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Abstract It is generally believed that the Maritime Continent (MC) is rarely affected by tropical cyclones (TCs) due to its equatorial location. However, this study reveals that TCs in the tropical western North Pacific can significantly suppress rainfall over the MC and its surrounding seas, based on the composite analysis. This suppression effect of TCs exists across all phases of the Madden–Julian Oscillation (MJO). TCs greatly alleviate rainfall enhancement during the convective phases of the MJO and aggravate rainfall suppression during the suppressive phases. Particularly, TCs reduce the likelihood of extremely high rainfall in convective MJO phases from 9% to 5% and increase the likelihood of extremely low rainfall in suppressive MJO phases from 10% to 16%. The rainfall suppression is attributed to the lower-tropospheric southwesterly anomalies to the south of TCs, which result in moisture divergence over the MC. Additionally, the upper-tropospheric equatorward outflows of TCs also promote subsidence and suppress rainfall. This study introduces a new factor influencing the rainfall over the MC from a synoptic climatology perspective.

Abstract Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by hyperglycemia resulting from the destruction of insulin-producing β-cells that is traditionally deemed irreversible, but partial remission (PR) with temporary reversal of hyperglycemia is sometimes observed. Here we use single-cell RNA sequencing to delineate the immune cell landscape across patients in different T1D stages. Together with cohort validation and functional assays, we observe dynamic changes in TIGIT+CCR7− Tregs and CD226+CCR7−CD8+ cytotoxic T cells during the peri-remission phase. Machine learning algorithms further identify TIGIT+CCR7− Tregs and CD226+CD8+ T cells as biomarkers for β-cell function decline in a predictive model, while cell communication analysis and in vitro assays suggest that TIGIT+CCR7− Tregs may inhibit CD226+CCR7−CD8+ T cells via TGF-β signaling. Lastly, in both cyclophosphamide-induced and streptozotocin (STZ)-induced mouse diabetes models, CD226 inhibition postpones insulitis onset and reduces hyperglycemia severity. Our results thus identify two interrelated immune cell subsets that may serve as biomarkers for monitoring disease progression and targets for therapeutic intervention of T1D.

Abstract Background maternal health during pregnancy can affect the intestinal microbial community of offspring, but currently the impact of intrauterine environmental changes resulting from gestational diabetes mellitus (GDM) on the microbiota of offspring as well as its interaction with the immune system remains unclear. Aims to explore the impact of intrauterine microbial exposure during pregnancy of gestational diabetes mellitus on the development of neonate’s intestinal microbiota and activation of immune responses. Methods Levels of lipopolysaccharides in cord blood from GDM and expression of microbial recognition-related proteins in the placenta were measured. To evaluate embryonic intestinal colonization, pregnant mice with GDM were administered with labeled Escherichia coli or Lactobacillus. The intestinal colonization of pups was analyzed through 16S rRNA gene sequencing and labeled microbial culture. Additionally, memory T lymphocyte and dendritic cell co-culture experiments were conducted to elucidate the immune memory of intestinal microbes during the embryonic stages. Result Gestational diabetes mellitus led to elevated umbilical cord blood LPS level and increased GFP labeled Escherichia coli in the offspring’s intestine after gestational microbial exposure. The mouse model of GDM exhibited increased immune markers including TLR4, TLR5, IL-22 and IL-23 in the placenta and a recall response from memory T cells in offspring’s intestines, with similar observations found in human experiments. Furthermore, reduced intestinal microbiome diversity and an increased ratio of Firmicutes/Bacteroidetes was found in GDM progeny, with the stability of bacterial colonization been interfered. Conclusions Our investigation has revealed a noteworthy correlation between gestational diabetes and intrauterine microbial exposure, as well as alterations in the neonatal microbiota and activation of immune responses. These findings highlight the gestational diabetes’s role on offspring’s gut microbiota and immune system interactions with early-life pathogen exposure.

Abstract Congenital anomalies of the external ear can have a significant impact on a child’s development and quality of life. While genetic factors play a crucial role in the etiology of these anomalies, environmental factors such as drug exposure during pregnancy may also contribute to their occurrence. This study aims to investigate the association between drug exposure and congenital anomalies of the external ear using data from an adverse drug reaction report database. Using OpenVigil 2.1, we queried the FAERS database to retrieve adverse event reports from the first quarter of 2004 to the first quarter of 2024. To identify relevant cases, we used Medical Dictionary for Regulatory Activities terms focusing on congenital anomalies of the external ear. Drug generic names were sourced from the DrugBank database. To assess safety signals and rank drugs by their signal strength, we conducted a disproportionality analysis, generating reporting odds ratios (ROR) and proportional reporting ratios (PRR). A total of 20,754,281 AE reports were identified in the FAERS database from Q1 2004 to Q1 2024, of which 1763 were related to congenital anomalies of the external ear. Valproic acid (122 cases) was associated with the most cases, followed by mycophenolate mofetil (105 cases) and lamotrigine (65 cases). According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were primidone (ROR: 397.05, 95% CI 147.21, 1070.9; PRR: 388.71, 95% CI 145.89, 1035.7), valproic acid (ROR: 239.46, 95% CI 123.75, 463.37; PRR: 236.42, 95% CI 123.82, 451.43), tapazole (ROR: 198.35, 95% CI 63.49, 619.67; PRR: 196.25, 95% CI 62.97, 611.67), nevirapine (ROR: 138.24, 95% CI 82.9, 230.51; PRR: 137.23, 95% CI 82.44, 228.44), and sebivo (ROR: 117.1, 95% CI 48.51, 282.67; PRR: 116.37, 95% CI 48.17, 281.12). This study identified several drugs significantly associated with congenital anomalies of the external ear in the FAERS database using disproportionality analysis. The findings can help healthcare professionals better recognize and manage drug-induced congenital anomalies of the external ear, particularly when prescribing high-risk medications. Further research is needed to elucidate the mechanisms underlying these associations and develop strategies for preventing and mitigating drug-induced congenital anomalies of the external ear.

Abstract Liposarcoma (LPS) is the second most common kind of soft tissue sarcoma, and a heterogeneous malignant tumor derived from adipose tissue. Up to now, the prognostic value of BAG1 or BAG2 in LPS has not been defined yet. Expression profiling data of LPS patients were collected from TCGA and GEO database. Survival curves were plotted to verify the outcome differences of patients based on BAG1 or BAG2 expression. Univariate and multivariate Cox regression models were used to analyze the prognostic ability of BAG1 or BAG2. Chaperone’s regulators BAG1 and BAG2 were identified as prognostic biomarkers for LPS patients, which exhibited distinct expression patterns and survival outcome prediction performances. Patients with high BAG2 expression and/or low BAG1 expression had worse prognosis. Enrichment analysis showed that BAG1 was involved in negative regulation of TGF-β signaling. Low expression of BAG1 was associated with high abundance of regulatory T cells (Tregs). The 2-gene signature model further confirmed the improved risk assessment performance of BAG1 and BAG2: high risk patients displayed poor prognosis. BAG1 and BAG2 are supposed to be potential prognostic biomarkers for LPS and have impacts on liposarcomagenesis and immune infiltration in distinctive manners, which may function as potential therapy targets (BAG1 agonists/BAG2 inhibitors) for LPS.

