Changes in microbial composition explain the contrasting responses of glucose and lignin decomposition to soil acidification in an alpine grassland.

Soil acidification often suppresses microbial growth and activities, resulting in a negative impact on soil organic carbon (C) decomposition. While the detrimental effects of acidification on soil and plant properties have been extensively studied, less attention has been paid on the shifts in soil microbial communities and their influences of the decomposition of organic C with different chemical complexities. Taking advantage of an acid addition experiment in a Tibetan alpine meadow, here we examined the response of soil microbial communities to soil acidification and microbial effect on the decomposition of organic C with different chemical complexities (i.e., glucose and lignin, representing labile and recalcitrant C respectively). We found that soil acidification had no impact on microbial respiration and microbial abundance even though it decreased bacterial diversity significantly. Soil acidification increased the relative abundance of some microbial taxa, like Alphaproteobacteria and Acidobacteriia in bacteria increased by 36 %, 284 %, and Eurotiomycetes, Sordariomycetes and Leotiomycetes in fungi increased by 145 %, 279 % and 12.7-fold, but decreased the relative abundance of Acidimicrobiia by 33 % in highest acid addition treatment. Changes in microbial communities (bacterial and fungal community composition, the diversity of bacterial community and the ratio of fungi to bacteria) are significantly related to the decomposition of glucose and lignin. More specifically, soil acidification decreased the decomposition of glucose but increased the decomposition of lignin, indicating a trade-off between the decomposition of labile and recalcitrant soil organic C under soil acidification. Overall, shifts in microbial communities under soil acidification might be accompanied by an increased ability to break down more recalcitrant C. This trade-off between the decomposition of labile and recalcitrant C may change soil C quality under future acid deposition scenarios.

Wideband low-RCS and gain-enhanced antenna using frequency selective absorber based on patterned graphene.

In this paper, a double-layer patterned graphene-based frequency-selective absorber (DGFSA) is proposed as a means of reducing an antenna's radar cross-section (RCS) while simultaneously increasing its gain. The antenna consists of a patch antenna with Multi-Graphene Frequency Selective Absorber (MGFSA) mounted on top. The DGFSA consists of double-layer patterned graphene and a band-pass frequency selective surface (FSS). Two patterned graphene lossy layers with different square resistances are used, which broaden the electromagnetic (EM) wave absorption bandwidth of the DGFSA, thus greatly reducing the out-band monostatic RCSs of the patch antenna. Meanwhile, due to the quasi-Fabry-Perot (F-P) effect, the gain of the proposed antenna is enhanced by 2.4 dB. Additionally, the low-RCS antenna reduces the monostatic RCS from 1.32 to 17 GHz under y-polarization and from 1.4 to 16.8 GHz under x-polarization, respectively. Furthermore, a decrease in the bistatic RCS is accomplished. Results from simulations and measurements match up nicely, which means the antenna we proposed has a good application on the stealth platform.

A real-world study of recombinant human endostatin combined with PD-1/PD-L1 blockade and chemotherapy for patients with advanced non-small cell lung cancer negative for actionable molecular biomarkers.

The ongoing ENPOWER study exploring the efficacy and safety of the recombinant human endostatin (endostar) combined with programmed cell death 1 antibody sintilimab and chemotherapy showed encouraging efficacy and safety in advanced non-squamous non-small cell lung cancer. To evaluate the real-world efficacy and safety of endostar combined with immune checkpoint inhibitor and chemotherapy (EIC) for advanced non-squamous non-small cell lung cancer patients negative for actionable molecular biomarkers (NSCLCnm), patients with advanced NSCLCnm hospitalized to Zhejiang Provincial People's Hospital from January 2020 to December 2022 were screened for eligibility. The included patients were analyzed for the objective response rate (ORR) and disease control rate (DCR). The pre- and posttreatment expression levels of serum tumor associated biomarkers, chemokines and subpopulations of immune cells in peripheral blood were compared. For the 31 patients with advanced NSCLCnm treated with EIC, the median follow-up and treatment cycles were 18.0 months and 4, respectively. The ORR and DCR were 38.7% and 90.3%, respectively. For those who received EIC as first-line treatment, the ORR and DCR were 63.2% and 94.7%, respectively. EIC significantly decreased expression levels of carcinoma antigen 125, carcinoma embryonic antigen and cytokeratin 19 (P<0.05) in patients who were partial remission or stable disease. Among the 31 patients, 27 (87.1%) experienced at least 1 treatment-related adverse events, and 13 (41.9%) had the treatment-related adverse events of grade 3 or higher. No antiangiogenesis-related adverse events were observed. The current study showed that EIC was potentially effective for patients with NSCLCnm, especially when used as first-line therapy, and well tolerated.

