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Purpose: Atropine, a non-selective muscarinic antagonist, effectively slows down myopia progression in human adolescents and several animal models. However, the underlying molecular mechanism is unclear. The current study investigated retinal protein changes of form-deprived myopic (FDM) guinea pigs in response to topical administration of 1% atropine gel (10 g/L).Methods: At the first stage, the differentially expressed proteins were screened using fractionated isobaric tags for a relative and absolute quantification (iTRAQ) approach, coupled with nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) (n = 24, 48 eyes) using a sample pooling technique. At the second stage, retinal tissues from another cohort with the same treatment (n = 12, 24 eyes) with significant ocular changes were subjected to label-free sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics for orthogonal protein target confirmation. The localization of Alpha-synuclein was verified using immunohistochemistry and confocal imaging.Results: A total of 1,695 proteins (8,875 peptides) were identified with 479 regulated proteins (FC ≥ 1.5 or ≤0.67) found from FDM eyes and atropine-treated eyes receiving 4-weeks drug treatment using iTRAQ-MS proteomics. Combining the iTRAQ-MS and SWATH-MS datasets, a total of 29 confident proteins at 1% FDR were consistently quantified and matched, comprising 12 up-regulated and 17 down-regulated proteins which differed between FDM eyes and atropine treated eyes (iTRAQ: FC ≥ 1.5 or ≤0.67, SWATH: FC ≥ 1.4 or ≤0.71, p-value of ≤0.05). Bioinformatics analysis using IPA and STRING databases of these commonly regulated proteins revealed the involvement of the three commonly significant pathways: EIF2 signaling; glycolysis; and dopamine secretion. Additionally, the most significantly regulated proteins were closely connected to Alpha-synuclein (SNCA). Using immunostaining (n = 3), SNCA was further confirmed in the inner margin of the inner nuclear layer (INL) and spread throughout the inner plexiform layer (IPL) of the retina of guinea pigs.Conclusion: The molecular evidence using next-generation proteomics (NGP) revealed that retinal EIF2 signaling, glycolysis, and dopamine secretion through SNCA are implicated in atropine treatment of myopia in the FDM-induced guinea pig model.

Immunotherapy has transformed the management of hepatocellular carcinoma (HCC), but effectiveness varies among patients. This study aimed to identify biomarkers and HCC subtypes responsive to immunotherapy. Patients were classified into Immunity-High (Immunity-H) and Immunity-Low (Immunity-L) subtypes using ssGSEA scores. Prognostic genes were identified through Cox regression, and immune cell infiltration was quantified with TIMER 2.0. Brother of CDO (BOC) expression, analyzed via immunohistochemistry, correlated with immunotherapy responses. Flow cytometry assessed immune cell infiltration relative to BOC levels, while CCK-8 and transwell assays evaluated BOC overexpression’s effects on cell proliferation and invasiveness. Clinically, immunity-H patients had better survival outcomes. Three hub genes—BOC, V-Set and Transmembrane Domain Containing 1 (VSTM1), and PRDM12—were identified as significantly associated with prognosis. Among these, BOC and VSTM1 demonstrated positive correlations with immune cell infiltration. Elevated expression of BOC was found to be predictive of favorable responses to immunotherapy and was associated with enhanced infiltration of T cells, dendritic cells, and B cells in the tumor microenvironment. Conversely, BOC overexpression in liver cancer cell lines led to decreased cell proliferation and invasiveness. This study underscores the prognostic significance of HCC subtypes defined by immunogenomic profiles and identifies BOC as a potential biomarker for immunotherapy selection and outcome prediction.

Abstract Background Extrachromosomal circular DNAs (eccDNAs) exist in human blood and somatic cells, and are essential for oncogene plasticity and drug resistance. However, the presence and impact of eccDNAs in type 2 diabetes mellitus (T2DM) remains inadequately understood. Methods We purified and sequenced the serum eccDNAs obtained from newly diagnosed T2DM patients and normal control (NC) subjects using Circle-sequencing. We validated the level of a novel circulating eccDNA named sorbin and SH3‐domain‐ containing‐1circle97206791–97208025 (SORBS1circle) in 106 newly diagnosed T2DM patients. The relationship between eccDNA SORBS1circle and clinical data was analyzed. Furthermore, we explored the source and expression level of eccDNA SORBS1circle in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Results A total of 22,543 and 19,195 eccDNAs were found in serum samples obtained from newly diagnosed T2DM patients and NC subjects, respectively. The T2DM patients had a greater distribution of eccDNA on chromosomes 1, 14, 16, 17, 18, 19, 20 and X. Additionally, 598 serum eccDNAs were found to be upregulated, while 856 eccDNAs were downregulated in T2DM patients compared with NC subjects. KEGG analysis demonstrated that the genes carried by eccDNAs were mainly associated with insulin resistance. Moreover, it was validated that the eccDNA SORBS1circle was significantly increased in serum of newly diagnosed T2DM patients (106 T2DM patients vs. 40 NC subjects). The serum eccDNA SORBS1circle content was positively correlated with the levels of glycosylated hemoglobin A1C (HbA1C) and homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM patients. Intracellular eccDNA SORBS1circle expression was significantly enhanced in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Moreover, the upregulation of eccDNA SORBS1circle in the HG/PA-treated HepG2 cells was dependent on generation of apoptotic DNA fragmentation. Conclusions These results provide a preliminary understanding of the circulating eccDNA patterns at the early stage of T2DM and suggest that eccDNA SORBS1circle may be involved in the development of insulin resistance.

