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Abstract Background HIIT has recently been widely used for health promotion in healthy people and patients with chronic diseases. Exercise can help SUD reduce drug cravings, enhance mental health and return to normal life. However, whether HIIT can bring better physical rehabilitation benefits to individuals with SUD than MICT is unclear. The study aimed to compare the effects of HIIT versus MICT on the physical fitness of individuals with SUD. Methods One hundred twenty individuals with amphetamine-type stimulant dependence voluntarily participated in this study. They were randomly assigned to the HIIT group and MICT group. Both groups received training three times a week. The intervention lasted from January 2019 to December 2019. Physical fitness was assessed at the baseline, 3 months, 6 months, 9 months and 12 months, including blood pressure (BP), vital capacity(VC), hand grip, push-up, sit-and-reach, one-leg standing with eyes closed and choice reaction time. The craving level was assessed using the Visual Analog Scale at baseline, 6 months and 12 months to see any change along with the improvement in physical fitness. Two-way repeated measures ANOVA was applied to analyse the differences in change by group (HIIT and MICT) and time (baseline, 3 months, 6 months, 9 months and 12 months). Results The within-group factor displayed significant changes in the HIIT and MICT groups in terms of systolic BP (F (4,336) = 12.799, P

The healing process of diabetic wounds is typically disordered and prolonged and requires both angiogenesis and epithelialization. Disruptions of the endogenous electric fields (EFs) may lead to disordered cell migration. Electrical stimulation (ES) that mimics endogenous EFs is a promising method in treating diabetic wounds; however, a microenvironment that facilitates cell migration and a convenient means that can be used to apply ES are also required. Chitosan-Vaseline® gauze (CVG) has been identified to facilitate wound healing; it also promotes moisture retention and immune regulation and has antibacterial activity. For this study, we created a wound dressing using CVG together with a flexible ES device and further evaluated its potential as a treatment for diabetic wounds. We found that high voltage monophasic pulsed current (HVMPC) promoted healing of diabetic wounds in vivo. In studies carried out in vitro, we found that HVMPC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) by activating PI3K/Akt and ERK1/2 signaling. Overall, we determined that the flexible ES-chitosan dressing may promoted healing of diabetic wounds by accelerating angiogenesis, enhancing epithelialization, and inhibiting scar formation. These findings provide support for the ongoing development of this multidisciplinary product for the care and treatment of diabetic wounds.

Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.

Transcription factors play key roles in cell-fate decisions by regulating 3D genome conformation and gene expression. The traditional view is that methylation of DNA hinders transcription factors binding to them, but recent research has shown that many transcription factors prefer to bind to methylated DNA. Therefore, identifying such transcription factors and understanding their functions is a stepping-stone for studying methylation-mediated biological processes. In this paper, a two-step discriminated method was proposed to recognize transcription factors and their preference for methylated DNA based only on sequences information. In the first step, the proposed model was used to discriminate transcription factors from non-transcription factors. The areas under the curve (AUCs) are 0.9183 and 0.9116, respectively, for the 5-fold cross-validation test and independent dataset test. Subsequently, for the classification of transcription factors that prefer methylated DNA and transcription factors that prefer non-methylated DNA, our model could produce the AUCs of 0.7744 and 0.7356, respectively, for the 5-fold cross-validation test and independent dataset test. Based on the proposed model, a user-friendly web server called TFPred was built, which can be freely accessed at http://lin-group.cn/server/TFPred/.

Abstract Background To investigate the clinicopathological characteristics of head and neck small cell carcinoma (H&NSmCC) and identify prognostic factors on the basis of the Surveillance, Epidemiology and End Results (SEER) database. Methods Total of 789 primary cases from 1973 to 2016 were included. Univariate and multivariate analyses were performed to identify independent prognostic indicators. An H&NSmCC-specific nomogram was constructed and compared with the AJCC staging system by calculating the time-dependent area under the curve (AUC) of the receiver operating characteristic (ROC) curves. Results The incidence of H&NSmCC peaked during the period of 50 to 70 years old, and the most frequent location was the salivary gland. The 5-year disease specific survival (DSS) was 27%. In the multivariate survival analysis, AJCC III + IV stage [HR = 2.5, P = 0.03, I + II stage as Ref], positive N stage [HR = 1.67, P = 0.05, negative N stage as Ref], positive M stage [HR = 4.12, P = 0.000, negative M stage as Ref] and without chemotherapy [HR = 0.56, P = 0.023, received chemotherapy as Ref] were independently associated with DSS. The H&NSmCC-specific nomogram was built based on the independent prognostic indicators. The nomogram demonstrated better predictive capacity than the AJCC staging system for 5-year DSS [(AUC: 0.75 vs 0.634; Harrell’s C-index (95% CI): 0.7(0.66–0.74) vs 0.59(0.55–0.62), P

