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Nowadays, human beings are exposed to Cu in varieties of environmental mediums, resulting in health risks needing urgent attention. Our research found that Cu shortened lifespan and induced aging-related phenotypes of Caenorhabditis elegans (C. elegans). Transcriptomics data showed differential expression genes induced by Cu were mainly involved in regulation of metabolism and longevity, especially in fatty acid metabolism. Quantitative detection of free fatty acid by GC/MS further found that Cu upregulated free fatty acids of C. elegans. A mechanism study confirmed that Cu promoted the fat accumulation in nematodes, which was owing to disorder of fatty acid desaturase and CoA synthetase, endoplasmic reticulum unfolded protein response (UPRER), mitochondrial membrane potential, and unfolded protein response (UPRmt). In addition, Cu activated oxidative stress and prevented DAF-16 translocating into nuclear with a concomitant reduction in the expression of environmental stress-related genes. Taken together, the research suggested that Cu promoted aging and induced fat deposition and oxidative damage.

With the deepening of cancer clinical research, miRNAs provide new ideas for molecular diagnosis and treatment of tumors. Improving the molecular delivery efficiency of miRNA is the key to the success of miRNA therapy. We have established self-assembly diagnosis and treatment technologies that can be used to achieve accurate targeting and "cargo" delivery at the cellular level. This technology builds a miRNA (let-7a) delivery system based on metal precursor [Au(III) and Fe(II)]-mediated tumor microenvironmental response to realize the self-assembly of AuFe-miRNA complexes for precise real-time imaging of tumor cells and targeted therapy. To accurately measure the changes in reactive oxygen species during complex formation in real time at the single-cell level, we employed small-size nanoscale devices as analytical tools. This study proposes an electrochemical sensor based on carbon fiber electrodes for ultraprecise and multiple monitoring of metal-ion-mediated miRNA delivery systems, precisely realizing targeted tracking of tumors and effective intervention inhibition.

Anode-free batteries (AFBs) have the potential of ultra-high energy density, but lithium dendrite has largely hindered their practical applications. In this work, an in-situ grown gradient solid electrolyte interface (SEI) layer on pre-designed micro-hole-grid (MHG) Cu reservoir is proposed to guide uniform lithium deposition and propagation, by which the electrode interface is stabilized and the surface stress is considerably decreased endowing the AFBs with outstanding areal capacity and cycling performance. The gradient SEI is confirmed by cryogenic-transmission electron microscopy (Cryo-TEM) and XPS to be composed of (1) an elastic organic top layer to hinder non-Li species migration and withstand volume fluctuation, and (2) a lithophilic LiCl-rich bottom layer to render the rapid lithium supply. Operando electron paramagnetic resonance (EPR) shows a dynamic Li deposition, unambiguously demonstrating a dendrites-free behavior. As a result, the full cells of a gradient SEI modified Cu reservoir paired with a LiFePO4 cathode exhibit high capacity of 95 mAh g–1 and Coulombic efficiency (CE) of 99.5% after 100 cycles, much better than the control cells with planar current collectors (1.6 mAh g–1, 2.6%). These findings are enlightening in engineering better interphases for high energy and safe rechargeable lithium metal batteries.

Supplementary Methods from MET-Independent Lung Cancer Cells Evading EGFR Kinase Inhibitors Are Therapeutically Susceptible to BH3 Mimetic Agents

Legends for Video and Figures 1-3 from MET-Independent Lung Cancer Cells Evading EGFR Kinase Inhibitors Are Therapeutically Susceptible to BH3 Mimetic Agents

Supplementary Video from MET-Independent Lung Cancer Cells Evading EGFR Kinase Inhibitors Are Therapeutically Susceptible to BH3 Mimetic Agents

Plant-mediated indirect interactions (PMIIs) between phytopathogenic fungi and herbivorous insects on shared host plants occur in nature. Knowledge of PMIIs is critical in plant molecular breeding and integrated pest management. We studied the response and chemical mechanism of beet armyworm, Spodoptera exigua (Hübner), adults to rose plants, Rosa chinensis Jacquin, infected with rose powdery mildew, Podosphaera pannosa (Wallr.: Fr.) de Bary. Using gas chromatography-electroantennographic detection (GC-EAD) coupled with electroantennogram (EAG), we found that beet armyworm antennae responded to 8, 11, and 3 volatile organic compounds (VOCs) from noninfected roses, mildew-infected roses, and mildew alone, respectively. The EAG analyses showed 11 chemicals (e.g., limonene [1], 2-ethyl-1-hexanol [2], linalool [3], nonanal [4], (E)-β-caryophyllene [5], 1-dodecanol [7], nhexadecane [9], 1-hexadecanol [11], methyl palmitate [12], 1-octadecanol [14], and n-butyl hexadecanoate [15]) elicited electrophysiological responses of beet armyworm antennae with significant dose-response relationships (P < 0.05). The EAG responses to the three chemicals (3, 11, and 15) were greater than that to the reference chemical [i.e., (E)-2-hexenal] at 0.5, 5.0, and 50.0 mg/ml. Olfactory and ovipositional behavior assays indicated that three chemicals (2, 3, and 5) significantly attracted beet armyworm females and four chemicals (7, 11, 14, and 15) strongly repelled females. Chemicals 2, 3, and 5 from healthy roses appear to be responsible for the attraction of beet armyworm moths to healthy roses, whereas chemicals 7, 11, 14, and 15 from mildew-infected roses play key roles in inhibiting attraction of moths. VOCs from mildew alone did not attract or repel beet armyworm moths.

Epidemiological evidence has shown a significant association between short-term exposure to air pollution and mortality risk for circulatory system diseases (CSD). However, informative insights on the significance and magnitude of its relationship in the process of government interventions on abating air pollution are still lacking, particularly in a burgeoning Chinese city. In this study, we conducted a time series study in Lishui District, Nanjing, to examine the effect of ambient particulate matter (PM), e.g., PM2.5 and PM10, on daily death counts of CSD which included cardiovascular disease (CVD), cerebrovascular disease (CEVD), and arteriosclerotic heart disease (ASHD) mortality from January 1, 2015, to December 31, 2019. The results revealed that each 10 μg/m3 increase in PM2.5 and PM10 concentration at lag0 day was associated with an increase of 1.33% (95% confidence interval, 0.08%, 2.60%) and 1.12% (0.43%, 1.82%) in CSD mortality; 2.42% (0.44%, 4.43%) and 1.43% (0.32%, 2.55%) in CVD mortality; 1.20% (− 0.31%, 2.73%) and 1.21% (0.38%, 2.05%) in CEVD mortality; and 2.78% (0.00%, 5.62%) and 1.66% (0.14%, 3.21%) in ASHD mortality, respectively. For cumulative risk, the corresponding increase in daily mortality for the same change in PM2.5 concentration at lag03 day was significantly associated with 1.94% (0.23%, 3.68%), 3.17% (0.58%, 5.84%), 2.38% (0.17%, 4.63%), and 4.92% (1.18%, 8.81%) for CSD, CVD, CEVD, and ASHD, respectively. The exposure–response curves were approximately nonlinear over the entire exposure range of the PM concentrations. We also analyzed the effect modifications by season (warm or cold), age group (0–64 years, 65–74 years, or ≥ 75 years), and sex (male or female). Although not statistically significant, stratified analysis showed greater vulnerability to PM exposure for cold season, population over 65 years of age, and female group.

