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Single-phase multiferroics exhibiting ferroelectricity and ferromagnetism are considered pivotal for advancing next-generation multistate memories, spintronic devices, sensors, and logic devices. In this study, the magnetic and electric characteristics of bismuth ferrite (BiFeO3) ceramics were enhanced through compositional design and grain engineering. BiFeO3 ceramic was co-substituted by neodymium (Nd) and niobium (Nb), two non-isovalent elements, via the spark plasma sintering process using phase-pure powder prepared via sol-gel as the precursor. The symmetry of the sintered Nd–Nb co-doped samples changed from R3c to Pnma, accompanied by a decrease in the loss tangent, grain size, and leakage current density. The reduction in the leakage current density of the co-doped samples was ~three orders of magnitude. Moreover, ferroelectric, dielectric, and magnetic properties were substantially improved. The remanent polarization and magnetization values of the optimized Nd–Nb co-doped BiFeO3 sample were 3.12 μC cm−2 and 0.15 emu g−1, respectively. The multiferroic properties were enhanced based on multiple factors such as structural distortion caused by co-doping, grain size reduction, suppression of defect charges via donor doping, space-modulated spin structure disruption, and an increase in magnetic ions. The synergistic approach of composition design and grain engineering sets a paradigm for the advancement of multiferroic materials. [ABSTRACT FROM AUTHOR]

Background and Aim: Visceral fat (VF) was proved to be a more precise predictor of atherosclerotic cardiovascular disease (ASCVD) risk in individuals with type 2 diabetes mellitus (T2DM) than body mass index (BMI) itself. Even when the BMI was normal, visceral fat area (VFA) ≥ 90 cm² could raise the ten-year risk of developing ASCVD. Therefore, it was worth evaluating the association of influencing factors with high VF in non-obese T2DM individuals. Methods: This study enrolled 1,409 T2DM participants with T2DM, of whom 538 had a normal BMI. Based on VFA, these subjects were divided into two groups: VF (+) (VFA ≥ 90cm2) (n = 110) and VF (-) (VFA < 90cm2) (n = 428). The measurement of VFA was conducted using an Omron VF measuring device. Anthropometric and metabolic parameters were detected. Novel insulin resistance indices, such as lipid accumulation product (LAP) was calculated. Factors associated with VF were screened using univariate analysis, multifactorial binary logistic regression models and chi-squared automatic interaction detector decision tree model. Results: The VF (+) OB (-) (BMI ≤ 23.9 kg/m2) prevalence were 7.8% in T2DM subjects (n = 1,409) and 20.4% in T2DM subjects with normal BMI (n = 538), respectively. In T2DM subjects with normal BMI, the logistic regression model suggested that neck circumference (NC) had an odds ratio (OR) of 1.891 (95% CI: 1.165–3.069, P = 0.010). The OR for VF gradually increased from the 1st to the 4th in LAP quartile (P < 0.05). LAP emerged as the root node, followed by NC in the decision tree model. Receiver operating characteristic curve (ROC) analysis demonstrated that the area under the curve (AUC) for NC in predicting high VF levels was 0.640 for males and 0.682 for females. Optimal NC cut-off points were 37.75 cm for males and 34.75 cm for females, respectively. Additionally, the AUC values of LAP in predicting high VF levels were 0.745 for males and 0.772 for females, with optimal LAP cut-off points of 22.64 and 26.45 for males and females, respectively. Conclusion: This study identified NC and LAP can be considered predictors of high VF in T2DM subjects with normal BMI. [ABSTRACT FROM AUTHOR]

Background: Preimplantation embryos in vivo are exposed to various growth factors in the female reproductive tract that are absent in in vitro embryo culture media. Cell-free fat extract exerts antioxidant, anti-ageing, and ovarian function-promoting effects. However, its effects on embryo quality are yet to be investigated. Methods: We assessed the effect of cell-free fat extract supplementation on embryo culture using a naturally ageing mouse model. We assessed the model's efficacy in influencing embryo development and pregnancy rates in older women with in vitro fertilization failure. In addition, we performed immunofluorescence staining, multiplex immunoassay, whole-genome amplification and DNA sequencing, time-lapse embryo monitoring, and in vitro experiments. Results: Cell-free fat extract-supplemented media has a suitable osmolarity and pH and contains high levels of bioactive growth factors. Cell-free fat extract promoted embryo development and implantation in aged mice, probably by increasing embryo growth rate, inhibiting cell apoptosis, and promoting blastocyst adhesion. Clinical results showed that the cell-free fat extract group had significantly higher rates of the day 3 available and high-quality embryos than the control group, and the rate of usable embryos tended to be higher in the cell-free fat extract group. Furthermore, implantation and clinical pregnancy rates improved in the cell-free fat extract group than in the control group. Conclusions: Our study implies that cell-free fat extract supplementation can promote embryo development and clinical outcomes and may serve as a rescue strategy for older women with in vitro fertilization failure. [ABSTRACT FROM AUTHOR]

Late embryogenesis abundant (LEA) proteins are a class of proteins associated with osmotic regulation and plant tolerance to abiotic stress. However, studies on the LEA gene family in the alpine cold-tolerant herb are still limited, and the phylogenetic evolution and biological functions of its family members remain unclear. In this study, we conducted genome-wide identification, phylogenetic evolution, and abiotic stress response analyses of LEA family genes in Notopterygium species, alpine cold-tolerant medicinal herbs in the Qinghai–Tibet Plateau and adjacent regions. The gene family identification analysis showed that 23, 20, and 20 LEA genes were identified in three Notopterygium species, N. franchetii, N. incisum, and N. forrestii, respectively. All of these genes can be classified into six LEA subfamilies: LEA_1, LEA_2, LEA_5, LEA_6, DHN (Dehydrin), and SMP (seed maturation protein). The LEA proteins in the three Notopterygium species exhibited significant variations in the number of amino acids, physical and chemical properties, subcellular localization, and secondary structure characteristics, primarily demonstrating high hydrophilicity, different stability, and specific subcellular distribution patterns. Meanwhile, we found that the members of the same LEA subfamily shared similar exon–intron structures and conserved motifs. Interestingly, the chromosome distributions of LEA genes in Notopterygium species were scattered. The results of the collinearity analysis indicate that the expansion of the LEA gene family is primarily driven by gene duplication. A Ka/Ks analysis showed that paralogous gene pairs were under negative selection in Notopterygium species. A promoter cis-acting element analysis showed that most LEA genes possessed multiple cis-elements connected to plant growth and development, stress response, and plant hormone signal transduction. An expression pattern analysis demonstrated the species-specific and tissue-specific expression of NinLEAs. Experiments on abiotic stress responses indicated that the NinLEAs play a crucial role in the response to high-temperature and drought stresses in N. franchetii leaves and roots. These results provide novel insights for further understanding the functions of the LEA gene family in the alpine cold-tolerant Notopterygium species and also offer a scientific basis for in-depth research on the abiotic stress response mechanisms and stress-resistant breeding. [ABSTRACT FROM AUTHOR]

During the self-healing process of Bacillus subtilis biofilms on a solid MSgg substrate, large-scale ordered clusters emerge within the biofilm, providing an invasive advantages. To investigate the self-healing mechanism, an agent-based model is employed to simulate the self-healing processes of biofilms at two ages. The study reveals that a uniform cell distribution facilitates the healing of biofilm incisions. The nutrient diffusion rate within the biofilm and the elastic modulus (comprising cell and EPS) play a dominant role in the healing of circumferential incisions, while the diffusion rate outside the biofilm governs the healing of radial and penetrating incisions. These influencing factors can adjust cellular ordering, providing valuable insights for controlling the self-healing of Bacillus subtilis biofilms. [ABSTRACT FROM AUTHOR]

