Inspecting the "health poverty trap" mechanism: self-reinforcing effect and endogenous force.

INTRODUCTION: The term "health poverty trap" describes a vicious cycle in which developing countries or regions become trapped in low levels of health and poverty during the process of modernization. Although significant progress has been made in alleviating poverty in China, there is still a need to further enhance the living conditions of its impoverished population. METHODS: This research utilizes the data of the three national representative panel surveys from 2014 to 2020. The primary objective is to gain a better understanding of the intricate relationship between health and poverty. To examine the self-reinforcing effects of the cumulative cycle between health and poverty, we employ unconditional quantile regression analysis. RESULT: The low-income group exhibits lower overall health status compared to the average level. Economic constraints partially hinder the ability of low-income individuals to access healthcare resources, thereby reinforcing the cyclical relationship between health and poverty. Additionally, the unique psychological and behavioral preferences of individuals in health poverty act as indirect factors that further strengthen this cycle. Health poverty individuals can generate endogenous force to escape the "health poverty trap" by enhancing their confidence levels and digital literacy. CONCLUSIONS: The research examines the coexistence of health gradients and economic inequality among Chinese residents. Additionally, the study explores the endogenous force mechanism of escaping the health poverty trap from psychological and behavioral perspectives. This research also offers insights into optimizing government poverty alleviation programs to effectively address this issue.

Danxiaibacter flavus gen. nov., sp. nov., a novel bacterium of the family Chitinophagaceae isolated from forest soil on Danxia Mountain.

A Gram-stain-negative, aerobic, short rod-shaped, yellow bacterium, designated SYSU DXS3180T, was isolated from forest soil of Danxia Mountain in PR China. Growth occurred at 15-37 °C (optimum, 28-30 °C), pH 6.0-10.0 (optimum, pH 7.0-8.0) and with 0-2.0 % NaCl (optimum, 0-0.5 %, w/v). Strain SYSU DXS3180T was positive for hydrolysis of Tween 20, Tween 60, Tween 80 and starch, but negative for urease, H2S production, nitrate reduction, Tween 40 and gelatin. Phylogenetic analysis based on 16S rRNA gene and genome sequences showed that SYSU DXS3180T belonged to the family Chitinophagaceae. The closely related members were Foetidibacter luteolus YG09T (94.2 %), Limnovirga soli KCS-6T (93.9 %) and Filimonas endophytica SR 2-06T (93.7 %). The genome of strain SYSU DXS3180T was 7287640 bp with 5782 protein-coding genes, and the genomic DNA G+C content was 41.4 mol%. The main respiratory quinone was MK-7 and the major fatty acids (>10 %) were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The major polar lipids consisted of phosphatidylethanolamine, two unidentified aminolipids and two unidentified polar lipids. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain SYSU DXS3180T is proposed to represent a novel species of a novel genus named Danxiaibacter flavus gen. nov., sp. nov., within the family Chitinophagaceae. The type strain is SYSU DXS3180T (=KCTC 92895T=GDMCC 1.3825 T).

Rubellimicrobium arenae sp. nov., isolated from desert soil.