The presence of anti-GQ1b antibodies in serum or cerebrospinal fluid is a diagnostic indicator of the Miller–Fisher variant of Guillain–Barré syndrome (GBS), whereas anti-GQ1b antibody syndrome is rarely presented as acute bilateral pain in the cheeks and masticatory muscle fatigue without ophthalmoplegia, ataxia, or limb weakness. Here, we report a case of a female patient diagnosed with GBS characterized only by the involvement of the facial and trigeminal nerves who was positive for serum anti-GQ1b antibodies secondary to Mycoplasma pneumoniae infection. The patient was treated with macrolide antibiotics and neurotrophic drugs, and her symptoms were significantly alleviated after 1 month. This case indicates a new clinical presentation of GBS and anti-GQ1b antibody syndrome with a differential diagnosis of multiple cranial nerve damage of which neurological physicians should be aware. Positive anti-GQ1b antibodies secondary to infection were observed in this case, and antibiotic treatment resulted in a favorable prognosis. The specific underlying mechanism requires further investigation.

Uracil DNA glycosylase (UDG) is one of the key initiators for the base excision repair pathway. Since abnormal UDG expression is associated with various diseases, sensitive detection of UDG activity is critical for early clinical diagnosis. Here, a smart catalyzed hairpin assembly (CHA)-DNAzyme nanosystem is developed for intracellular UDG imaging by incorporating CHA and DNAzyme onto MnO2 nanosheets. In this strategy, the biodegradable MnO2 nanosheets are employed as nanocarriers for efficiently adsorbing and delivering five DNA probes into cells by endocytosis. Then, the MnO2 nanosheets are degraded by cellular glutathione to release the DNA modules at the same intracellular position. Liberated Mn2+, an indispensable DNAzyme cofactor, was used to promote catalytic cleavage for facilitating the cascade process in cells. Based on the uracil site-recognition and -excision operation of the target UDG, the activated CHA-DNAzyme nanosystem generates lots of DNAzyme-assisted CHA products, turning on the fluorescence resonance energy transfer response. This autocatalytic CHA-DNAzyme nanosystem provides a detectable minimum UDG concentration of 0.23 mU/mL, which is comparable to some reported UDG detection approaches. As a multiple signal amplification strategy, the CHA-DNAzyme nanosystem realizes the UDG imaging in living cells with enhanced sensitivity, indicating great promise in the prediction and diagnosis of early-stage cancer.

The relationship between human papillomavirus (HPV) and esophageal cancer (EC) has been controversial, which may be caused by the difference in geographic regions of sample origin. Thus, we conducted a case-control study to find that HPV increased the risk of esophageal cancer, and the HPV18 detection rate is the highest (24.2%) among patients with EC, suggesting that HPV18 could be the most risk subtype of HPV infected. We then identified high-risk HPV18 and N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) to establish a model on the viral etiology cooperating with environmental carcinogens. Het-1A cells containing HPV18 were continuously exposed to MNNG or not; then the morphological phenotype and function assays were performed in 25th passage cells. MNNG promoted the proliferation and invasion abilities and inhibited apoptosis both in Het-1A-HPV18 and control group. However, the Het-1A-HPV18 had a stronger change in phenotypic features and formed more transformed foci in soft agar. Further, Western blot found p53 and p21 were down-regulated, and expression of c-Myc, MMP-2, and MMP-9 and Bcl-2/Bax ratio were up-regulated. Our results revealed that MNNG was easier to induce malignant transformation of Het-1A cells transfected with HPV18. It is good evidence for the close relationship between HPV and the etiology of EC, providing foundation for further study in molecular mechanism and specific intervention targets.

Noise-induced hearing loss (NIHL) remains a leading occupational related disease and is a serious public health problem. Hence, the identification of potential biomarkers for NIHL prevention and diagnosis has become an urgent work. To discover potential metabolic biomarkers of NIHL, plasma metabolomics analysis in 62 NIHL patients and 62 normal hearing controls was performed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF MS). Orthogonal partial least square-discriminant analysis (OPLS-DA) model was applied to distinguish metabolite profile alterations in plasma samples between the two groups. The metabolites with a variable importance of projection (VIP) value1 and P value0.05 were considered to be potential metabolic biomarkers. KEGG database was performed to explore the involved pathways of potential biomarkers. Three autophagy-related genes (PI3K, AKT, and ATG5) were selected for further verification, and mRNA levels were detected using RT-qPCR analysis. Twenty plasma metabolites with VIP1 and P0.05 were significantly altered between the two groups. Totally, seven metabolic pathways involving the glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, autophagy pathway, choline metabolism, the alpha-linolenic acid metabolism and linoleic acid metabolism, and retrograde endocannabinoid pathway were significantly related to NIHL. Furthermore, verification by RT-qPCR suggested that the mRNA expression levels of PI3K and AKT along with ATG5 were significantly lower in the NIHL patients compared with controls. In summary, the present study provides the first evidence that the identified aberrantly altered metabolites may be the potentially valuable biomarkers of NIHL for occupational noise-exposed workers. Autophagy signal pathway may be involved in the occurrence and development of NIHL. Moreover, this present study may be helpful to further better understand the metabolic changes in NIHL and be helpful for the understanding of pathogenic mechanism.

The widespread cyanotoxins in drinking water pose a threat to public health induced by Microcystins (MCs). MC-LR, a predominant toxic form of MCs, has been found to play critical roles in cancer progression. The role of MC-LR in hepatocarcinogenesis has attracted extensive attention. However, as a critical digestive organ, the precise mechanism of MC-LR-induced gastric cancer is still unclear. We found that 100 nM MC-LR promoted the proliferation, migration, invasion, and anti-apoptosis of SGC-7901 cells. Quantitative proteome and phosphoproteome analysis identified differential expression patterns and aberrant pathways of SGC-7901 cells exposed to MC-LR. The results indicated that 48,109 unique peptides from 6320 proteins and 1375 phosphoproteins with 3473 phosphorylation sites were detected after 24 h treatment of MC-LR. Proteome and phosphoproteome conjoint analysis indicated estrogen signaling pathway might play an essential step in MC-LR-treated molecular events. The mechanism underlying these changes may involve MC-LR excessively activating the estrogen signaling pathway by reducing Hsp90 phosphorylation, which results in nucleus translocation of activated ERα and Krt16 overexpression in gastric cells. In general, our results indicate multiple crucial signals triggered by MC-LR, among which MC-LR may promote the development of gastric cancer by exerting estrogenic potency.