Background and Aims: Inflammatory bowel disease (IBD) requires effective treatment options. Upadacitinib, a Janus kinase 1 (JAK1) inhibitor, has shown effectiveness in trials for Crohn's disease (CD) and ulcerative colitis (UC). This study evaluates its real-world effectiveness and safety. Methods: We conducted a multicenter retrospective cohort study in tertiary care centers, involving patients treated with upadacitinib from January 2023 to September 2024. The study included adult patients aged 18 years or older, diagnosed with UC or CD, who received at least 8 weeks of upadacitinib therapy. Treatment outcomes were evaluated using established clinical, endoscopic, imaging, histological, and laboratory parameters. Results: A total of 236 IBD patients received upadacitinib treatment. In 80 UC patients at 8 weeks, 64.0% achieved steroid-free remission, 57.6% clinical remission, and 81.8% response. Endoscopic remission was 35.8% (p = 0.039), with 63.3% response and 35.8% mucosal healing. Histological remission reached 29.2% (p = 0.009). For 156 CD patients at 12 weeks, 76.8% achieved steroid-free remission (p < 0.001), 77.8% clinical remission (p < 0.001), and 81.0% response. Mean CDAI decreased from 214.9 to 117.5 (p < 0.001). Endoscopic remission was 19.4%, with 48.9% response and 4.9% mucosal healing. Radiological remission was 9.1% with 85.7% response. Intestinal ultrasound showed 5.7% remission and 56.7% response. Conclusions: Upadacitinib demonstrates significant real-world effectiveness and safety in IBD, particularly in biologic-resistant cases, as evidenced by high rates of steroid-free remission and clinical response. These outcomes are likely due to its targeted JAK1 inhibition, which effectively reduces inflammation and promotes mucosal healing. Future research should focus on long-term safety, comparative effectiveness with other biologics, and its application in diverse patient populations. These findings support the integration of upadacitinib into IBD management strategies. [ABSTRACT FROM AUTHOR]

Achieving food sustainability is one of the biggest challenges in the new millennium. Plant factory cultivation systems provide an alternative for food sustainability, while they often suffer from algal blooms. The overuse of conventional algaecides has caused significant environmental pollution and concerns about food security. Here, we design a nanoenabled metal‐organic algaecide that is self‐assembled from natural polyphenols and two functional metal ions for providing shading effects and delivering active ingredients synergistically to suppress algal blooms. Black wattle tannin (BWT) and Fe3+ ions are utilized to develop self‐assembled FeBWT nanoalgaecides with significant shading effects for decreasing light transmission (up to 97 %) and effectively inhibiting algal photosynthesis. Further, the FeBWT is functionalized with Cu2+ ions (bimetallic Cu/FeBWT) to target the algal cells and release Cu2+ ions via phenolic‐mediated cell surface interactions, thus enhancing the inhibition efficiency. Importantly, the biosafety of Cu/FeBWT is demonstrated through toxicity tests on zebrafish and NIH3T3 cells. In our real‐world field test, the Cu/FeBWT demonstrates high algal inhibition performance (>95 %, over 30 days), and enhances the accumulation of food nutrients in model plant lettuces. Collectively, the supramolecular metal‐organic nanoalgaecide provides a promise for nanoagrochemical application and promotes food sustainability and security. [ABSTRACT FROM AUTHOR]

The beet webworm, Loxostege sticticalis, is a typical migratory pest. Although miRNAs participate in many physiological functions, little is known about the functions of miRNAs in olfactory regulation. In this study, 1120 (869 known and 251 novel) miRNAs were identified in the antennae of L. sticticalis by using high-throughput sequencing technology. Among the known miRNAs, 189 from 49 families were insect-specific, indicating that these miRNAs might play unique roles in insects. Furthermore, based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we found that 3647 and 1393 miRNAs were associated with localization and the regulation of localization, respectively, and 80 miRNAs were enriched in the neuroactive ligand–receptor interaction pathway. These miRNAs might be involved in the olfactory system of L. sticticalis. Notably, qRT-PCR showed that most of the tested miRNAs presented similar expression patterns compared with the RNA-seq data and that miR-87-3, novel-miR-78, and novel-miR-142 were significantly differentially expressed in the antennae of males and females. In addition, 21 miRNAs were predicted to target 23 olfactory genes, including 10 odorant-binding proteins (OBPs), 3 chemosensory proteins (CSPs), 4 odorant receptors (ORs), 1 ionotropic receptor (IR), and 5 gustatory receptors (GRs). The olfactory-related miRNAs exhibited low-abundance transcripts, except undef-miR-55 and undef-miR-523, and gender-biased expression was not observed for olfactory-related miRNAs. Our findings provide an overview of the potential miRNAs involved in olfactory regulation, which may provide important information on the function of miRNAs in the insect olfactory system. [ABSTRACT FROM AUTHOR]

There are differences in the litter quality and decomposition rate of kiwifruit varieties, but it is not clear whether these differences are related to microbial communities. The leaf litters of two kiwifruit varieties (A. chinensis cv 'Hongyang' and A. chinensis cv 'Jinyan') were taken as objects, and the structure, diversity, and succession of the soil microbial communities were analyzed using an in situ decomposition experiment. Moreover, the contents of C, N, P, and K in the litters during decomposition were analyzed. The results show that there were variety differences in community structure at the generic level. Lophotrichus, Acaulium, and Fusarium were relatively more abundant in the microbial community of the 'Hongyang' kiwifruit litter, and Humicola and Tausonia were relatively more abundant in the microbial community of the 'Jinyan' kiwifruit litter. Subgroup_6 and Sphingomonas were the dominant bacteria. The bacterial community diversity of 'Jinyan' kiwifruit was higher than that of the 'Hongyang' kiwifruit litter. The community diversity was higher in the middle and later periods. The contents of C and N in the litters were the main factors affecting microbial communities. The abundances of Humicola and Apiotrichum were negatively correlated with the contents of C and N, and the abundances of Sphingomonas and SC-I-84 were positively correlated with the content of C. There were variety differences in the microbial communities corresponding to the decomposition processes of the 'Hongyang' and 'Jinyan' kiwifruit litters. The mechanisms of the variety differences were related to litter quality and the initial soil microbial community. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), pose significant global health risks and represent a substantial public health concern in the contemporary era. A primary factor in the pathophysiology of these disorders is aberrant accumulation and aggregation of pathogenic proteins within the brain and spinal cord. Recent investigations have identified extracellular vesicles (EVs) in the central nervous system (CNS) as potential carriers for intercellular transport of misfolded proteins associated with neurodegenerative diseases. EVs are involved in pathological processes that contribute to various brain disorders including neurodegenerative disorders. Proteins linked to neurodegenerative disorders are secreted and distributed from cell to cell via EVs, serving as a mechanism for direct intercellular communication through the transfer of biomolecules. Astrocytes, as active participants in CNS intercellular communication, release astrocyte-derived extracellular vesicles (ADEVs) that are capable of interacting with diverse target cells. This review primarily focuses on the involvement of ADEVs in the development of neurological disorders and explores their potential dual roles – both advantageous and disadvantageous in the context of neurological disorders. Furthermore, this review examines the current studies investigating ADEVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases. The prospects and challenges associated with the application of ADEVs in clinical settings were also comprehensively reviewed. [ABSTRACT FROM AUTHOR]

