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Objective. To explore the associations between glucocorticoid use and the clinical outcome of patients with severe pneumonia. Methods. Medical databases including PubMed, EMBASE, and ScienceDirect were searched for relevant literature. Two independent researchers extracted the primary endpoint from the included literature. The Cochrane Q test and I 2 statistics were used to evaluate the interstudy heterogeneity. The combined risk estimates were calculated by random effect model, and the source of heterogeneity was evaluated by subgroup analysis. Funnel plot and Egger’s test were used to assess publication bias. P < 0.05 denoted statistical significance. Results. A total of 12 literature, including 8171 patients with 1083 deaths, were included in this study for meta-analysis. The use of glucocorticoids significantly increased the mortality ( RR = 1.44 , 95% CI: 1.13, 1.84, P < 0.001 ), the risk of requiring mechanical ventilation ( RR = 1.62 , 95% CI: 1.30, 2.02, P < 0.001 ), and the incidence of nosocomial infection ( RR = 1.36 , 95% CI: 1.01, 1.82, P = 0.04 ) in patients with severe pneumonia as compared with the control group. In addition, the use of glucocorticoids did not seem to be associated with length of treatment in the intensive care unit ( mean difference = 1.47 , 95% CI: -1.04, 3.96, P = 0.25 ) and the length of hospital stay ( mean difference = 0.55 , 95% CI: -3.90, 4.99, P = 0.81 ). Conclusion. The use of glucocorticoids may increase the mortality, the incidence of hospital-acquired pneumonia, and the need for mechanical ventilation in patients with severe pneumonia.

Purpose Sleep disorders are prevalent among patients with pituitary adenoma (PA) and may lead to disease aggravation and decreased health-related quality of life (HRQoL). Relatively scarce information is available on sleep disturbance in primary PA patients in China. Therefore, this study aims to evaluate the sleeping quality in Chinese primary PA patients and the prevalence, correlates, and impact of sleep disturbance. Methods A total of 203 primary PA patients were involved in this cross-sectional study. A series of questionnaires (Pittsburgh Sleep Quality Index (PSQI), MD Anderson Symptom Inventory Brain Tumor for clinical manifestations (MDASI-BT), Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Inventory (MFI-20), and the Short Form 36 health survey (SF-36)) were applied. Independent samples t tests, Mann-Whitney U test, Chi-square analysis, and logistic regression were used to analyze these data. Results Our results found that the prevalence of sleep disturbance was 47.8% in primary PA patients. The significant differences were found on the place of residence, alcohol use, depression, anxiety, fatigue, somatic symptom scores and counts, among poor sleepers and good sleepers. Binary logistic regression indicated that fatigue and alcohol use were independently associated with sleep disturbance of primary PA patients. Meanwhile, HRQL of sleep poor patients is clearly lower than those with good sleep. Conclusions Primary PA patients in China suffered from sleep disturbance. The results emphasize the importance of fatigue and alcohol use in the sleep disturbance of PA patients. Medical personnel should pay more attention to PA patients with sleep disturbance before the initial diagnosis and preparation for surgery in order to take effective measures early to improve sleep disturbance, with the ultimate goal to improve their QoL.

Exploiting precious-metal-free and high-activity oxygen evolution reaction (OER) electrocatalysts has been in great demands toward many energy storage and conversion processes, for example, carbon dioxide reduction, metal-air batteries, and water splitting. In this study, the simple solid-state method is employed for coupling Ni (electron donors) with lower-Fermi-level MoO2 or WOx (electron acceptors) into donor-acceptor ensembles with well-designed interfaces as robust electrocatalysts for OER. The resulting Ni/MoO2 and Ni/WOx electrocatalysts exhibit smaller overpotentials of 287 and 333 mV at 10 mA cm-2 as well as smaller Tafel slopes of 51 and 65 mV/dec, respectively, with respect to the single Ni, MoO2, WOx, and even the benchmark RuO2 in 1 M KOH. Specially, on account of a higher Fermi level of Ni in comparison with MoO2 and WOx, their strong electronic interaction results in directional interfacial electron transfer and increases the hole density over Ni, dramatically enriching the population of high-valence Ni3+ active sites and decreasing the Fermi level of Ni. The existence of Ni3+ can strengthen the chemisorption of OH-, and the downshift of the Ni Fermi level can significantly expedite migration of electrons toward the surface of catalysts during OER, thus synergistically boosting the OER catalytic performance. Furthermore, the inner Ni/MoO2 and Ni/WOx heterostructures and the electrochemically induced surface layers of oxides/hydroxides collectively boost the OER kinetics. This study highlights the importance of designing highly efficient OER electrocatalysts with high-valence active species (Ni3+) and better matched energy levels induced by the work function difference through interfacial engineering.

Aims Apelin is the endogenous ligand of G protein-coupled receptor APJ and play an important role in the regulation of cardiovascular homeostasis. We aimed to investigate whether apelin ameliorates vascular calcification (VC) by inhibition of endoplasmic reticulum stress (ERS). Methods and results VC model in rats was induced by nicotine plus vitamin D, while calcification of vascular smooth muscle cell (VSMC) was induced by beta-glycerophosphate. Alizarin Red S staining showed dramatic calcium deposition in the aorta of rats with VC, while calcium contents and ALP activity also increased in calcified aorta. Protein levels of apelin and APJ were decreased in the calcified aorta. In rats with VC, apelin treatment significantly ameliorated aortic calcification, compliance and stimulation of ERS. The ameliorative effect of apelin on VC and ERS was also observed in calcified VSMCs. ERS stimulator (tunicamycin or DTT) blocked the beneficial effect of apelin. Apelin treatment activated the PI3K/Akt signaling, blockage of which by wortmannin or inhibitor IV prevented the ameliorative effect of apelin, while ERS inhibitor 4-PBA rescued the blockade effect of wortmannin. Akt-induced GSK inhibition prevented the phosphorylation of PERK and IRE1, and the activation of these two major ERS branches. F13A blocked the ameliorative effect of apelin on VC and ERS, which was reversed by treatment with 4-PBA or Akt activator SC79 Conclusions Apelin ameliorated VC by binding to APJ and then prevented ERS activation by stimulating Akt signaling. These results might provide new target for therapy and prevention of VC.

