Gene features of tumor-specific T cells relevant to immunotherapy, targeted therapy and chemotherapy in lung cancer.

1 Background: In lung cancer, the use of small-molecule inhibitors, chemotherapy and immunotherapy has led to unprecedented survival benefits in selected patients. Considering most patients will experience a relapse within a short period of time due to single drug resistance, combination therapy is also particularly important to improve patient prognosis. Therefore, more robust biomarkers to predict responses to immunotherapy, targeted therapy, chemotherapy and rationally drug combination therapies may be helpful in clinical treatment choices. 2 Methods: We defined tumor-specific T cells (TSTs) and their features (TSTGs) by single-cell RNA sequencing. We applied LASSO regression to filter out the most survival-relevant TSTGs to form the Tumor-specific T cell score (TSTS). Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low TSTS groups. 3 Results: We identified six clusters of T cells as TSTs in lung cancer, and four most robust genes from 9 feature genes expressed only on tumor-specific T cells were screened to construct a tumor-specific T cells score (TSTS). TSTS was positively correlated with immune infiltration and angiogenesis and negatively correlated with malignant cell proliferation. Moreover, potential vascular-immune crosstalk in lung cancer provides the theoretical basis for combined anti-angiogenic and immunotherapy. Noticeable, patients in high TSTS had better response to ICB and targeted therapy and patients in the low TSTS group often benefit from chemotherapy. 4 Conclusion: The proposed TSTS is a promising indicator to predict immunotherapy, targeted therapy and chemotherapy responses in lung cancer patients for helping clinical treatment choices.

Self-reported perceptions of ethical and professional expectations of medical students in China and the influence of voluntary work during the COVID-19: a survey on "Five Characteristics".

In the post-pandemic era, there is a need for medical professionals with creativity, clinical expertise, and social responsibility. The Chinese government issued a directive to enhance the "Five Characteristics" perceptions of medical students, incorporating moral integrity and adeptness in saving lives and aiding the injured, embracing a compassionate approach to medical practice, possessing the knowledge essential for academic distinction, mastering technical expertise, and the artistry of applying scientific methodologies. The purpose of this study was to investigate the opinions related to ethics and professional behaviors of medical students at one Chinese medical school using a validated 19-item survey instrument and analyze its influencing factors. We conducted a survey in a medical university in Anhui Province, China, and collected 1966 valid questionnaires using the "Five Characteristics Rating Scale". The results indicated high perceptions of "Five Characteristics" among Chinese medical students (85.42 ± 8.727). Lower-grade-year medical students (86.59 ± 7.888) had higher "Five Characteristics" perceptions than upper-grade-year medical students (84.29 ± 9.327, P < 0.05). In addition, medical students experiencing voluntary work during the COVID-19 pandemic showed higher perceptions (86.21 ± 8.357) than those without such experience (85.13 ± 8.842, P < 0.05). Grade year and voluntary work experience during the COVID-19 pandemic were influencing factors of "Five Characteristics" perceptions. Our research offers a theoretical foundation for governments and medical schools to cultivate doctors with high ethical standards and professional expectations.

Analysis of related factors for neuropsychiatric comorbidities in children with epilepsy.

OBJECTIVE: To analyze the risk factors affecting psychiatric behavior and study the psychobehavioral conditions of children with epilepsy. METHOD: We randomly selected and enrolled 294 children with epilepsy who visited and were hospitalized in the pediatric clinic of Hebei General Hospital between January 2017 and January 2022, as the study participants. We comprehensively assessed their cognitive functions using the Gesell development schedule or Wechsler Intelligence Scales. The participants were divided into the study group (n = 123) with cognitive impairment and the control group (n = 171) with normal cognitive functions, for analysis. RESULTS: There were statistically significant differences between the two groups in disease course, frequency of epilepsy, status epilepticus, and the number of antiseizure medications (ASMs) used (P < 0.05), while there were no statistically significant differences in age, gender, age of onset, form of onset, interictal epileptiform discharge, history of febrile convulsion, and the time from onset to initial visit (P > 0.05). Based on multivariate logistic regression analysis, the course of disease, frequency of onset, status epilepticus and number of ASMs used were identified as high-risk factors for cognitive impairment in children with epilepsy. Similarly, early onset, long course of disease, known etiology, and combination of multiple drugs have a negative impact on behavioral problems, school education, and social adaptability. CONCLUSION: The course of disease, the frequency of onset, status epilepticus, and the number of ASMs used are high-risk factors for cognitive impairment in children with epilepsy, which can be prevented and controlled early. When selecting ASMs, their advantages and disadvantages should be weighed. Moreover, the availability of alternative treatment options must be considered. With the help of genomic technology, the causes of epilepsy should be identified as early as possible, and precision medicine and gene therapy for children with epilepsy should be actively developed.