Stellar white-light flares are believed to play an essential role in the physical and chemical properties of the atmosphere of the surrounding exoplanets. Here we report an optical monitoring campaign on the nearby flaring system EI Cnc carried out by the Ground-based Wide Angle Camera (GWAC) and its dedicated follow-up telescope. A superflare, coming from the brighter component EI CncA, was detected and observed, in which four components are required to properly model the complex decay light curve. The lower limit of flare energy in the R − band is estimated to be 3.3 × 10 ^32 erg. A total of 27 flares are additionally detected from the GWAC archive data with a total duration of 290 hr. The inferred cumulative flare frequency distribution follows a quite shallow power-law function with a slope of β = − 0.50 ± 0.03 over the energy range between 10 ^30 and 10 ^33 erg, which reinforces the trend that stars cooler than M4 show enhanced superflare activity. The flares identified in EI Cnc enable us to extend the τ – E relationship previously established in the white-light superflares of solar-type stars down to an energy as low as ∼10 ^30 erg (i.e., by 3 orders): τ ∝ E ^0.42±0.02 , which suggests a common flare mechanism for stars with a type from M to solar-like and implies an invariant of B ^1/3 υ _A in the white-light flares.

Background: Numerous studies have demonstrated that brain metastases patients may benefit from intracranial radiotherapy combined with immune checkpoint inhibitors (ICIs). However, it is unclear whether this treatment is effective for patients with small cell lung cancer brain metastases (SCLC‐BMs). Methods: We conducted a retrospective study by analyzing medical records of patients with SCLC‐BMs from January 1, 2017 to June 1, 2022. Data related to median overall survival (mOS), median progression‐free survival (mPFS), and intracranial progression‐free survival (iPFS) were analyzed. Results: A total of 109 patients were enrolled, of which 60 received WBRT and 49 received WBRT‐ICI. Compared to the WBRT alone cohort, the WBRT‐ICI cohort showed longer mOS (20.4 months vs. 29.3 months, p = 0.021), mPFS (7.9 months vs. 15.1 months, p < 0.001), and iPFS (8.3 months vs. 16.5 months, p < 0.001). Furthermore, WBRT‐ICI cohort had a better response rate for both BMs. (p = 0.035) and extracranial diseases (p < 0.001) compared to those receiving WBRT alone. Notably, the use of WBRT before ICI was associated with longer mOS compared to the use of WBRT after ICI (23.3 months for the ICI‐WBRT group vs. 34.8 months for the WBRT‐ICI group, p = 0.020). Conclusion: Our results indicated that WBRT combined with immunotherapy improved survival in SCLC‐BMs patients compared to WBRT monotherapy. Administering WBRT prior to ICI treatment is associated with improved survival outcomes compared to WBRT following ICI treatment, for patients with SCLC‐BMs. These findings highlight the significance of conducting further prospective researches on combination strategies of intracranial radiotherapy and ICI in SCLC‐BMs patients. [ABSTRACT FROM AUTHOR]

Abstract Background Alzheimer’s disease (AD) is an adult-onset mental disorder with aging as a major risk factor. Early and progressive degeneration of basal forebrain cholinergic neurons (BFCNs) contributes substantially to cognitive impairments of AD. An aging-relevant cell model of BFCNs will critically help understand AD and identify potential therapeutics. Recent studies demonstrate that induced neurons directly reprogrammed from adult human skin fibroblasts retain aging-associated features. However, human induced BFCNs (hiBFCNs) have yet to be achieved. Methods We examined a reprogramming procedure for the generation of aging-relevant hiBFCNs through virus-mediated expression of fate-determining transcription factors. Skin fibroblasts were obtained from healthy young persons, healthy adults and sporadic AD patients. Properties of the induced neurons were examined by immunocytochemistry, qRT-PCR, western blotting, and electrophysiology. Results We established a protocol for efficient generation of hiBFCNs from adult human skin fibroblasts. They show electrophysiological properties of mature neurons and express BFCN-specific markers, such as CHAT, p75NTR, ISL1, and VACHT. As a proof-of-concept, our preliminary results further reveal that hiBFCNs from sporadic AD patients exhibit time-dependent TAU hyperphosphorylation in the soma and dysfunctional nucleocytoplasmic transport activities. Conclusions Aging-relevant BFCNs can be directly reprogrammed from human skin fibroblasts of healthy adults and sporadic AD patients. They show promises as an aging-relevant cell model for understanding AD pathology and may be employed for therapeutics identification for AD.