This study aimed to investigate whether inhibition of endoplasmic reticulum stress (ERS) mediated the ameliorative effect of apelin on acute heart failure (AHF). Rabbit model of AHF was induced by sodium pentobarbital. Cardiac dysfunction and injury were detected in the rabbit models of AHF, including impaired hemodynamic parameters and increased levels of CK-MB and cTnI. Apelin treatment dramatically improved cardiac impairment caused by AHF. ERS, indexed by increased GRP78, CHOP, and cleaved-caspase12 protein levels, was simultaneously attenuated by apelin. Apelin also could ameliorate increased protein levels of cleaved-caspase3 and Bax, and improved decreased protein levels of Bcl-2. Two common ERS stimulators, tunicamycin (Tm) and dithiothreitol (DTT) blocked the ameliorative effect of apelin on AHF. Phosphorylated Akt levels increased after apelin treatment in the rabbit models of AHF. The Akt signaling inhibitors wortmannin and LY294002 could block the cardioprotective effect of apelin, which could be relieved by ERS inhibitor 4-phenyl butyric acid (4-PBA). The aforementioned beneficial effects of apelin could all be blocked by APJ receptor antagonist F13A. 4-PBA and SC79, an Akt activator, can restore the ameliorative effect of apelin on AHF blocked by F13A. Apelin treatment dramatically ameliorated cardiac impairment caused by AHF, which might be mediated by APJ/Akt/ERS signaling pathway. These results will shed new light on AHF therapy.

Social anhedonia, or the loss of motivation in and pleasure from social engagement, is an important feature in understanding the etiology and outcome of various psychopathologies. While the Revised Social Anhedonia Scale (RSAS) represents one of the most commonly used self-report measures of social anhedonia, little is known regarding the construct comparability across populations. We examined measurement invariance of the full and brief RSAS in a diverse, international sample of 14,064 participants across nine epidemiological dimensions, including gender, age, ethnicity, education, community income, continent, migrant status, ethnic density, and urbanicity. Both the full and brief RSAS, as represented by a three-factor structure, achieved metric invariance for all dimensions. The full version showed considerable scalar noninvariance for ethnicity and continent, which was significantly reduced in the brief version. These findings suggest that while the scales measure the same construct across diverse groups, mean comparisons are only appropriate for the brief, and not the full, version. Future research may consider using the brief RSAS to ensure cross-national comparability. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The recovery of blood supply after a period of myocardial ischaemia does not restore the heart function and instead results in a serious dysfunction called myocardial ischaemia-reperfusion injury (IRI), which involves several complex pathophysiological processes. Mitochondria have a wide range of functions in maintaining the cellular energy supply, cell signalling and programmed cell death. When mitochondrial function is insufficient or disordered, it may have adverse effects on myocardial ischaemia-reperfusion and therefore mitochondrial dysfunction caused by oxidative stress a core molecular mechanism of IRI. Peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) is an important antioxidant molecule found in mitochondria. However, its role in IRI has not yet been systematically summarized. In this review, we speculate the role of PGC-1α as a key regulator of mitonuclear communication, which may interacts with nuclear factor, erythroid 2 like -1 and -2 (NRF-1/2) to inhibit mitochondrial oxidative stress, promote the clearance of damaged mitochondria, enhance mitochondrial biogenesis, and reduce the burden of IRI.

Bacterial sigma (σ) factor, along with RNA polymerase core enzyme, initiates gene transcription from specific promoter regions and therefore regulates clusters of genes in response to a particular situation. The extracytoplasmic function (ECF) σ factors are a class of alternative σ factors that are often associated with environmental signal transduction across the bacterial membrane, in which external signal triggers the release of active σ from the membrane-anchored anti-σ factor. Gram-positive model organism Bacillus subtilis (B. subtilis) has seven ECF σ factors: σM, σV, σX, σW, σY, σZ and σYlaC. Although all these ECF σ factors were found to be involved in B. subtilis antibiotic resistance, σW is among the most studied and considered to play a pivotal role in responding to antimicrobial stresses. σW is under tight control and remains deactivated until exposure to external stimuli, after which proteases PrsW and RasP cleave the specific anti-sigma factor-RsiW to release and activate σW. Membrane anchored protein YsdB is a negative regulator of this activation, possibly via its direct interaction with PrsW and/or RsiW. Importantly, YsdB is well conserved among Bacilli, including pathogenic bacteria like Bacillus cereus. In this study, we describe the chemical shift assignments of the cytoplasmic domain of YsdB (29-130) of B. subtilis in solution as a basis for further interaction studies and structure determination. The near-complete assignment and the solution structure that will follow could provide a further understanding in σW regulation.

A 2-pyridone modified zinc phthalocyanine (denoted ZnPc-PYR) achieves a one stone for three birds outcome in the photodynamic therapy (PDT) treatment of cancer. ZnPc-PYR can be excited by both 665 and 808 nm light to treat superficial and deep tumors, store and slowly release singlet oxygen (1O2) to improve its utilization and downregulate the HIF-1 (hypoxia-inducible factor 1) expression level to enhance the tumor cell's sensitivity to PDT treatment under hypoxic conditions.

Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of COVID-19 cases is continuously increasing and no effective drugs or vaccines are currently available. Accurate and efficient diagnostic testing methods are desperately needed for the detection of SARS-CoV-2 and antiviral antibodies in infected individuals. Various assay techniques, including nucleic acid tests [eg, polymerase chain reaction (PCR), reverse transcription-PCR, real-time loop-mediated isothermal amplification, and CRISPR-Cas-based detection], serological tests [eg, immunoglobulin (Ig)A, IgM/G], imaging tests (eg, computed tomography and positron-emission tomography), and nanoparticle-based detections have been reported for COVID-19 diagnosis. This review aims to present the current diagnostic tools for SARS-CoV-2 and their performance characteristics to inform the appropriate selection of diagnostic and surveillance technologies at optimal testing times. We also describe the advantages of detection using combined nucleic acid and imaging tests, or serological testing and point-of-care diagnostics. Developing reliable protein biomarkers targeting the conserved proteins of SARS-CoV-2 rather than IgA, IgM, or IgG would be useful to manage SARS-CoV-2.

Background: Brain metastases (BMs), particularly synchronous brain metastases, in colorectal cancer (CRC) patients are uncommon. The survival benefit of primary tumor resection (PTR) in patients with metastatic colorectal cancer is controversial. Whether PTR can bring survival benefit to patients with BMs of CRC has not been reported. Methods: From 2010 to 2016, 581 CRC patients with BMs from the Surveillance, Epidemiology, and End Results (SEER) database were randomly divided into PTR and non-PTR group. The log-rank test was used to compare the survival distributions. The Kaplan-Meier method was used to estimate survival. By controlling additional prognostic factors, a Cox proportional multivariate regression analysis was used to estimate the survival benefit of PTR.Results: The median overall survival for CRC patients with synchronous BMs was 3 months, with a 1-year survival rate of 27.2% and a 2-year survival rate of 12.8%. The PTR group contained 171 patients (29.4%), whereas the non-PTR group had 410 patients (70.6%). Patients who underwent PTR had a 1-year survival rate of 40.2% compared to 21.7% in those who did not (p < 0.0001). Cox proportional analysis showed that patients ≥60 years (hazard ratio [HR] 1.718, 95% confidence interval [CI] 1.423-2.075, p< 0.0001) had a shorter OS than patients < 60 years of age. OS was better in CEA-negative than in CEA-positive patients (HR 0.652, 95% CI 0.472-0.899, p=0.009). Patients in whom the primary tumor was removed had a considerably improved prognosis (HR 0.654, 95% CI 0.531–0.805, p < 0.0001). Subgroup analysis revealed that the PTR group achieved a survival advantage except for patients with CEA negative.Conclusions: Patients with BMs from CRC may benefit from primary tumor resection (PTR).Independent prognostic risk factors for CRC patients with synchronous BMs were age, CEA level, and PTR.

Atopic dermatitis (AD) is a chronic skin disease, which is associated with intense itch, skin barrier dysfunction and eczematous lesions. Aberrant IL-20 expression has been implicated in numerous inflammatory diseases, including psoriasis. However, the role of IL-20 in AD remains unknown. Here, RNA-seq, Q-PCR, and immunocytochemistry were utilized to examine disease-driven changes of IL-20 and its cognate receptor subunits in skin from healthy human subjects, AD patients and murine AD-models. Calcium imaging, knockdown and cytokine array were used to investigate IL-20-evoked responses in keratinocytes and sensory neurons. The murine cheek model and behavioral scoring were employed to evaluate IL-20-elicited sensations in vivo. We found that transcripts and protein of IL-20 were upregulated in skin from human AD and murine AD-like models. Topical MC903 treatment in mice ear enhanced IL-20R1 expression in the trigeminal sensory ganglia, suggesting a lesion-associated and epidermal-driven mechanism for sensitization of sensory IL-20 signaling. IL-20 triggered calcium influx in both keratinocytes and sensory neurons, and promoted their AD-related molecule release and transcription of itch-related genes. In sensory neurons, IL-20 application increased TLR2 transcripts, implicating a link between innate immune response and IL-20. In a murine cheek model of acute itch, intradermal injection IL-20 and IL-13 elicited significant itch-like behavior, though only when co-injected. Our findings provide novel insights into IL-20 function in peripheral (skin-derived) itch and clinically relevant intercellular neuron-epidermal communication, highlighting a role of IL-20 signaling in the pathophysiology of AD, thus forming a new basis for the development of a novel antipruritic strategy via interrupting IL-20 epidermal pathways.

Chronic itch is a complex sensation of the skin frequently associated with skin diseases, such as atopic dermatitis (AD) and psoriasis. Although Serpin E1 is implicated in chronic itch, its receptor and signaling pathways involved in itch are not known. In this study, the clinical relevance of a putative Serpin E1 receptor PLAUR to chronic itch, and the neuro-cutaneous Serpin E1-PLAUR signaling are explored. We found that PLAUR is overexpressed in skin specimens of human lesional AD and lesional psoriasis, and sensory neurons innervating MC903-induced AD-like murine skin. Murine PLAUR

