The expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) has been observed in various epithelial-originated malignancies. However, whether the expression of PD-L1 on tumor cells or the expression of PD-1 on tumor-infiltrating lymphocytes (TILs) is associated with patients' survival remains controversial.Electronic databases were searched for eligible literatures. Data of hazard ratio (HR) for overall survival (OS) with 95% confidence interval (CI) according to the expression status of PD-L1 or PD-1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on random-effects model. Subgroup analyses were proposed.Twenty-nine studies covering 12 types of epithelial-originated malignancies involving 7319 patients (2030/3641 cases for PD-L1 positive/negative, 505/1143 cases for PD-1 positive/negative) with available data of the outcome stratified by PD-L1/PD-1 status were enrolled. Epithelial-originated cancer patients with positive expression of PD-L1 on tumor tissues were associated with significantly poorer OS when compared to those with negative expression of PD-L1 (HR 1.81, 95% CI 1.33-2.46, P < 0.001). Similarly, patients with PD-1 positive expression on TILs had significantly shorter OS than the PD-1 negative group (HR 2.53, 95% CI 1.22-5.21, P = 0.012). In analyses of PD-L1, all subgroups showed consistent trends toward unfavorable prognoses of patients with positive PD-L1 expression, regardless of antibodies and evaluation cutoffs. Subgroup analyses on PD-1 were not available due to limited data.PD-L1 or PD-1 expression status is a significant prognostic factor in epithelial-originated malignancies.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder defined by recurrent thoughts, intrusive and distressing impulses, or images and ritualistic behaviors. Although focal diverse regional abnormalities white matter integrity in specific brain regions have been widely studied in populations with OCD, alterations in the structural connectivities among them remain poorly understood.

The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source of tumor-derived DNA for mutation profiling. In this study, we investigated the potential of MPE supernatant as a liquid biopsy specimen by comparing its mutation profile with that of matched MPE cell pellets, tissue, and plasma samples.

It was reported that long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is involved in hepatocellular carcinoma (HCC). However, the underlying mechanism of tumorigenesis is still largely unclear. Here, we found that NEAT1 is remarkably upregulated in HCC tissues and cell lines. Overexpression of NEAT1 notably accelerated HCC cell proliferation, migration, and invasion. Knockdown of NEAT1 significantly inhibited HCC cell proliferation, migration and invasion. MiR-384 expression was lower in HCC tissues and cell lines than adjacent nontumor tissues and L02 cell. MiR-384 exhibited the functions of tumor-suppressive. The expression of miR-384 was negatively correlated with the expression of NEAT1. Overexpression of NEAT1 reduced miR-384 expression, whereas inhibition of miR-384 led to a distinct upregulation of NEAT1 expression. In addition, we provided evidence that miR-384 was directly bound to the sequence of NEAT1 by luciferase reporter and RNA-binding protein immunoprecipitation assays. Overexpression of miR-384 inhibited NEAT1 function. Thus, we demonstrated that NEAT1 promotes the malignant biological properties of hepatocellular carcinoma by negatively regulating miR-384.

Chronic hyperglycemia leads to myosin light chain kinase (MLCK) upregulation and induces neuronal damage. However, the underlying molecular mechanism of neuronal damage in hyperglycemia has not yet been fully elucidated. In the present study, hippocampal neuronal cells were cultured and treated with a high glucose concentration (45 mmol/l). The results demonstrated that high glucose induced shrinking of the synapses, nuclear shape irregularity and microfilament damage. Filamentous actin (F‑actin) filaments were rearranged, cell apoptosis rate was increased and the protein expression of MLCK and phosphorylated (p)‑MLC was upregulated. The MLCK inhibitor ML‑7 largely reversed the alterations in the microfilament cytoskeleton, inhibited F‑actin depolymerization, reduced apoptosis and downregulated MLCK and p‑MLC protein expression. Overall, these results indicated that high glucose upregulated MLCK to promote F‑actin depolymerization, which induced microfilament cytoskeleton rearrangement in hippocampal neuronal cells.

