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Abstract Background Fibroblast growth factors (FGFs) are cell signaling proteins that perform multiple biological processes in many biological processes (cell development, repair, and metabolism). The dynamics of tumor cells, such as angiogenesis, transformation, and proliferation, have a significant impact on neoplasia and are modulated by FGFs. FGFs’ expression and prognostic significance in ovarian cancer (OC), however, remain unclear. Methods Through a series of in silico analysis, we investigated the transcriptional, survival data, genetic variation, gene-gene interaction network, ferroptosis-related genes, and DNA methylation of FGFs in OC patients. Results We discovered that while FGF18 expression levels were higher in OC tissues than in normal OC tissues, FGF2/7/10/17/22 expression levels were lower in the former, and that FGF1/19 expression was related to the tumor stage in OC patients. According to the survival analysis, the clinical prognosis of individuals with OC was associated with the aberrant expression of FGFs. The function of FGFs and their neighboring genes was mainly connected to the cellular response to FGF stimulus. There was a negative correlation between FGF expression and various immune cell infiltration. Conclusions This study clarifies the relationship between FGFs and OC, which might provide new insights into the choice of prognostic biomarkers of OC patients.

Abstract T cells are fundamental components in tumour immunity and cancer immunotherapies, which have made immense strides and revolutionized cancer treatment paradigm. However, recent studies delineate the predicament of T cell dysregulation in tumour microenvironment and the compromised efficacy of cancer immunotherapies. CRISPR screens enable unbiased interrogation of gene function in T cells and have revealed functional determinators, genetic regulatory networks, and intercellular interactions in T cell life cycle, thereby providing opportunities to revamp cancer immunotherapies. In this review, we briefly described the central roles of T cells in successful cancer immunotherapies, comprehensively summarised the studies of CRISPR screens in T cells, elaborated resultant master genes that control T cell activation, proliferation, fate determination, effector function, and exhaustion, and highlighted genes (BATF, PRDM1, and TOX) and signalling cascades (JAK-STAT and NF-κB pathways) that extensively engage in multiple branches of T cell responses. In conclusion, this review bridged the gap between discovering element genes to a specific process of T cell activities and apprehending these genes in the global T cell life cycle, deepened the understanding of T cell biology in tumour immunity, and outlined CRISPR screens resources that might facilitate the development and implementation of cancer immunotherapies in the clinic.

Abstract Acne vulgaris is a type of chronic skin disorder caused by Propionibacterium acnes (P. acnes). Neutrophil extrinsic traps (NETs) play key role in many types of inflammatory skin diseases. Adipose-derived stem cells (ADSCs) was reported modulate immune responses and neutrophil activity. Here, we explored the potential role of ADSCs and the potential mechanism associated with neutrophil extracellular traps (NETs) in relieving acne vulgaris. In the P. acnes-infected ear skin model, histological staining was used to evaluate the inflammatory infiltration and NET formation in control, P. acnes, and P. acnes + ADSCs groups. Besides, western blot was used to detect the expression levels of cit-H3, MPO, and Nrf2 in ear tissue. In vitro, the immunofluorescence staining of MPO and cit-H3, and SYTOX green staining were performed to measure the NET formation. CCK-8 assay, EdU staining, and wound healing assay were used to detect the proliferation and migration abilities of keratinocytes. ELISA assay was utilized to detect the secretion of inflammatory cytokines. In P. acnes-infected ear skin, ADSC treatment significantly attenuated inflammation and NET formation via activating Nrf2 signaling pathway. In vitro, the conditioned medium of ADSCs reduced the formation of P. acne-induced NETs. Besides, ADSCs could inhibit that the NETs efficiently promoted the proliferation, migration, and inflammatory cytokine secretion of keratinocytes. Our study suggested that ADSCs could attenuate P. acne-related inflammation by inhibiting NET formation. This study provides a novel therapeutic perspective of ADSCs in combating acne vulgaris.

Melanoma is one of the most lethal cutaneous malignancies. Despite great advances in radiotherapy, chemotherapy, and immunotherapy, the survival rate and prognosis of patients with melanoma remain poor. The abundant and sophisticated reciprocal communication network between melanoma cells and non-tumor cells contributes to the high heterogeneity of the melanoma microenvironment and is intimately related to varying treatment responses and clinical courses. Extracellular vesicles (EVs) are membrane structures generated by nearly all cell types. EVs contain biologically active molecules, mainly comprising proteins, lipids, and RNAs, and undoubtedly play multifaceted roles in numerous diseases, represented by melanoma. Non-coding RNAs (ncRNAs) mainly encompass long non-coding RNAs, microRNAs, and circular RNAs and constitute the majority of the human transcriptome. Multiple ncRNAs encapsulated in EVs coordinate various pathophysiological processes in melanoma. This review summarizes the mechanisms by which EV-ncRNAs modulate biological behaviors and immunity, and their potential diagnostic and therapeutic applications in melanoma. Undoubtedly, further insight into EV-ncRNAs and their functions in melanoma will contribute to the clinical treatment of melanoma and the implementation of precision medicine.

Hearing loss has an extremely high prevalence worldwide and brings incredible economic and social burdens. Mechanisms such as epigenetics are profoundly involved in the initiation and progression of hearing loss and potentially yield definite strategies for hearing loss treatment. Non-coding genes occupy 97% of the human genome, and their transcripts, non-coding RNAs (ncRNAs), are widely participated in regulating various physiological and pathological situations. NcRNAs, mainly including micro-RNAs (miRNAs), long-stranded non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are involved in the regulation of cell metabolism and cell death by modulating gene expression and protein-protein interactions, thus impacting the occurrence and prognosis of hearing loss. This review provides a detailed overview of ncRNAs, especially miRNAs and lncRNAs, in the pathogenesis of hearing loss. We also discuss the shortcomings and issues that need to be addressed in the study of hearing loss ncRNAs in the hope of providing viable therapeutic strategies for the precise treatment of hearing loss.

