N6-methyladenosine-driven miR-143/145-KLF4 circuit orchestrates the phenotypic switch of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is characterized by vascular remodeling predominantly driven by a phenotypic switching in pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanisms for this phenotypic alteration remain incompletely understood. Here, we identified that RNA methyltransferase METTL3 is significantly elevated in the lungs of hypoxic PH (HPH) mice and rats, as well as in the pulmonary arteries (PAs) of HPH rats. Targeted deletion of Mettl3 in smooth muscle cells exacerbated hemodynamic consequences of hypoxia-induced PH and accelerated pulmonary vascular remodeling in vivo. Additionally, the absence of METTL3 markedly induced phenotypic switching in PASMCs in vitro. Mechanistically, METTL3 depletion attenuated m6A modification and hindered the processing of pri-miR-143/145, leading to a downregulation of miR-143-3p and miR-145-5p. Inhibition of hnRNPA2B1, an m6A mediator involved in miRNA maturation, similarly resulted in a significant reduction of miR-143-3p and miR-145-5p. We demonstrated that miR-145-5p targets Krüppel-like factor 4 (KLF4) and miR-143-3p targets fascin actin-bundling protein 1 (FSCN1) in PASMCs. The decrease of miR-145-5p subsequently induced an upregulation of KLF4, which in turn suppressed miR-143/145 transcription, establishing a positive feedback circuit between KLF4 and miR-143/145. This regulatory circuit facilitates the persistent suppression of contractile marker genes, thereby sustaining PASMC phenotypic switch. Collectively, hypoxia-induced upregulation of METTL3, along with m6A mediated regulation of miR-143/145, might serve as a protective mechanism against phenotypic switch of PASMCs. Our results highlight a potential therapeutic strategy targeting m6A modified miR-143/145-KLF4 loop in the treatment of PH.

Genomic Insights into the Role of TOP Gene Family in Soft-Tissue Sarcomas: Implications for Prognosis and Therapy.

This study focuses on the role of topoisomerases (TOPs) in sarcomas (SARCs), highlighting TOPs' influence on sarcoma prognosis through mRNA expression, genetic mutations, immune infiltration, and DNA methylation analysis using transcriptase sequencing and other techniques. The findings indicate that TOP gene mutations correlate with increased inflammation, immune cell infiltration, DNA repair abnormalities, and mitochondrial fusion genes alterations, all of which negatively affect sarcoma prognosis. Abnormal TOP expression may independently affect sarcoma patients' survival. Cutting-edge genomic tools such as Oncomine, gene expression profiling interactive analysis (GEPIA), and cBio Cancer Genomics Portal (cBioPortal) are utilized to explore the TOP gene family (TOP1/1MT/2A/2B/3A/3B) in soft-tissue sarcomas (STSs). This in-depth analysis reveals a notable upregulation of TOP mRNA in STS patients arcoss various SARC subtypes, French Federation Nationale des Centres de Lutte Contre le Cancer classification (FNCLCC) grades, and specific molecular profiles correlating with poorer clinical outcomes. Furthermore, this investigation identifies distinct patterns of immune cell infiltration, genetic mutations, and somatic copy number variations linked to TOP genes that inversely affect patient survival rates. These findings underscore the diagnostic and therapeutic relevance of the TOP gene suite in STSs.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis through promoting polarization of M2 macrophage.

BACKGROUND: Previous study implied that local M2 polarization of macrophage promoted mucosal edema and exacerbates Th2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We thought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: RT-qPCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 knockout mice were used to establish nasal polyp model with Th2 inflammation and investigate the effects of SIRT5 in macrophages on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophages markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 deficiency mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages through promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting the alternative polarization of macrophage and thus provides a potential target for CRSwNP interventions.

Prognostic value of elevated lipoprotein (a) in patients with acute coronary syndromes: a systematic review and meta-analysis.

