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BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of

Intentional electromagnetic interference is a serious threat to the safety of electronic devices. Multiple electromagnetic pulses will be coupled and transmitted to electronic devices through the cables. Accumulative effects are generated, which make it easier for damage to occur in the electronic devices. In this article, the working principle of micro-silicon acceleration sensors is introduced. The accumulative effects of multiple pulses on acceleration sensors is studied by a large number of injection experiments. The accumulation trends of multiple pulses with different pulse numbers and intervals are analyzed. The damaged structures inside abnormal sensor amplifiers were observed via optical microscopy and scanning electron microscopy. The experimental results show that the accumulative effect is strengthened with increased pulse number or decreased pulse interval, and the threshold voltage for multiple pulses on the acceleration sensor decreases. The threshold voltage for a single pulse is 321.57 V. When the pulse interval is 1 μs and the pulse number is 5, the threshold voltage for multiple pulses is 163.42 V, which is reduced by 49.12% compared with a single pulse. These results provide a reference for the damage design of electromagnetic pulse weapons.

Accompanied by the increasingly serious disordered electromagnetic radiation to trigger electromagnetic pollution become a new generation source which is harmful and difficult to protect, it is still a enormous challenge to develop a novel microwave absorbing materials (MAM) with low-density and wide absorption band. Here, we propose an advanced strategy to encapsulate red blood cell-like mesoporous carbon spheres with magnetic nanoparticles in terms of the problems of poor impedance matching, narrow absorption band of single dielectric loss material or high density of single magnetic loss material. A novel microwave absorber (MRBC), exhibited with the characteristics of ultra-high specific surface area (BET specific surface area: >500 m2/g), uniform mesoporous properties (Pore diameter: 7–8 nm) and special hollow structure and composed of carbon spheres with intact red blood cell morphology and magnetic nanoparticles, was obtained by the combination of double vacuum sintering processes and glycolate pyrolysis process. The unique microstructure and the synergistic effect of multiple dielectric loss and magnetic loss capability make MRBC-3 achieve an effective bandwidth of 5.77 GHz at a low filling rate (15 wt%) and an ultra-thin thickness (1.74 mm). Meanwhile, the minimum reflection loss of MRBC-4 is −64.26 dB. Furthermore, we use normalized input impedance to discuss the special properties of quarter wavelength matching layer, and verify the location of minimum reflection loss.

Aims Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin–ASK1 pathway, not the classical calcineurin–nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis. Methods and results Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages. Conclusion Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.

Objective To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding. Methods Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19 (COVID-19) in Wuhan Union Hospital. We compared clinical features among patients with prolonged (a positive SARS-CoV-2 RNA on day 23 after illness onset) and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis. Results Among 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) were administered with arbidol, 58.4% (139/238) were given arbidol in combination with interferon. The median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8–30 days) with a longest one of 51 days. The patients with prolonged virus shedding had higher value of D-dimer (P=0.002), IL-6 (P8 days after symptom onset [OR: 2.447, 95% CI (1.351–4.431)], ≥3 days from onset of symptoms to first medical visitation [OR: 1.880, 95% CI (1.035–3.416)], illness onset before Jan. 31, 2020 [OR: 3.289, 95% CI (1.474–7.337)]. Arbidol in combination with interferon was also significantly associated with shorter virus shedding [OR: 0.363, 95% CI (0.191–0.690)]. Conclusion Duration of SARS-CoV-2 virus shedding was long. Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11596-021-2434-y and is accessible for authorized users.

Several follow-up studies have found that COVID-19 (coronavirus disease 2019) patients had persistent symptoms after discharge. Gut microbiota play an important role in human health and immune responses. Therefore, this study investigated the gut microbiota of recovered COVID-19 patients and the correlations between gut microbiota and persistent symptoms after discharge. Stool samples were collected from 15 recovered healthcare workers (HCWs) with COVID-19 at three months after discharge, in addition, stool samples were collected from 14 healthy controls (HCs) to perform 16S rRNA gene sequencing between May and July 2020. Compared with HCs, recovered HCWs had reduced bacterial diversity at three months after discharge, with a significantly higher relative abundance of opportunistic pathogens, and a significantly lower relative abundance of beneficial bacteria. In addition, Escherichia unclassified was positively correlated with persistent symptoms at three months after discharge, including fatigue (r = 0.567, p = 0.028), chest tightness after activity (r = 0.687, p = 0.005), and myalgia (r = 0.523, p = 0.045). Intestinibacter bartlettii was positively correlated with anorexia (r = 0.629, p = 0.012) and fatigue (r = 0.545, p = 0.036). However, Faecalibacterium prausnitzii was negatively correlated with chest tightness after activity (r = −0.591, p = 0.02), and Intestinimonas butyriciproducens was negatively correlated with cough (r = −0.635, p = 0.011). In conclusion, the gut microbiota of recovered HCWs with COVID-19 at three months after discharge was different from that of HCs, and altered gut microbiota was correlated with persistent symptoms after discharge, highlighting that gut microbiota may play an important role in the recovery of patients with COVID-19. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s12275-021-1206-5.

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia. It is unknown why fibrosis in IPF distributes in the peripheral or named sub-pleural area. Migration of pleural mesothelial cells (PMC) should contribute to sub-pleural fibrosis. Calpain is known to be involved in cell migration, but the role of calpain in PMC migration has not been investigated. In this study, we found that PMCs migrated into lung parenchyma in patients with IPF. Then using Wt1tm1(EGFP/Cre)Wtp /J knock-in mice, we observed PMC migration into lung parenchyma in bleomycin-induced pleural fibrosis models, and calpain inhibitor attenuated pulmonary fibrosis with prevention of PMC migration. In vitro studies revealed that bleomycin and transforming growth factor-β1 increased calpain activity in PMCs, and activated calpain-mediated focal adhesion (FA) turnover as well as cell migration, cell proliferation, and collagen-I synthesis. Furthermore, we determined that calpain cleaved FA kinase in both C-terminal and N-terminal regions, which mediated FA turnover. Lastly, the data revealed that activated calpain was also involved in phosphorylation of cofilin-1, and p-cofilin-1 induced PMC migration. Taken together, this study provides evidence that calpain mediates PMC migration into lung parenchyma to promote sub-pleural fibrosis in IPF.

