METTL3 recruiting M2-type immunosuppressed macrophages by targeting m6A-SNAIL-CXCL2 axis to promote colorectal cancer pulmonary metastasis.

BACKGROUND: The regulatory role of N6-methyladenosine (m6A) modification in the onset and progression of cancer has garnered increasing attention in recent years. However, the specific role of m6A modification in pulmonary metastasis of colorectal cancer remains unclear. METHODS: This study identified differential m6A gene expression between primary colorectal cancer and its pulmonary metastases using transcriptome sequencing and immunohistochemistry. We investigated the biological function of METTL3 gene both in vitro and in vivo using assays such as CCK-8, colony formation, wound healing, EDU, transwell, and apoptosis, along with a BALB/c nude mouse model. The regulatory mechanisms of METTL3 in colorectal cancer pulmonary metastasis were studied using methods like methylated RNA immunoprecipitation quantitative reverse transcription PCR, RNA stability analysis, luciferase reporter gene assay, Enzyme-Linked Immunosorbent Assay, and quantitative reverse transcription PCR. RESULTS: The study revealed high expression of METTL3 and YTHDF1 in the tumors of patients with pulmonary metastasis of colorectal cancer. METTL3 promotes epithelial-mesenchymal transition in colorectal cancer by m6A modification of SNAIL mRNA, where SNAIL enhances the secretion of CXCL2 through the NF-κB pathway. Additionally, colorectal cancer cells expressing METTL3 recruit M2-type macrophages by secreting CXCL2. CONCLUSION: METTL3 facilitates pulmonary metastasis of colorectal cancer by targeting the m6A-Snail-CXCL2 axis to recruit M2-type immunosuppressive macrophages. This finding offers new research directions and potential therapeutic targets for colorectal cancer treatment.

The effect of sitting baduanjin in patients with ST-segment elevation acute myocardial infarction after percutaneous coronary intervention: A quasi-experimental study.

BACKGROUND: Early cardiac rehabilitation plays a crucial role in the recovery of patients with ST-segment elevation acute myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). This study sought to determine the effect of a program of sitting Baduanjin exercises on early cardiac rehabilitation. OBJECTIVE: The goal of this study was to investigate the effects of sitting Baduanjin exercises on cardiovascular and psychosocial functions in patients with STEMI following PCI. METHODS: This quasi-experimental study employed a randomized, non-equivalent group design. Patients in the intervention group received daily sitting Baduanjin training in addition to a series of seven-step rehabilitation exercises, whereas those in the control group received only the seven-step rehabilitation training, twice daily. Differences in heart rate variability (HRV) indicators, exercise capacity (Six-Minute Walking Distance; 6-MWD), anxiety (Generalized Anxiety Disorder-7; GAD-7), and depression (Patient Health Questionnaire-9; PHQ-9) between the two study groups during hospitalization were analyzed. RESULTS: Patients in the intervention group exhibited lower rates of abnormalities in the time domain and frequency domain parameters of HRV. The median scores of GAD-7 and PHQ-9 in both groups were lower than those at the time of admission, with the intervention group exhibiting lower scores than the control group (P < 0.001; P < 0.001, respectively). The 6-MWD after the intervention was greater in the intervention group compared to the control group (P = 0.014). CONCLUSIONS: We found that sitting Baduanjin training has the potential to enhance HRV, cardiac function, and psychological well-being in patients with STEMI after PCI. This intervention can potentially improve the exercise capacity of a patient before discharge.

Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors.

Immune Checkpoint Inhibitors (ICIs) therapy has advanced significantly in treating malignant tumors, though most 'cold' tumors show no response. This resistance mainly arises from the varied immune evasion mechanisms. Hence, understanding the transformation from 'cold' to 'hot' tumors is essential in developing effective cancer treatments. Furthermore, tumor immune profiling is critical, requiring a range of diagnostic techniques and biomarkers for evaluation. The success of immunotherapy relies on T cells' ability to recognize and eliminate tumor cells. In 'cold' tumors, the absence of T cell infiltration leads to the ineffectiveness of ICI therapy. Addressing these challenges, especially the impairment in T cell activation and homing, is crucial to enhance ICI therapy's efficacy. Concurrently, strategies to convert 'cold' tumors into 'hot' ones, including boosting T cell infiltration and adoptive therapies such as T cell-recruiting bispecific antibodies and Chimeric Antigen Receptor (CAR) T cells, are under extensive exploration. Thus, identifying key factors that impact tumor T cell infiltration is vital for creating effective treatments targeting 'cold' tumors.