BackgroundThe tertiary lymphatic structure (TLS) is an important component of the tumor immune microenvironment and has important significance in patient prognosis and response to immune therapy. However, the underlying mechanism of TLS in soft tissue sarcoma remains unclear.MethodsA total of 256 RNAseq and 7 single-cell sequencing samples were collected from TCGA-SARC and GSE212527 cohorts. Based on published TLS-related gene sets, four TLS scores were established by GSVA algorithm. The immune cell infiltration was calculated via TIMER2.0 and “MCPcounter” algorithms. In addition, the univariate, LASSO, and multivariate-Cox analyses were used to select TLS-related and prognosis-significant hub genes. Single-cell sequencing dataset, clinical immunohistochemical, and cell experiments were utilized to validate the hub genes.ResultsIn this study, four TLS-related scores were identified, and the total-gene TLS score more accurately reflected the infiltration level of TLS in STS. We further established two hub genes (DUSP9 and TNFSF14) prognosis markers and risk scores associated with soft tissue sarcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8, CD19, and CD11c positive immune cell infiltration in the tumor tissue dedifferentiated liposarcoma patients was significantly higher than that of liposarcoma patients. Cytological experiments showed that soft tissue sarcoma cell lines overexpressing TNFSF14 could inhibit the proliferation and migration of sarcoma cells.ConclusionThis study systematically explored the TLS and related genes from the perspectives of bioinformatics, clinical features and cytology experiments. The total-gene TLS score, risk score and TNFSF14 hub gene may be useful biomarkers for predicting the prognosis and immunotherapy efficacy of soft tissue sarcoma.

AIM: To investigate time trends in myopia and high myopia prevalence over 6y among young university adults in China. METHODS: This is a 6-year series cross-sectional study from 2016 to 2021. Totally 4910 freshmen were enrolled and completed a questionnaire concerning age, gender, and disease history. Students with eye diseases were excluded after a detailed eye examination. The refractive status was measured by non-cycloplegic objective refraction and ocular parameters were measured by Lenstar 900. The examination followed the same protocol each year. Trends over time in myopia and high myopia prevalence, as well as ocular biometry parameters, were analyzed. RESULTS: From 2016 to 2021, the axial length (AL) and corneal radius (CR) increased significantly (P=0.002 for AL; P=0.04 for CR). However, the spherical equivalent (SE) and the ratio of axial length to the corneal radius (AL/CR) did not change significantly (P=0.59 for SE; P=0.24 for AL/CR). The frequency of AL ≥26.0 mm increased from 26.6% in 2016 to 29.3% in 2021 (P=0.05 for trend). The prevalence of myopia and high myopia did not change significantly in our study (P≥0.18). Compared to a similar cross-sectional study conducted 10 years ago, the prevalence of myopia decreased significantly (94.9% vs 91.8%, P

AIM: To analyze the 5-year disease-free survival (DFS) of primary orbital lymphoma (POL) by clinical characteristics and imaging features. METHODS: A total of 72 patients, 43 males and 29 females, with histologically confirmed POL, were retrospectively recruited between January 2012 and May 2017. The information on clinical characteristics, imaging features, and 5-year DFS was obtained. Univariate and multivariate forward logistic regression analyses were used to identify the variables significantly associated with 5-year DFS. Kaplan-Meier was applied for survival analysis. RESULTS: Univariate analysis revealed that uni- or bilateral orbital involvement, single or multiple lesions, treatment methods, and contrast enhancement pattern on images were significant for 5-year DFS (P=0.022, 0.042,