The occurrence and development of Benggang is closely related to the decreased shear strength of collapsing walls. Plant roots can improve the soil shear resistance, and their soil reinforcing effect is restricted by soil moisture content (SMC). However, the effect and mechanism of SMC on the shear properties of rooted soil with different soil properties remain unknown. Therefore, the dominant soil erosion-resistant plant Dicranopteris linearis was selected as the research object, and shear tests were conducted to determine the shear strength response of rooted soil to SMC in the lateritic layer (LL), sandy layer (SL) and detritus layer (DL) with SMCs from 15% to 30%. The results showed that, compared with 15% SMC, the average decrease in shear strength of 30% SMC in the LL, SL and DL rooted soil were 17.37%, 21.96% and 23.36%, respectively. The rooted soil cohesion changed with increasing SMC in a binomial function, and the optimal SMC in the LL was 22.78%, which was higher than that of the SL (19.67%) and DL (18.39%). The cohesion increment of rooted soil weakened with increasing SMC, and the decrease was greatest in the SL. When the SMC increased from 15% to 30%, the internal friction angle of the rooted soil decreased by 34%, 11% and 12% in the LL, SL and DL, respectively. The Wu and Waldron’s model (WWM) correction parameters k′¯ of the LL, SL and DL were 0.59, 0.14 and 0.05, respectively. With the modified WWM, a new prediction model for the shear strength of rooted soil based on SMC was established. In short, a high SMC weakened the mechanical effect of Dicranopteris linearis-rooted soil, especially in the SL and DL of the collapsing wall, and attention should be given to drainage facilities when treating Benggang erosion.

Assessing the distribution and risks associated with the soil lead content in the Tieguanyin tea plantations of Anxi County is critical, given the county’s significance as the primary Tieguanyin tea production area in Fujian Province. This study examined the distribution characteristics of soil lead in Anxi County’s tea plantations according to the Kriging spatial interpolation of the parameters of the semivariance function of the exponential model. Moreover, the sources of lead content were analyzed, considering geological backgrounds and anthropogenic influences. Ecological risks and the issuance of early warnings were also assessed. The soil lead content in the rocks of the Tieguanyin tea plantations in Anxi County followed the order: andesite > dacite > rhyolite > granite. The soil lead content gradually decreased from the center toward the east and west, forming four distinct north–south parallel zones. High-lead-content areas were identified at the border of Jiandou, Bailai, and Hushang; in the central part of Lutian; and in the southern part of Huqiu. The high levels of soil lead in the tea plantations possibly originated from industrial and mining activities, automobile exhaust, and agricultural activities. The distribution of single-factor pollution indices and potential risk evaluation based on the Soil Environmental Quality Standard, Environmental Technical Conditions for Tea Production Area, and Environmental Technical Conditions for Organic Tea Production Area indicated that the soil in Tieguanyin tea plantations in Anxi County was clean and safe for tea cultivation.

To address the cost issue associated with pixel-level image annotation in fully supervised semantic segmentation, a method based on semi-supervised semantic segmentation is proposed for extracting winter wheat planting areas. This approach utilizes self-training with pseudo-labels to learn from a small set of images with pixel-level annotations and a large set of unlabeled images, thereby achieving the extraction. In the constructed initial dataset, a random sampling strategy is employed to select 1/16, 1/8, 1/4, and 1/2 proportions of labeled data. Furthermore, in conjunction with the concept of consistency regularization, strong data augmentation techniques are applied to the unlabeled images, surpassing classical methods such as cropping and rotation to construct a semi-supervised model. This effectively alleviates overfitting caused by noisy labels. By comparing the prediction results of different proportions of labeled data using SegNet, DeepLabv3+, and U-Net, it is determined that the U-Net network model yields the best extraction performance. Moreover, the evaluation metrics MPA and MIoU demonstrate varying degrees of improvement for semi-supervised semantic segmentation compared to fully supervised semantic segmentation. Notably, the U-Net model trained with 1/16 labeled data outperforms the models trained with 1/8, 1/4, and 1/2 labeled data, achieving MPA and MIoU scores of 81.63%, 73.31%, 82.50%, and 76.01%, respectively. This method provides valuable insights for extracting winter wheat planting areas in scenarios with limited labeled data.

Background: Melanoma is the most lethal, and one of the most aggressive forms of cutaneous malignancies, which poor response to treatment has always puzzled clinicians. As is known to all, aging and immune microenvironment are two crucial factors impacting melanoma biological progress through the tumor microenvironment (TME). However, reliable biomarkers for predicting melanoma prognosis based on aging and immune microenvironment and therapeutic efficacy of immune checkpoints remain to be determined.Methods: The aging-related genes (ARGs) were obtained from the Human Ageing Genomic Resources and immune-related genes (IRGs) were downloaded from the Immunology database as well as Analysis Portal (ImmPort) database. Next, we initially performed LASSO regression and multivariate Cox regression to identify prognostic ARGs and IRGs in the TCGA and GSE65904 datasets, and firstly constructed a novel comprehensive index of aging and immune (CIAI) signature. Finally, in vitro molecular biology experiments were performed to assess the regulatory role of CNTFR in melanoma cell lines proliferation and migration, macrophage recruitment, and M2 polarization.Results: This novel CIAI signature consisted of 7 genes, including FOXM1, TP63, ARNTL, KIR2DL4, CCL8, SEMA6A, and CNTFR, in which melanoma patients in the high-CIAI group had shorter OS, DSS, and PFI, indicating CIAI model served as an independent prognostic index. Moreover, we found the CIAI score was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Finally, CNTFR might function as oncogenes in melanoma cell lines and the silencing of CNTFR reduced macrophage recruitment and M2 polarization.Conclusion: In this study, we have first presented a novel prognostic CIAI model applied to assess immune checkpoint therapy and the efficacy of conventional chemotherapy agents in melanoma patients. Thus providing a new insight for combating melanoma.

Objectives: We examined the magnitude and determinants of socioeconomic disparities in disability-free life expectancy and life expectancy at age 65 (DFLE65 and LE65) in China.Methods: Data from Chinese Longitudinal Healthy Longevity Survey collected during 2011–2018 (8,184 participants aged ≥65) were used. Socioeconomic status (SES) was measured by economic status (ES), and education, respectively. Multistate Markov models and microsimulations were fitted to estimate DFLE65 and LE65.Results: LE65 between high- and low-ES groups differed by 2.20 years for males and 2.04 years for females. The DFLE65 disparity in ES was 1.51 and 1.29 years for males and females, respectively. Not undergoing physical examinations, inadequate fruit/vegetable intake, and stress contributed to 35.10% and 57.36% of DFLE65 disparity in ES, as well as 26.36% and 42.65% of LE65 disparity for males and females, respectively. These disparities in education and ES were of a similar magnitude, while the above factors contributed little to education disparity.Conclusion: Socioeconomic disparities in DFLE65 and LE65 existed in China. Physical examination, fruit/vegetable intake and stress partly explained these disparities.

