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Formononetin-inhibited IgE-mediated mast cell activation and attenuated IgE/Ag-induced allergic inflammation by suppressing USP5 or USP13 expression and increasing proteasome-mediated FcεRIγ degradation.

Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR-199a-5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR-199a-5p in myocardial I/R injury remain not well-studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR-199a-5p regulates whether miR-199a-5p contributes to ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis-induced cardiomyocyte death occurs and is accompanied by an increase in miR-199a-5p level in OGD/R-treated H9c2 cells. MiR-199a-5p inhibitor ameliorated ferroptosis-induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe

Thyroid cancer is considered to be one of the most common endocrine tumors worldwide. Cystathionine β-synthase (CBS) plays a crucial role in the occurrence of several types of malignancies. And yet, the mechanism of action of CBS in the growth of thyroid carcinoma cells is still unrevealed. We found that CBS level in thyroid carcinoma tissue was higher than that in adjacent normal tissue. The overexpression of CBS enhanced the proliferation, migration, and invasion of thyroid cancer cells, while the downregulation of CBS exerted reverse effects. CBS overexpression reduced the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase in thyroid cancer cells, whereas CBS knockdown showed reverse trends. CBS overexpression decreased reactive oxygen species (ROS) levels but increased the levels of Wnt3a and phosphorylations of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR), β-catenin, and glycogen synthase kinase-3 beta, while CBS knockdown exerted opposite effects. In addition, CBS overexpression promoted the growth of xenografted thyroid carcinoma, whereas CBS knockdown decreased the tumor growth by modulating angiogenesis, cell cycle, and apoptosis. Furthermore, aminooxyacetic acid (an inhibitor of CBS) dose-dependently inhibited thyroid carcinoma cell growth. CBS can regulate the proliferation, migration, and invasion of human thyroid cancer cells via ROS-mediated PI3K/AKT/mTOR and Wnt/β-catenin pathways. CBS can be a potential biomarker for diagnosing or prognosing thyroid carcinoma. Novel donors that inhibit the expression of CBS can be developed in the treatment of thyroid carcinoma.

Background Multiple sclerosis is a diffuse chronic demyelinating disease of the central nervous system. It is relatively uncommon in the Asian population and even more so in males. Despite the usual involvement of the brainstem, eight-and-a-half syndrome remains a rare first presentation in multiple sclerosis. Only a few cases have been reported previously, but none involving the Asian population. Eight-and-a-half syndrome, a neuro-ophthalmological condition, is characterized by one-and-a-half syndrome with ipsilateral lower facial nerve palsy, which localizes lesions to the pontine tegmentum. This case report demonstrates the first case of eight-and-a-half syndrome as the first presentation of multiple sclerosis in an Asian male. Case presentation A healthy 23-year-old Asian man presented with sudden onset of diplopia followed by left-sided facial asymmetry for 3 days. Assessment of extraocular movement revealed left conjugate horizontal gaze palsy. On right gaze, there was limited left eye adduction and horizontal nystagmus of the right eye. These findings were consistent with a left-sided one-and-a-half syndrome. Prism cover test revealed left esotropia of 30 prism diopters. Cranial nerve examination showed left lower motor neuron facial nerve palsy, while other neurological examination was normal. Magnetic resonance imaging brain showed multifocal T2 fluid attenuated inversion recovery hyperintense lesions, involving bilateral periventricular, juxtacortical, and infratentorial regions. A focal gadolinium contrast-enhanced lesion with open ring sign on T1 sequence was seen at the left frontal juxtacortical region. Multiple sclerosis was diagnosed on the basis of the clinical and radiological evidence, which fulfilled the 2017 McDonald criteria. Positive oligoclonal bands in cerebrospinal fluid analysis further confirmed our diagnosis. He had a complete resolution of symptoms 1 month after a course of pulsed corticosteroid therapy, and was subsequently placed on maintenance therapy with interferon beta-1a. Conclusion This case illustrates eight-and-a-half syndrome as the first presentation of a diffuse central nervous system pathology. A wide range of differential diagnoses needs to be considered in such a presentation as based on the patient’s demographics and risk factors.

A novel endophytic bacterium, designated strain BGMRC 0089T, was isolated from a surface-sterilized root of Sonneratia apetala. Cells were observed to be Gram-negative, rod-shaped and motile with polar flagella. Strain BGMRC 0089T was found to grow optimally at 28–30 °C, pH 7.0–8.0 and in the presence of 1 % (w/v) NaCl. Strain BGMRC 0089T contained ubiquinone Q-10 and the predominant fatty acid was summed feature 8. The polar lipid profile of strain BGMRC 0089T was found to contain diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine and phosphatidylethanolamine. Based on the results of 16S rRNA gene analysis, this isolate has the closest phylogenetic relationships with Rhizobium lemnae L6-16T (96.5 %) and Allorhizobium oryziradicis N19T (96.4 %). Average nucleotide identity, amino acid identity and digital DNA–DNA hybridization values of the isolate with the type strains of the genera Rhizobium and Allorhizobium were below 84.6, 73.9 and 22.1 %, respectively. Analysis the 4.55 Mb draft genome of strain BGMRC 0089T revealed several plant-associated genes, which may play important roles for the plant in the adaptation to the mangrove habitat. Based on its distinct phylogenetic, phenotypic and chemotaxonomic characteristics, strain BGMRC 0089T is proposed to represent a novel Allorhizobium species, for which the name Allorhizobium sonneratiae sp. nov. is proposed (type strain BGMRC 0089T=DSM 100171T=MCCC 1K04805T).