BACKGROUND Varied degrees of lockdown have been imposed for dozens of jurisdictions upon facing the SARS-CoV-2 epidemics during the past two years. Areal lockdown has been demonstrated effective to reduce the morbility and mortality of COVID-19. Even after the strict lockdown the peak of infection will appear around 9-25 days (median 18 days) thereafter. A wave of Omicron variant (BA.2 and BA.2.2) outbreak was seen from March to May 2022, in Shanghai, a megacity in China mainland. OBJECTIVE To understand the sources of infection cases from outside or inside the isolated locations before and after the strict city lockdown. METHODS The attributable addresses of SARS-CoV-2 infection were reported daily as well as the infected cases from March 18th, 2022 on through government website, which was publicly accessible. The address data and infected cases were collected until May 29th, 2022. The location (longitude and latitude) of these addresses were retrieved and the pattern of repeatedly reported addresses were analyzed. A tool of simple and meso-scale point-based (location-based) chronological graph was used to visualize and analyze the interactions of these locations. RESULTS From March 18th to May 29th 2022, 173,350 items representing 35,743 unique addresses and 636,279 infected cases were released. The infection cases peaked 16 days after the city lockdown and were highly clustered in much crowded districts. The proportion of repeatedly reported locations of the previous day increased from around 20% before lockdown to greater than 40% in the plateau and remained at this level for up to one third (20/62) of the lockdown phase. This significantly increased proportion of intra-address infection indicated a pattern shift from inter-addresses to intra-address (D=0.2954, p CONCLUSIONS During the strict areal isolation the intra-address infection may contribute significantly to infected cases of SARS-CoV-2 Omicron variant, the infection might have easily spilled over the boundary of family(with averaged family size of 2.3-3.1 people and family were required stay-at-home compulsively). This significant inter-addresses to intra-address pattern shift necessitated the understanding of intra-location transmission routes and corresponding interventions. Areal isolation and close off with homogeneous assumption inside and outside the isolated areas should be modified and the quantifing of the elevated risk for previously less exposed but much vulnerable sub-population was in pressing need.

BackgroundVaried degrees of lockdown have been imposed for dozens of jurisdictions upon facing the SARS-CoV-2 epidemics during the past two years. Areal lockdown has been demonstrated effective to reduce the morbility and mortality of COVID-19. Even after the strict lockdown the peak of infection will appear around 9-25 days (median 18 days) thereafter. A wave of Omicron variant (BA.2 and BA.2.2) outbreak was seen from March to May 2022, in Shanghai, a megacity in China mainland. Aim To understand the sources of infection cases from outside or inside the isolated locations before and after the strict city lockdown.MethodsThe attributable addresses of SARS-CoV-2 infection were reported daily as well as the infected cases from March 18th, 2022 on through government website, which was publicly accessible. The address data and infected cases were collected until May 29th, 2022. The location (longitude and latitude) of these addresses were retrieved and the pattern of repeatedly reported addresses were analyzed. A tool of simple and meso-scale point-based (location-based) chronological graph was used to visualize and analyze the interactions of these locations.ResultsFrom March 18thto May 29th2022, 173,350 items representing 35,743 unique addresses and 636,279 infected cases were released. The infection cases peaked 16 days after the city lockdown and were highly clustered in much crowded districts. The proportion of repeatedly reported locations of the previous day increased from around 20% before lockdown to greater than 40% in the plateau and remained at this level for up to one third (20/62) of the lockdown phase. This significantly increased proportion of intra-address infection indicated a pattern shift from inter-addresses to intra-address (D=0.2954, pInterpretationDuring the strict areal isolation the intra-address infection may contribute significantly to infected cases of SARS-CoV-2 Omicron variant, the infection might have easily spilled over the boundary of family(with averaged family size of 2.3-3.1 people and family were required stay-at-home compulsively). This significant inter-addresses to intra-address pattern shift necessitated the understanding of intra-location transmission routes and corresponding interventions. Areal isolation and close off with homogeneous assumption inside and outside the isolated areas should be modified and the quantifing of the elevated risk for previously less exposed but much vulnerable sub-population was in pressing need.Research in contextEvidence before this study It is commonly observable that the infection cases will continue to increase and peaked in several weeks after the first day of imposing areal lockdown. The search syntax of [(SARS-CoV-2 OR COVID-19) AND (transmission OR infection) AND (post-lockdown OR “during lockdown” OR “isolated area*”)] on PubMed hits 1372 records(on 2022-08-10). However, the viral transmission between the isolated locations or within them have not been studied thoroughly, maybe, due to the presumption that it would be stopped eventually by greatly reducing the inter-personal contact.The search syntax of [(SARS-CoV-2 OR COVID-19) AND (transmission OR infection) AND (post-lockdown OR “during lockdown” OR “isolated area*”) AND (strict)] on PubMed hits 57 records. The populations of different ages with heterogeneous risks of exposure to viruses have been revealed.Added values in this studyThe strict city lockdown of Shanghai in facing the Omicron outbreak provided a prototype to understand the sources of infection by using the daily reported address (isolated immediately) involving infected cases. A noticeable pattern shift was revealed in this study with significantly increased proportion of intra-location (small area) self-propagation after the city lockdown.Implication of all the available evidenceCounter measures should be provided to reduce the risk of transmmision within the small isolated areas; and the elevated risk for the much vulnerable sub-populations within the intra-location (small isolated areas) should be quantified and to trade off between the reduced inter-location risk and increased intra-location risk of infection in policy making.

