Abelmoschus manihot polysaccharide fortifies intestinal mucus barrier to alleviate intestinal inflammation by modulating Akkermansia muciniphila abundance.

The intestinal mucus barrier is an important line of defense against gut pathogens. Damage to this barrier brings bacteria into close contact with the epithelium, leading to intestinal inflammation. Therefore, its restoration is a promising strategy for alleviating intestinal inflammation. This study showed that Abelmoschus manihot polysaccharide (AMP) fortifies the intestinal mucus barrier by increasing mucus production, which plays a crucial role in the AMP-mediated amelioration of colitis. IL-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on IL-10. Moreover, bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia muciniphila. These findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut microbiota. This demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

Sulfonated Azocalix[4]arene: A Universal and Effective Taste-Masking Agent.

Many active pharmaceutical ingredients have a specific bitter taste. To enhance patient compliance and treatment efficacy, taste-masking agents are crucial in oral drug formulations. Confronting numerous bitter drug molecules with varied structures, the pharmaceutical field strives to explore and develop universal and effective masking approaches. Here, we reported sulfonated azocalix[4]arene (SAC4A), a universal supramolecular masking agent with deep cavity that provides stronger hydrophobic effect and larger interaction area during recognition, allowing high binding affinity to bitter drug molecules. Moreover, bitter drugs could deeply buried in the cavity, with the bitterness effectively masked. As a result, SAC4A can bind to 16 different bitter drugs with high affinities, encompassing alkaloids, flavonoids, terpenoids, and more, while maintaining high biocompatibility. As anticipated, SAC4A effectively masks the unpalatable bitter taste associated with these drugs. Consequently, SAC4A is a promising universal and effective supramolecular masking agent.

Potential Plasma Proteins (LGALS9, LAMP3, PRSS8 and AGRN) as Predictors of Hospitalisation Risk in COVID-19 Patients.

Background: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has posed unprecedented challenges to healthcare systems worldwide. Here, we have identified proteomic and genetic signatures for improved prognosis which is vital for COVID-19 research. Methods: We investigated the proteomic and genomic profile of COVID-19-positive patients (n = 400 for proteomics, n = 483 for genomics), focusing on differential regulation between hospitalised and non-hospitalised COVID-19 patients. Signatures had their predictive capabilities tested using independent machine learning models such as Support Vector Machine (SVM), Random Forest (RF) and Logistic Regression (LR). Results: This study has identified 224 differentially expressed proteins involved in various inflammatory and immunological pathways in hospitalised COVID-19 patients compared to non-hospitalised COVID-19 patients. LGALS9 (p-value < 0.001), LAMP3 (p-value < 0.001), PRSS8 (p-value < 0.001) and AGRN (p-value < 0.001) were identified as the most statistically significant proteins. Several hundred rsIDs were queried across the top 10 significant signatures, identifying three significant SNPs on the FSTL3 gene showing a correlation with hospitalisation status. Conclusions: Our study has not only identified key signatures of COVID-19 patients with worsened health but has also demonstrated their predictive capabilities as potential biomarkers, which suggests a staple role in the worsened health effects caused by COVID-19.

A SRC-slug-TGFß2 signaling axis drives poor outcomes in triple-negative breast cancers.

BACKGROUND: Treatment options for the Triple-Negative Breast Cancer (TNBC) subtype remain limited and the outcome for patients with advanced TNBC is very poor. The standard of care is chemotherapy, but approximately 50% of tumors develop resistance. METHODS: We performed gene expression profiling of 58 TNBC tumor samples by microarray, comparing chemosensitive with chemoresistant tumors, which revealed that one of the top upregulated genes was TGFß2. A connectivity mapping bioinformatics analysis predicted that the SRC inhibitor Dasatinib was a potential pharmacological inhibitor of chemoresistant TNBCs. Claudin-low TNBC cell lines were selected to represent poor-outcome, chemoresistant TNBC, for in vitro experiments and in vivo models. RESULTS: In vitro, we identified a signaling axis linking SRC, AKT and ERK2, which in turn upregulated the stability of the transcription factors, Slug and Snail. Slug was shown to repress TGFß2-antisense 1 to promote TGFß2 signaling, upregulating cell survival via apoptosis and DNA-damage responses. Additionally, an orthotopic allograft in vivo model demonstrated that the SRC inhibitor Dasatinib reduced tumor growth as a single agent, and enhanced responses to the TNBC mainstay drug, Epirubicin. CONCLUSION: Targeting the SRC-Slug-TGFß2 axis may therefore lead to better treatment options and improve patient outcomes in this highly aggressive subpopulation of TNBCs.

