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Chlorogenic acid (CGA) is a kind of traditional Chinese medicine, abundant in honeysuckle and eucommia, and has a wide range of biological activities, and pharmacological effects. Previous studies have shown that CGA can regulate learning, memory, cognitive ability, coupled with improvement to anxiety, depression, and other post-traumatic stress disorder (PTSD)-like symptoms. This article explores the protective effects of CGA on neurons through its anti-apoptotic effect, inhibition of neuroinflammation and oxidative stress, which may be the mechanisms of its improvement of PTSD-like symptoms. It may provide a new therapeutic strategy for the treatment of PTSD and its comorbidities.

Background China is facing big challenges to achieve the “90–90-90 targets”. The HIV prevalence of elderly (≥50 years) men have been steadily increasing in China, mainly through the sexual transmission route, but sexual behaviors of them are far from well-studied. In 2019, elderly men accounted for 59.2% of HIV/AIDS cases in Sichuan, China. Methods The research design is a cross-sectional study. Face-to-face interviews were conducted among 795 HIV negative elderly men from rural Chengdu, capital City of Sichuan. Bivariate and multivariate logistic regression models were applied to examine factors associated with commercial heterosexual behavior from a modified Knowledge-Attitude-Practice (KAP) perspective. Results 129 (16.23%) respondents admitted high-risk sexual behaviors, including 11.07% commercial heterosexual behavior, 6.16% extramarital, 2.89% casual and 0.25% homosexual behavior, and no one used condom consistently. 427(68.43%) had ever gotten HIV-related Health Education (HRHE), mainly through mass media (70.49%). The HIV-related knowledge awareness rate was only 31.41%. Migration history (AOR =2.46,95% CI = 1.02–5.91), age(≥60 vs. 50–59, OR = 0.41, 95% CI = 0.19–0.91), receiving HRHE from mass media (OR = 0.37, 95%CI = 0.16–0.85), marital status (married vs. never married, OR = 0.04, 95%CI = 0–0.52), and undecided (AOR =0.02, 95%CI = 0.01–0.09) and objection (AOR =0.04, 95%CI = 0.01–0.1) attitude toward commercial sex were related to lifetime commercial heterosexual behavior. Conclusions High-risk sexual behaviors are common among elderly men from rural areas in Chengdu. Receiving HRHE from mass media and undecided and objection attitude toward commercial sex prevent elderly from being involving in commercial heterosexual behavior. According to the results, health facilities should continue to conduct systematic interventions, paying more attention to 50–59 years old group. Sex and condom use need to be talked in public. Working with mass media, health facilities give elderly men education not only focusing on HIV/AIDS, but also on knowledge and skills of condom use.

A novel method to synthesize N-aryl-1-amino indoles was established by the photoinduced N-N coupling reaction. This protocol is by treatment of o-nitrobenzyl alcohols and indolines in the presence of TEAI and acetic acid with a 24 W ultraviolet (UV) light-emitting diode (LED) (385-405 nm) irradiation. The products bearing an aldehyde group can be further transformed to fluorescent probes based on Rhodamine 6G derivative 11, which shows a high specificity and sensitivity for Fe3+.

Herein, we develop a mild method for N-acylation of primary and secondary amines with α-diketones induced by ultraviolet (UV) light. Forty-six examples with various functional groups are explored at room temperature with irradiation by three 26 W UV lamps (350-380 nm). The yield reaches 97%. The gram scale experiment product yield is 76%. Moreover, this system can be applied to the synthesis of several amino acid derivatives. Mechanistic studies show that benzoin is generated in situ from benzil under UV irradiation.

