The roles of adenosine signaling in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

Cardioprotective effects of curcumin against Diabetic Cardiomyopathies: A systematic review and meta-analysis of preclinical studies.

BACKGROUND: As a common complication of diabetes, diabetic cardiomyopathy (DCM) often leads to further damage to the heart muscle. Curcumin has been proven to have a variety of cardioprotective effects, however, the protective effect against DCM has not been systematically reviewed. PURPOSE: In this study, we aimed to analyze the preclinical (animal model) evidence of curcumin's therapeutic effects in DCM. METHODS: Eight databases and two registry systems were searched from the time of library construction to 1 November 2023. We performed rigorous data extraction and quality assessment. The included studies' methodological quality was appraised using the SYRCLE RoB tool, statistical analyses were carried out using RevMan 5.4 software, and Funnel plots and Egger's test were performed using Stata 17.0 software to assess publication bias. RESULTS: This study included 32 trials with a total of 681 animals. Meta-analysis showed that curcumin significantly improved cardiac function indices (LVEF, LVFS, and LVSd) (p < 0.01), decreased markers of myocardial injury, HW/BW ratio, and randomized blood glucose compared to the control group, in addition to showing beneficial effects on mechanistic indices of myocardial oxidation, inflammation, apoptosis, and autophagy (p < 0.05). CONCLUSIONS: Curcumin may exert cardioprotective effects in DCM through its antioxidant, anti-inflammatory, autophagy-enhancing, and anti-apoptotic effects. Its protective effect is proportional to the dose, and the efficacy may be further increased at a concentration of more than 200 mg/kg, and further validation is needed.

Rare subcommunity maintains the stability of ecosystem multifunctionality by deterministic assembly processes in subtropical estuaries.

Microorganisms, especially rare microbial species, are crucial in estuarine ecosystems for driving biogeochemical processes and preserving biodiversity. However, the understanding of the links between ecosystem multifunctionality (EMF) and the diversity of rare bacterial taxa in estuary ecosystems remains limited. Employing high-throughput sequencing and a variety of statistical methods, we assessed the diversities and assembly process of abundant and rare bacterioplankton and their contributions to EMF in a subtropical estuary. Taxonomic analysis revealed Proteobacteria as the predominant phylum among both abundant and rare bacterial taxa. Notably, rare taxa demonstrated significantly higher taxonomic diversity and a larger species pool than abundant taxa. Additionally, our findings highlighted that deterministic assembly processes predominantly shape microbial communities, with heterogeneous selection exerting a stronger influence on rare taxa. Further analysis reveals that rare bacterial beta-diversity significantly impacts to EMF, whereas alpha diversity did not. The partial least squares path modeling (PLS-PM) analysis demonstrated that the beta diversity of abundant and rare taxa, as the main biotic factor, directly affected EMF, while temperature and total organic carbon (TOC) were additional key factors to determine the relationship between beta diversity and EMF. These findings advance our understanding of the distribution features and ecological knowledge of the abundant and rare taxa in EMF in subtropical estuaries, and provide a reference for exploring the multifunctionality of different biospheres in aquatic environments.

Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease.

Mouse models of autosomal dominant polycystic kidney disease (ADPKD) show that intact primary cilia are required for cyst growth following the inactivation of polycystin-1. The signaling pathways underlying this process, termed cilia-dependent cyst activation (CDCA), remain unknown. Using translating ribosome affinity purification RNASeq on mouse kidneys with polycystin-1 and cilia inactivation before cyst formation, we identify the differential 'CDCA pattern' translatome specifically dysregulated in kidney tubule cells destined to form cysts. From this, Glis2 emerges as a candidate functional effector of polycystin signaling and CDCA. In vitro changes in Glis2 expression mirror the polycystin- and cilia-dependent changes observed in kidney tissue, validating Glis2 as a cell culture-based indicator of polycystin function related to cyst formation. Inactivation of Glis2 suppresses polycystic kidney disease in mouse models of ADPKD, and pharmacological targeting of Glis2 with antisense oligonucleotides slows disease progression. Glis2 transcript and protein is a functional target of CDCA and a potential therapeutic target for treating ADPKD.