This study aimed to elucidate the potential regulatory mechanism of mung bean peptides (MBPs) on glucolipid metabolism in insulin-resistant mice induced by high-fat diet (HFD) using untargeted serum metabolomics, enzyme linked immunosorbent assay (ELISA), intraperitoneal injection glucose tolerance test (IPGTT), insulin tolerance test (IPITT), and hematoxylin-eosin staining (H&E). The regulatory effect of MBPs for alleviating insulin resistance was studied by measuring body weight, fasting blood glucose (FBG) and serum insulin levels, C-Peptide levels, inflammatory and antioxidant factors, and histopathological observation of C57BL/6 mice. The experimental results showed that dietary intervention with MBPs (245 mg/kg/d) for 5 weeks significantly relieved insulin resistance in HFD mice. The body weight, insulin resistance index, and the levels of FBG, C-Peptide, IL-6, TNF-α, and MDA in the serum of HFD mice significantly decreased (P < 0.05). Conversely, SOD content and pancreatic β cell function index significantly increased (P < 0.05), and the damaged pancreatic tissue was repaired. One biomarker associated with insulin resistance was glycine. In addition, there were four important differential metabolites: pyroglutamate, D-glutamine, aminoadipic acid, and nicotinamide, involved in 12 metabolic pathway changes. It was found that MBPs may regulate amino acid, glycerol phospholipid, fatty acid, alkaloid, and nicotinamide metabolism to regulate the metabolic profile of HFD mice in a beneficial direction.

Winter wheat is one of the most important food crops in China, and it is of great significance to ensure national food security. The accurate extraction of wheat-growing areas is a prerequisite for growth assessments, stress monitoring, and yield assessments. In this study, GF-6 (8 m resolution) and Sentinel-2 (10 m resolution) remote sensing images were used to create datasets for the accurate extraction of winter-wheat growing areas by improving the U-Net model. First, U-Net was used as the base network to extract features, and then the convolutional block attention module (CBAM) was embedded in the basic convolutional units in the coding and decoding layers of the network to enhance or suppress the features to improve the feature-expression capability of the model, and to finally complete the end-to-end winter-wheat planting-area extraction. SegNet, DeepLabV3+, and U-Net-CBAM were selected as the comparison models, and they were tested using the test set in the Sentinel-2 dataset. The precision of the U-Net-CBAM model trained on the GF-6 dataset was 84.92%, the MIoU was 77.1%, the recall was 88.28%, the overall precision (OA) was 91.64%, and the F1 was 86.45%. For training on Sentinel-2 dataset, those values were: 90.06% for precision, 83.18% for MIoU, 90.78% for recall, 93.93% for OA, and 90.52% for F1, which showed significantly better results than those of the comparison models, indicating that U-Net-CBAM improved the accuracy of winter-wheat area extraction. It also showed that the segmentation performance of the training and test sets from different datasets was much lower than the segmentation performance from the same dataset.

Failure of collapsing walls is an important process affecting the development of Benggang and is closely related to the soil shear strength. Plant roots can increase the soil shear strength. However, the effects and mechanisms of root reinforcement on the soil shear strength of collapsing walls remain unclear. To explore the shear strength characteristics of collapsing walls and their influencing factors under different vegetation conditions, Pennisetum sinese, Dicranopteris dichotoma, Odontosoria chinensis, and Neyraudia reynaudiana were adopted as experimental objects in the Benggang district of Anxi County, Southeast China. We measured the root characteristics and in situ shear strength of root–soil complexes by dividing soil with the four vegetation conditions into five soil layers: 0–5 cm, 5–10 cm, 10–15 cm, 15–20 cm, and 20–25 cm. The average shear strength of the root–soil complexes of the various plants ranked as follows: Pennisetum sinese (30.95 kPa) > Odontosoria chinensis (28.08 kPa) > Dicranopteris dichotoma (21.24 kPa) > Neyraudia reynaudiana (14.99 kPa) > bare soil (11.93 kPa). The enhancement effect of the root system on the soil shear strength was mainly manifested in the 0–5 cm soil surface layer. The soil shear strength attained an extremely significant positive correlation with the root length density, root surface area density, root volume density, root biomass density, for root diameters (L) less than or equal to 0.5 mm and between 0.5 and 1 mm, the soil shear strength could be simulated by using root volume density. The shear strength of undisturbed root–soil complexes measured with a 14.10 pocket vane tester was higher than the value obtained with the Wu–Waldron model (WWM). The correction coefficient k′ varied between 0.20 and 20.25, mostly exceeding 1, and the average correction coefficient k′ value was 4.94. The average correction coefficient determined in this test can be considered to modify the WWM model when conducting experiments under similar conditions.

Abstract The efficacy and safety of venetoclax in newly diagnosed pediatric acute myeloid leukemia (AML) are not well-established as they are in adults. Children newly diagnosed with AML were recommended for induction therapy with venetoclax and chemotherapy or hypomethylating agents (HMAs) as per for the ChiCTR1900027146 trial. Venetoclax was administered at a consistent dose of 200 mg/m2/day for 28 days, with adjustments when used concurrently with azoles. The study measured both the remission rates and the safety assessments of venetoclax. We enrolled 45 newly diagnosed pediatric patients with AML. The complete remission rates were 94.7% in the low/middle-risk group and 80.8% in the high-risk group; MRD-negative rates were 52.6% and 38.5% in the low/middle-risk group and high-risk group, respectively. Venetoclax based combination therapy was well tolerated by the majority of patients. The median duration of venetoclax dosing was 18 days (range 9–28), with hematological toxicity and infection being the most common adverse events. Venetoclax-based induction regimens demonstrated a high response rate and safety profile in newly diagnosed pediatric AML cases. This underscores the significance of venetoclax as a viable treatment option for untreated AML, extending beyond its role as salvage therapy for refractory/relapsed AML.