ABSTRACT: Objectives: Antibiotic therapy is widely used for patients with community-acquired pneumonia (CAP), and yet whether the efficacy of antibiotics differs based on the treatment mode remains unclear. This study aimed to summarize the evidence regarding the efficacy and safety of oral vs. parenteral administration of antibiotic therapy for the treatment of patients with CAP. Methods: The databases of PubMed, EmBase, and the Cochrane Central Register of Controlled Trials were systematically searched for eligible randomized controlled trials (RCTs) from inception until 11 December 2021. The effectiveness of oral vs. parenteral administration of antibiotic therapy was estimated using a random-effects model. Additional sensitivity, subgroup, and publication bias analyses were performed. Results: Of 912 identified articles, 12 RCTs involving 2158 patients with CAP were included in our pooled analysis. This mostly included trials with low certainty and some concerns regarding risk of bias, including lack of allocation concealment and blinding of participants and personnel. Overall, oral antibiotic therapy did not affect the incidence of clinical success at the end of treatment (relative risk [RR], 1.01; 95% confidence interval [CI], 0.98–1.05; P = 0.417), clinical success at follow-up (RR, 1.02; 95% CI, 0.98–1.06; P = 0.301), or adverse events (RR, 0.87; 95% CI, 0.56–1.35; P = 0.527). Moreover, oral antibiotic therapy had a beneficial effect on the risk of all-cause mortality (RR, 0.58; 95% CI, 0.35–0.96; P = 0.034). Conclusions: Oral administration of antibiotics is associated with a reduced risk of all-cause mortality compared with parenteral therapy based on RCTs with low to moderate quality. This finding should be verified in further large-scale RCTs.

AIM: To determine the students' satisfaction with the three teaching modes in the contact lens course and provide suggestions to improve teaching quality.METHODS: We conducted a survey at Tianjin Medical University in June 2021 using the Students' Evaluations of Educational Quality(SEEQ)questionnaire. We used descriptive statistics to analyze SEEQ items and the One-way ANOVA was used to determine differences in scores among the three modes.RESULTS: Among the 221 valid responses collected, 87(39.4%)respondents were males and 134(60.6%)were females. The total scores were 151.46(12.45), 148.71(13.14), and 147.97(14.56)for offline, online, and blended teaching, respectively, with no significant difference(F=1.10, P=0.33). Students had a longer interaction time with the teacher in offline teaching than in online and blended teaching(P=0.03). The three different teaching modes have no significant difference among genders or academic performance(P=0.33, P=0.91, respectively). Furthermore, 18.1% of students suggested that the amount of experiment time should be increased.CONCLUSION: Students were satisfied with all three teaching modes. However, they had more interaction time with teachers in traditional offline teaching compared with online and blended teaching. More time is needed to increase teachers' online teaching ability.

Durvalumab consolidation therapy is the standard treatment after concurrent chemoradiotherapy for patients with surgically unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Neoadjuvant therapy followed by surgery could reduce locoregional and distant recurrence and improve the survival rate for surgically resectable NSCLC. However, the value of neoadjuvant therapy in locally advanced potentially resectable NSCLC remains controversial. Herein, we report a locally advanced potentially resectable NSCLC case with a history of breast cancer who achieved a pathologic complete response (pCR) after preoperative treatment with pembrolizumab and chemotherapy. A 50-year-old woman developed squamous cell carcinoma (SCC) (left lower lobe of the lung, stage IIIA-N2) after two years of chemotherapy and anti-HER2 therapy following a diagnosis of HER2-overexpressing breast cancer. Surgical resection was attempted despite an MDT classification as unamenable to curative surgical resection. After two cycles of neoadjuvant chemotherapy combined with anti-PD1 immunotherapy, the tumor significantly shrank, then the patient underwent a left lower lobectomy. Complete resection with negative margins (R0 resection) was achieved in the patient. The patient experienced grade 1–2 adverse effects and no grade 3 or worse adverse effects occurred. Cardiotoxicity did not occur in the patient despite prior anti-HER2 treatment for breast cancer. Our case study contributes to the existing evidence on the feasibility, efficacy, and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC. Furthermore, future studies are needed to determine which patients can benefit from immunoadjuvant therapy and the duration and course of preoperative and postoperative immunotherapy.

