Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

Breaking the poverty trap in an ecologically fragile region through ecological engineering: A close-up look at long-term changes in ecosystem services.

Ecological vulnerability and poverty are interrelated and must be addressed together. The resolution of this issue will help us to meet the challenges during the process of implementing concrete actions for realizing the 2030 UN sustainable development goals (SDGs). Ecological restoration projects (ERPs) can enhance ecosystem services (ESs) while providing policy support for improving people's livelihoods. However, processes and mechanisms of ERPs on the ecological environment and socioeconomic development in poverty-stricken and ecologically fragile areas have rarely been studied. To address these issues, we conducted a comparative analysis on the changes of land use and land cover (LULC), ecosystem services (ESs), and socioeconomic development in Bijie City, a karst rocky desertification area in southwest China, before and after the implementation of ERPs in 2000, as well as the complex relationship between these factors. ERPs have affected LULCs, ESs, socioeconomics, and poverty reduction significantly since 2000. Specifically, the total ecosystem service value (ESV) in the study area has increased by more than 3 times in the past 30 years, with the ESV of tourism services and carbon storage increasing the most, from CNY 0.001 and 337.07 billion in 1990 to CNY 11.07 and 108.97 billion in 2019, respectively. The correlation between ESs is mainly synergistic, while the tradeoff between carbon storage and water yield is in a fluctuating upward trend. LULC conversion of cropland to green, and cropland to water, wetland and shrubs has positive effects on carbon storage and water yield, respectively. During study period, GDP, urbanization increased by over 70 times, 5 times, respectively, whereas poverty population, poverty incidence, and employment rate of various sectors (i.e., agriculture, forest, animal, and fishery, or AFAF) decreased by 96.4%, 97.7%, and 18.24%, respectively. Our findings emphasized that ERPs can effectively help poor and ecologically fragile areas to get out of the poverty trap and achieve the "win-win" goals of ecological and socio-economic sustainable development. These results have profound environmental management references to China and other developing countries around the world in realizing ecological restoration, poverty reduction, and the SDGs.

Salidroside Mediated the Nrf2/GPX4 Pathway to Attenuates Ferroptosis in Parkinson's Disease.

Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons, with ferroptosis playing a significant role. Salidroside (SAL) has shown neuroprotective potential, this study aims to explore its capacity to mitigate ferroptosis in PD, focusing on the modulation of the Nuclear Factor E2-Related Factor 2 (Nrf2)/ Glutathione Peroxidase 4 (GPX4) pathway. Male C57BL/6 mice were subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like symptoms, followed by SAL and Nrf2 inhibitor administration. Then behavioral tests, immunohistochemical staining, transmission electron microscopy, and Western blot analysis were conducted to assess motor functions, pathological changes, ferroptosis, and related protein expressions. In vitro, SH-SY5Y cells were treated with erastin to induce ferroptosis to assess the protective effects of SAL. Additionally, A53T-α-synuclein (α-syn) was used to stimulate the PD model, SAL and a Nrf2 inhibitor (ML385) was utilized to elucidate the role of the Nrf2/GPX4 pathway in mitigating ferroptosis in PD. In vivo, SAL significantly improved motor functions and reduced the expression of α-syn, while increasing tyrosine hydroxylase (TH) expression of PD mice. Additionally, SAL treatment notably enhanced the levels of antioxidants and reduced MDA and iron content in the substantia nigra of PD mice. In vitro, SAL treatment increased the TH, GPX4, Nrf2 expression, and mitochondrial membrane potential whereas alleviated ferroptosis through the Nrf2/GPX4 pathway, as evidenced in erastin-induced and α-syn overexpressing SH-SY5Y cells. While these effects were reversed upon Nrf2 inhibition. SAL demonstrates significant potential in mitigating PD pathology and ferroptosis, positioning the Nrf2/GPX4 pathway as a promising therapeutic target. However, future studies should focus on the long-term effects of SAL, its pharmacokinetics, addressing the multifactorial nature of PD pathogenesis.

The Interaction Mechanism of Picolinamide Fungicide Targeting on the Cytochrome bc1 Complex and Its Structural Modification.