Toxicity of VO2 micro/nanoparticles to nitrogen-fixing bacterium Azotobacter vinelandii.

Vanadium dioxide (VO2) has been used in a variety of products due to its outstanding phase transition properties. However, as potential heavy metal contaminants, the environmental hazards and risks of VO2 should be systematically investigated. Biological nitrogen fixation is one of the most dominant processes in biogeochemical cycle, which is associated with nitrogen-fixing bacteria. In this study, we reported the environmental bio-effects of VO2 micro/nanoparticles on the nitrogen-fixing bacterium Azotobacter vinelandii. VO2 at 10 and 30 mg/L caused severe hazards to A. vinelandii, such as cell apoptosis, oxidative damage, physical damage, genotoxicity, and the loss of nitrogen fixation activity. The up-regulated differentially expressed genes of A. vinelandii were related to stress response, and the down-regulated genes were mainly related to energy metabolism. Surprisingly, VO2 of 10 mg/L decreased the nif gene expression but elevated the vnf gene expression, which enhanced the ability of A. vinelandii to reduce acetylene in anaerobic environment. In addition, under tested conditions, VO2 nanoparticles exhibited insignificantly higher toxicity than VO2 microparticles.

AKG induces cell apoptosis by inducing reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing PI3K/AKT/mTOR-mediated autophagy in renal cell carcinoma.

BACKGROUND: Alpha-ketoglutarate (AKG) or 2-oxoglutarate is a key substance in the tricarboxylic acid cycle (TCA) and has been known to play an important role in cancerogenesis and tumor progression. Renal cell carcinoma (RCC) is the most common type of kidney cancer, and it has a high mortality rate. Autophagy is a phenomenon of self-digestion, and its significance in tumor genesis and progression remains debatable. However, the mechanisms underlying how AKG regulates autophagy in RCC remain unknown. Thus, the purpose of this study was to assess the therapeutic efficacy of AKG and its molecular mechanisms. METHODS: RCC cell lines 786O and ACHN were treated with varying doses of AKG for 24 h. CCK-8, Transwell, and scratch wound healing assays were utilized to evaluate the role of AKG in RCC cells. Autophagy protein and PI3K/AKT/mTOR pathway protein levels were analyzed by Western blot. RESULTS: AKG inhibited the proliferation of RCC cells 786O and ACHN in a dose-dependent manner according to the CCK-8 assay. In addition, flow cytometry and Western blot analysis revealed that AKG dose-dependently triggered apoptosis and autophagy in RCC cells. By promoting cell apoptosis and autophagy, AKG dramatically suppressed tumor growth. Mechanistically, AKG induces autophagy by promoting ROS generation and inhibiting the PI3K/AKT/mTOR pathway. CONCLUSIONS: The anti-tumor effect of AKG promotes autophagy in renal cancer cells via mediating ROS-PI3K/Akt/mTOR, and may be used as a potential anticancer drug for kidney cancer.

Stimulating effects of reduced graphene oxide on the growth and nitrogen fixation activity of nitrogen-fixing bacterium Azotobacter chroococcum.

Graphene has found important applications in various areas and hundred tons of graphene materials are annually produced. It is crucial to investigate both the negative and positive environmental effects of graphene materials to ensure the safe applications and develop environmental applications. In this study, we reported the stimulating effects of reduced graphene oxide (RGO) to nitrogen-fixing bacterium Azotobacter chroococcum. RGO stimulated the cell growth of A. chroococcum at 0.010-0.500 mg/mL according to the growth curves and the colony-forming unit (CFU) increases. RGO wrapped over the A. chroococcum cells without inducing ultrastructural changes. RGO decreased the leakage of cell membrane, but slight oxidative stress was observed in A. chroococcum. RGO promoted the nitrogen fixation activity of A. chroococcum at 0.5 mg/mL according to both isotope dilution method and acetylene reduction activity measurements. Consequently, the increases of soil nitrogen contents were evidenced, in particular about 30% increase of organic nitrogen occurred at 0.5 mg/mL of RGO. In addition, RGO might possibly benefit the plant growth through enhancing the indoleacetic acid production of A. chroococcum. These results highlighted the positive environmental effects of graphene materials to nitrogen-fixing bacteria in nitrogen cycle.