Fatty acid metabolism-related lncRNA prognostic signature for serous ovarian carcinoma.

Background: To explore the role of fatty acid metabolism (FAM)-related lncRNAs in the prognosis and antitumor immunity of serous ovarian cancer (SOC). Materials & methods: A SOC FAM-related lncRNA risk model was developed and evaluated by a series of analyses. Additional immune-related analyses were performed to further assess the associations between immune state, tumor microenvironment and the prognostic risk model. Results: Five lncRNAs associated with the FAM genes were found and used to create a predictive risk model. The patients with a low-risk profile exhibited favorable prognostic outcomes. Conclusion: The established prognostic risk model exhibits better predictive capabilities for the prognosis of patients with SOC and offers novel potential therapy targets for SOC.

A Five-gene Signature Based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma.

AIMS: We aimed to classify molecular subtypes and establish a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in Stomach adenocarcinoma (STAD). BACKGROUND: STAD is a common diagnosed gastrointestinal malignancy and its heterogeneity is a big challenge that influences prognosis and precision therapies. Present study was designed to classify molecular subtypes and construct a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in STAD. OBJECTIVE: The objective of this study is to investigate the molecular subtypes and prognostic model for STAD. METHODS: A STAD specific miRNA-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network was generated using the RNA-Seq and miRNA expression profiles from The Cancer Genome Atlas (TCGA) database, in which miRNA-related mRNAs were screened. Molecular subtypes were then determined using miRNA-related genes. Through univariate Cox analysis and multivariate regression analysis, a prognostic model was established in GSE84437 Train dataset and validated in GSE84437 Test, TCGA, GSE84437 and GSE66229 datasets. Immunotherapy datasets were employed for assessing the performance of the risk model. Finally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to validate the expression of hub genes used for the risk score signature. RESULTS: We constructed a ceRNA network containing 84 miRNAs and 907 mRNAs and determined two molecular subtypes based on 26 genes from the intersection of TCGASTAD and GSE84437 datasets. Subtype S2 had poor prognosis, lower tumor mutational burden, higher immune score and lower response to immunotherapy. Subtype S1 was more sensitive to Sorafenib, Pyrimethamine, Salubrinal, Gemcitabine, Vinorelbine and AKT inhibitor VIII. Next, a five-gene signature was generated and its robustness was validated in Test and external datasets. This risk model also had a good prediction performance in immunotherapy datasets. CONCLUSION: This study promotes the underlying mechanisms of miRNA-based genes in STAD and offers directions for classification. A five-gene signature accurately predicts the prognosis and helps therapeutic options.

Targeted phytogenic compounds against Vibrio parahaemolyticus biofilms.

As one of main culprit of seafood-associated human illness, Vibrio parahaemolyticus can readily accumulate on biotic or abiotic surfaces to form biofilms in the seafood processing environment. Biofilm formation on various surfaces can provide a protective barrier for viable bacterial cells that are resistant to most traditional bacteriostatic measures. This underscores the necessity and urgency of developing effective alternative strategies to control V. parahaemolyticus biofilms. Plants have always provided an extensive and infinite source of biologically active compounds for "green" antibiofilm agents. This review summarizes recent developments in promising multitargeted phytogenic compounds against V. parahaemolyticus biofilms. This review provides valuable insights into potential research targets that can be pursued further to identify potent natural antibiofilm agents in the food industry.

Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis.