Background: Elevated lipoprotein (a) level was recognized as an independent risk factor for significant adverse cardiovascular events in acute coronary syndrome (ACS) patients. Despite this recognition, the consensus in the literature regarding the prognostic significance of elevated lipoprotein (a) in ACS was also limited. Consequently, we conducted a thorough systematic review and meta-analysis to evaluate the prognostic relevance of elevated lipoprotein (a) level in individuals diagnosed with ACS. Methods and results: A thorough literature review was conducted by systematically searching PubMed, Embase, and Cochrane databases until September 2023. This review specifically examined cohort studies exploring the prognostic implications of elevated lipoprotein (a) level in relation to major adverse cardiovascular events (MACE), including death, stroke, non-fatal myocardial infarction (MI), and coronary revascularization, in patients with ACS. The meta-analysis utilized aggregated multivariable hazard ratios (HR) and their respective 95% confidence intervals (CI) to evaluate prognostic implications between high and low lipoprotein (a) levels [the cut-off of high lipoprotein (a) level varies from 12.5 to 60 mg/dl]. Among 18,168 patients in the identified studies, elevated lipoprotein (a) was independently associated with increased MACE risk (HR 1.26; 95% CI: 1.17-1.35, P < 0.00001) and all-cause mortality (HR 1.36; 95% CI: 1.05-1.76, P = 0.02) in ACS patients. In summary, elevated lipoprotein (a) levels independently forecast MACE and all-cause mortality in ACS patients. Assessing lipoprotein (a) levels appears promising for risk stratification in ACS, offering valuable insights for tailoring secondary prevention strategies. Systematic Review Registration: PROSPERO (CRD42023476543).

Lysine specific demethylase 1 inhibits sodium arsenite activation of HSCs by regulating SESN2/AMPK/ULK1 signaling pathway activity.

Lysine specific demethylase 1 (LSD1) is a histone demethylase that specifically catalyzes the demethylation of histone H3K4 (H3K4me1/2) and regulates gene expression. In addition, it can mediate the process of autophagy through its demethylase activity. Sestrin2 (SESN2) is a stress-induced protein and a positive regulator of autophagy. In NaAsO2-induced mouse fibrotic livers and activated hepatic stellate cells (HSCs), LSD1 expression is decreased, SESN2 expression is increased, and autophagy levels are also increased. Overexpression of LSD1 and silencing of SESN2 decreased the level of autophagy and attenuated the activation of HSCs induced by NaAsO2. LSD1 promoted SESN2 gene transcription by increasing H3K4me1/2 in the SESN2 promoter region. 3-methyladenine (3-MA) and chloroquine were used to inhibit autophagy of HSCs, and the degree of activation was also alleviated. Taken together, LSD1 positively regulates SESN2 by increasing H3K4me1/2 enrichment in the SESN2 promoter region, which in turn increases the level of autophagy and promotes the activation of HSCs. Our results may provide new evidence for the importance of LSD1 in the process of autophagy and activation of HSCs induced by arsenic poisoning. Increasing the expression and activity of LSD1 is expected to be an effective way to reverse the autophagy and activation of HSCs induced by arsenic poisoning.

[Chemical constituents from stems and leaves of Cratoxylum cochinchinense and their inhibitory effects on proliferation of synoviocytes in vitro].

The chemical constituents from the stems and leaves of Cratoxylum cochinchinense were isolated and purified using silica gel, ODS gel, and Sephadex LH-20 gel column chromatography, as well as preparative HPLC. The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, and the comparison of their physicochemical and spectroscopic data with the reported data in literature. As a result, 21 compounds were isolated from the 90% ethanol extract of the stems and leaves of C. cochinchinense, which were identified as cratocochine(1), 1-hydroxy-3,7-dimethoxyxanthone(2), 1-hydroxy-5,6,7-trimethoxyxanthone(3), ferrxanthone(4), 3,6-dihydroxy-1,5-dimethoxyxanthone(5), 3,6-dihydroxy-1,7-dimethoxyxanthone(6), 1,2,5-trihydroxy-6,8-dimethoxyxanthone(7), securixanthone G(8), gentisein(9), 3,7-dihydroxy-1-methoxyxanthone(10), pancixanthone B(11), garcimangosxanthone A(12), pruniflorone L(13), 9-hydroxy alabaxanthone(14), cochinchinone A(15), luteolin(16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol(17), N-benzyl-9-oxo-10E,12E-octadecadienamide(18), 15-hydroxy-7,13E-labdadiene(19), stigmasta-4,22-dien-3-one(20), and stigmast-5-en-3ß-ol(21). Among these isolates, compound 1 was a new xanthone, compounds 2-5, 7, 8, 12, and 16-21 were isolated from the Cratoxylum plant for the first time, and compounds 11 and 13 were obtained from C. cochinchinense for the first time. Furthermore, all isolated compounds 1-21 were appraised for their anti-rheumatoid arthritis activities by MTS method through measuring their anti-proliferative effect on synoviocytes in vitro. As a result, xanthones 1-15 displayed notable anti-rheumatoid arthritis activities, which showed inhibitory effects on the proliferation of MH7A synoviocytes with the IC_(50) values ranging from(8.98±0.12) to(228.68±0.32) µmol·L~(-1).

