A disproportionate impact of G9a methyltransferase deficiency on the X chromosome.

G9a is a histone methyltransferase responsible for the dimethylation of histone H3 at lysine 9 (H3K9me2). G9a plays key roles in transcriptional silencing of developmentally regulated genes, but its role in X-chromosome inactivation (XCI) has been under debate. Here, we uncover a female-specific function of G9a and demonstrate that deleting G9a has a disproportionate impact on the X chromosome relative to the rest of the genome. G9a deficiency causes a failure of XCI and female-specific hypersensitivity to drug inhibition of H3K9me2. We show that G9a interacts with Tsix and Xist RNAs, and that competitive inhibition of the G9a-RNA interaction recapitulates the XCI defect. During XCI, Xist recruits G9a to silence X-linked genes on the future inactive X. In parallel on the future Xa, Tsix recruits G9a to silence Xist in cis Thus, RNA tethers G9a for allele-specific targeting of the H3K9me2 modification and the G9a-RNA interaction is essential for XCI.

Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation.

Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.

Global profiling of ribosomal protein acetylation reveals essentiality of acetylation homeostasis in maintaining ribosome assembly and function.

Acetylation is a global post-translational modification that regulates various cellular processes. Bacterial acetylomic studies have revealed extensive acetylation of ribosomal proteins. However, the role of acetylation in regulating ribosome function remains poorly understood. In this study, we systematically profiled ribosomal protein acetylation and identified a total of 289 acetylated lysine residues in 52 ribosomal proteins (r-proteins) from Salmonella Typhimurium. The majority of acetylated lysine residues of r-proteins were found to be regulated by both acetyltransferase Pat and metabolic intermediate acetyl phosphate. Our results show that acetylation plays a critical role in the assembly of the mature 70S ribosome complex by modulating r-proteins binding to rRNA. Moreover, appropriate acetylation is important for the interactions between elongation factors and polysomes, as well as regulating ribosome translation efficiency and fidelity. Dysregulation of acetylation could alter bacterial sensitivity to ribosome-targeting antibiotics. Collectively, our data suggest that the acetylation homeostasis of ribosomes is crucial for their assembly and function. Furthermore, this mechanism may represent a universal response to environmental signals across different cell types.

Mechanistic insights into the subversion of the linear ubiquitin chain assembly complex by the E3 ligase IpaH1.4 of Shigella flexneri.

Shigella flexneri, a gram-negative bacterium, is the major culprit of bacterial shigellosis and causes a large number of human infection cases and deaths worldwide annually. For evading the host immune response during infection, S. flexneri secrets two highly similar E3 ligases, IpaH1.4 and IpaH2.5, to subvert the linear ubiquitin chain assembly complex (LUBAC) of host cells, which is composed of HOIP, HOIL-1L, and SHARPIN. However, the detailed molecular mechanism underpinning the subversion of the LUBAC by IpaH1.4/2.5 remains elusive. Here, we demonstrated that IpaH1.4 can specifically recognize HOIP and HOIL-1L through its leucine-rich repeat (LRR) domain by binding to the HOIP RING1 domain and HOIL-1L ubiquitin-like (UBL) domain, respectively. The determined crystal structures of IpaH1.4 LRR/HOIP RING1, IpaH1.4 LRR/HOIL-1L UBL, and HOIP RING1/UBE2L3 complexes not only elucidate the binding mechanisms of IpaH1.4 with HOIP and HOIL-1L but also unveil that the recognition of HOIP by IpaH1.4 can inhibit the E2 binding of HOIP. Furthermore, we demonstrated that the interaction of IpaH1.4 LRR with HOIP RING1 or HOIL-1L UBL is essential for the ubiquitination of HOIP or HOIL-1L in vitro as well as the suppression of NF-κB activation by IpaH1.4 in cells. In summary, our work elucidated that in addition to inducing the proteasomal degradation of LUBAC, IpaH1.4 can also inhibit the E3 activity of LUBAC by blocking its E2 loading and/or disturbing its stability, thereby providing a paradigm showing how a bacterial E3 ligase adopts multiple tactics to subvert the key LUBAC of host cells.