Adding heterogeneous fillers with high thermal conductivity (TC) to polymer has been recognized as an effective way to increase the effective thermal conductivity (ETC) of polymer composites. Extensive researches have been conducted on the ETC of composites with heterogeneous fillers. However, the heat transfer enhancement mechanism of heterogeneous fillers remains unknown, and the combined effects of filler size, filler contact, interface thermal resistance (Rc) and other parameters on the ETC have not been explored. In this study, above combined effects are investigated. The results show that the filler contact and Rc are the key factors determining the ETC. The ETC of composite with filler contacts reaches 2.35 at filler content of 25%, which is 11.9% higher than that without filler contacts. The ETC also strongly depends on the R*c (dimensionless form of Rc) ratio (R*c1/R*c2) between two fillers, with it becoming asymmetrical when the amount of R*c(R*c1 + R*c2) is larger. The ETCs decrease with the increase of R*c1/R*c2 when the R*c1/R*c21. When R*c1 + R*c2 is a constant, the ETC increases with the competing effects of R*c. The models with filler contacts exhibit higher accuracy than other classical models in calculating the ETC across the entire range of filler content.

Abstract Bitter gourd wilt, a severe vascular disease triggered by the soilborne pathogen Fusarium oxysporum f. sp. momordicae (FOM), markedly constrains bitter gourd yield. In this study, a novel strain BF19 of Brevibacillus brevis was isolated and identified, exhibiting strong antimicrobial activity against FOM through in vivo and in vitro experiments. To comprehensively assess the biocontrol potential of strain BF19, we conducted phenotypic, phylogenetic, and comparative genomics analyses. Phenotypic analysis revealed that BF19 exhibited 53.33% biocontrol efficacy and significantly increased the average plant height, root fresh weight, and dry weight. Whole-genome sequencing and comparative genomic analysis revealed numerous potential genes associated with biocontrol mechanisms in BF19. Importantly, the integration of metabolic cluster prediction with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) revealed the presence of a macrobrevin antibiotic, a product of polyketide synthases (PKSs), predominantly in BF19 fermentation products. The effectiveness of the Br. brevis strain BF19 and its crude extract against bitter gourd wilt has also been confirmed. This study provides a genetic framework for future investigations on PKSs and establishes a scientific basis for optimizing field applications of microbial biopesticides derived from Br. brevis BF19.

Abstract The Cape hare (Lepus capensis) is among the most widely distributed hare species globally, inhabiting extensive regions across Africa, the Middle East, and Central Asia. However, evolutionary and genetic research on L. capensis was seriously impeded by the absence of a reference genome. Here, we assembled and constructed a chromosome-level genome of L. capensis (with scaffolds anchored to 25 chromosomes and a total assembled length of 2.9 Gb, achieving a contig N50 length of 124.44 Mb) using PacBio HiFi sequencing and Hi-C assembly technology. Evaluation using BUSCO indicated the genome assembly to be 98.2% complete. The de novo prediction revealed that repetitive sequences constitute 46.13% of the entire genome, and long interspersed nuclear elements (LINEs) constituted the largest portion. We annotated a total of 13, 868 protein-coding genes using transcriptomes from two tissues (muscle and skin). This high-quality reference genome serves as a valuable genomic resource for advancing genetic studies in this species.

Abstract Clostridioides difficile toxin B (TcdB) is the key virulence factor accounting for C. difficile infection-associated symptoms. Effectively neutralizing different TcdB variants with a universal solution poses a significant challenge. Here we present the de novo design and characterization of pan-specific mini-protein binders against major TcdB subtypes. Our design successfully binds to the first receptor binding interface (RBI-1) of the varied TcdB subtypes, exhibiting affinities ranging from 20 pM to 10 nM. The cryo-electron microscopy (cryo-EM) structures of the mini protein binder in complex with TcdB1 and TcdB4 are consistent with the computational design models. The engineered and evolved variants of the mini-protein binder and chondroitin sulfate proteoglycan 4 (CSPG4), another natural receptor that binds to the second RBI (RBI-2) of TcdB, better neutralize major TcdB variants both in cells and in vivo, as demonstrated by the colon-loop assay using female mice. Our findings provide valuable starting points for the development of therapeutics targeting C. difficile infections (CDI).

Abstract Background Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine (TCM) formula primarily utilized for treating gut disorders. GQD showed therapeutic effects on several diseases in clinical and animal studies by targeting gut microbes. Our recent studies also found that GQD efficiently alleviated anxiety in methamphetamine-withdrawn mice via regulating gut microbiome and metabolism. Given that various studies have indicated the link between the gut microbiome and the development of depression, here we endeavor to explore whether GQD can manage depression disorders by targeting the gut microbiome. Methods and materials The depression-like model was induced in rats through chronic unpredictable mild stress (CUMS) and the depression levels were determined using the sucrose preference test (SPT). To address the depression-like behavior in rats, oral administration of GQD was employed. The colon microbiome and metabolite patterns were determined by 16s rRNA sequencing and untargeted metabolomics, respectively. Results We found 6 weeks of CUMS can induce depression-like behavior in rats and 4 weeks of GQD treatment can significantly alleviate the depression-like behavior. GQD treatment can also ameliorate the histological lesions in the colon of CUMS rats. Then, CUMS increased the abundance of gut microbes, while GQD treatment can restore it to a lower level. We further discovered that the abundances of 19 bacteria at the genus level were changed with CUMS treatment, among which the abundances of Ruminococcus, Lachnoclostridium, Pygmaiobacter, Bacteroides, Pseudomonas, and Pseudomonas Family_XIII_AD3011_group were stored by GQD treatment. Besides, we identified the levels of 36 colon metabolites were changed with CUMS treatment, among which the levels of Fasciculic acid B, Spermine, Fludrocortisone acetate, alpha-Ketoglutaric acid, 2-Oxoglutaric acid, N’-(benzoyloxy)-2-(2,2-dichlorocyclopropyl) ethanimidamide, N6-Succinyl Adenosine Oleanolic acid, KQH, Ergosta-5,7,9(11),22-Tetraen-3-beta-Ol, Gentisic acid, 4-Hydroxyretinoic Acid, FAHFA (3:0/16:0), Leucine-enkephalin and N-lactoyl-phenylalanine can be restored by GQD treatment. Conclusion Our findings provide evidence supporting the therapeutic efficacy of GQD in alleviating depression-like behavior in CUMS rats, potentially being targeted on colon bacteria (especially the abundance of Ruminococcus and Bacteroides) and metabolites (especially the level of Oleanolic acid).

