Effects of sulfur nanoparticles on rhizosphere microbial community changes in oilseed rape plantation soil under mercury stress.

In the present study, experiments were conducted to assess the influence of nanoscale sulfur in the microbial community structure of metallophytes in Hg-contaminated rhizosphere soil for planting rapeseed. The results showed that the richness and diversity of the rhizobacteria community decreased significantly under Hg stress, but increased slightly after SNPs addition, with a reduction in the loss of Hg-sensitive microorganisms. Moreover, all changes in the relative abundances of the top ten phyla influenced by Hg treatment were reverted when subjected to Hg + SNPs treatment, except for Myxococcota and Bacteroidota. Similarly, the top five genera, whose relative abundance decreased the most under Hg alone compared to CK, increased by 19.05%-54.66% under Hg + SNPs treatment compared with Hg alone. Furthermore, the relative abundance of Sphingomonas, as one of the dominant genera for both CK and Hg + SNPs treatment, was actively correlated with plant growth. Rhizobacteria, like Pedobacter and Massilia, were significantly decreased under Hg + SNPs and were positively linked to Hg accumulation in plants. This study suggested that SNPs could create a healthier soil microecological environment by reversing the effect of Hg on the relative abundance of microorganisms, thereby assisting microorganisms to remediate heavy metal-contaminated soil and reduce the stress of heavy metals on plants.

In this manuscript, we first comprehensively investigated the changes in the rhizosphere microbial community structure of metallophytes in Hg-contaminated soil with SNPs addition, as well as the relationship between soil microbiology and plant resistance to Hg stress. Our results demonstrated that SNPs exhibit a significant advantage in improving rhizosphere microecology by increasing the abundance of beneficial rhizobacteria, thereby alleviating heavy metal toxicity, and promoting plant growth. This study is the first study describing the response of soil microorganisms coexposed to heavy metals and SNPs, providing valuable information for the potential use of SNPs to assist phytoremediation of toxic metal pollution and its impact on soil microbial communities.

Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.

BACKGROUND: Despite advances in therapeutic strategies, resistance to immunotherapy and the off-target effects of targeted therapy have significantly weakened the benefits for patients with melanoma. MAIN BODY: Alternative splicing plays a crucial role in transcriptional reprogramming during melanoma development. In particular, aberrant alternative splicing is involved in the efficacy of immunotherapy, targeted therapy, and melanoma metastasis. Abnormal expression of splicing factors and variants may serve as biomarkers or therapeutic targets for the diagnosis and prognosis of melanoma. Therefore, comprehensively integrating their roles and related mechanisms is essential. This review provides the first detailed summary of the splicing process in melanoma and the changes occurring in this pathway. CONCLUSION: The focus of this review is to provide strategies for developing novel diagnostic biomarkers and summarize their potential to alter resistance to targeted therapies and immunotherapy.

Integrated mRNA- and miRNA-sequencing analyses unveil the underlying mechanism of tobacco pollutant-induced developmental toxicity in zebrafish embryos.

Tobacco pollutants are prevalent in the environment, leading to inadvertent exposure of pregnant females. Studies of these pollutants' toxic effects on embryonic development have not fully elucidated the potential underlying mechanisms. Therefore, in this study, we aimed to investigate the developmental toxicity induced by cigarette smoke extract (CSE) at concentrations of 0.25, 1, and 2.5% using a zebrafish embryo toxicity test and integrated transcriptomic analysis of microRNA (miRNA) and messenger RNA (mRNA). The findings revealed that CSE caused developmental toxicity, including increased mortality and decreased incubation rate, in a dose-dependent manner. Moreover, CSE induced malformations and apoptosis, specifically in the head and heart of zebrafish larvae. We used mRNA and miRNA sequencing analyses to compare changes in the expression of genes and miRNAs in zebrafish larvae. The bioinformatics analysis indicates that the mechanism underlying CSE-induced developmental toxicity was associated with compromised genetic material damage repair, deregulated apoptosis, and disturbed lipid metabolism. The enrichment analysis and RT-qPCR show that the ctsba gene plays a crucial function in embryo developmental apoptosis, and the fads2 gene mainly regulates lipid metabolic toxicity. The results of this study improve the understanding of CSE-induced developmental toxicity in zebrafish embryos and contribute insights into the formulation of novel preventive strategies against tobacco pollutants during early embryonic development.