Structural Fingerprinting of the Frontal Aslant Tract: Predicting Cognitive Control Capacity and Obsessive-Compulsive Symptoms.

White matter of the human brain is influenced by common genetic variations and shaped by neural activity-dependent experiences. Variations in microstructure of cerebral white matter across individuals and even across fiber tracts might underlie differences in cognitive capacity and vulnerabilities to mental disorders. The frontoparietal and cingulo-opercular networks of the brain constitute the central system supporting cognitive functions, and functional connectivity of these networks has been used to distinguish individuals known as "functional fingerprinting." The frontal aslant tract (FAT) that passes through the two networks has been implicated in executive functions. However, whether FAT can be used as a "structural fingerprint" to distinguish individuals and predict an individual's cognitive function and dysfunction is unknown. Here we investigated the fingerprinting property of FAT microstructural profiles using three independent diffusion MRI datasets with repeated scans on human participants including both females and males. We found that diffusion and geometric profiles of FAT can be used to distinguish individuals with a high accuracy. Next, we demonstrated that fractional anisotropy in different FAT segments predicted distinct cognitive functions, including working memory, inhibitory control, and relational reasoning. Finally, we assessed the contribution of altered FAT microstructural profiles to cognitive dysfunction in unmedicated patients with obsessive-compulsive disorders. We found that the altered microstructure in FAT was associated with the severity of obsessive-compulsive symptoms. Collectively, our findings suggest that the microstructural profiles of FAT can identify individuals with a high accuracy and may serve as an imaging marker for predicting an individual's cognitive capacity and disease severity.SIGNIFICANCE STATEMENT The frontoparietal network and cingulo-opercular network of the brain constitute a dual-network architecture for human cognitive functions, and functional connectivity of these two networks can be used as a "functional fingerprint" to distinguish individuals. However, the structural underpinnings of these networks subserving individual heterogeneities in their functional connectivity and cognitive ability remain unknown. We show here that the frontal aslant tract (FAT) that passes through the two networks distinguishes individuals with a high accuracy. Further, we demonstrate that the diffusion profiles of FAT predict distinct cognitive functions in healthy subjects and are associated with the clinical symptoms in patients with obsessive-compulsive disorders. Our findings suggest that the FAT may serve as a unique structural fingerprint underlying individual cognitive capability.

Integrated GelMA and interleukin 8-loaded liposome composite scaffold for endogenous BMSCs recruitment in bone repair.

Bone repair strategies, based on endogenous stem cell recruitment, can effectively avoid immune rejection and the low utilization of exogenous stem cells. Endogenous stem cells can be recruited to the implantation site by loading chemokines onto bone tissue-engineered scaffolds. However, challenges such as unstable chemokine activity and easy inactivation after implantation remain significant. In the present study, composite fiber scaffolds ((IL8@LIP)-GelMA) consisting of Interleukin 8 (IL8) -loaded liposomes and GelMA were constructed by electrospinning and photocrosslinking, and its ability to recruit bone marrow-derived mesenchymal stem cells (BMSCs) and immunomodulatory effect was investigated. Compared to GelMA loaded directly with IL8, scaffolds of (IL8@LIP)-GelMA demonstrated superior protection of IL8 activity, ensuring a slow and continuous release. Both in vivo and in vitro experiments demonstrated that the (IL8@LIP)-GelMA scaffolds effectively recruited BMSCs to the desired sites. Additionally, the (IL8@LIP)-GelMA scaffolds exhibited the capacity to recruit more macrophages to the implantation site. Importantly, they promoted the polarization of macrophages toward the M2 anti-inflammatory phenotype, facilitating the transition from the inflammatory stage to the tissue repair stage. Therefore, (IL8@LIP)-GelMA scaffolds show great potential for cell-free tissue engineering applications and provide insights into the loading mode of growth factors in scaffolds.