Picolinamide fungicides, structurally related to UK-2A and antimycin-A, bind into the Qi-site in the bc1 complex. However, the detailed binding mode of picolinamide fungicides remains unknown. In the present study, antimycin-A and UK-2A were selected to study the binding mode of picolinamide inhibitors with four protonation states in the Qi-site by integrating molecular dynamics simulation, molecular docking, and molecular mechanics Generalized Born surface area (MM/GBSA) calculations. Subsequently, a series of new picolinamide derivatives were designed and synthesized to further understand the effects of substituents on the tail phenyl ring. The computational results indicated that the substituted aromatic rings in antimycin-A and UK-2A were the pharmacophore fragments and made the primary contribution when bound to a protein. Compound 9g-hydrolysis formed H-bonds with Hie201 and Ash228 and showed an IC50 value of 6.05 ± 0.24 µM against the porcine bc1 complex. Compound 9c, with a simpler chemical structure, showed higher control effects than florylpicoxamid against cucumber downy mildew and expanded the fungicidal spectrum of picolinamide fungicides. The structural and mechanistic insights obtained from the present study will provide a valuable clue for the future designing of new promising Qi-site inhibitors.

Alternative Splicing Reveals Acute Stress Response of Litopenaeus vannamei at High Alkalinity.

Alkalinity is regarded as one of the primary stressors for aquatic animals in saline-alkaline water. Alternative splicing (AS) can significantly increase the diversity of transcripts and play key roles in stress response; however, the studies on AS under alkalinity stress of crustaceans are still limited. In the present study, we devoted ourselves to the study of AS under acute alkalinity stress at control (50 mg/L) and treatment groups (350 mg/L) by RNA-seq in pacific white shrimp (Litopenaeus vannamei). We identified a total of 10,556 AS events from 4865 genes and 619 differential AS (DAS) events from 519 DAS genes in pacific white shrimp. Functional annotation showed that the DAS genes primarily involved in spliceosome. Five splicing factors (SFs), U2AF1, PUF60, CHERP, SR140 and SRSF2 were significantly up-regulated and promoted AS. Furthermore, alkalinity activated the Leukocyte transendothelial migration, mTOR signaling pathway and AMPK signaling pathway, which regulated MAPK1, EIF3B and IGFP-RP1 associated with these pathways. We also studied three SFs (HSFP1, SRSF2 and NHE-RF1), which underwent AS to form different transcript isoforms. The above results demonstrated that AS was a regulatory mechanism in pacific white shrimp in response to acute alkalinity stress. SFs played vital roles in AS of pacific white shrimp, such as HSFP1, SRSF2 and NHE-RF1. DAS genes were significantly modified in immunity of pacific white shrimp to cope with alkalinity stress. This is the first study on the response of AS to acute alkalinity stress, which provided scientific basis for AS mechanism of crustaceans response to alkalinity stress.

Comparison of the efficacy of different frequency electroacupuncture in the treatment of polycystic ovary syndrome patients with abdominal obesity. / ä¸åŒé¢‘çŽ‡ç”µé’ˆæ²»ç–—è ¹éƒ¨è‚¥èƒ–åž‹å¤šå›Šåµå·¢ç»¼åˆå¾çš„ç–—æ•ˆæ¯”è¾ƒ.

OBJECTIVES: To compare the effects of 2 Hz continuous wave and 2 Hz/100 Hz dilatational wave setting in electroacupuncture(EA) on ovulation frequency, hormone levels, body fat parameters, quality of life and depression-anxiety level in polycystic ovary syndrome (PCOS) patients with abdominal obesity. METHODS: PCOS patients with abdominal obesity were randomly divided into low-frequency group (n=29) and dilatational wave group (n=29). Patients in both groups were treated with "Tongtiaodaimai" (regulating Dai Meridian) acupuncture therapy, and EA was applied to bilateral Daimai (GB26), Tianshu (ST25), Shenshu (BL23) and Ciliao (BL32). The low-frequency group received EA using a continuous wave at a frequency of 2 Hz, while the dilatational wave group received dilatational wave at a frequency of 2 Hz/100 Hz. Both groups received treatment for 30 min each time, 3 times per week for 12 consecutive weeks. Ovulation frequency was calculated according to the ovulation cycle. The contents of serum anti-Mullerian hormone (AMH) and sex hormone binding globulin (SHBG) were detected with electrochemiluminescence method. Body weight (BW) and waist circumference (WC) were measured, and body mass index (BMI) and waist-height ratio (WHtR) were calculated. PCOS questionnaire (Chi-PCOSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. RESULTS: Compared with before treatment, both the low-frequency group and the dilatational wave group showed an increase in ovulation frequency (P<0.01, P<0.05), and a decrease in BW, BMI, WC, WHtR, and SDS score (P<0.01, P<0.05)；the dilatational wave group showed decreased serum AMH contents (P<0.05) and increased serum SHBG contents (P<0.05), the scores related to acne, fatigue, and dysmenorrhea in the Chi-PCOSQ increased (P<0.01, P<0.05). Compared with the low-frequency group, the dilatational wave group showed a reduction (P<0.05) in WC after treatment. CONCLUSIONS: 2 Hz/100 Hz dilatational wave EA is equally effective as 2 Hz low-frequency EA in improving ovulation frequency. In terms of reducing WC in abdominal obesity type PCOS patients, 2 Hz/100 Hz dilatational wave EA is superior to 2 Hz low-frequency EA. 2 Hz/100 Hz dilatational wave EA can decrease serum AMH, increase serum SHBG, and improve symptoms of acne, fatigue, and dysmenorrhea.