Research progress of nano selenium in the treatment of oxidative stress injury during hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) is an additional injury to ischemic tissue after hepatic revascularization, and its pathological mechanism is complex. HIRI is not only involved in the molecular targets that mediate cell death, such as ion channel activation, abnormal protease activation and mitochondrial dysfunction, but also related to the down-regulation of endogenous protective signals. As a by-product of normal aerobic metabolism, reactive oxygen species (ROS) act as a multi effect physiological signal factor at low concentration. However, liver ischemia-reperfusion will lead to excessive ROS accumulation, destroy redox homeostasis, lead to oxidative stress, cause cell death through a variety of mechanisms, and drive the further damage of ischemic liver. Recent studies have found that the antioxidant treatment of nano selenium can reduce the excessive production of ROS and play a potential protective role in reducing HIRI. This paper reviews the molecular mechanism of the antioxidant effect of nano selenium for the prevention and treatment of HIRI, in order to provide further experimental basis for the clinical prevention and treatment of HIRI.

Patients need emotional support: Managing physician disclosure information to attract more patients.

BACKGROUND: Information asymmetry causes barriers for the patient's decision-making in the online health community. Patients can rely on the physician's self-disclosed information to alleviate it. However, the impact of physician's self-disclosed information on the patient's decision has rarely been discussed. OBJECTIVES: To investigate the impact of the physician's self-disclosed information on the patient's decision in the online health community and to examine the moderating effect of the physician's online reputation. METHODS: Drawing on the limited-capacity model of attention, we develop a theoretical model to estimate the impact of physician's self-disclosure information on patient's decision and the contingent roles of physician's online reputation in online healthcare community by econometric methods. We designed a web crawler based on R language program to collect more than 20,000 physicians' data from their homepage in Haodf-a leading online healthcare community platform in China. The attributes of the physician's information disclosure are measured by the following variables: emotion orientation, the quantity of information and the semantic topics diversity. RESULTS: The empirical analysis derives the following findings: (1) The emotion orientation in physician's self-disclosure information is positively associated with patient's decision; (2) Both excessive quantity of information and semantic topics diversity can raise barriers for patient's decision; (3) When the level of physician's online reputation is high, the negative effect of the quantity of information and semantic topics diversity are all strengthened while the positive effect of the emotion orientation is not strengthened. CONCLUSIONS: This study has a profound importance for a deep understanding of the impact of physician's self-disclosure information and contributes to the literature on information disclosure, the limited capacity model of attention, patient's decision. Also, this study provides implications for practice.

Pigmentibacter ruber gen. nov., sp. nov., a novel bacterium of the family Silvanigrellaceae isolated from human blood.

A Gram-negative, aerobic, non-motile, pleomorphic, red-pigmented bacterium, designated HNSRY-1T, was isolated from the blood sample of a near drowning patient in Republic of China. Strain HNSRY-1T grew at 15-37 °C (optimum, 35 °C), with pH 6.0-8.0 (optimum, pH 7.0) and 0-1.5% (W/V) NaCl (optimum, 1%). The predominant fatty acids (> 5%) in HNSRY-1T cells are iso-C15:0, C17:0, C17:1 ω8c, C16:0, and C16:1 ω6c/C16:1 ω7c. The major respiratory quinone is MK-8. The polar lipids are phosphatidylglycerol, phosphatidylethanolamine, three unidentified lipids and four unidentified aminolipids. The 16S rRNA gene sequence-based phylogenetic analysis indicated that strain HNSRY-1T belonged to the family Silvanigrellaceae, forming a distinct phylogenetic line distantly related (< 96.4% sequence similarity) to known species of the family. The ANI values of strain HNSRY-1T compared to the closely related species were below the determined genus division threshold limit (92-94% ANI), and AAI values were lower than the determined genus division threshold limit (80% AAI). Whole genome sequencing revealed a genome size of 3.63 Mb with a DNA G + C content at 29.6%. The half-lethal dose of strain HNSRY-1T on KM mice is about 1.12 × 108 CFU/ml. Virulence gene analysis showed that the pathogenicity of HNSRY-1T may be related to tufA, htpB, katA, wbtL, wbtM, pseB, clpP, cheY, cheV3, acpXL, pilB, fliN, ggt, flgG, fliP, nueB, pseA, bioB and flil. Based on these findings from the polyphasic taxonomy studies, a novel genus and species of the family Silvanigrellaceae. Pigmentibacter ruber gen. nov., sp. nov. is proposed, with type strain HNSRY-1T (= KCTC 72920T = CGMCC 1.18525T).

Toxicity and photosynthetic inhibition of metal-organic framework MOF-199 to pea seedlings.