In our study, we focused on a particular subtype of aggressive breast cancer called Triple-Negative Breast Cancer (TNBC). We investigated a complex series of events that contribute to poor outcomes in this disease and uncovered a crucial signaling cascade driving tumor growth and progression.At the core of this signaling cascade are three key proteins: SRC, AKT, and ERK2. Together, they form a pathway that activates a transcription factor called Slug. Transcription factors act like molecular switches, controlling the expression of genes. Once Slug is activated, it strongly suppresses genes that would normally restrict cell growth and cell spread.One of the genes downregulated by Slug is TGFB2-AS1. This product of the TGFB2-AS1 gene normally controls levels of its target protein called TGF-beta2 (TGFB2), a protein which has roles in cell growth, cell migration and differentiation. Slug downregulation of TGFB2-AS1 results in higher TGFB2 levels, and this in turn contributes to the uncontrolled growth and spread of cancer cells. TGFB2, and other proteins in this pathway (SRC, AKT, ERK2, and a Slug interactor called LSD1) all maintain the stability of Slug, meaning that Slug levels remain high and drive the aggressive features of this subtype of breast cancer.Overall, our research sheds light on the intricate molecular mechanisms driving aggressive TNBC. It also identifies potential targets for future therapies, aimed at disrupting this harmful signaling pathway and potentially improving patient outcomes for this disease.

Atomic-scale strain engineering of atomically resolved Pt clusters transcending natural enzymes.

Strain engineering plays an important role in tuning electronic structure and improving catalytic capability of biocatalyst, but it is still challenging to modify the atomic-scale strain for specific enzyme-like reactions. Here, we systematically design Pt single atom (Pt1), several Pt atoms (Ptn) and atomically-resolved Pt clusters (Ptc) on PdAu biocatalysts to investigate the correlation between atomic strain and enzyme-like catalytic activity by experimental technology and in-depth Density Functional Theory calculations. It is found that Ptc on PdAu (Ptc-PA) with reasonable atomic strain upshifts the d-band center and exposes high potential surface, indicating the sufficient active sites to achieve superior biocatalytic performances. Besides, the Pd shell and Au core serve as storage layers providing abundant energetic charge carriers. The Ptc-PA exhibits a prominent peroxidase (POD)-like activity with the catalytic efficiency (Kcat/Km) of 1.50 × 109 mM-1 min-1, about four orders of magnitude higher than natural horseradish peroxidase (HRP), while catalase (CAT)-like and superoxide dismutase (SOD)-like activities of Ptc-PA are also comparable to those of natural enzymes. Biological experiments demonstrate that the detection limit of the Ptc-PA-based catalytic detection system exceeds that of visual inspection by 132-fold in clinical cancer diagnosis. Besides, Ptc-PA can reduce multi-organ acute inflammatory damage and mitigate oxidative stress disorder.

Effects of combined ultrasound and calcium ion pretreatments on polyphenols during mung bean germination: Exploring underlying mechanisms.

Mung beans were pretreated with a combination of ultrasonic and calcium ion to enhance the polyphenol content and antioxidant capacity during germination. Changes in polyphenol content and antioxidant capacity during germination, along with underlying mechanisms, were investigated. Both single ultrasound and combined ultrasound-Ca2+ pretreatments significantly increased the polyphenol content and enhanced the antioxidant capacity (p < 0.05) of mung beans depending on germination period. Among 74 polyphenolic metabolites identified in germinated mung beans, 50 were differential. Notably, 23 of these metabolites showed a significant positive correlation with antioxidant activity. Ultrasound pretreatment promoted flavonoid biosynthesis, whereas ultrasound-Ca2+ pretreatment favored the tyrosine synthesis pathway. Polyphenol composition and accumulation changes were mainly influenced by metabolic pathways like flavonoid, isoflavonoid, anthocyanin, and flavone/flavonol biosynthesis. The results suggest that ultrasound alone or combined with calcium ion pretreatments effectively enhance mung bean polyphenol content and antioxidant capacity during germination.

Effect of tele-exercise interventions on quality of life in cancer patients: A meta-analysis.

