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Abstract Trillions of microbes colonize the ungulate gastrointestinal tract, playing a pivotal role in enhancing host nutrient utilization by breaking down cellulose and hemicellulose present in plants. Here, through large-scale metagenomic assembly, we established a catalog of 131,416 metagenome-assembled genomes (MAGs) and 11,175 high-quality species-level genome bins (SGBs) from 17 species of ungulates in China. Our study revealed the convergent evolution of high relative abundances of carbohydrate-active enzymes (CAZymes) in the gut microbiomes of plateau-dwelling ungulates. Notably, two significant factors contribute to this phenotype: structural variations in their gut microbiome genomes, which contain more CAZymes, and the presence of novel gut microbiota species, particularly those in the genus Cryptobacteroides, which are undergoing independent rapid evolution and speciation and have higher gene densities of CAZymes. Furthermore, these enrichment CAZymes in the gut microbiomes are highly enrichment in known metabolic pathways for short-chain fatty acid (SCFA) production. Our findings not only provide a valuable genomic resource for understanding the gut microbiomes of ungulates but also offer fresh insights into the interaction between gut microbiomes and their hosts, as well as the co-adaptation of hosts and their gut microbiomes to their environments.

Abstract Background The activation of the DNA damage response (DDR) heavily relies on post-translational modifications (PTMs) of proteins, which play a crucial role in the prevention of genetic instability and tumorigenesis. Among these PTMs, palmitoylation is a highly conserved process that is dysregulated in numerous cancer types. However, its direct involvement in the DDR and the underlying mechanisms remain unclear. Methods CRISPR-Cas9 technology was used to generate the PORCN KO and PORCN NLS KO cell lines. The effects of PORCN NLS in the DDR were verified by colony formation assays, MTT assays, the DR/EJ5 homologous recombination/non-homologous end-joining reporter system, xenograft tumor growth and immunofluorescence. Mechanisms were explored by mass spectrometry, acyl-biotin exchange (ABE) palmitoylation assay, Click-iT assay, cell subcellular fractionation assay, Western blot analysis, and in vivo and in vitro co-immunoprecipitation. Results In this study, we introduce evidence that Porcupine (PORCN) is an integral component of and plays a critical role in the DDR. PORCN deficiency hampers nonhomologous end joining (NHEJ) and highly sensitizes cells to ionizing radiation (IR) both in vitro and in vivo. We also provide evidence that PORCN possesses a nuclear fraction (nPORCN) with S-acyltransferase activity, unlike its membrane-bound O-acyltransferase in the endoplasmic reticulum. Furthermore, we show that nPORCN is necessary for the successful activation of NHEJ. Using mass spectrometry, we reveal the existence of an nPORCN complex and show that nPORCN mediates the S-palmitoylation of XRCC6/Ku70 at five specific cysteine sites in response to IR. Mutation of these sites causes a substantial increase in radiosensitivity and delays NHEJ. Additionally, we present evidence that nPORCN-dependent Ku70 palmitoylation is required for DNA-PKcs/Ku70/Ku80 complex formation. Conclusion Our findings underscore the crucial role of nPORCN-dependent Ku70 S-palmitoylation in the DDR.

Abstract Natural polymer substrates are gaining attention as substitutes for plastic substrates in electronics, aiming to combine high performance, intricate shape deformation, and environmental sustainability. Herein, natural wood veneer is converted into a transparent wood film (TWF) substrate. The combination of 3D printing and origami technique is established to create programmable wood-based origami electronics, which exhibit superior flexibility with high tensile strength (393 MPa) due to the highly aligned cellulose fibers and the formation of numerous intermolecular hydrogen bonds between them. Moreover, the flexible TWF electronics exhibit editable multiplexed configurations and maintain stable conductivity. This is attributed to the strong adhesion between the cellulose-based ink and TWF substrate by non-covalent bonds. Benefiting from its anisotropic structure, the programmability of TWF electronics is achieved through sequentially folding into predesigned shapes. This design not only promotes environmental sustainability but also introduces its customizable shapes with potential applications in sensors, microfluidics, and wearable electronics.