Synergistic anti-tumour activity of sorafenib in combination with pegylated resveratrol is mediated by Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways.

Introduction: To investigate the inhibitory effect of sorafenib combined with PEGylated resveratrol on renal cell carcinoma (RCC) and its potential mechanism. Methods: MTT assay was used to detect the inhibitory effects of PEGylated resveratrol and sorafenib alone or combination on proliferation of RCC cells. Scratch and transwell assays were performed to examine the effects on the in vitro migration and invasion of RCC cells, respectively. The anti-tumor activity as well as splenic lymphocyte proliferation of the combination therapy was evaluated in the RCC xenograft mouse model. Western blotting method was used to detect changes in proteins involved in the antitumor efficacy related signaling pathways. Results: Inhibitory effects of PEGylated resveratrol combined with sorafenib incubation on the proliferation of Renca cells was synergistically enhanced compared with the mono-incubation group (both P < 0.01, CI < 1). Scratch and transwell assays revealed that combined incubation could significantly inhibit the migration and invasion of 786-O cells in vitro. Combined PEGylated resveratrol with sorafenib could significantly inhibit the growth of Renca renal carcinoma in mice with the tumor growth inhibition (TGI) of 85.5% and one achieved complete remission on D14, while the two monotherapies were both below 43% on D14, suggesting that current combination may have synergistic anti-renal carcinoma activity. Compared with the control group, PEGylated resveratrol combined with sorafenib in vivo promoted the proliferation of unactivated splenic lymphocytes and the proliferation of lymphocytes stimulated with concanavalin A and lipopolysaccharide. Western blotting results showed that combination therapy may suppress the growth of renal cell carcinoma by inhibiting AKT/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways. Conclusion: PEGylated resveratrol combined with sorafenib can achieve synergistic anti-RCC activity, and the mechanism may be related to the inhibition of Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways.

Case Report: Life-threatening pancytopenia with tislelizumab followed by cerebral infarction in a patient with lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) are an integral antitumor therapy for many malignancies. Most patients show very good tolerability to ICIs; however, serious immune-related adverse events (irAEs) with ICIs have been well documented and prevent some patients from continuing ICIs or even become the direct cause of patient death. Cytopenia is a rare irAE but can be life-threatening. Here, we present the case of a 66-year-old male patient with metastatic lung adenocarcinoma who received two doses of chemotherapy + PD-1 antibody tislelizumab and developed pancytopenia after each dose. Although the first episode of pancytopenia resolved with a treatment regimen of granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), and red blood cell and platelet transfusion, the second episode showed extreme resistance to these treatments and improved only after the administration of steroids. His second pancytopenia episode resolved after a long course of treatment with methylprednisolone, G-CSF, TPO, hetrombopag and multiple red blood cell and platelet transfusions. However, he suffered a cerebral infarction when his platelet count was in the normal range and gradually recovered 1 week later. This case highlights the importance of the early recognition and management of hematological irAEs.