PURPOSE: To evaluate the impacts of tele-exercise intervention with cancer patients' quality of life, taking into account the influence of the duration of tele-exercise intervention, type of intervention, and gender of cancer patients on quality of life. METHODS: The PubMed (MEDLINE), Embase, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PsycINFO databases were searched from inception to August 21, 2023. The Cochrane Collaboration's Risk of Bias tool 2 was utilized to estimate the risk of bias, and the Grading of Recommendations, Assessment. For statistical analyses, R Studio was employed. RESULTS: This meta-analysis contained eight trials. When compared to controls, tele-exercise interventions (SMD=0.41, 95% CI: 0.12 to 0.70, p < .010; I2=54%, p=.030) have a positive influence on boosting the quality of life within cancer patients. Subgroup analyses demonstrated the greater effectiveness of tele-exercise in enhancing the quality of life of cancer patients when the duration was greater than or equal to 10 weeks. Furthermore, tele-exercise was found to have a stronger advantageous effect with quality of life among female cancer. In addition, among the types of interventions for tele-exercise, neither web-based nor telephone-based formats significantly enhanced quality of life among cancer patients. CONCLUSIONS: Tele-exercise interventions are a cost-effective and feasible non-pharmacologic complementary way to promote cancer patients' quality of life. Additional large-sample, carefully designed randomized controlled trials are warranted to further validate the impact of tele-exercise concerning cancer patients' quality of life. REGISTRATION NUMBER: CRD42023477147.

Melatonin Regulates Osteoblast Differentiation through the m6A Reader hnRNPA2B1 under Simulated Microgravity.

Recent studies have confirmed that melatonin and N6-methyladenosine (m6A) modification can influence bone cell differentiation and bone formation. Melatonin can also regulate a variety of biological processes through m6A modification. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) serves as a reader of m6A modification. In this study, we used the hindlimb unloading model as an animal model of bone loss induced by simulated microgravity and used 2D clinorotation to simulate a microgravity environment for cells on the ground. We found that hnRNPA2B1 was downregulated both in vitro and in vivo during simulated microgravity. Further investigations showed that hnRNPA2B1 could promote osteoblast differentiation and that overexpression of hnRNPA2B1 attenuated the suppression of osteoblast differentiation induced by simulated microgravity. We also discovered that melatonin could promote the expression of hnRNPA2B1 under simulated microgravity. Moreover, we found that promotion of osteoblast differentiation by melatonin was partially dependent on hnRNPA2B1. Therefore, this research revealed, for the first time, the role of the melatonin/hnRNPA2B1 axis in osteoblast differentiation under simulated microgravity. Targeting this axis may be a potential protective strategy against microgravity-induced bone loss and osteoporosis.

Global Analysis of Natural Products Biosynthetic Diversity Encoded in Fungal Genomes.

Fungal secondary metabolites (SMs) represent an invaluable source of therapeutic drugs. Genomics-based approaches to SM discovery have revealed a vast and largely untapped biosynthetic potential within fungal genomes. Here, we used the publicly available fungal genome sequences from the NCBI public database, as well as tools such as antiSMASH, BIG-SLiCE, etc., to analyze a total of 11,598 fungal genomes, identifying 293,926 biosynthetic gene clusters (BGCs), which were subsequently categorized into 26,825 gene cluster families (GCFs). It was discovered that only a tiny fraction, less than 1%, of these GCFs could be mapped to known natural products (NPs). Some GCFs that only contain a single BGC internally are crucial for the biodiversity of fungal biosynthesis. Evident patterns emerged from our analysis, revealing popular taxa as prominent sources of both actual and potential biosynthetic diversity. Our study also suggests that the genus rank distribution of GCF is generally consistent with NP diversity. It is noteworthy that genera Xylaria, Hypoxylon, Colletotrichum, Diaporthe, Nemania, and Calonectria appear to possess a higher potential for SM synthesis. In addition, 7213 BGCs match possible known compound structures, and homologous gene clusters of well-known drugs can be located in different genera, facilitating the development of derivatives that share structural similarity to these drugs and may potentially possess similar biological activity. Our study demonstrated the various types of fungi with mining potential, assisting researchers in prioritizing their research efforts and avoiding duplicate mining of known resources to further explore fungal NP producers.

TSC/mTORC1 mediates mTORC2/AKT1 signaling in c-MYC-induced murine hepatocarcinogenesis via centromere protein M.