Abstract Background The liver effects of concentrated vs. more evenly distributed moderate-to-vigorous physical activity (MVPA) patterns remain unclear. We aimed to examine the association of accelerometer-measured MVPA and different MVPA patterns with liver outcomes. Methods Eighty-eight thousand six hundred fifty-six participants without prior liver diseases from UK Biobank were included. MVPA was measured by a wrist-worn accelerometer. Based on the guideline-based threshold (≥ 150 min/week), MVPA patterns were defined as inactive (

Abstract Background CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. Method We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P

Complete wound healing without scar formation has attracted increasing attention, prompting the development of various strategies to address this challenge. In clinical settings, there is a growing preference for emerging biomedical technologies that effectively manage fibrosis following skin injury, as they provide high efficacy, cost-effectiveness, and minimal side effects compared to invasive and costly surgical techniques. This review gives an overview of the latest developments in advanced biomedical technologies for scarless wound management. We first introduce the wound healing process and key mechanisms involved in scar formation. Subsequently, we explore common strategies for wound treatment, including their fabrication methods, superior performance and the latest research developments in this field. We then shift our focus to emerging biomedical technologies for scarless wound healing, detailing the mechanism of action, unique properties, and advanced practical applications of various biomedical technology-based therapies, such as cell therapy, drug therapy, biomaterial therapy, and synergistic therapy. Finally, we critically assess the shortcomings and potential applications of these biomedical technologies and therapeutic methods in the realm of scar treatment.

Therapeutic antibodies are an important class of biopharmaceuticals. With the rapid development of deep learning methods and the increasing amount of antibody data, antibody generative models have made great progress recently. They aim to solve the antibody space searching problems and are widely incorporated into the antibody development process. Therefore, a comprehensive introduction to the development methods in this field is imperative. Here, we collected 34 representative antibody generative models published recently and all generative models can be divided into three categories: sequence-generating models, structure-generating models, and hybrid models, based on their principles and algorithms. We further studied their performance and contributions to antibody sequence prediction, structure optimization, and affinity enhancement. Our manuscript will provide a comprehensive overview of the status of antibody generative models and also offer guidance for selecting different approaches.

Abstract Mental fatigue during long-term motor imagery (MI) may affect intention recognition in MI applications. However, the current research lacks the monitoring of mental fatigue during MI and the definition of robust biomarkers. The present study aims to reveal the effects of mental fatigue on motor imagery recognition at the brain region level and explore biomarkers of mental fatigue. To achieve this, we recruited 10 healthy participants and asked them to complete a long-term motor imagery task involving both right- and left-handed movements. During the experiment, we recorded 32-channel EEG data and carried out a fatigue questionnaire for each participant. As a result, we found that mental fatigue significantly decreased the subjects’ motor imagery recognition rate during MI. Additionally the theta power of frontal, central, parietal, and occipital clusters significantly increased after the presence of mental fatigue. Furthermore, the phase synchronization between the central cluster and the frontal and occipital lobes was significantly weakened. To summarize, the theta bands of frontal, central, and parieto–occipital clusters may serve as powerful biomarkers for monitoring mental fatigue during motor imagery. Additionally, changes in functional connectivity between the central cluster and the prefrontal and occipital lobes during motor imagery could be investigated as potential biomarkers.

Abstract Background Endometriosis (EMs) is an enigmatic disease of yet-unknown pathogenesis. Disulfidptosis, a novel identified form of programmed cell death resulting from disulfide stress, stands a chance of treating diverse ailments. However, the potential roles of disulfidptosis-related genes (DRGs) in EMs remain elusive. This study aims to thoroughly explore the key disulfidptosis genes involved in EMs, and probe novel diagnostic markers and candidate therapeutic compounds from the aspect of disulfidptosis based on bioinformatics analysis, machine learning, and animal experiments. Results Enrichment analysis on key module genes and differentially expressed genes (DEGs) of eutopic and ectopic endometrial tissues in EMs suggested that EMs was closely related to disulfidptosis. And then, we obtained 20 and 16 disulfidptosis-related DEGs in eutopic and ectopic endometrial tissue, respectively. The protein-protein interaction (PPI) network revealed complex interactions between genes, and screened nine and ten hub genes in eutopic and ectopic endometrial tissue, respectively. Furthermore, immune infiltration analysis uncovered distinct differences in the immunocyte, human leukocyte antigen (HLA) gene set, and immune checkpoints in the eutopic and ectopic endometrial tissues when compared with health control. Besides, the hub genes mentioned above showed a close correlation with the immune microenvironment of EMs. Furthermore, four machine learning algorithms were applied to screen signature genes in eutopic and ectopic endometrial tissue, including the binary logistic regression (BLR), the least absolute shrinkage and selection operator (LASSO), the support vector machine-recursive feature elimination (SVM-RFE), and the extreme gradient boosting (XGBoost). Model training and hyperparameter tuning were implemented on 80% of the data using a ten-fold cross-validation method, and tested in the testing sets which determined the excellent diagnostic performance of these models by six indicators (Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, Accuracy, and Area Under Curve). And seven eutopic signature genes (ACTB, GYS1, IQGAP1, MYH10, NUBPL, SLC7A11, TLN1) and five ectopic signature genes (CAPZB, CD2AP, MYH10, OXSM, PDLIM1) were finally identified based on machine learning. The independent validation dataset also showed high accuracy of the signature genes (IQGAP1, SLC7A11, CD2AP, MYH10, PDLIM1) in predicting EMs. Moreover, we screened 12 specific compounds for EMs based on ectopic signature genes and the pharmacological impact of tretinoin on signature genes was further verified in the ectopic lesion in the EMs murine model. Conclusion This study verified a close association between disulfidptosis and EMs based on bioinformatics analysis, machine learning, and animal experiments. Further investigation on the biological mechanism of disulfidptosis in EMs is anticipated to yield novel advancements for searching for potential diagnostic biomarkers and revolutionary therapeutic approaches in EMs.

Abstract Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory responses that aim to contain and eliminate microbial invaders. Various lipid mediators (LMs) are biosynthesized and play a critical role in fighting viruses during inflammation; thus, by profiling the LMs in patients, researchers can obtain mechanistic insights into diseases, such as the pathways disrupted. To date, the relationship between molecular alterations in LMs and the pathogenesis of H1N1 influenza in children is poorly understood. Here, we employed a targeted liquid chromatography coupled with tandem mass spectrometry (LC‒MS/MS) to profile LMs in serum from children with H1N1 influenza (H1N1 children) and recovered children. We found that 22 LM species were altered in H1N1 children with mild symptoms. Analysis of the LM profiles of recovered children revealed a decrease in the levels of thromboxane B2 (TxB2) and thromboxane B3 (TxB3) and an increase in the levels of other 8 altered LM species associated with H1N1 influenza, including cytochrome P450 (CYP) enzyme-derived dihydroxyeicosatrienoic acids (DiHETrEs) and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid (AA), and epoxyoctadecamonoenoic acids (EpOMEs) from linoleic acid (LA). Taken together, the results of this study revealed that serum LMs change dynamically in H1N1 children with mild symptoms. The dramatically altered LMs in H1N1 children could serve as a basis for potential therapeutics or adjuvants against H1N1 influenza.