Background There is growing opinion that primary spontaneous pneumothorax (PSP) patients without hemodynamic compromise could be safely and successfully managed with observation alone. The aims of this meta-analysis were to estimate the safety and effectiveness of conservative treatment compared with that of interventional management as the initial treatment option for patients with PSP. Methods The PubMed, Embase and Cochrane library databases were systematically searched for randomized controlled trials (RCTs) and cohort studies (prospective or retrospective) until April 25, 2020, that compared conservative treatment and interventional treatment as the initial treatment for patients with PSP. The primary outcomes were success rates and recurrence rates. The secondary outcome was complication rates. Data extraction and quality assessment from eligible studies were independently conducted by two reviewers. Results 8 trials with a total of 1342 patients were identified. The success rates of conservative management were similar with interventional treatment, with a risk ratio 1.05 (95% confidence interval 0.94 to 1.17, I2 = 69.1%). There was no significant difference of recurrence rates between these two type managements. (RR, 1.43, 95% confidence interval 0.45 to 4.55, I2 = 86.7%). Complication rates were lower in conservative treatment group (13 of 215 [6.05%]) than in interventional treatment group (57 of 212, [26.89%]), although the difference did not reach statistical significance (RR, 0.15, 95% CI, 0.02 to 1.13, I2 = 56.7%). Conclusions Results of the meta-analysis suggest that conservative treatment offers a safe and effective alternative as compared with interventional management as the initial treatment approach for patients with PSP. However, more randomized clinical trials are need to provide more strong evidence to confirm our results.

The distribution of fibrosis in idiopathic pulmonary fibrosis (IPF) is subpleural with basal predominance. Alveolar epithelial cell was considered as the key cell in the initial phase of IPF. However, the idea of activation and damage of alveolar epithelial cells is very difficult to explain why fibrosis distributes in the subpleural area. In this study, human pleural mesothelial cell (PMC) line and primary rat PMC was used as in vitro model. Intraperitoneal injection of bleomycin was used for making a pulmonary fibrosis model. The integrity of cultured monolayer PMCs was determined by transepithelial electric resistance (TEER). Pleural permeability was estimated by measuring paracellular transport of fluorescein isothiocyanate (FITC)-conjugated dextran. Changes in lung tissue of patients with IPF were analyzed by Masson’s and immunofluorescence staining. We found bleomycin induced PMCs damage and increased PMCs permeability; increased PMCs permeability aggravated bleomycin-induced subpleural inflammation and pulmonary fibrosis. Moreover, bleomycin was found to activate VEGF/Src signaling which increased PMCs permeability. In vivo, inhibition of VEGF/Src signaling prevented bleomycin-induced subpleural pulmonary fibrosis. At last, activation of VEGF/Src signaling was confirmed in subpleural area in patients with IPF. Taken together, our findings indicate that VEGF/Src signaling mediated pleural barrier damage and increased permeability which contributes to subpleural pulmonary fibrosis.

Yaya Zhou,1,* Xing Shi,2,3,* Wei Fu,1,* Fei Xiang,1 Xinliang He,1 Bohan Yang,1 Xiaorong Wang,1 Wan-Li Ma1 1Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaorong Wang; Wan-Li MaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaTel +86-27-85726557Fax +86-27-85726557Email rong-100@163.com; whmawl@aliyun.comBackground: Most COVID-19 patients are moderate, and fever is the most common clinical manifestation and associated with poorer prognosis. Gut microbiota may also play important roles in COVID-19 pathogenesis. However, the association between gut microbiota and fever in individuals with moderate COVID-19 remains unclear.Methods: We compared the clinical features and laboratory results of 187 moderate COVID-19 patients with fever and without fever and identified several inflammatory markers in patients with fever. Then, we performed gut metagenome-wide association study for 31 individuals to identify the microbes and their epitopes which have potential role in fever and hyperinflammation.Results: Among 187 moderate COVID-19 patients, 127 (67.9%) patients presented with fever. Lymphocytes, CD3+ T cells, CD4+ T cells and the ratio of CD4+ T cells to CD8+ T cells were significantly reduced, while AST, LDH, CRP, IL-6 and IL-10 were significantly elevated in patients with fever. Gut microbiome composition was significantly altered in patients with fever compared with those with non-fever. Opportunistic pathogens such as Enterococcus faecalis and Saccharomyces cerevisiae were enriched in patients with fever. E. faecalis was positively correlated with LDH and D-dimer and negatively correlated with CD8+T cells and IL-4, while S. cerevisiae was positively correlated with diarrhea symptom. Furthermore, several species with anti-inflammatory and protective effects, such as Bacteroides fragilis and Eubacterium ramulus, were enriched in patients with non-fever. B. fragilis was positively correlated with lymphocytes, and E. ramulus was negatively correlated with LDH, AST and IL-6. Finally, we found that several bacterial epitopes of GroEL, a homolog of human HSP60, were enriched in patients with fever and positively correlated with IL-6, IL-10, WBC, neutrophils, D-dimer, LDH, CRP, and E. faecalis.Conclusion: Gut microbiota dysbiosis correlates with abnormal immune response in moderate COVID-19 patients with fever.Keywords: moderate COVID-19, fever, shotgun metagenomic sequencing, gut microbiota, epitopes

This study aimed to explore which age group out of the patients in quarantine wards with novel coronavirus pneumonia is the most susceptible to anxiety. The data of 32 Covid-19 patients isolated in the quarantine wards of the second Infectious Diseases Department of Baoding Hospital and 71 Covid-19 patients in Tangshan City Infectious Disease Hospital from January 24th to March 5th, 2020, a total of 103 patients, were analyzed. Among these patients, 97 isolated patients were scored with a self-rating anxiety scale (SAS) score seven days after quarantine, and the correlation between age and score was analyzed. These 97 isolated patients were then divided into three groups according to age: group A (up to 35 years old), group B (36-60 years), and group C (over 60 years). One-way analysis of variance was used to compare the scores among groups. The Q-test was used for pairwise comparison.P

Background The coronavirus disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated. Methods Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified. Results The overall HCFR in China was estimated to be 4.6% (95% CI 4.5–4.8%, P P P Conclusions This up-to-date and comprehensive picture of COVID-19 HCFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.

