary team on the diagnosis and treatment of difficult diseases.

Because of rapid emergence and circulation of the SARS-CoV-2 variants, especially Omicron which shows increased transmissibility and resistant to antibodies, there is an urgent need to develop novel therapeutic drugs to treat COVID-19. In this study we developed an in vitro cellular model to explore the regulation of ACE2 expression and its correlation with ACE2-mediated viral entry. We examined ACE2 expression in a variety of human cell lines, some of which are commonly used to study SARS-CoV-2. Using the developed model, we identified a number of inhibitors which reduced ACE2 protein expression. The greatest reduction of ACE2 expression was observed when CK869, an inhibitor of the actin-related protein 2/3 (ARP2/3) complex, was combined with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an inhibitor of sodium-hydrogen exchangers (NHEs), after treatment for 24 h. Using pseudotyped lentivirus expressing the SARS-CoV-2 full-length spike protein, we found that ACE2-dependent viral entry was inhibited in CK869 + EIPA-treated Calu-3 and MDA-MB-468 cells. This study provides an in vitro model that can be used for the screening of novel therapeutic candidates that may be warranted for further pre-clinical and clinical studies on COVID-19 countermeasures.

Acute promyelocytic leukemia (APL) is characterized by the balanced translocation of chromosomes 15 and 17, resulting in the formation of PML-RARA fusion gene. More than 98% of APL have PML-RARA fusion, and less than 2% have other types of RARA gene partners, which named variant APL (vAPL). In the present study, we reported a vAPL with BCOR-RARA, which was the third case of BCOR-RARA APL published. The patient achieved complete remission (CR) with all-trans retinoic acid (ATRA) monotherapy, and molecular CR with ATRA plus standard chemotherapy. After that, he underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and ATRA maintenance and maintained a molecular CR status. This case provided valuable insights into the accurate identification of vAPL. Moreover, ATRA combined with chemotherapy followed by allo-HSCT was suggested as an optimal choice for those vAPL patients who had a high risk of relapse.

Atezolizumab is an immune checkpoint inhibitor (ICI) targeting PD-L1 for treatment of solid malignancies. Immune checkpoints control the immune tolerance, and the adverse events such as hepatotoxicity induced by ICIs are often considered as an immune-related adverse event (irAE). However, PD-L1 is also highly expressed in normal tissues, e.g., hepatocytes. It is still not clear whether, targeting PD-L1 on hepatocytes, the atezolizumab may cause damage to liver cells contributing to hepatotoxicity. Here, we reveal a novel mechanism by which the atezolizumab induces hepatotoxicity in human hepatocytes. We find that the atezolizumab treatment increases a release of LDH in the cell culture medium of human hepatocytes (human primary hepatocytes and THLE-2 cells), decreases cell viability, and inhibits the THLE-2 and THLE-3 cell growth. We demonstrate that both the atezolizumab and the conditioned medium (T-CM) derived from activated T cells can induce necroptosis of the THLE-2 cells, which is underscored by the fact that the atezolizumab and T-CM enhance the phosphorylation of RIP3 and MLKL proteins. Furthermore, we also show that necrostatin-1, a necrosome inhibitor, decreases the amount of phosphorylated RIP3 induced by the atezolizumab, resulting in a reduced LDH release in the culture media of the THLE-2 cells. This finding is further supported by the data that GSK872 (a RIP3 inhibitor) significantly reduced the atezolizumab-induced LDH release. Taken together, our data indicate that the atezolizumab induces PD-L1-mediated necrosome formation, contributing to hepatotoxicity in PD-L1+-human hepatocytes. This study provides the molecular basis of the atezolizumab-induced hepatotoxicity and opens a new avenue for developing a novel therapeutic approach to reducing hepatotoxicity induced by ICIs.