Gastrochilus balangshanensis, a new orchid species from the Balang Mountain, Sichuan Province, Southwest China, is described and illustrated. It morphologically resembles G. affinis, but differs in having shorter stems, a reniform epichile and a sub-hemispherical hypochile (spur), obtuse-rounded at the apex. The results of molecular phylogenetic analyses based on nuclear ribosome internal transcribed spacer (nrITS) and four chloroplast DNA markers (matK, psbA–trnH, psbM–trnD and trnL–F) from 50 Gastrochilus species indicate that G. balangshanensis is closely related to G. heminii and G. bernhardtianus, also endemic to the Hengduan Mountains. The novelty is a branch and trunk epiphyte in mixed coniferous forest.

Abstract Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis of CRC is a testament to the dysregulation of these signaling cascades, which culminates in the malignant transformation of colonic epithelium. This review aims to dissect the foundational signaling mechanisms implicated in CRC, to elucidate the generalized principles underpinning neoplastic evolution and progression. We discuss the molecular hallmarks of CRC, including the genomic, epigenomic and microbial features of CRC to highlight the role of signal transduction in the orchestration of the tumorigenic process. Concurrently, we review the advent of targeted and immune therapies in CRC, assessing their impact on the current clinical landscape. The development of these therapies has been informed by a deepening understanding of oncogenic signaling, leading to the identification of key nodes within these networks that can be exploited pharmacologically. Furthermore, we explore the potential of integrating AI to enhance the precision of therapeutic targeting and patient stratification, emphasizing their role in personalized medicine. In summary, our review captures the dynamic interplay between aberrant signaling in CRC pathogenesis and the concerted efforts to counteract these changes through targeted therapeutic strategies, ultimately aiming to pave the way for improved prognosis and personalized treatment modalities in colorectal cancer.

Abstract Background Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. Methods The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. Results As parameterized in tertiles, titanium showed positive dose–response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. Conclusions In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk. Graphical Abstract

Predicting financial market trends poses significant challenges due to the complex, dynamic, and often chaotic nature of the market, especially when dealing with data featuring a multitude of characteristics. In this research, we propose an effective data mining approach that combines Least Absolute Shrinkage and Selection Operator (LASSO) and Principal Component Analysis (PCA) for two-stage feature dimensionality reduction, resulting in a refined dataset. To enhance the model’s capacity to capture medium- and long-term index trends, we implement a sliding time window approach, utilizing data from the preceding 60 trading days. Long-Short Term Memory (LSTM) and Gated Recurrent Unit (GRU) models are employed to predict the return rate of Securities Bank of China (399986) over a 30-day trading period. We conducted a comprehensive comparative analysis involving our proposed model and established methods, namely, LASSO, PCA, and Hybrid ‌Recurrent Neural Networks (RNN). Our empirical findings unequivocally demonstrate the superior performance of our model in terms of both prediction accuracy and stability. Specifically, our model exhibits significantly higher predictive accuracy when forecasting the return rate of Securities Bank of China (399986) over a 30-day trading period, all while maintaining enhanced stability. These results underscore the exceptional efficacy of our approach within the realm of financial market time series forecasting, thus providing robust support for further research and practical applications within this domain.

In this paper, we utilize the Littlewood–Paley decomposition theory to establish two regularity criteria for the 3D magneto-micropolar equations in Vishik spaces, specifically focusing on the gradient of the velocity field.

Abstract Dominant species occupy a pivotal role in plant community, influencing the structure and function of the ecosystem. The spatial distributions of dominant species can react to the effect of different grazing intensities, thereby reflecting their tolerance and adaptive strategies toward grazing. In this study, geostatistical methods were mainly used to study the spatial distribution characteristics of Stipa krylovii Roshev. and Leymus chinensis (Trin.) Tzvel. species at two interval scales (quadrat size 5 m × 5 m, 10 m × 10 m) and two treatments (free grazing, FG, 1.66 sheep·ha− 1·a− 1; control, CK, 0 sheep·ha− 1·a− 1) in typical steppe of Inner Mongolia. A systematic sampling method was used in each 100 m × 100 m representative sample plots to obtain the height, coverage, and density of all species in the community. The results showed that grazing altered the concentrated distribution of S. krylovii and the spatial mosaic distribution pattern of S. krylovii and L. chinensis while having no effect on the spatial clumped distribution of L. chinensis. It also found that the spatial distributions of dominant species are primarily affected by structural factors, and random factors such as long-term grazing led to a transition of S. krylovii from a concentrated distribution to a small patchy random pattern should not be overlooked. Our findings suggest that long-term grazing alters the spatial distribution pattern of dominant species and that adaptive strategies may be the key for maintaining the dominant role of structural factors.