Abstract Purpose Pancreatic cancer is one of the deadliest cancers worldwide. The extracellular matrix (ECM) microenvironment affects the drug sensitivity and prognosis of pancreatic cancer patients. This study constructed an 8-genes pancreatic ECM scoring (PECMS) model, to classify the ECM features of pancreatic cancer, analyze the impact of ECM features on survival and drug sensitivity, and mine key molecules that influence ECM features in pancreatic cancer. Methods GSVA score calculation and clustering were performed in TCGA-PAAD patients. Lasso regression was used to construct the PECMS model. The association between PECMS and patient survival was analyzed and validated in the CPTAC-3 dataset of TCGA and our single-center retrospective cohort. The relationships between PECMS and features of the matrix microenvironment were analyzed. Finally, PECMS feature genes were screened and verified in pancreatic cancer specimens to select key genes associated with the ECM microenvironment. Result The survival of the PECMS-high group was significantly worse. The PECMS-high group showed higher oxidative stress levels, lower levels of antigen presentation- and MHC-I molecule-related pathways, and less immune effector cell infiltration. Data from IMvigor-210 cohort suggested that PECMS-low group patients were more sensitive to immune checkpoint blockers. The PECMS score was negatively correlated with chemotherapy drug sensitivity. The negative association of PECMS with survival and drug sensitivity was validated in our retrospective cohort. KLHL32 expression predicted lower oxidative stress level and more immune cells infiltrate in pancreatic cancer. Conclusion PECMS is an effective predictor of prognosis and drug sensitivity in pancreatic cancer patients. KLHL32 may play an important role in the construction of ECM, and the mechanism is worth further study.

AIM: To evaluate the prevalence of refractive errors and ocular biometry in 3573 freshman students at Tianjin Medical University for 4 consecutive years. METHODS: In this university-based, cross-sectional study, comprising 3573 students, visual acuity (VA), slit-lamp examination, non-cycloplegic auto-refraction, and ocular biometry were recorded. RESULTS: The prevalence of myopia increased annually, from 2017 to 2020 were 93.5%, 94.5%, 95.9%, and 96.2%, respectively (P=0.03), and the prevalence of high myopia was 25.7%, 26.9%, 28.6%, and 28.6%, respectively. Males tended to have a higher percentage of total astigmatism than females, with astigmatism ≥0.75 and ≥1.0 D criteria. The percentage of with-the-rule astigmatism, against-the-rule astigmatism, and oblique astigmatism was 90.3%, 5.8%, and 3.9%, respectively, with astigmatism ≥1.00 D criteria. The mean spherical equivalent, axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), corneal radius (CR), and lens position (LP) were 4.37±2.52 D, 25.28±1.24 mm, 539.49±34.98 μm, 3.31±0.34 mm, 3.47±0.21 mm, 7.8±0.28 mm, and 5.04±0.32 mm, respectively. With diopter increase in myopia, the AL became longer, CR became steeper, ACD became deeper, LT became thinner, and LP became more posterior (all P

Introduction Oral health is a fundamental component of well-being, and is closely associated with overall health and quality of life. Oral health may also affect the next generation. The children of mothers with poor oral health are likely to also have poor oral health as they go through life. We aim to investigate associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health.Methods and analysis The Lifetime Impact of Oral Health study is a prospective, observational cohort study being done at a single centre in Chongqing, China. A total of 1000 pregnant women will be recruited in their first trimester (11–14 weeks gestation). After obtaining informed consent, general and oral health assessments will be undertaken. Maternal lifestyle, demographic data and biospecimens (blood, hair, urine, nail clippings, saliva, dental plaque, buccal, vaginal and anal swabs) will be collected. Pregnancy outcomes will be recorded at the time of delivery. Cord blood and placenta samples will be collected. The offspring will be followed up for general and oral health examinations, neurodevelopmental assessments and biospecimen (dental plaque, saliva, buccal swabs, exfoliated primary dentition, urine, hair, nail clippings) collection until they are 15 years old. Biological samples will undergo comprehensive metabolomic, microbiome and epigenome analyses. Associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health will be investigated and the underlying mechanisms explored.Ethics and dissemination This project has been approved by the Research Ethics Committee of the Affiliated Hospital of Stomatology of Chongqing Medical University (CQHS-REC-2021 LSNo.23). Participants will be required to provide informed consent to participate in the study. Dissemination of findings will take the form of publications in peer-reviewed journals and presentations at national and international conferences.Trial registration number ChiCTR2100046898.