Perioperative, functional, and oncological outcomes of robotic vs. laparoscopic partial nephrectomy for complex renal tumors (RENAL score ≥7): an evidence-based analysis.

Objective: To evaluate the current literature comparing outcomes of robotic partial nephrectomy (RPN) versus laparoscopic partial nephrectomy (LPN) treating complex renal tumors (RENAL nephrometry score ≥7). Methods: We systematically searched the Cochrane Library, PubMed, Google Scholar, EMBASE, and Scopus databases up to March 2023. Review Manager 5.4 performed a pooled analysis of the data for random effects. Besides, sensitivity and subgroup analyses to explore heterogeneity, Newcastle-Ottawa scale, and GRADE to evaluate study quality and level of evidence. Results: Eight observational studies comprising 1346 patients (RPN: 695; LPN: 651) were included in this study. Compared to LPN, RPN had a shorter operative time (OT) (weight mean difference [WMD]: -14.73 min; p = 0.0003), shorter warm ischemia time (WIT) (WMD: -3.47 min; p = 0.002), lower transfusion rate (odds ratio [OR]: 0.66; p = 0.04), shorter length of stay (LOS) (WMD: -0.65 days; p < 0.00001), lower postoperative estimated glomerular filtration rate (eGFR) change (WMD = -2.33 mL/min/1.73 m2; p = 0.002) and lower intraoperative complications (OR: 0.52; p = 0.04). No significant differences were observed between the two groups in terms of estimated blood loss (EBL) (p = 0.84), conversion to radical nephrectomy (p = 0.12), postoperative complications (p = 0.11), major complications (defined Clavien-Dindo grade 3 (p = 0.43), overall complications (p = 0.15), postoperative eGFR (p = 0.28), local recurrence (p = 0.35), positive surgical margin (PSM) (p = 0.63), overall survival (OS) (p = 0.47), cancer-specific survival (CSS) (p = 0.22) and 3-year recurrence-free survival (RFS) (p = 0.53). Conclusion: Patients with complex renal tumors (RENAL score ≥7), RPN is superior to LPN in decreasing the OT, WIT, LOS, transfusion rate, change in eGFR and the incidence of intraoperative complications while maintaining oncological control and avoiding a decline in renal function. However, our findings need further validation in a large-sample prospective randomized study.

Inhibition mechanisms of four ellagitannins from terminalia chebula fruits on acetylcholinesterase by inhibition kinetics, spectroscopy and molecular docking analyses.

Acetylcholinesterase (AChE) is an important therapeutic target for the treatment of Alzheimer's disease (AD), and the development of natural AChE inhibitors as candidates has played a significant role in drug discovery. In this study, the inhibition mechanisms of four ellagitannins, punicalagin, chebulinic acid, geraniin and corilagin, from Terminalia chebula fruits on AChE were investigated systematically by a combination of inhibition kinetics, multi-spectroscopic methods and molecular docking. The kinetic results showed that punicalagin, chebulinic acid and geraniin exhibited strong reversible inhibitory effects on AChE in an uncompetitive manner with the IC50 values of 0.43, 0.50, and 0.51 mM, respectively, while corilagin inhibited AChE activity in a mixed type with the IC50 value of 0.72 mM. The results of fluorescence and UV-vis spectra and fluorescence resonance energy transfer (FRET) revealed that four ellagitannins could significantly quenched the intrinsic fluorescence of AChE though a static quenching along with non-radiative energy transfer. Thermodynamic analyses showed that values of ΔG, ΔH and ΔS were negative, indicating that all binding processes were spontaneous, and the hydrogen bonding and Van der Waals forces might make a great contribution to the formation of inhibitor-AChE complexes. The synchronous fluorescence, three-dimensional (3D) fluorescence, UV-vis, and FT-IR spectra studies suggested that four ellagitannins could lead to alterations in the micro-environment and secondary structure of AChE, and thus the conformational change of AChE. Moreover, molecular docking demonstrated that four ellagitannins could interacted with main amino acid residues of AChE with affinity energies ranging from -9.9 to -8.7 kJ/mol, and further confirmed the above experimental results. This study provided valuable findings for the potential application of four ellagitannins as promising candidates in the exploration of natural AChE inhibitors for the treatment of AD.