Abstract Background Oil palm (Elaeis guineensis Jacq.) is a very important tropical woody oil plant with high commercial and ornamental value. The exocarp of the oil palm fruit is rich in anthocyanosides and proanthocyanidins, which not only give it a bright colour, but also mark the maturity of the fruit. The study of the dynamic change pattern of anthocyanoside content and important anthocyanoside metabolism-related regulatory genes during oil palm ripening is conducive to the improvement of the ornamental value of oil palm and the determination of the optimal harvesting period of the fruits. Methods We analyzed the virescens oil palm (AS) and nigrescens oil palm (AT) at 95 days (AS1, AT1), 125 days (AS2, AT2) and 185 days (AS3, AT3) after pollination were used as experimental materials for determining the changes in the total amount of anthocyanins as well as their metabolomics and transcriptomics studies by using the LC-MS/MS technique and RNA-Seq technique. Result The results showed that the total anthocyanin content decreased significantly from AS1 (119 µg/g) to AS3 (23 µg/g), and from AT1 (1302 µg/g) to AT3 (170 µg/g), indicating a clear decreasing trend during fruit development. Among them, the higher flavonoids in AS and AT included anthocyanins such as peonidin-3-O-rutinoside (H35), pelargonidin-3-O-rutinoside (H21), and cyanidin-3-O-glucoside (H7), as well as condensed tannins such as procyanidin B2 (H47), procyanidin C1 (H49), and procyanidin B3 (H48). Notably, nine genes involved in the anthocyanin biosynthetic pathway exhibited up-regulated expression during the pre-development stage of oil palm fruits, particularly during the AS1 and AT1 periods. These genes include: Chalcone synthase (CHS; LOC105036364); Flavanone 3-hydroxylase (F3H; LOC105054663); Dihydroflavonol 4-reductase (DFR; LOC105040724, LOC105048473); Anthocyanidin synthase (ANS; LOC105035842), UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT; LOC105039612); Flavonoid 3’,5’-hydroxylase (F3’5’H; LOC105036086, LOC105044124, LOC105045493). In contrast, five genes demonstrated up-regulated expression as the fruits developed, specifically during the AS3 and AT3 periods. These genes include: Chalcone synthase (CHS; LOC105036921, LOC105035716); Chalcone isomerase (CHI; LOC105045978); UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT; LOC105046326); Flavonoid 3’-hydroxylase (F3’H; LOC105036086). Conclusion Most of differentially expressed genes exhibited up-regulation during the early stages of fruit development, which may contribute to the elevated anthocyanin content observed in oil palm fruits of both types during the pre-developmental period. Furthermore, the expression levels of most genes were found to be higher in the AT fruit type compared to the AS fruit type, suggesting that the differential expression of these genes may be a key factor underlying the differences in anthocyanoside production in the exocarp of oil palm fruits from these two fruit types. The findings of this study provide a theoretical foundation for the identification and characterization of genes involved in anthocyanin synthesis in oil palm fruits, as well as the development of novel variations using molecular biology approaches.

Abstract Aristolochic acids are a class of naturally occurring compounds in Aristolochiaceae that have similar structural skeletons and chemical properties. Exposure to aristolochic acids is a risk factor for severe kidney disease and urinary system cancer. However, the carcinogenicity of aristolochic acids to the liver, which is the main site of aristolochic acid metabolism, is unclear. Although the characteristic fingerprint of aristolochic acid-induced mutations has been detected in the liver and aristolochic acids are known to be hepatotoxic, whether aristolochic acids can directly cause liver cancer is yet to be verified. This review summarizes the findings of long-term carcinogenicity studies of aristolochic acids in experimental animals. We propose that spatiotemporal heterogeneity in the carcinogenicity of these phytochemicals could explain why direct evidence of aristolochic acids causing liver cancer has never been found in adult individuals. We also summarized the reported approaches to mitigate aristolochic acid-induced hepatotoxicity to better address the associated global safety issue and provide directions and recommendations for future investigation.

Objectives: This study aimed to explore the effectiveness of the theory-based tailored mHealth physical activity (PA) intervention among patients with breast cancer undergoing chemotherapy. Methods: A quasi-experimental study design was adopted. A total of 60 breast cancer patients were selected from two tertiary hospitals in Shanghai and Hangzhou City from September 2019 to August 2021. According to the admission order, 30 patients were first included in the control group, followed by 30 patients in the intervention group. A smartphone application (app) named “Breast Care” was developed based on social cognitive theory, self-efficacy theory, and the theory of planned behavior. The app integrated various functions, including information browsing, PA monitoring and feedback, symptom reporting, and social interaction. Patients in the intervention group received three months of personalized online PA guidance in addition to routine care. The control group received routine care. Baseline and post-intervention investigations after three months were conducted in two groups using the Short Form of International Physical Activity Questionnaire, the Hospital Anxiety and Depression Scale, and the Functional Assessment of Cancer Therapy—Breast cancer. Results: After three months of intervention, compared to the control group, breast cancer patients in the intervention group showed significant improvements in walking, moderate PA, and overall PA (P

Abstract Fruit color substantially affects consumer preferences, with darker red strawberries being economically more valuable due to their higher anthocyanin content. However, the molecular basis for the dark red coloration remains unclear. Through screening of an ethyl methanesulfonate mutant library, we identified a rg418 mutant, that demonstrated anthocyanin accumulation during early fruit development stages. Furthermore, the ripening fruits of this mutant had higher anthocyanin content than wild-type (WT) fruits. An analysis of flavonoid content in WT and rg418 mutant fruits revealed substantial changes in metabolic fluxes, with the mutant exhibiting increased levels of anthocyanins and flavonols and decreased levels of proanthocyanidins. Bulked sergeant analysis sequencing indicated that the mutant gene was anthocyanidin reductase (ANR), a key gene in the proanthocyanidin synthesis pathway. Furthermore, transcriptome sequencing revealed the increased expression of MYB105 during the early development stage of mutant fruits, which promoted the expression of UFGT (UDP-glucose flavonoid 3-O-glucosyltransferase), a key gene involved in anthocyanin synthesis, thus substantially enhancing the anthocyanin content in the mutant fruits. Additionally, mutating ANR in a white-fruited strawberry variant (myb10 mutant) resulted in appealing pink-colored fruits, suggesting the diverse roles of ANR in fruit color regulation. Our study provides valuable theoretical insights for improving strawberry fruit color.