Two Gram-stain-negative strains, designated as SYSU D00286T and SYSU D00782, were isolated from a sand sample collected from the Kumtag Desert in Xinjiang, north-west China. Cells were aerobic, non-motile and positive for both oxidase and catalase. Growth occurred at 4-37 °C (optimum, 28-30 °C), pH 6.0-7.0 (optimum, pH 7.0) and NaCl concentration of 0-1.5 % (w/v; optimum, 0%). Growth was observed on Reasoner's 2A agar and nutrient agar, but not on Luria-Bertani agar and trypticase soy agar. The polar lipids were identified as diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, three unidentified aminolipids, one unidentified glycolipid and two unidentified phospholipids. The major respiratory quinone was ubiquinone-10 and the major fatty acids (>10 %) were C16 : 0 and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The 16S rRNA gene sequence similarity between strains SYSU D00286T and SYSU D00782 was 100%, and their average nucleotide identity (ANI), average amino acid identity and (AAI) digital DNA-DNA hybridization (dDDH) values were all 100.0 %. Phylogenetic analysis indicated that these two strains belong to the same species of the genus Rubellimicrobium and show the highest sequence similarity to Rubellimicrobium rubrum KCTC 72461T (98.2 %) and Rubellimicrobium roseum CCTCC AA 208029T (97.5 %). The ANI, AAI and dDDH values between SYSU D00286T (as well as SYSU D00782) and the other five Rubellimicrobium type strains were all less than or equal to 83.2, 80.1 and 23.6 %, respectively. Based on their phylogenetic, phenotypic and chemotaxonomical features, strains SYSU D00286T and SYSU D00782 represent a novel species of the genus Rubellimicrobium, for which the name Rubellimicrobium arenae sp. nov. is proposed. The type strain is SYSU D00286T (=MCCC 1K04981T=CGMCC 1.8626T=KCTC 82271T).

Aridibaculum aurantiacum gen. nov., sp. nov., isolated from the Kumtag Desert soil.

A novel orange-coloured bacterium, designated strain SYSU D00508T, was isolated from a sandy soil sampled from the Kumtag Desert in China. Strain SYSU D00508T was aerobic, Gram-stain-negative, oxidase-positive, catalase-positive and non-motile. Growth occurred at 4-45°C (optimum 28-30°C), pH 6.0-9.0 (optimum pH 7.0-8.0) and with 0-2.5 % NaCl (w/v, optimum 0-1.0 %). The major polar lipids consisted of phosphatidylethanolamine (PE), unidentified aminolipids (AL1-3) and unidentified polar lipids (L1-5) were also detected. The major respiratory quinone was MK-7 and the major fatty acids (>10 %) were iso-C17 : 0 3-OH, iso-C15 : 0 and iso-C15 : 1 G. The genomic DNA G+C content was 42.6 %. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D00508T belonged to the family Chitinophagaceae and showed 93.9 % (Segetibacter koreensis DSM18137T), 92.9 % (Segetibacter aerophilus NBRC 106135T), 93.0 % (Terrimonas soli JCM 32095T) and 92.8 % (Parasegetibacter terrae JCM 19942T) similarities. Based on the phylogenetic, phenotypic and chemotaxonomic data, strain SYSU D00508T is proposed to represent a novel species of a new genus, named Aridibaculum aurantiacum gen. nov., sp. nov., within the family Chitinophagaceae. The type strain is SYSU D00508T (=KCTC 82286T=CGMCC 1.18648T=MCCC 1K05005T).

Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis.

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown. Therefore, we further explored its possible mechanism. We subcutaneously injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)-/- (KO) mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated with hirudin in the presence of high glucose/lipopolysaccharides and ATP to measure the release of interleukin-18 and interleukin-1ß. Kidney injury induced by STZ injection was significantly ameliorated by hirudin through inhibiting Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury both in vivo and in vitro. We also found that hirudin regulated the expression of Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy to treat DN.

Contributions of Pharmaceuticals to DBP Formation and Developmental Toxicity in Chlorination of NOM-containing Source Water.

Pharmaceuticals have been considered a priority group of emerging micropollutants in source waters in recent years, while their role in the formation and toxicity of disinfection byproducts (DBPs) during chlorine disinfection remains largely unclear. In this study, the contributions of natural organic matter (NOM) and pharmaceuticals (a mixture of ten representative pharmaceuticals) to the overall DBP formation and toxicity during drinking water chlorination were investigated. By innovatively "normalizing" chlorine exposure and constructing a kinetic model, we were able to differentiate and evaluate the contributions of NOM and pharmaceuticals to the total organic halogen (TOX) formation for source waters that contained different levels of pharmaceuticals. It was found that at a chlorine contact time of 1.0 h, NOM (2 mg/L as C) and pharmaceuticals (total 0.0062-0.31 mg/L as C) contributed 79.8-99.5% and 0.5-20.2%, respectively, of TOX. The toxicity test results showed that the chlorination remarkably increased the toxicity of the pharmaceutical mixture by converting the parent compounds into more toxic pharmaceutical-derived DBPs, and these DBPs might contribute significantly to the overall developmental toxicity of chlorinated waters. This study highlights the non-negligible role of pharmaceuticals in the formation and toxicity of overall DBPs in chlorinated drinking water.