OBJECTIVES Recurrence rates of solitary fibrous tumours of the pleura (SFTP) after surgical resection vary widely in the published literature. Our objective was to systematically review the existing literature to determine an accurate estimate of SFTP recurrence rates after surgical resection and to determine risk factors associated with recurrence. METHODS PubMed, EMBASE and the Cochrane library were systematically searched for randomized controlled trials and observational studies (prospective or retrospective) through 20 June 2020 that reported the recurrence rates after surgical resection. The outcome of interest was recurrence. RESULTS Of the 23 included studies comparing 1262 patients, the overall recurrence of SFTP in patients who underwent surgical resection was 9% [95% confidence interval (CI) 7–12%; I2 = 52%]. In addition, pooled benign and malignant recurrence rates were 3% (95% CI 2–5%; I2 = 8%) and 22% (95% CI 15–32%; I2 = 52%), respectively. A benign SFTP was associated with a significantly lower recurrence rate than a malignant SFTP [odds ratio (OR) 0.11; 95% CI 0.06–0.20; I2 = 0%]. There was no significant difference in the recurrence rates between lesions originating from parietal versus visceral pleura (OR 1.30; 95% CI 0.28–6.02; I2 = 59%). Female sex was associated with increased recurrence (OR 5.29; 95% CI 1.66–16.92; I2 = 0%). CONCLUSIONS Collectively, this systematic review demonstrated a 9% SFTP post-resection recurrence rate. Furthermore, the recurrence rates for benign and malignant SFTP were 3% and 22%, respectively. Histological malignancy and female sex were associated with higher risk.

For some professionally, vocationally, or technically oriented careers, curricula delivered in higher education establishments may focus on teaching material related to a single discipline. By contrast, multidisciplinary, interdisciplinary, and transdisciplinary teaching (MITT) results in improved affective and cognitive learning and critical thinking, offering learners/students the opportunity to obtain a broad general knowledge base. Chemistry is a discipline that sits at the interface of science, technology, engineering, mathematics, and medicine (STEMM) subjects (and those aligned with or informed by STEMM subjects). This article discusses the significant potential of inclusion of chemistry in MITT activities in higher education and the real-world importance in personal, organizational, national, and global contexts. It outlines the development and implementation challenges attributed to legacy higher education infrastructures (that call for creative visionary leadership with strong and supportive management and administrative functions), and curriculum design that ensures inclusivity and collaboration and is pitched and balanced appropriately. It concludes with future possibilities, notably highlighting that chemistry, as a discipline, underpins industries that have multibillion dollar turnovers and employ millions of people across the world.

Background Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) is an irreversible pathologic condition of unknown cause, commonly involving the joint and the lung with variable amounts of fibrotic change. In contrast to rheumatoid arthritis or other chronic interstitial lung diseases such as interstitial pulmonary fibrosis, there is so far no extensively accepted or implemented animal model for this disease. Aims To provide guidance for those who are investigating the pathogenesis of RA‐ILD with animal models. Materials and Methods An analysis of papers from PubMed during 1978‐2020. Results We outline the present status quo for animal models of RA‐ILD about their modeling methods and pathogenesis, compare their pros and cons with respect to their ability to mimic the clinical and histological features of human disease and discuss their applicability for future research. Discussion There is no doubt that these animal models do provide valuable information relating to the pathogenesis of RA‐ILD and the development of effective therapeutic drugs. Nevertheless, these animal models can not entirely recapitulate clinical pathology and have some limitations in experimental research application. Therefore, it should be emphasized that we should improve and explore animal models in more accordance with the pathogenesis and clinical characteristics of human RA‐ILD. Conclusion These established animal models of the disease can significantly progress our understanding of the etiology of RA‐ILD, the fundamental mechanisms of its pathogenesis and the identification of new bio‐markers, and can contribute to the development and implementation of novel treatment strategies., The manuscript summarizes the characteristics of animal models about rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD), which can provide reference for those researchers who are interested in investigating the pathogenesis of RA‐ILD.

The calcium-sensitive receptor (CaSR) plays a role in several biological processes. However, its role in intestinal motility remains unclear. In this study, we aimed to determine the effect of electro-acupuncture (EA) at Shangjuxu (ST37) on CaSR in colonic dysplasia mice, and to explore the possible mechanism of EA regulating colonic movement. The mice were injected with nicardipine or hexamethonium bromide to induce colonic dysplasia. Intestinal transit function was assessed by twelve hours fecal granules and fecal water content percentage, while colonic slow wave was assessed by multi-channel physiological signal acquisition system, immunofluorescence and laser confocal microscopy were used to examine CaSR expression in the gastrointestinal (GI) tract of the mice. We found that the number of fecal particles, the frequency and amplitude of colonic slow wave were disrupted after nicardipine or hexamethonium bromide injection. In addition, CaSR expression in control group was mainly distributed in intestinal epithelial cells, and the morphological structure of mucosal layer was regular. Compared with control group, the structure of mucosal layer in nicardipine group and hexamethonium bromide group were all disorderly, the expression and fluorescence intensity of CaSR in nicardipine group were visible, but in hexamethonium bromide group were weakened. After EA intervention, these disorders were ameliorated, which suggested that EA at ST37 could therefore regulate colonic motility disorders via the involvement of CaSR.