Activated mTORC2/AKT signaling plays a role in hepatocellular carcinoma (HCC). Research has shown that TSC/mTORC1 and FOXO1 are distinct downstream effectors of AKT signaling in liver regeneration and metabolism. However, the mechanisms by which these pathways mediate mTORC2/AKT activation in HCC are not yet fully understood. Amplification and activation of c-MYC is a key molecular event in HCC. In this study, we explored the roles of TSC/mTORC1 and FOXO1 as downstream effectors of mTORC2/AKT1 in c-MYC-induced hepatocarcinogenesis. Using various genetic approaches in mice, we found that manipulating the FOXO pathway had minimal impact on c-MYC-induced HCC. In contrast, loss of mTORC2 inhibited c-MYC-induced HCC, an effect that was completely reversed by ablating TSC2, which activated mTORC1. Additionally, we discovered that p70/RPS6 and 4EBP1/eIF4E act downstream of mTORC1, regulating distinct molecular pathways. Notably, the 4EBP1/eIF4E cascade is crucial for cell proliferation and glycolysis in c-MYC-induced HCC. We also identified centromere protein M (CENPM) as a downstream target of the TSC2/mTORC1 pathway in c-MYC-driven hepatocarcinogenesis, and its ablation entirely inhibited c-MYC-dependent HCC formation. Our findings demonstrate that the TSC/mTORC1/CENPM pathway, rather than the FOXO cascade, is the primary signaling pathway regulating c-MYC-driven hepatocarcinogenesis. Targeting CENPM holds therapeutic potential for treating c-MYC-driven HCC.

Jawbone periosteum-derived cells with high osteogenic potential controlled by R-spondin 3.

The jawbone periosteum, the easily accessible tissue responding to bone repair, has been overlooked in the recent development of cell therapy for jawbone defect reconstruction. Therefore, this study aimed to elucidate the in vitro and in vivo biological characteristics of jawbone periosteum-derived cells (jb-PDCs). For this purpose, we harvested the jb-PDCs from 8-week-old C57BL/6 mice. The in vitro cultured jb-PDCs (passages 1 and 3) contained skeletal stem/progenitor cells and exhibited clonogenicity and tri-lineage differentiation capacity. When implanted in vivo, the jb-PDCs (passage 3) showed evident ectopic bone formation after 4-week subcutaneous implantation, and active contribution to repair the critical-size jawbone defects in mice. Molecular profiling suggested that R-spondin 3 was strongly associated with the superior in vitro and in vivo osteogenic potentials of jb-PDCs. Overall, our study highlights the significance of comprehending the biological characteristics of the jawbone periosteum, which could pave the way for innovative cell-based therapies for the reconstruction of jawbone defects.

Novel genomic and phenotypic traits of polyhydroxyalkanoate-producing bacterium ZZQ-149, the type strain of Halomonas qinghailakensis.

BACKGROUND: Polyhydroxyalkanoates (PHAs) are optimal potential materials for industrial and medical uses, characterized by exceptional sustainability, biodegradability, and biocompatibility. These are primarily from various bacteria and archaea. Bacterial strains with effective PHA formation capabilities and minimal production cost form the foundation for PHA production. Detailed genomic analysis of these PHA-generating bacteria is vital to understand their PHA production pathways and enhance their synthesis capability. RESULTS: ZZQ-149, a halophilic, PHA-producing bacterium, was isolated from the sediment of China's Qinghai Lake. Here, we decoded the full genome of ZZQ-149 using Single Molecule Real Time (SMRT) technology based on PacBio RS II platform, coupled with Illumina sequencing platforms. Physiological, chemotaxonomic traits, and phylogenetic analysis based on 16 S rRNA gene and single copy core genes of ninety-nine Halomonas type strains identified ZZQ-149 as the type strain of Halomonas qinghailakensis. Furthermore, a low average nucleotide identity (ANI, < 95%) delineated the genetic differences between ZZQ-149 and other Halomonas species. The ZZQ-149 genome, with a DNA G + C content of 52%, comprises a chromosome (3, 798, 069 bps) and a plasmid (6, 107 bps). The latter encodes the toxin-antitoxin system, BrnT/BrnA. Through comprehensive genome sequencing and analysis, we identified multiple PHA-synthesizing enzymes and an unprecedented combination of eight PHA-synthesizing pathways in ZZQ-149. CONCLUSIONS: Being a halophilic, PHA-producing bacterium, ZZQ-149 exhibits potential as a high PHA producer for engineered bacteria via genome editing while ensuring low-cost PHA production through continuous, unsterilized fermentation.