CMKLR1 Antagonist Alpha-NETA Protects against Diabetic Nephropathy in Mice.

INTRODUCTION: Diabetic nephropathy (DN) is a common complication in diabetic patients. Chemerin, a novel adipokine, has been associated with renal damage in DN. The chemerin chemokine-like receptor 1 (CMKLR1) has been reported to participate in DN. In this study, we aimed to investigate the effect of a CMKLR1 antagonist, 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA), on DN. METHODS: To induce diabetes, 8-week-old male C57BL/6J mice were given a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Diabetic mice were randomly assigned to receive daily doses of 0, 5, or 10 mg/kg α-NETA for 4 weeks. RESULTS: α-NETA dose-dependently induced body weight and reduced fasting blood glucose levels in STZ-induced diabetic mice. Furthermore, α-NETA significantly reduced the expressions of renal injury markers, including serum creatinine, kidney weight/body weight, urine volume, total proteins, and albumin in the urine, and increased creatinine clearance. Periodic acid-Schiff staining also indicated that α-NETA could effectively ameliorate renal injuries in DN mice. In addition, α-NETA inhibited renal inflammation and the expressions of chemerin and CMKLR1 in mice with DN. CONCLUSION: In summary, our findings suggested that α-NETA has beneficial effects on the management of DN. Specifically, α-NETA effectively ameliorated renal damage and inflammation in a dose-dependent manner in mice with DN. Thus, targeting the chemerin and CMKLR1 axis with α-NETA may be a promising therapeutic strategy for the treatment of DN.

Telluribacter roseus sp. nov., Isolated from the Kumtag Desert Soil.

A pink-pigmented bacterium, designated as strain SYSU D00476T, was isolated from sandy soil collected from the Kumtag Desert in China. Colonies were opaque, smooth and of a slight convexity with a clearly defined border. Cells were rod-shaped, Gram-stain-negative, catalase- and oxidase-positive. Growth occurred at 4-45 ℃ (optimum at 28-30 ℃), pH 6.0-8.0 (optimum at 7.0), and with 0-3.0% NaCl (w/v, optimum at 0-2.0%). Major fatty acids (> 10%) were C16:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), iso-C17:0 3-OH and iso-C15:0. Polar lipids comprised of three unidentified polar aminolipids (ALs), two unidentified aminophosphoglycolipids (APLs), one unidentified glycolipid (GL) and three unidentified phospholipids (PLs). The predominant respiratory quinone was MK-7. The genomic DNA G + C content was 50.5%. The low digital DNA-DNA hybridization (dDDH, 27.4%) and average nucleotide identity (ANI, 85%) values between strain SYSU D00476T and Telluribacter humicola KCTC 42819T indicated that SYSU D00476T represent a distinct species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D00476T belonged to the genus Telluribacter, showing 97.5% similarity with T. humicola KCTC 42819T. All these data support that strain SYSU D00476T represent a novel species of the genus Telluribacter within the family Spirosomataceae, named as Telluribacter roseus sp. nov. The type strain is SYSU D00476T (= KCTC 82285T = CGMCC 1.18647T = MCCC 1K04983T).

Longitalea arenae gen. nov., sp. nov. and Longitalea luteola sp. nov., two new members of the family Chitinophagaceae isolated from desert soil.