Abstract High-quality standard views in two-dimensional echocardiography are essential for accurate cardiovascular disease diagnosis and treatment decisions. However, the quality of echocardiographic images is highly dependent on the practitioner’s experience. Ensuring timely quality control of echocardiographic images in the clinical setting remains a significant challenge. In this study, we aimed to propose new quality assessment criteria and develop a multi-task deep learning model for real-time multi-view classification and image quality assessment (six standard views and “others”). A total of 170,311 echocardiographic images collected between 2015 and 2022 were utilized to develop and evaluate the model. On the test set, the model achieved an overall classification accuracy of 97.8% (95%CI 97.7–98.0) and a mean absolute error of 6.54 (95%CI 6.43–6.66). A single-frame inference time of 2.8 ms was achieved, meeting real-time requirements. We also analyzed pre-stored images from three distinct groups of echocardiographers (junior, senior, and expert) to evaluate the clinical feasibility of the model. Our multi-task model can provide objective, reproducible, and clinically significant view quality assessment results for echocardiographic images, potentially optimizing the clinical image acquisition process and improving AI-assisted diagnosis accuracy.

Assessing residents’ perceptions of urban ecosystem services (UESs) is crucial for incorporating it into environmental management. However, evaluations seldom consider variations in perceptions at sub-city scale. Our study demonstrates how UES perceptions varies at sub-city level through a case study in Beijing, China. We interviewed 550 residents of Beijing’s oldest and newest urban zones to obtain their perceptions of 10 UES types. We analysed participants’ responses using importance-performance analysis, optimal scale regression, and textual analysis. Results showed that residents confirmed the value of UES in both zones. However, differences existed in their perceptions of several UESs, reflecting different environmental problems between two zones. Additionally, education, gender, and age significantly affected residents’ perceptions. Residents in both zones prioritised greenery-expanding activities for improving UES performance. Based on these findings, we recommend that variances in UES perception be considered when managing urban ecosystems to improve its supply and contribute to human well-being.

Abstract During follicular development, changes in the composition of the follicular fluid are synchronized with the development of oocytes. Our aim was to screen the key factors affecting oocyte maturation and optimize the in vitro culture protocol by understanding the changes of proteins and metabolites in follicular fluid. Follicles are divided into three groups according to their diameter (small follicle fluid (SFF): 10 mm

Abstract Background The failure of proper recognition of the intricate nature of pathophysiology in colorectal cancer (CRC) has a substantial effect on the progress of developing novel medications and targeted therapy approaches. Imbalances in the processes of lipid oxidation and biosynthesis of fatty acids are significant risk factors for the development of CRC. Therapeutic intervention that specifically targets the peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream response element, in response to lipid metabolism, has been found to promote the growth of tumors and has shown significant clinical advantages in cancer patients. Methods Clinical CRC samples and extensive in vitro and in vivo experiments were carried out to determine the role of ZDHHC6 and its downstream targets via a series of biochemical assays, molecular analysis approaches and lipid metabolomics assay, etc. Results To study the effect of ZDHHC6 on the progression of CRC and identify whether ZDHHC6 is a palmitoyltransferase that regulates fatty acid synthesis, which directly palmitoylates and stabilizes PPARγ, and this stabilization in turn activates the ACLY transcription-related metabolic pathway. In this study, we demonstrate that PPARγ undergoes palmitoylation in its DNA binding domain (DBD) section. This lipid-related modification enhances the stability of PPARγ protein by preventing its destabilization. As a result, palmitoylated PPARγ inhibits its degradation induced by the lysosome and facilitates its translocation into the nucleus. In addition, we have identified zinc finger-aspartate-histidine-cysteine 6 (ZDHHC6) as a crucial controller of fatty acid biosynthesis. ZDHHC6 directly interacts with and adds palmitoyl groups to stabilize PPARγ at the Cys-313 site within the DBD domain of PPARγ. Consequently, this palmitoylation leads to an increase in the expression of ATP citrate lyase (ACLY). Furthermore, our findings reveals that ZDHHC6 actively stimulates the production of fatty acids and plays a role in the development of colorectal cancer. However, we have observed a significant reduction in the cancer-causing effects when the expression of ZDHHC6 is inhibited in in vivo trials. Significantly, in CRC, there is a strong positive correlation between the high expression of ZDHHC6 and the expression of PPARγ. Moreover, this high expression of ZDHHC6 is connected with the severity of CRC and is indicative of a poor prognosis. Conclusions We have discovered a mechanism in which lipid biosynthesis is controlled by ZDHHC6 and includes the signaling of PPARγ-ACLY in the advancement of CRC. This finding provides a justification for targeting lipid synthesis by blocking ZDHHC6 as a potential therapeutic approach.

Abstract Background Clinical events such as angina pectoris, acute coronary syndrome, and sudden death caused by myocardial bridge (MB) have attracted increasing attention. It is still a challenge to diagnose whether MB can cause the symptoms of patients with MB. For most MB patients, medication remains the primary treatment. Case presentation This article reports a case of chest pain in a patient with MB in the middle segment of the left anterior descending artery (LADm) with moderate stenosis in the proximal segment (LADp). Through functional assessment, we found that neither MB nor fixed stenosis had sufficient effect on coronary blood flow to cause myocardial ischemia, but their synergistic effect resulted in myocardial ischemia. Finally, a stent was implanted in LADp and good clinical results were achieved. Conclusions For symptomatic patients with MB combined with fixed stenosis, functional evaluation may be necessary, which has significant guiding significance for treatment strategy selection. For asymptomatic patients, early detection of myocardial ischemia may also improve the prognosis of patients.

Abstract The driving force behind the Cenozoic India-Asia collision remains elusive. Using global-scale geodynamic modeling, we find that the continuous motion of the Indian plate is driven by a prominent upper-mantle flow pushing the thick Indian lithospheric root, originated from the northward rollover of the detached Neo-Tethyan slab and sinking slabs below East Asia. The maximum mantle drag occurs within the strong Indian lithosphere and is comparable in magnitude to that of slab pull (1013 N m−1). The thick cratonic root enhances both lithosphere-asthenosphere coupling and upper-plate compressional stress, thereby sustaining the topography of Tibetan Plateau. We show that the calculated resistant force from the India-Asia plate boundary is also close to that due to the gravitational potential energy of Tibetan Plateau. Here, we demonstrate that this mantle flow is key for the formation of the Tibetan Plateau and represents part of a hemispheric convergent flow pattern centered on central Asia.

Objective Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Methods Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. Results In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤−1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Conclusion Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective.