Background Polycystic ovary syndrome with insulin resistance (PCOS-IR) is recognized as one of the most challenging subtypes of PCOS to treat due to its intricate pathogenesis and significant individual variability. Although Metformin, as a first-line medication, can ameliorate blood glucose levels and enhance insulin sensitivity, its efficacy in regulating hormonal imbalances and improving ovarian function is limited. Additionally, its gastrointestinal side effects often hinder patient adherence. Objective To evaluate the efficacy and safety of Yishen Quzhuo Formula compared to metformin in the treatment of PCOS-IR. Methods A prospective study enrolled 102 PCOS-IR patients from June 2022 to October 2023 at the Department of Gynecology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Patients were randomly assigned in a 2∶1 ratio to the experimental group (n=68) treated with Yishen Quzhuo Formula or the control group (n=34) treated with metformin. The comparison was made between the two groups in terms of ovulation rate, pregnancy rate, sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, testosterone (T), anti-Müllerian hormone (AMH) ], glucose and lipid metabolism indicators, BMI, waist-hip ratio (WHR), and incidence of adverse reactions. Results After treatment, the basal body temperature (BBT) ovulation rate in the experimental group increased compared to before treatment (P0.05). After treatment, both groups showed a decrease in LH/FSH compared to before treatment (P0.05). After treatment, the waist circumference of the control group was lower than that of the experimental group (P0.05). During treatment, adverse reactions such as hypoglycemia, fatigue, epigastric discomfort, and diarrhea occurred in patients, with a lower incidence of adverse reactions in the experimental group (5/68, 7.35%) than in the control group (15/31, 48.39%) (χ2=20.404, P

Triboelectrification, a process that transforms mechanical energy into electrical energy through friction, holds promise for eco-friendly wastewater treatment. This study delves into the enhancement of tribocatalytic dye degradation using SrTiO3, a material notable for its non-piezoelectric and centrosymmetric properties. The synthesis of uni- and bi-doped SrTiO3 particles, achieved through a solid-state reaction at 1000 °C, results in a high-purity cubic perovskite structure. Doping with rhodium (Rh) and carbon (C) causes crystal lattice contraction, internal stress, and significant oxygen vacancies. These changes notably improve tribocatalytic efficiency under solar irradiation, with Rh-doped SrTiO3 demonstrating an impressive degradation rate of approximately 88% for Rhodamine B (RhB), along with reaction rate constants near 0.9 h−1 at 554 nm and a noticeable blueshift. This study highlights that defects introduced by doping are integral to this process, boosting catalytic activity through energy state modification and enhancing surface redox radical production. Additionally, these defects are instrumental in generating a flexoelectric field, which markedly influences the separation of electron–hole pairs under solar irradiation. Our findings illuminate the complex interplay between material composition, defect states, and environmental conditions, paving the way for advanced strategies in environmental remediation through optimized tribocatalytic activity.

Owing to their limited accuracy and narrow applicability, current antimicrobial peptide (AMP) prediction models face obstacles in industrial application. To address these limitations, we developed and improved an AMP prediction model using Comparing and Optimizing Multiple DEep Learning (COMDEL) algorithms, coupled with high-throughput AMP screening method, finally reaching an accuracy of 94.8% in test and 88% in experiment verification, surpassing other state-of-the-art models. In conjunction with COMDEL, we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro, ultimately increasing AMPs yields to a range of 0.5–2.1 g/L within hours. Moreover, by multi-omics analysis using COMDEL, we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible probiotics. Following this, we developed a microdroplet sorting approach and successfully screened three L. plantarum mutants, each showing a twofold increase in antimicrobial ability, underscoring their substantial industrial application values.