The mechanisms of radiation-induced liver injury (RILI) has not been fully elucidated so far. In the present study, a RILI mouse model was constructed by exposing the liver to a single dose of 30 Gy X-rays. Liver injuries consisting of liver function damage and histopathological variations were confirmed after 2 weeks. And then the cellular atlas of RILI liver was generated by profiling 9,641 ​cells isolated from X-ray irradiated mice livers and control ones from RILI mice model using single-cell RNA sequencing (scRNA-seq). Seven cell types were identified, including B cells, natural killer cells, T cells, macrophages/Küpffer cells/Dendritic cells (DC), neutrophils, endothelial cells, and hepatocyte. Although there was no significant difference of overall cell typing was observed between the Control and RILI groups, hepatocytes and macro/Küpffer/DC cell types were chosen for further functional exploration. Gene expression profiles and bioinformatics analysis of hepatocytes revealed that multiple metabolic related pathways were enriched in livers exposed to IR. These scRNA-seq data were confirmed in RILI liver samples via adipose staining. Besides, obviously varied M1-/M2-macrophages polarization was observed in RILI liver, which was in accordance with the enzyme linked immunosorbent assay (ELISA) results of IR-induced M2 to pro-inflammatory M1 macrophages transformation in mouse macrophage cell line Raw264.7. In addition, we predicted that several genes were found to differentially expressed during the process of macrophage polarization from M2 to M1 subtype. Overall, our study provides a cellular landscape of RILI at single-cell resolution that indicates the characteristics of hepatocytes and macrophages, which will contribute to investigate the novel therapeutic or preventive management for RILI.

Knee osteoarthritis (KOA) is a joint degenerative arthropathy, characterized by cartilage degeneration of knee joint. Ligustrazine is an effective component of traditional Chinese medicine chuanqiong. It is reported that ligustrazine is used as a kind of anti-inflammatory medicine in folk prescription, especially in the treatment of knee osteoarthritis. The study is aimed to study the therapeutic effect of ligustrazine mediated by nanoparticle on knee osteoarthritis and its impact on MMPs and upstream NF-κB signaling pathway in synovial fluid. Nanoparticle-mediated system is a kind of nano traditional Chinese medicine preparation, which is made by taking nanoparticle and combining with the effective components, effective parts, raw materials, and their compounds in a certain way. We found that the combination of nanoparticle and ligustrazine can improve its bioavailability and targeting, reduce the adverse reactions in the treatment of knee osteoarthritis. The ligustrazine mediated by nanoparticle can effectively alleviate knee osteoarthritis by reducing the level of MMPs in synovial fluid and the expression of NF-κB in upstream NF-κB signaling pathway.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease and the third leading cause of death in the world. Dexmedetomidine has been reported to effectively inhibit histamine-induced bronchoconstriction. However, the molecular mechanism of dexmedetomidine in COPD has not been found. To explore the role and mechanism of dexmedetomidine in COPD, and to provide theoretical basis for clinical treatment of COPD. The expression of miR-146a was regulated by mimics or inhibitor and the relative expression of apoptotic proteins p53, Bax and Bcl-2 in human bronchial epithelial 16HBE cells was determined by real-time PCR and Western blot. Dexmedetomidine was treated for 16HBE cells and alveolar epithelial type II cells (AEC2), the cell apoptosis was detected by TUNEL and Hoechst33342 staining. A COPD rat model was established by smoking to test the effects of dexmedetomidine on the progression of COPD. The levels of IL-6, IL-1β and TNF-α in serum were measured by ELISA and the protein concentration of bronchoalveolar lavage fluid (BALF) was also detected in dexmedetomidine treated COPD rat model. miR-146a promoted 16HBE cell apoptosis and reduced cell proliferation. Additionally, dexmedetomidine was showed to reduce the 16HBEL cell apoptosis through reducing the expression of miR-146a. Moreover, dexmedetomidine regulated cell apoptosis and cell apoptosis through miR-146a in AEC2 cells. More importantly, dexmedetomidine attenuated the morphology and pathology of COPD rat model. Dexmedetomidine reduced 16HBE cells and AEC2 cell apoptosis and attenuated COPD by down-regulating miR-146a.