ObjectiveThis study aims to systematically evaluate the curative efficacy of different acupuncture methods in the treatment of obesity combined with insulin resistance in randomized clinical trials (RCTs) by network meta-analysis.MethodsFour Chinese databases (CNKI, WanFang Data, VIP, and SinoMed) and four English databases (PubMed, Embase, the Cochrane Library, and www.clinicaltrial.gov) were electronically searched to identify qualified studies. Two reviewers independently screened the literature in accordance with the inclusion/exclusion criteria by EndNote 20 software and extracted data by ADDIS1.16.8 software, and then the risk of bias of the included studies were evaluated by the Cochrane tool. Network meta-analysis was performed by Stata 15.1 software. The primary outcomes included fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment—insulin resistance (HOMA-IR), and body mass index (BMI). The secondary outcomes included waistline, waist–hip ratio, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL).ResultsFive RCTs with a total of 410 patients with obesity combined with insulin resistance were included. The results of the network meta-analysis showed that, compared with the control group, three kinds of acupuncture methods (electropuncture, acupoint catgut embedding, and acupuncture point patch) had significant efficacy in reducing FBG [electropuncture (MD = -0.44, 95% CI: -0.83, -0.05) and acupoint catgut embedding (MD = -0.36, 95% CI: -0.51, -0.21)], FINS [electropuncture (MD = -6.17, 95% CI: -9.69, -2.65), acupoint catgut embedding (MD = -5.87, 95% CI: -6.92, -4.82), and acupuncture point patch (MD = -5.86, 95% CI: -11.40, -0.32)], HOMA-IR [electropuncture (MD = -1.59, 95% CI: -2.73, -0.45) and acupoint catgut embedding (MD =-0.91, 95% CI: -1.07, -0.75)], BMI [electropuncture (MD = -1.68, 95% CI: -2.70, -0.66), acupoint catgut embedding (MD = -3.39, 95% CI: -4.38, -2.40), and acupuncture point patch [MD = -2.90, 95%CI: -4.93, -0.87)], and waistline [electropuncture (MD = -5.49, 95% CI: -8.56, -2.42) and acupoint catgut embedding (MD = -4.91, 95% CI: -7.51, -2.31)] in obese patients with insulin resistance, suggesting that their efficacy was better than that of the western medicine group in some of the outcome indicators. For the index related to blood lipid, the efficacy of electropuncture was significantly better than behavioral therapy and western medicine. Except that acupoint catgut embedding was superior to electroacupuncture in reducing the BMI, there was no statistically significant difference in efficacy among the three acupuncture methods.ConclusionsThe results showed that the therapeutic effect of acupuncture methods was superior to conventional western treatment alone. Acupuncture methods could serve as an alternative or adjunctive treatment in obese patients with insulin resistance.Systematic Review Registrationhttps://inplasy.com, identifier 202280075.

As an emerging flame retardant, organic phosphate flame retardants have been extensively used worldwide. The aim of this study is to determine the effects of TnBP on neurobehavior of Caenorhabditis elegans (C. elegans) and its mechanisms. L1 larvae of wild-type C. elegans N2 and transgenic nematodes (BZ555, DA1240 and EG1285) were exposed to TnBP of 0, 0.1, 1, 10 and 20 mg/L for 72 hours, respectively. Then, we observed that TnBP inhibited the body length and body width, increased the head swings and body bends, reduced the pump contraction times and chemical trend index, and increased the production of reactive oxygen species (ROS), altered the expression of genes (mev-1 and gas-1) related to mitochondrial oxidative stress, increased the expression of genes (pmk-1, sek-1 and nsy-1) related to p38 MAPK signal pathway, increased the production of dopamine, glutamate and Gamma-Amino Butyric Acid (GABA). When changes of motor behaviors were taken as the endpoint of toxicity evaluation, we found that the pmk-1 mutants led to the sensitivity of nematodes to TnBP. Therefore, the results showed that TnBP had harmful effects on the neurobehavior of nematodes, oxidative stress might be one of the mechanisms of neurotoxicity, and the activation of p38 MAPK signal pathway might play a protective role for nematodes against the harmful effects induced by TnBP. The research results revealed the potential effects of TnBP on the neurobehavior of C. elegans, put forward new expectations for the study of environmental hygiene and human survival risks of organic phosphate flame retardants.

Lithium–sulfur (Li–S) batteries possess overwhelming energy density of 2654 Wh kg−1, and are considered as the next-generation battery technology for energy demanding applications. Flooded electrolytes are ubiquitously employed in cells to ensure sufficient redox kinetics and preclude the interference of the electrolyte depletion due to side reactions with the lithium metal anode. This strategy is capable of enabling long-lasting, high-capacity and excellent-rate battery performances, but it mask the requirements of practical Li–S batteries, where high-sulfur-loading/content and lean electrolyte are prerequisite to realize the energy-dense Li–S batteries. Sparingly and highly solvating electrolytes have emerged as effective yet simple approaches to decrease the electrolyte/sulfur ratio through altering sulfur species and exerting new reaction pathways. Sparingly solvating electrolytes are characterized by few free solvents to solvate lithium polysulfides, rendering a quasi-solid sulfur conversion and decoupling the reaction mechanisms from electrolyte quantity used in cells; while highly solvating electrolytes adopt high-donicity or high-permittivity solvents and take their advantages of strong solvation ability toward polysulfide intermediators, thereby favoring the polysulfide formation and stabilizing unique radicals, which subsequently accelerate redox kinetics. Both solvation chemistry approaches have their respective features to allow the operation of cells under electrolyte-starved conditions. This Review discusses their unique features and basic physicochemical properties in the working Li–S batteries, presents remaining technical and scientific issues and provides future directions for the electrolyte chemistry to attain high-energy Li–S batteries.

Carbon dots (CDs) are a new class of carbon-based luminescence materials with fascinating properties. They have been given great expectations on superseding traditional semiconductor quantum dots due to their good dispersity and stability, relatively low toxicity, superior resistance to photobleaching, and excellent biocompatibility. The diversified luminescence properties of CDs are largely due to the synthetic strategies and precursors. In view of those described above, this study has explored the possibility to establish a facile one-step hydrothermal method for the one-pot synthesis of folic acid-modified cerium-doped CDs (Ce-CDs-FA), which could be further utilized as a sensitive fluorescent nanoprobe for biosensing. This investigation demonstrates that the Ce-CDs-FA nanocomposites have nice biocompatibility and bright fluorescent properties, which can be readily utilized to detect cancer cells through recognizing overexpressing folate receptors by virtue of folic acid. Meanwhile, it is noted that the Fe3+ ion can actualize a specific and hypersensitive quenching effect for these Ce-CDs-FA nanocomposites, which can be further explored for special ion recognition, including iron ions. It raises the possibility that the as-prepared Ce-CDs-FA nanocomposites could be extended as a dual fluorescence sensor for targeted cell imaging and Fe3+ ion detection.