Metal-organic framework (MOF) materials are star materials with unique structures and properties. To ensure safe production and applications, the toxicity and environmental hazards of MOF materials should be thoroughly investigated. However, the environmental impact of MOF materials on plants is completely unknown. Herein, we reported the toxicity and photosynthetic inhibitory properties of MOF-199 to pea plants (Pisum sativum L.). MOF-199 was synthesized by hydrothermal method. MOF-199 was copper containing double-pyramid of high surface area (668 m2/g). MOF-199 accelerated the germination of pea seeds, but the total germination rates were unchanged. MOF-199 inhibited the seedling growth at high concentrations. The net photosynthetic rate increased, while the total photosynthesis capability decreased. Damage to the acceptor side of photosystem II was evidenced by chlorophyll fluorescence. Mechanistically, MOF-199 released Cu2+ in the nutrient solution, led to Cu2+ accumulations in seedlings, and promoted oxidative stress. In addition, the photosynthetic inhibitions of MOF-199 were stronger than equivalent concentrations of Cu(NO3)2, implying that MOF-199 particles also contributed to the environmental hazards. Our results highlighted the potential threat of MOF materials to plant growth and photosynthesis.

Comprehensive profiling of circRNAs and the tumor suppressor function of circHIPK3 in clear cell renal carcinoma.

Increasing evidence has indicated that circular RNAs (circRNAs) play a key role in the development and progression of diverse cancers, but their role in clear cell renal carcinoma (CCRCC) tumorigenesis is not well understood. In this study, we firstly performed comprehensive circRNA-seq from CCRCC tissues and pair-matched adjacent normal tissues. In total, 1184 circRNAs were dysregulated in human CCRCC tissues compared with those in adjacent normal tissues. We randomly selected four circRNAs, including circHIPK3 (circBase ID: hsa_circ_0000284), to test the circRNA-seq data in another 40 CCRCC tissues by quantitative real-time PCR (qRT-PCR). Furthermore, we found that circHIPK3 was downregulated in CCRCC tissues and cell lines. Overexpression of circHIPK3 effectively suppressed CCRCC cell invasion and migration in vitro, and inhibited CCRCC cell proliferation in vitro and in vivo. Moreover, bioinformatic analysis and luciferase reporter assay showed that circHIPK3 targeted miR-637 in CCRCC cells. Hence, CircHIPK3 may represent a tumor suppressor and target miR-637 in clear cell renal carcinoma.

Fast Identification and Quantification of Graphene Oxide in Aqueous Environment by Raman Spectroscopy.

Today, graphene nanomaterials are produced on a large-scale and applied in various areas. The toxicity and hazards of graphene materials have aroused great concerns, in which the detection and quantification of graphene are essential for environmental risk evaluations. In this study, we developed a fast identification and quantification method for graphene oxide (GO) in aqueous environments using Raman spectroscopy. GO was chemically reduced by hydrazine hydrate to form partially reduced GO (PRGO), where the fluorescence from GO was largely reduced, and the Raman signals (G band and D band) were dominating. According to the Raman characteristics, GO was easily be distinguished from other carbon nanomaterials in aqueous environments, such as carbon nanotubes, fullerene and carbon nanoparticles. The GO concentration was quantified in the range of 0.001-0.6 mg/mL with good linearity. Using our technique, we did not find any GO in local water samples. The transport of GO dispersion in quartz sands was successfully quantified. Our results indicated that GO was conveniently quantified by Raman spectroscopy after partial reduction. The potential applications of our technique in the environmental risk evaluations of graphene materials are discussed further.

Combined effect of n-3 fatty acids and phytosterol esters on alleviating hepatic steatosis in non-alcoholic fatty liver disease subjects: a double-blind placebo-controlled clinical trial.

The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver-spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-ß (TGF-ß) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-ß was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.

Effects of hydrogen-rich water on the nutrient composition and antioxidative characteristics of sprouted black barley.

Hydrogen gas (H2), a multifunctional signaling molecule, has received increasing attention in recent years. In the present study, hydrogen-rich water (HRW) (2 ppm) was used for the processing of sprouted black barley (Hordeum distichum L.), and the results showed that the HRW treatment could significantly increase the germination rate and growth rate of black barley (P < 0.05). A chemical component analysis showed that in sprouted black barley, the HRW treatment could change the distribution of phytochemicals (e.g., the ionic strength of guanosine), increase the concentrations of free vanillic acid, coumaric acid, sinapic acid, conjugated sinapic acid, Ca and Fe and the hydroxyl radical scavenging rate, and decrease the protein, fat, starch and dietary fibre contents compared with the results obtained after treatment with ultra-pure water (P < 0.05). HRW can be used for the processing of sprouted grains to effectively increase their germination efficiency and concentrations of bioactive phytochemicals.