Background Non-magnifying endoscopy with narrow-band imaging (NM-NBI) has been frequently used in routine screening of esophagus squamous cell carcinoma (ESCC). The performance of NBI for screening of early ESCC is, however, significantly affected by operator experience. Artificial intelligence may be a unique approach to compensate for the lack of operator experience. Aim To construct a computer-aided detection (CAD) system for application in NM-NBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging (WLI). Methods A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions (Zhongshan Hospital of Fudan University, Xuhui Hospital, and Kiang Wu Hospital) as the training dataset, and 316 pairs of images, each pair including images obtained by WLI and NBI (same part), were collected for validation. Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems. The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Results The area under receiver operating characteristic curve for CAD-NBI was 0.9761. For the validation dataset, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CAD-NBI were 91.0%, 96.7%, 94.3%, 95.3%, and 93.6%, respectively, while those of CAD-WLI were 98.5%, 83.1%, 89.5%, 80.8%, and 98.7%, respectively. CAD-NBI showed superior accuracy and specificity than CAD-WLI (P = 0.028 and P ≤ 0.001, respectively), while CAD-WLI had higher sensitivity than CAD-NBI (P = 0.006). By using both CAD-WLI and CAD-NBI, the endoscopists could improve their diagnostic efficacy to the highest level, with accuracy, sensitivity, and specificity of 94.9%, 92.4%, and 96.7%, respectively. Conclusion The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI. Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI.

A 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease (IPD) was introduced in China in April 2017. We describe 105 children

BACKGROUND To investigate the clinical effect of percutaneous spinal nerve posteromedial ramus destruction in treatment for chronic facet arthrogenic low back pain. METHODS A total of 118 patients with chronic facet arthrogenic low back pain were enrolled in our hospital from October 2015 to October 2018 and randomly divided into two groups. Of these patients, 59 received conservative treatment as the control group while 59 patients were treated with percutaneous spinal nerve posteromedial ramus destruction as the observation group. Pain score (Visual Analogue Scale, VAS), functional score (Oswestry Disability Index, ODI), treatment score (Japanese Orthopaedic Association, JOA), life quality score (Short Form 36-item Health Survey, SF-36), and lumbar mobility (range of motion, ROM) were evaluated before and after treatment. The treatment effect between two groups was compared. RESULTS The VAS score and ODI score at 2, 4, and 12 weeks after treatment and last follow-up in the observation group were lower than those of the control group (P

Purpose To characterize plasma cell‐free cancer genome chromosomal instabilities (CIN) in patients with liver cancer and to evaluate the potential of CIN as minimally invasive biomarkers for primary liver cancer (PLC) diagnoses. Experimental Design We collected 196 plasma samples from 172 individuals in two cohorts, a discovery cohort of surgery ineligible PLC patients and a validation cohort of hepatectomy patients with pathological disease confirmations. All samples were subjected to HiSeq X10 sequencing followed by a customized bioinformatics workflow Ultrasensitive Chromosome Aneuploidy Detection (UCAD). Results In the discovery cohort, 29 significant copy number changes were identified in plasma from surgery‐ineligible PLC. Twenty‐two (95.7%) surgery‐ineligible liver cancers were identified as harboring copy number changes in at least 1 of 29 segments. Meanwhile 40/41 (97.6%) noncancers harbored no changes. In the validation cohort, 54 (69.4%) surgery‐eligible liver cancers were identified with positive screening, all of which were subsequently confirmed as cancer by pathological examination. Moreover, 26/27 = 96.3% noncancers were identified with negative screening. UCAD‐positive screening was significantly associated with microvascular invasion (OR > 10, 95% CI:[2.53,]), tumor stages B and C (OR = 8.59, 95% CI [1.07, 400]), and tumor size ≥ 3 cm (OR = 5.68, 95% CI [1.43, 28.1]). Furthermore, we collected 29 followed‐up plasma samples from 19 postsurgery patients. Nine (31.0%) postsurgery samples from 6 (31.5%) patients were identified with positive screening. Among them, 3 patients (50.0%) with positive screening were then confirmed as having disease recurrences. Conclusions In addition to AFP, plasma cell‐free DNA sequencing is a useful tool for primary liver cancer diagnoses., In addition to AFP, plasma cell‐free DNA sequencing is a useful tool for primary liver cancer diagnoses.