In this work, monolithic catalysts with single coating Ce0.75Zr0.25O2, Al2O3 and composite coating Ce0.75Zr0.25O2-Al2O3 were prepared by PMMA hard template-excessive impregnation method with 3DOM La0.7Ce0.3CoO3 as the active component and cordierite as the carrier, and characterized by SEM, XRD, BET, H2-TPR and XPS, and the catalytic performance for toluene was tested. The results showed that the active components of 3DOM La0.7Ce0.3CoO3/ Ce0.75Zr0.25O2-Al2O3/ Cordierite catalyst were highly dispersed, forming a complete macroporous structure with the largest specific surface area (10.57 m2·g-1), high surface adsorbed oxygen concentration and good low-temperature reducibility. Its catalytic activity (T50%=103℃, T90%=218℃) for toluene was obviously better than the others. According to the comprehensive analysis, the improvement of the performance of the catalyst may benefit from the excellent physicochemical properties and the synergistic effect between Ce0.75Zr0.25O2-Al2O3 composite coating and active components.

Health risks caused by crucial environmental carcinogens N-nitrosamines triggered ubiquitous attention. As the liver exerted vital function through metabolic process, lipid metabolism disorders have been confirmed as potential drivers for toxicological effects, and the mechanisms of lipid regulation related to hepatotoxicity induced by N-nitrosamines remained largely unclear. In this study, we comprehensively explored the disturbance of hepatic lipid homeostasis in mice induced by nitrosamines. The results implied that nitrosamines exposure induced hepatotoxicity accompanied by liver injury, inflammatory infiltration, and hepatic edema. Lipidomics profiling analysis indicated the decreased levels of phosphatidic acids (PA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), lyso-phosphatidylcholines (LPC), lyso-phosphatidylethanolamines (LPE), diacylglycerols (DAG) and triacylglycerols (TAG), the elevation of ceramides (Cer) and decomposition of free fatty acids (FFA) in high-dose nitrosamines exposure group. Importantly, nitrosamines exposure promoted fatty acid oxidation (FAO) by facilitating fatty acid uptake and decomposition, together with the upregulation of genes associated with FAO accompanied by the activation of inflammatory cytokines TNF-α, IL-1β and NLRP3. Furthermore, fatty acid translocase CD36-mediated fatty acid oxidation was correlated with the enhancement of oxidative stress in the liver caused by nitrosamines exposure. Overall, our results contributed to the new strategies to interpret the early toxic effects of nitrosamines exposure.

In this work, monolithic catalysts with single coating Ce

Background Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRNA RPL34-AS1 in the development and progression of ESCC. Methods The expression level of RPL34-AS1 in ESCC tissues and cell lines was determined by RT-qPCR. Functional experiments in vitro and in vivo were employed to explore the effects of RPL34-AS1 on tumor growth in ESCC cells. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between RPL34-AS1, miR-575 and ACAA2. Results RPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. Functionally, upregulation of RPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, invasion and migration in vitro, whereas knockdown of RPL34-AS1 elicited the opposite function. Consistently, overexpression of RPL34-AS1 inhibited tumor growth in vivo. Mechanistically, RPL34-AS1 acted as a competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC. Conclusions Our results reveal a role for RPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using RPL34-AS1 as a potential biomarker and an effect target for patients with ESCC.

Substantial outbreaks of cyanobacterial harmful algal blooms (cyanoHABs) are accompanied by the prevalent existence of microcystins (MCs) in eutrophic freshwater worldwide, which can compromise the safety of aquatic ecosystems and public health. However, the response of the sediment microbial community to MCs exposure remains unclear. In this study, the sediment microbial communities of Lake Taihu were continuously exposed to environmentally relevant concentration (10 μg/L) of microcystin-LR (MC-LR) in microcosms for three months to mimic MCs contamination during cyanoHABs. Meanwhile, the MC-LR degradation characteristics, metabolic profiles, functional genes, and structures of microbial communities were analyzed periodically. The results showed that the MC-LR degradation capacities of microbial communities significantly increased with prolonged toxin exposure time. The enhanced MC-LR degradation rate was positively correlated with the increase in the abundance of mlr genes, which corresponds to the MC-degrading bacterial community. However, the MC-LR degradation pathway was maintained, and one new biodegradation intermediate (Adda-Glu) was first identified. Moreover, the metabolic profiles of the microbial communities indicated that overall carbon metabolic activity displayed a stimulation-suppression trend, and the exposure led to different carbon utilization patterns. Furthermore, microbial community structure analysis showed that long-term MC-LR exposure enriched microbes associated with MC degradation (Pseudomonas, Stenotrophomonas, Sphingopyxis and Sphingomonas) but inhibited MC-sensitive bacterial genera. This study clearly elucidates that MC-LR exposure alters the function, metabolism, and structure of the sediment microbial community to adapt to polluted environments.

The health risks caused by environmental pollution have long been of substantial concern. With the development of epigenetics, a large number of studies have demonstrated that N6-methyladenosine (m6A) modification is involved in the regulation of various important life activities associated with various diseases. Recent studies have revealed that m6A plays a key role in health damage caused by environmental exposure by regulating post-transcriptional gene expression. Therefore, our study outlined the effects of environmental pollutant exposure on m6A methylation and its regulator levels. Moreover, we found that m6A methylation modifications were involved in the development of various health damages by regulating important life activities in vivo, such as reactive oxygen species imbalance, apoptosis, epithelial-mesenchymal transition (EMT), and inflammatory processes. More importantly, we delved into the regulatory mechanisms of m6A methylation dysregulation in environmental pollution-induced diseases. Finally, by examining the published literature, we found that methyltransferase-like protein 3 (METTL3) and fat mass- and obesity-associated protein (FTO) were potentially used as biomarkers of health damage induced by particulate matter exposure and heavy metal exposure, respectively. The current studies on regulators of METTL3 and FTO were more promising to bring new perspectives for the treatment of environmental health-related diseases.

Nitrosamines were a class of important environmental carcinogens associated with digestive tract neoplasms. As the early toxic effect of nitrosamines, inflammatory response participated in the malignant transformation of cells and promoted the occurrence and development of tumors. However, the role of NLRP3 inflammasome in the nitrosamines-induced inflammatory response was unclear. In this study, the human esophageal epithelial cells (Het-1A) were used to explore potential mechanisms of the activation of NLRP3 inflammasome under co-exposure to nine nitrosamines commonly found in drinking water at the doses of 0, 4, 20, 100, 500, and 2500 ng/mL. The results showed that nitrosamines stimulated activation of the NLRP3 inflammasome and induced cellular oxidative damage in a dose-dependent manner. Pretreatment of reactive oxygen species scavenger N-acetyl-L-cysteine (NAC), particularly mitochondrial reactive oxygen species (mtROS) scavengers Mito-TEMPO, effectively inhibited the activation of NLRP3 inflammasome, suggesting that nitrosamines could mediate the activation of NLRP3 inflammasome via mtROS. Furthermore, we found that nitrosamines co-exposure also promoted cell pyroptosis through the NLRP3/caspase-1/GSDMD pathway, which was demonstrated by adding the caspase-1 inhibitor Z-YVAD-FMK and constructing NLRP3 downregulated Het-1A cell line. This study revealed the underlying mechanism of the activation of NLRP3 inflammasome initiated by nitrosamines co-exposure and provided new perspectives on the toxic effects of nitrosamines.