OBJECTIVE: Metastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered. DESIGN: We performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). We also conducted immunofluorescence staining and functional experiments to examine the mechanism. RESULTS: Integrative analyses of epithelial cells reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O (PTPRO) and achaete scute-like 2 (ASCL2) expression as the metastatic culprit. This cell cluster comprising distinct subpopulations shows distinct liver or ovary metastatic preference. Population 1 (P1) cells with high delta-like ligand 4 (DLL4) and MAF bZIP transcription factor A (MAFA) expression are enriched in primary CRC and oCRC, thus may be associated with ovarian metastasis. P3 cells having a similar expression pattern as cholangiocytes are found mainly in primary CRC and lCRC, presuming to be likely the culprits that specifically metastasise to the liver. Stem-like cells interacted with cancer-associated fibroblasts and endothelial cells via the DLL4-NOTCH signalling pathway to metastasise from primary CRC to the ovary. In the oCRC microenvironment, myofibroblasts provide cancer cells with glutamine and perform a metabolic reprogramming, which may be essential for cancer cells to localise and develop in the ovary. CONCLUSION: We uncover a mechanism for organ-specific CRC metastasis.

Effecting mechanisms of iron-rich sludge on ash fusion characteristics of coal with high ash fusion temperature under reducing atmosphere.

Co-gasification is crucial for large-scale clean conversion of coal and sludge. In this study, the effects of municipal sewage sludge (MSS, Fe2O3:48.11 %) and pharmaceutical sewage sludge (PSS, Fe2O3: 67.80 %) on ash fusion temperature (AFT) of high AFT Xiangyuan coal (XY) were explored using an AFT analysis, X-ray fluorescence spectrometry, X-ray diffraction, scanning electronic microscopy, and thermodynamics FactSage calculation. The results showed that when MSS or PSS ash mass ratios reached 20 % or 16 % (for XY mixtures, the mass ratio of MSS or PSS should be >5.81 wt% or 5.07 wt%), respectively, the AFT met the requirement of liquid-slag discharge for entrained-flow bed gasification. Under a reducing atmosphere (6:4, CO/CO2, volume ratio), Fe2+ destroyed the bridging-oxygen bonds in the network structure and generated low melting-point (MP) hercynite (FeAl2O4). This resulted in the AFT decreases in the XY mixtures with the additions of PSS or MSS. Meanwhile, the high calcium content (CaO: 13.40 %) easily reacted with Al2O3 and SiO2 and formed anorthite (CaAl2SiO8), which inhibited high-MP mullite formation and decreased the mixed XY AFT. With the increasing SS mass ratio, the surface of the ash sample and thermodynamic FactSage calculation were in good agreement with the experimental results.

Current Situation and Prospect of Adoptive Cellular Immunotherapy for Malignancies.

Adoptive cell immunotherapy (ACT) is an innovative promising treatment for tumors. ACT is characterized by the infusion of active anti-tumor immune cells (specific and non-specific) into patients to kill tumor cells either directly or indirectly by stimulating the body's immune system. The patient's (autologous) or a donor's (allogeneic) immune cells are used to improve immune function. Chimeric antigen receptor (CAR) T cells (CAR-T) is a type of ACT that has gained attention. T cells from the peripheral blood are genetically engineered to express CARs that rapidly proliferate and specifically recognize target antigens to exert its anti-tumor effects. Clinical application of CAR-T therapy for hematological tumors has shown good results, but adverse reactions and recurrence limit its applicability. Tumor infiltrating lymphocyte (TIL) therapy is effective for solid tumors. TIL therapy exhibits T cell receptor (TCR) clonality, superior tumor homing ability, and low targeted toxicity, but its successful application is limited to a number of tumors. Regardless, TIL and CAR-T therapies are effective for treating cancer. Additionally, CAR-natural killer (NK), CAR-macrophages (M), and TCR-T therapies are currently being researched. In this review, we highlight the current developments and limitations of several types of ACT.

The prevalence rate, mortality, and 5-year overall survival of Schistosoma japonicum patients with human malignancy.