As a toxic element, excessive amounts of fluoride in environment can be harmful because of its antimicrobial activity, however little is known about the relationship between fluoride and the bacterial community in groundwater systems. Here, we use samples from a typical fluorosis area to test the hypothesis that fluoride concentration is a fundamental structuring factor for bacterial communities in groundwater. Thirteen groundwater samples were collected; high-throughput 16S rRNA gene sequencing and statistical analysis were conducted to compare the bacterial community composition in individual wells. The results showed that Proteobacteria, with most relative abundance in groundwater, decreased along the groundwater fluoride concentration. Additionally, relative abundances of 12 families were also statistically correlated with fluoride concentration. The bacterial community was significantly explained by TOC (P = 0.045) and fluoride concentration (P = 0.007) of groundwater. This suggests that fluoride and TOC likely plays an important role in shaping the microbial community structure in these groundwater systems. Our research suggest that fluoride concentration should be taken into consideration in future when evaluating microbial response to environmental conditions in groundwater system, especially for fluoride rich groundwater.

To compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC).

We tested the hypothesis that, similar to humans and rodents, exercise training would enhance mitochondrial (Mt) biogenesis and function in skeletal muscle of young horses. Twenty-four Quarter Horse yearlings were randomly assigned to either submaximal exercise training or no forced exercise (untrained). Biopsies were collected from the gluteus medius and triceps brachii before and after 9 wk of treatment. Citrate synthase activity was lower (P < 0.0001) and cytochrome c oxidase activity per Mt unit was higher (P < 0.0001) in gluteus compared to triceps, but neither changed over the trial period. From wk 0 to 9, intrinsic Mt respiration (P CI , P CI+II ; P = 0.008) and electron transport capacity (E CI+II ; P = 0.01) increased, and LEAK-related flux control factor (FCFL; P = 0.02) decreased in both muscles. After 9 wk of training, gluteus muscle exhibited higher (P < 0.05) intrinsic P CI , P CI+II , E CI+II , and FCFCI and FCF CI+II , and lower FCFL (P = 0.0002). Mitochondrial content did not change from wk 0 to 9, and also not in response to submaximal exercise training. Improvements in Mt function were most directly related to ongoing growth of horses independent of muscle group, and training further enhanced Mt function in the gluteus medius.

Leucine-rich repeats receptor-like kinases (LRR-RLKs) play important roles in plant growth and development as well as stress responses. Here, 56 LRR-RLK genes were identified in the Antarctic moss Pohlia nutans transcriptome, which were further classified into 11 subgroups based on their extracellular domain. Of them, PnLRR-RLK27 belongs to the LRR II subgroup and its expression was significantly induced by abiotic stresses. Subcellular localization analysis showed that PnLRR-RLK27 was a plasma membrane protein. The overexpression of PnLRR-RLK27 in Physcomitrella significantly enhanced the salinity and ABA tolerance in their gametophyte growth. Similarly, PnLRR-RLK27 heterologous expression in Arabidopsis increased the salinity and ABA tolerance in their seed germination and early root growth as well as the tolerance to oxidative stress. PnLRR-RLK27 overproduction in these transgenic plants increased the expression of salt stress/ABA-related genes. Furthermore, PnLRR-RLK27 increased the activities of reactive oxygen species (ROS) scavengers and reduced the levels of malondialdehyde (MDA) and ROS. Taken together, these results suggested that PnLRR-RLK27 as a signaling regulator confer abiotic stress response associated with the regulation of the stress- and ABA-mediated signaling network.

RHPN2, a member of rhophilin family of rho-binding proteins, regulates actin cytoskeleton and vesicular trafficking, and promotes mesenchymal transformation in cancer. We have found that RHPN2 was significantly mutated in lung adenocarcinoma (LUAD). However, the role of RHPN2 in lung cancer is not fully understood.