Background Laser photocoagulation is an effective procedure for the treatment of diabetic macular edema (DME). However, the beneficial effects of conventional laser photocoagulation (CLP) are accompanied by the destruction of retinal photoreceptors. Therefore, subthreshold micropulse laser photocoagulation (SMLP) was proposed for DME. Objectives This meta-analysis study was performed to evaluate the efficacy and safety of SMLP compared with CLP for the management of DME. Methods The PubMed, Embase, Web of Science, Cochrane, SinoMed, ClinicalTrials.gov, Wanfang and China National Knowledge Infrastructure (CNKI) databases, published until Dec 2021, were searched to identify studies evaluating the clinical outcomes of SMLP for DME. Results 8 randomized controlled trials (RCTs) were selected for this meta-analysis involving a total of 546 eyes (275 eyes in SMLP group and 271 eyes in CLP group). SMLP of different wavelengths (577nm and 810nm) and duty cycles (5% and 15%) were applied. The pooled outcomes showed that SMLP group, especially 577nm and 810nm 15% duty cycle parameter settings, had a statistically significant higher efficacy than CLP group in terms of BCVA(MD = -0.02, 95% CI: -0.03 to -0.01, P0.05); In the field of CS, SMLP group (no matter parameter settings) resulted in better preservation of CS compared to CLP group (MD = 1.96, 95% CI: 1.47 to 2.46, P

This post hoc analysis aimed to estimate eptinezumab’s therapeutic effect on health utilities and determined to which extent monthly migraine days (MMDs) explain changes in health utilities. DELIVER, a randomized, double-blind, placebo-controlled phase 3b trial (NCT04418765), investigated eptinezumab efficacy and safety in patients with 2-4 prior migraine treatment failures. Regression analysis explored the relationship between utility scores and MMDs, with eptinezumab treatment as a covariate along with MMDs to identify any MMD-independent effect on utilities. Path analysis quantified eptinezumab’s impact as mediated through MMD reduction. The base case model showed that each reduction in MMD was associated with a mean utility score increase (0.0189; 95% CI: 0.0180, 0.0198; P < 0.001). Mean utility score was generally higher for eptinezumab versus placebo, justifying addition of treatment effect to the base case model. Patients administered eptinezumab had on average 0.0562 (95% CI: 0.0382, 0.0742; P < 0.001) higher utility versus placebo when controlling for number of MMDs. From path analysis, MMD reduction resulting from eptinezumab treatment accounted for 53% additional utility gain observed in patients. Changes in MMDs alone inadequately captured migraine’s impact on patient utility, as there was also a positive eptinezumab-driven, treatment-specific impact on utility score. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04418765).

Refereed/Peer-reviewed Microplastics exposure is a new human health crisis. Although progress in understanding health effects of microplastic exposure has been made, microplastic impacts on absorption of co-exposure toxic pollutants such as arsenic (As), i.e., oral bioavailability, remain unclear. Microplastic ingestion may interfere As biotransformation, gut microbiota, and/or gut metabolites, thereby affecting As oral bioavailability. Here, mice were exposed to arsenate (6 μg As g−1) alone and in combination with polyethylene particles of 30 and 200 μm (PE-30 and PE-200 having surface area of 2.17 × 103 and 3.23 × 102 cm2 g−1) in diet (2, 20, and 200 μg PE g−1) to determine the influence of microplastic co-ingestion on arsenic (As) oral bioavailability. By determining the percentage of cumulative As consumption recovered in urine of mice, As oral bioavailability increased significantly (P < 0.05) from 72.0 ± 5.41% to 89.7 ± 6.33% with PE-30 at 200 μg PE g−1 rather than with PE-200 at 2, 20, and 200 μg PE g−1 (58.5 ± 19.0%, 72.3 ± 6.28%, and 69.2 ± 17.8%). Both PE-30 and PE-200 exerted limited effects on pre- and post-absorption As biotransformation in intestinal content, intestine tissue, feces, and urine. They affected gut microbiota dose-dependently, with lower exposure concentrations having more pronounced effects. Consistent with the PE-30-specific As oral bioavailability increase, PE exposure significantly up-regulated gut metabolite expression, and PE-30 exerted greater effects than PE-200, suggesting that gut metabolite changes may contribute to As oral bioavailability increase. This was supported by 1.58–4.07-fold higher As solubility in the presence of up-regulated metabolites (e.g., amino acid derivatives, organic acids, and pyrimidines and purines) in the intestinal tract assessed by an in vitro assay. Our results suggested that microplastic exposure especially smaller particles may exacerbate the oral bioavailability of As, providing a new angle to understand health effects of microplastics.

Intensive care unit (ICU) patients are critically ill and have low immunity. They will undergo various trauma medical procedures during diagnosis and treatment. The use of high-dose hormones and broad-spectrum antibiotics will increase the incidence of nosocomial infection in ICU patients. Therefore, it is necessary to explore the causes of nosocomial infection in ICU and provide basis for the prevention and control of nosocomial infection in ICU.To explore major pathogens of nosocomial infection in ICUs, methods of detection and drug resistance trends.Risk factors of multidrug-resistant infection were analyzed to provide a basis for clinical rational use of antimicrobial drugs in the ICU. These findings were used to standardize rational use of antimicrobial agents. BD PhoenixTM100 automatic bacterial identification analyzer was used to for cell identification in specimens collected from the ICU between January 2016 and December 2019. Drug sensitivity tests were carried out and drug resistance trends were analyzed using the optical disc diffusion method. Odds ratios and corresponding 95%CI of independent variables were calculated using a logistic regression model. Backward elimination (trend = 0.1) was used as an inclusion criterion for multivariate analysis. All data were analyzed using SPSS version 22.0, andWe collected 2070 samples from ICU patients between January 2016 and December 2019. Sample types comprised sputum (1139 strains, 55.02%), blood (521 strains, 25.17%), and drainage fluid (117 strains, 5.65%). A total of 1051 strains of major pathogens, includingThis study showed a high incidence of ICU infections. Mechanical ventilation and urine tube intubation were risk factors for infection with multidrug-resistant bacteria.