Comparative transcriptome analysis reveals the redirection of metabolic flux from cell growth to astaxanthin biosynthesis in Yarrowia lipolytica.

Engineering Yarrowia lipolytica to produce astaxanthin provides a promising route. Here, Y. lipolytica M2 producing a titer of 181 mg/L astaxanthin was isolated by iterative atmospheric and room-temperature plasma mutagenesis and diphenylamine-mediated screening. Interestingly, a negative correlation was observed between cell biomass and astaxanthin production. To reveal the underlying mechanism, RNA-seq analysis of transcriptional changes was performed in high producer M2 and reference strain M1, and a total of 1379 differentially expressed genes were obtained. Data analysis revealed that carbon flux was elevated through lipid metabolism, acetyl-CoA and mevalonate supply, but restrained through central carbon metabolism in strain M2. Moreover, upregulation of other pathways such as ATP-binding cassette transporter and thiamine pyrophosphate possibly provided more cofactors for carotenoid hydroxylase and relieved cell membrane stress caused by astaxanthin insertion. These results suggest that balancing cell growth and astaxanthin production may be important to promote efficient biosynthesis of astaxanthin in Y. lipolytica.

Mitochondrial GCN5L1 acts as a novel regulator for iron homeostasis to promote sorafenib sensitivity in hepatocellular carcinoma.

BACKGROUND: Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell death underlying the mechanism of sorafenib. Iron is crucial for synthesis of cofactors essential to mitochondrial enzymes and necessary for HCC proliferation, while mitochondrial iron overload and oxidative stress are associated with sorafenib induced ferroptosis. However, the crosstalk among iron homeostasis and sorafenib resistance is unclear. METHODS: We conducted bioinformatics analysis of sorafenib treated HCC datasets to analyze GCN5L1 and iron related gene expression with sorafenib resistance. GCN5L1 deleted HCC cell lines were generated by CRISPR technology. Sorafenib resistant HCC cell line was established to validate dataset analysis and evaluate the effect of potential target. RESULTS: We identified GCN5L1, a regulator of mitochondrial acetylation, as a modulator in sorafenib-induced ferroptosis via affecting mitochondrial iron homeostasis. GCN5L1 deficiency significantly increased sorafenib sensitivity in HCC cells by down-regulating mitochondrial iron transporters CISD1 expression to induce iron accumulation. Mitochondrial iron accumulation leads to an acceleration in cellular and lipid ROS. Sorafenib resistance is related to CISD1 overexpression to release mitochondrial iron and maintaining mitochondrial homeostasis. We combined CISD1 inhibitor NL-1 with sorafenib, which significantly enhanced sorafenib-induced ferroptosis by promoting mitochondrial iron accumulation and lipid peroxidation. The combination of NL-1 with sorafenib enhanced sorafenib efficacy in vitro and in vivo. CONCLUSIONS: Our findings demonstrate that GCN5L1/CISD1 axis is crucial for sorafenib resistance and would be a potential therapeutic strategy for sorafenib resistant HCC.

The transcription factor ThDOF8 binds to a novel cis-element and mediates molecular responses to salt stress in Tamarix hispida.