Effect of zinc supplementation on blood sugar control in the overweight and obese population: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although overweight and obese people have a higher risk of type 2 diabetes incidence than normal-weight individuals, the efficacy of zinc supplementation in blood sugar control in overweight and obese people remained unknown. This meta-analysis attempted to address this issue. METHODS: Databases including PubMed, Embase, and the Cochrane Library were searched from inception until May 2022 to identify randomized controlled trials (RCTs) investigating the effects of zinc supplementation among participants who were overweight or obese without language restriction. It is a random-effect meta-analysis that analyzed the impact of zinc supplementation on fasting glucose (FG) (i.e., primary outcome) and other variables including fasting insulin (FI), homeostasis model assessment-insulin resistance index (HOMA-IR), glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and 2-hour postprandial glucose (2 h- PG). RESULTS: Analysis of 12 eligible RCTs involving 651 overweight/obese participants demonstrated that zinc supplementation significantly improves FG (weighted mean difference [WMD]: -8.57 mg/dL; 95% confidence interval [CI]: -14.04 to -3.09 mg/dL, p = 0.002), HOMA-IR (WMD: -0.54; 95% CI: -0.78 to -0.30, p < 0.001), HbA1c (WMD: -0.25%; 95% CI: -0.43% to -0.07%, p = 0.006), and 2 h-PG (WMD: -18.42 mg/dL; 95% CI: -25.04 to -11.79 mg/dL, p < 0.001) compared to those in the control group. After conducting subgroup analyses, we found that the primary outcome, FG, showed more significant results in the subgroups with Asia, Zinc supplementation alone, higher dose (≥30 mg) and patients with diabetes. CONCLUSION: Our meta-analysis indicated that zinc supplementation benefits blood sugar control in overweight and obese populations, with an especially significant reduction in FG.

Sustainability of rural tourism in poverty reduction: Evidence from panel data of 15 underdeveloped counties in Anhui Province, China.

Based on the characteristics of underdeveloped areas, this paper selects the panel data of 15 underdeveloped counties in Anhui Province from 2013 to 2019 and uses the panel threshold model to empirically analyze the sustainability of rural tourism development. The results show that: (1) Rural tourism development has a non-linear positive impact on poverty alleviation in underdeveloped areas and has a double threshold effect. (2) When the poverty rate is used to express the poverty level, it can be found that the development of rural tourism at a high level can significantly promote poverty alleviation. (3) When the number of poor people is used to express the poverty level, it can be found that the poverty reduction effect shows a marginal decreasing trend with the phased improvement of the development level of rural tourism. (4) The degree of government intervention, industrial structure, economic development, and fixed asset investment play a more significant role in poverty alleviation. Therefore, we believe that we need to actively promote rural tourism in underdeveloped areas, establish a mechanism for the distribution and sharing of rural tourism benefits, and form a long-term mechanism for rural tourism poverty reduction.

Catalpol induces apoptosis in breast cancer in vitro and in vivo: Involvement of mitochondria apoptosis pathway and post-translational modifications.

Breast cancer is a fatal cancer with the highest mortality in female. New strategies for anti-breast cancer are still urgently needed. Catalpol, an iridoid glycoside extracted from the traditional Chinese medicinal plant Rehmannia glutinosa, has shown anticancer efficacy in various cancer cells. However, its effect on breast cancer remains unclear. In this study, we aim to investigate the anti-breast cancer activity of catalpol and elucidate its underlying mechanism. Cell counting kit-8 (CCK-8) and morphology change showed that catalpol could inhibit the proliferation and viability of MCF-7 cells. Catalpol administration reduced the tumor volume in xenograft model. Catalpol induced apoptosis in MCF-7 cells confirmed by Hoechst 33342 staining and Annexin V-FITC/PI double staining. In vivo, catalpol also induced apoptosis as seen from the increased level of terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) in tumor. According to JC-1 and Dichlorodi-hydrofluorescein Diacetate (DCFH-DA) staining, loss of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation was found in MCF-7 cells treated with catalpol. Furthermore, catalpol also increased the level of cytoplasmic cytochrome c and activity of caspase-3 in MCF-7 cells. Likewise, histopathological and immunohistochemical (IHC) assay also found that catalpol enhanced the levels of cytochrome c and caspase-3 in breast cancer tissues. Ultimately, acetylation, 2-hydroxyisobutyrylation and lactylation were dramatically increased, whereas succinylation, malonylation and phosphorylation were markedly decreased in the breast cancer tumor treated with catalpol. Taken together, catalpol inhibited breast cancer in vitro and in vivo through induction of apoptosis via mitochondria apoptosis pathway and regulation of protein post-translational modifications (PTMs). Thus, it can be considered as an excellent candidate compound for treatment of breast cancer.

Factors influencing terminal cancer patients' autonomous DNR decision: a longitudinal statutory document and clinical database study.