BackgroundMulti-slice spiral computerized tomography (MSCT) can be used as an auxiliary diagnosis of chest radiography in diagnosis of pneumoconiosis, but there are few studies on the correlations between interstitial images and stage classification of coal workers' pneumoconiosis in the existing literature. ObjectiveTo present MSCT imaging manifestations and distribution characteristics of coal workers' pneumoconiosis and complications, evaluate correlations between coal workers' pneumoconiosis stages and pulmonary interstitial lesions, and provide a reliable imaging diagnosis basis for pneumoconiosis interstitial lesions. MethodsFrom June 2022 to June 2023, a total of 1002 patients with coal workers' pneumoconiosis confirmed by the pneumoconiosis diagnostic and identification group in the Department of Occupational Diseases of the Emergency General Hospital were enrolled. MSCT was used to observe the abnormal imaging manifestations of the lungs of coal workers' pneumoconiosis patients and the diseases of pulmonary fibrosis related to their own diseases (thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, subpleural line, intralobular interstitial thickening, honeycomb, and subpleural interstitial thickening), the occurrence of coal workers' pneumoconiosis and complications (old tuberculosis, active tuberculosis, pneumonia, atelectasis, lung cancer, bronchiectasis), and the density, size, and location of pneumoconiosis nodules. Imaging data were analyzed and statistically processed. ResultsAll 1002 patients were male, with an average age of (60.71±6.87) years and an average dust exposure time of (23.01±7.80) years. Among them, there were 470 patients with stage I, 422 patients with stage II, and 110 patients with stage III. There were significant differences in the distribution of thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, intralobular interstitial thickening, subpleural interstitial thickening, and honeycomb across different stages (P

Abstract Background The taxonomy of Taxus Linn. remains controversial due to its continuous phenotypic variation and unstable topology, thus adversely affecting the formulation of scientific conservation strategies for this genus. Recently, a new ecotype, known as Qinling type, is mainly distributed in the Qinling Mountains and belongs to a monophyletic group. Here, we employed multiple methods including leaf phenotype comparison (leaf shapes and microstructure), DNA barcoding identification (ITS + trnL-trnF + rbcL), and niche analysis to ascertain the taxonomic status of the Qinling type. Results Multiple comparisons revealed significant differences in the morphological characters (length, width, and length/width ratio) among the Qinling type and other Taxus species. Leaf anatomical analysis indicated that only the Qinling type and T. cuspidata had no papilla under the midvein or tannins in the epicuticle. Phylogenetic analysis of Taxus indicated that the Qinling type belonged to a monophyletic group. Moreover, the Qinling type had formed a relatively independent niche, it was mainly distributed around the Qinling Mountains, Ta-pa Mountains, and Taihang Mountains, situated at an elevation below 1500 m. Conclusions Four characters, namely leaf curvature, margin taper, papillation on midvein, and edges were put forward as primary indexes for distinguishing Taxus species. The ecotype Qingling type represented an independent evolutionary lineage and formed a unique ecological niche. Therefore, we suggested that the Qingling type should be treated as a novel species and named it Taxus qinlingensis Y. F. Wen & X. T. Wu, sp. nov.

Utilizing the Multi-Voltage Threshold method, All-Digital PET technology, characterized by "All-Digital" and "accurate sampling," facilitates hardware and software decoupling and modular "LEGO-like" system construction. This innovation addresses the limitations of traditional PET system architectures, enabling a broader range of innovative applications. This paper reviews recent advancements in application-specific All-Digital PET systems, highlighting their applications and advantages in proton therapy monitoring, clinical and basic brain science research, and plant metabolism studies. Furthermore, we explore the development trends of All-Digital PET technology to meet the increasing demands of PET imaging applications.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. ObjectiveTo study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. MethodsPatients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. ResultsThere was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. ConclusionThe metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

BackgroundPneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. ObjectiveTo observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. MethodsA total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. ResultsThe dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P＜0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P＜0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P＜0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P＜0.05), but the differences in Chao1 index were not statistically significant (P＞0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P＞0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P＜0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P＜0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. ConclusionThere are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.

Abstract LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner. Fraction studies revealed that the 1–166aa fragment of LIMA1 was indispensable for the interaction with RNF40, and at least two domains of RNF40 might mediate the association of RNF40 with LIMA1. Notably, treatment with simvastatin dramatically decreased the levels of CHO and TG in control cells rather than cells with overexpressed LIMA1. Moreover, RNF40 significantly decreased lipid content, which could be reversed by LIMA1 overexpression. These findings suggest that E3 ubiquitin ligase RNF40 could directly target LIMA1 and promote its protein degradation in cytoplasm, leading to the suppression of lipid accumulation mediated by LIMA1. Collectively, this study unveils that RNF40 is a novel E3 ubiquitin ligase of LIMA1, which underpins its high therapeutic value to combat dysregulation of lipid metabolism.

Developing an efficient catalyst is the key to selective catalytic reduction (SCR) of NOx by CO (CO‐SCR) to simultaneously address the pollution of toxic NOx and CO. Herein, a novel Rh/TiO2/Ti monolithic catalyst is designed and synthesized, featuring Rh species in the form of single atoms (Rh1) and clusters (Rhn). This catalyst overcomes the inhibitory effects of oxygen, achieving low‐temperature NO conversion. The investigation substantively contributes insights into the strategic manipulation of active metal components, emphasizing the potential of single‐atom/cluster catalysts to enhance efficiency. The Rh/TiO2/Ti catalyst has demonstrated exceptional catalytic efficacy, achieving 100% NO conversion at a low temperature of 190 °C in the presence of oxygen. Additionally, it exhibits remarkable stability and water resistance for practical applications. Moreover, comprehensive characterization confirms that Rh clusters and single‐atom sites play an important role in the selective adsorption of NO and CO molecules, promoting the formation of –N2O species and ultimately resulting in the complete conversion of NO and CO to N2 and CO2. This study not only provides valuable guidance for designing high‐performance CO‐SCR catalysts but also underscores the potential of single atoms/clusters catalytic systems in both fundamental research and industrial catalysis.

Teacher absenteeism is one of the key factors that has been fingered as the bane of quality early childhood education in low- and middle-income countries. Failing to report to school as scheduled is considered symptomatic of emotional dysregulation. However, limited research has explored emotional labor as a possible predictor of teacher absenteeism. Therefore, this study, using the conservation of resources theory, examines the influence of emotional labor (i.e., surface and deep acting) on absenteeism, and the mediating roles of negative affect and psychological meaningfulness. Our study used cross-sectional data from 574 preschool teachers in Ghana and structural equation modeling (SEM) to test the hypotheses. The results reveal that surface acting increases absenteeism. Further, negative affect and psychological meaningfulness partially mediated surface acting and absenteeism relationship, but psychological meaningfulness fully mediated deep acting and absenteeism relationship. This study supports the theoretical assumption that teacher absence from school is a resource-based process that is associated with surface acting directly and indirectly via negative affect and psychological meaningfulness. Theoretical and practical implications of our findings are discussed.