Purpose Gastric cancer (GC) is aggressive cancer with a high mortality rate worldwide. N6-methyladenosine (m6A) RNA methylation is related to tumorigenesis, which is dynamically regulated by m6A modulators ("writer," "eraser," and "reader"). We conducted a comprehensive analysis of the m6A genes of GC patients in TCGA datasets to identify the potential diagnostic biomarkers. Materials and methods We analyzed the expression profile of m6A genes in the TCGA cohort and constructed a diagnostic-m6A-score (DMS) by the LASSO-logistic model. In addition, by consensus cluster analysis, we identified two different subgroups of GC risk individuals by the expression profile of m6A modulators, revealing that YTHDF1's expression variation profile in GC diagnosis. We also performed RT-qPCR and WB verification in 17 pairs of GC specimens and paired adjacent non-tumor tissues and GC cell lines, and verified the expression trend of YTHDF1 in five GEO GC datasets. YTHDF1 expression and clinical features of GC patients were assessed by the UALCAN. Results The DMS with high specificity and sensitivity (AUC = 0.986) is proven to distinguish cancer from normal controls better. Moreover, we found that the expression profile variation of YTHDF1 was significantly associated with the high-risk subtype of GC patients. RT-qPCR and Western blot results are consistent with silicon analysis, revealing that YTHDF1's potential oncogene role in GC tumor. Conclusion In conclusion, we developed the m6A gene-based diagnostic signature for GC and found that YTHDF1 was significantly correlated with the high-risk subtype of GC patients, suggesting that YTHDF1 might be a potential target in GC early diagnosis.

Inflammation is a complicated process and is considered to be responsible for the development of noise-induced hearing loss (NIHL). CARD8 is an important component of inflammasome that has been implicated in inflammation. To decide the relationship between the polymorphisms of CARD8 gene and NIHL risk and deduce the potential mechanism, three SNPs (rs2043211, rs1062808, and rs12459322) were genotyped in a Chinese population consisting of 610 NIHL cases and 612 normal hearing controls. The possible impacts of SNPs on CARD8 structure and function were assessed using a variety of bioinformatics tools. Plasmids expressing wild-type and/or mutated CARD8 were transfected into HEK293 cells to verify the effect of SNPs on CARD8 protein expression level by western blot. The results revealed that rs2043211 AA genotype and A allele were associated with decreased risk of NIHL. Stratified analysis found that the male, drinking and exposed to noise ≥ 92 dB, subjects harboring rs2043211 A allele had a low risk of NIHL. The haplotype AGG (rs2043211-rs1062808-rs12459322) was significantly associated with a decreased risk of NIHL. SNP rs2043211 was predicted to be deleterious and affects CARD8 protein structure and stability. Furthermore, the functional experiment showed the mutant CARD8 could significantly decrease the CARD8 protein expression level. This study confirms that rs2043211 A allele may reduce NIHL risk by causing the loss of PPI combined with the decreased CARD8 expression level leading to CARD8 functional changes, and it may be one valuable genetic biomarker of NIHL susceptibility for Chinese noise-exposed workers.

Lijuan Sheng,1 Lihong Yin,1 Dezhen Peng,1 Liping Zhao2 1Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Department of Nursing, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaCorrespondence: Liping ZhaoDepartment of Nursing, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaTel/ Fax +86 731-8529-4072Email zhaolp0818@csu.edu.cnBackground: Best evidence regarding enteral nutrition from continuous nasal feeding in stroke patients is limited. The aim of this study was to explore the best evidence of continuous nasal feeding in stroke patients and translate the evidence into clinical practice.Methods: This study utilized the standard procedures of the Joanna Briggs Institute (JBI) evidence-based nursing centers’ clinical evidence-practice application system. The baseline assessment of stroke patients in the neurology ward was conducted. A pre- and post-implementation audit approach was used in this study and adopted the Getting Research into Practice program. We analyzed the compliance of nurses with best practice and its impact on patients’ gastrointestinal function and complications, aspiration, aspiration pneumonia, nurses’ daily workload of nasal feeding, and the length of hospitalization before and after implementing the evidence-based strategies.Results: After application of the evidence-based strategies, nurses’ compliance with best practice was improved. The incidence of patients’ gastrointestinal complications including vomit (χ 2 = 5.195, P=0.023), palirrhea (χ 2 = 4.216, P=0.039), diarrhea (χ 2 = 4.514, P=0.042), constipation (χ 2 = 5.535, P=0.035) and gastric retention (χ 2 = 4.541, P=0.042) decreased significantly after the application of the best evidence. The working time of nurses undergoing nasal feeding decreased from 23.71 ± 3.22 min to 7.73 ± 1.14 min (P =0.000) and the length of patient’s hospitalization decreased from 35.63 ± 4.45 days to 35.00 ± 3.70 days (P=0.534). The rate of aspiration, aspiration pneumonia did not show a significant difference after implementation of the evidence-based strategies.Conclusion: The results revealed that the evidence-based practice of continuous nasal feeding in stroke patients is an effective method to improve nursing quality and reduce gastrointestinal complications, which was worthy of clinical application.Keywords: stroke, nasal feeding, evidence-based nursing, best evidence, complications

Fluorinated lithium-rich anti-perovskite (F-LiRAP) is proposed to enhance lithium ion conductivity by creating Frenkel defects that facilitate the formation of lithium-rich and lithium-vacancy couples. We successfully demonstrate an all-solid-state cell configuration based on F-LiRAP, precluding the employment of polymer or liquid additives.