INTRODUCTION This study aimed to assess understanding of the potential risks associated with medical imaging among caregivers and adolescent patients in a paediatric emergency department (PED) in Singapore. METHODS A prospective convenience sample survey was performed involving adolescents and caregivers presenting to our PED from December 2015 to May 2016. The questionnaire examined demographic data, knowledge of imaging procedures and radiation risks, and expectations regarding information provided about medical radiation. RESULTS A total of 349 questionnaires were returned (caregivers 82.5%, adolescents 17.5%). A mean of 6.2 ± 2.4 (out of 11) questions were correctly answered. Those who had tertiary education fared better than those who did not (36.4% vs. 17.2% scoring above the mean, p = 0.001). Age, gender, history of previous imaging and imaging performed during the visit did not affect the score. Two-thirds of the participants did not associate medical radiation with any negative lifetime risk of cancers or know that different scans entailed differing amounts of radiation. Most were unaware that the radiation dose in medical imaging is adjusted to a child’s size. Among patients who underwent imaging, 90.1% received explanations on the need for scans, and 26.5% were informed of the risks involved. Almost all participants wished to be informed of imaging indications and risks. More preferred to learn this from physicians (75.6%) or technicians (51.6%) rather than through educational pamphlets (34.4%) or Internet resources (22.9%). CONCLUSION Awareness regarding medical radiation needs to be improved in our patient population. A mismatch exists between caregiver expectations and the actual procedure of disclosure of the risk associated with radiation.

The role of hydrogen sulphide (H

Social information processing is important for successful romantic relationships and protection against depression, and depends on functional connectivity (FC) within and between large-scale networks. Functional architecture evident at rest is adaptively reconfigured during a task, and there were two possible associations between brain reconfiguration and behavioral performance during neurocognitive tasks (efficiency effect and distraction-based effect). This study examined the relationships between brain reconfiguration during social information processing and relationship-specific and more general social outcomes in marriage. Resting-state FC was compared with FC during social information processing (watching relationship-specific and general emotional stimuli) of 29 heterosexual couples, and the FC similarity (reconfiguration efficiency) was examined in relation to marital quality and depression 13 months later. The results indicated that wives’ reconfiguration efficiency (globally and in visual association network) during relationship-specific stimuli processing was related to their own marital quality. Higher reconfiguration efficiency (globally and in medial frontal, frontal-parietal, default mode, motor/sensory and salience networks) in wives during general emotional stimuli processing was related to their lower depression. These findings suggest efficiency effects on social outcomes during social cognition, especially among married women. The efficiency effects on relationship-specific and more general outcomes are, respectively, higher during relationship-specific stimuli or general emotional stimuli processing.

Objectives To analyse the patterns of transition of health burden for 110 causes of death by stratification of age, sex and geographic regions in Guangdong between 2005 and 2015. Methods We analysed the age-specific, sex-specific, region-specific mortality in Guangdong based on assembled databases. County-level surveillance data were calculated to inform city-level changes. Results The age-standardised mortality of all causes, non-communicable diseases (NCDs), communicable diseases, maternal diseases, neonatal diseases, malnutrition and injury declined progressively. Despite declining mortality of NCDs, the overall burden of disease was dominated by NCDs (ie, cerebrovascular disease, chronic obstructive pulmonary disease) that still accounted for 86.93% and 88.12% of death in 2005 and 2015, respectively. Considerable variations across geographic regions were observed (lowest in Pearl River Delta and highest in west Guangdong). There was a modest shift to transport injuries at younger ages and unintentional injuries in the elderly. Conclusions We have documented a dramatic change in the overall mortality and age-specific, sex-specific and cause-specific mortality in Guangdong province between 2005 and 2015. The significant burden of NCDs remains a major healthcare issue despite the notable progress in reducing mortality in Guangdong, China. Our findings highlight important unmet needs to refine healthcare services by taking into account the inequity of age, sex and geographic regions. Identification of the ‘treatable’ risk factors and improved disease surveillance should be continuously improved to minimised the overall and cause-specific mortality.

Testicular cancer is the most common malignant tumor in young men, and its incidence has increased in recent years. The tumor microenvironment (TME) plays a crucial role in the development and progression of tumors; however, the TME of testicular germ cell tumor (TGCT) is poorly understood. In this study, we downloaded information for 156 TGCT cases from The Cancer Genome Atlas (TCGA) database, used the ESTIMATE method to determine immune and stromal scores, and used CIBERSORT to calculate the proportion of tumor-infiltrating immune cells (TICs). The differentially expressed genes were subjected to a COX regression analysis and used for the construction of a protein–protein interaction (PPI) network. Toll-like receptor 2 (TLR2) was identified as a predictive marker by combining the results of the Cox regression analysis and PPI network. A survival analysis showed that TLR2 was positively correlated with TGCT survival. A gene set enrichment analysis indicated that genes in the high TLR2 expression group were enriched for cell adhesion molecules (CAMs) and the chemokine signaling pathway, and genes in the low TLR2 expression group were mainly enriched in the spliceosome. Regarding proportions of TICs, naive B cells and follicular helper T cells were negatively correlated with the expression of TLR2. This suggests that as TLR2 expression increases, the immunocompetence of the TME decreases. The expression of TLR2 may affect the prognosis of TGCT, suggesting that this locus can be used as a prognostic factor for TGCT.