Summary: Hydroxycarboxylic acid receptor 3 (HCAR3), a class A G-protein-coupled receptor, is an important cellular energy metabolism sensor with a key role in the regulation of lipolysis in humans. HCAR3 is deeply involved in many physiological processes and serves as a valuable target for the treatment of metabolic diseases, tumors, and immune diseases. Here, we report four cryoelectron microscopy (cryo-EM) structures of human HCAR3-Gi1 complexes with or without agonists: the endogenous ligand 3-hydroxyoctanoic acid, the drug niacin, the highly subtype-specific agonist compound 5c (4-(n-propyl)amino-3-nitrobenzoic acid), and the apo form. Together with mutagenesis and functional analyses, we revealed the recognition mechanisms of HCAR3 for different agonists. In addition, the key residues that determine the ligand selectivity between HCAR2 and HCAR3 were also illuminated. Overall, these findings provide a structural basis for the ligand recognition, activation, and selectivity and G-protein coupling mechanisms of HCAR3, which contribute to the design of HCAR3-targeting drugs with high efficacy and selectivity.

BackgroundElectroencephalogram (EEG) is widely used in emotion recognition due to its precision and reliability. However, the nonstationarity of EEG signals causes significant differences between individuals or sessions, making it challenging to construct a robust model. Recently, domain adaptation (DA) methods have shown excellent results in cross-subject EEG emotion recognition by aligning marginal distributions. Nevertheless, these methods do not consider emotion category labels, which can lead to label confusion during alignment. Our study aims to alleviate this problem by promoting conditional distribution alignment during domain adaptation to improve cross-subject and cross-session emotion recognition performance.MethodThis study introduces a multi-source domain adaptation common-branch network for EEG emotion recognition and proposes a novel sample hybridization method. This method enables the introduction of target domain data information by directionally hybridizing source and target domain samples without increasing the overall sample size, thereby enhancing the effectiveness of conditional distribution alignment in domain adaptation. Cross-subject and cross-session experiments were conducted on two publicly available datasets, SEED and SEED-IV, to validate the proposed model.ResultIn cross-subject emotion recognition, our method achieved an average accuracy of 90.27% on the SEED dataset, with eight out of 15 subjects attaining a recognition accuracy higher than 90%. For the SEED-IV dataset, the recognition accuracy also reached 73.21%. Additionally, in the cross-session experiment, we sequentially used two out of the three session data as source domains and the remaining session as the target domain for emotion recognition. The proposed model yielded average accuracies of 94.16 and 75.05% on the two datasets, respectively.ConclusionOur proposed method aims to alleviate the difficulties of emotion recognition from the limited generalization ability of EEG features across subjects and sessions. Though adapting the multi-source domain adaptation and the sample hybridization method, the proposed method can effectively transfer the emotion-related knowledge of known subjects and achieve accurate emotion recognition on unlabeled subjects.

Abstract Single‐drug therapies or monotherapies are often inadequate, particularly in the case of life‐threatening diseases like cancer. Consequently, combination therapies emerge as an attractive strategy. Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs, such as low water solubility and bioavailability, high toxicity, etc. However, it remains a significant challenge in encapsulating two drugs in a nanoparticle. To address this issue, computational methodologies are employed to guide the rational design and synthesis of dual‐drug‐loaded polymer nanoparticles while achieving precise control over drug loading. Based on the sequential nanoprecipitation technology, five factors are identified that affect the formulation of drug candidates into dual‐drug loaded nanoparticles, and then screened 176 formulations under different experimental conditions. Based on these experimental data, machine learning methods are applied to pin down the key factors. The implementation of this methodology holds the potential to significantly mitigate the complexities associated with the synthesis of dual‐drug loaded nanoparticles, and the co‐assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy. This approach provides a new strategy for enabling the streamlined, high‐throughput screening and synthesis of new nanoscale drug‐loaded entities.

IntroductionThis study examined the interplay between perceived feedback (PF), subjective wellbeing (SWB), and students’ sense of belonging to school (SBS). School belonging is a key factor for decisions regarding academic studies, and is usually impacted by PF. The current study explored whether SWB mediates the established relationship between PF and SBS.MethodThis was achieved by applying a mediation model to PISA 2018 data from 12,058 students in four areas of China.ResultsPerceived feedback positively affected students’ SBS (β = 0.26, p

BackgroundExcessive saturated fatty acids (SFAs) are known to be detrimental to human health. Although the majority of research and dietary guidelines have focused on the intake of SFAs, there has been limited attention to the relationship between circulating SFA levels and hormonal regulation, such as that of thyroid hormones.MethodsTo explore potential associations, we conducted an investigation with 579 participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Subgroup analyses and multivariable linear regression models were used to estimate the relationships between eleven distinct SFA concentrations and various thyroid parameters.ResultsFor 579 adults, subgroup analysis of thyroid stimulating hormone (TSH) revealed significant differences in nine specific SFAs and the total SFA levels (all p < 0.05). Furthermore, multivariable linear regression analysis identified positive correlations between certain SFAs and various parameters, including TSH, total triiodothyronine (TT3), free triiodothyronine (FT3), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), thyroglobulin (Tg), the ratio of FT3 to free thyroxine (FT4) (FT3/FT4), and the thyrotroph T4 resistance index (TT4RI). Conversely, negative correlations were observed between certain SFAs and total thyroxine (TT4), FT4, the ratio of FT3/TT3, and the thyroid feedback quantile-based index (TFQI) (all p < 0.05).ConclusionThese findings collectively suggest associations between SFAs and thyroid parameters, highlighting the need for future studies to elucidate the underlying mechanisms of these interactions.

An important goal in the opioid field is to discover effective analgesic drugs with minimal side effects. MCRT demonstrated potent antinociceptive effects with limited side effects, making it a promising candidate. However, its pharmacological properties and how it minimizes side effects remain unknown. Various mouse pain and opioid side effect models were used to evaluate the antinociceptive properties and safety at the spinal level. The targets of MCRT were identified through cAMP measurement, isolated tissue assays, and pharmacological experiments. Immunofluorescence was employed to visualize protein expression. MCRT displayed distinct antinociceptive effects between acute and chronic inflammatory pain models due to its multifunctional properties at the μ opioid receptor (MOR), µ-δ heterodimer (MDOR), and neuropeptide FF receptor 2 (NPFFR2). Activation of NPFFR2 reduced MOR-mediated antinociception, leading to bell-shaped response curves in acute pain models. However, activation of MDOR produced more effective antinociception in chronic inflammatory pain models. MCRT showed limited tolerance and opioid-induced hyperalgesia in both acute and chronic pain models and did not develop cross-tolerance to morphine. Additionally, MCRT did not exhibit addictive properties, gastrointestinal inhibition, and effects on motor coordination. Mechanistically, peripheral chronic inflammation or repeated administration of morphine and MCRT induced an increase in MDOR in the spinal cord. Chronic administration of MCRT had no apparent effect on microglial activation in the spinal cord. These findings suggest that MCRT is a versatile compound that provides potent antinociception with minimal opioid-related side effects. MDOR could be a promising target for managing chronic inflammatory pain and addressing the opioid crisis.