This study aimed to assess the psychological impact of the COVID-19 pandemic among the general public in Hunan Province, China, which could help develop psychological interventions and mental health programs.

A combination of programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non-small-cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta-analysis to summarize the related research.

Previous studies have shown that inhibition of inducible NO synthase (NOS2 or iNOS) with an inhibitor can selectively protect several normal tissues against radiation during radiotherapy. However, the role of NOS2 in ionizing radiation (IR)-induced bone marrow (BM) suppression is unknown and thus was investigated in the present study using NOS2-/- and wild-type mice 14 days after they were exposed to a sublethal dose of total body irradiation (TBI).

With the revolutionary progress of immune checkpoint inhibitors (ICIs) achieved in non-small cell lung cancers (NSCLC), identifying patients benefiting from ICIs becomes critical and urgent. The associations of genomic alterations in protein tyrosine phosphatase receptor-type (PTPRs) and ICIs responses are unknown.

Owing to metastases and drug resistance, the prognosis of breast cancer is still dismal. Therefore, it is necessary to find new prognostic markers to improve the efficacy of breast cancer treatment. Literature shows a controversy between moesin (MSN) expression and prognosis in breast cancer. Here, we aimed to conduct a systematic review and meta-analysis to evaluate the prognostic relationship between MSN and breast cancer. Literature retrieval was conducted in the following databases: PubMed, Web of Science, Embase, and Cochrane. Two reviewers independently performed the screening of studies and data extraction. The Gene Expression Omnibus (GEO) database including both breast cancer gene expression and follow-up datasets was selected to verify literature results. The R software was employed for the meta-analysis. A total of 9 articles with 3,039 patients and 16 datasets with 2,916 patients were ultimately included. Results indicated that there was a significant relationship between MSN and lymph node metastases (P < 0.05), and high MSN expression was associated with poor outcome of breast cancer patients (HR = 1.99; 95% CI 1.73-2.24). In summary, there is available evidence to support that high MSN expression has valuable importance for the poor prognosis in breast cancer patients.

Oral-facial-digital syndrome (OFDS) is a multisystemic ciliopathic disorder with an autosomal recessive mode of inheritance. OFDS usually manifests with typical craniofacial anomalies and variable occurrence of polydactyly. Germline variants in CPLANE1 cause OFDS VI. In this study, we investigated a 26-year-old Chinese female patient who was 23+1  weeks pregnant. She had a history of adverse pregnancy outcomes with multiple foetal malformations. We performed ultrasonography and identified the foetus as having a posterior fossa Blake cyst and postaxial polydactyly. The patient decided to terminate her pregnancy, and further genetic molecular analysis was performed. We identified the aborted foetus as having postaxial polydactyly. Whole-exome sequencing identified a missense variant (c.3599C>T, p.A1200V) in exon 20 and a c.834+1G>T variant in exon 7 of CPLANE1 (NM_023073.3) in the foetus. Sanger sequencing confirmed that these variants came from the parents of the foetus. In this study, we investigated a family with OFDS VI through genetic testing and bioinformatics analysis, which provided powerful help for prenatal diagnosis. Then, we demonstrated that the cell migration rate and the number of cilia were decreased after interference with CPLANE1 expression in NIH/3T3 cells. After CPLANE1 knockdown, the Hh signalling pathway was inhibited, and the Hh pathway activator SAG reversed the inhibitory effect. This is the first report of a family with OFDS VI in the Chinese population.

Renal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC.