Background The aim of this study was to evaluate the in vivo confocal microscopic morphology of corneal subbasal nerves and its relationship with clinical parameters in patients with primary Sjögren’s syndrome in China. Methods This was a case control study of 22 dry eye disease (DED) patients with primary Sjögren’s syndrome (pSS) and 20 control subjects with non-Sjögren dry eye disease (NSDE). Each patient underwent an evaluation of ocular surface disease using the tear film break-up time (TBUT), noninvasive tear film break-up time (NIKBUT), noninvasive tear meniscus height (NIKTMH), corneal staining (National Eye Institute scale, NEI), Schirmer I test, meibography, and corneal subbasal nerve analysis with in vivo confocal microscopy (IVCM). The right eye of each subject was included in this study. Results SS patients showed a shorter TBUT (P = 0.009) and Schirmer I test results (P = 0.028) than the NSDE group. However, there was no significant difference in NIKBUT between the two groups (P = 0.393). The nerve density of subbasal nerves, number of nerves and tortuosity of the SS group were significantly lower than those of the NSDE group (P = 0.001, P P = 0.039, respectively). In the SS group, the mean nerve length was correlated with age and the Schirmer I test (r = − 0.519, P = 0.013 and r = 0.463, P = 0.035, respectively). Corneal staining was correlated with nerve density and the number of nerves (r = − 0.534, P = 0.013 and r = − 0.487, P = 0.025, respectively). Conclusions Sjögren syndrome dry eye (SSDE) patients have more severe clinical dry eye parameters than non-Sjögren dry eye disease (NSDE) patients. Compared with NSDE patients, we found that SSDE patients showed decreased corneal subbasal nerve density and numbers.

Pulsed electric field (PEF) is a nonthermal technology resulting in the rupture of cell membranes and increasing the electrical conductivity and the permeability of intracellular material. There was little work about the safety of food treated by PEF. The acute, subacute oral, and genetic toxicities were investigated to explore the safety of canola oil extracted by aid of PEF treatment (PTCO). The results showed that no negative consequences were caused by PEF. PTCO was regarded as practically non-toxic with a LD

Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.

Obesity is considered as a risk factor for chronic health diseases such as heart diseases, cancer, and diabetes 2. Reduced physical activities, lifestyle, poor nutritional diet, and genetics are among the risk factors associated with the development of obesity. In recent years, several studies have explored the link between the gut microbiome and the progression of diseases including obesity, with the shift in microbiome abundance and composition being the main focus. The alteration of gut microbiome composition affects both nutrients metabolism and specific gene expressions thereby disturbing body physiology. Specifically, the abundance of fiber-metabolizing microbes is associated with weight loss and that of protein and fat-metabolizing bacteria with weight gain. Various internal and external factors such as genetics, maternal obesity, mode of delivery, breastfeeding, nutrition, antibiotic use, and the chemical compounds present in the environment are known to interfere with the richness of the gut microbiota (GM), thereby influencing weight gain/loss and ultimately the development of obesity. However, the effectiveness of each factor in potentiating the shift in microbes' abundance to result in significant changes that can lead to obesity is not yet clear. In this review, we will highlight the factors involved in shaping gut microbiota, their influence on obesity and possible interventions. Understanding the influence of these factors on the diversity of the GM and how to improve their effectiveness on disease conditions could be key in the treatment of metabolic diseases.

Bladder cancer is one of the most common malignant tumors worldwide. Accordingly, its incidence and mortality are high. One of the characteristics of cancer is genomic instability. New studies suggest that long non-coding RNAs (lncRNAs) play an important role in maintaining genomic instability. This study aimed to identify a genomic instability-associated lncRNA signature to predict the outcome of patients with bladder cancer. We downloaded data for bladder cancer patients from The Cancer Genome Atlas database to obtain lncRNA expression profiles as well as somatic mutation profiles. Using the lncRNA computational framework, a genomic instability-related lncRNA signature (GIlncSig) was established and the prognostic value of this signature was assessed and validated. A five-lncRNA signature based on genomic instability (CFAP58-DT, MIR100HG, LINC02446, AC078880.3, and LINC01833) was obtained from 58 differentially expressed lncRNAs. Patients were divided into high-risk and low-risk groups, with the high-risk group having a substantially worse prognosis than the low-risk group. Univariate and multivariate Cox analyses indicated that GIlncSig may be an independent prognostic factor; this finding was subsequently validated. In addition, enrichment analysis indicated that GIlncSig is associated with genomic instability in bladder cancer. GIlncSig has a predictive value for the prognosis of bladder cancer patients and provides guidance for the clinical treatment of these patients.

Dystocia is a serious problem for pregnant women, and it increases the cesarean section rate. Although uterine dysfunction has an unknown etiology, it is responsible for cesarean delivery and clinical dystocia, resulting in neonatal morbidity and mortality; thus, there is an urgent need for novel therapeutic agents. Previous studies indicated that statins, which inhibit the mevalonate (MVA) pathway of cholesterol synthesis, can reduce the incidence of preterm birth, but the safety of statins for pregnant women has not been thoroughly evaluated. Therefore, to unambiguously examine the function of the MVA pathway in pregnancy and delivery, we employed a genetic approach by using myometrial cell-specific deletion of geranylgeranyl pyrophosphate synthase (Ggps1) mice. We found that Ggps1 deficiency in myometrial cells caused impaired uterine contractions, resulting in disrupted embryonic placing and dystocia. Studies of the underlying mechanism suggested that Ggps1 is required for uterine contractions to ensure successful parturition by regulating RhoA prenylation to activate the RhoA/Rock2/p-MLC pathway. Our work indicates that perturbing the MVA pathway might result in problems during delivery for pregnant females, but modifying protein prenylation with supplementary farnesyl pyrophosphate or geranylgeranyl pyrophosphate might be a strategy to avoid side effects.