Dianthus spiculifolius is a perennial herbaceous flower with strong environmental adaptability and is an important ornamental ground cover plant. In this study, seeds of D. spiculifolius were used as explants for callus induction, adventitious bud differentiation, and rooting by adding different concentrations of 2,4-dichlorophenoxyacetic acid (2,4-D), 6-benzyl aminopurine (6-BA), and naphthaleneacetic acid (NAA) to Murashige and Skoog medium. The calli generated were co-cultured with Agrobacterium tumefaciens EHA105 containing pBI121-GUS or pBI121-GFP plasmids for 30 min, and transgenic regenerated plants were obtained by kanamycin (30 mg · L−1) screening. RT-PCR confirmed the stable expression of the exogenous GUS and GFP genes in the D. spiculifolius. The β-glucuronidase (GUS) histochemical staining confirmed GUS gene expression in transgenic calli, adventitious buds, and regenerated plants of D. spiculifolius. The green fluorescent protein (GFP) visual analysis showed GFP gene expression in transgenic calli. Furthermore, subcellular localization analysis showed that the three organelle marker proteins were not only successfully expressed but also accurately localized to their corresponding organelles in D. spiculifolius callus cells. These results indicated a successful establishment of a reliable and efficient A. tumefaciens-mediated genetic transformation system, which will contribute to functional gene research and genetic improvement of D. spiculifolius.

Introduction Osteoarthritis (OA), a chronic joint disease, combines with massive inflammation and plays a vital role in cartilage degeneration. The main strategy in clinic is controlling inflammation, thereby treating osteoarthritis. Salvianolic acid A (SAA) is a type of phenolic acid, derived from a traditional chinese herbal medicine Danshen that is extensively used clinically. Methods and results We observed the anti-inflammatory and antiarthritic effects of SAA in IL-1β-stimulated cells. We found that SAA evidently decreased the expression of mainly inflammatory factors, exerted the remarkable effects of anti-inflammation and anti-arthritis. Furthermore, SAA inhibited the expression of Matrix metalloproteinases (MMP1, MMP13), and ADAMTS-5 and raised the synthesis of collagen II and aggrecan. Additionally, the results indicated that SAA gave rise to the effects by down-regulation of NF-κB and p38/MAPK pathways. Discussion Our study demonstrates that SAA may be a promising anti-inflammatory for the treatment of OA in clinic.

Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.

The airway inflammatory response is closely associated with asthma. The purpose of this article was to study the roles of innate lymphoid cells (ILCs) in the process of airway inflammatory response in asthma. We established the asthmatic mice model with intraperitoneal injected ovalbumin medium, then with the flow cytometry analysis, we detected the ILCs and their surface proteins in the mice blood samples, besides, we analyzed the amounts of inflammatory cytokines and secreted proteins in the mice bronchoalveolar lavage fluid and blood serum. Moreover, Western blot analyzed the proteins in the mice bronchial epithelial tissues. The ILC2 amounts were obviously increased in young asthmatic mice model. And, the proteins CD25 and CCR10 were highly expressed in the sorted ILC2s. Besides, the cytokines interleukin (IL)-5, IL-13, IL-33, CCL22, and CCL27 were abundant in the bronchoalveolar lavage fluid of asthmatic mice model. And, the secretion of IL-5, IL-13, IL-33, TSLP, and CCL22 in blood serum was much more in asthmatic mice model than in the normal control mice, whereas the secretion of PGD2 was suppressed in asthmatic mice bronchoalveolar lavage fluid and blood serum. Additionally, the guanine nucleotide-binding proteins Gα12 and Gα13 were upregulated in asthmatic mice bronchial tissues, and the protein SERCA2 was downregulated; moreover, the proteins NFAT, IRF4, and its downstream signal STAT6 were all upregulated in the asthmatic mice bronchial tissues. ILC2s were involved in the response of airway inflammation through secretion of proinflammatory cytokines and chemokines to dysregulate the Ca2+ homeostasis in airway in the process of asthma. [Figure: see text].

Introduction: Transarterial chemoembolization (TACE) combined with PD-1 inhibitor is a novel and effective combination therapy. However, there is currently a gap in subsequent treatment when patients are diagnosed with PD-1 inhibitors-TACE refractoriness.Methods: This retrospective cohort study included enrolled patients with intermediate stage HCC who were diagnosed with PD-1 inhibitor-TACE refractoriness between January 2019 and December 2020 in the Eastern Hepatobiliary Surgery Hospital and the First Affiliated Hospital of Wenzhou Medical University. They were divided into two cohorts, (1) those who switched from TACE combined with PD-1 to stereotactic body radiation therapy (SBRT) combined with PD-1 and (2) those who continued TACE combined with PD-1. Progression free survival (PFS), overall survival (OS), and tumor response were assessed in both groups after refractory to PD-1 inhibitors combined with TACE.Results: Of the seventy-six patients included in this study, the median PFS was 19.6 months in the SBRT group (n=31) and 10.1 months in the TACE group (n=45, pConclusions: SBRT combined with PD-1 inhibitor improves PFS and OS in patients refractory to PD-1 inhibitor combined with TACE. Therefore, SBRT is recommended in case of failure of treatment with PD-1 inhibitors combined with TACE.