OBJECTIVE: Much of our knowledge of patient autonomy of DNR (do-not-resuscitate) is derived from the cross-sectional questionnaire surveys. Using signatures on statutory documents and medical records, we analyzed longitudinal data to understand the fact of terminal cancer patients' autonomous DNR decision-making in Taiwan. METHODS: Using the medical information system database of one public medical center in Taiwan, we identified hospitalized cancer patients who died between Jan. 2017 and Dec. 2018, collected their demographic and clinical course data and records of their statutory DNR document types, letter of intent (DNR-LOI) signed by the patient personally and the consent form signed by their close relatives. RESULTS: We identified 1,338 signed DNR documents, 754 (56.35%) being DNR-LOI. Many patients had the first DNR order within their last week of life (40.81%). Signing the DNR-LOI was positively associated with being under the care of a family medicine physician prior to death at last hospitalization and having hospice palliative care and negatively associated with patient age ≥ 65 years, no formal education, having ≥ 3 children, having the first DNR order to death ≤ 29 days, and the last admission in an intensive care unit. CONCLUSIONS: A substantial proportion of terminal cancer patients did not sign DNR documents by themselves. It indicates they may not know their actual terminal conditions and lose the last chance to grasp time to express their life values and wishes. Medical staff involving cancer patient care may need further education on the legal and ethical issues revolving around patient autonomy and training on communicating end-of-life options with the patients. We suggest proactively discussing DNR decision issues with terminal cancer patients no later than when their estimated survival is close to 1 month.

Effect of Supplementing Different Levels of L-Glutamine on Holstein Calves during Weaning.

Weaning stress affects the health and performance of calves. L-glutamine (L-Gln) is commonly used as a functional antioxidant and energy supplement in the body. However, dietary L-Gln supplementation improving weaning stress of calves is unclear. Thus, we aimed to explore the effects of L-Gln (provided by rumen-protected L-Gln) on calves during weaning. Seventy-five Holstein calves (54.0 ± 2.68 kg; 42 ± 2.1 d of age) were assigned to five groups: no supplementation and L-Gln with 1%, 2%, 3%, and 4% dry matter daily intake (DMI) supplementation groups, respectively. The experiment lasted for 28 days (42-70 d of age of calves), and the calves were weaned at 15 d of experiment. DMI and body weekly weight of all calves were recorded. Blood samples of nine healthy calves with similar body weight were collected from each group at 0, 7, 14, 16, 18, 21, and 28 d of experiment for detecting serum L-Gln, glucose, insulin, urea nitrogen, D-lactate, cortisol, haptoglobin, interleukin-8, immunoglobulin (Ig) G, IgA, IgM, total antioxidant capacity, superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde. At the end of the experiment, six healthy calves with similar body weight from each group were selected for slaughter and morphological analysis of small intestine tissue. The results showed that the L-Gln supplementation in the diets improved the negative effects of sudden weaning in calves. Furthermore, compared to the higher-level L-Gln supple-mentation (3 and 4% of DMI) groups, the dietary lower-level L-Gln supplementation (1 and 2% of DMI) had higher average daily gain, glutathione peroxidase and IgG concentration, and villus height/crypt depth of the duodenum and jejunum, as well as lower cortisol, haptoglobin, and interleukin-8 concentration of weaned calves. These results provided effective reference for relieving the negative effects of calves during weaning.

Does Agricultural Credit Input Promote Agricultural Green Total Factor Productivity? Evidence from Spatial Panel Data of 30 Provinces in China.

Improving agricultural green total factor productivity is crucial to promoting high-quality agricultural development. This paper selects the panel data of 30 provinces in China from 2009 to 2020 and uses the super-efficiency SBM model with undesirable outputs to measure the agricultural green total factor productivity of all regions in China. On this basis, this paper uses the panel data fixed-effect model and spatial Durbin model to empirically discuss the impact of agricultural credit input on agricultural green total factor productivity and its spatial spillover effect. The main conclusions are as follows: First, from 2009 to 2020, the average values of agricultural green total factor productivity in national, eastern, central, and western regions are 0.8909, 0.9977, 0.9231, and 0.8068, respectively, and the agricultural green total factor productivity needs to be further improved. Second, the agricultural green total factor productivity presents a significant and positive spatial correlation, and the spatial distribution of agricultural green total factor productivity is not random and irregular. Third, agricultural credit input can significantly promote agricultural green total factor productivity in the local region, but it hinders the improvement of agricultural green total factor productivity in the adjacent regions. Fourth, the impact of agricultural credit input on the agricultural green total factor productivity and its spillover effect has a significant regional heterogeneity. This paper believes that paying attention to the spatial spillover effect of agricultural total factor productivity, optimizing the structure and scale of agricultural credit input, and formulating reasonable agricultural credit policies can improve agricultural green total factor productivity.