[Distribution and Drug Resistance of Pathogens Causing Bloodstream Infection in Patients with Hematological Malignancies].

OBJECTIVE: To investigate distribution and drug resistance of pathogens of bloodstream infection in patients with hematological malignancies, in order to provide reference for clinical infection control and treatment. METHODS: The clinical information of blood culture patients in the hematology department of our hospital from January 2016 to December 2021 was reviewed. They were divided into transplantation group and non-transplantation group according to whether they had undergone hematopoietic stem cell transplantation. The types of pathogens and their drug resistance were analyzed. RESULTS: Two hundred and ninety-nine positive strains of pathogenic bacteria were detected. In the transplantation group, Gram-negative bacteria accounted for 68.5% (50/73), Gram-positive bacteria accounted for 6.8% (5/73), and fungi accounted for 24.7% (18/73). The resistance rate of Escherichia coli to the third-generation cephalosporins was 77.8%, and 11.5% to carbapenems. The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 50.0%, and 56.2% to carbapenems. In the non-transplantation group, Gram-negative bacteria accounted for 64.1% (145/226), Gram-positive bacteria accounted for 31.0% (70/226), and fungi accounted for 4.9% (11/226). Gram-positive bacteria were mainly Enterococcus faecium (6.6%, 15/226) and Coagulase-negative Staphylococci (6.2%, 14/226). The fungi were all Candida tropicalis. The resistance rate of Escherichia coli to the third-generation cephalosporins was 63.8%, and 10.3% to carbapenems. The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 46.3%, and 26.8% to carbapenems. CONCLUSION: The types of pathogenic bacteria in bloodstream infection in patients with hematological malignancies are varied. Gram-negative bacteria is the main pathogenic bacteria. The resistance of pathogenic bacteria to antibiotics is severe. Antibiotics should be used scientifically and reasonably according to the detection and resistance of pathogenic bacteria.

Resource diversity disturbs marine Vibrio diversity and community stability, but loss of Vibrio diversity enhances community stability.

Vibrio is a salt-tolerant heterotrophic bacterium that occupies an important ecological niche in marine environments. However, little is known about the contribution of resource diversity to the marine Vibrio diversity and community stability. In this study, we investigated the association among resource diversity, taxonomic diversity, phylogenetic diversity, and community stability of marine Vibrio in the Beibu Gulf. V. campbellii and V. hangzhouensis were the dominant groups in seawater and sediments, respectively, in the Beibu Gulf. Higher alpha diversity was observed in the sediments than in the seawater. Marine Vibrio community assembly was dominated by deterministic processes. Pearson's correlation analysis showed that nitrite (NO2--N), dissolved inorganic nitrogen (DIN), ammonium (NH4+-N), and pH were the main factors affecting marine Vibrio community stability in the surface, middle, and bottom layers of seawater and sediment, respectively. Partial least-squares path models (PLS-PM) demonstrated that resource diversity, water properties, nutrients, and geographical distance had important impacts on phylogenetic and taxonomic diversity. Regression analysis revealed that the impact of resource diversity on marine Vibrio diversity and community stability varied across different habitats, but loss of Vibrio diversity increases community stability. Overall, this study provided insights into the mechanisms underlying the maintenance of Vibrio diversity and community stability in marine environments.

NKAIN1, as an oncogene, promotes the proliferation and metastasis of breast cancer, affecting its prognosis.

Na, K-ATPase interaction (NKAIN) is a transmembrane protein family, which can interact with Na, K-ATPase ß1 subunit. NKAIN1 plays an important role in alcohol-dependent diseases such as endometrial and prostate cancers. However, the relationship between NKAIN1 and human breast cancer has not been studied. Hence, this study aimed to explore the relationship between NKAIN1 expression and breast cancer. Data used in this study were mainly from the Cancer Genome Atlas, including differential expression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, multiple Cox regression analysis, co-expression gene analysis, and gene set enrichment analysis. Analyses were performed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunohistochemistry on 46 collected samples. The knockdown or overexpression of NKAIN1 in vitro in MCF-7 and MDA-MB-231 cell lines altered the proliferation and migration abilities of tumor cells. In vivo experiments further confirmed that NKAIN1 knockdown effectively inhibited the proliferation and migration of cancer cells. Therefore, our study identified NKAIN1 as an oncogene that is highly expressed in breast cancer tissues. The findings highlight the potential of NKAIN1 as a molecular biomarker of breast cancer.