Objectives: This study aimed to describe and compare health-related quality of life (HRQoL) among populations with normal glycemic levels, prediabetes, and diabetes in southwest China and to offer baseline data that can be easily compared to other regions in China or across countries.Methods: A quality of life survey based on the EuroQoL-5 Dimension-5 level (EQ-5D-5L) scale was conducted through face-to-face or telephone interviews. A total of 403 respondents with diabetes, 404 with prediabetes, and 398 with normal blood glucose were enrolled in the survey. Propensity score matching (PSM) was used to decrease the bias of three groups, conditioned on age and gender, body mass index (BMI), and household income. For the three groups, we matched two groups first and then matched the result with the third group. Differences among groups were compared by chi-square test one-way ANOVA after adjusting by PSM.Results: In general, the blood glucose of people with diabetes was generally well-controlled in southwest China, but they were often accompanied by the circulatory system and nutritional metabolic diseases. Ninety-nine individuals from each group were matched. The EuroQoL-5 Dimension index of the population with normal glycemic levels, prediabetes, and patients with diabetes was 0.901, 0.948, and 0.897. The EuroQol-visual analog scales (EQ-VAS) scores of each group above were 73.76, 77.45, and 68.34. HRQoL in males was higher than that of females in the three study groups. The results after PSM were consistent with that before matching.Conclusion: There was a general trend that patients were associated with a decline of HRQoL from the prediabetic population, population with normal glycemic levels to diabetic population. Pain/discomfort and anxiety/depression might not be specific for the population with or without diabetes.

People are exposed to various magnetic fields, including the high static/steady magnetic field (SMF) of MRI, which has been increased to 9.4 T in preclinical investigations. However, relevant safety studies about high SMF are deficient. Here we examined whether 3.5-23.0 T SMF exposure for 2 h has severe long-term effects on mice using 112 C57BL/6J mice. The food/water consumption, blood glucose levels, blood routine, blood biochemistry, as well as organ weight and HE stains were all examined. The food consumption and body weight were slightly decreased for 23.0 T-exposed mice (14.6%, P 0.01, and 1.75-5.57%, P 0.05, respectively), but not the other groups. While total bilirubin (TBIL), white blood cells, platelet and lymphocyte numbers were affected by some magnetic conditions, most of them were still within normal reference range. Although 13.5 T magnetic fields with the highest gradient (117.2 T/m) caused spleen weight increase, the blood count and biochemistry results were still within the control reference range. Moreover, the highest field 23.0 T with no gradient did not cause organ weight or blood biochemistry abnormality, which indicates that field gradient is a key parameter. Collectively, these data suggest 3.5-23.0 T static magnetic field exposure for 2 h do not have severe long-term effects on mice.