Highlights • This study provides a risk score that predicts critical care admission and death in COVID-19. • Chest radiography severity scores are highly predictive of outcome. • The findings may inform admit/discharge decisions as well as patient selection for clinical trials., Background The COVID-19 pandemic continues to escalate. There is urgent need to stratify patients. Understanding risk of deterioration will assist in admission and discharge decisions, and help selection for clinical studies to indicate where risk of therapy-related complications is justified. Methods An observational cohort of patients acutely admitted to two London hospitals with COVID-19 and positive SARS-CoV-2 swab results was assessed. Demographic details, clinical data, comorbidities, blood parameters and chest radiograph severity scores were collected from electronic health records. Endpoints assessed were critical care admission and death. A risk score was developed to predict outcomes. Findings Analyses included 1,157 patients. Older age, male sex, comorbidities, respiratory rate, oxygenation, radiographic severity, higher neutrophils, higher CRP and lower albumin at presentation predicted critical care admission and mortality. Non-white ethnicity predicted critical care admission but not death. Social deprivation was not predictive of outcome. A risk score was developed incorporating twelve characteristics: age>40, male, non-white ethnicity, oxygen saturations3, neutrophil count>8.0 x109/L, CRP>40 mg/L, albumin100 µmol/L, diabetes mellitus, hypertension and chronic lung disease. Risk scores of 4 or higher corresponded to a 28-day cumulative incidence of critical care admission or death of 40.7% (95% CI: 37.1 to 44.4), versus 12.4% (95% CI: 8.2 to 16.7) for scores less than 4. Interpretation Our study identified predictors of critical care admission and death in people admitted to hospital with COVID-19. These predictors were incorporated into a risk score that will inform clinical care and stratify patients for clinical trials.

In this study, a total of 160 experimental data points of Henry's law constant of CO2 in 32 imidazole ionic liquids (ILs) were collected, with the temperatures range from 283 to 350 K. Herein intuitive and explanatory descriptors related to Henry's law constant (HLC) were suggested from the 2D structural features of the ILs according to experimental experience and laws. Temperature was used as another variable due to its significant effect on Henry's law constant. Three machine learning methods were used to construct models to fast predict the HLC based on suggested descriptors. Multi-layer Perceptrowas mainly used to build the model and compared with the results of Random forest and Multiple Linear Regression after investigating the outliers and variable selection. In addition, if only one data point was left at a similar temperature and the reduced dataset was also used to build models in the same procedure, the results were not as good as those of the full dataset but still satisfactory.

Objective To identify the potential associations of patient-, treatment-, and central venous access device (CVAD)-related factors with the CVAD-related thrombosis (CRT) risk in hospitalized children. Methods A systematic search of PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP database was conducted. RevMan 5.3 and Stata 12.0 statistical software were employed for data analysis. Results In terms of patient-related factors, the patient history of thrombosis (odds ratio [OR] = 3.88, 95% confidence interval [CI]: 2.57–5.85), gastrointestinal/liver disease (OR = 1.85, 95% CI: 0.99–3.46), hematologic disease (OR = 1.45, 95% CI: 1.06–1.99), and cancer (OR = 1.58, 95% CI: 1.01–2.48) were correlated with an increased risk of CRT. In terms of treatment-related factors, parenteral nutrition (PN)/total PN (OR = 1.70, 95% CI: 1.21–2.39), hemodialysis (OR = 2.17, 95% CI: 1.34–3.51), extracorporeal membrane oxygenation (OR = 1.51, 95% CI: 1.31–1.71), and cardiac catheterization (OR = 3.92, 95% CI: 1.06–14.44) were associated with an increased CRT risk, while antibiotics (OR = 0.46, 95% CI: 0.32–0.68) was associated with a reduced CRT risk. In terms of the CVAD-related factors, CRT risk was more significantly increased by peripherally inserted central catheter than tunneled lines (OR = 1.81, 95% CI: 1.15–2.85) or totally implantable venous access port (OR = 2.81, 95% CI: 1.41–5.60). And subclavian vein catheterization significantly contributed to a lower CRT risk than femoral vein catheterization (OR = 0.36, 95% CI: 0.14–0.88). Besides, multiple catheter lines (OR = 4.06, 95% CI: 3.01–5.47), multiple catheter lumens (OR = 3.71, 95% CI: 1.99–6.92), central line-associated bloodstream infection (OR = 2.66, 95% CI: 1.15–6.16), and catheter malfunction (OR = 1.65, 95% CI: 1.07–2.54) were associated with an increased CRT risk. Conclusion The exact identification of the effect of risk factors can boost the development of risk assessment tools with stratifying risks.

Triple-negative breast cancer (TNBC) is characterized by low expression of human epidermal growth factor receptor-2 (HER2), estrogen receptor (ER), and progesterone receptor (PR), which is the most aggressive subtype with poor outcome among breast cancers. The underlying mechanisms of TNBC remain unclear and there is a lack of biomarkers. In this study we conducted an in silico assay and found that FOXC1 was highly expressed in ER(−)/PR(−)/HER2(−) breast cancers, which was confirmed by qRT-PCR, immunohistochemistry, and Western blot analysis. FOXC1 was more highly expressed in TNBCs than the other breast cancers. Kaplan–Meier plotter revealed that expression of FOXC1 was associated with overall survival (OS) of patients with breast cancers. Expression of FOXC1 was reversely associated with level of H3K27me3, which was methylated by EZH2. In MCF-7 and T47D cells, inhibition of EZH2 by DZNeP or GSK343 concentration- and time-dependently increased expression of FOXC1. Finally, we demonstrated that the expression of FOXC1 was associated with resistance of doxorubicin treatment of breast cancer cells. In conclusion, these results suggest that FOXC1 may be a potential biomarker or drug target for TNBCs, and that downregulation of FOXC1 could have therapeutic value in treatment of TNBCs.

Emerging 3D printing technologies offer an exciting opportunity to create customized 3D objects additively from a digital design file. 3D printing may be further leveraged for personalized medicine, clinical trial, and controlled release applications. A wide variety of 3D printing methods exists, and many studies focus on extrusion-based 3D printing techniques that closely resemble hot melt extrusion. In this paper, we explore different pharmaceutical-grade feedstock materials for creating tablet-like dosage forms using a binder jet 3D printing method. In this method, pharmaceutical-grade powders are repeatedly spread onto a build plate, followed by inkjet printing a liquid binder to selectively bind the powders in a predetermined pattern. The physical properties of the pharmaceutical-grade powders and binders have been characterized and a molding method has been developed to select appropriate powder and binder materials for subsequent printing experiments. There was a correlation between the breaking forces of the molded and printed samples, but no clear correlation was observed for disintegration time, which was primarily controlled by the higher porosity of the printed samples. The breaking force and disintegration properties of as-printed and post-processed samples containing indomethacin as an active pharmaceutical ingredient have been measured and compared with relevant literature data.