Blood Eosinophil Count and Its Determinants in a Chinese Population-Based Cohort.

INTRODUCTION: Blood eosinophil count has been shown markedly variable across different populations. However, its distribution in Chinese general population remains unclear. We aimed to investigate blood eosinophil count and its determinants in a Chinese general population. METHODS: In this population-based study, general citizens of Sichuan province in China were extracted from the China Pulmonary Health study. Data on demographics, personal and family history, living condition, lifestyle, spirometry, and complete blood count test were obtained and analyzed. A stepwise multivariate binary logistic regression analysis was performed to identify determinants of high blood eosinophils (>75th percentile). RESULTS: A total of 3,310 participants were included, with a mean age (standard deviation) of 47.0 (15.6) years. In total population, the median blood eosinophil count was 110.0 (interquartile range [IQR]: 67.2-192.9) cells/µL, lower than that in smokers (133.4 cells/µL, IQR: 79.3-228.4) and patients with asthma (140.7 cells/µL, IQR: 79.6-218.2) or post-bronchodilator airflow limitation (141.5 cells/µL, IQR: 82.6-230.1), with a right-skewed distribution. Multivariate analyses revealed that oldness (aged ≥60 years) (odds ratio [OR]: 1.66, 95% confidence interval [CI]: 1.11-2.48), smoking ≥20 pack-years (OR: 1.90, 95% CI: 1.20-3.00), raising a dog/cat (OR: 1.72, 95% CI: 1.17-2.52), and occupational exposure to dust, allergen, and harmful gas (OR: 1.58, 95% CI: 1.15-2.15) were significantly associated with high blood eosinophils. CONCLUSION: This study identifies a median blood eosinophil count of 110.0 cells/µL and determinants of high blood eosinophils in a Chinese general population, including oldness (aged ≥60 years), smoking ≥20 pack-years, raising a dog/cat, and occupational exposure to dust, allergen, and harmful gas.

Integrated characterization of hepatobiliary tumor organoids provides a potential landscape of pharmacogenomic interactions.

Despite considerable efforts to identify human liver cancer genomic alterations that might unveil druggable targets, the systematic translation of multiomics data remains challenging. Here, we report success in long-term culture of 64 patient-derived hepatobiliary tumor organoids (PDHOs) from a Chinese population. A divergent response to 265 metabolism- and epigenetics-related chemicals and 36 anti-cancer drugs is observed. Integration of the whole genome, transcriptome, chromatin accessibility profiles, and drug sensitivity results of 64 clinically relevant drugs defines over 32,000 genome-drug interactions. RUNX1 promoter mutation is associated with an increase in chromatin accessibility and a concomitant gene expression increase, promoting a cluster of drugs preferentially sensitive in hepatobiliary tumors. These results not only provide an annotated PDHO biobank of human liver cancer but also suggest a systematic approach for obtaining a comprehensive understanding of the gene-regulatory network of liver cancer, advancing the applications of potential personalized medicine.

EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation.

Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, exhibits strong cancer plasticity. We find that ALK rearrangement is detectable in 5.1-7.5% of human LUAS, and transgenic expression of EML4-ALK drives lung adenocarcinoma (LUAD) formation initially and squamous transition at late stage. We identify club cells as the main cell-of-origin for squamous transition. Through recapitulating lineage transition in organoid system, we identify JAK-STAT signaling, activated by EML4-ALK phase separation, significantly promotes squamous transition. Integrative study with scRNA-seq and immunostaining identify a plastic cell subpopulation in ALK-rearranged human LUAD showing squamous biomarker expression. Moreover, those relapsed ALK-rearranged LUAD show notable upregulation of squamous biomarkers. Consistently, mouse squamous tumors or LUAD with squamous signature display certain resistance to ALK inhibitor, which can be overcome by combined JAK1/2 inhibitor treatment. This study uncovers strong plasticity of ALK-rearranged tumors in orchestrating phenotypic transition and drug resistance and proposes a potentially effective therapeutic strategy.