Abstract The negative effects of obesity and excess body fat on bone mineral density (BMD) have been widely reported. As opposed to waist circumference (WC) or body mass index (BMI), weight-adjusted waist index (WWI) is a superior method for assessing obesity. WWI also indicates centripetal obesity independently of the weight of the individual. An investigation of WWI and adolescents’ BMD was conducted in this study. The National Health and Nutrition Examination Survey (NHANES) 2011–2018 provided the data for this cross-sectional investigation. In this study, weighted multivariate logit models were employed to assess the correlation between teenage BMD and WWI. Additionally, we conducted interaction tests and subgroup analysis. Through multivariate linear regression, we discovered that WWI was negatively linked with lumbar, trunk, and total BMD but not pelvis BMD in this study, which included 6828 subjects. We found that each unit increase in WWI resulted in a lumbar BMD decline of 0.04 g/cm2 (95%CI −0.04, −0.04), a trunk BMD decrease of 0.03 g/cm2 (95%CI −0.03, −0.02), and a total BMD decrease of 0.02 g/cm2 (95%CI −0.02, −0.02). In conclusion, in US teenagers, there were negative connections discovered between WWI and lumbar, trunk, and total BMD, but not pelvis BMD.

Gastrochilus is an orchid genus containing 73 species of mainly epiphytic on trees or rocks in mountain forests of tropical and subtropical Asia. Previous phylogenetic analyses and morphological assessments have failed to produce a well-resolved phylogeny at the infrageneric level. In the present study, a new infrageneric classification of Gastrochilus is proposed based on thoroughly morphological and phylogenetic analyses based on 52 species. Our phylogenetic analysis divided the genus into six sections including three new sections, G. sect. Pseudodistichi, G. sect. Brachycaules and G. sect. Acinacifolii. We also reinstate G. suavis to the specific rank. Furthermore, two new species, G. armeniacus Jun Y. Zhang, B. Xu & Yue H. Cheng and G. minjiangensis Jun Y. Zhang, B. Xu & Yue H. Cheng, are described and illustrated. A key to six sections of the genus is presented.

Abstract Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan–Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan–Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P

Abstract Hydraulic systems play a pivotal and extensive role in mechanics and energy. However, the performance of intelligent fault diagnosis models for multiple components is often hindered by the complexity, variability, strong hermeticity, intricate structures, and fault concealment in real-world conditions. This study proposes a new approach for hydraulic fault diagnosis that leverages 2D temporal modeling and attention mechanisms for decoupling compound faults and extracting features from multisample rate sensor data. Initially, to address the issue of oversampling in some high-frequency sensors within the dataset, variable frequency data sampling is employed during the data preprocessing stage to resample redundant data. Subsequently, two-dimensional convolution simultaneously captures both the instantaneous and long-term features of the sensor signals for the coupling signals of hydraulic system sensors. Lastly, to address the challenge of feature fusion with multisample rate sensor data, where direct merging of features through maximum or average pooling might dilute crucial information, a feature fusion and decoupling method based on a probabilistic sparse self-attention mechanism is designed, avoiding the issue of long-tail distribution in multisample rate sensor data. Experimental validation showed that the proposed model can effectively utilize samples to achieve accurate fault decoupling and classification for different components, achieving a diagnostic accuracy exceeding 97% and demonstrating robust performance in hydraulic system fault diagnosis under noise conditions.

Abstract Objective To evaluate sanitary techniques for radical thyroid cancer surgery via the transaxillary approach without inflation single-port endoscopic surgery (TAWISES) and the conventional open anterior cervical approach (COACAS) in a controlled manner. Methods This work was a retrospective analysis of the clinical data of 60 patients admitted to our hospital for unilateral radical thyroid cancer surgery between 01/2021 and 12/2022. The control group underwent COACAS (30 patients), and the experimental group underwent TAWISES (30 patients). The patients’ operative time, intraoperative bleeding volume, 24-h postoperative pain index, drainage tube carrying time, hospitalization duration and complication rate were compared and analyzed. The patients were followed up for 3, 6 and 12 months postoperatively and evaluated based on numbness, muscular tightness, pain and other discomfort in the neck, as well as satisfaction with social adaptation and cosmetic incisions. The recurrence status was assessed for 1 year in both groups of patients. A questionnaire survey was conducted to assess patient acceptance of the two surgical approaches. The economic characteristics (cost-effectiveness and cost-utility) of the different approaches in our region were evaluated comprehensively. Results The length of the incision, drainage tube carrying time and hospitalization duration were greater in the experimental group than in the control group (P 0.05). Neck discomfort was greater in the control group, and the difference was statistically significant at the 3-month postoperative follow-up (P 0.05). However, mild discomfort was significantly more common in the experimental group (63.33% > 36.67%, 80% > 53.33%, P