Abstract Background Malignant tumours of the temporomandibular joint (MTTMJ) are extremely rare. Studies describing its unique epidemiology, clinicopathological features, treatment and prognosis comprehensively are limited. To address these issues, current investigation was performed. Methods A retrospective research was carried out by using population-based data from the Surveillance, Epidemiology, and End Results database (1973–2016). Results Data for a total of 734 patients, including 376 men and 358 women, was found. The median age was 47 years. The 5-year and 10-year disease specific survival (DSS) rates were 69.2 and 63.6%, respectively. Significant differences in DSS were found according to age, race, tumour type, AJCC/TNM stage, surgery, radiotherapy, chemotherapy and different treatment modalities (P 44 years and AJCC stage III and IV were associated with poor DSS. Conclusion MTTMJ was mostly found in white people with a median age of 47 years without any sex predominance. Patient’s age and AJCC stage was independent predictor of DSS.

The mechanisms and biological functions of migrating platelets in cancer remain largely unknown. Here, we analyzed platelet infiltration in hepatocellular carcinoma. We detected platelet extravasation in both mouse and human HCC tissues. CX3CL1 directly induced platelet migration, and hypoxia enhanced platelet migration by upregulating CX3CL1 expression. Knocking down CX3CL1 in HCC cells reduced platelet migration in vitro, as well as infiltration of HCC tissue in an orthotopic HCC mouse model. Components of the CX3CR1/Syk/PI3K pathway were essential for CX3CL1‐induced platelet migration. Migrating platelets induced HCC cell apoptosis in vitro, as indicated by a reduced mitochondrial membrane potential and an increased percentage of apoptotic cells. In the orthotopic tumor implantation model, decreased platelet infiltration was associated with accelerated tumor growth. Taken together, our findings indicate that HCC cell‐derived CX3CL1 contributes to tumor infiltration by platelets, which in turn promotes apoptosis of HCC cells.

Abstract Background To explore the relationship between the pathological changes of the colon, terminal ileum, lung, liver and kidney, and the changes of Bax, PCNA and PAF in a rat model of NEC. Methods One hundred and forty neonatal SD rats were randomly divided into NEC group and control group (70 in each group). NEC group was given hypoxia, cold stimulation and artificial feeding twice a day for 3 consecutive days. The control group was only fed normally. After modeling, From the 1st day to the 7th day, 10 rats were sampled in each group for pathological examination of colon, terminal ileum, lung, liver and kidney tissue. The levels of Bax, PCNA and PAF were investigated by immunohistochemistry. Results Compared with the normal group, in the NEC group, on the 1st day, the colon, terminal ileum, lung, liver and kidney showed inflammatory damage. On the 5th day, the inflammatory injury was reduced. The inflammation disappeared on the 7th day. There were differences in the time of apoptosis in the intestine. In the intestine, the proliferation of PCNA was weak at first and then strong. Bax in liver and kidney showed marked apoptosis and apoptosis time increased in the lung. The expression of PCNA increased in lung, liver and kidney, and the expression of PAF increased in lung and liver. Conclusions NEC can lead to secondary injury of different degrees in colon, terminal ileum, lung, liver and kidney, and the degree and time of injury and repair were different. In general, organ repair played a leading role on the 4th day after modeling.

Abstract Background Stem cells, including induced pluripotent stem cells (iPSCs), have tremendous potential in health care, though with several significant limitations. Each of the limitations, including immunogenicity, may block most of the therapeutic potentials. Beta2 microglobulin (B2M) and MHC II transactivator (CIITA) are critical for MHC I and II, respectively. MHCs are responsible for immunogenic recognition. Methods B2M and CIITA were knocked out from human iPSCs, either separately or simultaneously. The effects of single or dual knockout of B2M and CIITA on iPSC properties were evaluated in a xenogeneic model of human-to-monkey transplantation. Results B2M or CIITA knockout in human induced pluripotent stem cells (iPSCs) diminishes the expression of MHC I or II alleles, respectively, without changing iPSC pluripotency. Dual knockout was better than either single knockout in preserving the ability of human iPSCs to reduce infiltration of T and B lymphocytes, survive, and promote wound healing in monkey wound lesions. The knockouts did not affect the xenogeneic iPSC-induced infiltration of macrophages and natural killer cells. They, however, decreased the iPSC-promoted proliferation of allogeneic peripheral blood mononuclear cells and T lymphocytes in vitro, although not so for B lymphocytes isolated from healthy human donors. Although the dual knockout cells survived long enough for suiting therapeutic needs, the cells eventually died, possibly due to innate immune response against them, thereby eliminating long-term risks. Conclusions Having these iPSCs with diminished immunogenicity-recognizable to allogeneic recipient may provide unlimited reproducible, universal, standardized “ready-to-use” iPSCs and relevant derivatives for clinical applications.