Background: Increasing evidence illustrated that m6A regulator-mediated modification plays a crucial role in regulating tumor immune and angiogenesis microenvironment. And the combination of immune checkpoint inhibitor and anti-angiogenic therapy has been approved as new first-line therapy for advanced HCC. This study constructed a novel prognosis signature base on m6A-mediated modification and explored the related mechanism in predicting immune and anti-angiogenic responses.Methods: Gene expression profiles and clinical information were collected from TCGA and GEO. The ssGSEA, MCPCOUNT, and TIMER 2.0 algorithm was used to Estimation of immune cell infiltration. The IC50 of anti-angiogenic drugs in GDSC was calculated by the “pRRophetic” package. IMvigor210 cohort and Liu et al. cohort were used to validate the capability of immunotherapy response. Hepatocellular carcinoma single immune cells sequencing datasets GSE140228 were collected to present the expression landscapes of 5 hub genes in different sites and immune cell subpopulations of HCC patients.Results: Three m6A clusters with distinct immune and angiogenesis microenvironments were identified by consistent cluster analysis based on the expression of m6A regulators. We further constructed a 5-gene prognosis signature (termed as m6Asig-Score) which could predict both immune and anti-angiogenic responses. We illustrated that high m6Asig-Score is associated with poor prognosis, advanced TNM stage, and high TP53 mutation frequency. Besides, the m6Asig-Score was negatively associated with immune checkpoint inhibitors and anti-angiogenic drug response. We further found that two of the five m6Asig-Score inner genes, B2M and SMOX, were associated with immune cell infiltration, immune response, and the sensitivity to sorafenib, which were validated in two independent immunotherapy cohorts and the Genomics of Drug Sensitivity in Cancer (GDSC) database.Conclusion: We constructed a novel prognosis signature and identified B2M and SMOX for predicting immune and anti-angiogenic efficacy in HCC, which may guide the combined treatment strategies of immunotherapy and anti-angiogenic therapy in HCC.

Background: Copper metabolism plays an important role in the tumor microenvironment, and cuproptosis is the last discovered programmed cell death process. However, the potential mechanism of cuproptosis in regulating the immune microenvironment of HCC remains unclear.Methods: A total of 716 HCC patients with complete mRNA expression and survival information were collected from three public HCC cohorts (TCGA-LIHC cohort, n = 370; GSE76427 cohort, n = 115; ICGC-LIRI cohort, n = 231). The unsupervised clustering analysis (NMF) was performed to identify three different cuproptosis-related subtypes. The univariate-Cox, lasso-Cox and multivariate-Cox regression analyses were performed to screen the cuproptosis related and construct the cuproptosis-related prognosis signature (Cu-PS). The immune cell infiltration was estimated by both CIBERSORT and MCPcounter algorithms.Results: This study identified three distinct cuproptosis-related metabolic patterns, which presented different pathway enrichment and immune cell infiltration. The Cu-PS, a 5-genes (C7, MAGEA6, HK2, CYP26B1 and EPO) signature, was significantly associated with TNM stage, tumor mutational burden (TMB), drugs sensitivity, and immunotherapies response.Conclusion: This study performed a multi-genetic analysis of cuproptosis-related genes and further explored the regulatory mechanism of cuproptosis in HCC. The Cu-PS might be a useful biomarker for predicting immunotherapy response and enhancing the diagnosis and treatment of HCC.

Aim: The cardiac toxicity that occurs during administration of anti-tumor agents has attracted increasing concern. Fluoropyrimidines have been used for more than half a century, but their cardiotoxicity has not been well clarified. In this study, we aimed to assess the incidence and profile of fluoropyrimidine-associated cardiotoxicity (FAC) comprehensively based on literature data. Methods: A systematic literature search was performed using PubMed, Embase, Medline, Web of Science, and Cochrane library databases and clinical trials on studies investigating FAC. The main outcome was a pooled incidence of FAC, and the secondary outcome was specific treatment-related cardiac AEs. Random or fixed effects modeling was used for pooled meta-analyses according to the heterogeneity assessment. PROSPERO registration number: (CRD42021282155). Results: A total of 211 studies involving 63,186 patients were included, covering 31 countries or regions in the world. The pooled incidence of FAC, by meta-analytic, was 5.04% for all grades and 1.5% for grade 3 or higher. A total of 0.29% of patients died due to severe cardiotoxicities. More than 38 cardiac AEs were identified, with cardiac ischemia (2.24%) and arrhythmia (1.85%) being the most frequent. We further performed the subgroup analyses and meta-regression to explore the source of heterogeneity, and compare the cardiotoxicity among different study-level characteristics, finding that the incidence of FAC varied significantly among different publication decades, country/regions, and genders. Patients with esophagus cancer had the highest risk of FAC (10.53%), while breast cancer patients had the lowest (3.66%). The treatment attribute, regimen, and dosage were significantly related to FAC. When compared with chemotherapeutic drugs or targeted agents, such a risk was remarkably increased (χ2 = 10.15, p < 0.01; χ2 = 10.77, p < 0.01). The continuous 5-FU infusion for 3–5 consecutive days with a high dosage produced the highest FAC incidence (7.3%) compared with other low-dose administration patterns. Conclusions: Our study provides comprehensive global data on the incidence and profile of FAC. Different cancer types and treatment appear to have varying cardiotoxicities. Combination therapy, high cumulative dose, addition of anthracyclines, and pre-existing heart disease potentially increase the risk of FAC.

