Search

Introduction The risk of new onset depression associated with sodium-glucose co-transporter 2 inhibitor (SGLT2I) use in patients with type 2 diabetes mellitus (T2DM) remains unclear. This study investigated the risk of new onset depression between SGLT2I and dipeptidyl peptidase 4 inhibitor (DPP4I) users. Methods This was a population-based cohort study of T2DM patients in Hong Kong between January 1st, 2015, and December 31st, 2019. T2DM patients over 18 with either SGLT2I or DPP4I use were included. 1:1 propensity-score matching using the nearest-neighbour method was conducted based on demographics, past comorbidities and non-DPP4I/SGLT2I medication use. Cox regression analysis models were used to identify significant predictors for new onset depression. Results The study cohort included a total of 18,309 SGLT2I users and 37,269 DPP4I users (55.57% male, mean age: 63.5 ± 12.9 years) with a median follow-up duration of 5.56 (IQR: 5.23–5.8) years. After propensity score matching, SGLT2I use was associated with a lower risk of new onset depression compared to DPP4I use (HR: 0.52, 95% CI: [0.35, 0.77], P = 0.0011). These findings were confirmed by Cox multivariable analysis and sensitive analyses. Conclusion SGLT2I use is associated with significantly lower risk of depression compared to DPP4 use in T2DM patients using propensity score matching and Cox regression analyses.

Human papillomavirus (HPV) integration is a critical step in cervical cancer development; however, the oncogenic mechanism at the genome-wide transcriptional level is still poorly understood. In this study, we employed integrative analysis on multi-omics data of six HPV-positive and three HPV-negative cell lines. Through HPV integration detection, super-enhancer (SE) identification, SE-associated gene expression and extrachromosomal DNA (ecDNA) investigation, we aimed to explore the genome-wide transcriptional influence of HPV integration. We identified seven high-ranking cellular SEs generated by HPV integration in total (the HPV breakpoint-induced cellular SEs, BP-cSEs), leading to intra-chromosomal and inter-chromosomal regulation of chromosomal genes. The pathway analysis revealed that the dysregulated chromosomal genes were correlated to cancer-related pathways. Importantly, we demonstrated that BP-cSEs existed in the HPV–human hybrid ecDNAs, explaining the above transcriptional alterations. Our results suggest that HPV integration generates cellular SEs that function as ecDNA to regulate unconstrained transcription, expanding the tumorigenic mechanism of HPV integration and providing insights for developing new diagnostic and therapeutic strategies.

We accomplished the synthesis of efficient and stable CsPbI3 NCs by regulating structural rigidity under the synergistic effect of Mg2+ and AcO− ions.

Binaries consisting of a hot subdwarf star and an accreting white dwarf (WD) are sources of gravitational wave radiation at low frequencies and possible progenitors of type Ia supernovae if the WD mass is large enough. Here, we report the discovery of the third binary known of this kind: it consists of a hot subdwarf O (sdO) star and a WD with an orbital period of 3.495 hours and an orbital shrinkage of 0.1 s in 6 yr. The sdO star overfills its Roche lobe and likely transfers mass to the WD via an accretion disk. From spectroscopy, we obtain an effective temperature of $T_{\mathrm{eff}}=54\,240\pm1\,840$ K and a surface gravity of $\log{g}=4.841\pm0.108$ for the sdO star. From the light curve analysis, we obtain a sdO mass of $M_{\mathrm{sdO}}=0.55$ ${\mathrm{M_{\odot}}}$ and a mass ratio of $q=M_{\mathrm{WD}}/M_{\mathrm{sdO}}=0.738\pm0.001$. Also, we estimate that the disk has a radius of $\sim 0.41R_\odot$ and a thickness of $\sim 0.18R_\odot$. The origin of this binary is probably a common envelope ejection channel, where the progenitor of the sdO star is either an RGB star or, more likely, an early AGB star; the sdO star will subsequently evolve into a WD and merge with its WD companion, likely resulting in an R CrB star. The outstanding feature in the spectrum of this object is strong Ca H&K lines, which are blueshifted by $\sim$200 km/s and likely originate from the recently ejected common envelope, and we estimated that the remnant CE material in the binary system has a density $\sim 6\times 10^{-10} {\rm g/cm^3}$., 13 pages, 15 figures, to be published in MNRAS