Background: Only a few studies have focused on the association between Schistosoma japonicum and human malignancy. The aim of this study was to update the prevalence rate, mortality, and 5-year overall survival of S. japonicum patients with human malignancy. Methods: From January 20, 2018, to January 31, 2021, 5,866 inpatients were included in the study. A total of 656 S. japonicum patients with malignancy were identified. Cases were stratified by gender and age groups. The cancer sites, prevalence rate, mortality, and 5-year overall survival of the patients were reported. The S. japonicum patients with malignancy were further divided into a non-digestive system tumor group (n = 309) and a digestive system tumor group (n = 347), including those with cancer in the esophagus, stomach, colon, rectum, liver, gallbladder, bile duct, or pancreas. Chi-squared test and odds ratio with confidence intervals were performed between these two groups. Results: Lung cancer was found the most common malignancy, accounting for 18.6% of all malignancies, followed by colorectal, stomach, liver, and gallbladder cancers. These five leading malignancies accounted for approximately 61.8% of all cases. Colorectal cancer was the leading cause of malignancy death, followed by lung, stomach, gallbladder, and liver cancers. These five leading causes of death accounted for approximately 55.6% of all death cases. Statistical significance was found in the prevalence rate between S. japonicum and non-S. japonicum patients with/without digestive system tumor (p < 0.001). The odds ratio of S. japonicum patients with digestive system tumors was 1.6 (95%CI: 1.4-1.9). Conclusion: S. japonicum contributes to a significant prevalence and mortality in digestive system tumors, including colorectal, stomach, liver, and gallbladder cancers.

Pathogen evolution, prevention/control strategy and clinical features of COVID-19: experiences from China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported at the end of 2019 as a worldwide health concern causing a pandemic of unusual viral pneumonia and many other organ damages, which was defined by the World Health Organization as coronavirus disease 2019 (COVID-19). The pandemic is considered a significant threat to global public health till now. In this review, we have summarized the lessons learnt during the emergence and spread of SARS-CoV-2, including its prototype and variants. The overall clinical features of variants of concern (VOC), heterogeneity in the clinical manifestations, radiology and pathology of COVID-19 patients are also discussed, along with advances in therapeutic agents.

A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections.

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir (Paxlovid) therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30, 2022, were recruited. Laboratory parameters and chest CT (computed tomography) imaging were analyzed. The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days, whereas the control group included seven patients who received basic treatment. No serious adverse reactions or safety events were recorded. Four control patients progressed to moderate disease, and none in the treatment group showed progression of chest CT findings (P < 0.05). Paxlovid therapy tended toward early viral clearance and low viral load on Day 8. Moreover, 83.3% of the patients in the treatment group and 57.1% of the patients in the control group turned negative within 22 days. In the Paxlovid treatment group, we found significantly increased levels of lymphocytes (P=0.03) and eosinophils (P=0.02) and decreased levels of D-dimer on Day 8 compared with those on Day 1. Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients. The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

A C1qTNF3 collagen domain fusion chaperones diverse secreted proteins and anti-Aß scFvs: Applications for gene therapies.

Enhancing production of protein cargoes delivered by gene therapies can improve efficacy by reducing the amount of vector or simply increasing transgene expression levels. We explored the utility of a 126-amino acid collagen domain (CD) derived from the C1qTNF3 protein as a fusion partner to chaperone secreted proteins, extracellular "decoy receptor" domains, and single-chain variable fragments (scFvs). Fusions to the CD domain result in multimerization and enhanced levels of secretion of numerous fusion proteins while maintaining functionality. Efficient creation of bifunctional proteins using the CD domain is also demonstrated. Recombinant adeno-associated viral vector delivery of the CD with a signal peptide resulted in high-level expression with minimal biological impact as assessed by whole-brain transcriptomics. As a proof-of-concept in vivo study, we evaluated three different anti-amyloid Aß scFvs (anti-Aß scFvs), alone or expressed as CD fusions, following viral delivery to neonatal CRND8 mice. The CD fusion increased half-life, expression levels, and improved efficacy for amyloid lowering of a weaker binding anti-Aß scFv. These studies validate the potential utility of this small CD as a fusion partner for secretory cargoes delivered by gene therapy and demonstrate that it is feasible to use this CD fusion to create biotherapeutic molecules with enhanced avidity or bifunctionality.

Transition metal doped WSi2N4monolayer for water splitting electrocatalysts: a first-principles study.

High-performance water splitting electrocatalysts are urgently needed in the face of the environmental degradation and energy crisis. The first principles method was used in this study to systematically examine the electronic characteristics of transition metal (Sc, Ti, V, Cr, Mn, Fe, and Ru) doped WSi2N4(TM@WSi2N4) and its potential as oxygen evolution reaction (OER) catalysts. Our study shows that the doping of TM atoms significantly improves the catalytic performance of TM@WSi2N4, especially Fe@WSi2N4shows a low overpotential (ηOER= 470 mV). Interestingly, we found that integrated-crystal orbital Hamilton population and d-band center can be used as descriptors to explain the high catalytic activity of Fe@WSi2N4. Subsequently, Fe@WSi2N4exhibits the best hydrogen evolution reaction (HER) activity with a universal overpotential of 47 mV on N1sites. According to our research, Fe@WSi2N4offers a promising substitute for precious metals as a catalyst for overall water splitting with low OER and HER overpotentials.