Anomalies from the LHCb lepton flavour universality and Fermilab muon anomalous magnetic moment show tantalizing hints of possible new physics from the lepton sectors. Due to its large mass and shorter lifetime than muon, the tau lepton is believed to couple more to possible new physics beyond the Standard Model. Traditionally, tau leptons are probed through their decay products due to tau’s short lifetime. On the other hand, at a high energy scale, a large fraction of tau leptons could be boosted to a much longer lifetime and fly a visible distance from several centimetres up to kilometer length scale yet very informative to new physics beyond the standard model or high energy cosmic rays. In this article, we investigate rare, yet promising, tau-physics phenomena, where long-lived taus are exploited either as a microscope (for the measurement of tau’s anomalous magnetic moment to an unprecedented level of accuracy) or as a macroscope (for the detection of 1 TeV to 1 PeV cosmic neutrinos).

Background Members of the plant-specific YABBY gene family are thought to play an important role in the development of leaf, flower, and fruit. The YABBY genes have been characterized and regarded as vital contributors to fruit development in Arabidopsis thaliana and tomato, in contrast to that in the important tropical economic fruit star fruit (Averrhoa carambola), even though its genome is available. Methods In the present study, a total of eight YABBY family genes (named from AcYABBY1 to AcYABBY8) were identified from the genome of star fruit, and their phylogenetic relationships, functional domains and motif compositions, physicochemical properties, chromosome locations, gene structures, protomer elements, collinear analysis, selective pressure, and expression profiles were further analyzed. Results Eight AcYABBY genes (AcYABBYs) were clustered into five clades and were distributed on five chromosomes, and all of them had undergone negative selection. Tandem and fragment duplications rather than WGD contributed to YABBY gene number in the star fruit. Expression profiles of AcYABBYs from different organs and developmental stages of fleshy fruit indicated that AcYABBY4 may play a specific role in regulating fruit size. These results emphasize the need for further studies on the functions of AcYABBYs in fruit development.

Summary: Background: Diabetes is a major health concern and is influenced by lifestyle, which can be affected by the neighbourhood environment. Specifically, a fast-food environment can influence eating behaviours and thus diabetes prevalence. Therefore, our aim was to assess the relationship between fast-food environment and diabetes prevalence for urban and rural environments in the Netherlands, using multiple indicators and buffer sizes. Methods: In this cross-sectional study, data on a nationwide sample of adults older than 19 years in the Netherlands were taken from the 2012 Dutch national health survey (from Public Health Monitor), in which participants were surveyed on topics related to health and lifestyle behaviour. Fast-food outlet exposures were determined within street-network buffers of 100 m, 400 m, 1000 m, and 1500 m around residential addresses. For each of these buffers, three indicators were calculated: presence (yes or no) of fast-food outlets, fast-food outlet density, and ratio. Logistic regression analyses were carried out to assess associations of these indicators with diabetes, adjusting for potential confounders and stratifying into urban and rural areas. Findings: 387 195 adults were surveyed, 284 793 of whom were included in the study. 22 951 (8%) reported having diabetes. Fast-food outlet exposures were positively associated with diabetes prevalence. We did not observe large differences between urban and rural areas. The effect estimates were small for all indicators. For example, in the 400 m buffer in the urban environment, the odds ratio (OR) for having diabetes among people with a fast-food outlet present compared with those without, was 1·006 (95% CI 1·003–1·009) using the presence indicator. The presence indicator showed higher effect estimates and the most consistent results across buffer sizes (ranging from OR 1·005 [95% CI 1·000–1·010] with the 1000 m buffer to 1·016 [1·005–1·028] with the 1500 m buffer in urban areas and from 1·002 [0·998–1·005] with the 1500 m buffer to 1·009 [1·006–1·018] with the 100 m buffer in rural areas) compared with the density and ratio indicators. Interpretation: The results confirm the evidence that the fast-food outlet environment is a diabetes risk factor. All data included were at the individual level and the variability was ensured by the spatial distribution and number of participants. In this study, we only accounted for residential exposure because we were unable to account for exposure outside the residential environment. The findings of this study encourage local governments to consider the potential adverse effects of fast-food exposures and aim at minimising unhealthy food access. Funding: Global Geo Health Data Centre, Utrecht University, Netherlands.

Abstract Background TdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment, and outcomes of this potentially fatal arrhythmia. Objective Our goals were as follows: (1) to validate cases presenting with Torsade de Pointes (TdP), (2) to identify modifiable risk factors, and (3) to describe the management strategies used for TdP and its prognosis in a real‐world healthcare setting. Methods Case–control study (with 2:1 matching on age, sex, and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow‐up of the cohort for case ascertainment was between January 01, 2005 and December 31, 2018. Results A total of 56 cases of TdP were confirmed (incidence rate = 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female, and 16 percent were non‐white. The independent predictors of TdP were potassium concentration 480 ms (OR = 4.4) and prior history of coronary artery disease (OR = 2.6). Exposure to furosemide and amiodarone was significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in‐hospital and 1‐year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively. Conclusions These findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.