Anaplastic thyroid carcinoma (ATC) is a highly malignant and aggressive thyroid malignancy with rapid onset and poor prognosis. There is no effective treatment for ATC yet. Molecular targeted therapy provides a new idea for ATC treatment. Tyrosine kinase inhibitor lenvatinib has potential in treating ATC patients with favorable efficacy in clinical trials. The effectiveness of the v-raf murine sarcoma viral oncogene homologue B1 ( BRAF) gene inhibitor dabrafenib in combination with trametinib for the treatment of BRAF (V600E) positive ATC patients has been demonstrated in clinical trials. The NCCN clinical practice guidelines in oncology has proposed dabrafenib in combination with trametinib as the preferred modality for the treatment of patients with BRAF (V600E) positive ATC. The immune checkpoint inhibitor pembrolizumab can be applied to treat thyroid cancer with high tumor mutational load and may be considered as the preferred modality for the treatment of ATC patients with high programmed death ligand-1 expression. The mammalian target of rapamycin pathway inhibitors, peroxisome proliferators-activated receptor γ agonists, endothelial growth factor receptors-targeting monoclonal antibody cetuximab and novel vascular blocker fosbretabulin are still in the clinical research stage, which are expected to provide new directions for the development of novel targeted drugs. This article reviews the current research progress on targeted drugs for the treatment of ATC.

Oral diseases are among the most common human diseases yet less studied. These diseases affect both the physical, mental, and social health of the patients resulting in poor quality of life. They affect all ages, although severe stages are mostly observed in older individuals. Poor oral hygiene, genetics, and environmental factors contribute enormously to the development and progression of these diseases. Although there are available treatment options for these diseases, the recurrence of the diseases hinders their efficiency. Oral volatile sulfur compounds (VSCs) are highly produced in oral cavity as a result of bacteria activities. Together with bacteria components such as lipopolysaccharides, VSCs participate in the progression of oral diseases by regulating cellular activities and interfering with the immune response. Hydrogen sulfide (H2S) is a gaseous neurotransmitter primarily produced endogenously and is involved in the regulation of cellular activities. The gas is also among the VSCs produced by oral bacteria. In numerous diseases, H2S have been reported to have dual effects depending on the cell, concentration, and donor used. In oral diseases, high production and subsequent utilization of this gas have been reported. Also, this high production is associated with the progression of oral diseases. In this review, we will discuss the production of H2S in oral cavity, its interaction with cellular activities, and most importantly its role in oral diseases.

Light energy can be harnessed by photosensitizers or photocatalysts so that some chemical reactions can be carried out under milder conditions compared to the traditional heat-driven processes. To facilitate the photodriven reactions, a large variety of chromophores that operate via charge transfer excitations have been reported because of their typically longer excited-state lifetimes, which are key to the downstream photochemical processes. Although both metal-to-ligand charge transfers and ligand-to-metal charge transfers are well-established light absorption pathways, the former has been widely adopted in photocatalysis, whereas the latter has taken on greater importance in photosensitization applications only recently. In this article, we review the latest developments on ligand-to-metal charge transfer photosensitization by molecular complexes across the periodic table, with a focus on homogeneous photocatalysis and the use of photophysical measurements and computational calculations to understand the electronic structures, photochemical processes, structure-activity relationships, and reaction mechanisms. We also present our perspectives on the possible future developments in the field. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version H.S.S. acknowledges that this project is supported by A*STAR under the AME IRG grant A2083c0050. H.S.S. is also grateful for the Singapore Ministry of Education Academic Research Fund Tier 1 grant RT 05/19. H.S.S. and X.Y.K. thank the Singapore National Academy of Science (SNAS) and the National Research Foundation (NRF) Singapore for funding under its SNAS ASEAN Postdoctoral Fellowship (NRF-MP-2020-0001) program. Part of this work was also supported by the Nanyang Technological University 5th ACE grant call and the 2021 American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable Ignition Grant. Z.H.T thanks the Nanyang Technological University - CN Yang Scholars Program for financial support.

Introduction We evaluated the risk factors associated with Type 1 retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants and compared ophthalmologic outcomes between cases with Type 1 ROP who received treatment and gestational age-matched controls with mild or no ROP not requiring treatment. Methods This was a retrospective case-control study of VLBW infants born in National University Hospital, Singapore, from January 2001 to December 2013. 17 cases with Type 1 ROP were each matched for gestational age with controls who had either mild (below Stage 2) or no ROP. Antenatal, perinatal and postnatal variables, as well as childhood ophthalmologic outcomes, were collected from their clinical records and analysed. Results The number of packed cell transfusions and highest fraction of inspired oxygen given at weeks 7-10 were found to be statistically significant on multivariate analysis (p = 0.045 and p = 0.049, respectively). None of the infants had blindness or retinal detachment, and there were no significant differences in refractive errors between the groups at 1-4 years of age. Strabismus at four years of age was more common in the group with Type 1 ROP (p = 0.023). Conclusion Increased episodes of blood transfusions and chronic lung disease requiring high oxygen supplementation at 7-10 weeks of life are significant risk factors associated with Type 1 ROP in VLBW infants in our study. Strabismus at four years is more common in this group of patients. This study highlights the importance of long-term ophthalmologic surveillance for these high-risk children.