Peridynamic Simulation to Fracture Mechanism of CBN Grain in the Honing Wheel Dressing Process.

Regularly dressing of CBN honing wheel is an effective way to keep its sharpness and correct geometry during honing process. This study aims to understand the fracture mechanism of single CBN grain in the dressing process of honing wheel. The honing wheel dressing process was simplified into the dressing process of grinding wheel, and the bond-based Peridynamic method considering bond rotation effect was developed to investigate the progressive fracture evolution, stress characteristics, and fracture modes of CBN grains in this process. It was found that fracture evolution of CBN grains mainly underwent four stages: elastic deformation, damage initiation, crack formation, and macro fracture. In addition, the fracture initiation and propagation were mainly determined by the tensile and shear stress, where the former led to mode I fractures and the latter led to mode II fractures. The propagation of mode I fractures was stable while the propagation of mode II fracture was unstable. The results show that the Peridynamic approach has great potential to predict the fracture mechanism of CBN grain in the dressing process of honing and grinding wheels.

Cutting Performance of Randomly Distributed Active Abrasive Grains in Gear Honing Process.

In power gear honing, the random distribution of abrasive grains on the tooth surface of the honing wheel is the main factor that influences the machining performance of high-quality hardened gears. In order to investigate the micro-edge cutting performance of the active abrasive grains on the workpiece gear, the real honing process is simplified into a micro-edge cutting model with random distribution of active abrasive grains in the cells of the meshing area by obtaining the random distribution states such as the position, orientation and quantity of the honing wheel teeth. The results show that although the active abrasive grains are distributed at different locations, they all experience three types of material removal-slip rubbing, plowing and cutting-allowing the gear honing process to have the combined machining characteristics of grinding, lapping and polishing. The active abrasive grains in first contact produce high honing force, high material removal efficiency and poor surface roughness on the machined workpiece, while the latter ones have the opposite effects. The dislocation angle affects the chip shape and chip discharging direction, and the highest honing force and material removal efficiency is achieved with a dislocation angle of 135°. The higher the number of active abrasive grains in a given contact area, the higher the material removal efficiency.

Use of Coronary Computed Tomography Angiography to Screen Hospital Employees with Cardiovascular Risk Factors.

The objective of this study was to determine how coronary computed tomography angiography (CCTA) can be employed to detect coronary artery disease in hospital employees, enabling early treatment and minimizing damage. All employees of our hospital were assessed using the Framingham Risk Score. Those with a 10-year risk of myocardial infarction or death of >10% were offered CCTA; the Coronary Artery Disease Reporting and Data System (CAD-RADS) score was the outcome. A total of 3923 hospital employees were included, and the number who had received CCTA was 309. Among these 309, 31 (10.0%) had a CAD-RADS score of 3-5, with 10 of the 31 (32.3%) requiring further cardiac catheterization; 161 (52.1%) had a score of 1-2; and 117 (37.9%) had a score of 0. In the multivariate logistic regression, only age of ≥ 55 years (p < 0.05), hypertension (p < 0.05), and hyperlipidemia (p < 0.05) were discovered to be significant risk factors for a CAD-RADS score of 3-5. Thus, regular and adequate control of chronic diseases is critical for patients, and more studies are required to be confirmed if there are more significant risk factors.

Predominant role of soil moisture in regulating the response of ecosystem carbon fluxes to global change factors in a semi-arid grassland on the Loess Plateau.