Purpose Lung cancer is the leading cause of cancer-related mortality. STEAP1 and STEAP2 are overexpressed in various cancers. The purpose of this study was to evaluate the expression and prognostic value of STEAP1 and STEAP2 in patients with lung cancer. Methods The mRNA expression and protein expression of STEAP1 and STEAP2 and their prognostic characteristics were examined using Oncomine, GEPIA, and Kaplan-Meier (KM) plotters. The correlation analysis of STEAP1 and STEAP2 gene and protein levels was conducted using GeneMANIA and STRING. KEGG pathway analysis was used to explore the related signal pathways of STEAP 1 and STEAP2. Immunohistochemical methods were used to compare the expression of STEAP2 in normal lung and non-small cell lung cancer (NSCLC) tissues. Real-time quantitative polymerase chain reaction, western blotting, and immunocytochemistry were used to evaluate the expression of STEAP1 and STEAP2 in three lung cancer cell lines and normal lung epithelial cell lines. Results Analysis of the Oncomine database and GEPIA showed that STEAP1 was upregulated and STEAP2 was downregulated in lung cancer tissue, and both expressions were related to the clinical stage of lung cancer. Immunohistochemical analysis showed that STEAP1 protein expression was significantly upregulated in lung cancer compared to that in adjacent tissues. The expression of STEAP1 was positively correlated with the migration and invasion abilities of lung cancer cells. Compared with paracancer tissues, the expression of STEAP2 protein in lung cancer was significantly downregulated and was correlated with the histological grade of squamous cell carcinoma, pathological classification of adenocarcinoma, tumor, lymph node, and metastasis clinical stage, and lymph node metastasis. The expression of STEAP2 was negatively correlated with the migration and invasion abilities of lung cancer cells. The KM curve showed that the downregulation of STEAP1 expression and upregulation of STEAP2 expression were related to a good lung cancer prognosis. Conclusion STEAP1 and STEAP2 are expected to be potential diagnostic and prognostic markers for lung cancer, which may provide more accurate prognostic indicators for lung cancer.

The contrastive analysis of soil bulk density, moisture content, organic matter spatial heterogeneity karst hillslopes can serves as theoretical guidance for preventing soil degradation in Nandong subterranean stream basin. This study analysis the 0-20cm, 20-40cm soil bulk density, moisture and organic matter spatial heterogeneity Zhumashao depression basing on classical statistics and geostatistics methods. Research results showed that: the soil organic matter aberrance in Zhumashao depression is the largest, up to 70.62%, the variation of bulk density and water, respectively 15.25% and 11.29%. According to the statistical analysis of different types of land use, the soil moisture content can be ordered as follows, cultivated land ＜grassland＜shrubs, and the bulk density can be ordered as shrubs ＜grassland＜cultivated land, and organic matter content can be ordered as cultivated land＜grassland＜shrubs. The bulk density of the northern slope is higher than the southern slope, and the coefficient of variation is lower than the southern slope. The soil moisture and organic matter are lower than the southern slope, and the coefficient of variation is higher than the southern slope. It also showed a significant negative correlation between soil bulk density and soil moisture, as well as a significant negative correlation between soil bulk density and organic matter, and the correlation coefficients were -0.609 and -0.581, respectively. In 0-20 cm, the soil moisture, bulk density, organic matter and the spherical model are fitter and fitting degree of R2 were 0.911, 0.977, and 0.922, respectively. In 20-40 cm, the soil moisture, bulk density, organic matter and Gauss model match better and fitting degree of R2 were 0.647, 0.730, and 0.881, respectively. The nugget coefficient shows that the spatial correlation of 0-20 cm factors, 20-40 cm is weak, which may be related to human activities in space. Through the analysis of normal kriging interpolation, soil bulk density in the south slope of the depression is less than those in the north slope, as well as the water and organic matter is more than those in the north slope. The soil moisture and organic matter at the bottom of the depression have the minimum value, while the bulk density has the maximum value. The water content and organic matter at the bottom and middle slope are the lowest, and the bulk density is the highest; the moisture and organic matter are higher on the downhill and uphill, and the bulk density is lower.Key words: spatial heterogeneity; karst slope; land use, soil moisture, bulk density, organic matter

In karst areas, underground riverine sediment has been widely used to reflect the subterranean stream basin erosion, which influenced by both of precipitation and anthropogenic factors. In this study, 15-years of the sediment yield across Nandong underground river system of China were monitored, Mann-Kendal mutation test and simple proxy indicators were used for detecting the influences of human activities and precititation on sediment yield. The results showed that: 1) both of the anthropologic factor and rainfall impacted sediment yield, although the influence of anthropologic factor on sediment yield was greater (76.38%), and 2) rainfall showed a hysteresis effect on soil and water loss. There were three distinct stages based on the mutation points and variation characteristics of sediment yield from 1998 to 2014, resulting from different driving forces. Before 2004, the decease of sediment yield was caused by natural forest protection project in the whole basin. During 2004 to 2008, because of drought, flood disaster and cultivation on steeper slope, sediment yield of the basin increased. After 2009, sediment yield decreases due to the construction of soil conservation projects and mushrooming reservoirs. As human population is expected to increase, these findings are expected to provide insights for watershed management and ecological restoration in the fragile karst ecosystem.

Current suicidal ideation and suicide attempts among psychiatric patients during the COVID-19 pandemic were studied through systematic review and meta-analysis. We searched the following electronic databases using the relevant search terms: Medline, Embase, PubMed and Web of Science, with the search time as of January 31,2022. Forest plots were obtained using Stata statistical software and a random-effects model was used to conduct a meta-analysis of the prevalence of suicidal ideation. We found 21 eligible studies, 11 of which provided suitable data for meta-analysis. 10 studies explored current suicidal ideation and reported a pooled prevalence of 20.4% (95%CI 14.0-26.8). Six studies examined suicide attempts, with a pooled prevalence of 11.4% (95%CI 6.2-16.6). The prevalence of suicidal ideation and suicide attempts varied by the study method used and by the study sites. This work highlights the need for real-time monitoring of suicidal ideation and suicide in psychiatric patients during the covid-19 pandemic r to inform clinical practice and help identify research questions for future epidemiological studies.

Inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract, is a global health care problem. Compelling evidence shows sex differences regarding the prevalence, pathophysiology, clinical presentation, and treatment outcome of IBD. Sex hormones, including estrogen, progesterone, and androgen, have been proposed to have a role in the pathogenesis of sexual dimorphism in IBD. Clinical and experimental data support the modulatory effects of sex hormones on various clinical characteristics of the disease, including intestinal barrier dysfunction and mucosal immune activation. Additionally, the potential role of sex hormones in the modulation of gut microbiota is attracting increasing attention. Here, we discuss the sex dimorphic disease profile and address the potential mechanisms involved in the sex-specific pathogenesis of IBD. Improved understanding of these sex differences in the clinic could improve the knowledge of patients with IBD with heterogeneous disease profiles.

