Crystalline silica-induced endoplasmic reticulum stress promotes the pathogenesis of silicosis by augmenting proinflammatory interstitial pulmonary macrophages.

Crystalline silica (CS) particles are ubiquitously present in the environment, particularly in occupational settings, and exposure to respirable CS causes silicosis, imposing a significant disease burden. However, the pathogenesis of silicosis remains unclear. Exposure to external stimuli, such as CS, leads to the accumulation of unfolded proteins and triggers endoplasmic reticulum (ER) stress, disrupting tissue immune homeostasis and accelerating pathological progression. While pulmonary macrophages phagocytose CS particles to initiate the immune response, the role of ER stress in this process is unknown. Herein, we used a murine model of silicosis to simulate the pathological progression from acute inflammation to fibrosis in silicosis and conducted in vivo pharmacological inhibition of ER stress to explore the underlying mechanism. Using flow cytometry, we further classified pulmonary macrophages into monocyte-like macrophages (monocytes), interstitial macrophages (IMs), and alveolar macrophages (AMs). Our results showed that CS-induced ER stress primarily contributed to the augmentation of IMs and thereby exerted a significant impact on pulmonary macrophages. Despite coexpressing M1- and M2-like markers, IMs predominantly exhibited an M1-like polarization state and played a proinflammatory role by expressing the cytokines pro-IL-1ß and TNF-α during the pathological progression of silicosis. Additionally, IMs recruited by CS-induced ER stress also exhibited high expression of MHCII and exerted active immunomodulatory effects. Overall, our study demonstrates that ER stress induced by CS particles triggers a proinflammatory immune microenvironment dominated by IMs and reveals novel insights into the pulmonary toxicological effects of CS particles.

Abnormalities in emotion regulation are associated with negative, but not positive or disorganized schizotypy: An experience sampling study.

BACKGROUND: Schizotypy, a multidimensional construct with positive, negative, and disorganized dimensions, represents a vulnerability marker for the development of schizophrenia. Although there has been increasing evidence linking schizotypy to emotion regulation (ER) deficits, the specific association between different schizotypal dimensions and alterations in ER strategy use in daily life remains poorly understood. METHODS: Using the experience sampling method (ESM), the present study examined the associations between positive, negative, and disorganized schizotypy and ER strategy use in daily life in a nonclinical young adult sample (N = 258). Participants were instructed to report their ER strategy use 5 times a day for 14 days. Four adaptive ER strategies (reflection, reappraisal, social sharing, and distraction) and two maladaptive ER strategies (suppression and rumination) were included. RESULTS: Multilevel modeling analyses showed that positive schizotypal traits predicted greater use of adaptive ER strategies, while negative schizotypal traits predicted less use of adaptive ER strategies and more frequent use of emotional suppression in daily life. No associations between disorganized schizotypal traits and any ER strategy use were found. CONCLUSION: Schizotypy dimensions are differentiated by preferences for different ER strategies in daily life. The findings suggest a strong association between negative schizotypy and notable dysfunctions in ER, emphasizing the significance of negative schizotypy as a vulnerability factor for psychosis.

Association between Pericoronary Fat Attenuation Index Values and Plaque Composition Volume Fraction Measured by Coronary Computed Tomography Angiography.

RATIONALE AND OBJECTIVES: The pericoronary fat attenuation index (FAI) values around plaques may reveal the relationship between periplaque vascular inflammation and different plaque component volume fractions. We aimed to evaluate the potential associations between periplaque FAI values and plaque component volume fractions. MATERIALS AND METHODS: 496 patients (1078 lesions) with coronary artery disease, who underwent computed tomography angiography (CCTA) between September 2022 and August 2023, were analyzed retrospectively. Each lesion was characterized and the plaque component volume fractions and periplaque FAI values were measured. Multiple linear regression, weighted quantile sum (WQS) regression, and quantile g-computation (Qgcomp) were used to explore the relationship between plaque component volume fractions and the risk of elevated periplaque FAI values. RESULTS: After adjusting for clinical characteristics, multiple linear regression identified that lipid components volume fraction (ß = 0.162, P < 0.001) were independent risk factors for elevated periplaque FAI values whereas calcified components volume fraction (ß = -0.066, P = 0.025) were independent protective factors. The WQS regression models indicated an increase in the overall confounding effect of the adjusted lipid indices and plaque composition volume fraction on the risk of elevated periplaque FAI values (P = 0.004). Qgcomp analysis indicated lipid component volume fraction and calcified component volume fraction was positively and negatively correlated with elevated plaque FAI values, respectively (all P < 0.05). CONCLUSIONS: Periplaque FAI values quantified by CCTA were strongly correlated with lipid and calcification component volume fractions.