Structure-Based Discovery of New Succinate Dehydrogenase Inhibitors via Scaffold Hopping Strategy.

Scaffold hopping strategy has become one of the most successful methods in the process of molecular design. Seeking to develop novel succinate dehydrogenase inhibitors (SDHIs), we employed a scaffold hopping strategy to design compounds featuring geminate dichloralkenes (gem-dichloralkenes) fragment. After stepwise modifications, a series of N-cyclopropyl-dichloralkenes-pyrazole-carboxamide derivatives was synthesized. Among them, compounds G28 (IC50 = 26.00 nM) and G40 (IC50 = 27.00 nM) were identified as the best inhibitory activity against porcine SDH, with IC50 values reaching the nanomolar range, outperforming the lead compound pydiflumetofen. Additionally, the greenhouse assay indicated that compounds G37 (EC90 = 0.031 mg/L) and G34 (EC90 = 1.67 mg/L) displayed extremely high activities against wheat powdery mildew (WPM) and cucumber powdery mildew (CPM), respectively. Computational results further revealed that the gem-dichloralkene fragment and fluorine substituted pyrazole form an extra hydrophobic interaction and dipolar-dipolar interaction with SDH. In summary, our study provides a novel gem-dichloralkene scaffold with outstanding fungicidal properties, obtained through scaffold hopping, that holds great potential for future research on PM control.

Mitochondrial RNA m3C methyltransferase METTL8 relies on an isoform-specific N-terminal extension and modifies multiple heterogenous tRNAs.

Methyltransferase-like 8 (METTL8) encodes a mitochondria-localized METTL8-Iso1 and a nucleolus-distributed METTL8-Iso4 isoform, which differ only in their N-terminal extension (N-extension), by mRNA alternative splicing. METTL8-Iso1 generates 3-methylcytidine at position 32 (m3C32) of mitochondrial tRNAThr and tRNASer(UCN). Whether METTL8-Iso4 is an active m3C32 methyltransferase and the role of the N-extension in mitochondrial tRNA m3C32 formation remain unclear. Here, we revealed that METTL8-Iso4 was inactive in m3C32 generation due to the lack of N-extension, which contains several absolutely conserved modification-critical residues; the counterparts were likewise essential in cytoplasmic m3C32 biogenesis by methyltransferase-like 2A (METTL2A) or budding yeasts tRNA N3-methylcytidine methyltransferase (Trm140), in vitro and in vivo. Cross-compartment/species tRNA modification assays unexpectedly found that METTL8-Iso1 efficiently introduced m3C32 to several cytoplasmic or even bacterial tRNAs in vitro. m3C32 did not influence tRNAThrN6-threonylcarbamoyladenosine (t6A) modification or aminoacylation. In addition to its interaction with mitochondrial seryl-tRNA synthetase (SARS2), we further discovered an interaction between mitochondrial threonyl-tRNA synthetase (TARS2) and METTL8-Iso1. METTL8-Iso1 substantially stimulated the aminoacylation activities of SARS2 and TARS2 in vitro, suggesting a functional connection between mitochondrial tRNA modification and charging. Altogether, our results deepen the mechanistic insights into mitochondrial m3C32 biogenesis and provide a valuable route to prepare cytoplasmic/bacterial tRNAs with only a m3C32 moiety, aiding in future efforts to investigate its effects on tRNA structure and function.