Liver cancer is the most common cancer and is the epitome of a recalcitrant cancer. Increasing evidence shown that long noncoding RNAs (lncRNA) were associated with cancer‐related death and could function as a competing endogenous RNA (ceRNA). To explore regulatory roles and potential prognostic biomarkers of lncRNA for liver cancer, RNA‐sequencing expression data were downloaded from the TCGA database and GEO database. A total of 357 patients were randomly divided into a discovery group and a validation group, of which 313 patients can obtain clinical data. In discovery phrase, 58 lncRNAs, 16 miRNAs, and 34 mRNAs were screened to construct the ceRNA network based on 252 patients employed from discovery group. Univariate and multivariate Cox hazard regression analysis model revealed that five lncRNAs (AATK‐AS1, C10orf91, LINC00162, LINC00200, and LINC00501) from 58 lncRNAs were formulated to predict the overall survival (OS). We used the value of gene expression and regression coefficients to construct a risk score based on the five lncRNAs. Next, we validated our model in the GSE116174 dataset (n = 64) and the validation group (n = 94) from TCGA database. Subgroup analysis suggest that the five lncRNAs played critical parts in early stage in cancer from both discovery and validation groups. The five lncRNAs were also found to be associated with immune cells infiltration including CD4+ memory activated, NK cells activated and mast cells activated, then the results were also validated according to the validation group. Furthermore, KEGG pathway enrichment analysis showed that these nine coexpressed modules using the method of WGCNA, and many of these pathways are associated with the development and progression of disease. At last, the transcription factor binding sites (TFBS) of the five lncRNAs were predicted, which help us to understand the potential mechanism that the TFBS adjusted the ceRNA network. In summary, the ceRNA regulatory network may contribute to a better understanding of liver cancer mechanism and provide potential prognostic biomarkers and therapeutic targets., lncRNA play critical roles in the development of cancer and may have close relation to prognosis. we constructed a ceRNA network, and a risk‐score model based on eight‐lncRNA to predicted the OS time of HCC patients.

Prostaglandin E2 (PGE2), an essential endogenous lipid mediator for normal physiological functions, can also act as an inflammatory mediator in pathological conditions. We determined whether Staphylococcus aureus lipoproteins are essential for inducing PGE2 secretion by immune cells and whether pattern recognition receptors mediate this process. PGE2 levels secreted by mouse peritoneal macrophages infected with the S. aureus isogenic mutant, lgt::ermB (Δlgt; deficient in lipoprotein maturation), decreased compared with those from macrophages infected with wild-type (WT) S. aureus. Experiments using toll-like receptors 2 (TLR2)-deficient, TLR4-deficient, and NLRP3-deficient mice indicated that these 3 proteins are involved in macrophage PGE2 secretion in response to S. aureus, and lipoproteins were essential for S. aureus invasion and survival within macrophages. Inhibition of endogenous PGE2 synthesis had no effect on bacterial invasion. Exogenous PGE2 inhibited phagocytosis in the WT S. aureus and its isogenic mutant but increased intracellular killing accompanied by enhanced IL-1β secretion. Our data demonstrate that S. aureus can induce macrophage TLR/mitogen-activated protein kinase/NF-κB signaling and that PGE2 treatment upregulates NLRP3/caspase-1 signaling activation. Thus, macrophage PGE2 secretion after S. aureus infection depends on bacterial lipoprotein maturation and macrophage receptors TLR2, TLR4, and NLRP3. Moreover, exogenous PGE2 regulates S. aureus-induced macrophage activation through TLRs and NLRP3 inflammasome signaling.

HS2 molecules play an important role in the photochemical processes in combustion, atmosphere, and interstellar medium, yet our knowledge about the electronic excited states in the UV region is limited. In this study, we perform high-level ab initio calculations on electronic states of HS2 using the internally contracted multireference configuration interaction method including the Davidson correction (icMRCI + Q) method. The vertical transition energies, oscillator strengths, electron configurations, and transitions of thirteen electronic states of HS2 with energy up to 8 eV are calculated at the icMRCI + Q/aug-cc-pv(5 + d)Z level. Based on the calculated potential energy curves, we investigate the interaction and photodissociation mechanism of the electronic states, which should shed some light on the decomposition processes of the gas-phase HS2 molecules in the ultraviolet region.

A convenient photocatalyst-free method for the synthesis of redox-active 1,2-dihydro-3H-indazol-3-one derivatives from (2-nitroaryl)methanol and amines was developed. The reaction proceeded efficiently at room temperature by irradiation of UV light under CO2 atmosphere (1.0 atm, flow) without any photocatalysts or additives. This mild, operationally simple method shows wide functional tolerance. The carbamate formed in situ from CO2 and amine is proposed to be the key of this reaction. Some of these compounds synthesized by the present method were found to exhibit high anticancer activities, which can lower the viability of cancerous cell lines such as HeLa, MCF-7 and U87.