B7-H3 promotes proliferation and migration of lung cancer cells by modulating PI3K/AKT pathway via ENO1 activity.

Background: B7-H3 (CD276) is overexpressed in diverse malignant tumors and plays critical roles in tumorigenesis and metastasis. However, the mechanism of B7-H3 in lung cancer remains unclear. This study aimed to explore the mechanism of interaction between B7-H3 and α-enolase (ENO1) in lung cancer progression. Methods: Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) databases were used to analyze the B7-H3 messenger RNA (mRNA) expression levels in lung cancer. The Kaplan-Meier (KM) plotter was used to analyze the correlation between B7-H3 and prognosis. Immunoprecipitation and glutathione S-transferase (GST) pull-down were used to verify the B7-H3 and ENO1 interaction. Cell counting kit-8 (CCK-8) and wound healing assays were used to investigate the effect of B7-H3 on the lung cancer growth. Results: Based on the public databases, the analysis showed that B7-H3 mRNA expression levels were up-regulated and correlated with patient prognosis in lung cancer. By using B7-H3 gain and off cell model, we concluded that B7-H3 overexpression promoted proliferation and migration of SBC5 cells. Subsequently, we found that both B7-H3 and ENO1 knockdown could inhibit cell proliferation and migration, in the meanwhile, and the phosphorylation levels of PI3K-p85α, and AKT were significantly reduced. Interestingly, we determined that B7-H3 regulated ENO1 activity rather than changing its expression levels. Furthermore, we used an AP-III-a4 to block ENO1 activity in the experiments, which attenuated the roles of B7-H3 not only on phosphorylation levels of those molecules, but also on cell growth and migration. Conclusions: B7-H3 directly interacts with ENO1 in lung cancer cells. B7-H3 can promote proliferation and migration of lung cancer cells by modulating PI3K/AKT pathway via ENO1 activity.

The evaluation of cystatin protein vaccines based on the stress response of ticks triggered by low-temperature and toxin stress in Haemaphysalis doenitzi.

BACKGROUND: Ticks, which are obligate blood-feeding parasites, transmit a wide range of pathogens during their hematophagic process. Certain enzymes and macromolecules play a crucial role in inhibition of several tick physiological processes, including digestion and reproduction. In the present study, genes encoding type 2 cystatin were cloned and characterized from Haemaphysalis doenitzi, and the potential role of cystatin in tick control was further assessed. RESULTS: Two cystatin genes, HDcyst-1 and HDcyst-2, were successfully cloned from the tick H. doenitzi. Their open reading frames are 390 and 426 base pairs, and the number of coding amino acids are 129 and 141, respectively. In the midgut, salivary glands, Malpighian tubules and ovaries of ticks, the relative expression of HDcyst-1 was higher in the midgut and Malpighian tubules, and HDcyst-2 was higher in the salivary glands of H. doenitzi, respectively. Lipopolysaccharide (LPS) injection and low-temperature stress elevated cystatin expression in ticks. Enzyme-linked immunosorbent assay showed that both rHDcyst-1 and rHDcyst-2 protein vaccines increased antibody levels in immunized rabbits. A vaccination trial in rabbits infected with H. doenitzi showed that both recombinant cystatin proteins significantly reduced tick engorgement weights and egg mass weight, in particular, rHDcyst-1 significantly prolonged tick engorgement time by 1 day and reduced egg hatching rates by 16.9%. In total, rHDcyst-1 and rHDcyst-2 protein vaccinations provided 64.1% and 51.8% protection to adult female ticks, respectively. CONCLUSION: This is the first report on the immunological characterization of the cystatin protein and sequencing of the cystatin gene in H. doenitzi. Cystatin proteins are promising antigens that have the potential to be used as vaccines for infestation of H. doenitzi control. © 2024 Society of Chemical Industry.