Comparative study of different sewage sludge incineration treatments based on environmental and economic life cycle assessment.

Incineration is one of the most widely used treatments in the field of sewage sludge disposal. However, the choice of sewage sludge incineration process is still controversial. In this study, the comparative life cycle assessment of sewage sludge incineration processes, including the mono-incineration, co-incineration in coal-fired power plants and co-incineration in municipal solid waste (MSW) incineration plants, was carried out from the perspective of environment, carbon footprint and economy. The environmental assessment results show that terrestrial ecotoxicity, freshwater ecotoxicity, marine ecotoxicity, human carcinogenic toxicity and human non-carcinogenic toxicity are the most significant environmental impacts. And the environmental performance of co-incineration in coal-fired power plants is the best. Moreover, the environmental impact is most sensitive to the dehydrant, electricity and fly ash chelating agent. Co-incineration in MSW incineration plants has the lowest carbon emissions, with only 70.50% and 82% of the carbon emissions from mono-incineration and co-incineration in coal-fired power plants, respectively. Furthermore, sewage sludge mono-incineration has the highest disposal costs because of the higher depreciation and solid waste disposal costs. The comprehensive evaluation results reveal that the optimization should focus on the selection of dehydrant and fly ash chelating agent, as well as the improvement of the equipment efficiency.

Rh(III)-catalyzed [3 + 3] spirocyclization of 3-aryl-3-hydroxyisoindolinones with vinylene carbonate as a three-atom unit.

A [3 + 3] annulation of 3-aryl-3-hydroxyisoindolinones for the efficient synthesis of isoindolinone-derived spiroisochromenes is reported. In this Rh(III)-catalyzed spirocyclization reaction, vinylene carbonate is used as the coupling partner and acts as a three-atom synthon (C-C-O) through the decarboxylation process. This atom-economic reaction worked efficiently under mild conditions via a C-H activation pathway. It is the first example where 3-aryl-3-hydroxyisoindolinones are used as the building blocks to construct spiroheterocycles.

Unraveling the capture mechanism of gaseous As2O3 over H-ZSM-5 zeolite from coal-fired flue gas: Experimental and theoretical insights.

Gaseous As2O3 discharged from coal-fired power plants results in severe detriments to the ecological environment. It is of great urgency to develop highly efficient As2O3 capture technology for reducing atmospheric arsenic contamination. Utilizing solid sorbents for gaseous As2O3 capture is a promising treatment for As2O3 capture. The zeolite of H-ZSM-5 was applied for As2O3 capture at high temperatures of 500-900 °C. Special attention was paid to clarifying its capture mechanism and identifying the influence of flue gas components via density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations. Results revealed that due to high thermal stability with large specific areas, H-ZSM-5 demonstrated excellent arsenic capture at 500-900 °C. The captured arsenic consisted of As3+ and As5+ speciations, ascribed to As2O3 adsorption and oxidation. Moreover, As3+ and As5+ compounds were both through physisorption or chemisorption at 500-600 °C while dominant chemisorption at 700-900 °C. In particular, As3+ compounds were much more steadily fixed in products at all operating temperatures. Combining the characterization analysis and DFT calculations, it further verified that both Si-OH-Al groups and external Al species of H-ZSM-5 could chemisorb As2O3, and the latter exhibited much stronger affinities via orbital hybridization and electron transfer. The introduced O2 could facilitate As2O3 oxidation and fixation in H-ZSM-5, especially at a lower concentration of 2%. Additionally, H-ZSM-5 possessed great acid gas resistance for As2O3 capture under the concentration of NO or SO2 less than 500 ppm. AIMD simulations further identified that compared to NO and SO2, As2O3 was far more competitive and occupied the active sites of the Si-OH-Al groups and external Al species of H-ZSM-5. Overall, it demonstrated that H-ZSM-5 is a promising sorbent for As2O3 capture from coal-fired flue gas.