Abstract Objective Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. Methods A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40–60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. Results Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P 0.05). Conclusions These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation.

Abstract Background The rapid growth of artificial intelligence (AI) technologies has been driven by the latest advances in computing power. Although, there exists a dearth of research on the application of AI in medical education. Methods this study is based on the TAM-ISSM-UTAUT model and introduces STARA awareness and chilling effect as moderating variables. A total of 657 valid questionnaires were collected from students of a medical university in Dalian, China, and data were statistically described using SPSS version 26, Amos 3.0 software was used to validate the research model, as well as moderated effects analysis using Process (3.3.1) software, and Origin (2021) software. Results The findings reveal that both information quality and perceived usefulness are pivotal factors that positively influence the willingness to use AI products. It also uncovers the moderating influence of the chilling effect and STARA awareness. Conclusions This suggests that enhancing information quality can be a key strategy to encourage the widespread use of AI products. Furthermore, this investigation offers valuable insights into the intersection of medical education and AI use from the standpoint of medical students. This research may prove to be pertinent in shaping the promotion of Medical Education Intelligence in the future.

Abstract Background Primary osteoporosis (POP) is recognized as a “silent disease” and often ignored. This meta-analysis aimed to determine the prevalence of POP in the Chinese population over the past 20 years to raise awareness of the disease’s epidemiology, which is hoped to help prevent and treat the condition better. Methods Eight English and three Chinese language databases were searched systematically from January 2002 to December 2023. Relevant data were analysed using Stata 16.0. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. A funnel plot was further drawn in combination with Egger and Begg tests to determine publication bias. Results A total of 45 studies (241,813 participants) were included. The meta-analysis revealed that the overall prevalence of POP in the Chinese population was 18.2% (95% CI: 14.7–21.7%), showing a positive correlation with age. Specifically, prevalence rates were 23.4% (18.3–28.5%) in women and 11.5% (9.1–13.9%) in men. A notable increase was observed within the span of 20 years (16.9% before 2010 and 20.3% in 2011–2020). Notably, regional variations were observed, with southern China reporting a lower prevalence of 16.4% compared to 20.2% in northern China. Meta-regression suggested that sample size significantly influenced the estimation of point prevalence (P = 0.037). Conclusions Over the past two decades, there has been an increase in the prevalence of POP within the Chinese population. The growing prevalence of older individuals and women further highlights the urgency for tailored disease prevention and control measures.

Abstract Background Nonpharmaceutical interventions (NPIs) implemented to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have suppressed the spread of other respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to explore the epidemiological trends and clinical characteristics of Mycoplasma pneumoniae (MP) infection among inpatient children with lower respiratory tract infection (LRTI) before and during the COVID-19 pandemic, and investigate the long-term effects of China’s NPIs against COVID-19 on the epidemiology of MP among inpatient children with LRTI. Methods Children hospitalised for LRTI at the Department of Pulmonology, The Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2019 and December 2022 were tested for common respiratory pathogens, including Mycoplasma pneumoniae (MP), Chlamydia trachomatis (CT) and other bacteria. Clinical data on age, sex, season of onset, disease spectrum, and combined infection in children with MP-induced LRTI in the past 4 years were collected and analysed. Results Overall, 15909 patients were enrolled, and MP-positive cases were 1971 (34.0%), 73 (2.4%), 176 (5.8%), and 952 (20.6%) in 2019, 2020, 2021, and 2022, respectively, with a significant statistical difference in the MP-positive rate over the 4 years (p

Pain highly impacts the quality of life of patients. Morphine is used for pain treatment; however, its side effects, especially morphine tolerance, limit its use in the clinic. The problem of morphine tolerance has plagued health workers and patients for years. Unfortunately, the exact mechanism of morphine tolerance has not been fully clarified. The mechanisms of morphine tolerance that are currently being studied may include μ-opioid receptor (MOR) desensitization and internalization, mitogen-activated protein kinase (MAPK) pathway activation and crosstalk, the effects of microglia and the increase in inflammatory factors. Morphine tolerance can be alleviated by improving the pathophysiological changes that lead to morphine tolerance. Previous studies have shown that a cannabinoid type 2 (CB2) receptor agonist could attenuate morphine tolerance in a variety of animal models. Many studies have shown an interaction between the cannabinoid system and the opioid system. The CB2 receptor may modulate the effect of morphine through a pathway that is common to the MOR, since both receptors are G protein-coupled receptors (GPCRs). This study introduces the potential mechanism of morphine tolerance and the effect of CB2 receptor agonists on reducing morphine tolerance, which can provide new ideas for researchers studying morphine and provide beneficial effects for patients suffering from morphine tolerance.

IntroductionAs the development process of medical industry informatization has entered the stage of smart healthcare, health management applications (apps) have played an important role in improving people’s health and preventing diseases, especially among female college students.MethodsThis study combines the UTAUT model and the Fogg behavioral model (FBM) as a theoretical framework to investigate the factors affecting female college students’ willingness to use health management apps. A survey was conducted with 624 female college students regarding their usage of AI health management mobile applications.ResultsThe analysis reveals that social influence (β = 0.497, p

Traditional denitrification methods for coal-fired power boilers face challenges like reduced flue gas temperature at low loads, decreased efficiency of existing denitrification devices, and increased ammonia consumption. Biomass, a renewable energy source, has proven effective for denitrification in medium to high-temperature ranges. To improve denitrification efficiency at low loads, this study focuses on optimizing re-burning denitrification of biomass by nitrogen-impregnated of corncob at room temperature. Investigating the effects of nitrogen impregnation and washing on biomass re-burning denitrification reactivity within 550–950 °C, the study finds that denitrification efficiency improvement is not caused only by surface-covered urea or washing. Nitrogen impregnation enhances biomass pyrolysis, releasing more CO, HCN, and NH3 products, thereby enhancing NO reduction during denitrification. Additionally, nitrogen impregnation boosts nitrogen-containing functional groups such N-6 on biomass char surfaces during the re-burning process, improving denitrification efficiency. The maximum denitrification efficiency of the nitrogen impregnated sample reached 97.52 % at 950 °C, while it reached 76.51 % at 650 °C when the coated urea was washed. Furthermore, chlorine and alkali metal contents in biomass notably decrease after nitrogen-impregnation and washing, optimizing biomass combustion conditions for furnace protection. This study offers theoretical insights for promoting and applying biomass denitrification techniques.