Enhancing Neuroprotection in Mouse Model of Parkinson's Disease through Protein Nanosystem Conjugation with ApoE Peptide for miR-124 Delivery.

Parkinson's disease (PD) affects millions of people's lives worldwide. The main pathogenesis of PD is dopaminergic neuron necrosis and neuroinflammation mediated by activated microglia cells. In recent years, the anti-inflammatory ability and neuroprotective effects of miR-124 in PD models were well proved, but the in vivo delivery of miR-124 remains challenging. Herein, we report a protein nanosystem modified with a brain-targeting peptide ApoE that could efficiently deliver miR-124 across the blood-brain barrier (BBB). This nanosystem showed good cell viability on brain endothelial cells and microglia cells, and administration of this nanosystem significantly decreased the neuroinflammation and dopaminergic neuron loss, as well as recovered parts of neurobehavioral deficits. This ApoE peptide-based protein nanosystem holds great promise for the delivery of RNA therapeutics to the brain and for realizing neuron protection in PD treatment.

A synthetic agent ameliorates polycystic kidney disease by promoting apoptosis of cystic cells through increased oxidative stress.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of chronic kidney disease and the fourth leading cause of end-stage kidney disease, accounting for over 50% of prevalent cases requiring renal replacement therapy. There is a pressing need for improved therapy for ADPKD. Recent insights into the pathophysiology of ADPKD revealed that cyst cells undergo metabolic changes that up-regulate aerobic glycolysis in lieu of mitochondrial respiration for energy production, a process that ostensibly fuels their increased proliferation. The present work leverages this metabolic disruption as a way to selectively target cyst cells for apoptosis. This small-molecule therapeutic strategy utilizes 11beta-dichloro, a repurposed DNA-damaging anti-tumor agent that induces apoptosis by exacerbating mitochondrial oxidative stress. Here, we demonstrate that 11beta-dichloro is effective in delaying cyst growth and its associated inflammatory and fibrotic events, thus preserving kidney function in perinatal and adult mouse models of ADPKD. In both models, the cyst cells with homozygous inactivation of Pkd1 show enhanced oxidative stress following treatment with 11beta-dichloro and undergo apoptosis. Co-administration of the antioxidant vitamin E negated the therapeutic benefit of 11beta-dichloro in vivo, supporting the conclusion that oxidative stress is a key component of the mechanism of action. As a preclinical development primer, we also synthesized and tested an 11beta-dichloro derivative that cannot directly alkylate DNA, while retaining pro-oxidant features. This derivative nonetheless maintains excellent anti-cystic properties in vivo and emerges as the lead candidate for development.

Effect of Rhythmically Cued Exercise Interventions on Functions in Patients With Parkinson Disease: A Meta-Analysis.

OBJECTIVE: The purpose of this review was to investigate the efficacy of rhythmically cued exercise interventions on motor function, cognition, and mental state in patients with Parkinson disease. METHODS: PubMed, Cochrane Database, Web of Science, Embase, and CINAHL were searched June 15, 2023. Original studies investigating the efficacy of rhythmically cued exercise interventions on the functions of patients with Parkinson disease were included. The Cochrane risk-of-bias assessment tool was used to evaluate the risk of bias. The protocol was registered in PROSPERO (CRD42022371203). RESULTS: A total of 38 original studies involving 1486 participants were included. Rhythmically cued exercise interventions demonstrated superior effects on motor function compared to exercise therapy without rhythm (standardized mean difference [SMD] = -0.31). However, no significant improvements were observed in cognition and mental state. Overall, significant improvements were observed in motor examination (SMD = -0.61), Timed "Up & Go" Test (mean difference [MD] = -0.91), activities of daily living (SMD = -0.49), balance (SMD = 0.59), walking velocity (MD = 0.06), step length (MD = 2.65), and stride length (MD = 0.04) following rhythmically cued exercise interventions. No significant improvements were observed in freezing of gait and cadence. Assessment of publication bias showed no significant evidence of publication bias. Meta-regression analyses revealed a significant association between treatment duration and improvement in motor function. Furthermore, adverse events and dropout rates did not significantly differ between the 2 groups. CONCLUSION: Rhythmically cued exercise interventions are effective in improving motor function in the early to middle stages of Parkinson disease. More than 10 weeks of intervention yielded better results. However, these interventions do not have a significant impact on cognition and mental states. Importantly, rhythmically cued exercise interventions are safe and well tolerated. Large-scale trials are needed for further confirmation. IMPACT: This study contributes to the development of safe and reliable home rehabilitation programs, aiming to enhance the quality of life for patients with Parkinson disease.