Abstract Introduction Although there has been abundant evidence of the association between dyslipidemia as a single factor and osteoporosis, the non-linear relationship between osteoporosis and the Atherogenic Index of Plasma (AIP) has not yet been thoroughly investigated. This study aimed to investigate the complex relationship between AIP and bone mineral density (BMD) to elucidate their interrelationship. Methods An analysis of 2007–2018 National Health and Nutrition Survey (NHANES) data was conducted for this study. The study enrolled 5,019 participants. Logarithmically multiplying triglycerides and high-density lipoprotein cholesterol yields the AIP (base 10). The measured variables consisted of BMD in the total femur (TF), femoral neck (FN), and lumbar spine (LS). The association between AIP and BMD was examined using a range of statistical models, such as weighted multivariable logistic regression, generalized additive model, etc. Results It was found that AIP was positively associated with BMD after adjusting for age, gender, race, socioeconomic status, degree of education, income, Consuming alcoholic beverages, osteoporosis status (Yes or No), ALT, AST, serum creatinine, and total calcium levels. Further studies supported the association link between elevated BMD and AIP. Furthermore, compared to men, females had a higher positive connection between AIP and BMD. In general, there was a curve in the reverse L-shape seen, with a point of change around 0.877, indicating a relationship between AIP and TF BMD. Moreover, a curve exhibiting an L-formed pattern, with a point of inflection at around 0.702, was seen between AIP and FN BMD. In addition, a J-shaped curve was seen, with a point of inflection at 0.092, which demonstrates the association between AIP and LS BMD. Conclusion The AIP and TF BMD curves resemble inverted L shapes, as do the AIP and FN BMD curves. The relationship between AIP and LS BMD was further demonstrated by a J-shaped curve. The results indicate a possible association between AIP and bone mineral density, which should be explored in more detail.

Objective To investigate the effect of fluid flow shear stress (FFSS) on the fluid mechanic threshold of high-mobility group box 1 (HMGB1) release by synovial cells and chondrocytes. Moreover, the mechanism of chondrocyte and synovial cell damage induced by abnormal mechanical force was investigated to provide an experimental basis for exploring the pathogenesis and pathology of temporomandibular joint osteoarthritis. Methods With the approval of the Ethics Committee for Animal Experiments of the hospital, synovial tissue and cartilage tissue blocks were obtained from the knee joints of Sprague-Dawley (SD) rats, and synovial cells and chondrocytes were cultured and digested for subsequent experiments. Synovial cells and chondrocytes of 3-4 generations were acquired, and FFSS was applied to synovial and cartilage cells using a fluid shear mechanical device. The cells were divided according to the FFSS values of different sizes. Synovial cells were stimulated for 1 h with 1, 3, 5, or 10 dyn/cm2 of FFSS, and chondrocytes were stimulated for 1 h with 4, 8, 12, or 16 dyn/cm2 of FFSS. Resting cultures (0 dyn/cm2) were used as the control group. Changes in the morphology of the cells were observed. The expression and distribution of HMGB1 and interleukin-1β (IL-1β) were observed by immunohistochemistry. The expression of HMGB1 and IL-1β in the supernatant was analyzed by ELISA. The protein expression levels of intracellular HMGB1 and IL-1β were detected by Western blot. Results With increasing FFSS, the synovial cells and chondrocytes gradually swelled and ruptured, and the number of cells decreased. With increasing FFSS, the localizationof HMGB1 and IL-1β gradually shifted from the nucleus to the cytoplasm. In synovial cells, compared with those in the control group, the expression levels of HMGB1 and IL-1β were increased both in the supernatant and cells in the 1, 3, 5 and 10 dyn/cm2 intervention groups (P2 intervention groups (PP2 intervention groups (P2 intervention groups (P2 group, the protein expression levels of IL-1β gradually increased with increasing FFSS (P2 and 8 dyn/cm2, respectively. Therefore, upon stimulation with a mechanical force, synovial damage was damaged before chondrocytes.