This article estimates agglomeration effects via calculating EG (Elilsion & Glaeser) and TFP growth (Total Factor Production) by considering the undesired output of the industrial enterprise database and the entropy weight method. Using panel data of 207 county-level cities in China and 28 two-digit manufacturing industries from 2003 to 2013 based on SIC codes, this paper analyzes the relationship between agglomeration and TFP growth through the smooth transition model under different regions and factor-intensity. The results are as follows. (1) A negative relationship appears in manufacturing productivity. The agglomeration effect changes to the crowded effect. Environmental pollution is also generated by transportation and inadequate pollution treatment technology. (2) The excessive agglomeration phenomenon of developed areas (eastern region) is less than the less developed areas (central and western regions). (3) Resource-intensity industries present two thresholds that indicate complex regional features. For various intensive industries in different regions, the relationship between GML and agglomeration is different. High agglomeration does not always promote TFP growth. (4) At different levels of urban industrial agglomeration, the influences of efficiency change and technical change on GML are different. Overall, moderate agglomeration in all regions helps promote economic development.

To design a new breast vacuum bag to reduce global and local setup errors in post-mastectomy radiation therapy (PMRT). A total of 24 PMRT patients were immobilized with an old vacuum bag and 26 PMRT patients were immobilized with a new vacuum bag. The registration results were analysed using four regions of interest (ROI): the global ROI [including the whole region of the planning target volume (PTV), GROI], the supraclavicular area (SROI), the ipsilateral chest wall region (CROI) and the ipsilateral arm region (AROI). The global and local setup errors of the two groups were compared. The global setup errors of the new vacuum group were significantly smaller than those in the old vacuum group with the exception of yaw axes (P

Acute lung injury (ALI) is a severe lung syndrome with high morbidity and mortality, due to its complex mechanism and lack of effective therapy. The use of placenta‑derived mesenchymal stem cells (pMSCs) has provided novel insight into treatment options of ALI. The effects of pMSCs on lipopolysaccharide (LPS)‑induced inflammation were studied using a co‑culture protocol with LPS‑stimulated RAW264.7 cells. An LPS‑induced ALI Sprague‑Dawley rat model was developed by intravenously injecting 7.5 mg/kg LPS, and intratracheal instillation of 1x105 pMSCs was performed after administration of LPS to investigate the therapeutic potential of these cells. pMSCs ameliorated LPS‑induced ALI, as suggested by downregulated pro‑inflammatory cytokine tumor necrosis factor‑α and increased anti‑inflammatory cytokine interleukin‑10 in both cell and animal models. Moreover, the protein and leukocyte cells in bronchoalveolar lavage fluid decreased at a rapid rate after treatment with pMSCs. Histopathology demonstrated that pMSCs alleviated the infiltration of inflammatory cells, pulmonary hyperemia and hemorrhage, and interstitial edema. In addition, pMSC reduced the LPS‑induced expression of C‑X‑C motif chemokine ligand 12 in RAW264.7 macrophages and in lung tissue of ALI rats. This demonstrated that pMSCs are therapeutically effective in LPS‑induced ALI.

Using a systemic approach, this study investigates the time-varying linkages among currency markets of Japan, the People's Republic of China, the Republic of Korea, and the five core ASEAN economies to understand financial integration in Asia. We first construct a vector autoregressive model and use the Diebold and Yilmaz ( 2014 ) approach to quantitatively identify the connectedness within the system, accompanied by a rolling-window approach to allow for time-varying dynamics and pairwise Granger causality tests to check the robustness of our main results. We find that though systemic interconnectedness varies over time, the Singapore dollar is constantly a top net contributor, explaining most of the variation in East Asian currency markets.

Vascular cognitive impairment (VCI) is a type of cerebral vascular disorder that leads to learning and memory decline. VCI models can be induced by chronic cerebral hypoperfusion via permanent bilateral common carotid artery occlusion. 3‑N‑Butylphthalide (NBP) is a neuroprotective drug used for the treatment of ischemic cerebrovascular diseases. Silent information regulator 1 (SIRT1) plays an important role in memory formation and cognitive performance, and its abnormal reduction is associated with cognitive dysfunction in neurodegenerative diseases. Brain‑derived neurotrophic factor (BDNF) is a neurotrophic factor that plays critical roles in promoting neuronal growth and injury repair. The present study was performed to investigate the effects and the underlying mechanism of NBP on learning deficits in a rat model of VCI. Rats were divided into a control group, model group, low‑NBP‑dose group (30 mg/kg/day), high‑NBP‑dose group (60 mg/kg/day), NBP + SIRT1 inhibitor group and NBP + BDNF inhibitor group. Rats were then subjected to Morris water maze and T‑maze tests, which identified that NBP treatment significantly attenuated memory impairments in VCI rats. Molecular examination indicated that SIRT1 and BDNF expression levels in the hippocampus were increased by NBP treatment. However, NBP failed to ameliorate cognitive function after inhibition of the SIRT1/BDNF signaling pathway. In addition, NBP in combination with a SIRT1 inhibitor suppressed BDNF protein expression, but inhibition of BDNF did not inhibit SIRT1 protein expression in rats with VCI. The present results suggested that the neuroprotective effects of NBP on learning deficits in a rat model of VCI may be via regulation of the SIRT1/BDNF signaling pathway, in which SIRT1 may be the upstream signaling molecule. Therefore, the SIRT1/BDNF pathway could be a potential therapeutic target for VCI.

Background The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. Methods The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3–40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and consistency rate. Results The seroconversion of specific IgM and IgG antibodies were observed as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, respectively, and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, respectively, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity. Conclusions The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.