Objective To confirm the role of long noncoding RNA differentiation antagonizing non‐protein coding RNA (DANCR) in chondrocyte inflammatory injury in osteoarthritis (OA) in vitro, as well as its molecular mechanism. Methods Human primary chondrocytes were treated with lipopolysaccharide (LPS) to construct a chondrocyte inflammatory injury in human OA cell model. Gene expression was detected using real‐time quantitative polymerase chain reaction. Cell inflammatory injury was evaluated by Cell Counting Kit‐8 assay, flow cytometry, and enzyme‐linked immunosorbent assay. The interplay between miRNA‐19a‐3p (miR‐19a) and DANCR was validated by dual‐luciferase reporter assay and RNA immunoprecipitation. Results Expression of DANCR was upregulated, and miR‐19a was downregulated in human OA cartilage and LPS‐treated primary chondrocytes in vitro. Moreover, DANCR expression was inversely correlated with miR‐19a in OA patients. LPS reduced cell viability and increased the apoptotic rate and secretion of interleukin (IL)‐1β, IL‐6, IL‐8, as well as tumor necrosis factor (TNF)‐α in primary chondrocyte cells in vitro, suggesting an inflammatory injury model of OA. Functionally, knockdown of DANCR could attenuate LPS‐induced apoptosis and inflammatory response, as evidenced by improved cell viability, and reduced apoptotic rate and products of IL‐1β, IL‐6, IL‐8, and TNF‐α. Notably, DANCR negatively regulated miR‐19a expression, presumably via sponging. Furthermore, miR‐19a deletion eliminated the effect of DANCR knockdown on apoptosis and the inflammatory response of primary chondrocytes under LPS stress. Conclusion Differentiation antagonizing non‐protein coding RNA silencing could protect human chondrocyte cells against LPS‐induced inflammatory injury and apoptosis through targeting miR‐19a, suggesting a vital role of the DANCR/miR‐19a axis in OA.

Based on Materials Studio and Aspen Plus, the reaction mechanism of producing benzene and styrene from ethane steam heat lysis was investigated through the addition reaction of free radicals + alkenes or free radicals + alkynes to form large free radicals and then through the cyclization and dehydrogenation of large free radicals to form aromatic hydrocarbons. It was found the thermal cracking of ethane had 2 paths to form benzene and 1 path to form styrene. The 1st path to form benzene is that the product ethylene form C2H3• through a chain transfer, then C2H3• and ethylene additively react to form 1-C4H7•-4, which then reacts with ethylene to form C6H11•, and finally, benzene is produced by dehydrogenation and transfer of C6H11•. The 2nd path to form benzene is that acetylene is produced by dehydrogenation of C2H3•, and then acetylene reacts via two sub-paths to form 1,3-C4H5•-4, which is cyclized to form C6H9•, and finally, benzene is formed through dehydrogenation and transfer. The path to form styrene is that 1,3-C4H5•-4 and 1,3-butadiene are cyclized to form C8H11•, and styrene is finally formed through dehydrogenation and chain transfer. Comparative analysis with industrial data showed there were 3 cycles in the ethane thermal cracking reaction network. The simulation data were well consistent with the industrial production data.

Epstein–Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a specific molecular subtype of gastric carcinoma with a high proportion of tumor-infiltrating lymphocytes. It is a highly immunogenic tumor that may benefit from immunotherapy. Hence, it is imperative to analyze the immune landscape and identify immunotherapy biomarkers for EBVaGC. In our study, we investigated the immune landscape and identified 10 hub genes for EBVaGC via integrated bioinformatics analysis. We found that EBVaGC expressed more immune-related genes, including common immune checkpoints and human leukocyte antigen (HLA) genes than EBV-negative gastric carcinoma (EBVnGC). The immune score in EBVaGC was higher, which means EBVaGC has greater immune cell infiltration. Ten hub genes (CD4, STAT1, FCGR3A, IL10, C1QA, CXCL9, CXCL10, CXCR6, PD-L1, and CCL18) were detected as candidate biomarkers for EBVaGC. Two hub genes, CXCL9 and CXCR6, were identified as novel immunotherapy-related genes. Taken together, the results of our comprehensive analysis of the immune microenvironment of EBVaGC revealed its unique immune landscape, demonstrating that it is a highly immunogenic tumor. Moreover, we identified hub genes that may serve as potential immunotherapy biomarkers for EBVaGC.