In-situ exsolution of Fe-Ni alloy catalysts for H2 and carbon nanotube production from microwave plasma-initiated decomposition of plastic wastes.

The management of plastic wastes has become an urgent issue due to the overconsumption of single-use plastic products. As a promising avenue for plastic waste valorization, chemical recycling by converting plastics into value-added products has attracted tremendous attention. In this paper, the Fe-Ni alloy catalysts via in-situ exsolution were employed for the straightforward microwave plasma-initiated decomposition of plastic wastes for high yield H2 and carbon nanotubes. The partial substitution of Fe by Ni promoted in-situ exsolution of alloy nanoparticles homogeneously. Specifically, characterization results showed that the introduction of Ni modulated metal-support interaction, which further affected the crystalline phase, nanoparticle size and oxygen vacancies. The exsolved Fe-Ni alloy catalyst exhibited the highest catalytic activity, over which 96 % hydrogen of plastic wastes rapidly evolved out in the form of gas products accompanied with high-purity carbon nanotubes. The H2 yield was 415 mmol·g-1Hplastic, which exhibited an over 2 times improvement versus the supported catalyst. Moreover, the successive cycle test displayed the potential for converting plastic wastes into H2-rich fuels and high-quality CNTs continuously. Generally, the in-situ exsolution strategy of Fe-Ni alloy catalysts contributed to the sustainable and high-efficient recycling of plastic wastes into H2-rich gas products and carbon nanotubes under microwave plasma.

Experimental Investigation of Solar-Driven Hollow Fiber Membrane Liquid Dehumidification System.

The hollow fiber membrane modules act as dehumidifiers and regenerators to avoid gas-liquid entrainment problems in direct-contact dehumidification systems. A solar-driven hollow fiber membrane dehumidification experimental rig was designed to investigate its performance from July to September in Guilin, China. The dehumidification, regeneration, and cooling performance of the system between 8:30 and 17:30 are analyzed. The energy utilization of the solar collector and system is investigated. The results show that solar radiation has a significant influence on the system. The hourly regeneration of the system has the same trend as the temperature of solar hot water, which ranges from 0.13 g/s to 0.36 g/s. The regeneration capacity of the dehumidification system is always larger than the dehumidification capacity after 10:30, which increases the solution concentration and the dehumidification performance. Further, it ensures stable system operation when the solar radiation is lower (15:30-17:50). In addition, the hourly dehumidification capacity and efficiency of the system ranges from 0.15 g/s to 0.23 g/s and 52.4 to 71.3%, respectively, with good dehumidification performance. The COP of the system and solar collector have the same trend, in which their maximum values are 0.874 and 0.634, respectively, with high energy utilization efficiency. The solar-driven hollow fiber membrane liquid dehumidification system performs better in regions with larger solar radiation.

Orbital-resolved photoelectron momentum distributions of F- ions in a counter-rotating bicircular field.

We present a theoretical study of the orbital-resolved photoelectron momentum distributions (PMDs) of F- ions by a two-color counter-rotating circularly polarized field. We show that the PMDs of F- ions can be modulated from an isotropic symmetric distribution into a three-lobe one by adding a weak fundamental counter-rotating field to the intense second harmonic circularly polarized field, and this modulation strongly depends on the initial atomic orbital. The PMDs simulated by the strong-field approximation method show good agreement with those obtained by solving the time-dependent Schrödinger equation. Based on the strong-field approximation method, we find that the radial momentum shift of PMDs for different orbitals is the fingerprint of orbital-dependent initial momentum at the tunnel exit. More importantly, we demonstrate that the lobes in PMDs appear in sequential order, highlighting that the scheme can be viewed as controllable rotating temporal Young's two-slit interferometer.

Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice.