Porcine circovirus-like virus P1 can infect many kinds of animals and mainly causes postweaning multisystemic wasting syndrome. In China, the genetic diversity, variation, and evolutionary processes of this virus have not been described yet. To improve our knowledge of its genetic diversity, evolution, and gene flow, we performed a bioinformatics analysis using the available nucleotide sequences of the P1 virus; among them, 12 nucleotide sequences were from ten pig farms in Jiangsu Province in this epidemiological survey, and 84 sequences were downloaded from GenBank. The P1 sequences showed a rich composition of AT nucleotides. Analyses of the complete genomic sequences were polymorphic and revealed high haplotype (gene) diversity and nucleotide diversity. A phylogenetic analysis based on the NJ method showed that all P1 virus sequences formed two distinct groups: A and B. High genetic differentiation was observed between strains from groups A and B. The codon usage pattern of P1 was affected by dinucleotide compositions. Dinucleotide UU/CC was overrepresented, and dinucleotide CG was underrepresented. The mean evolutionary rate of the P1 virus was estimated to be 3.64 × 10−4 nucleotide substitutions per site per year (subs/site/year). The neutrality tests showed negative values. The purifying selection and recombination events may play a major driving role in generating the genetic diversity of the P1 population. The information from this research may be helpful to obtain new insights into the evolution of P1.

As a new type of flame retardant, Organic Phosphate Flame Retardant has been widely used worldwide. The purpose of our research is to determine the neurotoxicity of Tris (1,3-dichloroisopropyl) phosphate (TDCPP) to Caenorhabditis elegans and its mechanism. L1 larvae wild-type C. elegans were exposed to different concentrations of TDCPP, and the effects on motor behavior (head thrashes, body bends, pumping times, chemotaxis index), ROS levels, and p38MAPK signaling pathway-related gene expression levels were measured. Three transgenic nematode strains, BZ555, DA1240, and EG1285, were also used to study the effects of TDCPP on nematode dopamine neurons, glutamate neurons, and GABA neurons. The results showed that TDCPP can inhibit the head thrashes and body bends of the nematode, reduce dopamine production, increase the level of ROS in the body, and affect the expression of genes related to the p38MAPK signaling pathway. We next employed ROS production and motor behavior as toxicity assessment endpoints to determine the involvement of p38 MAPK signaling in the regulation of response to TDCPP. The results showed that the nematodes with low expression of pmk-1 were less sensitive to the TDCPP. It was suggested that TDCPP had neurotoxicity and regulated neurotoxicity to C. elegans by activating the p38-MAPK signaling pathway. The research in this article provides important information for revealing the environmental health risks of organophosphorus flame retardants and their toxic mechanism of action.

This study aimed to assess the prevalence of noise-induced hearing loss (NIHL) and hypertension, and the association between NIHL and hypertension using occupational physical examination data of 42,588 noise-exposed workers from local enterprises in Yangzhou between 2015 and 2017. The average binaural high-frequency threshold on average (BHFTA), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 23.09 ± 11.32 dB, 126.85 ± 15.94 mm Hg and 79.94 ± 11.61 mm Hg. The prevalence of NIHL and hypertension were 24.38% and 25.40%. An increased risk of NIHL and hypertension was observed in the groups of males, aged35 years, noise exposure time5 years, noise exposure level85 dB(A) and smoking. 32.25% NIHL workers had hypertension. NIHL workers were at higher risk of hypertension (adjusted OR = 1.07, 95%CI = 1.02-1.13). This study shows that the noise-exposed workers have high risk of developing NIHL and hypertension.

It has been reported that disordered Cu metabolism is associated with several neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the underlying mechanism is still unclear. In this study, 4-week-old male mice were exposed to Cu by free-drinking water for three months. Then, the effects of Cu on cognitive functions in mice were tested by Morris water maze tests, and the potential mechanisms were investigated by the ELISA, immunochemistry, TUNEL, and Western blot tests. It was found that Cu exacerbates learning and memory impairment, and leads to Cu-overload in the brain and urine of mice. The results showed that Cu induces neuronal degeneration and oxidative damage, promotes the expression of apoptosis-related protein Bax, cuproptosis-related proteins FDX1 and DLAT and the proteotoxic stress marker HSP70, and decreases Fe-S cluster proteins. In addition, Cu affects the pre-synaptic and post-synaptic regulatory mechanisms through inhibiting the expression of PSD-95 and SYP. Cu also suppresses phosphorylation levels in CREB and decreases the expression of BDNF and TrkB in the mouse hippocampus. In conclusion, Cu might mediate cuproptosis, damage synaptic plasticity and inhibit the CREB/BDNF pathway to cause cognitive dysfunction in mice.

Microplastics and Nanoplastics (MNPLs) pollution has been recognized as the important environmental pollution caused by human activities in addition to global warming, ozone layer depletion and ocean acidification. Most of the current studies have focused on the toxic effects caused by plastics and have not actively investigated the mechanisms causing cell death, especially at the subcellular level. The main content of this paper focuses on two aspects, one is a review of the current status of MNPLs contamination and recent advances in toxicological studies, which highlights the possible concentration levels of MNPLs in the environment and the internal exposure of humans. It is also proposed to pay attention to the compound toxicity of MNPLs as carriers of other environmental pollutants and pathogenic factors. Secondly, subcellular toxicity is discussed and the modes of entry and intracellular distribution of smaller-size MNPLs are analyzed, with particular emphasis on the importance of organelle damage to elucidate the mechanism of toxicity. Importantly, MNPLs are a new type of environmental pollutant and researchers need to focus not only on their toxicity, but also work with governments to develop measures to reduce plastic emissions, optimize degradation and control plastic aggression against organisms, especially humans, from multiple perspectives.

Concerns are raised over the risk to digestive system's tumors from the N-nitrosamines (NAs) exposure in drinking water. Albeit considerable studies are conducted to explore the underlying mechanism responsible for NAs-induced esophageal squamous cell carcinoma (ESCC), the exact molecular mechanisms remain largely unknown, especially at the epigenetic regulation level. In this study, it is revealed that the urinary concentration of N-Nitrosodiethylamine is higher in high incidence area of ESCC, and the lncRNA-UCA1(UCA1) is significantly decreased in ESCC tissues. In vitro and in vivo experiments further show that UCA1 is involved in the malignant transformation of Het-1A cells and precancerous lesions of the rat esophagus induced by N-nitrosomethylbenzylamine (NMBzA). Functional gain and loss experiments verify UCA1 can affect the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Mechanically, through binding to heterogeneous nuclear ribonucleoprotein F (hnRNP F) protein, UCA1 regulates alternative splicing of fibroblast growth factor receptor 2 (FGFR2), which promotes the FGFR2IIIb isoform switching to FGFR2 IIIc isoform, and the latter activates epithelial-mesenchymal transition via PI3K-AKT signaling pathways impacting tumorigenesis. Therefore, NAs-mediated downregulation of UCA1 promotes ESCC progression through targeting hnRNP F/FGFR2/PI3k-AKT axis, which provides a new chemical carcinogenic target and establishes a previously unknown mechanism for NAs-induced ESCC.