Background. BRAF exon 15 p.V600E (BRAF V600E) mutation has been established as an important molecular marker for papillary thyroid carcinoma diagnosis by ultrasound-guided fine-needle aspiration biopsy (FNAB). Sanger sequencing is the gold standard for detecting BRAF V600E mutations but fails to identify low-frequency mutations. However, droplet digital PCR (ddPCR) is a popular new method for detecting low-frequency mutations. Here, we compare the efficiency of droplet digital PCR (ddPCR) and Sanger sequencing for detection of the BRAF V600E mutation in thyroid fine-needle aspiration (FNA) samples. Methods. Thyroid fine-needle aspiration samples from 278 patients with 310 thyroid nodules were collected. Sanger sequencing and ddPCR were conducted to detect the BRAF V600E mutation. Results. The BRAF V600E mutation was found in 94 nodules (30.32%) by ddPCR and 40 nodules (12.90%) by Sanger sequencing in 310 FNA samples. A total of 119 nodules were confirmed PTC by postsurgical pathology. Among which the BRAF mutation was found in 80 (67.23%) nodules by ddPCR and 31 (26.05%) by Sanger sequencing. All nodules carrying the mutation detected by Sanger sequencing (SS+) were verified by ddPCR (ddPCR+). Also, all nodules with no mutation detected by ddPCR were interpreted as wild-type by Sanger sequencing (SS−). In addition. Almost all SS+/ddPCR + nodules (95.00%; 38/40) and SS−/ddPCR + nodules (100.00%; 54/54) displayed a BRAF mutation rate of >5% and

Abstract A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY.

From the first illustrations of neuronal morphology by Ramón y Cajal to the recent three-dimensional reconstruction of synaptic connections, the development of modern neuroscience has greatly benefited from breakthroughs in imaging technology. This also applies specifically to the study of neurodegenerative diseases. Much of the research into these diseases relies on the direct visualisation of intracellular structures and their dynamics in degenerating neural cells, which cannot be fully resolved by diffraction-limited microscopes. Progress in the field has therefore been closely linked to the development of super-resolution imaging methods. Their application has greatly advanced our understanding of disease mechanisms, ranging from the structural progression of protein aggregates to defects in organelle morphology. Recent super-resolution studies have specifically implicated the disruption of inter-organelle interactions in multiple neurodegenerative diseases. In this article, we describe some of the key super-resolution techniques that have contributed to this field. We then discuss work to visualise changes in the structure and dynamics of organelles and associated dysfunctions. Finally, we consider what future developments in imaging technology may further our knowledge of these processes.

Rheumatoid arthritis (RA) is a classic autoimmune disease characterized by uncontrolled synovial proliferation, pannus formation, cartilage injury, and bone destruction. The specific pathogenesis of RA, a chronic inflammatory disease, remains unclear. However, both key glycolysis rate-limiting enzymes, hexokinase-II (HK-II), phosphofructokinase-1 (PFK-1), and pyruvate kinase M2 (PKM2), as well as indirect rate-limiting enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), are thought to participate in the pathogenesis of RA. In here, we review the latest literature on the pathogenesis of RA, introduce the pathophysiological characteristics of HK-II, PFK-1/PFKFB3, and PKM2 and their expression characteristics in this autoimmune disease, and systematically assess the association between the glycolytic rate-limiting enzymes and RA from a molecular level. Moreover, we highlight HK-II, PFK-1/PFKFB3, and PKM2 as potential targets for the clinical treatment of RA. There is great potential to develop new anti-rheumatic therapies through safe inhibition or overexpression of glycolysis rate-limiting enzymes.

In this study, a novel metal-organic framework (M-ZIF-8@ZIF-67) was successfully prepared using the single layer Fe3O4-ZIF-8 as magnetic core and wrapped a layer of ZIF-67 outer. This M-ZIF-8@ZIF-67 was employed as an adsorbent for the adsorption and removal of fipronil and its metabolites from environmental water and cucumber samples. The characterization results suggested that M-ZIF-8@ZIF-67 has the double layer structure a polyhedral structure with uniform pores, while ZIF-67 was successfully coated on the surface of Fe3O4-ZIF-8. The unique structure endowed M-ZIF-8@ZIF-67 a high surface area (219 m2/g) and high adsorption capacity for fipronil, fipronil desulfinyl, fipronil sulfide and fipronil sulfone. To our knowledge, this is the first report detailing the adsorption properties of M-ZIF-8@ZIF-67 with double layer structure relating to the adsorption and removal of pesticides. Furthermore, the adsorption model analysis demonstrated that the static adsorption data fitted the Freundlich bimolecular layer adsorption model better than the Langmuir monolayer adsorption model. This study indicates that M-ZIF-8@ZIF-67 has significant potential in the adsorption and removal of fipronil and its metabolites in water and vegetable samples.