Purpose. The current clinical classification of hepatocellular carcinoma (HCC) cannot well predict the patient’s possible response to the treatment plan, nor can it predict the patient’s prognosis. We use the gene expression patterns of patients with hepatocellular carcinoma to reveal the heterogeneity of hepatocellular carcinoma and analyze the differences in prognosis and immunotherapy response of different immune subtypes. Methods. Firstly, using the hepatocellular carcinoma expression profile data of TCGA, combined with the single sample gene set enrichment analysis (ssGSEA) algorithm, the immune enrichment of the patient’s tumor microenvironment was analyzed. Subsequently, the spectral clustering algorithm was used to extract different classifications, and the cohort of hepatocellular carcinoma was divided into 3 subtypes, and the correlation between immune subtypes and clinical characteristics and survival prognosis was established. The patient’s risk index is obtained through the prognostic prediction model, suggesting the correlation between the risk index and various types of immune cells. Results. We can divide the liver cancer cohort into three subtypes: stromal cell activated immune-enriched type (A-IS), general immune-enriched type (N-IS), and non-immune-enriched type (non-IS). The 3-year survival rate of TCGA’s A-IS is higher than that of N-IS and non-IS, and the three components are significantly different ( p = 0.017 ). The 3-year survival rates of ICGC’s A-IS and N-IS groups were higher than those of the non-IS group. The analysis of the correlation between the risk index and immune cells showed that the patient’s disease risk was significantly positively correlated with cancer-associated fibroblast (CAF) stimulated cell, activated stroma cell, and anti-PD-1 resistant cell. Conclusion. The tumor gene expression characteristics of patients with hepatocellular carcinoma can be used as a basis for clinical patient classification. Different immune subtypes are closely related to survival prognosis. Different immune cell states of patients may lead to different disease risk levels. All these provide important references for the clinical identification and prognosis prediction of hepatocellular carcinoma.

Patients with chronic obstructive pulmonary disease (COPD) are characterized by an imbalance between oxidant enzymes and antioxidant enzymes. In the present study, we explored the protective effect of vitamin E on COPD and the underlying mechanisms. Targets of vitamin E were predicted by bioinformatics analysis. After establishing cigarette smoke (CS)-induced COPD rats, the expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX2), and transcriptional activity of signal transducer and activator of transcription 3 (STAT3) were measured. Additionally, the effects of vitamin E on CS-induced COPD were explored by assessing inflammation, the reactive oxygen species (ROS), the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA), viability of human bronchial epithelioid (HBE) cells, and the expression of EGFR/MAPK pathway-related factors after loss- and gain- function assays. Vitamin E alleviated COPD. Vitamin E inhibited MAPK signaling pathway through decreasing EGFR expression. Additionally, vitamin E suppressed CS-induced HBE cell damage. Functionally, vitamin E attenuated CS-induced inflammation, apoptosis, and ROS by inhibiting the EGFR/MAPK axis, thereby inhibiting COX2-mediated p-STAT3 nuclear translocation. Moreover, overexpression of COX2 attenuated the protective effect of vitamin E on COPD rats. The present study shows that vitamin E inhibits the expression of COX2 by negatively regulating the EGFR/MAPK pathway, thereby inhibiting the translocation of phosphorylated STAT3 to the nucleus and relieving COPD.

A genome editing tool targeting the high-risk human papillomavirus (HPV) oncogene is a promising therapeutic strategy to treat HPV-related cervical cancer. To improve gene knockout efficiency, we developed a gene knockout chain reaction (GKCR) method for continually generating mutagenic disruptions and used this method to disrupt the HPV18 E6 and E7 genes. We verified that the GKCR Cas9/guide RNA (gRNA) cassettes could integrated into the targeted loci via homology-independent targeted insertion (HITI). The qPCR results revealed that the GKCR method enabled a relatively higher Cas9/gRNA cassette insertion rate than a control method (the common CRISPR-Cas9 strategy). Tracking of Indels by DEcomposition (TIDE) assay results showed that the GKCR method produced a significantly higher percentage of insertions or deletions (indels) in the HPV18 E6 and E7 genes. Furthermore, by targeting the HPV18 E6/E7 oncogenes, we found that the GKCR method significantly upregulated the P53/RB proteins and inhibited the proliferation and motility of HeLa cells. The GKCR method significantly improved the gene knockout efficiency of the HPV18 E6/E7 oncogenes, which might provide new insights into treatment of HPV infection and related cervical cancer.