Studies have confirmed that rituximab (RTX) can improve the efficacy of BL, but there is a certain effect on the level of immunoglobulin, which will lead to the verification of infection, and the previous study of our center has confirmed that reducing the dose of RTX (4 doses) can achieve a similar effect to the standard dose of RTX (6 doses), can it reduce the effect on the level of immunoglobulin? To date, few studies have concentrated on the effects of immunoglobulin (Ig) on Chinese paediatric patients. This study aimed to examine whether there is a variation in the impact of different doses of RTX on immunoglobulin levels in the high-risk group of children with BL. Clinical data of high-risk pediatric patients with BL who were treated in Beijing Children's Hospital (Beijing, China) were retrospectively analysed. Baseline characteristics and serum Ig levels were collected at four distinct time points (t0 = pre-chemotherapy, t1 = at the end of chemotherapy, t2 = 6 months post-chemotherapy, t3 = 12 months post-chemotherapy). Ig levels were measured at various time points before and after treatment within three RTX treatment groups: R0 group (standard chemotherapy without RTX), R6 group (6 doses of RTX + chemotherapy), and R4 group (4 doses of RTX + chemotherapy). The objective was to compare whether differences existed among the three groups. The results revealed that the study enrolled 300 high-risk BL patients, including 256 boys and 44 girls, distributed across three groups based on RTX dosage: R0 group (n = 38), R6 group (n = 87), and R4 group (n = 175). Median Ig levels were assessed at four time points (t0, t1, t2, t3) for each group. In the R0 group, IgA and IgM levels significantly decreased at t1 compared with t0 (P = 0.006 and 0.002, respectively), while were gradually recovered at t2, returning to t0 levels at t3 (P = 0.073 and 0.293, respectively). IgG levels exhibited no significant difference between t0 and t1 (P = 0.89), reaching their lowest levels at t2 and returning to t0 levels at t3 (P = 0.14). In the R4 group, the minimum levels of IgA, IgM, and IgG were identified at t1 (P < 0.001, < 0.001, and < 0.001, respectively), which were gradually recovered at t2, while remained lower than t0 levels at t3 (P < 0.001, < 0.001, and = 0.005, respectively). The R6 group exhibited reduction in IgA and IgM levels at t1, with gradual recovery at t2 and t3, while remained lower than t0 levels (P = 0.003 and < 0.001, respectively). IgG levels in the R6 group decreased at t1 (P < 0.001) and did not return to t0 levels at t3 (P = 0.004). In the R4 and R6 groups, it was observed that children with hypogammaglobulinemia pre-RTX were more likely to combine with persistent hypogammaglobulinemia (PH-Ig) post-RTX. A 1:1 matched comparison between R4 and R6 groups (78 patients each) revealed consistently higher IgA, IgM, and IgG levels in the R4 group at each time point after chemotherapy. Notably, IgA and IgG levels recovered earlier in the R4 group than those in the R6 group (P < 0.05). Burkitt lymphoma in the high-risk group were more likely to complicated hypoimmunoglobulinemia after treatment, it is important to monitor Ig levels before and during treatment, and to inform replacement therapy for Ig. Compared with standard chemotherapy group, the RTX group had a longer time of low Ig and a slower recovery, reducing the dosage of rituximab can improve the recovery of IgA and IgG levels. [ABSTRACT FROM AUTHOR]

Objective: Previous research has highlighted a heightened occurrence of social isolation and loneliness in older adults diagnosed with chronic lung diseases. Nevertheless, there exists a dearth of studies that have explored the influence of impoverished social relationships on lung function. This study aimed to examine the longitudinal association between social isolation, loneliness and lung function over 4 years among middle‐aged and older Chinese adults. Methods: This study employed two waves (2011 and 2015) of data from the China Health and Retirement Longitudinal Study (CHARLS). The analysis was limited to participants aged 45 years and above and stratified based on gender (3325 men and 3794 women). The measurement of peak expiratory flow (PEF) served as an indicator for assessing lung function. Lagged dependent variable regression models, accounting for covariates, were employed to explore the relationship between baseline social isolation and loneliness and the subsequent PEF. Results: For women, social isolation was significantly associated with the decline in PEF at follow‐up (β = −.06, p <.001) even after adjusting for all covariates; no significant correlation was observed between loneliness and PEF. Among men, there was no significant association found between either social isolation or loneliness and PEF. Conclusions: Social isolation is prospectively associated with worse lung function in middle‐aged and older Chinese women but not men. The results highlight the importance of promoting social relationships in public health initiatives, especially in groups that are more vulnerable. [ABSTRACT FROM AUTHOR]

Purpose: Taxol is the first-line chemo-drug for advanced non-small cell lung cancer (NSCLC), but it frequently causes acquired resistance, which leads to the failure of treatment. Therefore, it is critical to screen and characterize the mechanism of the taxol-resistance reversal agent that could re-sensitize the resistant cancer cells to chemo-drug. Method: The cell viability, sphere-forming and xenografts assay were used to evaluate the ability of ASIV to reverse taxol-resistance. Immunohistochemistry, cytokine application, small-interfering RNA, small molecule inhibitors, and RNA-seq approaches were applied to characterize the molecular mechanism of inhibition of epiregulin (EREG) and downstream signaling by ASIV to reverse taxol-resistance. Results: ASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes. Finally, it was observed that TGFβ and Hedgehog signaling were downstream of EREG/ErbB/ERK, which could be targeted using inhibitors to reverse the taxol resistance of NSCLC. Conclusions: These findings revealed that inhibition of EREG by ASIV reversed taxol-resistance through suppression of the stemness of NSCLC via EREG/ErbB/ERK—TGFβ, Hedgehog axis. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2DM) is characterised by insulin resistance and a relative shortage of insulin secretion. Tumour necrosis factor‐α (TNF‐α) plays an important role in insulin resistance by impairing insulin signal transduction. The variants of the TNF‐α promoter region are considered to influence its transcription and are associated with the TNF‐α level. Therefore, it is worth detecting the association of the variants in the TNF‐α gene with the development of T2DM. The aim of this study was to investigate the association of five variants (rs1799964, rs1800630, rs1799724, rs1800629 and rs361525) in the TNF‐α gene promoter region with T2DM in a Chinese Han population. A total of 713 subjects with T2DM and 751 nondiabetic subjects were genotyped using the TaqMan method. The associations of the five variants with the development of T2DM were evaluated. The associations of the five variant genotypes with metabolic traits in nondiabetic subjects were analysed. Our data showed that the A allele of rs1800629 could increase the risk of developing T2DM (p =.002, OR = 1.563; 95% CI: 1.18–2.08). According to inheritance mode analysis, compared with the G/G genotype, the G/A+2A/A genotype of rs1800629 showed a risk effect on T2DM in the log‐additive mode (p =.002, OR = 1.56; 95% CI: 1.17–2.07). The haplotypes analysis identified that the rs1799724‐rs1800629CA was associated with high risk of the development of T2DM (p =.002, OR = 1.559, 95% CI: 1.173–2.072). Conversely, the rs1799724‐rs1800629CG was a protective haplotype of T2DM (p =.001, OR = 0.732, 95% CI: 0.607–0.884). Moreover, compared with the rs1799964 (T/T+C/T) genotype, the rs1799964 C/C genotype was associated with higher glycosylated haemoglobin (HbA1c) levels in nondiabetic subjects (p =.017). Our results revealed that the rs1800629 in the TNF‐α gene promoter region was associated with T2DM in a Chinese Han population. [ABSTRACT FROM AUTHOR]