Renal fibrosis is a complex and multifactorial process that involves inflammation, cell proliferation, collagen, and fibronectin deposition in the kidney, ultimately leading to chronic kidney disease and even end-stage renal disease. The main goal of treatment is to slow down or halt the progression of fibrosis and to improve or preserve kidney function. Despite significant progress made in understanding the underlying mechanisms of renal fibrosis, current therapies have limited renal protection as the disease progresses. Exosomes derived from stem cells are a newer area of research for the treatment of renal fibrosis. Exosomes as nano-sized extracellular vesicles carry proteins, lipids, and nucleic acids, which can be taken up by local or distant cells, serving as mediators of intercellular communication and as drug delivery vehicles. Exosomes deliver molecules that reduce inflammation, renal fibrosis and extracellular matrix protein production, and promote tissue regeneration in animal models of kidney disease. Additionally, they have several advantages over stem cells, such as being non-immunogenic, having low risk of tumor formation, and being easier to produce and store. This review describes the use of natural and engineered exosomes containing therapeutic agents capable of mediating anti-inflammatory and anti-fibrotic processes during both acute kidney injury and chronic kidney disease. Exosome-based therapies will be compared with stem cell-based treatments for tissue regeneration, with a focus on renal protection. Finally, future directions and strategies for improving the therapeutic efficacy of exosomes are discussed.

We reviewed research on SARS-CoV-2 and influenza virus detection on surfaces, their persistence under various conditions, and response to disinfectants. Viral contamination in community and healthcare settings was analyzed, emphasizing survival on surfaces influenced by temperature, pH, and material. Findings showed higher concentrations enhance survivability at room temperature, whereas stability increases at 4°C. Both viruses decline in low pH and high heat, with influenza affected by salinity. On various material surfaces, SARS-CoV-2 and influenza viruses demonstrate considerable variations in survival durations, and SARS-CoV-2 is more stable than influenza virus. On the skin, both virus types can persist for ≥2 h. Next, we delineated the virucidal efficacy of disinfectants against SARS-CoV-2 and influenza viruses. In daily life, exposure to ethanol (70%), isopropanol (70%), bleach (10%), or hydrogen peroxide (1–3%) for 15–30 min can effectively inactive various SARS-CoV-2 variants. Povidone-iodine (1 mg/mL, 1 min) or cetylpyridinium chloride (0.1 mg/mL, 2 min) may be used to inactive different SARS-CoV-2 variants in the mouth. Chlorine disinfectants (500 mg/L) or ultraviolet light (222 nm) can effectively inhibit different SARS-CoV-2 variants in public spaces. In conclusion, our study provides a scientific basis and practical guidance for reduction of viral persistence (retention of infectivity) on surfaces and environmental cleanliness.

BackgroundPancreatic cancer (PC) is a malignant tumour with poor prognosis and high mortality, and high fasting plasma glucose (HFPG) is considered to be one of its important risk factors.MethodsPC disease burden data were obtained from the Global Burden of Disease Study 2021 (GBD 2021) database. Annual percent change (APC), average APC (AAPC), and 95% confidence interval (95% CI) were analysed using joinpoint linkpoint regression models to assess the trend of PC burden of disease between 1990 and 2021. An age-period-cohort model was used to estimate the independent effects of age, period, and cohort on PC burden, and data on PC mortality attributable to HFPG in China from 2022 to 2032 were analysed on the basis of a Bayesian age-period-cohort model projection.ResultsThe number of Pc deaths due to HFPG continue to rise in China from 1990 to 2021, with age-standardised mortality (ASMR) and age-standardised disability-adjusted life-year rates with increasing AAPC values of 1.12% (95% CI, 0.73–1.52) and 1.00% (95% CI, 0.63–1.37), respectively. Throughout the study, we found that the overall level of PC disease burden was significantly higher in men than that in women. In age-period-cohort analyses, the age effect of PC showed an increasing and then decreasing trend, the period effect showed an overall increasing trend during the study period, and the cohort effect showed an overall slow decreasing trend. In addition, the BAPC model predicted that ASMR is expected to decline significantly in both men and women from 2022 to 2032.ConclusionsIt was found that PC attributable to HFPG was generally on the rise in China from 1990 to 2021 and has been on the decline in recent years, and projections suggest that the country’s future PC disease burden will continue to show a downward trend. Age and period of birth are the main factors affecting the disease burden, especially in men and older age groups. Early prevention, regular screening, and research into the pathogenesis of PC have, therefore, become particularly important.

Thiacloprid is one of the first generation of neonicotinoid insecticide with a chloropyridine structure like imidacloprid and acetamiprid. Recent studies have revealed its environmental and non-target organism toxicity, leading to restrictions on its use in many countries and regions. Despite limitations, thiacloprid has been detected in various environmental samples, food sources, and biological specimens, posing a significant threat to human health, necessitating advanced detection methods for monitoring. In this study, a highly specific monoclonal antibody against thiacloprid via a multi-immunogen strategy was prepared and a rapid and sensitive enzyme-linked immunosorbent assay for the detection of thiacloprid residues in honey and medicinal herbs was established. The half maximal inhibitory concentration (IC50) of this method was 0.38 ng/mL, improving the sensitivity by 1.2−480.6 times compared to existing reports, and the limit of detection (IC20) was 0.097 ng/mL. The method was successfully applied to the determination of thiacloprid residues in honey and medicinal herbs (Crataegi fructus, Citri reticulatae pericarpium), achieving recovery rates ranging from 87.50 % to 116.11 %. The obtained results were verified using the LC-MS/MS method. The multi-immunogen strategy proposed in this study provides an approach for the preparation of highly sensitive and specific monoclonal antibodies, and immunoassay established based on it has good application prospects in complex matrices.