The spatial resolution of remote sensing images is continuously improved by the development of remote sensing satellite and sensor technology. Hence, background information in an image becomes increasingly complex and causes considerable interference to the object detection task. Can we pay as much attention to the object in an image as human vision does? This letter proposes a multi-scale spatial and channel-wise attention (MSCA) mechanism to answer this question. MSCA has two advantages that help improve object detection performance. First, attention is paid to the spatial area related to the foreground, and compared with other channels, more attention is given to the feature channel with a greater response to the foreground region. Second, for objects with different scales, MSCA can generate an attention distribution map that integrates multi-scale information and applies it to the feature map of the deep network. MSCA is a flexible module that can be easily embedded into any object detection model based on deep learning. With the attention exerted by MSCA, the deep neural network can efficiently focus on objects of different backgrounds and sizes in remote sensing images. Experiments show that the mean average precision of object detection is improved after the addition of MSCA to the current object detection model.

Autoantibodies to beta amyloid (Aβ) have been suggested to be involved in the pathogenesis of Alzheimer's disease (AD). However, data from clinical studies were inconsistent on autoantibody to Aβ levels in patients with AD. Therefore, we systematically searched the literature and performed meta-analysis to summarize the data of autoantibodies to Aβ in AD patients. The systematic search from PubMed and Web of Science included thirty case-control studies with a total of 2901 individuals (1311 AD patients and 1590 healthy control subjects). Random-effect meta-analysis showed a significant increased endogenous IgG autoantibody to Aβ levels in blood when compared with controls (Hedges' g = 0.337, 95% CI = 0.020 to 0.654, P = 0.03). In contrast, blood IgM autoantibody to Aβ levels was significantly decreased in patients with AD relative to control subjects (Hedges' g = - 0.962, 95% CI = - 1.797 to - 0.126, P = 0.024). Furthermore, cerebrospinal fluid Aβ levels were not significantly different between AD patients and control subjects (Hedges' g = - 0.446, 95% CI = - 2.357 to 1.464, P = 0.647). Subgroup analysis revealed that detection method contributed to the heterogeneity for studies measuring blood IgG autoantibody to Aβ levels in AD patients. Meta-regression analyses suggested that sex is a confounder for the outcome of the meta-analysis. Taken together, the results of this meta-analysis clarified circulating autoantibodies to Aβ levels in AD patients and suggested that endogenous IgG and IgM-class antibodies to Aβ may play a role in the pathogenesis of AD.

Traffic speed prediction is a critically important component of intelligent transportation systems. Recently, with the rapid development of deep learning and transportation data science, a growing body of new traffic speed prediction models have been designed that achieved high accuracy and large-scale prediction. However, existing studies have two major limitations. First, they predict aggregated traffic speed rather than lane-level traffic speed; second, most studies ignore the impact of other traffic flow parameters in speed prediction. To address these issues, the authors propose a two-stream multi-channel convolutional neural network (TM-CNN) model for multi-lane traffic speed prediction considering traffic volume impact. In this model, the authors first introduce a new data conversion method that converts raw traffic speed data and volume data into spatial–temporal multi-channel matrices. Then the authors carefully design a two-stream deep neural network to effectively learn the features and correlations between individual lanes, in the spatial–temporal dimensions, and between speed and volume. Accordingly, a new loss function that considers the volume impact in speed prediction is developed. A case study using 1-year data validates the TM-CNN model and demonstrates its superiority. This paper contributes to two research areas: (1) traffic speed prediction, and (2) multi-lane traffic flow study.

Background Platinum resistance is an important cause of clinical recurrence and death for ovarian cancer. This study tries to systematically explore the molecular mechanisms for platinum resistance in ovarian cancer and identify regulatory genes and pathways via text mining and other methods. Methods Genes in abstracts of associated literatures were identified. Gene ontology and protein-protein interaction (PPI) network analysis were performed. Then co-occurrence between genes and ovarian cancer subtypes were carried out followed by cluster analysis. Results Genes with highest frequencies are mostly involved in DNA repair, apoptosis, metal transport and drug detoxification, which are closely related to platinum resistance. Gene ontology analysis confirms this result. Some proteins such as TP53, HSP90, ESR1, AKT1, BRCA1, EGFR and CTNNB1 work as hub nodes in PPI network. According to cluster analysis, specific genes were highlighted in each subtype of ovarian cancer, indicating that various subtypes may have different resistance mechanisms respectively. Conclusions Platinum resistance in ovarian cancer involves complicated signaling pathways and different subtypes may have specific mechanisms. Text mining, combined with other bio-information methods, is an effective way for systematic analysis.

Recently, deep learning models have shown promising performances in many research areas, including traffic states prediction, due to their ability to model complex nonlinear relationships. However, deep learning models also have drawbacks that make them less preferable for certain short-term traffic prediction applications. For example, they require a large amount of data for model training, which is also computationally expensive. Moreover, deep learning models lack interpretability of the results. This paper develops a short-term traffic states forecasting algorithm based on partial least square (PLS) to help enhance real-time decision-making and build better insights into traffic data. The proposed model is capable of predicting short-term traffic states accurately and efficiently by capturing dominant spatiotemporal features and day-to-day variations from collinear and correlated traffic data. Three case studies are developed to demonstrate the proposed model in short-term traffic prediction applications.