In this study, we employed a luminescenct agent CsPbCl3 perovskite nanocrystal for Cu2+ detection, and achieved a prominent enhancement in sensitivity by the introduction of ytterbium acetate (Yb(OAc)3). The introduced Yb(OAc)3 is capable of causing a morphology transformation of CsPbCl3 nanocrystals from initial nanocubes into one-dimensional (1D) nanowires (NWs). The formed 1D CsPbCl3 NWs paved a direct charge transport path and exhibited low defect density as well as superior conductivity, which were beneficial to accelerating the rapid electron transport from the luminescent agent to Cu2+, and to give rise to an efficient inhibition of undesired charge trap, respectively. Besides, AcO− rendered a reduced steric hindrance during the formation of a copper-based counter-ion pair, thus improving the adsorption capacity of Cu2+ on the surface of the luminescent agent, CsPbCl3 nanocrystals. As results, the 1D Yb(OAc)3 passivated CsPbCl3 NWs exhibited efficient luminescence quenching for enhanced detection sensitivity. This Yb(OAc)3-involved system exhibited a detection limit as low as 0.06 nM in the Cu2+ detection window range from 0 to 1000 nM, and such value is optimal in the documented works for Cu2+ detection based on luminescent perovskite materials.

PurposeWith an increasing demand for postoperative cosmetic effects in breast diseases, the single port by trans-axillary incision and air-inflation system, which provided better space and spared the assistant the effort of retraction, is widely used in clinic surgical treatment for multiple breast diseases.MethodsAccording to inclusion and exclusion criteria, patients who underwent trans-axillary single-incision surgery at Tianjin Medical University Cancer Hospital between December 2020 and July 2022 were included in the study. We collected and analyzed data on age, fertility history, ultrasound grade, clinical stage, pathological results, oncological prognosis, patient-centered cosmetic outcome, etc.ResultsA total of 115 cases were included, of which 33 patients with benign disease underwent mass resection, 68 patients with malignant tumors underwent mastectomy. 10 patients had a special type of breast lesion. A mastectomy was performed in 4 patients with male mammary gland development. Of the 115 cases, the maximum mass diameter was 3.00 ± 1.644 (0.6–8.5) cm. Blood loss during surgery was 85.77 ± 50.342 (10-200) ml. The surgery took 131.84 ± 59.332 (30-280) minutes to complete. The patient spent a total of 5.05 ± 2.305 (2-18) days in the hospital. And the length of surgical incision in all patients was 3.83 ± 0.884 (3-8) cm. All patients were very satisfied with the appearance of their breasts after dressing. 94.78% of patients were satisfied with the position of the incision.ConclusionThrough this study, we believe that in benign breast diseases and malignant breast tumors, trans-axillary single port insufflation technique-assisted endoscopic surgery has oncological safety and an aesthetic effect for most people with breast diseases.