Abstract Background To explore the clinicopathologic characteristics, treatment and prognostic factors of head and neck acinar cell carcinoma (HNACC) comprehensively. Methods A population-based study was conducted using data from the Surveillance, Epidemiology, and End Results database (1975–2016). Overall survival (OS) and HNACC-specific survival of patients with different clinicopathologic variables were compared using the Kaplan-Meier method and Cox multivariate regression. Results A total of 2624 primary HNACC cases (1052 males, 1572 females) were identified. There was a significant difference in gender distribution. Among the total cohort, 2416 cases originated from salivary glands, including 2325 parotid gland ACC cases. Regardless of confounding factors, the 10-year and 20-year disease-specific survival (DSS) was 93.6 and 90%, respectively. Surgery was favourably associated with better DSS and OS [HR = 0.13, P = 0.0092 and HR = 0.23, P = 0.0203]. Gender was the only demographic independent prognostic factor for both DSS and OS [Male vs female, HR = 3.3, P = 0.0028 for DSS; HR = 2.44, P = 0.0376 for OS]. Higher pathological grade was adversely associated with DSS and OS [Grade II, HR = 4.03, P = 0.0444; Grade III + IV, HR = 35.64, P = 0.0000 for DSS; Grade III + IV, HR = 4.49, P = 0.0000 for OS, Grade I as reference]. In addition, TNM/AJCC stage was commonly associated with prognosis. Conclusion Surgery was the only favourable prognostic indicator for both DSS and OS. Gender, age, pathological differentiation and TNM/AJCC stage were independent prognostic factors for survival.

Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) are a major public-health threat. The most important mechanism of carbapenem resistance in CRE is carbapenemase production. Early identification of carbapenemase-producing Enterobacteriaceae (CPE) leads to improved clinical outcomes. This systematic review aimed to assess the accuracy and applicability of the modified Hodge test (MHT), the carbapenemase Nordmann–Poirel (Carba NP) test, the modified carbapenem inactivation method (mCIM) and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) for CPE detection. Methods: The meta-analysis included pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic (SROC) curve and area under the curve (AUC). Results: A total of 67 studies were included in the analysis. Pooled effect sizes (95% confidence interval) of the MHT, Carba NP, mCIM and MALDI-TOF/MS, respectively, were as follows: sensitivity, 92% (87–95%), 97% (94–98%), 99% (99–100%) and 99% (96–100%); specificity, 93% (86–97%), 100% (99–100%), 99% (96–100%) and 99% (96–100%); diagnostic odds ratio, 98.156 (48.175–199.995), 1277.710 (751.391–2172.692), 3597.352 (1287.575–10000) and 1781.360 (651.827–4868.228); and AUC, 0.97, 1, 1 and 1. Conclusion: Carba NP, mCIM and MALDI-TOF/MS all demonstrated high accuracy in CPE detection, whereas the MHT is not recommended owing to some clear drawbacks. We recommend the selection of carbapenemase detection tests in the order of mCIM, Carba NP and MALDI-TOF/MS according to their simplicity, cost, and equipment and skills involved.

Abstract Background The association between the residential fast food environment and diet has gained growing attention. However, why the food environment affects food consumption is under-examined. This study aimed to investigate neighbourhood social norms with respect to fast food consumption as a potential mediating pathway between residential fast food outlet exposure and residents’ fast food consumption. Methods A correlational study was conducted in which a nationwide sample of 1038 respondents living across The Netherlands completed a survey. Respondents reported their fast food consumption (amount/week) as well as perceived descriptive and injunctive norms regarding fast food consumption in their neighbourhood. Fast food outlet exposure was measured by the average count of fast food outlets within a 400 m walking distance buffer around the zip-codes of the respondents, using a retail outlet database. Regression models were used to assess associations between residential fast food outlet exposure, fast food consumption, and social norm perceptions, and a bootstrapping procedure was used to test the indirect -mediation- effect. Separate analyses were performed for descriptive norms and injunctive norms. Results There was no overall or direct association between residential fast food outlet exposure and residents’ fast food consumption. However, fast food outlet exposure was positively associated with neighbourhood social norms (descriptive and injunctive) regarding fast food consumption, which in turn were positively associated with the odds of consuming fast food. Moreover, results of the bootstrapped analysis provided evidence of indirect effects of fast food outlet exposure on fast food consumption, via descriptive norms and injunctive norms. Conclusions In neighbourhoods with more fast food outlets, residents were more likely to perceive fast food consumption in the neighbourhood as more common and appropriate. In turn, stronger neighbourhood social norms were associated with higher fast food consumption. Acknowledging the correlational design, this study is the first that implies that neighbourhood social norms may be a mediating pathway in the relation between the residential fast food environment and fast food consumption. Future research may examine the role of neighbourhood social norms in other contexts and explore how the changing food environment may shift our consumption norms.