Penta-MP5 (M = B, Al, Ga, In) monolayers as high-performance photocatalysts for overall water splitting.

Two-dimensional (2D) phosphorus-rich phosphides generally preserve the excellent electronic properties of phosphorene, making them promising photocatalysts for water splitting. Despite tremendous efforts in the search for potential photocatalysts in 2D phosphides, few known 2D phosphides fully meet the requirements for photocatalytic water splitting. Herein, we systemically investigate a set of penta-MP5 (M = B, Al, Ga, and In) monolayers by first-principles calculations and identify them as potential photocatalysts for water splitting. These penta-MP5 monolayers are found to feature favorable bandgaps of about 2.70 eV with appropriate band edge positions, a high carrier mobility of 1 × 104 cm-2 V-1 s-1, an excellent optical absorption coefficient (OAC) of 1 × 105 cm-1, and a good solar-to-hydrogen (STH) efficiency of 8%. Meanwhile, free energy calculations indicate that these penta-MP5 monolayers present both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) photocatalytic activities under light conditions. All these excellent properties demonstrate that penta-MP5 monolayers are suitable candidates as photocatalysts for promising applications in overall water splitting.

The interaction of ammonia and manganese in abnormal metabolism of minimal hepatic encephalopathy: A comparison metabolomics study.

This study was to investigate the effects of ammonia and manganese in the metabolism of minimal hepatic encephalopathy (MHE). A total of 32 Sprague-Dawley rats were divided into four subgroups: chronic hyperammonemia (CHA), chronic hypermanganese (CHM), MHE and control group (CON). 1H-NMR-based metabolomics was used to detect the metabolic changes. Sparse projection to latent structures discriminant analysis was used for identifying and comparing the key metabolites. Significant elevated blood ammonia were shown in the CHA, CHM, and MHE rats. Significant elevated brain manganese (Mn) were shown in the CHM, and MHE rats, but not in the CHA rats. The concentrations of γ-amino butyric acid (GABA), lactate, alanine, glutamate, glutamine, threonine, and phosphocholine were significantly increased, and that of myo-inositol, taurine, leucine, isoleucine, arginine, and citrulline were significantly decreased in the MHE rats. Of all these 13 key metabolites, 10 of them were affected by ammonia (including lactate, alanine, glutamate, glutamine, myo-inositol, taurine, leucine, isoleucine, arginine, and citrulline) and 5 of them were affected by manganese (including GABA, lactate, myo-inositol, taurine, and leucine). Enrichment analysis indicated that abnormal metabolism of glutamine and TCA circle in MHE might be affected by the ammonia, and abnormal metabolism of GABA might be affected by the Mn, and abnormal metabolism of glycolysis and branched chain amino acids metabolism might be affected by both ammonia and Mn. Both ammonia and Mn play roles in the abnormal metabolism of MHE. Chronic hypermanganese could lead to elevated blood ammonia. However, chronic hyperammonemia could not lead to brain Mn deposition.

The Effect of MSTN Mutation on Bile Acid Metabolism and Lipid Metabolism in Cattle.

Myostatin (MSTN) is a negative regulator of skeletal muscle genesis during development. MSTN mutation leads to increased lean meat production and reduced fat deposition in livestock. However, the mechanism by which MSTN promotes myogenesis by regulating metabolism is not clear. In this study, we compared the metabolomics of the livers of wild-type (WT) and MSTN mutation cattle (MT), and found changes in the content and proportion of fatty acids and bile acids in MT cattle. The differential metabolites were enriched in sterol synthesis and primary bile acid synthesis. We further analyzed the expression of genes involved in the regulation of lipid and bile acid metabolism, and found that the loss of MSTN may alter lipid synthesis and bile acid metabolism. This study provides new basic data for MSTN mutations in beef cattle breeding.