Introduction Clinical studies have shown that a combination of a tyrosine kinase inhibitor (TKI) and pemetrexed overcame acquired resistance to epidermal growth factor receptor (EGFR) TKI in NSCLC. Previously, pemetrexed+gefintib (P+G) had improved progression-free survival (PFS) compared with gefitinib. We present OS, updated PFS, biomarker analysis, and safety of P+G versus gefitinib. Methods This was a phase 2, multicenter, randomized study conducted in East Asian patients with advanced nonsquamous NSCLC with EGFR mutations. Patients were randomized (2:1) to receive P+G (500 mg/m2 intravenously 3-weekly + 250 mg/day orally) or gefitinib. Results In total, 191 patients (P+G, n=126; gefitinib, n=65) comprised the intent-to-treat and safety populations. Median OS was 43.4 months in P+G versus 36.8 months in gefitinib arm; adjusted HR 0.77 (95% CI, 0.5-1.2); one-sided P=0.105. Median PFS was significantly longer in the P+G (16.2 months) versus gefitinib arm (11.1 months); adjusted HR 0.67 (95% CI, 0.5-0.9); one-sided P=0.009. In the P+G and gefitinib arms, median PFS was 22.6 and 11.0 months, respectively, in patients with low thymidylate synthase (TS) expression, and 12.6 and 9.9 months, respectively, in patients with high TS expression. Common second-line post-discontinuation systemic therapies were EGFR-TKIs and chemotherapy. Most patients experienced at least one adverse event. Conclusions Addition of pemetrexed to EGFR TKI gefitinib resulted in significantly improved PFS and numerically longer OS compared with gefitinib in treatment-naive patients with EGFR-mutated advanced nonsquamous NSCLC. Low TS expression appeared to be a good predictor for treatment outcomes.

The Beijing-Tianjin-Hebei region boasts rich geothermal resources and new achievements have been made in the exploration and development of geothermal resources in this region based on previous regional investigation. In detail, geothermal reservoirs of Gaoyuzhuang Formation of Jixian System and Changcheng System in Xiongan New Area have been recently discovered, opening up the second space of geothermal resources; the calculation method of the recoverable resources of geothermal fluid with reinjection being considered has been improved in Beijing-Tianjin-Hebei region, and uniform comprehensive assessment of shallow geothermal energy, hydrothermal geothermal resources, and hot dry rocks (HDR) geothermal resources in the whole Beijing-Tianjin-Shijiazhuang region has been completed. The scientific research base for cascade development and utilization of geothermal resources in Beijing-Tianjin-Hebei region has applied hydraulic fracturing technology to the geothermal reservoirs in Gaoyuzhuang Formation. As a result, the production capacity doubled and two-stage cascade utilization composed of geothermal power generation and geothermal heating were realized, with the first-phase installed capacity of 280 kW and the geothermal hearing is 30000 m2. In this way, a model of the exploration, development, and utilization of geothermal resources formed. Large-scale utilization has become the future trend of geothermal resource development in Beijing-Tianjin-Hebei region, and great efforts shall be made to achieve breakthroughs in reinjection technology, geothermal reservoir reconstruction technology, thermoelectric technology and underground heat exchange technology.

Carbon nitride (CN) films have emerged as promising photoelectrodes in photoelectrochemical (PEC) water-splitting cells. However, due to their intrinsic poor charge transfer dynamics and the absence of a controllable film deposition method, their performance remains unsatisfactory. Here, we report an in situ textured CN film that is strengthened by a band-gap state modulation strategy with superior PEC performance. The optimized film possesses a 15-fold improvement in photocurrent density over pristine CN film, reaching up to 119.2 μA cm−2 at 1.23 V versus RHE without any hole scavengers. Through experimental characterizations and theoretical verifications, we found that the remarkable photocurrent density originates from the synergistic effect of long wavelength photon harvesting and efficient charge migration. The substantial enhancement of PEC activity highlights the importance of nanoengineering in terms of controlling the macroscopic film morphology and modulating the microscopic electronic structure for the precise design of multipurpose photoelectrodes.

Aberrant activation of the epidermal growth factor receptor (EGFR/ERBB1) by erythroblastic leukemia viral oncogene homolog (ERBB) ligands contributes to various tumor malignancies, including lung cancer and colorectal cancer (CRC). Epiregulin (EREG) is one of the EGFR ligands and is low expressed in most normal tissues. Elevated EREG in various cancers mainly activates EGFR signaling pathways and promotes cancer progression. Notably, a higher EREG expression level in CRC with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) is related to better efficacy of therapeutic treatment. By contrast, the resistance of anti-EGFR therapy in CRC was driven by low EREG expression, aberrant genetic mutation and signal pathway alterations. Additionally, EREG overexpression in non-small cell lung cancer (NSCLC) is anticipated to be a therapeutic target for EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, recent findings indicate that EREG derived from macrophages promotes NSCLC cell resistance to EGFR-TKI treatment. The emerging events of EREG-mediated tumor promotion signals are generated by autocrine and paracrine loops that arise from tumor epithelial cells, fibroblasts, and macrophages in the tumor microenvironment (TME). The TME is a crucial element for the development of various cancer types and drug resistance. The regulation of EREG/EGFR pathways depends on distinct oncogenic driver mutations and cell contexts that allows specific pharmacological targeting alone or combinational treatment for tailored therapy. Novel strategies targeting EREG/EGFR, tumor-associated macrophages, and alternative activation oncoproteins are under development or undergoing clinical trials. In this review, we summarize the clinical outcomes of EREG expression and the interaction of this ligand in the TME. The EREG/EGFR pathway may be a potential target and may be combined with other driver mutation targets to combat specific cancers.

Quantum key distribution (QKD) provides information theoretically secure key exchange requiring authentication of the classic data processing channel via pre-sharing of symmetric private keys to kick-start the process. In previous studies, the lattice-based post-quantum digital signature algorithm Aigis-Sig, combined with public-key infrastructure (PKI), was used to achieve high-efficiency quantum security authentication of QKD, and we have demonstrated its advantages in simplifying the MAN network structure and new user entry. This experiment further integrates the PQC algorithm into the commercial QKD system, the Jinan field metropolitan QKD network comprised of 14 user nodes and 5 optical switching nodes, and verifies the feasibility, effectiveness and stability of the post-quantum cryptography (PQC) algorithm and advantages of replacing trusted relays with optical switching brought by PQC authentication large-scale metropolitan area QKD network. QKD with PQC authentication has potential in quantum-secure communications, specifically in metropolitan QKD networks.