Background Several members of the tripartite motif-containing (TRIM) protein family have been reported to serve as vital regulators of tumorigenesis. Recent studies have demonstrated an oncogenic role of TRIM 14 in multiple human cancers; however, the importance of this protein in glioblastoma remains to be elucidated. Methods The expression levels of TRIM14 were analyzed in a series of database and were examined in a variety of glioblastoma cell lines. Two independent TRIM14 shRNA were transfected into LN229 and U251 cells, and the effect of TRIM14 depletion was confirmed. Transwell assay and wound healing assay assay were carried out to assess the effect of TRIM14 depletion on glioblastoma cell invasion and migration. Western blotting was performed to screen the downstream gene of TRIM14. The stability analysis and Ubiquitylation assays and Orthotopic xenograft studies were also performed to investigate the role of TRIM14 and the relationship with downstream gene. Human glioblastoma tissues were obtained and immunohistochemical staining were carried out to confirm the clinical significance of TRIM14. Results In this study, we showed that TRIM14 was upregulated in human glioblastoma specimens and cell lines, and correlated with glioblastoma progression and shorter patient survival times. Functional experiments showed that decreased TRIM14 expression reduced glioblastoma cell invasion and migration. Furthermore, we identified that zinc finger E-box binding homeobox 2 (ZEB2), a transcription factor involved in epithelial–mesenchymal transition, is a downstream target of TRIM14. Further investigation revealed that TRIM14 inactivation significantly facilitated ZEB2 ubiquitination and proteasomal degradation, which led to aggressive invasion and migration. Our findings provide insight into the specific biological role of TRIM14 in tumor invasion. Conclusions Our findings provide insight into the specific biological role of TRIM14 in tumor invasion, and suggest that targeting the TRIM14/ZEB2 axis might be a novel therapeutic approach for blocking glioblastoma.

Bacterial contamination often impairs uterine function in cattle leading to uterine diseases such as endometritis. Inflammatory responses to bacterial infections in the uterus of cattle are generated through pattern recognition receptors, including Toll-like receptor 2 (TLR2), which is responsible for Pam3CSK4 recognition. This cellular response induces inflammatory responses through stimulation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling activation, stimulating the expression of inflammatory mediators. Prostaglandin (PG) E2 has important actions in bacterial endometritis, although details through which these mechanisms regulate Pam3CSK4-induced inflammatory responses in cattle endometrial epithelial cells (bEECs) remain unclear. In the present study there was examination of the actions of exogenous PGE2 in Pam3CSK4-induced inflammatory responses. The bEECs pre-treated with exogenous PGE2 prior to Pam3CSK4 treatment had an augmented Pam3CSK4-stimulated phosphorylation of protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and IκB-α; stimulation of TLR2, cyclooxygenase-2, and interleukin-6 functions; and suppression of the activation of PGE2 receptor 4. Thus, Pam3CSK4-induced inflammatory responses through TLR2 signaling in bEECs were enhanced by exogenous PGE2 pre-treatment.

Genetic analyses have linked microRNA-137 (MIR137) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder. miR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss-of-function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline knockout or nervous system knockout (cKO) leads to postnatal lethality, while heterozygous germline knockout and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior. Transcriptomic and proteomic analyses revealed that the miR-137 mRNA target, phosphodiesterase 10a (Pde10a), is elevated in heterozygous knockout mice. Treatment with the Pde10a inhibitor papaverine or knockdown of Pde10a ameliorates the deficits observed in the heterozygous cKO mice. Collectively, our results suggest that MIR137 plays essential roles in postnatal neurodevelopment and that dysregulation of miR-137 potentially contributes to neuropsychiatric disorders in humans.