Two strains designated as SYSU D01084T and SYSU D00799T, were isolated from a sandy soil sample collected from Gurbantunggut Desert in Xinjiang, north-west China. Cells of both strains were Gram-stain-negative, strictly aerobic, long-rod-shaped, oxidase- and catalase-negative, motile or non-motile. Colonies were circular, translucent, convex, smooth and light-yellow in color on R2A agar. The two isolates were found to grow at 4-50 ºC, at pH 6.0-8.0 and with 0-1.0% (w/v) NaCl. Analysis of their 16S rRNA gene sequences indicated that they belonged to the family Chitinophagaceae, and closely related to the genera Paraflavitalea, Niastella, Pseudoflavitalea and Flavitalea. The two novel strains shared 98.1% 16S rRNA sequence similarity and represent different species on the basis of low average nucleotide identity (ANI, 83.8%) and digital DNA-DNA hybridization (dDDH, 51.4%) values. The genomic DNA G + C contents of strains SYSU D01084T and SYSU D00799T were 46.0 and 45.6%, respectively. Phylogenetic trees showed that the two isolates were clustered in an individual lineage and not grouped consistently into any specific genus. The polar lipids contained of phosphatidylethanolamine, four unidentified aminolipids, two unidentified aminoglycolipids, and three or four unidentified lipids. The predominant respiratory quinone was MK-7 and the major fatty acids (> 10%) were identified as iso-C15:0, iso-C17:0 3-OH, and iso-C15:1 G. Based on the combined phenotypic, genomic and phylogenetic analyses, the two strains represent two novel species of a new genus in the family Chitinophagaceae, for which the name Longitalea gen. nov. is proposed, comprising the type species Longitalea arenae sp. nov. (type strain SYSU D01084T = CGMCC 1.18641T = MCCC 1K05006T = KCTC 82283T) and Longitalea luteola sp. nov. (type strain SYSU D00799T = MCCC 1K04987T = KCTC 82282T = NBRC 114888T).

Sabulibacter ruber gen. nov., sp. nov., a novel bacterium in the family Hymenobacteraceae, isolated from desert soil.

A novel Gram-stain-negative, aerobic, oxidase-positive, catalase-positive, non-motile, short rod-shaped, red-pigmented strain, designated as SYSU D00434T, was isolated from a dry sandy soil sample collected from the Gurbantunggut desert in Xinjiang, north-west PR China. Strain SYSU D00434T was found to grow at 4-37 °C (optimum, 28-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-1.5 % (w/v) NaCl (optimum, 0-0.5 %). The predominant respiratory quinone was MK-7 and the major fatty acids (>10 %) were C16 : 1 ω5c, iso-C15 : 0, summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) and summed feature 4 (anteiso-C17 : 1 B and/or iso-C17 : 1 I). The polar lipids consisted of phosphatidylethanolamine, two unidentified polar lipids, two unidentified aminolipids, two unidentified phospholipids and two unidentified glycolipids. The genomic DNA G+C content of strain SYSU D00434T was 50.6 mol%. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SYSU D00434T belonged to the family Hymenobacteraceae, and shared a sequence similarity of less than 94.6 % to all validly named taxa. Based on the phenotypic, phylogenetic and chemotaxonomic properties, strain D00434T is proposed to represent a new species of a new genus, named Sabulibacter ruber gen. nov., sp. nov., within the family Hymenobacteraceae. The type strain is SYSU D00434T (=CGMCC 1.18624T=KCTC 82276T=MCCC 1K04975T).

Formation of Larger Molecular Weight Disinfection Byproducts from Acetaminophen in Chlorine Disinfection.

Acetaminophen is widely used to treat mild to moderate pain and to reduce fever. Under the worldwide COVID-19 pandemic, this over-the-counter pain reliever and fever reducer has been drastically consumed, which makes it even more abundant than ever in municipal wastewater and drinking water sources. Chlorine is the most widely used oxidant in drinking water disinfection, and chlorination generally causes the degradation of organic compounds, including acetaminophen. In this study, a new reaction pathway in the chlorination of acetaminophen, i.e., oxidative coupling reactions via acetaminophen radicals, was investigated both experimentally and computationally. Using an ultraperformance liquid chromatograph coupled to an electrospray ionization-triple quadrupole mass spectrometer, we detected over 20 polymeric products in chlorinated acetaminophen samples, some of which have structures similar to the legacy pollutants "polychlorinated biphenyls". Both C-C and C-O bonding products were found, and the corresponding bonding processes and kinetics were revealed by quantum chemical calculations. Based on the product confirmation and intrinsic reaction coordinate computations, a pathway for the formation of the polymeric products in the chlorination of acetaminophen was proposed. This study suggests that chlorination may cause not only degradation but also upgradation of a phenolic compound or contaminant.