Effects of Inner-Row Ground Management on the Volatomics of 'Cabernet Sauvignon' Grapes and Wines in the Region of the Eastern Foothills of the Ningxia Helan Mountains in Northwest China.

This two-consecutive-year study aimed to evaluate the effects of ground management methods on the volatomics of 'Cabernet Sauvignon' grapes and wines in Northwest China, in which inner-row crop covering with purslane (GRASS) and mulching with black plastic film (FILM) treatments were carried out, respectively. Compared with clean tillage (CK), the GRASS and FILM treatments changed the microclimates of grapevine fruit zones and rhizospheres, which delayed the ripening of grape berries and affected the accumulation of aroma substances in the mature grapes effectively. GRASS increased the concentration of terpenes and C13-norisoprenoids in berries and gave more floral, fruity, and caramel fragrances to wines, while FILM had the opposite effect of significantly increasing the synthesis of C6/C9 compounds and brought more green leaf flavors, showing that inner-row purslane covering is a potential and stable viticultural practice to improve the wine quality in this booming wine region.

Sequencing trait-associated mutations to clone wheat rust-resistance gene YrNAM.

Stripe (yellow) rust, caused by Puccinia striiformis f. sp. tritici (Pst), can significantly affect wheat production. Cloning resistance genes is critical for efficient and effective breeding of stripe rust resistant wheat cultivars. One resistance gene (Yr10CG) underlying the Pst resistance locus Yr10 has been cloned. However, following haplotype and linkage analyses indicate the presence of additional Pst resistance gene(s) underlying/near Yr10 locus. Here, we report the cloning of the Pst resistance gene YrNAM in this region using the method of sequencing trait-associated mutations (STAM). YrNAM encodes a non-canonical resistance protein with a NAM domain and a ZnF-BED domain. We show that both domains are required for resistance. Transgenic wheat harboring YrNAM gene driven by its endogenous promoter confers resistance to stripe rust races CYR32 and CYR33. YrNAM is an ancient gene and present in wild wheat species Aegilops longissima and Ae. sharonensis; however, it is absent in most wheat cultivars, which indicates its breeding value.

Crucial Role of the Ca2+/CN Signaling Pathway in the Antifungal Activity of Seselin against Botrytis cinerea.

Botrytis cinerea causes gray mold in many fruit and vegetable crops. We previously found that Seselin (SL) displayed antifungal activity against B. cinerea (EC50 = 6.1 µg·mL-1), and this study investigated the effects of Ca2+ and the Ca2+/CN signaling pathway on its antifungal activity against B. cinerea. The results indicated that exogenous Ca2+, Cyclosporine A, and Verapamil reduced the sensitivity of SL against B. cinerea; SL significantly reduced the intracellular Ca2+ concentration in the hyphae; the sensitivity of strains ΔbcCCH1 and ΔbcMID1 to SL were significantly increased; and the expressions of CCH1, MID1, CNA, PMC1, and PMR1 genes of the Ca2+/CN signaling pathway were significantly downregulated by SL treatment. Hence, SL is a potential compound for developing fungicides against B. cinerea. SL dramatically reduces intracellular Ca2+ concentration and disturbs Ca2+ homeostasis, leading to cell death. The Ca2+/CN signaling pathway plays an important role in the antifungal activity of SL against B. cinerea.

Flexible Self-Powered Friction Piezoelectric Sensor Based on Structured PVDF-Based Composite Nanofiber Membranes.

With the rapid development of the economy and technology, intelligent wearable devices have gradually entered public life. Flexible sensors, as the main component of wearable devices, have been widely concerned. However, traditional flexible sensors need an external power supply, lacking flexibility and sustainable power supply. In this study, structured poly(vinylidene fluoride) (PVDF)-based composite nanofiber membranes doped with different mass fractions of MXene and zinc oxide (ZnO) were prepared by electrospinning and were then assembled to flexible self-powered friction piezoelectric sensors. The addition of MXene and ZnO endowed PVDF nanofiber membranes with better piezoelectric properties. The structured PVDF/MXene-PVDF/ZnO (PM/PZ) nanofiber membranes with a double-layer structure, interpenetrating structure, or core-shell structure could further enhance the piezoelectric properties of PVDF-based nanofiber membranes through the synergistic effects of filler doping and structural design. In particular, the output voltage of the self-powered friction piezoelectric sensor made of a core-shell PM/PZ nanofiber membrane showed a good linear relationship with the applied pressure and could produce a good piezoelectric response to the bending deformation caused by human motion.