A carboxymethyl chitosan/oxidized hyaluronic acid composite hydrogel dressing loading with stem cell exosome for chronic inflammation wounds healing.

Stem cell exosomes (Exo) play an important role in the transformation of macrophages, but the rapid clearance of Exo in vivo limits their therapeutic effects for chronic inflammation wounds healing. Here, stem cell Exo was isolated and introduced to a composite hydrogel including carboxymethyl chitosan (CMCS) and oxidized hyaluronic acid (OHA) through chemical cross-linking, which formed an Exo-loaded (CMCS/OHA/Exo) hydrogel. The CMCS/OHA/Exo hydrogel exhibited a function of Exo sustained release and an Exo protection within 6 days. This CMCS/OHA/Exo hydrogel was much better than CMCS/OHA hydrogel or Exo solution in macrophage cell phagocytosis, proliferation and migration in vitro, especially, played an obviously positive role in the transformation of macrophages compared with the reference groups. For the treatment of the chronic inflammation wounds in vivo, the CMCS/OHA/Exo hydrogel had the best results at wound heal rate and inhibiting the secretion of inflammatory factors, and it was far superior to reference groups in wound re-epithelization and collagen production. CMCS/OHA/Exo hydrogels can promote Exo release based on hydrogel degradation to regulate macrophages transformation and accelerate chronic wound healing. The study offers a method for preparing Exo-loaded hydrogels that effectively promote the transformation of macrophages and accelerate chronic inflammatory wound healing.

Influence of nanoscale sulfur on mercury accumulation and plant growth in oilseed rape seedlings (Brassica napus L.) grown on mercury-contaminated soil.

Mercury (Hg) pollution has seriously threatened the crop productivity and food security. In the present research, experiments were conducted to assess the influence of nanoscale sulfur/sulfur nanoparticles and the corresponding bulk and ionic sulfur forms on the growth and Hg accumulation of oilseed rape seedlings grown on Hg-contaminated soil, as well as the transformation of soil Hg fractions. The results showed a significant reduction in fresh biomass for seedlings grown on 80-200 mg/kg Hg-polluted soil after 30 days. At 120 mg/kg Hg treatment, 100-300 mg/kg sulfur nanoparticles (SNPs) application counteracted Hg toxicity more effectively compared to the corresponding bulk sulfur particles (BSPs) and ionic sulfur (sulfate) treatments. The seedlings treated with 120 mg/kg Hg + 300 mg/kg SNPs gained 54.2 and 56.9% more shoot and root biomass, respectively, compared to those treated with Hg alone. Meanwhile, 300 mg/kg SNPs application decreased Hg accumulation by 18.9 and 76.5% in shoots and roots, respectively, relative to Hg alone treatment.SNPs treatment caused more Hg to be blocked in the soil and accumulating significantly less Hg in plants as compared to other S forms. The chemical fractions of Hg in the soil were subsequently investigated, and the solubility of Hg was significantly decreased by applying SNPs to the soil. Especially 200-300 mg/kg SNPs treatments caused the ratio of the soluble/exchangeable and the specifically absorbed fraction to be the lowest, accounting for 1.95-4.13% of the total Hg of soil. These findings suggest that adding SNPs to Hg-contaminated soils could be an effective measure for immobilizing soluble Hg and decreasing the Hg concentration in the edible parts of crops. The results of the current study hold promise for the practical application of SNPs to Hg-contaminated farmland for better yields and simultaneously increasing the food safety.