Which Micropollutants in Water Environments Deserve More Attention Globally?

Increasing chemical pollution of aquatic environments is a growing concern with global relevance. A large number of organic chemicals are termed as "micropollutants" due to their low concentrations, and long-term exposure to micropollutants may pose considerable risks to aquatic organisms and human health. In recent decades, numerous treatment methods and technologies have been proposed to remove micropollutants in water, and typically several micropollutants were chosen as target pollutants to evaluate removal efficiencies. However, it is often unclear whether their toxicity and occurrence levels and frequencies enable them to contribute significantly to the overall chemical pollution in global aquatic environments. This review intends to answer an important lingering question: Which micropollutants or class of micropollutants deserve more attention globally and should be removed with higher priority? Different risk-based prioritization approaches were used to address this question. The risk quotient (RQ) method was found to be a feasible approach to prioritize micropollutants in a large scale due to its relatively simple assessment procedure and extensive use. A total of 83 prioritization case studies using the RQ method in the past decade were compiled, and 473 compounds that were selected by screening 3466 compounds of three broad classes (pharmaceuticals and personal care products (PPCPs), pesticides, and industrial chemicals) were found to have risks (RQ > 0.01). To determine the micropollutants of global importance, we propose an overall risk surrogate, that is, the weighted average risk quotient (WARQ). The WARQ integrates the risk intensity and frequency of micropollutants in global aquatic environments to achieve a more comprehensive priority determination. Through metadata analysis, we recommend a ranked list of 53 micropollutants, including 36 PPCPs (e.g., sulfamethoxazole and ibuprofen), seven pesticides (e.g., heptachlor and diazinon), and 10 industrial chemicals (e.g., perfluorooctanesulfonic acid and 4-nonylphenol) for risk management and remediation efforts. One caveat is that the ranked list of global importance does not consider transformation products of micropollutants (including disinfection byproducts) and new forms of pollutants (including antibiotic resistance genes and microplastics), and this list of global importance may not be directly applicable to a specific region or country. Also, it needs mentioning that there might be no best answer toward this question, and hopefully this review can act as a small step toward a better answer.

Multiscale Study of the Charge Transport Properties of Silicone Rubber Oligomers.

Polymer dielectrics are widely used as insulation in electronic and electrical equipment. The charge transport process in polymer dielectrics under a high electric field, which is considered to result in electrical aging and even breakdown of equipment insulation, has attracted considerable attention. Based on a localized charge transfer model, the charge transport mechanism for typical silicone rubber (SR) insulating materials was studied by multiscale methods. A model of silicone rubber oligomers under standard conditions was generated by classical molecular dynamics. The frontier molecular orbitals and projected density of states for the SR oligomer were obtained via quantum chemistry methods. The electronic coupling, reorganization energy, and free energy difference for both electron and hole transfer processes between adjacent SR molecules in the molecular dynamics model were calculated. Both hole transfer and electron transfer in SR conform to an intermolecular hopping mechanism due to their high intramolecular reorganization energy and low intermolecular electronic coupling. The results of normal mode analysis for reorganization energy indicate that the high-temperature approximation holds for charge transport in SR around or above room temperature. The charge transfer trajectory and charge mobility in SR were simulated based on kinetic Monte Carlo simulations. The hole and electron mobilities at room temperature were calculated to be 7.24 × 10-11 and 2.76 × 10-9 cm2/Vs, respectively, which agrees with the experimental data. Both electron transport and hole transport in SR show thermal activation characteristics, with corresponding activation energies of 358 and 314 meV, respectively. This work suggests a physical model to describe the charge transport process in SR polymer dielectrics.