Serum neutralization of SARS-CoV-2 Omicron BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1 and XBB.1.5 in individuals receiving Evusheld.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is undergoing continuous evolution and convergent mutation. These new subvariants are raising concerns that they may evade neutralizing monoclonal antibodies (mAbs). We investigated the serum neutralization efficacy of Evusheld (cilgavimab and tixagevimab) against SARS-CoV-2 Omicron BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1, and XBB.1.5. A total of 90 serum samples from healthy individuals were collected in Shanghai. Anti-RBD antibodies were measured and symptoms of infection with COVID-19 were compared among those individuals. The neutralizing activity of serum against Omicron variants was analyzed by pseudovirus neutralization assays in 22 samples. Evusheld retained neutralizing activity against BA.2, BA.2.75, and BA.5, albeit with somewhat reduced titers. However, the neutralizing activity of Evusheld against BA.2.76, BF.7, BQ.1.1, and XBB.1.5 significantly decreased, with XBB.1.5 showing the greatest escape activity among the subvariants. We also observed that Evusheld recipients displayed elevated antibody levels in their serum, which efficiently neutralized the original variant, and exhibited different characteristics of infection than those who did not receive Evusheld. The mAb has partial neutralization activity against Omicron sublineages. However, the increasing doses of mAb and a larger size of population should be further investigated.

Dual-duty NiCo2S4 nanosheet-based solar rechargeable batteries toward multi-scene solar energy conversion and storage.

Solar energy has the potential to be the next-generation power source if the intermittent nature can be overcome via rational energy storage engineering. The competitiveness of solar rechargeable batteries can be further enhanced if the demand for multiple energy storage scenarios can be met within one device. Moreover, active electrochemical materials with different energy storage types are the critical component of this energy storage system. In this work, dual-duty electrochemical functional materials were introduced to guide multi-scene solar energy storage device design and fabrication. Furthermore, dual-duty NiCo2S4 nanosheets were prepared and applied to solar rechargeable batteries. A photo-assisted aqueous polysulfide/iodide flow battery was designed and fabricated with a charging voltage as low as 0.05 V, showing the good electrocatalytic performance of NiCo2S4 nanosheets for aqueous redox couples. Moreover, the low charging voltage leads to 93.5% of input electric energy saving under one sun illumination (AM 1.5, 100 mW cm-2). On the other hand is the photo-assisted sodium-ion battery with a NiCo2S4 anode, showing a remarkably low charging voltage of 0.67 V and a high discharge medium voltage of 1.05 V. The battery can save about 67.6% of input electric energy under 1 sun illumination.

PD1hi CD200hi CD4+ exhausted T cell increase immunotherapy resistance and tumour progression by promoting epithelial-mesenchymal transition in bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is one of the most diagnosed cancers in humans worldwide. Recently, immunotherapy has become a main treatment option for BC. However, most BLCA patients do not respond to immune checkpoint inhibitors or relapse after immunotherapy. Therefore, it is very important to identify novel biomarkers for the prediction of immunotherapy response in B patients. METHODS: Pancancer single-cell RNA sequencing (scRNA-seq) data were used to identify the clusters of CD4+ T cells in the tumour microenvironment (TME). The clinical significance of key CD4+ T-cell clusters was evaluated based on the survival data of two independent immunotherapy bladder cancer (BLCA) cohorts. We also investigated the function of key clusters of CD4+ T cell in the TME of BC cells in vitro. RESULTS: This study identified two novel exhausted CD4+ T-cell subpopulations with the expression of PD1hi CD200hi or PD1hi CD200low in BC patients. Moreover, BLCA patients with a high level of PD1hi CD200hi CD4+ exhausted T cell showed immunotherapy resistance. Cell function analysis demonstrated that PD1hi CD200hi CD4+ exhausted T cell can promote epithelial-mesenchymal transition (EMT) and angiogenesis in BLCA cells. In addition, PD1hi CD200hi CD4+ exhausted T cells were shown to communicate with malignant BLCA cells through the GAS6-AXL axis. Finally, we also found that GAS6 expression is upregulated in B cells by METTL3-mediated m6A modification. CONCLUSIONS: PD1hi CD200hi CD4+ exhausted T cell may serve as a novel biomarker for poor prognosis and immunotherapy resistance in B. Targeted inhibitors of PD1hi CD200hi CD4+ exhausted T cells may help improve the efficacy of immunotherapy.