Purpose Ovarian cancer (OC) has the highest mortality among gynecological malignancies. Therefore, it is urgent to explore prognostic biomarkers to improve the survival of OC patients. One of the most prominent metabolic characteristics of cancer is effective glycolysis. Hexokinase 1 (HK1), as the first rate-limiting enzyme in glycolysis, is closely related to cancer progression. However, the role of HK1 in OC remains unclear. Materials and Methods The Cancer Genome Atlas (TCGA) database was used to detect the expression of HK1 in OC patients. The chi-squared test was performed to examine the correlations between HK1 and patients’ clinical characteristics. Survival analyses were undertaken to determine the relationship between HK1 and patient survival, while the univariate/multivariate Cox model was used to evaluate the role of HK1 in patient prognosis. Gene Set Enrichment Analysis (GSEA) was performed to ascertain the related signaling pathways of HK1. RT-qPCR was implemented to validate the mRNA expression of HK1 in OC cells. MTT was used to detect cell viability after adding 2DG and knocking down HK1 in OC cells. HK1 protein expression was examined by Western blotting. Glucose uptake, lactate production, and ATP assays were undertaken following knockdown of HK1 in OC cells. Colony formation assays were performed to determine OC cell proliferation after HK1 knockdown. Transwell and wound healing assays were carried out to detect the invasion and migration of OC cells after HK1 knockdown. Results We found that HK1 expression was increased in OC tissues and cells, and HK1 was related to the clinical characteristics of OC patients. Survival analysis revealed that OC patients in the HK1 overexpression group had poor survival. Moreover, univariant/multivariate analyses showed that HK1 may be an independent biomarker for the poor prognosis of OC patients. OC cell viability and proliferation decreased after knockdown of HK1. Consistently, glucose uptake, lactic acid production, ATP production, invasion, and migration were also decreased. Finally, GSEA enrichment analysis and Western blotting showed that HK1 was involved in MAPK/ERK signaling. Conclusion HK1 may be a biomarker for the poor prognosis of OC patients and a potential therapeutic target.

Stimulator of interferon genes (STING) has been shown to play a critical role in orchestrating immune responses to various pathogens through sensing cyclic dinucleotides. However, how STING regulates intestinal homeostasis is still not completely understood. In this study, we found that STING(−/−) mice were more susceptible to enteric infection with Citrobacter rodentium compared to WT mice evidenced by more severe intestinal inflammation and impaired bacterial clearance. STING(−/−) mice demonstrated lower expression of REG3γ, but not β-defensins and Cramp, in IECs. Consistently, STING(−/−) IECs showed reduced capacity to inhibit bacterial growth. STING agonists, both 10-carboxymethyl-9-acridanone (CMA) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA), promoted REG3γ expression IECs. Furthermore, STING agonists promoted WT but not REG3γ-deficient IEC bacterial killing. Mechanistically, STING agonists activated STAT3 and promoted glycolysis in IECs. Inhibition of STAT3 pathway and glycolysis suppressed STING induced REG3γ production in IECs, and abrogated STING-mediated IEC killing of Citrobactor rodentium. Additionally, treatment with the STING ligand, 2,3-cGAMP, inhibited Citrobactor rodentium-induced colitis in vivo. Overall, STING promotes IEC REG3γ expression to inhibit enteric infection and intestinal inflammation, thus, maintaining the intestinal homeostasis.

STUDY QUESTION Whether the testis-specific extracellular vesicle (EV) long noncoding RNAs (lncRNAs) in seminal plasma could be utilized to predict the presence of testicular spermatozoa in nonobstructive azoospermia (NOA) patients? SUMMARY ANSWER Our findings indicate that the panel based on seminal plasma EV lncRNAs was a sensitive and specific method in predicting the presence of testicular spermatozoa and may improve clinical decision-making of NOA. WHAT IS KNOWN ALREADY The adoption of sperm retrieval techniques, especially microdissection testicular sperm extraction (mTESE), in combination with ICSI has revolutionized treatment for NOA. However, there are no precise and noninvasive methods for predicting whether there are testicular spermatozoa in NOA patients before mTESE. STUDY DESIGN, SIZE, DURATION RNA sequencing was performed on seminal plasma EVs from 6 normozoospermic men who underwent IVF due to female factor and 5 idiopathic NOA patients who failed to obtain testicular spermatozoa by mTESE and were diagnosed as having Sertoli cell-only syndrome by postoperative pathology. A biomarker panel of lncRNAs was constructed and verified in 96 NOA patients who underwent mTESE. Decision-making process was established based on the panel in seminal plasma EVs from 45 normozoospermia samples, 43 oligozoospermia samples, 62 cryptozoospermia samples, 96 NOA samples. PARTICIPANTS/MATERIALS, SETTING, METHODS RNA sequencing was done to examine altered profiles of EV lncRNAs in seminal plasma. Furthermore, a panel consisting of EV lncRNAs was established and evaluated in training set and validation sets. MAIN RESULTS AND THE ROLE OF CHANCE A panel consisting of nine differentially expressed testis-specific lncRNAs, including LOC100505685, SPATA42, CCDC37-DT, GABRG3-AS1, LOC440934, LOC101929088 (XR_927561.2), LOC101929088 (XR_001745218.1), LINC00343 and LINC00301, was established in the training set and the AUC was 0.986. Furthermore, the AUC in the validation set was 0.960. Importantly, the panel had a unique advantage when compared with models based on serum hormones from the same group of NOA cases (AUC, 0.970 vs 0.723; 0.959 vs 0.687, respectively). According to the panel of lncRNAs, a decision-making process was established, that is when the score of an NOA case exceeds 0.532, sperm retrieval surgery may be recommended. LIMITATIONS, REASONS FOR CAUTION In the future, the sample size needs to be further expanded. Meanwhile, the regulatory functions and mechanism of lncRNAs in spermatogenesis also need to be elucidated. WIDER IMPLICATIONS OF THE FINDINGS When the score of our panel is below 0.532, subjecting the NOA patients to ineffective surgical interventions may not be recommended due to poor sperm retrieval rate. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (81871110, 81971314 and 81971759); the Guangdong Special Support Plan-Science and Technology Innovation Youth Top Talents Project (2016TQ03R444); the Science and Technology Planning Project of Guangdong Province (2016B030230001 and 201707010394); the Key Scientific and Technological Program of Guangzhou City (201604020189); the Pearl River S&T Nova Program of Guangzhou (201806010089); the Transformation of Scientific and Technological Achievements Project of Sun Yat-sen University (80000-18843235) and the Youth Teacher Training Project of Sun Yat-sen University (17ykpy68 and 18ykpy09). There are no competing interests related to this study. TRIAL REGISTRATION NUMBER N/A.