Glioma is one of the most common malignant tumors and shows a high metastasis rate and poor prognosis. KLHDC8A has been implicated in several cancers, but its role in glioma and its potential as a biomarker remain unclear. We conducted a pan-cancer analysis of KLHDC8A using multiple databases and assessed its expression levels, survival associations, and diagnostic utility. Kaplan–Meier survival analysis and Receiver Operating Characteristic (ROC) curves were utilized to evaluate KLHDC8A's prognostic and diagnostic potential. Additionally, we investigated KLHDC8A's role in glioma cell proliferation and its involvement in the Wnt/β-catenin signaling pathway. Our pan-cancer analysis revealed significant dysregulation of KLHDC8A across various tumors. Elevated KLHDC8A expression was associated with poor overall survival (OS) in cancers including ACC, KIRP, LGG, and STAD. Disease-specific survival (DSS) analysis indicated worse outcomes in ACC, KIRP, and LGG with high KLHDC8A levels. ROC curve analysis demonstrated KLHDC8A's strong diagnostic potential for glioblastoma multiforme (GBM) and lower-grade gliomas (LGG), with AUC values of 0.920 and 0.748, respectively. In glioma patients, high KLHDC8A expression correlated with shorter OS and DSS in LGG, while no significant correlation was observed in GBM. Multivariate Cox regression confirmed KLHDC8A as an independent prognostic factor for OS and DSS in LGG. Knockdown experiments in glioma cell lines U251 and U87 showed that KLHDC8A silencing led to reduced cell proliferation and colony formation, which was associated with downregulation of key proteins in the Wnt/β-catenin pathway. Overall, KLHDC8A is a promising biomarker for the diagnosis and prognosis of LGG, and its high expression is linked to poor survival outcomes. The gene's involvement in the Wnt/β-catenin signaling pathway underscores its role in glioma progression, highlighting KLHDC8A's potential as a therapeutic target and diagnostic marker, particularly for LGG. [ABSTRACT FROM AUTHOR]

Kiwifruit (Actinidia spp.), celebrated for its unique flavor and rich nutritional content, is a globally popular fruit. This fruit requires post-harvest ripening before consumption. However, the unpredictable ripening pace significantly impacts consumer acceptance and sales, thereby hindering the commercial growth of kiwifruit. To address this, understanding the key molecular mechanisms and metabolites governing postharvest ripening and senescence could offer valuable insights for developing storage strategies and breeding techniques in yellow-fleshed kiwifruits. We constructed two models that integrated these findings with existing theories. The first model suggests that, unlike the T6P-sucrose regulatory mechanism observed in plant leaves, the separation of harvested kiwifruit from the mother plant leads to an insufficient supply of T6P, which activates the SnRK1 kinase. This, in turn, inhibits the TOR kinase signaling pathway, regulating starch metabolism. The T6P-SnRK1-TOR-starch metabolism pathway plays a regulatory role during postharvest ripening, limiting excessive starch degradation that could accelerate aging and decay in yellow-fleshed kiwifruit. The second model highlights the role of abscisic acid (ABA), cytokinins (CKs), and ethylene in regulating the process, inducing the activation of ERFs and cell wall-degrading enzymes, promoting fruit postharvest softening. These findings indicate that at least two models, the T6P-SnRK1-TOR-starch metabolism model and the ABA-CKs-ethylene-cell wall degradation model, regulate postharvest fruit ripening, offering new insights into the artificial regulation of yellow-fleshed kiwifruit ripening speed. [ABSTRACT FROM AUTHOR]

Background: The mental health of patients with chronic liver disease (CLD) warrants greater attention and understanding, especially concerning its risk factors. Method: Patients from our hospital's hepatology clinic were consecutively enrolled and completed a questionnaire assessing anxiety, depression, and sleep quality using the GAD-7, PHQ-9, and PSQI scales, respectively. Reliability and validity were evaluated with Cronbach's α and Kaiser-Meyer-Olkin (KMO). Continuous and categorical variables were analyzed using the Mann-Whitney U and Chi-square tests. Univariate and multivariate logistic regression were used to identify risk factors, while restricted cubic spline (RCS) were used to explored non-linear associations. Subgroup analyses were stratified by sex, age, and education. Result: A total of 1030 questionnaires were collected, and after quality control, 1003 were included. 56.2% (564/1003), 53.2% (534/1003), and 67.4% (676/1003) individuals had anxiety, depression, and sleep disorders. Differences in age, gender, and education level were observed (P <0.05). Subgroup analysis showed similar demographic trends. Univariate and multivariate regression analysis found age negatively correlated with anxiety (OR=0.98, 95%CI=0.97-0.99, P =0.02) and depression (OR=0.98, 95%CI=0.96-0.99, P <0.001), but positively correlated with sleep disorders (OR=1.03, 95%CI= 1.01-1.05, P < 0.001); males are less prone to anxiety (OR=0.68, 95%CI=0.52-0.88, P =0.004) and sleep disorders (OR=0.72, 95%CI: 0.55-0.94, P =0.02); university degree is more susceptible to depression (OR=1.36, 95%CI=1.04-1.77, P =0.02) and anxiety (OR=1.45, 95%CI=1.11-1.89, P =0.007). RCS analysis suggested a linear relationship between the age and affective disorders among different population. Conclusion: Young individuals, female, and those with higher education are more vulnerable to mental health, warranting increased attention. [ABSTRACT FROM AUTHOR]

In this paper, the state estimation problem of physical plants with unknown system dynamic is revisited from the perspective of limited output information measurement, which corresponds to those with characteristics of high-dimensional, wide-area coverage and scatter. Given this fact, a network of sensors are used to carry out the measurement with each one accessing only partial outputs of the targeted systems and a novel model-free state estimation approach, named distributed stochastic variational inference state estimation, is proposed. The key idea of this method is to compensate for the impacts of local output measurements by adding nearest-neighbor rule-based information interaction among estimators to complete the state estimation. It finds from the numerical experiments that the proposed method has clear advantages in both estimation accuracy and speed, and it also provides guidance on how to improve the efficiency of state estimation under local measurements. [ABSTRACT FROM AUTHOR]

The accurate prediction of dam deformation is essential for ensuring safe and efficient dam operation and risk management. However, the nonlinear relationships between deformation and time-varying environmental factors pose significant challenges, often limiting the accuracy of conventional and deep learning models. To address these issues, this study aimed to improve the predictive accuracy and interpretability in dam deformation modeling by proposing a novel LSTM seq2seq model that integrates a chaos-based arithmetic optimization algorithm (AOA) and an attention mechanism. The AOA optimizes the model's learnable parameters by utilizing the distribution patterns of four mathematical operators, further enhanced by logistic and cubic mappings, to avoid local optima. The attention mechanism, placed between the encoder and decoder networks, dynamically quantifies the impact of influencing factors on deformation, enabling the model to focus on the most relevant information. This approach was applied to an earth-rock dam, achieving superior predictive performance with RMSE, MAE, and MAPE values of 0.695 mm, 0.301 mm, and 0.156%, respectively, outperforming conventional machine learning and deep learning models. The attention weights provide insights into the contributions of each factor, enhancing interpretability. This model holds potential for real-time deformation monitoring and predictive maintenance, contributing to the safety and resilience of dam infrastructure. [ABSTRACT FROM AUTHOR]