Abstract Objective The purpose of this study was to evaluate the efficacy and clinical value of US, FNAC,FNA-Tg and FNAC + FNA-Tg, as well as the cutoff values of FNA-Tg to evaluate LN metastasis. Methods We analyzed the diagnostic value of different US signs, the efficiency of US, FNAC, FNA-Tg and FNAC + FNA-Tg among the LN- and LN + groups, and the cutoff value of FNA-Tg to evaluate LN metastasis. We punctured LNs multiple times and measured the levels of FNA-Tg. Furthermore, the LNs were marked with immunohistochemical Tg and LCA to distinguish the presence of Tg in the para-cancerous tissue of the LNs. Results The s-Tg and FNA-Tg of the LN + group were higher than those of the LN- group (P = 0.018, ≤ 0.001). The LN + group had more abnormal US signs than the LN- group. The cutoff value of FNA-Tg was 3.2 ng/mL. US had a high sensitivity (92.42), but the specificity was not satisfactory (55.1). FNA-Tg had a higher sensitivity (92.42 vs. 89.39), specificity (100 vs. 93.88), and accuracy (92.42 vs. 83.27) than FNAC. However, the sensitivity of FNAC + FNA-Tg increased further, while the specificity and accuracy decreased slightly. The presence of Tg in the normal lymphocytes adjacent to the cancer was confirmed. Conclusion Ultrasonography provides a noninvasive, dynamic, multidimensional assessment of LNs. With a cutoff value of 3.2 ng/mL, FNA-Tg has higher accuracy and a lower false-negative rate than various single diagnoses. However, FNAC combined with FNA-Tg does not cause additional pain to patients and offers a higher diagnostic efficacy and clinical value.

ABSTRACT This study explores the effects of disinfectant and antibiotic exposure on gut health, focusing on gut microbiota balance and gut immune function. Our analysis indicates that disinfectants increase the proportion of Gram-positive bacteria, particularly increasing Staphylococcus levels, while antibiotics increase the proportion of Gram-negative bacteria, especially Bacteroides levels. These changes disrupt microbial harmony and affect the gut microbiome’s functional capacity. Additionally, our research reveals that both disinfectants and antibiotics reduce colon length and cause mucosal damage. A significant finding is the downregulation of NLRC4, a key immune system regulator in the gut, accompanied by changes in immune factor expression. This interaction between chemical exposure and immune system dysfunction increases susceptibility to inflammatory bowel disease and other gut conditions. Given the importance of disinfectants in disease prevention, this study advocates for a balanced approach to their use, aiming to protect public health while minimizing adverse effects on the gut microbiome and immune function.IMPORTANCEDisinfectants are extensively employed across various sectors, such as the food sector. Disinfectants are widely used in various sectors, including the food processing industry, animal husbandry, households, and pharmaceuticals. Their extensive application risks environmental contamination, impacting water and soil quality. However, the effect of disinfectant exposure on the gut microbiome and the immune function of animals remains a significant, unresolved issue with profound public health implications. This highlights the need for increased scrutiny and more regulated use of disinfectants to mitigate unintended consequences on gut health and maintain immune system integrity.

IntroductionHeterostyly is a genetically controlled style polymorphism, that plays an important role in promoting outcrossing and improving reproductive fitness. Although distyly is often studied in plants of the Rubiaceae family, little attention has been paid to the reproductive strategies of distylous species in fragmented habitats. Here, We report for the first time the growth of Ophiorrhiza alatiflora, a type distylous species, in karst areas and evaluate its reciprocity between long styled morph and short one. We analyze the two distyly morph differences in the ancillary polymorphic of flowers and explore their reproductive strategy in fragmented habitats.MethodsIn this study, we measured the floral characteristics of different morphs and performed differential secondary metabolite analysis on different morphs and tissue organs; Different pollination treatments were carried out to observe the fruit set, pollen germination, and pollen tube elongation of O. alatiflora.Results and discussionOur research indicates that O. alatiflora is a typical distylous plant for the distyly has high reciprocity. Both morphs exhibit the highest fruit set of intermorph outcrossing; The pollen germination and pollen tube elongation experiments have also demonstrated that the affinity of pollen from intermorph outcrossing is highest, regardless of whether it is the long or short morph as the maternal parent; Meanwhile, O. alatiflora is an incompletely self-incompatible plant that exhibits a certain degree of self-pollination and intramorph outcrossing, which may be one of the important means to ensure sustainable reproduction in severely disturbed habitats. In the ancillary polymorphic of flowers, L-morphs flowers produce more pollen, and S-morph flowers produce more ovules to improve their male-female fitness and compensate for the asymmetry of pollen flow; Compared with S-morphs, L-morphs contain significantly higher levels of several kinds of terpenoids. S-morphs produce more flavonoids than L-morphs. The differences in secondary metabolites between L-morphs and S-morphs are mainly reflected in the different nutritional organs (including stems and leaves). Overall, our work has revealed the unique reproductive strategy of O. alatiflora in fragmented habitats based on the characteristics of distyly, verifying the hypothesis that the distyly of O. alatiflora promotes outcrossing and avoids male-female interference, improving male-female fitness and this is the first time in the Ophiorrhiza genus.