BACKGROUND: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage. METHODS: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing (scRNA-seq) was then carried out on TCS- or mock-treated mouse livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the molecular and cellular events after TCS exposure. To verify the TCS-induced liver fibrosis, the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson's trichrome and Sirius red staining. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies. RESULTS: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control group profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells (HSCs) were significantly increased in TCS-treated group. We found that TCS promoted fibrosis-associated proliferation of hepatocytes, in which Gata2 and Mef2c are the key driving TFs. Our data also suggested that TCS induced the proliferation and activation of HSCs, which was experimentally verified in both liver tissue and cell model. In addition, other changes including the dysfunction and capillarization of endothelial cells, an increase of fibrotic characteristics in B plasma cells, and M2 phenotype-skewing of macrophage cells, were also deduced from the scRNA-seq analysis, and these changes are likely to contribute to the progression of liver fibrosis. Lastly, the key differential ligand-receptor pairs involved in cellular communications were identified and we confirmed the role of GAS6_AXL interaction-mediated cellular communication in promoting liver fibrosis. CONCLUSIONS: TCS modulates the cellular activities and fates of several specific cell types (including hepatocytes, HSCs, endothelial cells, B cells, Kupffer cells and liver capsular macrophages) in the liver, and regulates the ligand-receptor interactions between these cells, thereby promoting the proliferation and activation of HSCs, leading to liver fibrosis. Overall, we provide the first comprehensive single-cell atlas of mouse livers in response to TCS and delineate the key cellular and molecular processes involved in TCS-induced hepatotoxicity and fibrosis.

The eisosomes contribute to acid tolerance of yeast by maintaining cell membrane integrity.

Microbes have evolved multiple mechanisms to resist environmental stresses, which are regulated in complex and delicate ways. Though the role of cell membranes in acid resistance from the perspective of physicochemical properties and membrane proteins has been deeply studied, the function of eisosomes is still in its infancy. In this study, we firstly reported the dynamic changes of eisosomes under acid stress and the decreased acid tolerance of yeasts caused by eisosome disruption. Physiological indicators and non-targeted lipid profiling revealed that eisosome disruption caused changes in multiple lipids and imbalances in lipid homeostasis, which are responsible for membrane integrity damage. Thus the increased infiltration of carboxylic acids and the raised ROS levels were detected in strains with disrupted eisosome assembly, resulting in decreased cellular tolerance. The results here provide novel insights into the acid-resistant mechanism of yeasts from the perspective of the cell membrane subdomain, which has practical impacts on green biological manufacturing and food preservation.

[Dithiothreitol promotes apoptosis in rat hepatocytes by inhibiting family with sequence similarity 134 member B (FAM134B)-mediated endoplasmic reticulophagy].

Objective To investigate the effect of family with sequence similarity 134 member B (FAM134B)-mediated endoplasmic reticulophagy on apoptosis of hepatocytes induced by endoplasmic reticulum stress (ERS) and identify its potential regulatory mechanism. Methods BRL-3A cells were treated with 0, 0.5, 1.0, 2.0, 4.0, 6.0 mmol/L dithiothreitol (DTT) for 48 hours. The effect of DTT treatment on the proliferation and apoptosis was analyzed using real time cellular dynamic analysis (RTCA) and flow cytometry. The level of proteins related to ERS, endoplasmic reticulophagy, mitochondria-endoplasmic reticulum contact sites (MERCs), and mitochondrial apoptosis pathway were determined using Western blot analysis. Co-localization of ER and lysosomes were detected using ER and lysosomal fluorescence probes. A Ca2+ fluorescence probe was used to detect the level of Ca2+ in mitochondria. Results DTT treatment significantly inhibited cell proliferation and promoted apoptosis in hepatocytes. The levels of proteins related to ERS and endoplasmic reticulophagy, MERCs and the mitochondrial apoptosis pathway significantly increased in BRL-3A cells treated with DTT. DTT treatment decreased the ER-lysosome co-localization and enhanced the fluorescence intensity of Ca2+ in mitochondria. Conclusion DTT aggravates hepatocyte apoptosis by inhibiting FAM134B-mediated endoplasmic reticulophagy and enhancing the level of mitochondrial Ca2+.

Roles of C/EBP-homologous protein and histone H3 lysine 4 methylation in arsenic-induced mitochondrial apoptosis in hepatocytes.