Biochemical and structural characterizations of a protein are the prerequisite for the further understanding of its biological role and potential applications. The expression of recombinant protein is almost unavoidable to produce the amount of the protein required for these studies, especially at the industrial level. Escherichia coli is the single most used system for recombinant protein expression and the first choice for a trial expression. Besides the inherited defects of its prokaryotic origin, the E. coli system has problems like low protein solubility and formation of inclusion bodies. To improve the solubility while assisting correct folding of the target protein, fusing a tag protein prior to its N-terminus is one of the common approaches. GST, MBP, Trx and SUMO proteins are among the most used tags by providing different advantages during recombinant protein expression. Msyb, a small and acidic protein native to E. coli, is another example that could improve the solubility of the target protein. While the biophysical and biochemical properties of these common tag proteins have been studied to a great extent, Msyb protein remains largely uncharacterized. Here, using solution-state NMR, our near-complete resonance assignment of Msyb provides a basis for future structure determination which would help to expand its usage as a common tag protein.

Erastin was initially discovered as a small molecule compound that selectively kills tumor cells expressing ST and RASV12 and was later widely investigated as an inducer of ferroptosis. Ferroptosis is a recently discovered form of cell death caused by peroxidation induced by the accumulation of intracellular lipid reactive oxygen species (L-ROS) in an iron-dependent manner. Erastin can mediate ferroptosis through a variety of molecules including the cystine-glutamate transport receptor (system XC -), the voltage-dependent anion channel (VDAC), and p53. Erastin is able to enhance the sensitivity of chemotherapy and radiotherapy, suggesting a promising future in cancer therapy. We hope that this review will help to better understand the role of erastin in ferroptosis and lay the foundation for further research and the development of erastin-based cancer therapies in the future.

The microstructure and magnetic properties of multiferrioc polycrystalline Y-type hexaferrite Ba0.5Sr1.5Zn2Fe12−xNixO22 (BSZFNO, x = 0, 0.05, 0.1, 0.2, 0.35 and 0.5) synthesized by the solid-state reaction method are investigated. It is found that the shrink of BSZFNO lattice constant and the increase of grain size appear after substituting Fe ion with Ni ion, and Ni doping depresses the formation of Z-type and M-type impurity phases. BSZFNO undergoes two main magnetic phase transitions. Near room temperature, the temperature of phase transition from proper screw spin phase to collinear ferromagnetic phase increases with Ni amount increasing, suggesting the enhancement of exchange interaction of Fe(4)–O–Fe(5). The magnetic phase transition at lower temperature is attributed to the spin transition from a longitudinal conical spin order to a proper screw spin order, whose transition temperature varies due to different magnetocrystalline anisotropy with introducing Ni into BSZFO lattices. Furthermore, Ni doping leads to the expansion of the range of field-driven magnetic phases, especially intermediate-II and intermediate-III helical spin phase. The saturation magnetization at 5 K increases with Ni doping and arrives at a maximum value with Ni content x = 0.2, finally decreases with x. The increasing of the pitch of spin helix in initial Ni-doping leads to the enhancement of the magnetization. However, the conical spin phase eventually collapses in higher-concentration Ni-doping.

Individuals at risk for schizophrenia-spectrum disorders display abnormalities related to motivational salience, or the ability of stimuli to elicit attention due to associations with rewards or punishments. However, the nature of these abnormalities is unclear because most focus on responses to stimuli from broad “pleasant” and “unpleasant” categories and ignore the variation of motivational salience within these categories. In two groups at risk for schizophrenia-spectrum disorders—a Social Anhedonia group and a Psychotic-like Experiences group—and a control group, the current study examined event-related potential components sensitive to motivational salience—the Early Posterior Negativity (EPN), reflecting earlier selective attention, and the Late Positive Potential (LPP), reflecting sustained attention. Compared to controls, the Social Anhedonia group showed smaller increases in the EPN in response to erotica and smaller increases in the LPP as the motivational salience of pleasant images increased (excitinglarger increases in LPP amplitudes as the motivational salience of pleasant images increased. Also, both at-risk groups showed larger increases in the LPP to threatening images but smaller increases to mutilation images. These findings suggest that examining abnormalities beyond those associated with broad categories may be a way to identify mechanisms of dysfunction.

By taking advantage of electronic influence of ligand design, the novel neutral nickel complexes bearing strong electron-donating N-acylated imidazolin-2-imine ligand were synthesized and characterized. The nickel catalysts conducted ethylene polymerization with high activity and good thermal stability, affording semicrystalline polyethylene with short chain branches (32–46/1000 C atoms). The complex Ni2 bearing adamantyl substituent on the imidazoline ligand showed higher activity than phenyl substituted complex Ni1, and highest activity was observed at 60 °C (up to ~106 g⋅mol−1⋅h−1). Most importantly, the catalysts were also effective for the copolymerization of ethylene and 5-hexenyl acetate with moderate activity (~105 g⋅mol−1⋅h−1). The microstructure analyses by the 13C NMR spectroscopy indicated that the 5-hexenyl acetate was successfully incorporated into the polyethylene main chain with reasonable comonomer content.