Melatonin prevents glyphosate-induced hepatic lipid accumulation in roosters via activating Nrf2 pathway.

BACKGROUND: Glyphosate (GLY) is a widely used herbicide with well-defined hepatotoxic effects, in which oxidative stress has been shown to be involved in the pathogenesis of hepatotoxicity. Melatonin (MET), an effective free radical scavenger, has been revealed to alleviate drug-induced liver damage by inhibiting oxidative stress. METHODS: In this study, a rooster model with primary chicken embryo hepatocytes was applied to elucidate the therapeutic effects of MET against GLY-induced hepatic damage and the potential mechanism. Histopathological examinations, biochemical tests and immunoblotting analysis were used to monitor the protective effects of MET on GLY-induced hepatic lipid accumulation. Molecular docking analysis was used to reveal the key reason of MET-improved hepatic lipid deposition. RESULTS: Data firstly showed that MET administration markedly improved GLY-induced hepatic injury, as evidenced by normalized liver enzymes and alleviated pathological changes of liver tissues. Moreover, MET supplementation alleviated GLY-induced hepatic lipid accumulation, which was correlated with improved serum and hepatic lipid profiles and normalized expression of lipolysis- and lipogenesis-related proteins. Notably, MET significantly inhibited vital enzymes involved in stimulating oxidative stress. Moreover, MET enhanced GLY-inhibited Nrf2 nuclear transcription and increased the expressions of its downstream target genes HO1 and NQO1. Further studies revealed that MET may interact with Nrf2 to enhance nuclear translocation of Nrf2. CONCLUSION: Collectively, our results provide the first direct evidence that MET is a novel regulator of Nrf2, highlighting that Nrf2 may be a potential therapeutic target for GLY-induced lipotoxic liver injury.

A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence.

The planarian Schmidtea mediterranea is being studied as a model species for regeneration, but the assembly of planarian genomes remains challenging. Here, we report a high-quality haplotype-phased, chromosome-scale genome assembly of the sexual S2 strain of S. mediterranea and high-quality chromosome-scale assemblies of its three close relatives, S. polychroa, S. nova, and S. lugubris. Using hybrid gene annotations and optimized ATAC-seq and ChIP-seq protocols for regulatory element annotation, we provide valuable genome resources for the planarian research community and a first comparative perspective on planarian genome evolution. Our analyses reveal substantial divergence in protein-coding sequences and regulatory regions but considerable conservation within promoter and enhancer annotations. We also find frequent retrotransposon-associated chromosomal inversions and interchromosomal translocations within the genus Schmidtea and, remarkably, independent and nearly complete losses of ancestral metazoan synteny in Schmidtea and two other flatworm groups. Overall, our results suggest that platyhelminth genomes can evolve without syntenic constraints.

Enhanced Self-Cementation of Arsenic-Contaminated Soil via Activation of Non-Thermal Plasma-Irradiated Ferromanganese: A Mechanistic Investigation.

The self-cementation characteristics of arsenic (As)-contaminated soil were comprehensively investigated in this study. Different non-thermal plasma-irradiated binary (hydro)oxides of polyvalent ferromanganese (poly-Fe-Mn) were synthesized and exploratorily dispersed to soil samples to activate solidification and stabilization during the self-cemented process. The maximum compressive strength of 56.35 MPa and the lowest leaching toxicity of 0.004 mg/L were obtained in the proof test under optimal conditions (i.e., the mass ratio of the poly-Fe-Mn to the soil sample of 0.05; the mass ratio of the composite alkali activator (NaOH + CaO) to the soil sample of 0.25; the mass ratio of CaO to NaOH of 1.5; the mass ratio of the DI water to the binder of 0.515). The composite alkaline activator primarily contributed to the strength formation of the self-cemented matrix while the poly-Fe-Mn significantly influenced the reduction of the As-leaching toxicities. The poly-Fe-Mn maintained diffusion-controlled polycondensation and strengthened the nucleation process during self-cementation. The amount of water and the dosage of poly-Fe-Mn caused an interactive influence on the self-cemented solidification of contaminated soils. The solidified samples with poly-Fe-Mn exhibited better thermal decomposition than their counterparts, reflecting the enhancement of poly-Fe-Mn to the matrix. Some minerals including C-S-H, kaolinite, gehlenite, diopside sodian, augite, and albite were matched in the samples, directly demonstrating the geopolymerization-steered self-cementation of the As soil. The employment of poly-Fe-Mn not only reinforced the immobilization of As pollutants in the matrix but also induced the self-cementation of soils by intensifying the composite alkaline-activated geopolymerization kinetics.