The novelty of this study is the selection of oilseed rape and nanoscale sulfur (NS) or sulfur nanoparticles (SNPs) as nontoxic nanomaterial to counteract the Hg toxicity and accumulation. Oilseed rape was selected due to its wide adaptability to various environmental conditions and the high-value oil for human consumption and biofuels production. These advantages make oilseed rape a highly valuable crop for various applications. NS was selected due to its reported ability to limit the uptake of heavy metals in oilseed rape, rice, and wheat along with other crops and subsequently restrict the toxicity of heavy metals in these plants and improve food safety. In this study, we evaluated the growth, Hg accumulation, and the resulting toxicity in oilseed rape grown on Hg-contaminated soil, with or without amendments with NS. The outcomes from this study provided evidence of the significant potential of NS in preventing Hg bioaccumulation and improving crop yields in oilseed rape. This provides opportunity to use NS as an ideal non-GMO approach to limit toxic metals in crops.

Colon-Targeted Oral Delivery of Hydroxyethyl Starch-Curcumin Microcapsules Loaded with Multiple Drugs Alleviates DSS-Induced Ulcerative Colitis in Mice.

Combination therapy through colon-targeted oral delivery of multiple drugs presents a promising approach for effectively treating ulcerative colitis (UC). However, the codelivery of drugs with diverse physicochemical properties in a single formulation remains a formidable challenge. Here, microcapsules are designed based on hydroxyethyl starch-curcumin (HES─CUR) conjugates to enable the simultaneous delivery of hydrophobic dexamethasone acetate (DA) and hydrophilic cefazolin sodium (CS), yielding multiple drug-loaded microcapsules (CS/DA-loaded HES─CUR microcapsules, CDHC-MCs) tailored for colon-targeted therapy of UC. Thorough characterization confirms the successful synthesis and exceptional biocompatibility of CDHC-MCs. Biodistribution studies demonstrate that the microcapsules exhibit an impressive inflammatory targeting effect, accumulating preferentially in inflamed colons. In vivo experiments employing a dextran-sulfate-sodium-induced UC mouse model reveal that CDHC-MCs not only arrest UC progression but also facilitate the restoration of colon length and alleviate inflammation-related splenomegaly. These findings highlight the potential of colon-targeted delivery of multiple drugs within a single formulation as a promising strategy to enhance UC treatment, and the CDHC-MCs developed in this study hold great potential in developing novel oral formulations for advanced UC therapy.

A case report and literature review on reactive cutaneous capillary endothelial proliferation induced by camrelizumab in a nasopharyngeal carcinoma patient.

Camrelizumab, a monoclonal antibody, blocks programmed cell death protein-1 from binding to T cells and programmed cell death ligand 1 on tumor cells, thereby ensuring sustained T cell activation and blocking immune escape of various types of cancer, including nasopharyngeal carcinoma. Reactive cutaneous capillary endothelial hyperplasia (RCCEP) is the most common immune-related adverse event in patients treated with camrelizumab. We report a case nasopharyngeal carcinoma in a patient with camrelizumab-induced RCCEP. A 68-year-old man diagnosed with nasopharyngeal carcinoma developed RCCEP at multiple locations after 3 months of camrelizumab treatment. RCCEP of the right lower eyelid affected closure of the right eye. In this report, we also reviewed previous literature on camrelizumab-induced RCCEP. In summary, the mechanism underlying camrelizumab-induced RCCEP remains unclear. RCCEP typically gradually subsides after discontinuing camrelizumab treatment. Larger nodules can be treated with lasers, ligation, or surgery. Although surgical excision is effective, RCCEP may recur in patients undergoing camrelizumab treatment. RCCEP management may not be required in the absence of adverse effects on the patient's daily life.

Comparative analysis of two arecoline-induced oral submucous fibrosis models.