Patients with newly diagnosed acute promyelocytic leukemia (APL) are often obese or overweight, accompanied by metabolic disorders, such as dyslipidemia. However, the link between dyslipidemia and leukemia is obscure. Here, we conducted a retrospective study containing 1,412 cases (319 newly diagnosed APL patients, 393 newly diagnosed non-APL acute myeloid leukemia patients, and 700 non-tumor controls) and found that APL patients had higher triglyceride levels than non- APL and control groups. Using clinical data, we revealed that hypertriglyceridemia served as a risk factor for early death in APL patients, and there was a positive correlation between triglyceride levels and leukocyte counts. RNA sequencing analysis of APL patients having high or normal triglyceride levels highlighted the contribution of peroxisome proliferatoractivated receptor-α (PPARα), a crucial regulator of cell metabolism and a transcription factor involved in cancer development. The genome-wide chromatin occupancy of PPARα revealed that PPARα co-existed with PML/RARα within the super-enhancer regions to promote cell proliferation. PPARα knockdown affected the expression of target genes responsible for APL proliferation, including FLT3, and functionally inhibited the proliferation of APL cells. Moreover, in vivo results in mice having high fat diet-induced high triglyceride levels supported the connection between high triglyceride levels and the leukemic burden, as well as the involvement of PPARα-mediated-FLT3 activation in the proliferation of APL cells. Our findings shed light on the association between APL proliferation and high triglyceride levels and provide a genetic link to PPARα-mediated hyperlipidemia in APL.

Abstract Background E3 ubiquitin ligase HRD1 (HMG-CoA reductase degradation protein 1, alias synoviolin with SYVN1 as the official gene symbol) was found downregulated and acting as a tumor suppressor in breast cancer, while the exact expression profile of HRD1 in different breast cancer subtypes remains unknown. Recent studies characterized circular RNAs (circRNAs) playing an regulatory role as miRNA sponge in tumor progression, presenting a new viewpoint for the post-transcriptional regulation of cancer-related genes. Methods Examination of the expression of HRD1 protein and mRNA was implemented using public microarray/RNA-sequencing datasets and breast cancer tissues/cell lines. Based on public RNA-sequencing results, online databases and enrichment/clustering analyses were used to predict the specific combinations of circRNA/miRNA that potentially govern HRD1 expression. Gain-of-function and rescue experiments in vitro and in vivo were executed to evaluate the suppressive effects of circNR3C2 on breast cancer progression through HRD1-mediated proteasomal degradation of Vimentin, which was identified using immunoblotting, immunoprecipitation, and in vitro ubiquitination assays. Results HRD1 is significantly underexpressed in triple-negative breast cancer (TNBC) against other subtypes and has an inverse correlation with Vimentin, inhibiting the proliferation, migration, invasion and EMT (epithelial-mesenchymal transition) process of breast cancer cells via inducing polyubiquitination-mediated proteasomal degradation of Vimentin. CircNR3C2 (hsa_circ_0071127) is also remarkably downregulated in TNBC, negatively correlated with the distant metastasis and lethality of invasive breast carcinoma. Overexpressing circNR3C2 in vitro and in vivo leads to a crucial enhancement of the tumor-suppressive effects of HRD1 through sponging miR-513a-3p. Conclusions Collectively, we elucidated a bona fide circNR3C2/miR-513a-3p/HRD1/Vimentin axis that negatively regulates the metastasis of TNBC, suggesting that circNR3C2 and HRD1 can act as potential prognostic biomarkers. Our study may facilitate the development of therapeutic agents targeting circNR3C2 and HRD1 for patients with aggressive breast cancer.

Since China is the largest developing country in the world, its urban reconstruction has significance for countries undergoing rapid urbanization. The recent development of its central cities has gradually changed from large-scale incremental expansion to stock optimization. District boundary reorganization has become a new trend in reforming China’s administrative division of central cities. From the perspective of scalar reorganization and regional reconstruction, the adjustment of urban administrative divisions can be regarded as a regional construction strategy initiated by city governments to reshape the spatial structure, improve the governance relationship, and enhance the cities’ competitiveness. This study takes Hangzhou, an important central city in eastern China, as a case study to illustrate two ways in which a central city can optimize its urban spaces through district boundary recombination: scale recombination and regional recombination. The findings demonstrate two advantages of district boundary reorganization for China’s central cities: it eases the integration of new city districts and urban areas and promotes balanced development within the city. In the future, more Chinese cities will likely choose to reorganize their district boundaries.