Background Determining the status of breast cancer susceptibility genes (BRCA) is crucial for guiding breast cancer treatment. Nevertheless, the need for BRCA genetic testing among breast cancer patients remains unmet due to high costs and limited resources. This study aimed to develop a Bi-directional Self-Attention Multiple Instance Learning (BiAMIL) algorithm to detect BRCA status from hematoxylin and eosin (H&E) pathological images. Methods A total of 319 histopathological slides from 254 breast cancer patients were included, comprising two dependent cohorts. Following image pre-processing, 633,484 tumor tiles from the training dataset were employed to train the self-developed deep-learning model. The performance of the network was evaluated in the internal and external test sets. Results BiAMIL achieved AUC values of 0.819 (95% CI [0.673–0.965]) in the internal test set, and 0.817 (95% CI [0.712–0.923]) in the external test set. To explore the relationship between BRCA status and interpretable morphological features in pathological images, we utilized Class Activation Mapping (CAM) technique and cluster analysis to investigate the connections between BRCA gene mutation status and tissue and cell features. Significantly, we observed that tumor-infiltrating lymphocytes and the morphological characteristics of tumor cells appeared to be potential features associated with BRCA status. Conclusions An interpretable deep neural network model based on the attention mechanism was developed to predict the BRCA status in breast cancer. Keywords: Breast cancer, BRCA, deep learning, self-attention, interpretability.

The combination of biochar and nitrogen (N) fertilization in agricultural salt-affected soils is an effective strategy for amending the soil and promoting production. To investigate the effect of nitrogen reduction combined with biochar application on a soda saline soil and soybean growth in black soil areas, a pot experiment was set up with two biochar application levels, 0 (B0) and 4.5 t/hm2 (B1); two biochar application depths, 0-20 cm (H1) and 0-40 cm (H2); and two nitrogen application levels, conventional nitrogen application (N0) and nitrogen reduction of 15% (N1). The results showed that the application of biochar improved the saline soil status and significantly increased soybean yield under lower nitrogen application. Moreover, increasing the depth of biochar application enhanced the effectiveness of biochar in reducing saline soil barriers to crop growth, which promoted soybean growth. Increasing the depth of biochar application increased the K+ and Ca2+ contents, soil nitrogen content, N fertilizer agronomic efficiency, leaf total nitrogen, N use efficiency, AN, Tr, gs, SPAD, leaf water potential, water content and soybean yield and its components. However, the Na+ content, SAR, ESP, Na+/K+, Ci and water use efficiency decreased with increasing biochar depth. Among the treatments with low nitrogen input and biochar, B1H1N1 resulted in the greatest soil improvement in the 0-20 cm soil layer compared with B0N0; for example, K+ content increased by 61.87%, Na+ content decreased by 44.80%, SAR decreased by 46.68%, and nitrate nitrogen increased by 26.61%. However, in the 20-40 cm soil layer, B1H2N1 had the greatest effect on improving the soil physicochemical properties, K+ content increased by 62.54%, Na+ content decreased by 29.76%, SAR decreased by 32.85%, and nitrate nitrogen content increased by 30.77%. In addition, compared with B0N0, total leaf nitrogen increased in B1H2N1 by 25.07%, N use efficiency increased by 6.7%, N fertilizer agronomic efficiency increased by 32.79%, partial factor productivity of nitrogen increased by 28.37%, gs increased by 22.10%, leaf water potential increased by 27.33% and water content increased by 6.44%. In conclusion, B1H2N1 had the greatest effect on improving the condition of saline soil; it not only effectively regulated the distribution of salt in soda saline soil and provided a low-salt environment for crop growth but also activated deep soil resources. Therefore, among all treatments investigated in this study, B1H2N1 was considered most suitable for improving the condition of soda saline soil in black soil areas and enhancing the growth of soybean plants.