Background: Laparoscopic cholecystectomy (LC) is the most common intra-abdominal surgical procedure globally, which frequently leads to substantial postoperative pain. Opioids play a major role in pain management previously. Some studies found that esketamine could reduce pain and opioid consumption. However, the relationship between esketamine and the postoperative quality of recovery and pain is uncertain undergoing LC. Thestudy aimed to evaluate the effects of intraoperative intravenous esketamine infusion on the quality of recovery (QoR) and pain after laparoscopic cholecystectomy (LC). Patients and methods: A total of 152 patients were randomly divided into the control (0.9% saline), 0.2 mg (esketamine bolus 0.2 mg/kg, followed by 0.2 mg/kg/h) and 0.3 mg (esketamine bolus 0.3 mg/kg, followed by 0.3 mg/kg/h) groups. A bolus of 0.9% saline/esketamine was administered before endotracheal intubation, followed by continuous infusion until gallbladder removal. The primary outcomes were 40-item QoR (QoR-40) score on postoperative day 1 (POD-1) and pain (Numerical Rating Scale, NRS) score during rest and coughing at different time points. The secondary outcomes were hemodynamic parameters, propofol and remifentanil consumption, 48-h cumulative consumption of flurbiprofen axetil and tropisetron hydrochloride, postoperative parameters, and adverse events. Results: The global QoR-40 score on POD-1 was lower in the control group than in the 0.2 and 0.3 mg groups. The NRS score during rest and coughing was lower in the 0.2 and 0.3 mg groups than in the control group at alltime points. Hemodynamic parameters were more stable in the esketamine groups. Propofol and remifentanil consumption was higher in the control group than in the esketamine groups. The 48-h cumulative consumption of flurbiprofen axetil and tropisetron hydrochloride was lower in the esketamine groups. The extubation time was longer in the 0.3 mg group than in the control and 0.2 mg groups. The control group had more patients with oxygen saturation (SpO2) Conclusions: Intravenous esketamine infusion improved the QoR on POD-1 after LC. It provided a good analgesic effect, reduced the 48-h cumulative consumption of flurbiprofen axetil and tropisetron hydrochloride, and resulted in stable hemodynamic parameters. However, a higher esketamine dose prolonged the extubation time and increased the incidence of adverse events. Trial registration: This study was approved by the Ethics Committee of Xuzhou Central Hospital (XZXY-LK-20211209-051) and registered at ClinicalTrials.gov (19/12/2021, ChiCTR2100054508). This randomized triple-blind placebo-controlled trial was performed from December 2021 to August 2022. Written informed consent was obtained from all patients. The study was terminated after follow-up completion of the last study participant.

Prime editing (PE) holds tremendous potential in the treatment of genetic diseases because it can install any desired base substitution or local insertion/deletion. However, the full-length PE effector size (6.3-kb) was beyond the packaging capacity of adeno-associated virus (AAV), hindering its clinical transformation. Various splitting strategies have been used to improve its delivery, but always accompanied by compromised PE efficiency. Here, we developed a modular and efficient SunTag-PE system that splits PE effectors into GCN4-nCas9 and single-chain variable fragment (scFv) tethered reverse transcriptase (RT). We observed that SunTag-PEs with 1×GCN4 in the N terminus of nCas9 was the most efficient configuration rather than multiple copies of GCN4. This SunTag-PE strategy achieved editing levels comparable to canonical fused-PE and higher than other split-PE strategies (including sPE and MS2-PE) in both PE2 and PE3 forms with no increase in insertion–deletion (indel) byproducts. Moreover, we successfully validated the modularity of SunTag-PE system in the Cas9 orthologs of SauCas9 and FrCas9. Finally, we employed dual AAVs to deliver SunTag-ePE3 and efficiently corrected the pathogenic mutation in HBB mutant cell line. Collectively, our SunTag-PE system provides an efficient modular splitting strategy for prime editing and further facilitate its transformation in clinics.

The current study aimed to determine the expression of carnitine palmitoyltransferase 1A (Cpt1a) in the lung tissue of chronic obstructive pulmonary disease (COPD) patients and its correlation with lung function. An increase in Cpt1a expression improved lung function in patients with COPD by inhibiting apoptosis and the inflammatory response of lung endothelial cells. Lung tissues of 20 patients with COPD and 10 control patients were collected, their Cpt1a expression was determined by western blotting and apoptosis and inflammation were assessed by haematoxylin-eosin staining, TUNEL assay and ELISA. Mice with knockout or overexpression of Cpt1a were constructed by lentivirus