ABHD5 regulates midgut-specific lipid homeostasis in Bombyx mori.

Lipids are an important energy source and are utilized as substrates for various physiological processes in insects. Comparative gene identification 58 (CGI-58), also known as α/ß hydrolase domain-containing 5 (ABHD5), is a highly conserved and multifunctional gene involved in regulating lipid metabolism and cellular energy balance in many organisms. However, the biological functions of ABHD5 in insects are poorly understood. In the current study, we describe the identification and characterization of the ABHD5 gene in the lepidopteran model insect, Bombyx mori. The tissue expression profile investigated using quantitative reverse transcription polymerase chain reaction (RT-qPCR) reveals that BmABHD5 is widely expressed in all tissues, with particularly high levels found in the midgut and testis. A binary transgenic CRISPR/Cas9 system was employed to conduct a functional analysis of BmABHD5, with the mutation of BmABHD5 leading to the dysregulation of lipid metabolism and excessive lipid accumulation in the larval midgut. Histological and physiological analysis further reveals a significant accumulation of lipid droplets in the midgut of mutant larvae. RNA-seq and RT-qPCR analysis showed that genes related to metabolic pathways were significantly affected by the absence of BmABHD5. Altogether, our data prove that BmABHD5 plays an important role in regulating tissue-specific lipid metabolism in the silkworm midgut.

Insight into the mechanisms of combined toxicity of cadmium and flotation agents in luminescent bacteria: Role of micro/nano particles.

Currently, risk assessment and pollution management in mines primarily focus on toxic metals, with the flotation agents being overlooked. However, the combined effects of metals and flotation agents in mines remain largely unknown. Therefore, this study aimed to evaluate the combined effects of Cd and two organic flotation agents (ethyl xanthate (EX) and diethyldithiocarbamate (DDTC)), and the associated mechanisms. The results showed that Cd + EX and Cd + DDTC exhibited synergistic toxicity. The EC50 values for luminescent bacteria were 1.6 mg/L and 1.0 mg/L at toxicity unit ratios of 0.3 and 1, respectively. The synergistic effects were closely related with the formation of Cd(EX)2 and Cd(DDTC)2 micro/nano particles, with nano-particles exhibiting higher toxicity. We observed severe cell membrane damage and cell shrinkage of the luminescent bacteria, which were probably caused by secondary harm to cells through the released CS2 during their decomposition inside cells. In addition, these particles induced toxicity by altering cellular levels of biochemical markers and the transcriptional levels of transport proteins and lipoproteins, leading to cell membrane impairment and DNA damage. This study has demonstrated that particulates formed by Cd and flotation agents contribute to the majority of the toxicity of the binary mixture. This study helps to better understand the complex ecological risk of inorganic metals and organic flotation agents in realistic mining environments.

Pathogenic fungi synergistically cooperate with Serratia marcescens to increase cockroach mortality.

The abuse of chemical insecticides has led to strong resistance in cockroaches, and biopesticides with active ingredients based on insect pathogens have good development prospects; however, their slow effect has limited their practical application, and improving their effectiveness has become an urgent problem. In this study, the interaction between Serratia marcescens and Metarhizium anisopliae enhanced their virulence against Blattella germanica and exhibited a synergistic effect. The combination of S. marcescens and M. anisopliae caused more severe tissue damage and accelerated the proliferation of the insect pathogen. The results of high-throughput sequencing demonstrated that the gut microbiota was dysbiotic, the abundance of the opportunistic pathogen Weissella cibaria increased, and entry into the hemocoel accelerated the death of the German cockroaches. In addition, the combination of these two agents strongly downregulated the expression of Imd and Akirin in the IMD pathway and ultimately inhibited the expression of antimicrobial peptides (AMPs). S. marcescens released prodigiosin to disrupted the gut homeostasis and structure, M. anisopliae released destruxin to damaged crucial organs, opportunistic pathogen Weissella cibaria overproliferated, broke the gut epithelium and entered the hemocoel, leading to the death of pests. These findings will allow us to optimize the use of insect pathogens for the management of pests and produce more effective biopesticides.