Clinical value of ACR O-RADS combined with CA125 in the risk stratification of adnexal masses.

Purpose: To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. Methods: A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. Results: The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). Conclusion: The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

Extragastrointestinal stromal tumors with diffuse membranous distribution with bleeding: A case report.

BACKGROUND: Extragastrointestinal stromal tumors (EGIST) and gastrointestinal stromal tumors are of similar pathological type and form. Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity, the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors. CASE SUMMARY: The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days. Upon physical examination, the patient had flat and tough abdomen with mild pressing pain at lower abdomen, no obvious abdominal mass was touchable, and shifting dullness was positive. Positron emission tomography-computed tomography (CT) showed that in his peritoneal cavity, there were multiple nodules of various sizes, seroperitoneum, multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules. Plain CT scanning at epigastrium/hypogastrium/pelvic cavity + enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity, peritoneum and right groin. Tumor marker of carbohydrate antigen 125 was 808 U/mL, diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia, and postoperative pathological examination confirmed EGIST. Imatinib was administered with better therapeutic effect. CONCLUSION: Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation, and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.

Pb-based metal organic framework as substrate: Chemical vapor generation-visual/smartphone colorimetric analytical system for sensitive and selective detection of sulfide ion in water and beers.

A visual/smartphone colorimetric system was developed for the sensitive and selective detection of sulfide ion (S2-) using chemical vapor generation (CVG) as a gaseous sampling technique. S2- in samples were converted into H2S after the addition of H2SO4, which separated from the solution during CVG process, ensuring high efficiency of vapor generation (sensitivity) and eliminated interferences (selectivity). The H2S was subsequently reacted with Pb-BTC and PbS was thus formed, causing the test paper turned to black. It was utilized for the detection of S2- by visual/smartphone colorimetric system. Detectable limits of 0.05 µg/mL and 0.2 µg/mL were obtained under smartphone mode and visual mode, respectively. Furthermore, this colorimetric system was successfully used for the analysis of S2- in several beer samples and water samples, with recoveries ranging 97 %-111 %. This system represents a potential miniaturized, easy used and high-effective method for rapid and on-site detection of S2-.

A convenient research strategy for functional verification of epigenetic regulators during spermatogenesis.

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.

17ß-Trenbolone Exposure Enhances Muscle Activity and Exacerbates Parkinson's Disease Progression in Male Mice.

Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder, and while the neuroprotective effects of estrogen are well-documented, the impact of androgens on neurological disorders remains understudied. The consequences of exposure to 17-trenbolone (17-TB), an environmental endocrine disruptor with androgen-like properties, on the mammalian nervous system have received limited attention. Therefore, in this study, we aimed to investigate the biological effects of 17-TB exposure on PD. In our investigation using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we discovered that 17-TB exposure elevated testosterone hormone levels prevented androgen receptor (AR) reduction, upregulated the expression of muscular dystrophic factors (Atrogin1, MuRF1, Musa1, and Myostatin), improved muscle strength, and enhanced locomotor activity in the open field test. However, it is noteworthy that exposure to 17-TB also led to an upregulation of neuroinflammatory cytokines (NLRP3, IL-6, IL-1α, and IL-1ß) in PD mice. Crucially, 17-TB exposure induced downregulation of nigral apoptotic proteins DJ-1 and Bcl-2 while upregulating Bax and Caspase-3 in PD mice. This exacerbated neuronal apoptosis, ultimately intensifying dopaminergic neuronal degeneration and death in the substantia nigra and striatum of PD mice. In conclusion, our findings indicate that while 17-TB mitigates muscle atrophy and enhances motor activity in PD mice, it concurrently exacerbates neuroinflammation, induces neuronal apoptosis, and worsens dopaminergic neuronal death, thereby aggravating the progression of MPTP-induced Parkinsonism. This underscores the importance of considering potential environmental risks in neurodegeneration associated with Parkinson's disease, providing a cautionary tale for our daily exposure to environmental endocrine chemical disruptors.