Atmospheric pollutants' real-time changes and the internal interactions among various data make it challenging to efficiently predict concentration variations. In order to extract more information from the time series of pollutants and improve the accuracy of prediction models, we propose a type of Multilayer Perceptron model based on wavelet decomposition, named Wavelet Transform-based Multilayer Perceptron (WTMP) model. This model decomposes pollutant data through overlapping discrete wavelet transforms to extract non-stationarity and nonlinear dependencies in the time series. It combines the decomposed data with static covariate information such as data collection time and inputs them into an improved Multilayer Perceptron (MLP) model, reconstructing and outputting the prediction results. Finally, the model is validated using atmospheric pollutant data collected at a specific location in Ruian City, Zhejiang Province, China. The results indicate that the model performs well with minimal prediction errors. [ABSTRACT FROM AUTHOR]

Filamentous bacteria are one of the main components of activated sludge microorganisms, which not only support flocculent bacteria in forming sludge flocs but also easily lead to sludge bulking. This article summarizes the high-throughput sequencing technology and database construction that integrates the FISH probe and 16s rRNA gene of filamentous bacteria. The detection frequency and abundance were statistically analyzed to determine the core filamentous bacteria. The filamentous bacteria searchable in the NCBI database belong to six phyla and 42 genera, with a total of 94 species. The core filamentous bacteria in the expanded activated sludge include Microthrix parvicella (M. parvicella), type 0092, Mycobacterium fortuitum, etc. The physiological ecology of the core filamentous bacteria is discussed in detail, aiming to establish targeted sludge expansion control strategies, reduce the incidence and harm of sludge expansion, and propose that future research needs to promote further development in the field of environmental microbiology. [ABSTRACT FROM AUTHOR]

The role of social determinants of health (SDOH) in controlling hypertension (HTN) in cancer patients is unknown. We hypothesize that high SDOH scores correlate with uncontrolled HTN in hypertensive cancer patients. In our prospective study, patients completed the Protocol for Responding to & Assessing Patients' Assets, Risks & Experiences questionnaire. After integrating home and clinic blood pressure readings, uncontrolled HTN was defined as systolic blood pressure greater than or equal to 140 mm Hg and/or diastolic blood pressure greater than or equal to 90 mm Hg. Using Cox regression, we analyzed the impact of SDOH on HTN control, adjusting for relevant factors. The study involved 318 participants (median age 66.4, median follow-up 166 days, SDOH score 6.5 ± 3.2), with stress, educational insecurity, and social isolation as prevalent adverse SDOH. High SDOH scores led to 77% increased risk of uncontrolled HTN (adjusted hazards ratio = 1.77; 95% confidence interval = 1.10 to 2.83, P  = .018). Urban residents with high SDOH scores were at an even greater risk. Identifying SDOH and mitigating underlying factors may help control HTN, the most typical disease process treated in all cardio-oncology clinics. [ABSTRACT FROM AUTHOR]

Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non‐amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate‐limiting step for amyloid‐β production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1‐mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment. [ABSTRACT FROM AUTHOR]

Rationale: The application of infliximab (IFX) to immune‐mediated disease is limited by the significant individual variability and associated clinical nonresponse, emphasizing the importance of therapeutic drug monitoring (TDM). Because of the cross‐reactivity, limited linear range, and high costs, the clinical application of the previous reported methods was limited. Here, an improved high‐performance liquid chromatography tandem mass spectrometry (HPLC‐MS/MS) method was developed to address the issues. Methods: This study developed an improved bioanalytical HPLC‐MS/MS method coupling nanosurface and molecular‐orientation limited proteolysis technology. The commercially available compound P14R was selected as the internal standard. This method was developed with fewer volume of reagents and was thoroughly validated. The validated method was applied to TDM in pediatric inflammatory bowel disease (IBD). Results: Chromatography was performed using a Shim‐pack GISS‐HP C18 metal‐free column (3 μm, 2.1 × 100 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile at 0.4 mL/min. Detection and quantitation were performed using electrospray ionization (ESI) and multiple reaction monitoring in the positive ion mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect, and stability. The method exhibited a linear dynamic range of 0.3–100 μg/mL, with intra‐ and inter‐day precision and relative errors below 15%. The recovery and matrix effect were measured as 87.28%–89.72% and 41.98%–67.17%, respectively, which were effectively compensated by the internal standard. A total of 32 samples collected from 24 pediatric patients with IBD were analyzed using the validated method, and only 46.9% achieved the reported targeted trough level. Conclusion: This study developed an improved HPLC‐MS/MS method for the quantitative determination of IFX concentration in human plasma. The accurate, reliable, and cost‐effective method was validated and utilized in the analysis of clinical samples. The results confirmed the importance of TDM on IFX and the clinical application prospects of the improved method. [ABSTRACT FROM AUTHOR]

Some patients with polycystic ovarian syndrome (PCOS) suffered from metabolic syndrome (MetS) including dyslipidemia, hyperinsulinism, but the underlying mechanism is unclear. Although C-terminal Binding Protein 1 (CTBP1) is a transcriptional co-repressor frequently involved in hormone secretion disorders and MetS-associated diseases, the role of CTBP1 in PCOS is rarely reported. In the present study, we found that CTBP1 expression was significantly elevated in primary granulosa cells (pGCs) derived from the PCOS with MetS patients and was positively associated with serum triglyceride, but negatively correlated with serum estradiol (E2) or high-density lipoprotein. Mechanistic study suggested that CTBP1 physically bound to the promoter II of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) to inhibit the aromatase gene transcription and expression, resulting in the reduced E2 synthesis. Moreover, CTBP1 interacted with the phosphorylated SREBP1a at S396 in nuclei, leading to the FBXW7-dependent protein degradation, resulting in the reduced lipid droplets formation in pGCs. Therefore, we conclude that CTBP1 in GCs dysregulates the synthesis of steroid hormones and lipids through suppression of aromatase expression and promotion of SREBP1a protein degradation in PCOS patients, which may offer some fresh insights into the potential pathological mechanism for this tough disease.CTBP1 in granulosa cells of PCOS patients represses transcription of aromatase CYP19A1 and regulates stability of SREBP1a, which both contributes to dysregulation of hormone synthesis and lipid metabolism. [ABSTRACT FROM AUTHOR]

Rationale: The application of infliximab (IFX) to immune‐mediated disease is limited by the significant individual variability and associated clinical nonresponse, emphasizing the importance of therapeutic drug monitoring (TDM). Because of the cross‐reactivity, limited linear range, and high costs, the clinical application of the previous reported methods was limited. Here, an improved high‐performance liquid chromatography tandem mass spectrometry (HPLC‐MS/MS) method was developed to address the issues. Methods: This study developed an improved bioanalytical HPLC‐MS/MS method coupling nanosurface and molecular‐orientation limited proteolysis technology. The commercially available compound P14R was selected as the internal standard. This method was developed with fewer volume of reagents and was thoroughly validated. The validated method was applied to TDM in pediatric inflammatory bowel disease (IBD). Results: Chromatography was performed using a Shim‐pack GISS‐HP C18 metal‐free column (3 μm, 2.1 × 100 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile at 0.4 mL/min. Detection and quantitation were performed using electrospray ionization (ESI) and multiple reaction monitoring in the positive ion mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect, and stability. The method exhibited a linear dynamic range of 0.3–100 μg/mL, with intra‐ and inter‐day precision and relative errors below 15%. The recovery and matrix effect were measured as 87.28%–89.72% and 41.98%–67.17%, respectively, which were effectively compensated by the internal standard. A total of 32 samples collected from 24 pediatric patients with IBD were analyzed using the validated method, and only 46.9% achieved the reported targeted trough level. Conclusion: This study developed an improved HPLC‐MS/MS method for the quantitative determination of IFX concentration in human plasma. The accurate, reliable, and cost‐effective method was validated and utilized in the analysis of clinical samples. The results confirmed the importance of TDM on IFX and the clinical application prospects of the improved method. [ABSTRACT FROM AUTHOR]