C/EBP-homologous protein (CHOP) and histone H3 lysine 4 (H3K4) methylation have been verified to be correlated with apoptosis, whereas their biological function in arsenic-induced hepatocyte apoptosis through the mitochondrial pathway is still unclear. This study aimed to explore the specific regulatory mechanism of CHOP and H3K4me1/2 in arsenic-induced mitochondrial apoptosis in hepatocytes. Apoptosis and proliferation results showed arsenic promoted apoptosis and inhibited cell growth in BRL-3A cells. Meanwhile, arsenic treatment significantly upregulated the 78-kDa glucose-regulated protein (GRP78), CHOP, su(var)-3-9,enhancer-of-zeste,trithorax (SET) domain containing 7/9 (SET7/9), H3K4me1/2, BIM and BAX expression, while markedly downregulated lysine-specific histone demethylase 1 (LSD1) and BCL2 expression. After down-regulating CHOP, LSD1, and (su(var)-3-9,enhancer-of-zeste,trithorax) domain-containing protein 7/9 (SET7/9) in BRL-3A cells by siRNA, silencing CHOP and SET7/9 notably attenuated the pro-apoptotic and anti-proliferative effects of arsenic treatment on BRL-3A cells, which was reversed after inhibiting LSD1. In addition, our results suggested that knockdown of CHOP altered the expression of mitochondrial-associated proteins BCL2 and BIM, whereas knockdown of LSD1 and SET7/8 regulated the level of H3K4me1/2 modification and BAX protein. Coupled with chromatin immunoprecipitation results, we found that the level of CHOP in the promoter regions of BCL2 and BIM was significantly increased in BRL-3A cells exposed to 30 µmol/L NaAsO2 for 24 h, whereas the levels of H3K4me1/2 in the promoter regions of BAX were unchanged. Collectively, these data indicated that arsenic triggered the mitochondrial pathway to induce hepatocyte apoptosis by up-regulating the levels of CHOP and H3K4me1/2.

Changing Effects of Minimally Invasive Surgical Intervention on ALT, AST, and UA in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome.

Background: This study aims at exploring the effect of obstructive sleep apnea-hypopnea syndrome (OSAHS) on the liver and kidney function indexes of patients and analyze the changes in these indexes after minimally invasive surgery. Method: Patients with OSAHS (n = 51) who were diagnosed via polysomnography (PSG) and received minimally invasive surgery in the sleep disorders diagnosis and treatment center of the West China Fourth Hospital of Sichuan University from January 2017 to January 2019 were selected as test subjects and placed in the OSAHS group. At the same time, 79 healthy people with no snoring or breathing difficulties were selected from the medical examination center of the hospital as the control group (tested as normal by PSG). These two groups were used to compare the differences in the related indexes of serum liver and kidney function and evaluate the changes in sleep monitoring and related liver and kidney function indexes in patients with OSAHS after minimally invasive surgery. Results: The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and uric acid (UA) levels were higher in the OSAHS group (48.98 ± 36.34, 28.88 ± 14.80, and 422.30 ± 98.65, respectively) than in the control group (21.91 ± 11.61, 22.18 ± 6.19, and 330.49 ± 64.45 and t = 6.514, 3.549, and 6.373, respectively; p < 0.05). Of the patients with OSAHS, 17 were followed up for one year. After minimally invasive surgery, ALT decreased from 44.29 ± 20.61 to 26.47 ± 9.91 (t = 4.395), AST decreased from 27.71 ± 8.32 to 21.82 ± 4.81 (t = 3.673), and UA decreased from 397.35 ± 92.14 umol/L to 362.94 ± 106.76 umol/L (t = 2.580), and these differences were statistically significant (p < 0.05).The changes in ALT (r = -0.635) and AST (r = -0.504) were related to the difference in the lowest blood oxygen saturation (p < 0.05), and the change in UA was related to the difference in the apnea-hypopnea index (r = -0.532, p < 0.05). Conclusion: There are some abnormalities in liver- and kidney-function-related indexes in patients with OSAHS, and minimally invasive surgery can help to improve liver and kidney function in these patients.

Airway foreign body caused by pepper inhalation 7 years previously retrieved under conscious sedation with spontaneous respiration: a case report.

A 26-year-old man who had inhaled a dried pepper 7 years previously was admitted to our hospital for repeated coughing with yellow sputum and occasional hemoptysis. A thoracic high-resolution computed tomography scan revealed a foreign body at the proximal end of the right lower bronchus. We attempted to remove the foreign body by flexible bronchoscopy, but this was unsuccessful because the foreign body fell deeper into the bronchus. After a multidisciplinary team meeting, the foreign body was successfully extracted by bronchoscope suction and forceps under conscious sedation with spontaneous respiration. We avoided rigid bronchoscopy and traumatic surgery, thus decreasing the patient's risk and cost. We herein share our successful experience with this case.