Abstract Background This study was to investigate of the mechanism by which histone deacetylase (HDAC) 8 inhibitor ameliorated airway hyperresponsiveness (AHR) and allergic airway inflammation. Methods Mice were sensitized and then treated with budesonide (BUD) or PCI-34051 (PCI) prior to exposing to normal saline (NS) or ovalbumin (OVA). The raw264.7 cells were treated with interleukin (IL)-4 and PCI or shRNA alone. Repetitive measurements of enhanced pause (Penh) were executed by increasing concentrations of acetyl-β-methacholine chloride (0 - 50 mg/ml). Cells in bronchoalveolar lavage fluid (BALF) and pathological changes of lungs were examined, respectively. The expression levels of HDAC8, Galecitn (Gal)-3, CD68, CD86, CD163, Arg1 and NOS2 in lungs were measured. Co-regulation of HDAC8 and Gal-3 proteins was observed by immunofluorescence staining and co-immunoprecipitation assay (Co-IP). Results Significant increases in Penh and IL-4 level were detected with a large inflammatory infiltrate, comprised predominantly of macrophages and eosinophils, into the BALF in OVA-exposed lungs. HDAC8, Gal-3, CD68, CD86, CD163, Arg1 and NOS2 proteins were over-expressed with the significant changes in the Arg1 and NOS2 mRNA levels in the lungs and the IL-4-treated cells. PCI intervention obviously reduced the counts of CD163+ cells. Furthermore, Gal-3 knockdown suppressed Arg1 expression in the cells. Immunofluorescence staining displayed simultaneous changes in HDAC8 and Gal-3 expression in the investigated samples. Treatment with PCI resulted in synchronous reduction of HDAC8 and Gal-3 expression in the Co-IP complexes. Conclusions The HDAC8 inhibitor ameliorates AHR and airway inflammation in animal model of allergic asthma through reducing HDAC8-Gal-3 interaction and M2 macrophage polarization.

The study of covalent organic frameworks (COFs) in electrocatalytic CO2 reduction reaction (CO2RR) has drawn much attention. Here the authors show a series of tetrathiafulvalene based COFs designed and exfoliated into nanosheets which exhibit high electrocatalytic CO2RR performance.

Abstract Objective Endoplasmic reticulum (ER) stress and mitochondrial function affected intramuscular fat accumulation. However, there is no clear evident on the effect of the regulation of ER stress and mitochondrial function by Angiotensin-converting enzyme 2 (ACE2) on the prevention of intramuscular fat metabolism. We investigated the effects of ACE2 on ER stress and mitochondrial function in skeletal muscle lipid metabolism. Methods The triglyceride (TG) content in skeletal muscle of ACE2 knockout mice and Ad-ACE2-treated db/db mice were detected by assay kits. Meanwhile, the expression of lipogenic genes (ACCα, SREBP-1c, LXRα, CPT-1α, PGC-1α and PPARα), ER stress and mitochondrial function related genes (GRP78, eIF2α, ATF4, BCL-2, and SDH6) were analyzed by RT-PCR. Lipid metabolism, ER stress and mitochondrial function related genes were analyzed by RT-PCR in ACE2-overexpression C2C12 cell. Moreover, the IKKβ/NFκB/IRS-1 pathway was determined using lysate sample from skeletal muscle of ACE2 knockout mice. Results ACE2 deficiency in vivo is associated with increased lipid accumulation in skeletal muscle. The ACE2 knockout mice displayed an elevated level of ER stress and mitochondrial dysfunctions in skeletal muscle. In contrast, activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced TG content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice. Additionally, ACE2 improved skeletal muscle lipid metabolism and ER stress genes in the C2C12 cells. Mechanistically, endogenous ACE2 improved lipid metabolism through the IKKβ/NFκB/IRS-1 pathway in skeletal muscle. Conclusions ACE2 was first reported to play a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function. This study may provide a strategy for treating insulin resistance in skeletal muscle.

Abstract Background Modern applications such as bioinformatics collecting data in various ways can easily result in heterogeneous data. Traditional variable selection methods assume samples are independent and identically distributed, which however is not suitable for these applications. Some existing statistical models capable of taking care of unwanted variation were developed for gene identification involving heterogeneous data, but they lack model predictability and suffer from variable redundancy. Results By accounting for the unwanted heterogeneity effectively, our method have shown its superiority over several state-of-the art methods, which is validated by the experimental results in both unsupervised and supervised gene identification problems. Moreover, we also applied our method to a pan-cancer study where our method can identify the most discriminative genes best distinguishing different cancer types. Conclusions This article provides an alternative gene identification method that can accounting for unwanted data heterogeneity. It is a promising method to provide new insights into the complex cancer biology and clues for understanding tumorigenesis and tumor progression.

Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within‐person QT change over time in relation to risk of incident CVD and all‐cause mortality in a real‐world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non‐White) with 3 or more ECGs (baseline in 2005–2009; mean±SD follow‐up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all‐cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all‐cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all‐cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long‐term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.