Background: Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. Objective: To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. Methods: The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. Results: The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P < 0.0001). As compared with placebo, dexmedetomidine treatment led to more subjects achieving Ramsay scale ≥ 3 or UMSS ≥ 2, and shorter time to reach desired parental separation, Ramsay scale ≥ 3 and UMSS ≥ 2 (all P < 0.0001). Adverse events were reported in 90.7% and 84.0% of subjects in the dexmedetomidine and placebo groups, respectively, and all the events were mild or moderate in severity. Conclusions: This novel dexmedetomidine nasal spray presented effective pre-anesthetic sedation in children with a tolerable safety profile. [ABSTRACT FROM AUTHOR]

Background and Aims: Over the last few decades, rampant nitrogen fertilization has exacerbated soil acidification in agricultural ecosystems. To counteract this, liming has become an essential technique for rehabilitating fertility in acid-degraded agricultural soils. Our research aimed to shed light on the response of ammonia oxidizers to liming in acidic soils within a controlled rice paddy experiment. We conducted a pot experiment with rice, featuring three different treatments: a control with only soil, a low dolomite dose (LD), and a high dolomite dose (HD). Various soil properties were investigated throughout the study. Under flooding, soil pH values rose across the treatments, from 5.4 in the control to 6.8 in HD. Ammonium and nitrate levels peaked in the HD treatment, reaching 30 and 22 mg kg−1, respectively. Similarly, dissolved organic carbon and microbial biomass carbon surged at mid-season aeration, hitting highs of 101 and 30 mg kg−1, respectively, in the HD treatment. Ammonia-oxidizing bacteria (AOB) and archaea (AOA) were responsive to dolomite-lime application, with distinct reactions; AOB abundance and potential nitrification rates were positively affected by higher lime doses, whereas AOA numbers decreased over time and with dolomite application. Additionally, soil enzymes such as urease, catalase, invertase, phenol oxidase, and phosphatase also increased progressively, mirroring the rise in soil pH. This study identified increased soil pH as the critical factor influencing various soil parameters, especially the balance between AOA and AOB populations. Both AOB and AOA were sensitive to liming; AOA decreased while liming stimulated AOB abundance. [ABSTRACT FROM AUTHOR]

Background: The interaction between physical activity, skeletal muscle health, and adiposity has been explored in normal weight and overweight/obesity grouped together; however, the overall risks associated with being overweight are less than those observed with obesity and can be confounded by disparities in both sex and race. Thus, the present study sought to investigate the intricate interplay of daily physical activity and skeletal muscle oxidative capacity (SMOC) in overweight and obesity, while exploring how sex and race impact this dynamic relationship. Methods: One hundred and forty participants were grouped by body mass index (BMI) as overweight (n = 73; BMI >25–<30 kg/m2) or obese (n = 67; BMI ≥30 kg/m2). SMOC was assessed using near‐infrared spectroscopy and daily physical activity was assessed for 7 days using accelerometry. Results: Overweight individuals exhibited a higher (p = 0.004) SMOC and engaged in more (p = 0.007) vigorous physical activity compared to obese individuals. In addition, SMOC was lower (p = 0.005) in obese non‐Hispanic Black (NHB) men compared to overweight NHB men. No relationships between physical activity and SMOC were observed. Conclusion: Physical activity is not associated with differences in SMOC in overweight and obesity. Obese individuals engage in less vigorous physical activity and exhibit lower SMOC compared to overweight individuals and these differences are emphasised in NHB men. [ABSTRACT FROM AUTHOR]

In order to study Bacillus subtilis biofilm formation in microdroplets, we use microfluidics technology to make the droplets and confocal microscopy to capture bacterial movement and biofilm formation in the droplets. We develop a multi-target tracking methodology, using a YOLOv5 detector to identify cells and a DeepSORT algorithm to track cell movements. We find that Bacillus subtilis bacteria with autonomous migration and biofilm-forming ability prefer to cluster and swarm near the microdroplet surface, rather than in the droplet interior. Bacterial mobility depends on phenotype and spatial location within the droplet. The motile cells move about 3.5 times faster than the matrix-producing cells. When the cells are near the wall of the droplet, the direction of the motion of motile cells is along that wall. When the cells are inside the droplet, the direction of the motion of motile cells is disordered, i.e., there is no clear directional or goal-oriented movement. This contrast increases the cell contact probability and facilitates the formation of a Bacillus subtilis biofilm in the droplet. Furthermore, we develop a mathematical model to describe the motion behavior of Bacillus subtilis in microdroplets, which is useful for exploring the influence of motility on biofilm formation. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese Medicine Astragalus was commonly used to assist chemo-drug treatment in clinical cancer patients. However, whether Astragalus injection (AGI) reverses drug resistance remains unclear. Therefore, a meta-analysis is necessary to assess the effect of AGI on resistance reversement in cancer patients. Method: The studies presenting tumor response rates in cancer patients receiving chemo-drugs treatment in combination with AGI were systematically searched from six common scientific databases until February 2024. The relative risks (RRs) indicating the tumor response rate, 1-year survival rate, and quality of life improvement in clinical patients among two groups were calculated in metan package. The pooled RRs with 95% confidence intervals (CIs) were used to explore the effect of AGI on enhancing drug sensitivity in terms of tumor response, 1-year survival rate and quality of life improvement in cancer patients. Result: Fifty-one studies were included for meta-analysis following a thorough screening process that adhered to the inclusion and exclusion criteria. A total of 4613 patients were enrolled in all included trials. Results obtained indicated that AGI significantly enhanced the sensitivity of cancers to chemo-drugs with pooled RRs (95% CI) of 1.25 (1.18, 1.32), prolonged the 1-year survival rate of patients with pooled RRs (95% CI) of 1.34 (1.14, 1.57), improved the quality of life with pooled RRs (95% CI) of 1.61 (1.34, 1.93). Similarly, Astragalus's main component, astragaloside polysaccharides (APS), also enhances drug sensitivity in clinical cancer patients. Conclusion: Our findings demonstrated that AGI had the ability to resensitize cancers to chemo-drugs and improve the quality of life of cancer patients. Therefore, AGI could potentially be used as a drug resistance reversal for resistant cancer treatment. [ABSTRACT FROM AUTHOR]

Conjugated polymers with integrating properties of delayed fluorescence and photovoltaic responses simultaneously are scarcely reported due to the generally contradictory requirements for molecular structures to achieve the two properties. Herein, an O‐B(F)←N functionalized fused unit (M) with multiple resonance features, small energy gap between lowest singlet excited state (S1) and triplet excited state (T1) (ΔEST = 0.23 eV), and delayed fluorescence (τD = 0.75 µs), is designed. Selecting three benzodithiophene (BDT) derivatives as co‐units to copolymerize with M, leading to a series of O‐B(F)←N embedded polymers also maintaining delayed fluorescence (τD = 0.4–0.5 µs). Moreover, p‐type semiconductor characteristics are tested for these polymers with hole mobilities in the range of 10−6–10−5 cm2/Vs. Devices with obviously photovoltaic responses are prepared using these polymers as donors and Y6 as the acceptor, affording a preliminary efficiency of 5.05%. This work successfully demonstrates an effective strategy to design conjugated polymers with integrating properties of delayed fluorescence and photovoltaic performance simultaneously by introducing O‐B(F)←N functional groups to polymer backbones. [ABSTRACT FROM AUTHOR]