Sulfur-doped biochar (S4BC) was prepared with cherry kernel powder as carbon source, Na2S2O3 as sulfur source and chemical activator. Na2S2O3 can activate biochar through the reaction with carbon, intercalation of alkali metals and the generated gas rushing out of pores, and at the same time, active sulfur atoms are doped into biochar during pyrolysis. The physical and chemical properties of S4BC adsorbent were evaluated by various characterization techniques. The results show that S4BC calcined at 800 °C has huge specific surface area of 959.6 m2/g, developed pore structure, and high content of S (18.84 wt%). Moreover, due to the existence of sulfur and oxygen functional groups, S4BC-800 provides sufficient active sites for the adsorption of Hg2+. According to Langmuir model, the maximum adsorption capacity of S4BC-800 for Hg2+ is 724 mg/g at 313 K, and the adsorption speed is fast with excellent stability and reusability. The microfiltration membrane device based on S4BC-800 can effectively remove the low concentration of Hg2+ in the solution. In this study, a simple method for preparing SBC materials is developed, which is not only of great significance as an adsorbent for Hg2+, but also provides a new choice for the preparation of heteroatom-doped materials.

IntroductionSepsis poses a serious threat to individual life and health. Early and accessible diagnosis and targeted treatment are crucial. This study aims to explore the relationship between microbes, metabolic pathways, and blood test indicators in sepsis patients and develop a machine learning model for clinical diagnosis.MethodsBlood samples from sepsis patients were sequenced. α-diversity and β-diversity analyses were performed to compare the microbial diversity between the sepsis group and the normal group. Correlation analysis was conducted on microbes, metabolic pathways, and blood test indicators. In addition, a model was developed based on medical records and radiomic features using machine learning algorithms.ResultsThe results of α-diversity and β-diversity analyses showed that the microbial diversity of sepsis group was significantly higher than that of normal group (p < 0.05). The top 10 microbial abundances in the sepsis and normal groups were Vitis vinifera, Mycobacterium canettii, Solanum pennellii, Ralstonia insidiosa, Ananas comosus, Moraxella osloensis, Escherichia coli, Staphylococcus hominis, Camelina sativa, and Cutibacterium acnes. The enriched metabolic pathways mainly included Protein families: genetic information processing, Translation, Protein families: signaling and cellular processes, and Unclassified: genetic information processing. The correlation analysis revealed a significant positive correlation (p < 0.05) between IL-6 and Membrane transport. Metabolism of other amino acids showed a significant positive correlation (p < 0.05) with Cutibacterium acnes, Ralstonia insidiosa, Moraxella osloensis, and Staphylococcus hominis. Ananas comosus showed a significant positive correlation (p < 0.05) with Poorly characterized and Unclassified: metabolism. Blood test-related indicators showed a significant negative correlation (p < 0.05) with microorganisms. Logistic regression (LR) was used as the optimal model in six machine learning models based on medical records and radiomic features. The nomogram, calibration curves, and AUC values demonstrated that LR performed best for prediction.DiscussionThis study provides insights into the relationship between microbes, metabolic pathways, and blood test indicators in sepsis. The developed machine learning model shows potential for aiding in clinical diagnosis. However, further research is needed to validate and improve the model.

The widespread occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) in aquatic environments and its hazards to aquatic species underscore the necessity of comprehending its environmental fate. Here, we investigated the transformation from 6PPD to 6PPD-Q and the attenuation of 6PPD-Q in surface water under natural conditions. Contrary to prior findings, this work revealed that 6PPD-Q and its precursor 6PPD-OH/6PPD-(OH)2, were not detected through target analysis and suspect screening during 6PPD transformation in the surface water under the natural conditions. 6PPD-Q predominantly accumulated in TWPs in ambient atmosphere with 1.28 % mass yield from the 6PPD dissipation. Subsequently, 6PPD-Q was eluted from TWPs and released to the water environment. The investigation on the natural attenuation of 6PPD-Q in the surface water demonstrated that direct and indirect photolysis facilitated the rapid dissipation of 6PPD-Q with a half-life of 2.57 h. Utilizing the liquid chromatography high resolution mass spectrometry (LC-HRMS), including both time of flight (TOF) MS and Orbitrap MS, twelve novel transformation products (TPs) of 6PPD-Q were identified by using a comprehensive non-targeted screening strategy. The results from two dimensions gas chromatography (GC×GC) TOF-MS revealed additional two TPs. Based on the molecular structure of TPs, four major pathways of 6PPD-Q attenuation were proposed, including bond cleavage, hydroxylation, quinone cleavage and rearrangement. All TPs were predicted to exhibit lower toxicity, indicating the natural attenuation of 6PPD-Q reduced its toxicity and potential environmental risks. This study provides crucial insights into the environmental fate of 6PPD-Q, highlighting the significance of understanding both its formation from 6PPD and its subsequent attenuation processes under natural conditions.

Probiotics are one of the management tools to improve the host’s healthy microbiota. The positive effects of probiotics on host health are species-specific, so probiotics isolated from host’s own gut may be most beneficial. Many of the metabolites (e.g., short-chain fatty acids, bacteriocins, and hydrogen peroxide) produced by Lactobacillus johnsonii have specific inhibitory profiles against invading pathogens. In this study, we isolated L. johnsonii GJ231 from the intestinal tract of healthy female beagles. The genome size of 1.763 M encoded a total of 1,691 predicted genes. Many carbohydrate-active enzymes responsible for carbohydrate degradation and the production of short-chain fatty acids were also predicted. The metabolic profile of short-chain fatty acids in L. johnsonii GJ231 was determined using LC–MS/MS. The bacteriocin-producing gene bacteriocin (lactacin F) in L. johnsonii GJ231 was also predicted. In vitro, experiments demonstrated that GJ231 can thrive in weak acids, 0.3% bile salts, and artificial gastrointestinal fluid models. It was tolerant of to high temperatures up to 70°C, was non- hemolytic, inhibited pathogenic bacteria, and had a high antioxidant capacity. In vivo safety experiments conducted in mice revealed that oral administration of GJ231 not only had no toxic side effect but also increased their antioxidant capacity. In conclusion, combining the above test results, which collectively demonstrate that canine-derived L. johnsonii GJ231 was a non-pathogenic, acid-tolerant and bile-salt-tolerant probiotic strain that inhibits pathogenic bacteria and improves host antioxidant function. This may make it a promising candidate for the development of innovative functional foods for pets.