Background Heterotopic pancreas is a common lesion found in the gastrointestinal tract and is usually considered a benign disease. Reports of malignant change of heterotopic pancreas are scarce. Case summary A 44-year-old Chinese female underwent a gastroscopy to assess abdominal distension that had persisted for 2 months. A protruding lesion in the gastric antrum was revealed but no malignant tissue was found in the biopsy specimen. The patient's symptom persisted and progressed to repeated vomiting. Endoscopy after 4 months revealed obstruction of the gastric outlet caused by the protruding lesion. A distal gastrectomy was performed. Histopathological examination of the surgical specimen showed the malignant transformation of aberrant pancreas in the stomach. Chemotherapy consisting of folinic acid, fluorouracil, and oxaliplatin was administered for three cycles, and was changed to gemcitabine monotherapy because of adverse effects and increased serum tumor marker levels. The patient remained asymptomatic during a 12-month follow-up. Conclusion Pancreatic heterotopy should be considered as source of a potentially malignant lesion, and early treatment or close monitoring for aberrant pancreas is recommended.

Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout the world. Previously, there were two outbreaks of severe coronavirus caused by different coronaviruses worldwide, namely Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a global health threat and caused a universal psychosocial impact on the general population. Therefore, the knowledge, attitude, and perceptions (KAPs) of the general population are critical for the development and effective implementation of standard operating procedures (SOP) to contain the contagion and minimize the losses. Therefore, the current study was conducted to understand and evaluate the KAPs of Pakistani populations toward the COVID-19.Methods: An online cross-sectional study was carried out among participants from 1 May to 30 July 2020 in different areas of Pakistan. The respondents of the study were the general population with age ≥ 18 years. The poll URL was posted on several channels after a call for participation. Other social media platforms such as WeChat, WhatsApp, Facebook, Twitter, Instagram, Messenger, and LinkedIn were engaged to maximize general population engagement. The questionnaire included details about sociodemographic, knowledge about COVID-19, perceptions toward universal safety precautions of COVID-19, and beliefs attitude toward the COVID-19. The obtained data were exported into a Microsoft Excel spreadsheet and SPSS software version 21 for windows. The descriptive statistics values were presented in frequencies and percentages. Binary logistic regression, Chi-square test, and one-way ANOVA were applied to analyze the participants' socio-demographic characteristics and variables related to KAPs. P-value < 0.05 was recorded as significant.Results: A total of 1,000 participants were invited of which 734 participated in this study. The response rate was 73.4% (734/1,000). The gender, marital status, education, and residence showed a significant association with the knowledge score. The majority of the study participants were thinking that COVID-19 may be more dangerous in elderly individuals 94.5% (n = 700), and individuals with chronic diseases or severe complications 96.7% (n = 710) (p = 0.00). More than half of the participants 52.5% (n = 385) showed their concern that either they or their family members might get the infection. More than 98% (n = 703), (P-value = 0.00) of the participants held that COVID-19 would be successfully controlled in Pakistan by following the standard SOPs and government guidelines.Conclusion: This study showed that the general population of Pakistan has good awareness and reasonable attitudes and perceptions toward the full features of the COVID-19. The current study suggests that mass-level effective health education programs are necessary for developing countries to improve and limit the gap between KAP toward COVID-19.

The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL).To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes.We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type.According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers.Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL.

Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin), is a small molecule glycoprotein associated with cell secretions. The purpose of our research is to clarify the clinicopathological and prognostic significance of SPARC expression in breast cancer. In this study, we performed a meta-analysis and bioinformatics analysis using the PubMed, Web of Science, Wanfang Data, and CNKI databases. The meta-analysis showed that SPARC expression was elevated in breast cancer tissue, compared with normal tissue, while SPARC expression in tumor stromal cells was higher than that of tumor cells. The expression of SPARC was positively correlated with histological grade and TNM staging. The Kaplan-Meier plotter showed that low SPARC expression was negatively correlated with the overall, postprogression, and distant metastasis survival rates of patients. According to Oncomine database, SPARC expression was upregulated in breast cancer than normal tissues. In TCGA database, univariate analysis showed that lymph node metastasis, distant metastasis, and TNM staging were negatively correlated with patient prognosis in breast cancers. Cox multivariate analysis showed that age, lymph node metastasis, distant metastasis, and TNM staging were important factors affecting the survival time of breast cancer patients. SPARC expression can be employed as a good indicator of prognosis of breast cancer patients, which will provide new methods and ideas of preventive treatment.

BackgroundThis is the first study to investigate the effect of parental psychological abuse on potential psychopathological symptoms in gender minority youth subgroups, including transgender women, transgender men, and gender queer individuals.MethodsData was analysed from the Chinese National Transgender Survey in 2017; the survey was distributed through community-based organizations to transgender adolescents and adults residing in China, with representation from all 32 provinces and autonomous regions. A total of 1293 youth that self-identified as transgender or gender queer completed the study. Measures covered psychopathological symptoms including depression, anxiety, risk of suicideand self-harm. Parental psychological abuse was assessed in terms of neglect and avoidance, force to change, and verbal insults. Both the edges and centralities were computed via network analysis, and the network properties were then compared among the three gender minority subgroups. In addition, linear regression was adopted to test the predictive ability of node centrality for low self-esteem.ResultsDescriptive analysis revealed that among the three subgroups, transgender women had more severe psychopathological symptoms and reported the most psychological abuse. Network analysis revealed that the risk of suicide and self-harm was directly connected with one type of parental psychological abuse (“neglect and avoidance”). Node centrality was significantly associated with the predicting value of the nodes on low self-esteem (r2= 0.25, 0.17, 0.31) among all three gender minority subgroups.ConclusionsThe distinctive core psychopathological symptoms, within the networks of the gender minority subgroups, revealed specific symptoms across each group. The significant association between node centrality and low self-esteem indicated the extent of parental psychological abuse. Parental psychological abuse directed towards gender minority youth should be recognized as a form of family cold violence. It is recommended that schools and local communities should support early intervention to improve psychological well-being.