Assessment of Auricularia cornea var. Li. polysaccharides potential to improve hepatic, antioxidation and intestinal microecology in rats with non-alcoholic fatty liver disease.

Non-alcoholic fatty acid liver disease (NAFLD) is a reputed global health concern, affecting children and young adults. Accumulating evidence suggests that edible fungi polysaccharides have the potential to relieve NAFLD. Our previous study found that Auricularia cornea var. Li. polysaccharides (ACP) could improve immune by regulating gut microbiota. However, its NAFLD-alleviating potentials have been scarcely reported. This study analyzed the protective effects of Auricularia cornea var. Li. polysaccharides on high-fat diet (HFD)-induced NAFLD and mechanistic actions. We first analyzed the histology and hepatic lipid profile of animals to evaluate this variant's ameliorating effects on NAFLD. Then, antioxidant and anti-inflammatory potentials of ACP were studied. Finally, we explored changes in the gut microbiome diversity for mechanistic insights from the gut-liver region. Results showed that supplementation with ACP substantially reduced homeostasis model assessment-insulin resistance (HOMA-IR), body fat, liver index rates and weight gain (p < 0.05). This variant also improved HDL-C levels while decreasing triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels which were initially triggered by HFD. ACP mediation also decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels considerably with H&E technique indicating that it can reduce liver lipid accumulation, thus lowering liver damages risks (p < 0.05). The antioxidant potentials of ACP were also demonstrated as it decreased the hepatic levels of malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). Proinflammatory markers like IL-6, IL-1ß and TNF-α concentrations were decreased by ACP supplementation, accompanied with increased IL-4 levels. Finally, ACP supplementation regulated the intestinal microbiota to near normal patterns. In all, ACP protects HFD-induced NAFLD by improving liver characteristics and regulating colonic flora composition, our findings assert that ACP can be a promising strategy in NAFLD therapy.

Green-Solvent-Processable Composite Micro/Nanofiber Membrane with Gradient Asymmetric Structure for Efficient Microfiltration.

Electrospinning technology has attracted extensive attention in recent decades and is widely used to prepare nanofiber membranes from hundreds of polymers. Polyvinyl formal acetal (PVFA), as a polymer with excellent properties such as high strength and heat resistance, is not reported on the electrospun water treatment membrane. In this paper, the preparation process of electrospun PVFA nanofiber membrane is optimized, and the effect of sodium chloride (NaCl) addition on the physical and mechanical properties and microfiltration performance of nanofiber membrane is also explored. And the hydrophobic PVFA nanofiber filter layer is then combined with a hydrophilic nonwoven support layer to construct a composite micro/nanofiber membrane with a pore-size gradient structure and a hydrophilic/hydrophobic asymmetric structure. Finally, unidirectional water transport and water treatment performance are further investigated. The results show that the tensile breaking strength of the composite membrane can reach up to 37.8 MPa, the retention rate for particles with the size of 0.1-0.3 µm is 99.7%, and the water flux is 513.4 L m-2 h-1 under the hydrostatic pressure. Moreover, it still has a retention of more than 98% after three repeated uses. Therefore, the electrospun PVFA composite membrane has a great potential in microfiltration.

Research Progress of Water Treatment Technology Based on Nanofiber Membranes.

In the field of water purification, membrane separation technology plays a significant role. Electrospinning has emerged as a primary method to produce nanofiber membranes due to its straightforward, low cost, functional diversity, and process controllability. It is possible to flexibly control the structural characteristics of electrospun nanofiber membranes as well as carry out various membrane material combinations to make full use of their various properties, including high porosity, high selectivity, and microporous permeability to obtain high-performance water treatment membranes. These water separation membranes can satisfy the fast and efficient purification requirements in different water purification applications due to their high filtration efficiency. The current research on water treatment membranes is still focused on creating high-permeability membranes with outstanding selectivity, remarkable antifouling performance, superior physical and chemical performance, and long-term stability. This paper reviewed the preparation methods and properties of electrospun nanofiber membranes for water treatment in various fields, including microfiltration, ultrafiltration, nanofiltration, reverse osmosis, forward osmosis, and other special applications. Lastly, various antifouling technologies and research progress of water treatment membranes were discussed, and the future development direction of electrospun nanofiber membranes for water treatment was also presented.