Tri-n-butyl phosphate (TnBP), a typical alkyl organophosphate ester is widely used as an emerging flame retardant for polybrominated diphenyl ethers alternatives, but the potential toxicity and mechanism are unclear. In this study, the reproductive toxicity of TnBP and its related mechanisms were explored using the Caenorhabditis elegans (C. elegans) model. After TnBP (100–1000 μg/L) exposure, brood size and the number of fertilized eggs in the uterus in C. elegans were significantly reduced, the relative area of gonad arm and the number of total germline cells in C. elegans were significantly reduced, germ cell apoptosis and germ cell DNA damage in C. elegans were significantly increased, the level of ROS in C. elegans was significantly increased. Furthermore, TnBP exposure caused abnormal gene expressions of cell apoptosis (ced-9, ced-4 and ced-3), DNA damage (hus-1, clk-2, cep-1 and egl-1) and oxidative stress (mev-1 and gas-1). TnBP exposure can lead to reproductive ability decreased and gonad development impaired in C. elegans, the mechanism of TnBP reduced reproductive ability may be related to germ cell apoptosis, germ cell DNA damage and oxidative stress. Environmental exposure to TnBP may have potential reproductive toxicity.

Lithium-rich antiperovskites (LiRAPs) hold great promise to be the choice of solid-state electrolytes (SSEs) owing to their high ionic conductivity, low activation energy, and low cost. However, processing sheet-type solid-state Li metal batteries (SSLiB) with LiRAPs remains challenging due to the lack of robust techniques for battery processing. Herein, we propose a scalable slurry-based procedure to prepare a flexible composite electrolyte (CPE), in which LiRAP (e.g., Li2OHCl0.5Br0.5, LOCB) and nitrile butadiene rubber (NBR) serve as an active filler and as a polymer scaffold, respectively. The low-polar solvent helps to stabilize the LiRAP phase during slurry processing. It is found that the addition of LOCB into the NBR polymer enhances the Li ion conductivity for 2.3 times at 60°C and reduces the activation energy (max. 0.07 eV). The as-prepared LOCB/NBR CPE film exhibits an improved critical current of 0.4 mA cm−2 and can stably cycle for over 1000 h at 0.04 mA cm−2 under 60°C. In the SSLiB with the sheet-type configuration of LiFePO4(LFP)||LOCB/NBR CPE||Li, LFP exhibits a capacity of 137 mAh/g under 60 at 0.1°C. This work delivers an effective strategy for fabrication of LiRAP-based CPE film, advancing the LiRAP-family SSEs toward practical applications.

Noise-induced hearing loss (NIHL) has always been an important occupational hazard, but the exact etiopathogenesis underlying NIHL remains unclear. Herein, we aimed to find metabolic biomarkers involved in the development of NIHL based on a mouse model using a gas chromatography coupled with mass spectrometry (GC-MS) metabolomics technique. We showed that the auditory brainstem response (ABR) thresholds at the frequencies of 4, 8, 12, 16, 24, and 32 kHz were all significantly elevated in the noise-exposed mice. Noise could cause outer hair cell (OHC) loss in the base of the cochlea. A total of 17 differential metabolites and 9 metabolic pathways were significantly affected following noise exposure. Spermidine acting as an autophagy modulator was found to be 2.85-fold higher in the noise-exposed group than in the control group and involved in β-alanine metabolism and arginine and proline metabolism pathways. Additionally, we demonstrated that LC3B and Beclin1 were expressed in the spiral ganglion neurons (SGNs), and their mRNA levels were increased after noise. We showed that SOD activity was significantly decreased in the cochlea of noise-exposed mice. Further experiments suggested that SOD1 and SOD2 proteins in the SGNs were all decreased following noise exposure. The upregulation of spermidine may induce LC3B- and Beclin1-mediated autophagy in the cochlear hair cells (HCs) through β-alanine metabolism and arginine and proline metabolism and be involved in the NIHL. ROS-mediated oxidative damage may be a pivotal molecular mechanism of NIHL. Taken together, spermidine can be regarded as an important metabolic marker for the diagnosis of NIHL.

Background: Noise is a widespread occupational hazardous factor affecting the health of workers in occupational health field. Noise-induced hearing loss (NIHL) and hypertension are the important biological adverse effects caused by occupational noise exposure. This study aimed to determine the binaural high frequency (3, 4, and 6 kHz) threshold on average (BHFTA) and levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), to assess the prevalence of NIHL and hypertension and determine the factors influencing the risk of both, and to evaluate the association between NIHL and hypertension among occupational noise-exposed workers. Methods: Questionnaire and occupational health checkup were performed to collect the personal information and physical examination data. Finally, baseline data from 42,588 occupational noise-exposed workers were analyzed. Noise intensity in the workplaces was measured using sound level meter. Pure tone audiometry (PTA) was measured at 3, 4 and 6 kHz using diagnostic audiometer. Moreover, blood pressure level was measured using automated sphygmomanometer. Results: The mean levels of BHFTA, SBP, and DBP were 23.09 ± 11.32 dB, 126.85 ± 15.94 mm Hg, 79.94 ± 11.61 mm Hg. Of the 42,588 subjects, the prevalence of NIHL and hypertension were 24.38% (n = 10,383) and 25.40% (n = 10,816). The results suggested that higher risk of NIHL and hypertension were more likely to be the subgroups of male gender, aged > 35 years, noise exposure time > 5 years, noise exposure level > 85 dB (A) and smoking. The BHFTA, SBP, and DBP levels increased with the age, noise exposure time and exposure level (Ptrend < 0.001). Besides, similar trends were also observed in the prevalence of NIHL and hypertension. Furthermore, there was a significant association of NIHL with hypertension. We found that 32.25% (n = 3,348) workers with NIHL had hypertension. The mean levels of SBP and DBP in NIHL workers were significantly higher than those with normal hearing (P < 0.001). Besides, workers with NIHL had a significantly higher risk of developing hypertension than normal hearing workers (adjusted OR = 1.07, 95%CI = 1.02-1.13). Conclusion: Our current findings suggest that the prevalence of NIHL and hypertension are high in the studied workers and occupational noise exposure is an important factor. Therefore, it is urgent to reduce noise exposure in the workplaces and to strengthen industrial noise monitoring.

As one of the most common forms of RNA modification, N6-methyladenosine (m6A) RNA modification has attracted increasing research interest in recent years. This reversible RNA modification added a new dimension to the post-transcriptional regulation of gene expression. In colorectal cancer (CRC), the role of m6A modification has been extensively studied, not only on mRNAs but also on non-coding RNAs (ncRNAs). In the present review, we depicted the role of m6A modification in CRC, systematically elaborate the interaction between m6A modification and regulatory ncRNAs in function and mechanism. Moreover, we discussed the potential applications in clinical.