OBJECTIVE: The limited understanding of the molecular mechanism for oral submucosal fibrosis (OSF) poses challenges to the development of effective prevention and treatment strategies. The lack of suitable animal models is a major hindrance. Therefore, this study aimed to address this issue by comparing commonly used arecoline-induced water drinking and injection mouse models. MATERIALS AND METHODS: The mice were subjected to two protocols: receiving 2 mg/mL arecoline in drinking water and 4 mg/mL arecoline saline solution injections every other day. Tissues were collected at regular 4-week intervals, with a final time point of 20 weeks. Stereo microscopy and histomorphological analysis were performed on live and harvested tissues, respectively. RESULTS: During arecoline treatment, collagen deposition and myofibroblast proliferation progressively increased in both models. Changes in the collagen I/III ratio indicated that both models exhibited characteristics of the early and intermediate stages of OSF after 20 weeks of arecoline induction. The water-drinking model also demonstrated multi-organ fibrosis involving the tongue, lungs, and small intestine. CONCLUSION: Both the water drinking and injection mouse models effectively induced OSF, but the water-drinking model better mirrored the observed pathogenesis in patients with OSF. These models provide valuable tools for investigating the mechanisms underlying OSF.

Transcriptomic analysis approach towards an improved tolerance of Escherichia coli to gallic acid stress.

As a natural green additive, gallic acid has been widely used in food production. However, it can inhibit the physiological metabolism of Escherichia coli, which severely limits the ability and efficiency of gallic acid production. To explore the adaptation mechanism of E. coli under gallic acid stress and further explore the target of genetic modification, the effects of gallic acid stress on the fermentation characteristics of E. coli W3110 ATCC (82057) were investigated by cell biomass and cell morphometry. Moreover, transcriptome analysis was used to analyze the gene transcription level of E. coli W3110 ATCC (82057) to explore effects of gallic acid stress on important essential physiological processes. The results showed that under high concentration of gallic acid, the biomass of E. coli W3110 ATCC (82057) decreased significantly and the cells showed irregular morphology. Transcriptome analysis showed that E. coli W3110 ATCC (82057) improved its adaptive capacity through three strategies. First, genes of bamD, ompC, and ompF encoding outer membrane protein BamD, OmpC, and OmpC were decreased 5-, 31.1- and 8.1-fold, respectively, under gallic acid stress compared to the control, leading to the reduction of gallic acid absorption. Moreover, genes (mdtA, mdtB, mdtC, mdtD, mdtE, and mdtF) related to MdtABC multidrug efflux system and multidrug efflux pump MdtEF were up-regulated by1.0-53.0 folds, respectively, and genes (aaeA, aaeB, and aaeX) related to AaeAB efflux system were up-regulated by 8.0-13.3 folds, respectively, which contributed to the excretion of gallic acid. In addition, genes of acid fitness island also were up-regulated by different degrees under the stress of an acidic environment to maintain the stability of the intracellular environment. In conclusion, E. coli W3110 ATCC (82057) would enhance its tolerance to gallic acid by reducing absorption, increasing excretion, and maintaining intracellular environment stability. This study provides research ideas for the construction of engineered strains with high gallic acid yield.

Developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether induced endoplasmic reticulum stress on early life stages of zebrafish (Danio rerio).