Electrospun PVDF-based piezoelectric nanofibers: materials, structures, and applications.

Polyvinylidene fluoride (PVDF) has been considered as a promising piezoelectric material for advanced sensing and energy storage systems because of its high dielectric constant and good electroactive response. Electrospinning is a straightforward, low cost, and scalable technology that can be used to create PVDF-based nanofibers with outstanding piezoelectric characteristics. Herein, we summarize the state-of-the-art progress on the use of filler doping and structural design to enhance the output performance of electrospun PVDF-based piezoelectric fiber films. We divide the fillers into single filler and double fillers and make comments on the effects of various dopant materials on the performance and the underlying mechanism of the PVDF-based piezoelectric fiber film. The effects of highly oriented structures, core-shell structures, and multilayer composite structures on the output properties of PVDF-based piezoelectric nanofibers are discussed in detail. Furthermore, the perspectives and opportunities for PVDF piezoelectric nanofibers in the fields of health care, environmental monitoring, and energy collection are also discussed.

Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration.

Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible mechanisms behind these effects. A549 cells were treated with TGF-[Formula: see text]1 and TFA to observe the potential effects of TFA on regulating alveolar epithelial cell proliferation, TGF-[Formula: see text]1-induced EMT, and the underlying mechanisms in vitro. Then, mouse pulmonary fibrosis was induced with a single intra-tracheal injection of bleomycin, and TFA was administrated by i.p. injection. Lung fibrosis was evaluated through histological and molecular analyses, and the possible mechanisms were explored using immunological methods. The results demonstrated that TFA could promote cell proliferation but inhibit TGF-[Formula: see text]1-induced EMT on A549 cells. TFA attenuated BLM-induced pulmonary fibrosis in mice by modulating inflammatory infiltration and M2 macrophage polarization; it furthermore modulated EMT through regulating the TGF-[Formula: see text]1/Smad pathway. In addition, TFA augmented the expression of the Wnt7b protein, which plays an important role in alveolar epithelium reparation. In conclusion, TFA alleviated bleomycin-induced mouse lung fibrosis by preventing the fibrotic response and increasing epithelium regeneration.

α-Klotho: An Early Risk-Predictive Biomarker for Acute Kidney Injury in Patients with Acute Myocardial Infarction.

Background: Acute kidney injury (AKI) was a common and serious complication in patients with acute myocardial infarction (AMI). Novel biomarkers and therapies were deficient and imperative for AKI's early diagnosis and therapy after AMI. α-Klotho was considered as an early biomarker and potential therapy for AKI recently. Previous studies reported that the expression of α-Klotho was decreased in AKI rodents, and supplement of α-Klotho alleviated kidney injury. Nevertheless, its effect has not been studied in patients presenting with AMI. Methods: A total of 155 consecutive diagnosed with AMI at emergency department whose eGFR >60 ml/min ∗ 1.73 m2 were enrolled in this prospective observational cohort study which conducted between May 2016 and April 2019 in Peking University People's Hospital. AKI was defined according to the KDIGO criteria in 2012. At admission, the clinical data of patients were collected and serum α-Klotho was tested by ELISA. The relationship between α-Klotho, serum creatinine, eGFR, systolic pressure, BNP, LVEF, and Hgb of AKI were analyzed and their discrimination performances were compared. The association variables were calculated (adjusted odds ratio) with a confidence interval (CI) of 95% by binary logistic regression. And, we followed up the incidence of CKD and rehospitalization after patients' discharge in one year. Our study was approved by the ethics committee (no. 2016PHB042-01). Results: AKI incidence was 17.4% (27/155) during hospitalization. Compared to patients without AKI, the AKI group had obviously higher mortality and was more female and had higher incidence of chronic kidney disease, worse cardiac function, more cardiac complications, larger doses of diuretics, and less use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker. By contrary to previous animal experiments, we found serum α-Klotho levels were increased significantly in AKI patients (740.2 ± 306.8 vs. 419.0 ± 272.6 pg/mL, p < 0.001). And, the areas under the receiver operating curves indicated serum α-Klotho levels had a superior discriminative power for predicting AKI after AMI compared with other risk factors (0.792, 95% CI, 0.706-0.878, p < 0.001). Meanwhile, logistic regression model indicates extensive anterior myocardial infarction, Killip classification ≥2 grade, α-Klotho ≥516.9 pg/mL, eGFR (decrease per 10 ml/min ∗ 1.73 m2), Hgb, and nonuse of ACEI/ARB were the risk factors of AKI after AMI. Moreover, one-year follow-up presented AMI patients developed CKD had higher α-Klotho levels (739.7 ± 315.2 vs. 443.8 ± 292.5 pg/mL, p = 0.001), but no significant difference in rehospitalization. And, patients with α-Klotho ≥516.9 pg/ml was 6.699 times more likely to develop CKD than those with α-Klotho <516.9 pg/ml (relative risk 6.699, 95% CI 1.631-27.519, p = 0.007). Conclusion: Compared with traditional cardiac and renal biomarkers, serum α-Klotho could be a more appropriate predict biomarker for AKI after AMI in patients' eGFR >60 ml/min ∗ 1.73 m2. Higher α-Klotho levels are related to the development of AKI during hospitalization and suggest a higher prevalence of CKD after discharge. By contrary to animal experiments, whether the increased expression of α-Klotho could be a protective factor secreted by AKI after AMI, is remained to be further studied.