Marital quality may decrease during the early years of marriage. Establishing models predicting individualized marital quality may help develop timely and effective interventions to maintain or improve marital quality. Given that marital interactions have an important impact on marital well-being cross-sectionally and prospectively, neural responses during marital interactions may provide insight into neural bases underlying marital well-being. The current study applies connectome-based predictive modeling, a recently developed machine-learning approach, to functional magnetic resonance imaging (fMRI) data from both partners of 25 early-stage Chinese couples to examine whether an individual’s unique pattern of brain functional connectivity (FC) when responding to spousal interactive behaviors can reliably predict their own and their partners’ marital quality after 13 months. Results revealed that husbands’ FC involving multiple large networks, when responding to their spousal interactive behaviors, significantly predicted their own and their wives’ marital quality, and this predictability showed gender specificity. Brain connectivity patterns responding to general emotional stimuli and during the resting state were not significantly predictive. This study demonstrates that husbands’ differences in large-scale neural networks during marital interactions may contribute to their variability in marital quality and highlights gender-related differences. The findings lay a foundation for identifying reliable neuroimaging biomarkers for developing interventions for marital quality early in marriages.

Salvianolic acid B (Sal B) is a representative component of phenolic acids derived from the dried root and rhizome ofIn the present study, ischemic stroke models were induced in rats by middle cerebral artery occlusion (MCAO), and Sal B (10 or 20 mg/kg/d) was intraperitoneally injected according to a previous study. Neurological deficits were evaluated by the modified Longa five-point scale, modified Bederson scores and cerebral infarction sizes by triphenyltetrazolium chloride (TTC) staining. Apoptotic cells were tested by cleaved-caspase3 immunofluorescence staining and an in situ cell death (TUNEL) detection kit. Human umbilical vein endothelial cells (HUVECs) exposed to hypoxia were used to investigate the effects of Sal B on angiogenesis and tube formationSal B ameliorated the neurological deficits, decreased the cerebral infarction volumes in rats with ischemic stroke, significantly increased the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and VEGFA and promoted angiogenesis bothThis study showed that Sal B promoted angiogenesis and alleviated neurological apoptosis in rats with ischemic stroke by promoting STC1.

Neopterygii is a taxonomically diverse clade of ray-finned fishes, including Teleostei, Holostei and closely related fossil taxa. The Colobodontidae is a stem group of large-sized neopterygians with a durophagous feeding adaption from the Middle to Late Triassic marine ecosystems in Europe and South China. Here, we report the discovery of a new colobodontid, Feroxichthys panzhouensis sp. nov., based on a well-preserved specimen from the early Middle Triassic (Anisian) of Panzhou (formerly known as Panxian), Guizhou, China. The discovery extends the geographical distribution of Feroxichthys from eastern Yunnan into western Guizhou, and demonstrates a more rapid diversification of early colobodontids than previously thought. The new species possesses diagnostic features of Feroxichthys (e.g., a fused lacrimal-maxilla), but it is easily distinguished from the type species Feroxichthys yunnanensis and other colobodontids by some derived features on the skull and, especially, the relatively short and deep body with a prominent postcranial hump. This body form, previously unknown in colobodontids, implicates a morphological adaptation to structurally complex habitats in light of ecological studies of modern ray-finned fishes with a similar body form. In addition, the feeding apparatus suggests a more obligate durophagous diet for F. panzhouensis sp. nov. than other colobodontids. Results of a cladistic analysis recover the new species as a sister taxon of F. yunnanensis within the Colobodontidae, and suggest that a hump-backed body form has independently evolved multiple times in Triassic neopterygians. As such, the new finding provides an important addition for our understanding of the morphological and ecological diversity of neopterygian fishes from the Triassic marine ecosystems in South China.

Plasmacytoma variability translocation 1 (PVT1), an oncogene, has been reported to be highly expressed in many tumors, including human glioma, gastric cancer, and non-small cell lung cancer. Functionally, it could also regulate the development of tumor cells. However, its specific roles and pathogenesis in human gliomas are still not clear. This study investigated the function and mechanism of PVT1 knockdown in the proliferation and malignant transformation of human gliomas. We first examined the expression levels of PVT1 and miR-424 in human glioma tissues and cell lines. We also used gene manipulation techniques to explore the effects of PVT1 knockdown on cell viability, migration, invasion, and miR-424. We found that PVT1 knockdown effectively inhibited cell viability, migration, and invasion of human glioma cells and increased miR-424 expression. Based on the negative correlation between PVT1 and miR-424, we then confirmed the direct interaction between PVT1 and miR-424 using RNA immunoprecipitation (RIP) and luciferase reporter assays. Further, we established a xenograft nude mouse model to determine the role and mechanism of PVT1 on tumor growth in vivo. In addition, PVT1 knockdown was shown to promote miR-424 in vivo. In summary, the present study demonstrated that PVT1 knockdown could negatively regulate miR-424 to inhibit human glioma cell activity, migration, and invasiveness. PVT1 knockdown could negatively regulate miR-424 to inhibit cellular activity, migration, and invasiveness in human gliomas, which explained the oncogenic mechanism of PVT1 in human gliomas. It also suggested that PVT1 might be a novel therapeutic target for human gliomas.