Polybrominated diphenyl ether flame retardants are known to have adverse effects on the development of organisms. We investigated the molecular mechanisms associated with the developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in zebrafish, as well as the behavioral and morphological alterations involved, focusing on endoplasmic reticulum stress (ERS), oxidative stress, and apoptosis. Our study revealed behavioral alterations in zebrafish exposed to BDE-47, including impaired motor activity, reduced exploration, and abnormal swimming patterns. In addition, we observed malformations in craniofacial regions and other developmental abnormalities that may be associated with ERS-induced cellular dysfunction. BDE-47 exposure showed apparent changes in ERS, oxidative stress, and apoptosis biomarkers at different developmental stages in zebrafish through gene expression analysis and enzyme activity assays. The study indicated that exposure to BDE-47 results in ERS, as supported by the upregulation of ERS-related genes and increased activity of ERS markers. In addition, oxidative stress-related genes showed different expression patterns, suggesting that oxidative stress is involved in the BDE-47 toxic effects. Moreover, an assessment of apoptotic biomarkers revealed an imbalance in the expression levels of pro- and anti-apoptotic genes, suggesting that BDE-47 exposure activated the apoptotic pathway. These results highlight the complex interactions between ERS, oxidative stress, apoptosis, behavioral alterations, and morphological malformations following BDE-47 exposure in zebrafish. Understanding the mechanisms of toxicity of developmental hazards is essential to elucidate the toxicological effects of environmental contaminants. The knowledge can help develop strategies to mitigate their adverse effects on the health of ecosystems and humans.

Primary or metastatic branchial cleft carcinoma?: a case report.

The brachial cleft carcinoma is an extremely rare head and neck facial malignancy, and there is some disagreement about its differential diagnosis. In this paper, we report a 63-year-old male patient who had a mass on the left side of the neck and diagnosed as the brachial cleft carcinoma by intraoperative biopsy pathology. However, this patient was diagnosed with the carcinoma of the left soft palate more than 20 days after surgery and esophageal cancer 2 years later, and was treated accordingly. Therefore, it is hard to confirm whether the branchial cleft carcinoma is primary or metastatic. In fact, the diagnostic criteria for primary squamous cell carcinoma of branchial cleft cysts are very rigorous. Confirmation of the diagnosis is based on pathological examination of the branchial cleft cyst epithelium lined with squamous cells, meanwhile, a thorough examination should also be performed to exclude the presence of other primary cancers.

First report of leaf spot disease caused by Alternaria alternata in Tilia miqueliana in Jiangsu Province, China.