Background Because of the complexity and heterogeneity, therapeutic effect of breast cancer varies in each subtype, which is classified based on the molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2. Thus, novel comprehensive and precise molecular indicators in breast carcinogenesis are urgently in need. Methods The expression of ZNF133 in breast cancer tissues was detected by immunohistochemical staining. The interaction between KAP1 complex and ZNF133 was identified by affinity purification-coupled mass spectrometry. The regulatory mechanisms were validated by luciferase reporter assay and co-immunoprepitation. The target genes of ZNF133 was determinged by chromatin immunoprecipitation-based deep sequencing. Gain-or-loss-of-function assays were used to identify the function and underlying mechanisms of ZNF133 in breast cancer. Cancer cell proliferation, invasion, and tumorigenesis of breast cancer cells were analyzed using cell counting assays, colony formation, transwell, and xenograft tumor models. Results Here we report that ZNF133, a zinc-finger protein, is negatively associated with advanced pathological staging and poor survival of breast carcinomas. Moreover, ZNF133 is a transcription repressor, physically associated with the KAP1 complex and transcriptionally represses a cohort of genes including L1CAM that are critically involved in cell proliferation and motility. We demonstrate that the ZNF133/KAP1 complex inhibits the proliferation and invasion of breast cancer cells in vitro and suppresses breast cancer growth and metastasis in vivo through dampening the transcription of L1CAM. Conclusion Our study ascertains the value of ZNF133 and L1CAM level in the diagnosis and prognosis of breast cancer, contributes to the deeper understanding of the regulation mechanism of ZNF133 for the first time, and provides a new therapeutic strategy and precise intervention target for breast cancer.

Cost-effectively improving the performance of biochar is essential for its large-scale practical application. In this work, the agro-industrial by-products copper slag and tobacco straw were employed for the preparation of modified biochar (CSBC). The obtained CSBC exhibited satisfactory capacity on Se(IV) immobilization of 190.53 mg/g, with surface interactions determined by the monolayer and mainly chemisorption. The removal mechanisms included chemical reduction, electrostatic attraction, co-precipitation, and formation of complexations. Interestingly, the existence of Cu2Se structure after adsorption indicated the involvement of Cu species within Se(IV) elimination. Moreover, the industrial agricultural practicality of CSBC was evaluated by regeneration tests, economic assessment, and pot experiments. The results demonstrate that iron species-modified biochar prepared from two agro-industrial by-products is a promising and feasible candidate for selenite removal from wastewater.

This study explored the effects of consumption guidance on sensory evaluation and risk perception of betel nut consumers and compared the effects of different consumption guidance methods on consum...

Low disturbance lunar soil profile samples play an important role in the study of the evolution of the Moon and the exploration of lunar mineral resources. At present, two methods have been applied to collect lunar soil profile samples, namely drill coring (including rotary drilling and rotary-percussive drilling) and impact penetration coring. Among them, the impact penetration coring has little disturbance to the sample, but the high resistance and low filling rate limit its application prospects. In this study, the cause of the above problems was discussed and a method of reducing resistance and increasing efficiency based on the particle unidirectional flow effect was proposed. The particle unidirectional behavior was analyzed by employing the numerical simulation based on the discrete element method (DEM). Then the feasibility of this drag reduction and efficiency enhancement method was verified experimentally. The results show that the asymmetric wedge-shaped arrays on the inner and outer walls of the coring tube and the simultaneous application of a simple harmonic vibration (with a frequency of 50 Hz and amplitude of 0.6 mm) significantly improved the coring performance. Compared with the impact penetration coring, the specific energy consumption was reduced by 38.5%, the coring rate was increased by 16.4%, and the force required removing the coring tube after sampling was reduced by 84%. When the wedge-shaped arrays were replaced with the wheat awn arrays whose height was close to the median size of the simulated lunar soil particles, more particles were discharged. Compared with the impact penetration coring as well, the specific energy consumption was reduced by 48.6%, the coring rate was increased by 22.2%, and the force required removing the coring tube was reduced by 86.7%.

Cost-effectively improving the performance of biochar is essential for its large-scale practical application. In this work, the agro-industrial by-products copper slag and tobacco straw were employed for the preparation of modified biochar (CSBC). The obtained CSBC exhibited satisfactory capacity on Se(IV) immobilization of 190.53 mg/g, with surface interactions determined by the monolayer and mainly chemisorption. The removal mechanisms included chemical reduction, electrostatic attraction, co-precipitation, and formation of complexations. Interestingly, the existence of Cu