Salt stress is a common abiotic factor that restricts plant growth and development. As a halophyte, Tamarix hispida is a good model plant for exploring salt-tolerance genes and regulatory mechanisms. DNA-binding with one finger (DOF) is an important transcription factor (TF) that influences and controls various signaling substances involved in diverse biological processes related to plant growth and development, but the regulatory mechanisms of DOF TFs in response to salt stress are largely unknown in T. hispida. In the present study, a newly identified Dof gene, ThDOF8, was cloned from T. hispida, and its expression was found to be induced by salt stress. Transient overexpression of ThDOF8 enhanced T. hispida salt tolerance by enhancing proline levels, and increasing the activities of the antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD). These results were also verified in stably transformed Arabidopsis. Results from TF-centered yeast one-hybrid (Y1H) assays and EMSAs showed that ThDOF8 binds to a newly identified cis-element (TGCG). Expression profiling by gene chip analysis identified four potential direct targets of ThDOF8, namely the cysteine-rich receptor-like kinases genes, CRK10 and CRK26, and two glutamate decarboxylase genes, GAD41, and GAD42, and these were further verified by ChIP-quantitative-PCR, EMSAs, Y1H assays, and ß-glucuronidase enzyme activity assays. ThDOF8 can bind to the TGCG element in the promoter regions of its target genes, and transient overexpression of ThCRK10 also enhanced T. hispida salt tolerance. On the basis of our results, we propose a new regulatory mechanism model, in which ThDOF8 binds to the TGCG cis-element in the promoter of the target gene CRK10 to regulate its expression and improve salt tolerance in T. hispida. This study provides a basis for furthering our understanding the role of DOF TFs and identifying other downstream candidate genes that have the potential for improving plant salt tolerance via molecular breeding.

Expression of Toll-like receptors and host defence peptides in the cecum of chicken challenged with Eimeria tenella.

Chicken coccidiosis, caused by Eimeria protozoa, affects poultry farming. Toll-like receptors (TLRs) and host defence peptides (HDPs) help host innate immune responses to eliminate invading pathogens, but their roles in Eimeria tenella infection remain poorly understood. Herein, 14-day-old chickens were treated orally with 50,000 E. tenella oocysts and the cecum was dissected at different timepoints. mRNA expression of 10 chicken TLRs (chTLRs) and five HDPs was measured by quantitative real-time PCR. chTLR7 and chTLR15 were upregulated significantly at 3 h post-infection while other chTLRs were downregulated (p < .05). chTLR1a, chTLR1b, chTLR2b and chTLR4 peaked at 36 h post-infection, chTLR3, chTLR5 and chTLR15 peaked at 72 h post-infection and chTLR21 expression was highest among chTLRs, peaking at 48 h post-infection (p < 0.05). For HDPs, cathelicidin (CATH) 1 to 3 and B1 peaked at 48 h post-infection, liver-expressed antimicrobial peptide 2 peaked at 96 h post-infection, and CATH 2 expression was highest among HDPs. CATH2 and CATH3 were markedly upregulated at 3 h post-infection (p < .05). The results provide insight into innate immune molecules during E. tenella infection in chicken, and indicate that innate immune responses may mediate resistance to chicken coccidiosis.

The relationship between alcohol consumption and chronic kidney disease in patients with nonalcoholic fatty liver disease.

Objective: To examine the impact of moderate alcohol consumption on the progression of chronic kidney disease (CKD) in individuals diagnosed with non-alcoholic fatty liver disease (NAFLD), as NAFLD has been identified as an autonomous risk factor for CKD and previous research has demonstrated a reduction in overall mortality in NAFLD patients who consume alcohol in moderation.Methods: This study included participants from ten consecutive rounds of the National Health and Nutrition Examination Survey (NHANES:1998-2018). Multivariate logistic regression models were employed to assess the impact of moderate alcohol consumption on chronic kidney disease (CKD) in both male and female populations. Subgroup analysis was conducted by categorizing patients with non-alcoholic fatty liver disease (NAFLD) based on the Fibrosis-4 (FIB-4) index.Results: 17040 participants were eligible to be included in the study. The logistic regression analysis model showed that moderate alcohol consumption was a protective factor for CKD in male NAFLD patients, with an unadjusted OR: 0.37 (0.22,0.65), and p < 0.001. After further adjustment, the association persisted. However, the association was not significant in female patients with NAFLD. Among men with low risk of liver fibrosis group, moderate alcohol consumption remained a protective factor for CKD (OR = 0.32, 95% CI 0.12-0.84, p = 0.02), but the association was not significant in the high risk of liver fibrosis group. In female patients, both moderate alcohol consumption and excessive alcohol consumption were not significantly associated with CKD in either the low-risk group or the high-risk group.Conclusion: Moderate alcohol consumption is associated with a lower prevalence of CKD in men with NAFLD.