Climate warming, altered precipitation and nitrogen deposition may critically affect plant growth and ecosystem carbon fluxes. However, the underlying mechanisms are not fully understood. We conducted a 2-yr, multi-factor experiment (warming (W), altered precipitation (+30% and - 30%) and nitrogen addition (N)) in a semi-arid grassland on the Loess Plateau to study how these factors affect ecosystem carbon fluxes. Surprisingly, no interactive effects of warming, altered precipitation and nitrogen addition were detected on parameters of ecosystem carbon fluxes, including net ecosystem CO2 exchange (NEE), ecosystem respiration (ER), gross ecosystem productivity (GEP) and soil respiration (SR). Warming marginally reduced NEE and GEP mainly due to its negative effects on them in July and August. Altered precipitation significantly affected all parameters of carbon fluxes with precipitation reduction decreasing NEE, ER and GEP, whereas precipitation addition increasing SR. In contrast, nitrogen addition had little effect on any parameters of carbon fluxes. Soil moisture was the most important driver and positively correlated with ecosystem carbon fluxes and warming impacted ecosystem carbon fluxes indirectly by decreasing soil moisture. While plant community cover did not show significant association with carbon fluxes, semi-shrubs cover was positively related to NEE, ER and GEP. Together, these results suggest that soil water availability, rather than soil temperature and nitrogen availability, may dominate the effect of the future multi-faceted global changes on semi-arid grassland carbon fluxes on the Loess Plateau.

Interactive global change factors mitigate soil aggregation and carbon change in a semi-arid grassland.

The ongoing global change is multi-faceted, but the interactive effects of multiple drivers on the persistence of soil carbon (C) are poorly understood. We examined the effects of warming, reactive nitrogen (N) inputs (12 g N m-2  year-1 ) and altered precipitation (+ or - 30% ambient) on soil aggregates and mineral-associated C in a 4 year manipulation experiment with a semi-arid grassland on China's Loess Plateau. Our results showed that in the absence of N inputs, precipitation additions significantly enhanced soil aggregation and promoted the coupling between aggregation and both soil fungal biomass and exchangeable Mg2+ . However, N inputs negated the promotional effects of increased precipitation, mainly through suppressing fungal growth and altering soil pH and clay-Mg2+ -OC bridging. Warming increased C content in the mineral-associated fraction, likely by increasing inputs of root-derived C, and reducing turnover of existing mineral-associated C due to suppression of fungal growth and soil respiration. Together, our results provide new insights into the potential mechanisms through which multiple global change factors control soil C persistence in arid and semi-arid grasslands. These findings suggest that the interactive effects among global change factors should be incorporated to predict the soil C dynamics under future global change scenarios.

Sensitivity of plant species to warming and altered precipitation dominates the community productivity in a semiarid grassland on the Loess Plateau.

Global warming and changes in precipitation patterns can critically influence the structure and productivity of terrestrial ecosystems. However, the underlying mechanisms are not fully understood. We conducted two independent but complementary experiments (one with warming and precipitation manipulation (+ or - 30%) and another with selective plant removal) in a semiarid grassland on the Loess Plateau, northwestern China, to assess how warming and altered precipitation affect plant community. Our results showed that warming and altered precipitation affected community aboveground net primary productivity (ANPP) through impacting soil moisture. Results of the removal experiment showed competitive relationships among dominant grasses, the dominant subshrub and nondominant species, which played a more important role than soil moisture in the response of plant community to warming and altered precipitation. Precipitation addition intensified the competition but primarily benefited the dominant subshrub. Warming and precipitation reduction enhanced water stresses but increased ANPP of the dominant subshrub and grasses, indicating that plant tolerance to drought critically meditated the community responses. These findings suggest that specie competitivity for water resources as well as tolerance to environmental stresses may dominate the responses of plant communities on the Loess Plateaus to future climate change factors.

Chronic intermittent hypobaric hypoxia attenuates skeletal muscle ischemia-reperfusion injury in mice.