In this study, an experiment based on the Dynamical-Statistical-Analog Ensemble Forecast model for Landfalling Typhoon Gale (DSAEF_LTG model) was conducted to predict tropical cyclone (TC)-induced potential maximum gales in South China for the first time. A total of 21 TCs with maximum gales greater than or equal to 17.2 m/s (at least one station) during 2011–2018 were selected for this experiment. Among them, 16 TCs in 2011–2015 were selected as the training samples aimed at identifying the best forecast scheme, while 5 TCs in 2016–2018 were selected as the independent samples to verify the best forecast scheme. Finally, the forecast results were compared with four numerical weather prediction (NWP) models (i.e., CMA, ECMWF, JMA and NCEP) based on four forecasting skill scores (Threat Score, False Alarm Ratio, Missing Ratio and Bias Score) at thresholds above Beaufort Scale 7 and 10, and two more indicators (Mean Absolute Error and pearson correlation coefficient). The results revealed encouraging forecasting ability in South China for the DSAEF_LTG model. In general, the DSAEF_LTG model showed higher forecasting skill than the NWP models above the critical thresholds. While the DSAEF_LTG model was prone to false alarms, the NWP models were prone to missing alarms, especially for an intense scale (≥Beaufort Scale 10). In addition, the DSAEF_LTG model also performed best with the smallest forecasting error. Furthermore, the DSAEF_LTG model had distinct advantages in predicting target TCs with typical tracks and widespread gales, both in terms of the wind field pattern and the magnitude of central wind speeds. However, for sideswiping TCs with small-scale gales, the DSAEF_LTG model tended to over-predict and held no advantage over the NWP models, which could perhaps be improved by introducing more reasonable ensemble forecast schemes in further research.

Background: Nasogastric tube inserted before laparoscopic cholecystectomy is a preoperative common preparation, which is an invasive procedure and exacerbates the patient’s anxiety level. This prospective, observational, cohort study aimed to explore the effects of preoperative anxiety level in patients with nasogastric tube inserted on the postoperative quality of recovery and pain undergoing laparoscopic cholecystectomy, and analyze the correlation between preoperative anxiety level and the postoperative quality of recovery. Method: Patients with STAI-S＞40 were excluded the day before surgery. After entering the operating room, patients were assessed anxiety level using the Anxiety - Visual Analog Scale. The quality of recovery was assessed using 15 - items quality of recovery on postoperative day 1 and 2. The pain was evaluated with the Numerical Rating Scale. 17 cases were excluded, and a total of 80 patients were enrolled in this study.Results: Compared with the group N, Anxiety Visual Analog Scale scores were higher in the group Y (with nasogastric tube inserted) after entering the operating room (P < 0.001), 15 - items quality of recovery scores on postoperative day 1 in the group Y was lower than group N (without nasogastric tube inserted) (P < 0.001). Pain intensity was higher in group Y at 2, 4, 8, 12, 24 and 48h after surgery than in Group N (P < 0.050). Anxiety Visual Analog Scale scores were significantly and negatively correlated with the 15- items quality of recovery scores (r = -0.91, P < 0.001). Compared with group N, group Y had longer time to get out of bed and postoperative first flatus time (P < 0.001). The AIS scores were higher on the night after surgery in group Y than in group (P < 0.001). Conclusion: In summary, nasogastric tube inserted increases preoperative anxiety level, which is associated with lower postoperative quality of recovery and higher pain intensity after surgery, and affects the patient's emergence time and postoperative sleep quality. We can implement intervention measures according to patients' conditions to relieve patients' preoperative anxiety level, improve the postoperative quality of recovery, improve patients' satisfaction and speed up recovery.Trial registration: This prospective, observational, cohort study selected patients who underwent laparoscopic cholecystectomy at Xuzhou Central Hospital from April 2022 to June 2022. The study was approved by the Ethics Committee of Xuzhou Central Hospital (XZXY-LK-20220318-024) and registered on Clinicaltrials.gov (10/04/2022, ChiCTR2200058548).

In the past few years, with the rapid growth of digital technologies, Facebook, Twitter, and other social media platforms have become the digital oligarchies, which have the enormous capabilities to potentially control what is discussed in cyberspace. In the digital oligarchy era, social perception and social influence in different complex social systems have evolved quickly. In this article, we conducted large-scale empirical studies on social perception and social influence regarding the Trump phenomenon from personal perception, media, and public attention perspectives. We found that there exist obvious correlations between the posting behavior of Trump and the attention of news media. By constructing public attention networks using complex networks based on Google search information, we further reveal that digital platforms could affect social perception and social influence significantly. Especially, we obtained that the public attention can always be influenced by the political moments.