Male late-onset hypogonadism is an age-related disease, the core mechanism of which is dysfunction of senescent Leydig cells. Recent studies have shown that elimination of senescent cells can restore proper homeostasis to aging tissue. In the present study, we found that the fork head box O (FOXO) transcription factor FOXO4 was specially expressed in human Leydig cells and that its translocation to the nucleus in the elderly was related to decreased testosterone synthesis. Using hydrogen peroxide-induced senescent TM3 Leydig cells as an in vitro model, we observed that FOXO4 maintains the viability of senescent Leydig cells and suppresses their apoptosis. By disrupting the FOXO4-p53 interaction, FOXO4-DRI, a specific FOXO4 blocker, selectively induced p53 nuclear exclusion and apoptosis in senescent Leydig cells. In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion insufficiency. These findings reveal the therapeutic potential of FOXO4-DRI for the treatment of male late-onset hypogonadism.

The incorporation of even a small number of polar functional groups in the polyolefin backbone is sufficient to improve the polyolefin properties. Compared with palladium catalyzed direct copolymerization of olefins with polar vinyl monomers, the development of low-cost nickel-based catalysts is more challenging because of their higher oxophilicity. On the basis of the advantage of reducing the electrophilicity of the nickel center by the installation of strongly electron-donating ligands, we herein report the synthesis of novel bis(N-acylated imidazolin-2-imine) nickel complexes for norbornene polymerization and copolymerization with polar monomers. Moreover, the phenyl substituent on the imidazoline ligand is expected to enhance the tolerance of the nickel catalyst toward polar functional groups, thus allowing the copolymerization of norbornene with commercial methyl acrylate to afford high molecular weight functionalized cyclic olefin copolymers (COCs) with moderate activity and reasonable comonomer content.

With the increasing demand for blue dyes, it is of vital importance to develop a green and efficient biocatalyst to produce indigo. This study constructed a hydrogen peroxide-dependent catalytic system for the direct conversion of indole to indigo using P450BM3 with the assistance of dual-functional small molecules (DFSM). The arrangements of amino acids at 78, 87, and 268 positions influenced the catalytic activity. F87G/T268V mutant gave the highest catalytic activity with kcat of 1402 min−1 and with a yield of 73%. F87A/T268V mutant was found to produce the indigo product with chemoselectivity as high as 80%. Moreover, F87G/T268A mutant was found to efficiently catalyze indole oxidation with higher activity (kcat/Km = 1388 mM−1 min−1) than other enzymes, such as the NADPH-dependent P450BM3 (2.4-fold), the Ngb (32-fold) and the Mb (117-fold). Computer simulation results indicate that the arrangements of amino acid residues in the active site can significantly affect the catalytic activity of the protein. The DFSM-facilitated P450BM3 peroxygenase system provides an alternative, simple approach for a key step in the bioproduction of indigo.

Since 2008, soil and water treatment and ecological restoration have been applied in the karst areas of Southwest China, but the effect of the treatments in karst fault basins is not clear. As a typical watershed of a faulted basin, studying the influence of landscape pattern changes on runoff and sediment yields in the Nandong underground river system (NURS) helps to establish the relationship between watershed and runoff and sediment changes. It provides a theoretical basis and effective method for water and soil management assessment, and soil and water treatment in karst fault basins. The vegetation topographic factor (VTF) was constructed using the normalized vegetation index (NDVI), digital elevation model (DEM) and water-system map from 2000 to 2018. On the basis of VTF classification, the vegetation topographic landscape index (VTLI) was calculated using the FRAGSTATS software, and the effects of VTLI changes on NURS runoff and sediment yield were analyzed. The study found the following: (1) PD, IJI, LSI and SHDI were positively correlated with runoff and sediment yield (p < 0.01), and the correlation coefficients were 0.693, 0.668, 0.551 and 0.582 and 0.62, 0.635, 0.627 and 0.63, respectively. AI and CONNECT were significantly negatively correlated with runoff and sediment yield (p < 0.01), and the correlation coefficients were −0.551 and −0.596, −0.627 and −0.446, respectively. The LPI and DIVISION index were not significantly correlated with discharge, but were significantly correlated with sediment yield (p < 0.05), and the correlation coefficients were −0.179 and 0.271, respectively. (2) The interpretation of VTLI for runoff increased from 0.639 to 0.778, and the interpretation of sediment transport decreased from 0.809 to 0.613. (3) In urban areas, VTF decreased and was persistent. VTF increased in the basin mountain edge area. In mountainous areas, VTF was unchanged, but has an antipersistence trend. The NURS ecological restoration project had achieved obvious results, and the change in the watershed increased runoff production and reduced sediment production. The capacity of soil and water conservation in the high slope area of the mountain edge of the basin recovered and showed a trend of sustainable development. Due to the urban expansion brought about by economic development, the capacity of soil and water conservation around the city has declined, and it showed a sustainable development trend. Policymakers should strengthen the ecological environment of urban areas and coordinate development within mountainous areas.

Background and Aims: Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. Methods: RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Results: Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. Conclusion: High LUCAT1 expression is an independent prognostic factor for liver cancer.