Ti4+ functionalized zirconium metal-organic frameworks with polymer brushes for specific identification of phosphopeptides in human serum and skimmed milk.

In the present study, click chemistry and Schiff base reactions were simultaneously applied to prepare polymer brush (PEG)-functionalized MOF materials (UiO-66-NH2) and immobilized with Ti4+ (MOF-Brush-THBA-Ti4+) for phosphopeptide analysis. The material has a detection limit of 0.5 fmol, a selectivity of 2000:1, and a loading capacity of 133 mg/g for phosphopeptides. It also demonstrated great repeatability (10 cycles) and recovery rate (96.7 ± 1.4%). During the analysis of bio-samples, 4 specific phosphopeptides were identified in endogenous breast cancer serum, while 11 phosphopeptides were identified in skimmed milk. Moreover, 47 phosphopeptides correlated with 29 phosphorylated proteins were selectively identified from normal control serum, and 66 phosphopeptides correlated with 26 phosphorylated proteins were identified from breast cancer serum. Further analysis of gene ontology (GO) revealed that the detected phosphorylated proteins associated with breast cancer included positive regulation of receptor-mediated endocytosis, proteolysis, extracellular exosome, heparin binding, and chaperone binding. These findings suggest that these associated pathways might contribute to the etiology of breast cancer. Overall, this application exhibits enormous potential in the identification of phosphorylated peptides within bio-samples.

Effects of first-line nucleot(s)ide analogues on lipid profiles in patients with chronic hepatitis B: a network meta-analysis.

INTRODUCTION: Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. OBJECTIVE: To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. METHODS: Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. RESULTS: A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). CONCLUSION: TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.

Acute kidney injury in hospitalized patients with nonmalignant pleural effusions: a retrospective cohort study.

BACKGROUND: Nonmalignant pleural effusion (NMPE) is common and remains a definite health care problem. Pleural effusion was supposed to be a risk factor for acute kidney injury (AKI). Incidence of AKI in NMPE patients and whether there is correlation between the size of effusions and AKI is unknown. OBJECTIVE: To assess the incidence of AKI in NMPE inpatients and its association with effusion size. STUDY DESIGN AND METHOD: We conducted a retrospective cohort study of inpatients admitted to the Chinese PLA General Hospital with pleural effusion from 2018-2021. All patients with pleural effusions confirmed by chest radiography (CT or X-ray) were included, excluding patients with diagnosis of malignancy, chronic dialysis, end-stage renal disease (ESRD), community-acquired AKI, hospital-acquired AKI before chest radiography, and fewer than two serum creatinine tests during hospitalization. Multivariate logistic regression and LASSO logistic regression models were used to identify risk factors associated with AKI. Subgroup analyses and interaction tests for effusion volume were performed adjusted for the variables selected by LASSO. Causal mediation analysis was used to estimate the mediating effect of heart failure, pneumonia, and eGFR < 60 ml/min/1.73m2 on AKI through effusion volume. RESULTS: NMPE was present in 7.8% of internal medicine inpatients. Of the 3047 patients included, 360 (11.8%) developed AKI during hospitalization. After adjustment by covariates selected by LASSO, moderate and large effusions increased the risk of AKI compared with small effusions (moderate: OR 1.47, 95%CI 1.11-1.94 p = 0.006; large: OR 1.86, 95%CI 1.05-3.20 p = 0.028). No significant modification effect was observed among age, gender, diabetes, bilateral effusions, and eGFR. Volume of effusions mediated 6.8% (p = 0.005), 4.0% (p = 0.046) and 4.6% (p < 0.001) of the effect of heart failure, pneumonia and low eGFR on the development of AKI respectively. CONCLUSION: The incidence of AKI is high among NMPE patients. Moderate and large effusion volume is independently associated with AKI compared to small size. The effusion size acts as a mediator in heart failure, pneumonia, and eGFR.

Metabolic syndrome increases osteoarthritis risk: findings from the UK Biobank prospective cohort study.