Background and aims: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and the sixth leading cause of cancer death worldwide, and it is urgent to find safe and effective drugs for treatment. As an important therapeutic method, small-molecule drugs are continually being updated to achieve improved therapeutic effects. The purpose of this study was to investigate the structural effects of various FDA-listed small-molecule drugs sorafenib, cabozantinib, lenvatinib, and regorafenib on the corresponding HCC targets and possible structural optimization methods, and to explore the mechanism for identifying potential therapeutic drugs that offer better efficacy and fewer side effects. Methods: The structure-activity relationship, pharmacological actions, and clinical applications of small-molecule drugs were reviewed by referencing MEDLINE, Web of Science, CNKI, and other databases, summarizing and integrating the relevant content. Results: The results showed that small-molecule drugs can inhibit HCC primarily by forming hydrogen bonds with Glu885, Asp1046, and Cys919 on the HCC target. HCC can be targeted by inhibiting the activation of multiple pathways, blocking the conduction of downstream signaling, and reducing the formation of tumor blood vessels. In general, small-molecule drugs primarily target four key receptors in HCC: VEGFR, PDGFR, EGFR, and FGFR, to achieve effective treatment. Conclusions: By revealing their structure-activity relationships, pharmacological actions, and clinical trials, small-molecule drugs can offer broad prospects for the development of new medications.

The antitumor activity of a fermented juice (called Shaduojin, SDJ) made from sea buckthorn, raspberry, etc. was investigated using CT26 bearing mice. The results showed a dose-dependent inhibition of tumor growth in the SDJ groups compared to the model group. The number of CD8+ T and dendritic cells were increased while the Treg cells and monocytes was decreased in both the tumor and spleen in the SDJ groups. The TNF-α and INF-γ increased and the IL-1β, IL-6, and IL-10 decreased in the SDJ groups. Additionally, there was an increase in the abundance of beneficial bacteria (Firmicutes, Coildextribacter, and Lachnospiraceae) which contribute to intestinal health and produce short-chain fatty acids (SCFAs). On the other hand, harmful bacteria (Muribaculaceae and uncultured Bacteroidales) decreased. The SCFA content in the intestine also increased in the SDJ groups. Therefore, it has been showed that SDJ may elicit its effect on preventing colorectal cancer by regulating the immune system and gut microbiota.

Research on high‐surface‐area supports and synergic promoters has been made, however, there is still much room for improvement on the catalytic‐particles morphology and interaction with the support. A first approach for designing nanoplate supports to improve CDM catalysts was made. Amorphous aluminosilicates nanoplates (a‐AS.np) with an average particle size of 23.4 nm and an average height of 2.8 nm, and α‐Ni(OH)2 nanoplates (Ni.np) with an average particle size of 23.2 nm and an average thickness of 8.4 nm, were successfully synthesized, using a two‐dimensional reactor in amphiphilic phases (TRAP). Nickel loaded in a‐AS materials with different morphologies and promotion effects of lantana (La3+) & chromium (Cr3+) species were studied. La‐Cr promoted a‐AS support showed an average increase of 13% on H2 yield in severe conditions due to improved crystallization of Ni particles on mesoporous support and the electron promotion of La to Ni species. Furthermore, we evaluate the Ni.np as novel morphology support for La3+ & copper (Cu2+) species in the methane decomposition reaction. La‐Cu Ni.np showed outstanding performance and stability, a max H2 yield of 15.9% (at 700 °C), and more than 400 min of H2 generation (at 550 °C) compared to its a‐AS support counterparts.

Abstract The uneven growth of lithium dendrites not only compromise the performance of lithium metal batteries, but also has security risks. In this sutudy, double coating with MgF2 and hydroxypropyl methylcellulose was synthesized on the surface of polyethylene separator through a simple soaking and in‐situ chemical precipitation method, achieve the purpose of protecting lithium metal anode. Utilizing the MgF2/HPMC@PE separator, the Li||Li symmetric cell was capable of cycling for over 1000 hours with a voltage hysteresis of only 11.4 mV, comparing the voltage hysteresis based on the cell use of PE separator increases rapidly after 200 h. Furthermore, the initial discharge capacity of Li||LiNi0.6Co0.2Mn0.2O2(NCM622) is 144.6 mAh g−1 and the capacity retention is 87.2 % after 200 cycles at 1 C, which is higher than that of the PE separator (135.3 mAh g−1, with retention of 74.9 %). All improvements can be credited with the formation of stable solid electrolyte interphase(SEI) film induced by HPMC/MgF2 double coating, which is reduced the Li nucleation overpotential and ultimately promoted uniform Li deposition. This study provides a simple and effective strategy for improving the cycling performance and safety of lithium metal batteries.

Abstract Visual defect recognition techniques based on deep learning models are crucial for modern industrial quality inspection. The backbone, serving as the primary feature extraction component of the defect recognition model, has not been thoroughly exploited. High‐performance vision transformer (ViT) is less adopted due to high computational complexity and limitations of computational resources and storage hardware in industrial scenarios. This paper presents LSA‐Former, a lightweight transformer architectural backbone that integrates the benefits of convolution and ViT. LSA‐Former proposes a novel self‐attention with linear computational complexity, enabling it to capture local and global semantic features with fewer parameters. LSA‐Former is pre‐trained on ImageNet‐1K and surpasses state‐of‐the‐art methods. LSA‐Former is employed as the backbone for various detectors, evaluated specifically on the PCB defect detection task. The proposed method reduces at least 18M parameters and exceeds the baseline by more than 2.2 mAP.

Ferroptosis is a novel form of programmed cell death, which is different from apoptosis, pyroptosis and autophagy in morphology and biochemistry. Ferroptosis is characterized by condensed mitochondrial membrane densities, vanished of mitochondria crista and outer membrane rupture in morphology, and the accumulation of intracellular iron, lipid peroxidation (LPO), decrease of GSH and inhibition of GPX4 in biochemistry. Japanese encephalitis virus (JEV) and Herpes simplex virus (HSV) are both common neurotropic viruses that can cause neurological disorders, such as severe encephalitis. JEV and HSV have been demonstrated to be able to induce ferroptosis. This process is closely related to the inhibition of the GSH-GPX4 system, ACSL4 phosphorylation, and Nrf2 ubiquitination. In this review, we summarized the mechanisms by which JEV and HSV induced ferroptosis in the current study. In addition, we found a strong relationship between endoplasmic reticulum (ER) stress and ferroptosis, and we therefore speculated that sustained ER stress might be a prerequisite for ferroptosis in JEV and HSV-induced diseases.