S670, an amide derivative of 3-O-acetyl-11-keto-ß-boswellic acid, induces ferroptosis in human glioblastoma cells by generating ROS and inhibiting STX17-mediated fusion of autophagosome and lysosome.

Glioblastoma (GBM) is the most common malignant tumor in the brain with temozolomide (TMZ) as the only approved chemotherapy agent. GBM is characterized by susceptibility to radiation and chemotherapy resistance and recurrence as well as low immunological response. There is an urgent need for new therapy to improve the outcome of GBM patients. We previously reported that 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) inhibited the growth of GBM. In this study we characterized the anti-GBM effect of S670, a synthesized amide derivative of AKBA, and investigated the underlying mechanisms. We showed that S670 dose-dependently inhibited the proliferation of human GBM cell lines U87 and U251 with IC50 values of around 6 µM. Furthermore, we found that S670 (6 µM) markedly stimulated mitochondrial ROS generation and induced ferroptosis in the GBM cells. Moreover, S670 treatment induced ROS-mediated Nrf2 activation and TFEB nuclear translocation, promoting protective autophagosome and lysosome biogenesis in the GBM cells. On the other hand, S670 treatment significantly inhibited the expression of SXT17, thus impairing autophagosome-lysosome fusion and blocking autophagy flux, which exacerbated ROS accumulation and enhanced ferroptosis in the GBM cells. Administration of S670 (50 mg·kg-1·d-1, i.g.) for 12 days in a U87 mouse xenograft model significantly inhibited tumor growth with reduced Ki67 expression and increased LC3 and LAMP2 expression in the tumor tissues. Taken together, S670 induces ferroptosis by generating ROS and inhibiting STX17-mediated fusion of autophagosome and lysosome in GBM cells. S670 could serve as a drug candidate for the treatment of GBM.

GREB1L overexpression is associated with good clinical outcomes in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor among women worldwide. GREB1L is a protein-coding gene. Previous studies have shown that GREB1L plays a vital role in lung and gastric adenocarcinoma. Currently, there is no relevant report about its role in breast cancer. METHODS: The Cancer Genome Atlas database was used to compare the expression level of GREB1L between tumor and normal tissues. The TISIDB website was used for prognosis analysis. The LinkedOmics database was used to predict the potential biological mechanism of GREB1L in breast cancer. Immunohistochemistry was used to detect the GREB1L expression level in breast tissue. Western blotting was used to detect the GREB1L expression level in cell lines. Transwell assays, CCK-8 cell proliferation assays, and colony formation assays were used to detect the migration, invasion, proliferation, and colony formation abilities of cells. Subcutaneous xenograft models were used to detect the in vivo tumor formation abilities of cells. RESULTS: GREB1L is highly expressed in breast cancer tissues and breast cancer cells. KEGG enrichment analysis suggested that GREB1L participates in the regulation of the Hedgehog signaling pathway; changes in GREB1L expression affected the migration and invasion abilities of MCF7 and MDA-MB-231 cells. Although changes in GREB1L expression did not affect their proliferation and colony formation abilities in vitro and in vivo, they affected the expression of tumor metastasis-related genes in vivo. The overexpression of GREB1L in breast cancer predicted a favorable prognosis. CONCLUSION: These results showed that GREB1L is involved in the development of breast cancer, and it may be a potential molecular marker for predicting the prognosis of breast cancer.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Down-regulation of DPP4 by TGFß1/miR29a-3p inhibited proliferation and promoted migration of ovarian cancer cells.