CoH-catalyzed asymmetric remote hydroalkylation of heterocyclic alkenes: a rapid approach to chiral five-membered S- and O-heterocycles.

Saturated heterocycles, which incorporate S and O heteroatoms, serve as fundamental frameworks in a diverse array of natural products, bioactive compounds, and pharmaceuticals. Herein, we describe a unique cobalt-catalyzed approach integrated with a desymmetrization strategy, facilitating precise and enantioselective remote hydroalkylation of unactivated heterocyclic alkenes. This method delivers hydroalkylation products with high yields and excellent stereoselectivity, representing good efficiency in constructing alkyl chiral centers at remote C3-positions within five-membered S/O-heterocycles. Notably, the broad scope and good functional group tolerance of this asymmetric C(sp3)-C(sp3) coupling enhance its applicability.

Phenethyl isothiocyanate inhibits the carcinogenic properties of hepatocellular carcinoma Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways.

Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited effective treatment options. Phenethyl isothiocyanate (PEITC) is a bioactive substance present primarily in the cruciferous vegetables. PEITC has exhibited anti-cancer properties in various cancers, including lung, bile duct, and prostate cancers. It has been demonstrated that PEITC can inhibit the proliferation, invasion, and metastasis of SK-Hep1 cells, while effectively inducing apoptosis and cell cycle arrest in HepG2 cells. However, knowledge of its anti-carcinogenic effects on Huh7.5.1 cells and its underlying mechanism remains elusive. In the present study, we aim to evaluate the anti-carcinogenic effects of PEITC on human HCC Huh7.5.1 cells. Methods: MTT assay and colony formation assay was performed to investigate the anti-proliferative effects of PEITC against Huh7.5.1 cells. The pro-apoptosis effects of PEITC were determined by Annexin V-FITC/PI double staining assay by flow cytometry (FCM), mitochondrial transmembrane potential (MMP) measurement, and Caspase-3 activity detection. A DAPI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was conducted to estimate the DNA damage in Huh7.5.1 cells induced by PEITC. Cell cycle progression was determined by FCM. Transwell invasion assay and wound healing migration assay were performed to investigate the impact of PEITC on the migration and invasion of Huh7.5.1 cells. In addition, transcriptome sequencing and gene set enrichment analysis (GSEA) were used to explore the potential molecular mechanisms of the inhibitory effects of PEITC on HCC. Quantitative real-time PCR (qRT-PCR) analysis was performed to verify the transcriptome data. Results: MTT assay showed that treatment of Huh7.5.1 cells with PEITC resulted in a dose-dependent decrease in viability, and colony formation assay further confirmed its anti-proliferative effect. Furthermore, we found that PEITC could induce mitochondrial-related apoptotic responses, including a decrease of mitochondrial transmembrane potential, activation of Caspase-3 activity, and generation of intracellular reactive oxygen species. It was also observed that PEITC caused DNA damage and cell cycle arrest in the S-phase in Huh7.5.1 cells. In addition, the inhibitory effect of PEITC on the migration and invasion ability of Huh7.5.1 cells was assessed. Transcriptome sequencing analysis further suggested that PEITC could activate the typical MAPK, PI3K-Akt, and p53 signaling pathways, revealing the potential mechanism of PEITC in inhibiting the carcinogenic properties of Huh7.5.1 cells. Conclusion: PEITC exhibits anti-carcinogenic activities against human HCC Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways. Our results suggest that PEITC may be useful for the anti-HCC treatment.

A novel three-layer module BoMYB1R1-BoMYB4b/BoMIEL1-BoDFR1 regulates anthocyanin accumulation in kale.