Background In China, 13-valent pneumococcal conjugate vaccine (PCV13) has been available since 2017, but only via the private market with low uptake rate. We assessed the direct effectiveness of PCV13 against community acquired pneumonia (CAP) associated with PCV13 serotype carriage (VT-CAP). Methods We conducted an observational cohort study of children born during 12-Dec-2016 to 30-Nov-2018 identified in the Suzhou Centers for Disease Control vaccine registry database, and who had at least one inpatient or outpatient record at the Suzhou University Affiliated Children’s hospital (SCH) health-information-system (HIS) database. The vaccine registry cohort was followed through the HIS database through 30-Jun-2019 to identify hospitalized VT-CAP. Pneumococci were isolated from deep upper respiratory aspirates and serotyped with Quellung reactions. Results We included 139,127 children of whom 9024 (6.5%) received 1 + PCV13 doses (95.8% received 2 + doses). Within the total cohort, we identified 548 children hospitalized at SCH for VT-CAP, of whom 10 had received 2 + PCV13 doses. Adjusted for demographics, receipt of other childhood vaccines, and underlying medical conditions, the first visit vaccine effectiveness among children who had received 2 + PCV13 doses was 60.9% (95% CI: 25.8% to 79.4%) for VT-CAP and 17.9% (95% CI: 5.5% to 28.6%) for clinical CAP. Incidence rate reductions per 100,000 child-years of observation for all visits were 208 (95% CI: 118 to 298) for VT-CAP and 720 (95% CI: 304 to 1135) for clinical CAP. Conclusions PCV13 was protective against hospitalized VT-CAP and clinical CAP with large associated incidence rate reductions among children living in Suzhou, China.

Objectives: Glioma is the most common and aggressive type of primary central nervous system (CNS) tumor in adults and is associated with substantial mortality rates. The aim of our study was to evaluate the prognostic significance and function of the complement factor I (CFI) in glioma.Materials and Methods: The expression levels of CFI in glioma tissues and the survival of the CFIhigh and CFIlow patient groups were analyzed using The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). The correlation between CFI expression and clinicopathological features of glioma was determined by univariate and multivariate Cox regression analyses in the Chinese Glioma Genome Atlas (CGGA) database. The functional role of CFI in glioma was established through routine in vitro and in vivo assays.Results: CFI is overexpressed in glioma and its high levels correlated with poor outcomes in both TCGA and CGGA datasets. Furthermore, CFI was identified as an independent prognostic factor of glioma in the CGGA database. CFI knockdown in glioma cell lines inhibited growth in vitro and in vivo, whereas its ectopic expression increased glioma cell proliferation, migration, and invasion in vitro. CFI protein levels were also significantly higher in the glioma tissues resected from patients and correlated to worse prognosis.Conclusions: CFI is a potential prognostic biomarker in glioma and drives malignant progression.

COVID-19 has broken out rapidly in nearly all countries worldwide, and has blossomed into a pandemic. Since the beginning of the spread of COVID-19, many scientists have been cooperating to study a vast array of old drugs and new clinical trial drugs to discover potent drugs with anti-COVID-19 activity, including antiviral drugs, antimalarial drugs, immunosuppressants, Chinese medicines, Mpro inhibitors, JAK inhibitors, etc. The most commonly used drugs are antiviral compounds, antimalarial drugs and JAK inhibitors. In this review, we summarize mainly the antimalarial drugs chloroquine and hydroxychloroquine, the antiviral drugs Favipiravir and Remdesivir, and JAK inhibitor Ruxolitinib, discussing their biological activities, clinical trials and synthesis progress.

The tumor microenvironment (TME) plays an important role in the development of breast cancer. Due to limitations in experimental conditions, the molecular mechanism of TME in breast cancer has not yet been elucidated. With the development of bioinformatics, the study of TME has become convenient and reliable. Gene expression and clinical feature data were downloaded from The Cancer Genome Atlas database and the Molecular Taxonomy of Breast Cancer International Consortium database. Immune scores and stromal scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data algorithm. The interaction of genes was examined with protein-protein interaction and co-expression analysis. The function of genes was analyzed by gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis. The clinical significance of genes was assessed with Kaplan-Meier analysis and univariate/multivariate Cox regression analysis. Our results showed that the immune scores and stromal scores of breast invasive ductal carcinoma (IDC) were significantly lower than those of invasive lobular carcinoma. The immune scores were significantly related to overall survival of breast IDC patients and both the immune and stromal scores were significantly related to clinical features of these patients. According to the level of immune/stromal scores, 179 common differentially expressed genes and 5 hub genes with prognostic value were identified. In addition, the clinical significance of the hub genes was validated with data from the molecular taxonomy of breast cancer international consortium database, and gene set enrichment analysis analysis showed that these hub genes were mainly enriched in signaling pathways of the immune system and breast cancer. We identified five immune-related hub genes with prognostic value in the TME of breast IDC, which may partly determine the prognosis of breast cancer and provide some direction for development of targeted treatments in the future.