OBJECTIVE: To explore the DPP4 expression changes and functions in ovarian cancer (OV), as well as the regulation mechanism for DDP4. METHODS: GEPIA2, GSE18520, GSE26712 and UALCAN were used to analyze differences in DPP4 expression between OV tumors and control tissues. Serum DPP4 levels were measured by ELISA. The prognostic values of DPP4 were evaluated using a Kaplan-Meier (KM) plotter. Small interfering RNA was used for DPP4 knockdown in OVCAR-3 and SKOV-3 cells. CCK-8 and scratch healing assays were used to determine the cells' proliferation and migration abilities. Flow cytometry (FCM) was used to detect the cell cycle and apoptosis. A dual-luciferase assay was designed to confirm the regulatory effect of miR-29a-3p on DPP4. RESULTS: The expressions of DPP4 mRNA and protein were decreased in OV tumor tissues. Serum DPP4 levels decreased in OV patients. KM plotter analysis showed correlation between high DPP4 expression and a poor prognosis in OV patients. By targeting knockdown of DPP4, we found that OVCAR-3 and SKOV-3 cells' proliferation was inhibited, while cell's migration ability was significantly promoted. FCM analysis showed that DPP4 knockdown induced a decrease in the S phase. Furthermore, DPP4 was shown to be downregulated by miR-29a-3p and TGFß1 in OVCAR-3 cells, and miR-29a-3p expression was upregulated by TGFß1. The effects of miR-29a-3p and TGFß1 on OVCAR-3 cells' biological behaviors were consistent with DPP4 knockdown. CONCLUSION: DPP4 was downregulated in OV patients. DPP4 knockdown significantly inhibited OVCAR-3 and SKOV-3 cell proliferation and promoted cell migration. DDP4 can be downregulated by TGFß1 through the upregulation of miR-29a-3p in OV cells.

Molecular subtyping and characterization of clear cell renal cell carcinoma by tumor differentiation trajectories.

Previous bulk RNA sequencing or whole genome sequencing on clear cell renal cell carcinoma (ccRCC) subtyping mainly focused on ccRCC cell origin or the complex tumor microenvironment (TME). Based on the single-cell RNA sequencing (scRNA-seq) data of 11 primary ccRCC specimens, cancer stem-cell-like subsets could be differentiated into five trajectories, whereby we further classified ccRCC cells into three groups with diverse molecular features. These three ccRCC subgroups showed significantly different outcomes and potential targets to tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). Tumor cells in three differentiation directions exhibited distinct interactions with other subsets in the ccRCC niches. The subtyping model was examined through immunohistochemistry staining in our ccRCC cohort and validated the same classification effect as the public patients. All these findings help gain a deeper understanding about the pathogenesis of ccRCC and provide useful clues for optimizing therapeutic schemes based on the molecular subtype analysis.

Molecular Identification and Genetic Characterization of Public Health Threatening Ticks - Chongming Island, China, 2021-2022.

What is already known about this topic?: Although ticks and tick-borne diseases are prevalent throughout China, there remains a knowledge gap regarding their biology and potential risk of distribution to human and animal populations on Chongming Island. The island, being China's third largest and a crucial component in the ecological preservation of the Yangtze Delta region, has yet to be comprehensively studied in this context. What is added by this report?: In this study, employing molecular methodologies, a significant prevalence of Haemaphysalis (H.) longicornis and H. flava ticks - widely recognized for their high pathogenicity - is reported from Chongming Island. Additionally, the identification of two previously unreported species on the island, namely, H. doenitzi and H. japonica, expands our understanding of both the range and evolution of tick species. What are the implications for public health practice?: The populations of humans and animals in nearly all 18 towns on Chongming Island are potentially at risk for transmission of tick-borne infectious agents. As a result, there is a pressing necessity for public health alerts, proactive tick surveillance, and effective screening of suspected clinical cases of tick-borne diseases within the Chongming population.