Relative energy deficiency in sport (RED-S), which underpins the concept of low energy availability (LEA), can negatively affect athletes’ health and performance. This study aims to investigate the prevalence of RED-S among national athletes in Malaysia. A total of 192 national athletes (97 males, 18–39 years old) responded to an online survey regarding the RED-S risk. Most athletes (67.2%) were classified as having a medium/high RED-S risk. Female (41.2%), weight-class (23.9%), and intermittent sports (20.3%) had the highest prevalence of medium/high RED-S risk. Overall, most athletes spent 2–5 h daily (55.2%) and 6–7 days weekly (53.6%) practicing or playing their sport, and 47.9% reported feeling tired recently. The athletes were also terrified of being overweight (61.5%), worried about what they eat (64.7%), concerned about having fat on their bodies (62.6%), and thinking about burning calories while exercising (69.3%). Only 16.7% of the athletes had a prior history of stress fractures, and 40.6% continued to participate in activities 6–7 days per week while injured. The majority of female athletes (88.3%) had regular menstrual cycles. These findings support the notion that RED-S screening should be addressed in the athletic community. Future research is needed to clinically assess these athletes and investigate the impacts of RED-S on their health and sports performance.

COVID-19 is spreading widely, and the pandemic is seriously threatening public health throughout the world. A comprehensive study on the optimal sampling types and timing for an efficient SARS-CoV-2 test has not been reported. We collected clinical information and the values of 55 biochemical indices for 237 COVID-19 patients, with 37 matched non-COVID-19 pneumonia patients and 131 healthy people in Inner Mongolia as control. In addition, the results of dynamic detection of SARS-CoV-2 using oropharynx swab, pharynx swab, and feces were collected from 197 COVID-19 patients. SARS-CoV-2 RNA positive in feces specimen was present in approximately one-third of COVID-19 patients. The positive detection rate of SARS-CoV-2 RNA in feces was significantly higher than both in the oropharynx and nasopharynx swab (P < 0.05) in the late period of the disease, which is not the case in the early period of the disease. There were statistically significant differences in the levels of blood LDH, CRP, platelet count, neutrophilic granulocyte count, white blood cell number, and lymphocyte count between COVID-19 and non-COVID-19 pneumonia patients. Finally, we developed and compared five machine-learning models to predict the prognosis of COVID-19 patients based on biochemical indices at disease onset and demographic characteristics. The best model achieved an area under the curve of 0.853 in the 10-fold cross-validation.

Disaster risk management (DRM) is the application of disaster risk reduction policies and strategies to reduce existing disaster risk and manage residual risk. However, due to dynamic human factors, it is challenging to depict and assess the effectiveness of DRM measures, and their implementation usually lacks a sufficient evidence-based evaluation process. Therefore, this study developed an agent-based model to integrate dynamic human behaviors into the DRM measures and evaluated their effectiveness in casualty reduction. The model was calibrated to simulate the debris flow event at Longchi town, China in 13 August 2010. The early warning system (EWS) and related DRM measures were taken as examples. The effectiveness of different DRM measures was quantitated by comparing the number of potential casualties. The main findings were: 1) EWS was very effective for community-based DRM as it could significantly decrease the average casualties by 30%. 2) Credibility of EWS was critical to its effectiveness. Less credible EWS might reduce its effectiveness by 9%. 3) EWS could be supplemented by other measures to further reduce casualties by 6%. 4) The downside effects of other DRM measures to EWS might exist and reduce its effectiveness by up to 5%. This study put forward an evidence-based approach to help policymakers select more cost-effective DRM measure, especially in the less developed countries where the available resources for DRM are limited.

Time-varying system identification is an appealing but challenging research area. Existing identification algorithms are usually subject to either low estimation accuracy or bad numerical stability. These deficiencies motivate the development of an iterative learning identification algorithm in this paper. Three distinguished features of the proposed method result in the achievement of high estimation accuracy and high numerical stability: i) recursion along the iteration axis, ii) bias compensation, and iii) singular value decomposition (SVD). Firstly, an extra iteration axis associated with the original time axis is introduced in the parameter estimation process. A norm-optimal identification approach with the balance between convergence speed and noise robustness is then proposed along the iteration axis, followed by further analysis on the accuracy and the numerical stability. Secondly, in order to eliminate the estimation bias in the presence of noise and thus to improve the accuracy, a bias compensation algorithm along the iteration axis is proposed. Thirdly, a SVD-based update algorithm for the covariance matrix is developed to avoid the possible numerical instability during iterations. Numerical examples are finally provided to validate the algorithm and confirm its effectiveness.