OBJECTIVE: The association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank. METHODS: A prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan-Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk. RESULTS: A total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12-1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5-1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1-1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05-1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02-1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3-1.4). CONCLUSION: MetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.

Role of early hearing aid experience in speech recognition in patients with bilateral congenital microtia following Bonebridge implantation: a retrospective cohort study.

PURPOSE: To identify audiological and demographic variables that predict speech recognition abilities in patients with bilateral microtia who underwent Bonebridge (BB) implantation. METHODS: Fifty patients with bilateral microtia and bilateral conductive hearing loss (CHL) who underwent BB implantation were included. Demographic data, preoperative hearing aid use experience, and audiological outcomes (including pure-tone hearing threshold, sound field hearing threshold [SFHT], and speech recognition ability) for each participant were obtained. The Chinese-Mandarin Speech Test Materials were used to test speech recognition ability. The word recognition score (WRS) of disyllabic words at 65 dB SPL signals was measured before and after BB implantation in quiet and noisy conditions. RESULTS: The mean preoperative WRS under quiet and noisy conditions was 10.44 ± 12.73% and 5.90 ± 8.76%, which was significantly improved to 86.38 ± 9.03% and 80.70 ± 11.34%, respectively, following BB fitting. Multiple linear regression analysis revealed that lower preoperative SFHT suggested higher preoperative WRS under both quiet and noisy conditions. Higher age at implantation predicted higher preoperative WRS under quiet conditions. Furthermore, patients with more preoperative hearing aid experience and lower postoperative SFHT were more likely to have higher postoperative WRS under both quiet and noisy testing conditions. CONCLUSIONS: This study represents the first attempt to identify predictors of preoperative and postoperative speech recognition abilities in patients with bilateral microtia with BB implantation. These findings emphasize that early hearing intervention before implantation surgery, combined with appropriate postoperative fitting, contributes to optimal benefits in terms of postoperative speech recognition ability.

A new active bone-conduction implant: surgical experiences and audiological outcomes in patients with bilateral congenital microtia.

PURPOSE: First-generation bone bridges (BBs) have demonstrated favorable safety and audiological benefits in patients with conductive hearing loss. However, studies on the effects of second-generation BBs are limited, especially among children. In this study, we aimed to explore the surgical and audiological effects of second-generation BBs in patients with bilateral congenital microtia. METHODS: This single-center prospective study included nine Mandarin-speaking patients with bilateral microtia. All the patients underwent BCI Generation 602 (BCI602; MED-EL, Innsbruck, Austria) implant surgery between September 2021 and June 2023. Audiological and sound localization tests were performed under unaided and BB-aided conditions. RESULTS: The transmastoid and retrosigmoid sinus approaches were implemented in three and six patients, respectively. No patient underwent preoperative planning, lifts were unnecessary, and no sigmoid sinus or dural compression occurred. The mean function gain at 0.5-4.0 kHz was 28.06 ± 4.55-dB HL. The word recognition scores improved significantly in quiet under the BB aided condition. Signal-to-noise ratio reduction by 10.56 ± 2.30 dB improved the speech reception threshold in noise. Patients fitted with a unilateral BB demonstrated inferior sound source localization after the initial activation. CONCLUSIONS: Second-generation BBs are safe and effective for patients with bilateral congenital microtia and may be suitable for children with mastoid hypoplasia without preoperative three-dimensional reconstruction.

A Study on the Nonsurgical Correction Treatment Age Window and Long-Term Follow-Up of Infants With Congenital Ear Anomalies in China.