Nitric oxide (NO) can play both prosurvival and prodeath roles in photodynamic therapy (PDT). The generation efficiency of peroxynitrite anions (ONOO-), by NO and superoxide anions (O2•-), significantly influenced the outcome. Reports indicated that such efficiency is closely related to the distance between NO and O2•-. Thus, in this manuscript, l-arginine (Arg) ethyl ester-modified zinc phthalocyanine (Arg-ZnPc) was designed and synthesized as a photosensitizer (PS) and NO donor. Post light irradiation, the guanido of Arg-ZnPc can be effectively oxidized by the generated reactive oxygen species (ROS) in the PDT process to release NO. Such a strategy could ensure O2•- and NO generation in the same place at the same time to guarantee effective ONOO- formation. In addition, NO has other multiple synergistic cancer treatment functions, including tumor tissue vasodilatation for drug extravasation promotion, P-glycoprotein (P-gp) downregulation for drug efflux inhibition, and glutathione depletion for cancer cell endogenous antioxidant defense destruction. In vitro and in vivo results indicated that the effective ONOO- formation and multiple functions of Arg-ZnPc could synergistically enhance its PDT activity and ensure satisfactory cancer treatment outcome.

Liver cancer is a high morbidity and low survival disease all over the world. Chromosomal instability is hallmark of liver cancer. Microtubule-associated serine and threonine kinase 2 (MAST2), as a microtubule associated protein, may involve in tumorous chromosomal instability and plays important roles in cell proliferation and survival. The role of MAST2 in liver cancer has not been well elucidated, which is the aim of our study. In this study, The Cancer Genome Atlas database was used to study the MAST2 mRNA expression in liver cancer, and Chi-squared tests were performed to test the correlation between clinical features and MAST2 expression. ROC curve was performed to examined the diagnostic capacity. The prognostic value of MAST2 in liver cancer was assessed through Kaplan–Meier curves as well as Cox analysis. Our results showed MAST2 was upregulated in liver cancer, and the area under the curve (AUC) was 0.925 and indicated powerful diagnostic capability. High MAST2 expression was associated with advanced clinical status such as histological type (p = 0.0059), histologic grade (p = 0.0142), stage (p = 0.0008), T classification (p = 0.0028), N classification (p = 0.0107), survival status (p = 0.0062), and poor prognosis of patients. Importantly, MAST2 was an independent risk factor for patients’ prognosis after adjusting for other risk factors including stage, T classification, and residual tumor. In total, MAST2 is a potential diagnostic and prognostic biomarker of liver cancer.

Stigma, besides aggravating the damage caused by the disease, may also lead to unhealthy characteristics in patients and unhealthy situations in society. Individuals with acromegaly disease may suffer from stigma concerns, and the associated factors remain largely unknown. Therefore, the present cross-sectional study aimed to investigate the levels of perceived stigma in patients with acromegaly and explore the associated factors.A total of 138 patients with acromegaly were evaluated for having stigma using five previously validated scales: (i) the Stigma Scale for Chronic Illness, (ii) the Hamilton Anxiety Scale, (iii) the Rosenberg Self-Esteem Scale, (iv) the Body Image Concern scale, and (v) the Acromegaly Quality of Life scale. The potential determinants of stigma were evaluated using the univariate statistical analysis. A multivariate linear regression model was adopted to assess the predictors of stigma in patients with acromegaly. Pearson's correlation analysis was performed to analyze the relationship between stigma and the quality of life of the patients.Among the 138 respondents, 102 provided consent for participation.The evaluated patients exhibited critically high levels of perceived stigma. The multiple regression analysis revealed high BMI, serious body image concerns, inferiority complex personality, and critical levels of anxiety as the potential predictors of stigma in patients with acromegaly. The overall stigma and internalized stigma were significantly correlated with QoL in these patients.The patients with acromegaly exhibited critically high levels of perceived stigma, which led to psychological distress and disruptions in their daily lives. This finding highlights the importance of addressing the stigma concerns and the necessity for providing additional support to these patients in this regard during follow-up sessions. Further research should focus on developing intervention strategies to decrease the levels of perceived stigma in patients with acromegaly to promote their quality of life and for the psychosocial rehabilitation of these patients.

To explore the genetic etiology of a neonate with suggestive features of Cornelia de Lange Syndrome (CdLS).Chromosome karyotyping, copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the child. Meanwhile, peripheral venous blood samples were taken from his parents for verifying the suspected pathogenic variants detected in the child.The child has exhibited developmental delay, microcephaly, ptosis, micrognathia, and low ear setting, and was suspected as CdLS. No abnormality was found by karyotyping and CNV-seq analysis. WES has detected 5 heterogeneous variants and 1 hemizygous variant on the X chromosome. Combining the genetic pattern and result of family verification, a hemizygous C.3500TC (p.ile1167thr) of the SMC1A gene was predicted to underlay the clinical manifestations of the patient. This variant was not recorded in the dbSNP and gnomAD database. PolyPhen2, Provean, SIFT all predicted the variant to be harmful, and PhastCons conservative prediction is was a conservative mutation. ACMG variant classification standard evidence supports are PM2, PP2, and PP3.The novel c.3500TC (p.Ile1167Thr) missense mutation of the SMC1A gene probably underlay the genetic etiology of CdLS in this child. Above results has enriched the mutation spectrum of CdLS type II, and facilitated clinical counseling for this family.

There is a critical need for identifying time-sensitive and cost-effective markers of psychosis riskearly in the illness course. One solution may lie in affect dynamics, or the fluctuations of affect across time, which have been demonstrated to predict transitions in psychopathology. Across three studies, the current research is the first to comprehensively investigate affect dynamics in relation to subthreshold positive symptoms (perceptual aberration and magical ideation) and negative symptoms (social anhedonia) of the psychosis spectrum. Across multiple timescales and contexts, affect dynamics were modeled from inexpensive laboratory paradigms and social media text. Findings provided strong evidence for positive symptoms linked to heightened magnitude and frequency of affective fluctuations in response to emotional materials. Alternatively, negative symptoms showed modest association with heightened persistence of baseline states. These affect dynamic signatures of psychosis risk provide insight on the distinct developmental pathways to psychosis and could facilitate current risk detection approaches.