Recent Advances in Wearable Biosensors for Non-Invasive Detection of Human Lactate.

Lactate, a crucial product of the anaerobic metabolism of carbohydrates in the human body, is of enormous significance in the diagnosis and treatment of diseases and scientific exercise management. The level of lactate in the bio-fluid is a crucial health indicator because it is related to diseases, such as hypoxia, metabolic disorders, renal failure, heart failure, and respiratory failure. For critically ill patients and those who need to regularly control lactate levels, it is vital to develop a non-invasive wearable sensor to detect lactate levels in matrices other than blood. Due to its high sensitivity, high selectivity, low detection limit, simplicity of use, and ability to identify target molecules in the presence of interfering chemicals, biosensing is a potential analytical approach for lactate detection that has received increasing attention. Various types of wearable lactate biosensors are reviewed in this paper, along with their preparation, key properties, and commonly used flexible substrate materials including polydimethylsiloxane (PDMS), polyethylene terephthalate (PET), paper, and textiles. Key performance indicators, including sensitivity, linear detection range, and detection limit, are also compared. The challenges for future development are also summarized, along with some recommendations for the future development of lactate biosensors.

RNA granule-clustered mitochondrial aminoacyl-tRNA synthetases form multiple complexes with the potential to fine-tune tRNA aminoacylation.

Mitochondrial RNA metabolism is suggested to occur in identified compartmentalized foci, i.e. mitochondrial RNA granules (MRGs). Mitochondrial aminoacyl-tRNA synthetases (mito aaRSs) catalyze tRNA charging and are key components in mitochondrial gene expression. Mutations of mito aaRSs are associated with various human disorders. However, the suborganelle distribution, interaction network and regulatory mechanism of mito aaRSs remain largely unknown. Here, we found that all mito aaRSs partly colocalize with MRG, and this colocalization is likely facilitated by tRNA-binding capacity. A fraction of human mitochondrial AlaRS (hmtAlaRS) and hmtSerRS formed a direct complex via interaction between catalytic domains in vivo. Aminoacylation activities of both hmtAlaRS and hmtSerRS were fine-tuned upon complex formation in vitro. We further established a full spectrum of interaction networks via immunoprecipitation and mass spectrometry for all mito aaRSs and discovered interactions between hmtSerRS and hmtAsnRS, between hmtSerRS and hmtTyrRS and between hmtThrRS and hmtArgRS. The activity of hmtTyrRS was also influenced by the presence of hmtSerRS. Notably, hmtSerRS utilized the same catalytic domain in mediating several interactions. Altogether, our results systematically analyzed the suborganelle localization and interaction network of mito aaRSs and discovered several mito aaRS-containing complexes, deepening our understanding of the functional and regulatory mechanisms of mito aaRSs.