Abstract The combination of semiconductivity and tunable ferromagnetism is pivotal for electrical control of ferromagnetism and next‐generation low‐power spintronic devices. However, Curie temperatures (TC) for most traditional intrinsic ferromagnetic semiconductors (≤200 K) and recently discovered two‐dimensional (2D) ones (

The dispersion distribution characteristics of prefabricated fragments from an improvised explosive device (IED) are essential in defense technology development. To improve warhead design, it is essential to predict a fragment’s velocity and dispersion distribution accurately. This paper investigates a fragment’s flying angle from a detonated warhead with a cylindrical charge under a one-end central detonation. A modified formula for calculating the fragment dispersion distribution at each axial position of the warhead was obtained based on experimental data and model analysis. The impacts of the following parameters on the flying angle were considered in the formula: ratio of charge mass to shell mass, charge diameter, axial sparse effect, and relative axial shell position. The formula was verified by experimentation to be suitable for wide applications using different validation samples. Theoretical calculations with the formula show good accuracy in predicting the flying angle of cylindrical-shell fragments, agreeing with experimental data. The proposed model meets the error requirements of engineering applications. This work provides a theoretical foundation for subsequent research on damage effectiveness and IED damage assessment.

Summary: Pancreatic endocrine cell differentiation is orchestrated by the action of transcription factors that operate in a gene regulatory network to activate endocrine lineage genes and repress lineage-inappropriate genes. MicroRNAs (miRNAs) are important modulators of gene expression, yet their role in endocrine cell differentiation has not been systematically explored. Here we characterize miRNA-regulatory networks active in human endocrine cell differentiation by combining small RNA sequencing, miRNA over-expression, and network modeling approaches. Our analysis identified Let-7g, Let-7a, miR-200a, miR-127, and miR-375 as endocrine-enriched miRNAs that drive endocrine cell differentiation-associated gene expression changes. These miRNAs are predicted to target different transcription factors, which converge on genes involved in cell cycle regulation. When expressed in human embryonic stem cell-derived pancreatic progenitors, these miRNAs induce cell cycle exit and promote endocrine cell differentiation. Our study delineates the role of miRNAs in human endocrine cell differentiation and identifies miRNAs that could facilitate endocrine cell reprogramming. : Molecular Mechanism of Gene Regulation; Molecular Network; Endocrinology; Stem Cells Research Subject Areas: Molecular Mechanism of Gene Regulation, Molecular Network, Endocrinology, Stem Cells Research

Earthquakes–induced landslides generally provide abundant loose materials at hillslopes, possibly triggering morphological reshaping processes at river channels and riverbeds during the large flash flood hydrograph and bringing huge risk downstream. Therefore, in a Wenchuan earthquake-affected catchment, the collected hydro-meteorological data and high-precision small Unmanned Aerial Vehicle (sUAV) data were used to quantitatively analyze channel evolution by a large flash flood event on 25 and 26 June 2018. It was found that the stable riverbed structure formed by the armour layer appeared in the tenth year after the Wenchuan earthquake. In a confined channel, the layer can protect the channel and resist the drastic change after the flash flood event with only a small bed elevation from 0.2 m to 2 m. Without the protection of the armour, the change could reach 6 m in the unconfined channel. Meanwhile, more materials with a deposition volume of about 7450 m3 from tributaries were generally taken to the main channel, and more intense erosion with a volume of 105 m3 mostly occurred downstream of tributaries. It was noted that, in the cross-section, the increased channel width could lead to a significant change with the large volume of 35 m3. Additionally, a conceptual diagram of the generalized channel response to large flash floods was provided during multi-stage periods after the Wenchuan earthquake. It determined the rebalance processes of channel evolution in the tenth year after the earthquake. This study will contribute to understanding the post-earthquake long-term channel evolutions and could provide decision-makers of assessing the mitigation strategies for higher-magnitude flood disasters triggered by channel change in earthquake-affected watersheds.