Astroviruses are single-stranded, positive-sense RNA viruses capable of infecting humans as well as a wide range of mammalian and avian species, with a length of approximately 6.6–7.7 kb. In this study, 139 goat fecal samples collected from the Guangxi province were used for the RT-PCR detection, and two of these were positive for goat astrovirus, with a positivity rate of 1.44% (2/139). The complete genome sequence of an astrovirus strain and the partial genome sequence of a strain astrovirus, named GX WZ 2023 and GX HC 2023, were amplified and sequenced, and their sequence lengths were 6284 nt and 6213 nt, respectively. Among them, the capsid protein of goat astrovirus GX HC 2023 showed the highest amino acid identity of 95.9% with ovine astrovirus GX, which belonged to the MAstV-2 genotype. However, the closest relative of the GX WZ 2023 strain was found to be the caprine astrovirus Sichuan, with a nucleotide sequence identity of 76.8%. The ORF1ab nonstructural protein of this strain showed the highest amino acid identities of 89.2 and 95.8% with the ovine astrovirus S5.1 and caprine astrovirus G5.1 strains, respectively. However, its ORF2 capsid protein has 68.4% amino acid identity with the bovine astrovirus (BAstV) 16 2021 CHN strain and only 21.9–64% amino acid identity with all available strains of goat astrovirus. The GX WZ 2023 strain was recombined with the Chinese (BAstV 16 2021 CHN) and Japanese bovine strains (BAstV JPN 2015) in the ORF2 region. Therefore, the goat astrovirus GX WZ 2023 is proposed as a new member of the family goat astroviridae based on the species classification criteria of the International Committee on Taxonomy of Viruses. These findings enhance our understanding of the prevalence and genetic evolution of goat astrovirus and provide a scientific basis for future studies of these viruses in other animals. [ABSTRACT FROM AUTHOR]

Summary: Effectively targeting transcription factors in therapeutic interventions remains challenging, especially in core‐binding factor‐acute myeloid leukaemia (CBF‐AML) characterized by RUNX1::ETO and CBFβ::MYH11 fusions. However, recent studies have drawn attention towards aberrant amino acid metabolisms as actionable therapeutic targets. Here, by integrating the expression profile and genetic makeup in AML cohort, we found higher BCAT1 expression in CBF‐AML patients compared with other subtypes. Metabolic profiling revealed that high BCAT1 expression led to reprogrammed branch amino acid metabolism in CBF‐AML and was associated with sphingolipid pathway relating to the fitness of leukaemia cells, supported by transcriptomic profiling. Mechanistically, we demonstrated in cell lines and primary patient samples that BCAT1 was directly activated by RUNX1::ETO and CBFβ::MYH11 fusion proteins similarly in a RUNX1‐dependent manner through rewiring chromatin conformation at the BCAT1 gene locus. Furthermore, BCAT1 inhibition resulted in blunted cell cycle, enhanced apoptosis and myeloid differentiation of CBF‐AML cells in vitro, and alleviated leukaemia burden and prolonged survival in vivo. Importantly, pharmacological inhibition of BCAT1 using the specific inhibitor Gabapentin demonstrated therapeutic effects, as evidenced by delayed leukaemia progression and improved survival in vivo. In conclusion, our study uncovers BCAT1 as a genetic vulnerability and a promising targeted therapeutic opportunity for CBF‐AML. [ABSTRACT FROM AUTHOR]

Distributed observer is an effective scheme for state estimation of a targeted system, utilizing a network of sensors to perform local output measurements. In this article, the problem of designing a distributed observer for a linear time‐invariant system with external disturbances is addressed. The objective is to perform state estimation of such a system while simultaneously mitigating the impact of external disturbances and maintaining the distributed communication characteristics among the sensors. To achieve this, a completely distributed observer with robustness against disturbances is developed by combining the high‐gain observer technique and the adaptive coupling strength strategy. Initially, a traditional high‐gain observer is used for the state estimation on the observable subsystem, and subsequently a high‐gain observer without peaking is introduced to avoid the peaking phenomenon. Finally, numerical simulations are presented to verify the theoretical results. [ABSTRACT FROM AUTHOR]

Organic fluorides are widely used in pharmaceuticals, agrochemicals, material sciences, and other fields due to the special physical and chemical properties of fluorine atoms. The synthesis of alkyl fluorinated compounds bearing multiple contiguous stereogenic centers is the most challenging research area in synthetic chemistry and has received extensive attention from chemists. This review summarized the important research progress in the field over the past decade, including asymmetric electrophilic fluorination and the asymmetric elaboration of fluorinated substrates (such as allylic alkylation reactions, hydrofunctionalization reactions, Mannich addition reactions, Michael addition reactions, aldol addition reactions, and miscellaneous reactions), with an emphasis on synthetic methodologies, substrate scopes, and reaction mechanisms. [ABSTRACT FROM AUTHOR]

Ex vivo red blood cell (RBC) production generates unsatisfactory erythroid cells. A deep exploration into terminally differentiated cells is required to understand the impairments for RBC generation and the underlying mechanisms. Here, we mapped an atlas of terminally differentiated cells from umbilical cord blood mononuclear cells (UCBMN) and pluripotent stem cells (PSC) and observed their dynamic regulation of erythropoiesis at single‐cell resolution. Interestingly, we detected a few progenitor cells and non‐erythroid cells from both origins. In PSC‐derived erythropoiesis (PSCE), the expression of haemoglobin switch regulators (BCL11A and ZBTB7A) were significantly absent, which could be the restraint for its adult globin expression. We also found that PSCE were less active in stress erythropoiesis than in UCBMN‐derived erythropoiesis (UCBE), and explored an agonist of stress erythropoiesis gene, TRIB3, could enhance the expression of adult globin in PSCE. Compared with UCBE, there was a lower expression of epigenetic‐related proteins (e.g., CASPASE 3 and UBE2O) and transcription factors (e.g., FOXO3 and TAL1) in PSCE, which might restrict PSCE's enucleation. Moreover, we characterized a subpopulation with high proliferation capacity marked by CD99high in colony‐forming unit‐erythroid cells. Inhibition of CD99 reduced the proliferation of PSC‐derived cells and facilitated erythroid maturation. Furthermore, CD99–CD99 mediated the interaction between macrophages and erythroid cells, illustrating a mechanism by which macrophages participate in erythropoiesis. This study provided a reference for improving ex vivo RBC generation. [ABSTRACT FROM AUTHOR]

Cancer, a prevalent and complex disease, presents a significant challenge to the medical community. It is characterized by irregular cell differentiation, excessive proliferation, uncontrolled growth, invasion of nearby tissues, and spread to distant organs. Its progression involves a complex interplay of several elements and processes. Extracellular vesicles (EVs) serve as critical intermediaries in intercellular communication, transporting critical molecules such as lipids, RNA, membrane, and cytoplasmic proteins between cells. They significantly contribute to the progression, development, and dissemination of primary tumors by facilitating the exchange of information and transmitting signals that regulate tumor growth and metastasis. However, EVs do not have a singular impact on cancer; instead, they play a multifaceted dual role. Under specific circumstances, they can impede tumor growth and influence cancer by delivering oncogenic factors or triggering an immune response. Furthermore, EVs from different sources demonstrate distinct advantages in inhibiting cancer. This research examines the biological characteristics of EVs and their involvement in cancer development to establish a theoretical foundation for better understanding the connection between EVs and cancer. Here, we discuss the potential of EVs from various sources in cancer therapy, as well as the current status and future prospects of engineered EVs in developing more effective cancer treatments. [ABSTRACT FROM AUTHOR]