How Much of the Total Organic Halogen and Developmental Toxicity of Chlorinated Drinking Water Might Be Attributed to Aromatic Halogenated DBPs?

Although >700 disinfection byproducts (DBPs) have been identified, >50% of the total organic halogen (TOX) in drinking water chlorination is unknown, and the DBPs responsible for the chlorination-associated health risks remain largely unclear. Recent studies have revealed numerous aromatic halo-DBPs, which generally present substantially higher developmental toxicity than aliphatic halo-DBPs. This raises a fascinating and important question: how much of the TOX and developmental toxicity of chlorinated drinking water can be attributed to aromatic halo-DBPs? In this study, an effective approach with ultraperformance liquid chromatography was developed to separate the DBP mixture (from chlorination of bromide-rich raw water) into aliphatic and aromatic fractions, which were then characterized for their TOX and developmental toxicity. For chlorine contact times of 0.25-72 h, aromatic fractions accounted for 49-67% of the TOX in the obtained aliphatic and aromatic fractions, which were equivalent to 26-36% of the TOX in the original chlorinated water samples. Aromatic halo-DBP fractions were more developmentally toxic than the corresponding aliphatic fractions, and the overall developmental toxicity of chlorinated water samples was dominated by aromatic halo-DBP fractions. This might be explained by the considerably higher potentials of aromatic halo-DBPs to bioconcentrate and then generate reactive oxygen species in the organism.

Silencing of peroxisome proliferator-activated receptor-alpha alleviates myocardial injury in diabetic cardiomyopathy by downregulating 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 expression.

Diabetic cardiomyopathy (DCM) is a cardiac disorder, which affects around 12% diabetic patients, resulting in overt heart death. Our initial bioinformatic analysis identified the differentially expressed gene 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (HMGCS2) in DCM, which may be activated by peroxisome proliferator-activated receptor-alpha (PPARα) based on previous evidence. Therefore, the present study aims to explore the effect of PPARα on the development of DCM through regulating HMGCS2. The expression of PPARα and HMGCS2 was detected by reverse transcription quantitative polymerase chain reaction in cardiomyocytes and high-glucose-cultured cardiomyocytes. The proliferation and apoptosis of cardiomyocytes were examined by 5-ethynyl-2'-deoxyuridine assay and flow cytometry, separately. Mitoehondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) levels were determined. Then, the protein levels of B-cell lymphoma 2, Bcl-2-associated X protein, and cleaved Caspase-3 were detected by Western blot analysis. The myocardial apoptosis index, heart weight, and serum lipids of rats were examined. At last, the expressions of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transforming growth factor ß1 (TGFß1), peroxisome proliferator activator receptor gamma coactivator-1 alpha (PGC1α), nuclear respiratory factor (NRF)-1, NRF-2, NAD(P)H oxidase 1, and superoxide dismutase-1 were examined. HMGCS2 was the most differentially expressed gene in DCM. The levels of HMGCS2 and PPARα were upregulated in patients with DCM. HMGCS2 silencing was shown to inhibit HMGCS2 expression to suppress the apoptosis of high-glucose-induced cardiomyocytes and the loss of MMP, reduce the accumulation of ROS, and promote cardiomyocyte proliferation. Silencing of HMGCS2 and PPARα alleviated myocardial injury, decreased blood glucose, and lipid in DCM rats, downregulated the expression of ANP, BNP, and TGFß1 to reduce myocardial injury, and elevated PGC1α, NRF-1, and NRF-2 levels to enhance oxidative stress levels. Our results demonstrated that silencing of PPARα could alleviate cardiomyocyte injury and oxidative stress via a mechanism related to the downregulation of HMGCS2, which could provide a novel target for DCM treatment.

LncRNA TTN-AS1/miR-134-5p/PAK3 axis regulates the radiosensitivity of human large intestine cancer cells through the P21 pathway and AKT/GSK-3ß/ß-catenin pathway.