Unisexual taxa are commonly considered short-lived as the absence of meiotic recombination is supposed to accumulate deleterious mutations and hinder the creation of genetic diversity. However, the gynogenetic gibel carp (Carassius gibelio) with high genetic diversity and wide ecological distribution has outlived its predicted extinction time of a strict unisexual reproduction population. Unlike other unisexual vertebrates, males associated with supernumerary microchromosomes have been observed in gibel carp, which provides a unique system to explore the rationales underlying male occurrence in unisexual lineage and evolution of unisexual reproduction. Here, we identified a massively expanded satellite DNA cluster on microchromosomes of hexaploid gibel carp via comparing with the ancestral tetraploid crucian carp (Carassius auratus). Based on the satellite cluster, we developed a method for single chromosomal fluorescence microdissection and isolated three male-specific microchromosomes in a male metaphase cell. Genomic anatomy revealed that these male-specific microchromosomes contained homologous sequences of autosomes and abundant repetitive elements. Significantly, several potential male-specific genes with transcriptional activity were identified, among which four and five genes displayed male-specific and male-biased expression in gonads, respectively, during the developmental period of sex determination. Therefore, the male-specific microchromosomes resembling common features of sex chromosomes may be the main driving force for male occurrence in gynogenetic gibel carp, which sheds new light on the evolution of unisexual reproduction.

The incidence of nonalcoholic fatty liver disease (NAFLD)-associated liver cancer is rising particularly in western societies. Dietary fructose has been increasingly reported as a significant contributor for the onset of NAFLD. However, the association between a high-fructose diet and liver cancer incidence is not fully understood. In this study, we investigated the effect of dietary fructose on liver tumorigenesis. In a mouse model of diethylnitrosamine (DEN)-induced liver tumor initiation, high-fructose diet was found to significantly increased hepatic lipid deposition and expression of inflammatory cytokines in mouse livers. Besides, DEN administration induced the malignant transformation of hepatic progenitor cells (HPCs) into malignant tumor initiating cells, while DEN + Fructose mice had significantly enriched HPCs with enhanced proliferation, invasion, chemoresistance, and tumorigenic capabilities. This study for the first time demonstrates that fructose promotes liver carcinogenesis via increasing tumorigenic HPCs and inflammatory microenvironment, which warrants precautionary control of the excessive intake of dietary fructose.

Realizing the green recycling of sludge is an important link to effectively solve the problem of sludge disposal. In this paper, sewage sludge (SS) and rice husk (RH) were utilized as raw materials in preparing novel ceramsite (SRC) for the treatment of lead-containing wastewater, and its adsorption mechanism was explored. The results showed that the optimal preparation conditions were 40% RH + 60% SS mixture, a sintering temperature of 1190 °C, and a sintering time of 20 min. The basic properties of SRC met Chinese artificial ceramsite filter material standards for water treatment (CJ/T 299-2008). Under optimum adsorption conditions (pH = 6, 1 g/L SRC dosage, 20 mg/L Pb(NO)3 concentration, 18 h), the removal rate of Pb2+ reached 94.7%, and the equilibrium adsorption capacity was 18.94 mg/g. The adsorption process was more consistent with the pseudo-second-order kinetic model and the Langmuir isotherm model, indicating that the adsorption process was dominated by chemisorption. Thermodynamic parameters (ΔH0 > 0, ΔG0 < 0, ΔS0 > 0) indicated that the adsorption reaction was spontaneous and endothermic. The possible adsorption mechanisms are as follows: (1) SRC is rich in layered mesoporous structure, which provides sufficient reaction sites for Pb adsorption; (2) the sintered lawsonite and muscovite can strongly attract Pb and then form a new phase (Pb10[Si2O7]3(OH)2); (3) Pb2+ can bond with the Si–O- bond in aluminosilicates, and the introduction of Pb elevates the degree of polymerization of aluminosilicates in turn, indicating that the adsorption process is stable.

Fiber biochar–metal organic framework (MOF) composites were successfully prepared by three different biochar preparation methods, namely, the ionic liquid method, the pyrolysis method, and the direct composite method. The effects of the different preparation methods of fiber biochar on the physical and chemical properties of the biochar–MOF composites showed that the composite prepared by the ionic liquid method with the Zeolite-type imidazolate skeleton -67 (ZIF-67) composite after high temperature treatment exhibited a better microstructure. Electrochemical tests showed that it had good specific capacity, a fast charge diffusion rate, and a relatively good electrochemical performance. The maximum specific capacity of the composite was 63.54 F/g when the current density was 0.01 A/g in 1 mol/L KCl solution. This work explored the preparation methods of fiber biochar–MOF composites and their application in the electrochemical field and detailed the relationship between the preparation methods of the composites and the electrochemical properties of the electrode materials.