AIM: The aim of this study was to investigate the protective effect of chronic intermittent hypobaric hypoxia (CIHH) against skeletal muscle ischemia-reperfusion (IR) injury and to determine the underlying mechanism. MAIN METHODS: C57BL/6 mice were randomly divided into 3 groups: skeletal muscle IR injury group (IR), CIHH pretreatment following IR group (IR + CIHH), and sham operation group (Sham). The skeletal muscle IR injury model was induced by the unilateral application of a tourniquet on a hind limb for 3 h and then releasing it for 24 h. CIHH pretreatment simulating a 5000-m altitude was applied 6 h per day for 28 days. The functional and morphological performance of IR-injured gastrocnemius muscle was evaluated using contraction force, H&E staining, and transmission electron microscopy. IR injury-induced CD68+ macrophage infiltration was assessed by immunofluorescence. TNFα levels in serum and muscle were measured by ELISA and western blotting, respectively. Apoptosis was examined by TUNEL staining and Cleaved Caspase-3 protein expression. KEY FINDINGS: Acute IR injury resulted in reduced contraction tension, morphological destruction, macrophage infiltration, increased TNFα levels, and apoptosis in gastrocnemius muscle. CIHH pretreatment significantly ameliorated contraction function and morphological performance in IR-injured skeletal muscle. In addition, CIHH pretreatment resulted in marked decreases in CD68+ macrophage infiltration, TNFα levels, and apoptosis. SIGNIFICANCE: These data demonstrated that CIHH has a protective effect against acute IR injury in skeletal muscle via inhibition of inflammation and apoptosis.

Prevalence and risk factors for colonization by extended-spectrum ß-lactamase-producing or ST 131 Escherichia coli among asymptomatic adults in community settings in Southern Taiwan.

Purpose: Fecal carriage of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and mcr-1-positive E. coli in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 E. coli have been published. Patients and methods: From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium. ST131 and mcr1-positive E. coli were also investigated using multiplex PCR. Clinical data from all participating adults were collected to analyze the risk factors for fecal ESBL-EC or ST131 E. coli carriage. Results: The prevalence rate of asymptomatic ESBL-EC fecal carriage in adults was 1.9% (14/724). ST131 was found in 22 (3.0%) adults and mcr-1-positive E. coli was found in three (0.4%) adults. A multivariate analysis showed that the risk factors associated with ESBL-EC carriage were diabetes mellitus (adjusted odds ratio [aOR]: 5.5, 95% confidence interval [CI]: 1.3-22.7), a history of colonic polyps (aOR: 6.4, 95% CI: 1.6-24.9), and chronic renal insufficiency (aOR: 20.7, 95% CI: 1.4-305.7). Underlying cancer (aOR: 4.8, 95% CI: 1.0-22.5) and stroke (aOR: 18.0, 95% CI: 1.6-207.5) were associated with ST131 E. coli fecal carriage. In our cohort, travel to Asian countries and food habit were not associated with ST131 or ESBL-EC fecal carriage. Conclusions: The ESBL-EC or ST131 E. coli fecal carriage rate is low among asymptomatic adults in Taiwan. Certain underlying medical conditions were associated with their fecal carriage.

Methyl-CpG Binding Domain Protein 2 Inhibits the Malignant Characteristic of Lung Adenocarcinoma through the Epigenetic Modulation of 10 to 11 Translocation 1 and miR-200s.

It has been reported that disorders of epigenetic modulation play a critical role in carcinogenesis. Methyl-CpG binding domain protein 2 (MBD2) is known to act as an epigenetic modulator in various types of tumors; however, the role of MBD2 in lung adenocarcinoma (LUAD) remains unclear. Herein, we demonstrated the down-regulation of MBD2 in LUAD compared with adjacent nontumor tissues. The down-regulation of MBD2 in LUAD was correlated with metastasis and poor survival. In addition, MBD2 inhibited tumor metastasis by maintaining the expression of the miR-200s, which suppressed the invasive properties of tumors. Also, MBD2 positively correlated with 5-hydroxymethylcytosine content in the promoter of miR-200s. The conventional view is that MBD2 acts as a transcriptional suppressor. However, the data revealed that MBD2 may act as a transcriptional activator by recruiting 10 to 11 translocation 1 (TET1) and forming a chromatin-remodeling complex. The MBD2-TET1 complex locates to the TET1 promoter and removes the methyl residues in this region, thereby activating TET1 transcription. TET1 also acted as a tumor suppressor in LUAD. Taken together, the data demonstrate the correlation between MBD2, miR-200s, and TET1, and tumor suppressive effect of MBD2 through up-regulation of TET1 and the miR-200s.