With the rapid expansion of artificial light in the global nocturnal environment, the ecological impacts of artificial light at night (ALAN) on plant communities have garnered increasing research interest. However, the role of phyllosphere microorganisms as mediators in the regulation between ALAN and plants remains unclear. In this study, we conducted a field experiment in natural grassland plots, employing two treatments: one with no artificial light at night (control) and another with artificial light at night (ALAN). We then investigated the response of phyllosphere microorganisms in three grassland plant species (Leymus chinensis, Vicia sepium, and Aster altaicus) to ALAN exposure. The results revealed that the constructive species L. chinensis demonstrated a markedly higher diversity of phyllosphere bacteria and fungi compared to V. sepium and A. altaicus and thus had the most abundant microbial community. However, ALAN exposure reduced the diversity of phyllosphere bacteria and fungi in all three plant species to varying degrees. ALAN induced certain changes to the phyllosphere bacterial community composition, particularly manifesting in a reduction in the abundance of beneficial bacteria, including Sphingomonas, Hymenobacter, Methylobacterium-Methylorubrum, and Bacillus. Compared with phyllosphere bacterial communities, the alterations in phyllosphere fungal communities were more sensitive, characterized by a significant decrease in the abundance of certain fungi, including Zymoseptoria, Mycosphaerella, Cladosporium, and Epicoccum. The functional predictions of phyllosphere bacteria and fungi further corroborate these conclusions. In summary, ALAN exposure may suppress the functional capacity of phyllosphere microorganisms in grassland plants while decreasing the probability of fungal pathogen occurrence.

Retinoblastoma (RB) is the most common intraocular malignant tumor in children, primarily attributed to the bi-allelic loss of the RB1 gene in the developing retina. Despite significant progress in understanding the basic pathogenesis of RB, comprehensively unravelling the intricate network of genetics and epigenetics underlying RB tumorigenesis remains a major challenge. Conventional clinical treatment options are limited, and despite the continuous identification of genetic loci associated with cancer pathogenesis, the development of targeted therapies lags behind. This review focuses on the reported genomic and epigenomic alterations in retinoblastoma, summarizing potential therapeutic targets for RB and providing insights for research into targeted therapies.

Cr(VI) and phenol commonly coexist in wastewater, posing a great threat to the environment and human health. However, it is still a challenge for microorganisms to degrade phenol under high Cr(VI) stress. In this study, the phenol-degrading strain Bacillus cereus ZWB3 was co-cultured with the Cr(VI)-reducing strain Bacillus licheniformis MZ-1 to enhance phenol biodegradation under Cr(Ⅵ) stress. Compared with phenol-degrading strain ZWB3, which has weak tolerance to Cr(Ⅵ), and Cr(Ⅵ)-reducing strain MZ-1, which has no phenol-degrading ability, the co-culture of two strains could significantly increase the degraded rate and capacity of phenol. In addition, the co-cultured strains exhibited phenol degradation ability over a wide pH range (7–10). The reduced content of intracellular proteins and polysaccharides produced by the co-cultured strains contributed to the enhancement of phenol degradation and Cr(Ⅵ) tolerance. The determination coefficients R2, RMSE, and MAPE showed that the BP-ANN model could predict the degradation of phenol under various conditions, which saved time and economic cost. The metabolic pathway of microbial degradation of phenol was deduced by metabolic analysis. This study provides a valuable strategy for wastewater treatment containing Cr(Ⅵ) and phenol. HIGHLIGHTS Co-culture can degrade phenol under high concentrations of Cr(VI).; Co-culture improves the degraded rate and concentration of phenol under Cr(VI) stress.; Co-culture synergistically enhances the ability to resist phenol and Cr(VI) toxicity.; BP-ANN predicted the degradation of phenol under different conditions.;

Abstract Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a highly heterogeneous disease. According to large-scale RNA sequencing (RNA-seq) data, B-ALL patients can be divided into more than 10 subgroups. However, many genomic defects associated with resistance mechanisms have not yet been identified. As an individual clinical tool for molecular diagnostic risk classification, RNA-seq and gene expression pattern-based therapy could be potential upcoming strategies. In this study, we retrospectively analyzed the RNA-seq gene expression profiles of 45 children whose molecular diagnostic classifications were inconsistent with the response to chemotherapy. The relationship between the transcriptome and chemotherapy response was analyzed. Fusion gene identification was conducted for the included patients who did not have known high-risk associated fusion genes or gene mutations. The most frequently detected fusion gene pair in the high-risk group was the DHRSX duplication, which is a novel finding. Fusions involving ABL1, LMNB2, NFATC1, PAX5, and TTYH3 at onset were more frequently detected in the high-risk group, while fusions involving LFNG, TTYH3, and NFATC1 were frequently detected in the relapse group. According to the pathways involved, the underlying drug resistance mechanism is related to DNA methylation, autophagy, and protein metabolism. Overall, the implementation of an RNA-seq diagnostic system will identify activated markers associated with chemotherapy response, and guide future treatment adjustments.

Abstract Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPS L.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPS L.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPS L. p -delivered OVA compared to OVA alone. Notably, NAPS L.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPS L.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPS L.p -based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPS L.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.

Abstract Background We recently reported that supplementing glycine to soybean meal-based diets is necessary for the optimum growth of 5- to 40-g (Phase-I) and 110- to 240-g (Phase-II) hybrid striped bass (HSB), as well as their intestinal health. Although glycine serves as an essential substrate for syntheses of creatine and glutathione (GSH) in mammals (e.g., pigs), little is known about these metabolic pathways or their nutritional regulation in fish. This study tested the hypothesis that glycine supplementation enhances the activities of creatine- and GSH-forming enzymes as well as creatine and GSH availabilities in tissues of hybrid striped bass (HSB; Morone saxatilis♀ × Morone chrysops♂). Methods Phase-I and Phase-II HSB were fed a soybean meal-based diet supplemented with 0%, 1%, or 2% glycine for 8 weeks. At the end of the 56-d feeding, tissues (liver, intestine, skeletal muscle, kidneys, and pancreas) were collected for biochemical analyses. Results In contrast to terrestrial mammals and birds, creatine synthesis occurred primarily in skeletal muscle from all HSB. The liver was most active in GSH synthesis among the HSB tissues studied. In Phase-I HSB, supplementation with 1% or 2% glycine increased (P 0.05) in these variables between the 1% and 2% glycine groups. In Phase-II HSB, supplementation with 1% and 2% glycine increased (P

The thermal evolution of the Earth’s interior and its dynamic effects are the focus of Earth sciences. However, the commonly adopted grid-based temperature solver is usually prone to numerical oscillations, especially in the presence of sharp thermal gradients, such as when modeling subducting slabs and rising plumes. This phenomenon prohibits the correct representation of thermal evolution and may cause incorrect implications of geodynamic processes. After examining several approaches for removing these numerical oscillations, we show that the Lagrangian method provides an ideal way to solve this problem. In this study, we propose a particle-in-cell method as a strategy for improving the solution to the energy equation and demonstrate its effectiveness in both one-dimensional and three-dimensional thermal problems, as well as in a global spherical simulation with data assimilation. We have implemented this method in the open-source finite-element code CitcomS, which features a spherical coordinate system, distributed memory parallel computing, and data assimilation algorithms.