Hydrogen sulfide (H2S), a colorless gas smelling of rotten egg, has long been recognized as a toxic gas and environment pollutant. However, increasing evidence suggests that H2S acts as a novel gasotransmitter and plays important roles in a variety of physiological and pathological processes in mammals. H2S is involved in many hepatic functions, including the regulation of oxidative stress, glucose and lipid metabolism, vasculature, mitochondrial function, differentiation, and circadian rhythm. In addition, H2S contributes to the pathogenesis and treatment of a number of liver diseases, such as hepatic fibrosis, liver cirrhosis, liver cancer, hepatic ischemia/reperfusion injury, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, hepatotoxicity, and acute liver failure. In this review, the biosynthesis and metabolism of H2S in the liver are summarized and the role and mechanism of H2S in liver health and disease are further discussed.

Quercetin, a typical flavonoid, possesses diverse biochemical and physiological actions, including antiplatelet, estrogenic, and anti-inflammatory properties. This review mainly centers on recent ten years findings with respect to intervening diabetes and its complications with the well-known flavonoid quercetin. After a short introduction of quercetin, major in vitro and in vivo findings are summarized showing that quercetin is a promising molecule for the treatment of these diseases. Finally, we contemplate future development and application prospects of quercetin. Despite the wealth of in animal research results suggesting the anti-diabetic and its complications potential of quercetin, its efficacy in diabetic human subjects is yet to be explored. The problem may become an important direction in the future research.

This study was designed to establish a modified prediction score system to improve the safety and success rate of vaginal birth after cesarean delivery (VBAC). We recruited 406 patients (between January 2012 and December 2016) and generated a modified score system in predicting the success rate of VBAC. All patients were required to sign informed consent forms. There were 87.2% of patients who had successful VBAC deliveries and 12.8% patients who had repeated cesarean sections. We conducted multivariable logistic regression and found seven variables that were associated with VBAC success, including previous primary indication of cesarean delivery (odds ratio (OR), 2.1; 95% confidence interval (CI), 1.4–3.0), previous vaginal birth history (OR, 2.5; 95% CI, 1.8–3.8)

Neuropathic pain is still a critical public health problem worldwide. Thereby, the search for novel and more effective strategies against neuropathic pain is urgently considered. It is known that neuroinflammation plays a crucial role in the pathogenesis of neuropathic pain. SedumLineare Thunb. (SLT), a kind of Chinese herb originated from the whole grass of Crassulaceae plant, was reported to possess anti-inflammatory activity. However, whether SLT has anti-nociceptive effect on neuropathic pain and its possible underlying mechanisms remains poorly elucidated. In this study, a rat model of neuropathic pain induced by spared nerve injury (SNI)was applied. SLT (p.o.) was administered to SNI rats once every day lasting for 14 days. Pain-related behaviors were assessed by using paw withdrawal threshold (PWT) and CatWalk gait parameters. Expression levels of inflammatory mediators and pain-related signaling molecules in the spinal cord were detected using western blotting assay. The results revealed that SLT (30, 100, and 300 mg/kg, p.o.) treatment for SNI rats ameliorated mechanical hypersensitivity in a dose-dependent manner. Application of SLT at the most effective dose of 100 mg/kg to SNI rats not only significantly blocked microglial activation, but also markedly reduced the protein levels of spinal HMGB1, TLR4, MyD88, TRAF6, IL-1β, IL-6, and TNF-α, along with an enhancement in gait parameters. Furthermore, SLT treatment dramatically inhibited the phosphorylation levels of both IKK and NF-κB p65 but obviously improved both IκB and IL-10 protein expression in the spinal cord of SNI rats. Altogether, these data suggested that SLT could suppress spinal TLR4/NF-κB signaling pathway in SNI rats, which might at least partly contribute to its anti-nociceptive action, indicating that SLT may serveas a potential therapeutic agent for neuropathic pain.

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

Various research works have piled up conflicting evidence questioning the effect of oxidative stress in cancer. Reactive oxygen and nitrogen species (RONS) are the reactive radicals and nonradical derivatives of oxygen and nitrogen. RONS can act as a double-edged weapon. On the one hand, RONS can promote cancer initiation through activating certain signal transduction pathways that direct proliferation, survival, and stress resistance. On the other hand, they can mitigate cancer progression via their resultant oxidative stress that causes many cancer cells to die, as some recent studies have proposed that high RONS levels can limit the survival of cancer cells during certain phases of cancer development. Similarly, eukaryotic translation initiation factors are key players in the process of cellular transformation and tumorigenesis. Dysregulation of such translation initiation factors in the form of overexpression, downregulation, or phosphorylation is associated with cancer cell’s altering capability of survival, metastasis, and angiogenesis. Nonetheless, eIFs can affect tumor age-related features. Data shows that alternating the eukaryotic translation initiation apparatus can impact many downstream cellular signaling pathways that directly affect cancer development. Hence, researchers have been conducting various experiments towards a new trajectory to find novel therapeutic molecular targets to improve the efficacy of anticancer drugs as well as reduce their side effects, with a special focus on oxidative stress and initiation of translation to harness their effect in cancer development. An increasing body of scientific evidence recently links oxidative stress and translation initiation factors to cancer-related signaling pathways. Therefore, in this review, we present and summarize the recent findings in this field linking certain signaling pathways related to tumorigeneses such as MAPK and PI3K, with either RONS or eIFs.

Autophagy means self-eating, and it is a natural and regulated mechanism of cells that remove unwanted or dysfunctional...