Glioma is the most common primary malignant brain tumor in adults with very poor prognosis. The limited new therapeutic strategies for glioma patients can be partially attributed to the complex tumor microenvironment. However, knowledge about the glioma immune microenvironment and the associated regulatory mechanisms is still lacking. In this study, we found that, different immune subtypes have a significant impact on patient survival. Glioma patients with a high immune response subtype had a shorter survival compared with patients with a low immune response subtype. Moreover, the number of B cell, T cell, NK cell, and in particular, the macrophage in the immune microenvironment of patients with a high immune response subtype were significantly enhanced. In addition, 132 genes were found to be related to glioma immunity. The functional analysis and verification of seven core genes showed that their expression levels were significantly correlated with the prognosis of glioma patients, and the results were consistent at tissue levels. These findings indicated that the glioma immune microenvironment was significantly correlated with the prognosis of glioma patients and multiple genes were involved in regulating the progression of glioma. The identified genes could be used to stratify glioma patients based on immune subgroup analysis, which may guide their clinical treatment regimen.

BackgroundThe novel coronavirus disease 2019 (COVID-19) pandemic causes great disruption to cancer care services, which might bring about psychological problems and further lower both physical and mental life quality in cancer patients. Until now, very few studies focused on the psychological distress of patients with advanced melanoma before or during the epidemic. This study aimed to elucidate the fear of progression (FoP), anxiety, depression, and related independent predictors in patients with advanced melanoma during the COVID-19 outbreak.MethodsTwo hundred and seventy-three patients with unresectable stage III or metastatic melanoma were recruited from February 2020 to November 2021, and completed the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), State Trait Anxiety Inventory (STAI-6), and Patient Health Questionnaire (PHQ-9).ResultsOne hundred and seventy-four (64.7%) patients experienced heighted FoP (FoP-Q-SF: 39.9 ± 11.0), 198 (72.5%) patients reported elevated anxiety (STAI-6: 13.1 ± 3.0), and 62 (22.7%) patients had increased depression (PHQ-9: 6.4 ± 6.1). In multivariate analysis, illness duration (OR = 0.987 for FoP; OR = 0.984 for depression), cancer stage (OR = 14.394 for anxiety) and disease progression (OR = 1.960 for FoP; OR = 23.235 for anxiety; OR = 1.930 for depression) were independent predictors for FoP, anxiety or depression. Additionally, the high levels of FoP, anxiety and depression were significantly positive correlated with each other (r = 0.466 for FoP and anxiety; r = 0.382 for FoP and depression; r = 0.309 for anxiety and depression).ConclusionOur study indicates that FoP, anxiety and depression are persisting among patients with advanced melanoma in the COVID-19 and post-COVID-19 era. Effective psycho-oncological interventions are needed for melanoma patients with psychological distress during the ongoing COVID-19 pandemic.

The Gravitational Wave High-energy Electromagnetic Counterpart All-sky Monitor (GECAM) is a pair of microsatellites (i.e., GECAM-A and GECAM-B) dedicated to monitoring gamma-ray transients including the high-energy electromagnetic counterparts of gravitational waves, such as gamma-ray bursts, soft gamma-ray repeaters, solar flares, and terrestrial gamma-ray flashes. Since launch in 2020 December, GECAM-B has detected hundreds of astronomical and terrestrial events. For these bursts, localization is the key for burst identification and classification as well as follow-up observations in multiple wavelengths. Here, we propose a Bayesian localization method with Poisson data with Gaussian background profile likelihood to localize GECAM bursts based on the distribution of burst counts in detectors with different orientations. We demonstrate that this method can work well for all kinds of bursts, especially extremely short ones. In addition, we propose a new method to estimate the systematic error of localization based on a confidence level test, which can overcome some problems of the existing method in the literature. We validate this method by Monte Carlo simulations, and then apply it to a burst sample with accurate location and find that the mean value of the systematic error of GECAM-B localization is ∼2.°5. By considering this systematic error, we can obtain a reliable localization probability map for GECAM bursts. Our methods can be applied to other gamma-ray monitors.

Salt stress is one of the major abiotic stresses affecting soybean growth. Genetic improvement for salt tolerance is an effective way to protect soybean yield under salt stress conditions. Successful improvement of salt tolerance in soybean relies on identifying genetic variation that confers tolerance in soybean germplasm and subsequently incorporating these genetic resources into cultivars. In this review, we summarize the progress in genetic diversity and genetics of salt tolerance in soybean, which includes identifying genetic diversity for salt tolerant germplasm; mapping QTLs conferring salt tolerance; map-based cloning; and conducting genome-wide association study (GWAS) analysis in soybean. Future research avenues are also discussed, including high throughput phenotyping technology, the CRISPR/Cas9 Genome-Editing System, and genomic selection technology for molecular breeding of salt tolerance.