Radiotherapy is an important adjuvant treatment for large intestine cancer even though it does not cause any response in many patients. The present study aimed to investigate the effects of the TTN antisense RNA 1 (TTN-AS1) long noncoding RNA (lncRNA) on radiotherapy dynamics of large intestine cancer cells and to explore the underlying molecular mechanisms. TTN-AS1 expression was evaluated by reverse-transcription quantitative polymerase chain reaction, western blot, and cellular immunofluorescence, and flow cytometry analysis was used to measure apoptosis. Radiotherapy was simulated in vitro by exposing cancer cells to X-ray. TTN-AS1 was highly expressed in large intestine cancer cells after an X-ray exposition for 24 hr. TTN-AS1 knockdown improved the radiosensitivity of large intestine cancer cells and promoted apoptosis by increasing Bax/Bcl2 protein expression and the active-caspase 3/caspase 3 ratios following X-ray treatment. In addition, TTN-AS1 negatively regulated miR-134-5p expression, and miR-134-5p-mimic transfection decreased PAK3 protein expression in large intestine cancer cells. Importantly, TTN-AS1 promoted PAK3 and P21 protein expression in HT29 cells after X-ray treatment. Moreover, the knockdown of P21 protein expression improved radiosensitivity and promoted X-ray-induced apoptosis of HT29 cells. Finally, PAK3 knockdown expression decreased the p-AKT/AKT and p-GSK-3ß/GSK-3ß ratios and promoted the ß-catenin transfer from the nucleus to the cytoplasm. These data suggest that the TTN-AS1 lncRNA promoted resistance to radiotherapy of large intestine cancer cells by increasing PAK3 expression via miR-134-5p inhibition, and this may be related to the P21 and AKT/GSK-3ß/ß-catenin pathway.

Nonhalogenated Aromatic DBPs in Drinking Water Chlorination: A Gap between NOM and Halogenated Aromatic DBPs.

Halogenated disinfection byproducts (DBPs) are generated via reactions with natural organic matter (NOM) in chlorine disinfection of drinking water. How large NOM molecules are converted to halogenated aliphatic DBPs during chlorination remains a fascinating yet largely unresolved issue. Recently, many relatively toxic halogenated aromatic DBPs have been identified in chlorinated drinking waters, and they behave as intermediate DBPs to decompose to halogenated aliphatic DBPs. There is still one gap between NOM and halogenated aromatic DBPs. In this study, nine nonhalogenated aromatic compounds were identified as new intermediate DBPs in chlorination, including 4-hydroxybenzaldehyde, 4-hydroxybenzoic acid, 3-formyl-4-hydroxybenzoic acid, salicylic acid, 5-formyl-2-hydroxybenzoic acid, 4-hydroxyphthalic acid, 4'-hydroxyacetophenone, 4-methylbenzoic acid, and 4-hydroxy-3-methylbenzaldehyde. These nonhalogenated aromatic DBPs formed quickly and reached the maximum levels at relatively low chlorine doses within a short contact time, and their formation pathways were proposed. The formation kinetics of three nonhalogenated aromatic DBPs and their corresponding monochloro-/dichloro-substitutes during chlorination were then modeled. The nonhalogenated aromatic DBPs contributed up to 84% of the formed monochloro-substitutes and 22% of the formed dichloro-substitutes, demonstrating that they somewhat acted as intermediates between NOM and halogenated aromatic DBPs. Furthermore, the formed nonhalogenated aromatic DBPs were found to be removed by >50% by granular activated carbon adsorption.

Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations.