Tilia miqueliana Maxim., a tall deciduous tree in the Malvaceae family, is native to china and is cultivated in the Jiangsu, Zhejiang, Anhui, and Jiangxi provinces as an ornamental plant. T. miqueliana has currently received increased attention because of its value as timber, a source plant for honey, and in formal landscape architecture (Wang et al. 2022). In the last three years, symptoms of leaf spot disease were observed in T. miqueliana fields （9-year-old tree）and a breeding nursery _(1-year-old saplings) in Nanjing, Jiangsu Province, China. Field surveys showed that, the disease incidence was approximately 10% and 40% in the fields and breeding nursery, respectively. Symptoms of leaf spot disease on T. miqueliana appeared as small, circular, or near-circular/irregular black lesions on the upper surfaces of the leaves. As the disease progressed, the spots expanded into irregular shapes with the center turning yellow to black and leaves wilted from margins to centers. In severe cases, the yellow necrotic area extended to the margin, which ultimately led to leaf curling and death. To analyze the presence of the pathogenic microorganism, pieces of leaf at the junction of diseased and healthy tissue (about 3x3 mm) were taken from symptomatic plants, sterilized with 75% ethanol for 1 min and 2% sodium hypochlorite (NaClO) for 2 min, and washed 3 times with ddH2O. The leaf pieces were transferred onto Potato Dextrose Agar (PDA) plates and incubated at 28°C for 3 days in the dark. Colonies were observed and transferred to fresh PDA plates. Sixteen fungal isolates were obtained and one (named D4-2) of them was verified using Koch's assumption. Single spores of D4-2 were cultured in PDA medium, while its initial colony morphology was fluffy white colonies, which then gradually turned dark yellow from the centre to the edge. To further analyze the form of the spores, a hypha was incubated on fresh synthetic low-nutrient agar (SNA) using cellophane and inverted cultivation was performed for 20 days in the dark. Obclavate or obpyriform conidia (10 to 30 × 2 to 18 µm, n=5) were produced in chains and were pale brown to brown in color. The morphology was consistent with that of Alternaria sp.. The molecular identification of the isolated representative fungus D4-2 was conducted via the amplification of the internal transcribed spacer (ITS) (White et al. 1990),translation elongation factor 1 alpha (TEF) (Carbone and Kohn. 1999), glyceraldehyde-3-dehydrogenase (GAPDH) (Berbee et al. 1999) and RNA polymerase II beta subunit (RPB2) using the primer pairs ITS1/ITS4, EF1-728F/EF1-986R, GPD1/GPD2, and RPB2-5F2/fRPB2-7cR (Sung et al. 2007) respectively. All these sequences were deposited in GenBank under accession numbers OP108438 (ITS), OP168372 (RPB2), OQ473880 (TEF), and OP168374 (GAPDH). Based on the GAPDH, RPB2, and TEF regions of D4-2, MEGA-11 was used to construct a neighbor-joining tree (1000 replications) with 31 other known species that had a relatively close evolutionary relationship with species from the Alternaria genus (Woudenberg et al. 2013). The phylogenetic tree indicated 100% bootstrap support between D4-2 and A. alternata. The branches showing the distribution of other species were exactly the same as that of the consensus tree based on the Bayesian 50 % majority rule that represented the Alternaria-complex (Woudenberg et al. 2013). The initial Koch's Postulates was verified using PDA slices with mycelium (pure PDA slices were used as control) that were inverted on the leaves at 25℃ for 3 days before removing slices and observing the phenotype after 7 days. Only leaves infected with D4-2 showed the same symptoms. Moreover, the spore suspension (at a concentration of 107 spores/mL) of D4-2 was applied to the leaves of T. miqueliana seedlings. After 15 days of incubation at 26 ℃ , the leaves showed the same symptoms. Subsequently, the pathogen was reisolated and cultured from these invaded leaves using the same method described above. Morphological and molecular identifications were consistent with those of D4-2. Above all, the pathogenic fungus (D4-2) isolated from T. miqueliana leaves was confirmed to be A. alternata. T. miqueliana is considered to be an endangered species due to the deep dormancy of its seeds that result in a low natural germination rate (Wu and Shen. 2021). At present, research on T. miqueliana mainly focuses on seed germination and breeding technology, and there is hardly any research on the diseases occurring in T. miqueliana. Therefore, we believe that this is the first report of leaf spot disease caused by A. alternata on T. miqueliana in China.

TNFSF10, an autophagy related gene, was a prognostic and immune infiltration marker in skin cutaneous melanoma.

Autophagy exerts a pivotal effect on skin cutaneous melanoma (SKCM). This study was aimed to investigate the expression of autophagy related genes (ARGs) in SKCM as well as its clinical value. Differentially expressed (DE) ARGs were downloaded from the intersection of SKCM data in GEPIA2 database and ARGs in Human Autophagy Database (HADB) database, and were verified in SKCM datasets GSE46517 and GSE15605. DE ARGs were enriched by Metascape online tools. According to GEPIA2 database, tumor necrosis factor-related apoptosis-inducing ligand (TNFSF10) was identified as a closely related factor and prognostic marker of SKCM. Then the correlation analysis of clinicopathological characteristics between TNFSF10 and SKCM was completed by several online tools such as TISCH, HPA, BEST and qRT-PCR. Subsequently, we investigated TNFSF10 related functions and signal pathways with LinkedOmics online tool, and immune infiltration using Assistant for Clinical Bioinformatics online tool. Furthermore, correlation analysis between TNFSF10 expression and immunotherapy response was performed by TIDE algorithm and BEST online tool. And Kaplan-Meier Plotter was used to assessing the prognosis of SKCM patients receiving immunotherapy. Finally, the correlation analysis among TNFSF10 methylation, TNFSF10 expression and patient prognosis was completed by the DiseaseMeth version 2.0, UCSC XENA and qRT-PCR. ARGs are DE in SKCM and participate in the ERBB signaling pathway, as well as the processing and presentation of antigens. Moreover, TNFSF10's expression along with methylation expression were significantly associated with the prognosis. Low expression of TNFSF10 was associated with malignant clinicopathological features, lower immune signal activity and lower immunocytes abundance in patients with SKCM. As an ARG, TNFSF10 has a potential capacity in predicting the prognosis of SKCM patients, meanwhile, may be a novel immunotherapy marker for SKCM.