Purpose: Polypharmacy presents many challenges to patient medication self-management. This study aims to explore the self-management processes of medication in polypharmacy from the perspectives of both patients and healthcare providers, which can help identify barriers and facilitators to effective management.Methods: A systematic review of qualitative studies was performed by searching seven databases: PubMed, Web of Science, Cochrane Library, Embase, CINAHL, PsycINFO, and MEDLINE, from their establishment until August 2024. The Critical Appraisal Skills Programme (CASP) tool was employed to evaluate the quality of the studies included. The extracted data were then analysed thematically and integrated into The Taxonomy of Everyday Self-management Strategies (TEDSS) framework.Results: A total of 16 studies were included, involving 403 patients and 119 healthcare providers. Patient management measures were mapped into TEDSS framework, including categories such as medical management, support-oriented domains, and emotional and role management.Conclusion: Enhancing patients’ proactive health awareness, improving medication literacy, balancing lifestyle adjustments with medication therapy, dynamically reviewing and optimizing medications, strengthening patients’ social support networks, and helping patients integrate medication management into their daily life are the key elements that can effectively assist patients in self-managing their medications. Future interventions to improve patient medication self-management ability should be designed for these issues.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024524742.

Summary: Adjuvant radiation therapy is a common treatment for breast cancer, yet its effectiveness is often limited by radioresistance in patients. Identifying novel targets to combat this radioresistance is imperative. Recent investigations show that gp78 is upregulated in drug-resistant breast cancer cells. Our study reveals that gp78 markedly increased the phosphorylation of KAP1 and promoted DNA damage repair caused by ionizing radiation. Mechanistically, gp78 degrades phosphatases (PPP1CC/PPP2CA) in a ubiquitination-dependent manner. PPP1CC and PPP2CA are crucial regulators of KAP1 phosphorylation in response to DNA damage. Therefore, gp78 leads to a notable elevation in the phosphorylation of KAP1 by degrading phosphatases, thereby promoting the DNA damage repair process and increasing the radioresistance of tumor cells. The identification of gp78 as a pivotal regulator in radioresistance suggests a promising avenue for intervention. Combining blockade strategies targeting gp78 holds a signification potential for reversing radioresistance and improving the efficacy of breast cancer radiotherapy.

BackgroundArtificial intelligence (AI) is transforming healthcare, yet little is known about Chinese oncologists’ attitudes towards AI. This study investigated oncologists’ knowledge, perceptions, and acceptance of AI in China.MethodsA cross-sectional online survey was conducted among 228 oncologists across China. The survey examined demographics, AI exposure, knowledge and attitudes using 5-point Likert scales, and factors influencing AI adoption. Data were analyzed using descriptive statistics and chi-square tests.ResultsRespondents showed moderate understanding of AI concepts (mean 3.39/5), with higher knowledge among younger oncologists. Only 12.8% used ChatGPT. Most (74.13%) agreed AI is beneficial and could innovate healthcare, 52.19% respondents expressed trust in AI technology. Acceptance was cautiously optimistic (mean 3.57/5). Younger respondents (∼30) show significantly higher trust (p = 0.004) and acceptance (p = 0.009) of AI compared to older respondents, while trust is significantly higher among those with master’s or doctorate vs. bachelor’s degrees (p = 0.032), and acceptance is higher for those with prior IT experience (p = 0.035).Key drivers for AI adoption were improving efficiency (85.09%), quality (85.53%), reducing errors (84.65%), and enabling new approaches (73.25%).ConclusionsChinese oncologists are open to healthcare AI but remain prudently optimistic given limitations. Targeted education, especially for older oncologists, can facilitate AI implementation. AI is largely welcomed for its potential to augment human roles in enhancing efficiency, quality, safety, and innovations in oncology practice.