Schizophrenia Auxiliary Diagnosis System Based on Data Mining Technology.

In order to use digital medical technology to develop and design an auxiliary diagnosis system for schizophrenia to assist doctors at all levels to diagnose and predict the cure of patients, improve the accuracy of diagnosis of symptoms, find complications in advance, and reduce the risk of disease, the application of Bayesian network in auxiliary diagnosis system of schizophrenia is studied, and an auxiliary diagnosis system of schizophrenia is designed. Based on data mining technology, knowledge information can be found from patient data and used to diagnose the nature of patients. The demand analysis of auxiliary diagnosis system is briefly introduced, and an auxiliary diagnosis system for schizophrenia based on Bayesian network is designed.

Well-being loss in informal care for the elderly people: Empirical study from China national baseline CHARLS.

INTRODUCTION: Well-being is an important component of health, while informal care plays a vital role in daily care of the elderly. However, the effects of informal care on the well-being of the elderly remain unclear. This study was aimed to estimate such effects, in which well-being was measured by 2 subjective indicators: happiness and life satisfaction. METHODS: Potential endogeneity was purified using instrumental variables. Data were collected from national baseline China Health and Retirement Longitudinal Study (CHARLS). RESULTS: Receiving informal care would decrease the elderly's happiness score and life satisfaction score significantly. The health produced from informal care cannot offset the health depreciation caused by aging. DISCUSSION: To improve the well-being of the elderly, caregivers have more to do and policymakers can design designated care policies based on our results.

Depression and sleep duration: findings from middle-aged and elderly people in China.

OBJECTIVE: This study aims to investigate whether depression is associated with subsequent sleep duration among middle-aged and elderly people in China. STUDY DESIGN: Cross-sectional study. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). Depression was evaluated from the 2011 baseline survey data using the Chinese version of the Center for Epidemiologic Studies Depression scale (CES-D). All other data were extracted from CHARLS 2013 survey data. Sleep duration was assessed according to the American National Sleep Foundation. Participants were divided into subgroups based on their gender (male or female) and age (45-59 years [middle-aged] or ≥60 years [elderly people]). The relative risk ratios (RRRs) were calculated using the multinomial logistic regression analysis method. RESULTS: No significant associations were found between depression and subsequent long sleep duration among middle-aged and elderly people in China; in addition, no association was found during subgroup analysis. The adjusted RRR (RRR = 1.71; 95% confidence interval [CI] = 1.56-1.88) shows there is a significant association between depression and subsequent short sleep duration among subgroups. The RRR of the male, female, middle-aged, and elderly people were 1.64 (95% CI=1.38-1.95), 1.74 (95% CI=1.56-1.95), 1.68 (95% CI = 1.47-1.92), 1.74 (95% CI = 1.52-1.99), respectively, which revealed that this association was still significant in subgroups. CONCLUSIONS: Findings from this study suggest that there is a complex association between depression and subsequent alternations in sleep duration among middle-aged and elderly people in China.

The association between depressive symptoms and fall accidents among middle-aged and elderly people in China.

BACKGROUND: Depressive symptoms are a worldwide health problem. However, the research about the effect of depressive symptoms on the fall among the Chinese mid-aged and elderly people is lacking. Therefore, this study aims to investigate the association between depressive symptoms and fall accidents among middle-aged and elderly people in China. METHODS: This study was conducted based on 12,527 sets of data from China Health and Retirement Longitudinal Survey (CHARLS). The 2011 depressive symptoms data and the 2013 fall data were chosen for this study. The depressive symptom-related data was assessed by the Chinese version of Center for Epidemiologic Studies Depression scales (CES-D). Individuals were divided into subgroups according to gender (male or female), age (45-59, middle-aged or ≥ 60, elderly people), and residence (rural or urban). The odds ratios (ORs) were compared between subgroups using multivariable logistic regression analysis method. RESULTS: The adjusted OR value (OR = 1.19 [95% CI 1.07-1.33]) shows there is a significant association between depressive symptoms and subsequent fall accidents. The ORs of the female, elderly people, rural, and urban subgroups are 1.31 (95% CI 1.11-1.55), 1.24 (95% CI 1.08-1.43), 1.17 (95% CI 1.02-1.33), and 1.25 (95% CI 1.04-1.49), respectively, which reveals that this association is also statistically significant in these subgroups. CONCLUSIONS: This study shows that there is a significant association between depressive symptoms and their subsequent fall accidents among the Chinese middle-aged and elderly people.