CBX3 promotes clear cell renal carcinoma through PI3K/AKT activation and aberrant immunity.

BACKGROUND: A chromobox homologue 3 (CBX3) is elevated in various cancers and significantly contributes to the promotion of malignant behavior; despite this, its exact involvement in clear cell renal cell carcinoma (ccRCC) is yet unknown. METHODS: The Cancer Genome Atlas database served to evaluate CBX3 production and its connection to survival in patients with ccRCC. Our team evaluated the effects of knockdown of CBX3 levels in ccRCC cell populations using in vitro together with in vivo models. CBX3, proteins related to death, and epithelial-to-mesenchymal transition (EMT)-related proteins were measured in ccRCC cells using western blotting and immunohistochemical assays. Through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO) and Gene Set Enrichment Analysis (GSEA), the biological processes and signal pathways related to CBX3 expression were identified. Immune-related activity reduced by CBX3 was assessed using various online tools. RESULTS: Both genomic and protein expression showed that CBX3 was upregulated in ccRCC. Further functional analyses revealed that CBX3 played a crucial role in enhancing cell growth, migration, and EMT in vitro along with in vivo. Moreover, the study results provided distinct mechanistic evidence that CBX3 exerts its pathological functions in ccRCC by activating the PI3K/AKT pathway. Finally, immunoassays revealed that CBX3, a possible biomarker of ccRCC, was significantly associated with immunity. CONCLUSIONS: Our results suggest that the overexpression of CBX3 promotes ccRCC advancement through PI3K/AKT activation and even immunological dysregulation, making it a potentially viable and beneficial therapeutic target.

Metabolic classification suggests the GLUT1/ALDOB/G6PD axis as a therapeutic target in chemotherapy-resistant pancreatic cancer.

Metabolic reprogramming is known as an emerging mechanism of chemotherapy resistance, but the metabolic signatures of pancreatic ductal adenocarcinomas (PDACs) remain unclear. Here, we characterize the metabolomic profile of PDAC organoids and classify them into glucomet-PDAC (high glucose metabolism levels) and lipomet-PDAC (high lipid metabolism levels). Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression. Pharmacological inhibition of GLUT1 or G6PD enhances the chemotherapy response of glucomet-PDAC. Our findings uncover potential metabolic heterogeneity related to differences in chemotherapy sensitivity in PDAC and develop a promising pharmacological strategy for patients with chemotherapy-resistant glucomet-PDAC through the combination of chemotherapy and GLUT1/ALDOB/G6PD axis inhibitors.

Contrastively generative self-expression model for single-cell and spatial multimodal data.

Advances in single-cell multi-omics technology provide an unprecedented opportunity to fully understand cellular heterogeneity. However, integrating omics data from multiple modalities is challenging due to the individual characteristics of each measurement. Here, to solve such a problem, we propose a contrastive and generative deep self-expression model, called single-cell multimodal self-expressive integration (scMSI), which integrates the heterogeneous multimodal data into a unified manifold space. Specifically, scMSI first learns each omics-specific latent representation and self-expression relationship to consider the characteristics of different omics data by deep self-expressive generative model. Then, scMSI combines these omics-specific self-expression relations through contrastive learning. In such a way, scMSI provides a paradigm to integrate multiple omics data even with weak relation, which effectively achieves the representation learning and data integration into a unified framework. We demonstrate that scMSI provides a cohesive solution for a variety of analysis tasks, such as integration analysis, data denoising, batch correction and spatial domain detection. We have applied scMSI on various single-cell and spatial multimodal datasets to validate its high effectiveness and robustness in diverse data types and application scenarios.