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

Sodium toxicity and potassium insufficient are important factors affecting the growth and development of soybean in saline soil. As the capacity of plants to maintain a high cytosolic, K+/Na+ ratio is the key determinant of tolerance under salt stress. The aims of the present study were to identify and analyse expression patterns of the soybean K+ efflux antiporter (KEA) gene and Na+/H+ antiporter (NHX) gene family, and to explore their roles under abiotic stress. As a result, 12 soybean GmKEAs genes and 10 soybean GmNHXs genes were identified and analyzed from soybean genome. Interestingly, the novel soybean KEA gene Glyma16g32821 which encodes 11 transmembrane domains were extremely up-regulated and remained high level until 48 h in root after the excessive potassium treatment and lack of potassium treatment, respectively. The novel soybean NHX gene Glyma09g02130 which encodes 10 transmembrane domains were extremely up-regulated and remained high level until 48 h in root with NaCl stress. Imaging of subcellular locations of the two new Glyma16g32821-GFP and Glyma09g02130-GFP fusion proteins indicated all plasma membrane localizations of the two novel soybean genes. The 3D structures indicated that the two soybean novel proteins Glyma09g02130 (NHX) and Glyma16g32821 (KEA) all belong to the cation/hydrogen antiporter family.

Using homology cloning method, a heat shock transcription factor (Hsf) like gene, ZmHsf-like, was cloned from maize (Zea mays) leaves. Sequence analyses showed that the open reading frame (ORF) of the gene ZmHsf-like is 1 404 bp long, encoding 467 amino acids. The sequence of amino acids encoded by ZmHsf-like contains the most conserved and typical DNA-binding domain of Hsf family. By bombardment into onion epidermis, we firstly found that the ZmHsf-like was subcellular-located in nucleus. NucPred analysis revealed there is a classic NLS of KKRR peptide in protein. Real-time PCR showed that ZmHsf-like gene expressed in leaves, stems and roots of maize seedlings under normal growth conditions, and the highest expression level was in roots, lower in leaves and the lowest in stems. The ZmHsf-like gene expression could be up-regulated by heat shock, PEG, ABA, and H2O2 in different degrees, among which the heat shock and ABA worked more efficiently. Obvious differences of the peak value and its corresponding time point of ZmHsf-like gene expression were observed among treatments. Experiments with inhibitor further suggested that the up-regulation ZmHsf-like gene expression of heat shock was H2O2-dependent while the induction of ZmHsf-like with PEG did not depend on the existence of H2O2. These results pointed out that ZmHsf-like gene probably regulates responsive reactions to abiotic stresses especially heat shock and drought through different signal transduction pathways.

According to the existing domestic and foreign research results as well as the characteristics of the guide fund, this paper constructs the index system of guide fund performance evaluation, selects the data of the part of the enterprises shared by the government guide venture capital fund and uses the factor analysis method to optimize the evaluation model, then uses empirical analysis based on DEA-BCC model. The result shows that the optimized evaluation model can fully evaluate the performance of the guide fund. At the same time, empirical analysis based on DEA-BCC model shows that the results can objectively reflect the operating conditions of companies accepted investment, which provides the objective reference for government venture capital fund and companies accepted investment.

BACKGROUND:Giardia lamblia is one of the most common infectious protozoans in human that may cause diarrhea in travelers. Searching for antigens that induced effectively protective immunity has become a key point in the development of vaccine against giardiasis. METHODOLOGY/PRINCIPAL FINDINGS:Mice vaccinated with G. lamblia trophozozite-specific α1-giardin DNA vaccine delivered orally by attenuated Salmonella typhimurium SL7027 elicited 74.2% trophozoite reduction, but only 28% reduction in cyst shedding compared with PBS buffer control. Oral vaccination with Salmonella-delivered cyst-specific CWP2 DNA produced 89% reduction in cysts shedding in feces of vaccinated mice. Significantly, the mice vaccinated with Salmonella-delivered bivalent α1-giardin and CWP2 DNA vaccines produced significant reduction in both trophozoite (79%) and cyst (93%) in feces of vaccinated mice. This parasite reduction is associated with the strong local mucosal IgA secretion and the IgG2a-dominant systemic immune responses in vaccinated mice. CONCLUSIONS:The results demonstrate that bivalent vaccines targeting α1-giardin and CWP2 can protect mice against the colonization of Giardia trophozoite and block the transformation of cyst in host at the same time, and can be used to prevent Giardia infection and block the transmission of giardiasis.