The aminotransferase from Bacillus circulans (BtrR), which is involved in the biosynthesis of butirosin, catalyzes the pyridoxal phosphate (PLP)-dependent transamination reaction to convert valienone to ß-valienamine (a new ß-glycosidase inhibitor for the treatment of lysosomal storage diseases) with an optical purity enantiomeric excess value. To explore the stereoselective mechanism of valienamine generated by BtrR, multiple molecular dynamics (MD) simulations were performed for the BtrR/PLP/valienamine and BtrR/PLP/ß-valienamine complexes. The theoretical results showed that ß-valienamine could make BtrR more stable and dense than valienamine. ß-valienamine could increase the hydrogen bond probability and decrease the binding free energy between coenzyme PLP and BtrR by regulating the protein structure of BtrR, which was conducive to the catalytic reaction. ß-valienamine maintained the formation of cation-p interactions between basic and aromatic amino acids in BtrR, thus enhancing its stability and catalytic activity. In addition, CAVER 3.0 analysis revealed that ß-valienamine could make the tunnel of BtrR wider and straight, which was propitious to the removal of products from BtrR. Steered MD simulation results showed that valienamine interacted with more residues in the tunnel during dissociation compared with ß-valienamine, resulting in the need for a stronger force to be acquired from BtrR. Taken together, BtrR was more inclined to catalyze the substrates to form ß-valienamine, either from the point of view of the catalytic reaction or product removal.

ERp44 depletion exacerbates ER stress and aggravates diabetic nephropathy in db/db mice.

Diabetic nephropathy (DN) is a major complication of diabetes, and the dysfunction of endoplasmic reticulum (ER) plays an important role in its pathogenesis. ERp44, an ER resident chaperone protein, has been implicated in the modulation of ER stress, however, its role and mechanism in DN are not determined. Here, we show that ERp44 expression is upregulated in the glomeruli of db/db mice, a rodent model of type 2 diabetes. When ERp44 is depleted by in vivo shRNA-mediated knockdown, the features associated with DN including albuminuria level and glomerular basement membrane (GBM) thickness are aggravated, therefore suggesting a detrimental role of ERp44 depletion in DN progression. We further show that ERp44 depletion exacerbates ER stress in DN in db/db mice, and that attenuating ER stress with the chemical chaperone TUDCA remarkably diminishes the aggravated DN features caused by ERp44 depletion. These results suggest that the exacerbated ER stress is a critical factor for the detrimental effect of ERp44 depletion on DN progression in db/db mice. Thus, our study links the role of ERp44 in DN with ER stress regulation and may offer a potential therapeutic strategy to interfere DN progression.

Evaluating the Comparative Toxicity of DBP Mixtures from Different Disinfection Scenarios: A New Approach by Combining Freeze-Drying or Rotoevaporation with a Marine Polychaete Bioassay.

The unintended formation of disinfection byproducts (DBPs) may compromise the safety of drinking water. Since no specified DBPs have been found to be responsible for the overall adverse effects and over half of total organic halogen (TOX) remains unidentified, DBP mixture toxicity is gaining increasing interest as a potential indicator of how risky drinking water might be. In this study, a new approach to evaluating the toxicity of drinking water DBP mixtures was developed by combining freeze-drying or rotoevaporation pretreatment with an in vivo high-salinity-tolerance bioassay with the embryos of a marine polychaete Platynereis dumerilii. The DBP recoveries by freeze-drying or rotoevaporation were compared with those by commonly applied liquid-liquid-extraction (LLE). For drinking water subjected to typical disinfection processes (i.e., chlorination, chloramination, chlorine dioxide treatment, and ozonation with or without postchlorination), LLE led to the lowest TOX recovery (11-18%) and the loss of all inorganic DBPs, while freeze-drying and rotoevaporation recovered 28-58% and 35-61% of TOX, respectively, and effectively recovered 81-99% and 85-104% of inorganic DBPs, respectively. Thus, LLE caused an underestimation of the toxicity of DBP mixtures compared with freeze-drying and rotoevaporation. Besides, the comparative toxicity varied significantly for water samples pretreated with different methods due to the effect of inorganic DBPs and a synergistic effect of organic and inorganic DBPs. The new approach revealed that the bromide-rich source water disinfected with ozone caused the highest developmental toxicity, followed by those disinfected with chlorine, chlorine dioxide, and chloramine in that order.