Dysregulated immune response plays a pivotal role in Ulcerative colitis. In lamina propria of inflammatory colonic mucosa, macrophages tend to polarize into M1 type and metabolically reprogram to aerobic glycolysis. PKM2 orchestrates glucose metabolic switch in macrophages, which tetramer has high pyruvate kinase activity, while which dimer mainly works as a protein kinase to stabilize HIF-1α and mediate anabolism. Shikonin is a potent PKM2 inhibitor derived from traditional Chinese medicine Arnebiae Radix with anti-inflammatory and anticarcinogen activities. However, it is unclear which conformation of PKM2 is inhibited by Shikonin, and whether this inhibition mediates pharmacological effect of Shikonin. In this study, we examined the efficacy of Shikonin on dextran sulfate sodium-induced mice colitis and determined the states of PKM2 aggregation after Shikonin treatment. Results showed that Shikonin dose-dependently alleviated mice colitis, down-regulated expression of F4/80, iNOS and CD86, decreased IFN-γ, IL-1β, IL-6 and TNF-α, while increased IL-10 in mice colon. Furthermore, Shikonin suppressed the pyruvate, lactate production and glucose consumption, inhibited the pyruvate kinase activity and nuclear translocation of PKM2, and decreased both dimerization and tetramerization of PKM2 in macrophages. In vitro assay revealed that Shikonin bounded to PKM2 protein, inhibited the formation of both dimer and tetramer, while promoted aggregation of PKM2 macromolecular polymer. TEPP-46, an activator of PKM2 tetramerization, attenuated the ameliorative effect of Shikonin on disuccinimidyl suberate mice. In summary, Shikonin improved mice colitis, which mechanism may be mediated by inhibiting dimerization and tetramerization of PKM2, suppressing aerobic glycolysis reprogram, improving mitochondrial dynamic, and therefore alleviating inflammatory response of macrophages.

Cancer vaccine, which can promote tumor-specific immunostimulation, is one of the most important immunotherapeutic strategies and holds tremendous potential for cancer treatment/prevention. Here, we prepare a series of nanoparticles composed of doxorubicin- and tyrosine kinase inhibitor-loaded and hyaluronic acid-coated dendritic polymers (termed HDDT nanoparticles) and find that the HDDT nanoparticles can convert various cancer cells to micrometer-sized vesicles (1.6-3.2 μm; termed HMVs) with ~100% cell-to-HMV conversion efficiency. We confirm in two tumor-bearing mouse models that the nanoparticles can restrain tumor growth, induce robust immunogenic cell death, and convert the primary tumor into an antigen depot by producing HMVs in situ to serve as personalized vaccines for cancer immunotherapy. Furthermore, the HDDT-healed mice show a strong immune memory effect and the HDDT treatment can realize long-term protection against tumor rechallenge. Collectively, the present work provides a general strategy for the preparation of tumor-associated antigen-containing vesicles and the development of personalized cancer vaccines.

Inadvertent oral ingestion is an important exposure pathway of arsenic (As) containing soil and dust. Previous researches evidenced health risk of bioaccessible As from soil and dust, but it is unclear about As mobilization mechanisms in health implications from As exposure. In this study, we investigated As release behaviors and the solid-liquid interface reactions toward As(V)-containing iron minerals in simulated gastrointestinal bio-fluids. The maximum As release amount was 0.57 mg/L from As-containing goethite and 0.82 mg/L from As-containing hematite at 9 h, and the As bioaccessibility was 10.8% and 21.6%, respectively. The higher exposure risk from hematite-sorbed As in gastrointestinal fluid was found even though goethite initially contained more arsenate than hematite. Mechanism analysis revealed that As release was mainly coupled with acid dissolution and reductive dissolution of iron minerals. Proteases enhanced As mobilization and thus increased As bioaccessibility. The As(V) released and simultaneously transformed to high toxic As(III) by gastric pepsin, while As(V) reduction in intestine was triggered by pancreatin and freshly formed Fe(II) in gastric digests. CaCl2 reduced As bioaccessibility, indicating that calcium-rich food or drugs may be effective dietary strategies to reduce As toxicity. The results deepened our understanding of the As release mechanisms associated with iron minerals in the simulated gastrointestinal tract and supplied a dietary strategy to alleviate the health risk of incidental As intake.