Background: Among the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported. Methods: This retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves. Results: Under optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles. Conclusions: The patients of POSEIDON group 3 may not be considered as traditional "low prognosis" in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial. [ABSTRACT FROM AUTHOR]

Ganoderma triterpenes and spore powder have shown promising results in mitigating cadmium-induced renal and hepatic injuries. Ganoderma lucidum active peptide GLP4 is a natural protein with dual antioxidant activities derived from the mycelium of Ganoderma lucidum. However, its efficacy in alleviating cadmium-induced lung injury remains unexplored. This study aims to investigate the protective effects of GLP4 against cadmium-induced lung injury in mice. Mice were exposed to cadmium chloride via nebulization to induce lung injury. The protective effect of GLP4 was assessed by measuring the total cell count in BALF, levels of inflammatory cytokines, and the expression of NLRP3 in lung tissues a through histopathological examination of lung tissue changes. The results showed that GLP4 significantly mitigated histopathological damage in lung tissues, decreased the secretion of inflammatory cytokines, and reduced the expression of NLRP3, which was elevated in cadmium-exposed mice. In vitro studies further revealed that GLP4 inhibited the cadmium-induced activation of the NLRP3 inflammasome. Notably, acute cadmium exposure by the respiratory tract did not affect the liver and kidneys of the mice. The findings suggest that GLP4 reduces cadmium-induced lung injury in mice by inhibiting the activation of the NLRP3 inflammasome, which provides a theoretical foundation for using Ganoderma lucidum as a preventive and therapeutic agent against cadmium poisoning. [ABSTRACT FROM AUTHOR]

Artificial reefs have been advocated and implemented as management tools for aquaculture, species conservation and habitat replacement. However, the shelter capacity of artificial reefs and its influencing factors are still not well understood. In this study, we identified factors that may limit the shelter capacity of artificial reefs for sea cucumber (Apostichopus japonicas) with a laboratory experiment. We investigated how water flow and food availability affect the shelter capacity and conducted shelter utilization experiments to determine whether sea cucumber sheltering behavior was density dependent. The results revealed that shelter capacity of artificial reefs in high velocity is significantly higher than that of artificial reefs in low velocity or no velocity. The artificial reefs that were provided food had significantly higher shelter capacity than those that did not have food. The densities did not affect the sheltering capacity of artificial reefs in the laboratory experiment. There was a logarithmic relationship between the shelter capacity and shelter availability assessed by the exposed surface area of the artificial reefs. In conclusion, abundant food resources and high water flow may have a positive effect on the shelter capacity of artificial reefs. [ABSTRACT FROM AUTHOR]

Camellia oleifera is a crucial cash crop in the southern region of China. Timely flowering is a crucial characteristic for maximizing crop productivity. Nevertheless, the cold temperature and wet weather throughout the fall and winter seasons in South China impact the timing of flowering and the yield produced by C. oleifera. This study examined the miRNAs, transcriptomes, and phytohormones that are part of the flowering time regulatory networks in distinct varieties of C. oleifera (Sep, Oct, and Nov). This study provides evidence that phytohormones significantly impact the timing of flowering in C. oleifera leaves. There is a positive correlation between the accumulation variations of zeatin (cZ), brassinolide (BL), salicylic acid (SA), 1-amino cyclopropane carboxylic acid (ACC), and jasmonic acid (JA) and flowering time. This means that blooming occurs earlier when the quantity of these substances in leaves increases. Abscisic acid (ABA), trans-zeatin-riboside (tZR), dihydrozeatin (dh-Z), and IP (N6-Isopentenyladenine) exhibit contrasting effects. Furthermore, both miR156 and miR172 play a crucial function in regulating flowering time in C. oleifera leaves by modulating the expression of SOC1, primarily through the miR156-SPL and miR172-AP2 pathways. These findings establish a strong basis for future research endeavors focused on examining the molecular network associated with the flowering period of C. oleifera and controlling flowering time management through external treatments. [ABSTRACT FROM AUTHOR]

Background: Ticks are blood-feeding significant arthropods that can harbour various microorganisms, including pathogens that pose health risks to humans and animals. Tick-symbiont microorganisms are believed to influence tick development, but the intricate interactions between these microbes and the relationships between different tick-borne microorganisms remain largely unexplored. Results: Based on 111 tick pool samples presenting questing and engorged statuses including 752 questing tick and 1083 engorged tick from cattle and goats, which were collected in two types of geographic landscape (semi-desert and alpine meadow). We observed significant variations in the composition of tick-borne microorganisms across different environments and blood-engorgement statuses, with a pronounced divergence in symbionts compared to environmental bacteria. Metabolic predictions revealed over 90 differential pathways for tick-borne microorganisms in distinct environments and more than 80 metabolic variations in response to varying blood engorgement statuses. Interestingly, nine pathways were identified, particularly related to chorismate synthesis and carbohydrate metabolism. Moreover, microbial network relationships within tick-borne microorganism groups were highly distinct across different environments and blood-engorgement statuses. The microbial network relationships of symbionts involve some pathogenic and environmental microorganisms. Regression modelling highlighted positive correlations between the Coxiella symbiont and related pathogens, while some environmental bacteria showed strong negative correlations with Coxiella abundance. We also identified commensal bacteria/pathogens in bacterial cooccurrence patterns. Furthermore, we tested pathogenic microorganisms of each tick sample analysis revealed that 86.36% (1601/1855) of the tick samples carried one or more pathogenic microorganisms, The total carrier rate of bacterial pathogens was 43.77% ((812/1855). Most blood samples carried at least one pathogenic microorganism. The pathogens carried by the ticks have both genus and species diversity, and Rickettsia species are the most abundant pathogens among all pathogens. Conclusion: Our findings underscore that the bacterial pattern of ticks is dynamic and unstable, which is influenced by the environment factors and tick developmental characteristics. [ABSTRACT FROM AUTHOR]

Background and objectives: Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references. Methods: A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug. Results: Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01–9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74–9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15–32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98–57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43–52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26]. Conclusion: Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir's potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) is an intractable pain that results from primary nervous system injury and dysfunction. Herein, we demonstrated in animal models that peripheral nerve injury induced enhanced pain perception and anxiety-like behaviors. According to previous reports, nucleus accumbens (NAc) shell is required for complete expression of neuropathic pain behaviors and mood alternations, we found the elevated mRNA and protein level of Prokineticin-2 (Prok2) in the NAc shell after Chronic Constriction Injury (CCI). Prok2 knockdown in the NAc shell reversed NP and anxiety-like behaviors in rats, indicating that Prok2 might play a fundamental role in NP and anxiety co-morbidity. CCI significantly enhanced Prok2 co-expression with NF-κB P-p65 in comparison with control animals. In addition to reversing the established nociceptive hypersensitivities and anxiety simultaneously, NAc microinjection of NF-κB siRNA or specific inhibitor PDTC reversed Prok2 upregulation. Besides, Prok2 was significantly decreased in vitro when co-transfected with si-NF-κB. Dual-Luciferase assay showed NF-κB directly activated Prok2 gene transcriptional activity. Overall, these findings provide new insights into the neurobiological mechanisms behind NP and comorbid anxiety. The NF-κB/Prok2 pathway could be a potential therapeutic target for NP and anxiety disorders. [ABSTRACT FROM AUTHOR]