OBJECTIVES: To evaluate the efficacy of ear molding across various initial ages and analyze challenges encountered by infants beyond the optimal treatment age window. METHODS: A retrospective review of 331 infants (527 ears) treated with EarWell was conducted over 5 years from January 2017 to March 2022 at a single center. The treatment duration of the ear molding, success rate, recurrence rate, and complication rate were analyzed among the 3 age groups. Concentrate on evaluating treatment outcomes for infants with an initial age exceeding 42 days. RESULTS: The mean age at initial treatment was 25±28 days. In addition, it includes a child with cryptotia who is 3.5 years old (1278 d). The mean duration of treatment was 7±5 weeks. In the long-term follow-up, the overall treatment success rate was 92%, with 467 ears (88.6%) showing improvement without recurrence, 30 ears (5.7%) experiencing varying degrees of recurrence, and 30 ears (5.7%) showing no improvement or complete recurrence. A total of 20 infants (3%) developed mild skin complications during treatment. CONCLUSIONS: Ear molding is a safe and effective option for the treatment of congenital ear anomalies, with a low recurrence rate during long-term follow-up. For infants with congenital auricular anomalies aged over 42 days, ear molding remains a viable option. Treatment success may be influenced by the age at treatment, the subtype of anomalies, and relies on the assessment of a specialized otologist, expert procedural techniques, as well as thorough understanding and cooperation from parents.

Analysis of Volatile Aroma Components in Different Parts of Shiitake Mushroom (Lentinus edodes) Treated with Ultraviolet C Light-Emitting Diodes Based on Gas Chromatography-Ion Mobility Spectroscopy.

Further assessment of ultraviolet C light-emitting diode (UVC-LED) irradiation for influencing shiitake mushrooms' (Lentinus edodes) volatile and sensory properties is needed. In this study, a comparison of UVC-LED irradiation treatment on the flavor profiles in various parts of shiitake mushrooms was conducted using gas chromatography-ion mobility spectrometry (GC-IMS) and sensory analysis. Sixty-three volatile compounds were identified in shiitake mushrooms. The fresh shiitake mushrooms were characterized by the highest values of raw mushroom odors. After UVC-LED treatment, the content of C8 alcohols decreased, especially that of 1-octen-3-ol, while the content of aldehydes increased, especially the content of nonanal and decanal. The score of fatty and green odors was enhanced. For fresh samples, the mushroom odors decreased and the mushroom-like odors weakened more sharply when treated in ethanol suspension than when treated with direct irradiation. The fruit odors were enhanced using direct UVC-LED irradiation for fresh mushroom samples and the onion flavor decreased. As for shiitake mushroom powder in ethanol suspension treated with UVC-LED, the sweaty and almond odor scores decreased and the vitamin D2 content in mushroom caps and stems reached 668.79 µg/g (dw) and 399.45 µg/g (dw), respectively. The results obtained from this study demonstrate that UVC-LED treatment produced rich-flavored, quality mushroom products.

Non-Fluorinated Ethers to Mitigate Electrode Surface Reactivity in High-Voltage NCM811-Li Batteries.

Lithium (Li) metal batteries (LMBs) with nickel (Ni)-rich layered oxide cathodes exhibit twice the energy density of conventional Li-ion batteries. However, their lifespan is limited by severe side reactions caused by high electrode reactivity. Fluorinated solvent-based electrolytes can address this challenge, but they pose environmental and biological hazards. This work reports on the molecular engineering of fluorine (F)-free ethers to mitigate electrode surface reactivity in high-voltage Ni-rich LMBs. By merely extending the alkyl chains of traditional ethers, we effectively reduce the catalytic reactivity of the cathode towards the electrolyte at high voltages, which suppresses the oxidation decomposition of the electrolyte, microstructural defects and rock-salt phase formation in the cathode, and gas release issues. The high-voltage Ni-rich NCM811-Li battery delivers capacity retention of 80 % after 250 cycles with a high Coulombic efficiency of 99.85 %, even superior to that in carbonate electrolytes. Additionally, this strategy facilitates passivation of the Li anode by forming a robust solid-electrolyte interphase, boosting the Li reversibility to 99.11 % with a cycling life of 350 cycles, which outperforms conventional F-free ether electrolytes. Consequently, the lifespan of practical LMBs has been prolonged by over 100 % and 500 % compared to those in conventional carbonate- and ether-based electrolytes, respectively.