Abstract Background Intravascular lithotripsy (IVL) represents a novel approach in the management of coronary calcification. This technique employs acoustic pressure waves, generated by a shockwave balloon, to effectively fracture both superficial and deep calcification in situ. The efficacy and safety of IVL have been convincingly demonstrated through the Disrupt CAD I-IV studies. While IVL is associated with the occurrence of atrial and ventricular arrhythmias, there is no evidence to indicate it causes myocardial ischemia. Case Description A 71-year-old man was admitted presenting with chest pain. His previous coronary angiography revealed stenosis and calcification in the left anterior descending branch. An attempt to predilate the lesion using two Lacrosse non-slip element balloons was unsuccessful. Ventricular premature beats and transient ST-segment depression were captured during the utilization of IVL. The operator gradually extended the pulse emission interval across two consecutive cycles to mitigate myocardial ischemia. Notably, when the interval reached 30s, the patient had no chest pain or ST-segment changes. Subsequent images of intravascular ultrasound confirmed calcification ruptures. Therapeutic intervention included the placement of a stent and the application of a drug-coated balloon in the left anterior descending branch. A telephonic follow-up six months later indicated the patient had no discomfort. Conclusions This case underscores the effectiveness of gradually extending the pulse emission interval as a strategic complement to the clinical application of IVL. In certain clinical scenarios, it may become imperative to suspend the pulse delivery to improve myocardial blood supply.

Abstract Background Mobile health (mHealth) may be an ideal solution for breast cancer (BC) patients in China to access weight management interventions. User retention and engagement are the main challenges faced by mHealth applications. A user persona, which is a user-centered design process, can lead to the development of mHealth that is more acceptable to the needs of target users. This study aimed to investigate the variety of experiences in weight management and the behavioral preferences of BC patients receiving chemotherapy to develop users’ personal information and persona development for the design and implementation of mHealth interventions. Methods Sixteen individual semi-structured in-depth interviews were conducted with BC patients receiving chemotherapy. We employed the thematic analysis method to analyze the interview transcripts in NVivo 11 software. The themes obtained from the analysis were used as the subdomains of personas. A proforma was designed to extract each participant’s experience in each subdomain. Patients who exhibited similar experience in subdomains were grouped into a persona using affinity diagrams. The personas were named according to their prominent features. A questionnaire survey was conducted to validate the personas and to test whether the personas that were generated from the qualitative interview data were applicable to the Chinese population with BC. Results Four themes were identified as subdomains of weight management personas: the perception of weight management while undergoing chemotherapy, symptoms and emotional disturbance, changes in diet and exercise, and health literacy and information seeking. Five personas were ultimately obtained: (1) positive weight controllers, (2) patients who were inactive due to fatigue, (3) young patients who avoided communication, (4) overweight patients with treatment priority, and (5) patients who engaged in irregular exercise. Finally, the quantitative study showed that 51.58% of patients chose one of these five personas to represent themselves in weight management. None of the patient reported selecting options that were not explicitly outlined in the questionnaire and provided personalized descriptions of their weight management characteristics. Conclusions The selected personas were developed from in-depth interviews on biopsychosocial areas. They highlight different weight management patterns in Chinese BC patients and provide implications for both the design of mHealth systems and traditional interventions.

Abstract Designing two-dimensional halide perovskites for high-performance optoelectronic applications requires deep understanding of the structure-property relationship that governs their excitonic behaviors. However, a design framework that considers both intra and interlayer structures modified by the A-site and spacer cations, respectively, has not been developed. Here, we use pressure to synergistically tune the intra and interlayer structures and uncover the structural modulations that result in improved optoelectronic performance. Under applied pressure, (BA)2(GA)Pb2I7 exhibits a 72-fold boost of photoluminescence and 10-fold increase of photoconductivity. Based on the observed structural change, we introduce a structural descriptor χ that describes both the intra and interlayer characteristics and establish a general quantitative relationship between χ and photoluminescence quantum yield: smaller χ correlates with minimized trapped excitons and more efficient emission from free excitons. Building on this principle, we design a perovskite (CMA)2(FA)Pb2I7 that exhibits a small χ and an impressive photoluminescence quantum yield of 59.3%.

Abstract Background Chimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients’ cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative. Methods In this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation. Results Our findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo. Conclusions In summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.

Drug repurposing offers an efficient approach to therapeutic development. In this study, our bioinformatic analysis first predicted an association between obesity and lansoprazole (LPZ), a commonly prescribed drug for gastrointestinal ulcers. We went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity, insulin resistance, and hepatic steatosis in mice. Treatment with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes, and induced cold tolerance in cold-exposed mice, suggesting the activity of LPZ in promoting adipose thermogenesis and energy metabolism. Mechanistically, LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1 (PHOSPHO1) and produces metabolic benefits in a PHOSPHO1-dependent manner. Our results suggested that LPZ may stimulate adipose thermogenesis by inhibiting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid (2-AG-LPA) to 2-arachidonoylglycerol (2-AG) and reduce the activity of the thermogenic-suppressive cannabinoid receptor signaling. In summary, we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome, and identified a potential metabolic basis by which LPZ improves energy metabolism.

Longhorn beetles (Cerambycidae) play a vital role in global ecosystems. Some of them contribute to nutrient cycling and pollination, while others, pose a threat to forestry production. Despite their ecological importance, there has been a lack of comprehensive analyses on the mitochondrial genomes of Cerambycidae beetles. In this study, we have conducted mitochondrial genome sequencing and annotation for four Cerambycidae beetles: Monochamus sutor, Monochamus guerryi, Monochamus galloprovincialis, and Monochamus latefasciatus. Our analysis revealed a high degree of conservation in these mitochondrial genomes, with rare gene rearrangements observed across the Cerambycidae family. Additionally, a notable bias towards AT content was identified, with most genes using ATN as the start codon and TAA as the stop codon. Except for trnS1, all tRNA genes showed typical cloverleaf secondary structures. Phylogenetic analysis using IQ-TREE and Phylobayes consistently produced congruent topologies. At the gene level analyses, our results highlighted the remarkable conservation of the COX1 gene. Furthermore, at the species level, we observed strong adaptability in the Spondylidinae and Lepturinae subfamilies. We also offer our insights into contentious aspects of the phylogeny. Overall, our research contributes to a deeper understanding of the phylogeny and evolution of Cerambycidae, laying the groundwork for future population genetic investigations.