Background and PurposeMyasthenia gravis (MG) is a T cell-dependent antibody-mediated autoimmune disorder that can seriously affect patients' quality of life. However, few studies have focused on the severity of MG. Moreover, existing therapeutic efforts, including those targeting biomarkers for MG, remain unsatisfactory. Therefore, it is vital that we investigate the pathogenesis of MG and identify new biomarkers that can not only evaluate the severity of the disease but also serve as potential therapeutic targets. Long noncoding RNA LINC00680 has been found to be associated with the progression of a variety of diseases as a competing endogenous RNA (ceRNA). However, the specific role of LINC00680 in MG has yet to be clarified. Here, we aimed to investigate the association between LINC00680 and the severity of MG.MethodsBioinformatics tools, quantitative real-time PCR, Western blotting, and luciferase assays were selected to investigate key signaling pathways and RNA expression in patients with MG. The Quantitative MG Score scale and the MG Composite scale were used to evaluate the severity of MG in the included patients. Cell viability assays and flow cytometry analysis were selected to analyze cell proliferation and apoptosis.ResultsCompared with control subjects, the expression levels of LINC00680 and mitogen-activated protein kinase 1 (MAPK1) in peripheral blood mononuclear cells of patients with MG were both upregulated; the levels of miR-320a were downregulated. A positive correlation was detected between LINC00680 expression and the severity of MG. Luciferase reporter assays identified that LINC00680 acts as a target for miR-320a. The in vitro analysis confirmed that LINC00680 regulates the expression of MAPK1 by sponging miR-320a. Finally, the functional analysis indicated that LINC00680 promoted Jurkat cell proliferation and inhibited cellular apoptosis by sponging miR-320a.ConclusionLINC00680 may be associated with the severity of MG as a ceRNA by sponging miR-320a to upregulate MAPK1. These findings suggest that LINC00680 may represent a potential biomarker which evaluates the severity of MG and may serve as a therapeutic target.

Background: Since its outbreak in late December 2019, the coronavirus disease 2019 (COVID-19) has culminated in a global pandemic, and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has continued to mutate, with increasing rates of transmission and pathogenicity, having a serious worldwide impact. This study aims to assess the benefits of the health-related quality of life of using N-acetylcysteine(NAC).Methods: In this prospective observational research, 63 confirmed COVID-19 patients who were treated between the ends of January and March 2020 were divided into patients treated with NAC-treatment (32 cases) and non-NAC-treatment groups (31 cases). Patients were followed up at discharge and at 1, 3, and 6 months after discharge. The clinical treatment effects of the two groups were compared, and the St. George’s Respiratory Questionnaire (SGRQ) evaluated patient-reported outcomes.Results: There were strong correlations between SGRQ component scores (0.728, 0.749, 0.850; P < 0.001 for all items) as well as between each SGRQ component score and the total patient score (0.822, 0.958, 0.957; P < 0.001 for all items). In the univariate analysis, the change differences of one month after discharge compared with discharge between two groups patients were statistically significant in the impacts and total scores (753.000, P < 0.001; 644.000, P = 0.042); the change differences of three months after discharge compared with discharge were also significant in the activity, impacts, and total scores (660.500, P = 0.022; 800.000, P < 0.001; 707.000, P = 0.004). In the multivariate analysis, the factors that have statistically significant influence on the unit value of SGRQ total score difference (UVDSGRQ) is NAC treatment (β = 1.954, P < 0.001), disease severity (β = 3.179, P < 0.001), follow-up duration (β = -0.232, P = 0.001), as well as NAC treatment and follow-up duration interaction item (β = -0.436, P = 0.004).Conclusion: Our study shows as the follow-up time increases, the SGRQ total scores of patients treated with NAC decreases significantly faster than those who were treated without NAC. In the treatment of COVID-19 patients, increasing the use of NAC has clinical significance.

Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as important regulators of the immune system and are involved in the control of immune cell biology, disease pathogenesis, as well as vaccine responses. A repository of ncRNA-immune associations will facilitate our understanding of ncRNA-dependent mechanisms in the immune system and advance the development of therapeutics and prevention for immune disorders. Here, we describe a comprehensive database, RNA2Immune, which aims to provide a high-quality resource of experimentally supported database linking ncRNA regulatory mechanisms to immune cell function, immune disease, cancer immunology, and vaccines. The current version of RNA2Immune documents 50,433 immune-ncRNA associations in 42 host species, including: (1) 6690 ncRNA associations with immune functions involving 31 immune cell types; (2) 38,672 ncRNA associations with 348 immune diseases; (3) 4833 ncRNA associations with cancer immunology; and (4) 238 ncRNA associations with vaccine responses involving 26 vaccine types targeting 22 diseases. RNA2Immune provides a user-friendly interface for browsing, searching, and downloading ncRNA-immune system associations. Collectively, RNA2Immune provides important information about how ncRNAs influence immune cell function, how dysregulation of these ncRNAs leads to pathological consequences (immune diseases and cancers), and how ncRNAs affect immune responses to vaccines. RNA2Immune is available at http://bio-bigdata.hrbmu.edu.cn/rna2immune/home.jsp.

Objectives The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks. Methods This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between 1 January 2015 and 31 December 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. Results This study included 43 201 patients [median age: 63.23 years old (Interquartile range, IQR): 55.21–71.95, 53.74% males; SGLT2I group: n = 16 144; DPP4I group: n = 27 057] with a median follow-up of 5.59 years (IQR: 5.27–5.81 years) since initial drug exposure. The incidence rate of developing gout [Incidence rate (IR): 2.5; 95% CI: 2.2, 2.9] among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8, 5.8). SGLT2I was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42, 0.58; P-value Conclusions SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use.

Ischemic stroke (IS) is a high-incidence disease that seriously threatens human life and health. Neuroinflammation and immune responses are key players in the pathophysiological processes of IS. However, the underlying immune mechanisms are not fully understood. In this study, we attempted to identify several immune biomarkers associated with IS. We first retrospectively collected validated human IS immune-related genes (IS-IRGs) as seed genes. Afterward, potential IS-IRGs were discovered by applying random walk with restart on the PPI network and the permutation test as a screening strategy. Doing so, the validated and potential sets of IS-IRGs were merged together as an IS-IRG catalog. Two microarray profiles were subsequently used to explore the expression patterns of the IS-IRG catalog, and only IS-IRGs that were differentially expressed between IS patients and controls in both profiles were retained for biomarker selection by the Random Forest rankings. CLEC4D and CD163 were finally identified as immune biomarkers of IS, and a classification model was constructed and verified based on the weights of two biomarkers obtained from the Neural Network algorithm. Furthermore, the CIBERSORT algorithm helped us determine the proportions of circulating immune cells. Correlation analyses between IS immune biomarkers and immune cell proportions demonstrated that CLEC4D was strongly correlated with the proportion of neutrophils (r = 0.72). These results may provide potential targets for further studies on immuno-neuroprotection therapies against reperfusion injury.

The measurement of influence on online platforms has been an important issue for various applications, including viral marketing, recommender systems, and the Internet celebrity economy. Generally, the citation frequency, mention frequency, and in-degree of users are the three major criteria for evaluating online influence in existed studies. However, some online media platforms neither provide social networking functions nor support social relationship labeling, making it infeasible to measure the user influence via the above three criteria. Such platforms can be named nonexplicit-relationship platforms. In this article, we propose three new criteria, explicit conversion rate (ER), frequency of promotion (FP), and average participation density (APD), and design a novel algorithm to effectively calculate and evaluate users’ influence on these platforms. The stability and sustainability of user influence are evaluated to distinguish the real influentials from the disguised ones, while the latter usually appears for temporary commercial advertisement purposes. The experiments proved the effectiveness of the proposed criteria and the algorithm in determining influentials’ influence, as well as the corresponding stability and sustainability.

We explain the effect of asset redeployability on corporate investment and equity value in the framework of contract theory with asymmetric information. Our theoretical study suggests that asset redeployability tends to enhance a financially-constrained firm’s investment level, investment-cash flow sensitivity and equity value, but does not have such effects on an unconstrained firm. Empirically, we use 2318 Chinese listed companies as sample over the period 2008–2014 and find evidence confirming theoretical predictions. Our findings demonstrate that asset redeployability is important in determining the corporate investment and equity value of constrained firms, thus managers should be aware of the asset characteristics and liquidation values when making asset transactions.