Background Identifying or prioritizing genes for chronic obstructive pulmonary disease (COPD), one type of complex disease, is particularly important for its prevention and treatment. Methods In this paper, a novel method was proposed to Prioritize genes using Expression information in Protein–protein interaction networks with disease risks transferred between genes (abbreviated as PEP). A weighted COPD PPI network was constructed using expression information and then COPD candidate genes were prioritized based on their corresponding disease risk scores in descending order. Results Further analysis demonstrated that the PEP method was robust in prioritizing disease candidate genes, and superior to other existing prioritization methods exploiting either topological or functional information. Top-ranked COPD candidate genes and their significantly enriched functions were verified to be related to COPD. The top 200 candidate genes might be potential disease genes in the diagnosis and treatment of COPD. Conclusions The proposed method could provide new insights to the research of prioritizing candidate genes of COPD or other complex diseases with expression information from sequencing or microarray data.

Head and neck cancer (HNC) tumorigenesis involves a combination of multiple genetic alteration processes. Tumour necrosis factor-alpha-induced proteins (TNFAIPs) are involved in tumour development and progression, but few studies have been conducted on these factors in HNC. We aimed to analyse TNFAIPs and assess their potential as prognostic biomarkers and therapeutic targets using the Oncomine, UALCAN, Human Protein Atlas, LinkedOmics, cBioPortal, GeneMANIA, Enrichr, and Tumor IMmune Estimation Resource databases. We found that the transcript levels of TNFAIP1, TNFAIP3, EFNA1, TNFAIP6 and TNFAIP8 were increased, while those of TNFAIP8L3 and STEAP4 were reduced in HNC tissues versus normal tissues. The EFNA1, TNFAIP8 and TNFAIP8L3 expression levels were significantly correlated with the pathological stage. In HNC patients, high PTX3 and TNFAIP6 transcript levels were significantly associated with shorter overall survival (OS). Moreover, genetic alterations in TNFAIP1, TNFAIP6, and STEAP4 resulted in poorer disease-free survival, progression-free survival, and OS, respectively. TNFAIPs may mediate HNC tumorigenesis by regulating PI3K-Akt, Ras and other signalling pathways. TNFAIPs are also closely correlated with the infiltration of immune cells, including B cells, CD8+ T cells, CD4+ T cells, etc. The data above indicate that TNFAIPs may be potential biomarkers and therapeutic targets for HNC.

Apolipoprotein B plays an essential role in systemic lipid metabolism, and it is closely related to cardiovascular diseases. Exercise-training can regulate systemic lipid metabolism, improve heart function, and improve exercise capacity, but the molecular mechanisms involved are poorly understood. We used a Drosophila model to demonstrate that exercise-training regulates the expression of apoLpp (a homolog of apolipoprotein B) in cardiomyocytes, thereby resisting heart insufficiency and low exercise capacity caused by obesity. The apoLpp is an essential lipid carrier produced in the heart and fat body of Drosophila. In a Drosophila genetic screen, low expression of apoLpp reduced obesity and cardiac dysfunction induced by a high-fat diet (HFD). Cardiac-specific inhibition indicated that reducing apoLpp in the heart during HFD reduced the triglyceride content of the whole-body and reduced heart function damage caused by HFD. In exercise-trained flies, the result was similar to the knockdown effect of apoLpp. Therefore, the inhibition of apoLpp plays an important role in HFD-induced cardiac function impairment and low exercise capacity. Although the apoLpp knockdown of cardiomyocytes alleviated damage to heart function, it did not reduce the arrhythmia and low exercise capacity caused by HFD. Exercise-training can improve this condition more effectively, and the possible reason for this difference is that exercise-training regulates climbing ability in ways to promote metabolism. Exercise-training during HFD feeding can down-regulate the expression of apoLpp, reduce the whole-body TG levels, improve cardiac recovery, and improve exercise capacity. Exercise-training can downregulate the expression of apoLpp in cardiomyocytes to resist cardiac function damage and low exercise capacity caused by HFD. The results revealed the relationship between exercise-training and apoLpp and their essential roles in regulating heart function and climbing ability.

Background Long non‐coding RNA taurine‐upregulated gene 1 (lncRNA TUG1) is reported to be involved in the progression and development of several malignancies; however, its role in Philadelphia chromosome‐negative acute lymphoblastic leukemia (Ph−ALL) is unknown. The present study aimed to explore the correlation of lncRNA TUG1 with disease risk, disease condition, and prognosis of adult Ph−ALL. Methods Total 101 adult Ph− ALL patients and 40 bone marrow (BM) donors were included, followed by detection of BM monocyte cell lncRNA TUG1 expression by reverse transcription‐quantitative polymerase chain reaction. According to the quantiles of lncRNA TUG1 expression in Ph− ALL patients, these patients were divided into four tiers: tier 1 (ranked in 0%~25%), tier 2 (ranked in 25%~50%), tier 3 (ranked in 50%~75%), and tier 4 (ranked in 75%~100%). Results LncRNA TUG1 was upregulated in Ph− ALL patients compared with healthy donors. Further analysis indicated that in Ph− ALL patients, higher lncRNA TUG1 tier was correlated with the presence of central nervous system leukemia, increased white blood cell level, and bone marrow blasts. Furthermore, higher lncRNA TUG1 tier was negatively associated with complete remission (CR) within 4 weeks, total CR, and allogeneic hematopoietic stem cell transplant achievement. In addition, higher lncRNA TUG1 tier was associated with decreased disease‐free survival and overall survival, which was further verified to be an independent factor by Cox's regression analysis. Conclusion lncRNA TUG1 presents potential to be a novel biomarker for disease risk assessment and survival surveillance in Ph− ALL management., Long non‐coding RNA taurine‐upregulated gene 1 (lncRNA TUG1) is upregulated and correlates with poor treatment response and unfavrable survival profiles in Philadelphia chromosome‐negative Acute lymphoblastic leukemia (Ph‐ALL) patients, suggesting its potential as a candidate biomarker in ALL managment.

Targeted therapy with combined dabrafenib and trametinib has been proven to provide clinical benefits in patients with NSCLC with a BRAF V600E mutation. Nevertheless, the treatment strategy for patients with NSCLC with BRAF non-V600E mutations remains limited. Here, we present a patient with NSCLC with a BRAF K601E mutation, a class II BRAF mutation, who had a durable response to targeted therapy with combined dabrafenib and trametinib.