Anthocyanin is an important pigment responsible for plant coloration and beneficial to human health. Kale (Brassica oleracea var. acephala), a primary cool-season flowers and vegetables, is an ideal material to study anthocyanin biosynthesis and regulation mechanisms due to its anthocyanin-rich leaves. However, the underlying molecular mechanism of anthocyanin accumulation in kale remains poorly understood. Previously, we demonstrated that BoDFR1 is a key gene controlling anthocyanin biosynthesis in kale. Here, we discovered a 369-bp InDel variation in the BoDFR1 promoter between the two kale inbred lines with different pink coloration, which resulted in reduced transcriptional activity of the BoDFR1 gene in the light-pink line. With the 369-bp insertion as a bait, an R2R3-MYB repressor BoMYB4b was identified using the yeast one-hybrid screening. Knockdown of the BoMYB4b gene led to increased BoDFR1 expression and anthocyanin accumulation. An E3 ubiquitin ligase, BoMIEL1, was found to mediate the degradation of BoMYB4b, thereby promoting anthocyanin biosynthesis. Furthermore, the expression level of BoMYB4b was significantly reduced by light signals, which was attributed to the direct repression of the light-signaling factor BoMYB1R1 on the BoMYB4b promoter. Our study revealed that a novel regulatory module comprising BoMYB1R1, BoMIEL1, BoMYB4b, and BoDFR1 finely regulates anthocyanin accumulation in kale. The findings aim to establish a scientific foundation for genetic improvement of leaf color traits in kale, meanwhile, providing a reference for plant coloration studies.

Association between higher intermuscular adipose tissue and decreased renal function in patients with systemic lupus erythematosus mediated by insulin resistance.

OBJECTIVES: To quantify the relationship between abdominal computed tomography (CT)-based body composition parameters and renal function in systemic lupus erythematosus (SLE) patients and evaluate the potential effect of insulin resistance on this relationship. METHODS: SLE patients from institutions A and B between January 2017 and August 2023 were enrolled. Areas and attenuation values of subcutaneous adipose tissue, visceral adipose tissue, intermuscular adipose tissue (IMAT), and skeletal muscle index on CT images were measured at the L3 vertebral level. Logistic regression analysis was used to identify risk factors associated with decreased renal function. Linear regression models were used to describe the relationships between body composition parameters and estimated glomerular filtration rate (eGFR). Finally, we used a single-point insulin sensitivity estimator to indirectly reflect the degree of insulin resistance and assess its mediating effect on the association between IMAT area and decreased renal function. RESULTS: Three-hundred thirty-nine SLE patients from institution A (internal dataset) and 114 SLE patients from institution B (external validation dataset) were included. Multivariate logistic regression revealed that IMAT area (odds ratio (OR)institution A: 1.05 (95% confidence intervals (95% CI): 1.01, 1.10), and ORinstitution B: 1.19 (95% CI: 1.03, 1.39)) was an independent risk factor for decreased renal function in SLE patients. In the adjusted linear regression model, high IMAT area was significantly associated with reduced eGFR (ßinstitution A = -1.15, Pinstitution A = 0.005; ßinstitution B = -0.98, Pinstitution B = 0.049). Additionally, insulin resistance contributed a mediating role of 22.8% to the association. CONCLUSION: High IMAT area was associated with decreased renal function in SLE patients and insulin resistance mediated this relationship. CRITICAL RELEVANCE STATEMENT: High intermuscular adipose tissue area is associated with decreased renal function in systemic lupus erythematosus patients mediated by insulin resistance and is correlated with chronicity index in lupus nephritis patients. KEY POINTS: High intramuscular adipose tissue (IMAT) area was associated with decreased renal function in systemic lupus erythematosus (SLE) patients. Insulin resistance mediated the association between IMAT area and eGFR. IMAT area was associated with chronicity index in lupus nephritis patients.

Micellar-type aggregates of HP-ß-CD/GML inclusion complex: Increased water-solubility and effective antibacterial capabilities.

The inclusion complex (IC) was successfully obtained by encapsulating glycerol monolaurate (GML) into the cavity of hydroxypropyl-ß-cyclodextrin (HP-ß-CD). Compared with solubility of pure GML <80 µg/mL in water, and the water-solubility of encapsulated GML was significantly improved and reached to 270,000 µg/mL. IC can form nanoparticles by self-assembly, probably assigned to its strong capability to form micellar-type aggregates. A Higuchi's AL-type phase-solubility diagram indicated the strong interaction between host and guest molecules with the formation of 1:1 GML/HP-ß-CD complex and the stability constant at 6248 L/mol. Compared with pure GML, encapsulated GML at the same concentration can also show good antibacterial capabilities against S. aureus and E. coli in sterile water, and the effective preservative capabilities towards beef meatballs. The boosted enhancement in water-solubility of GML and the effective antibacterial capabilities endowed IC with potential in the application of food decontamination.

Exoskeleton rehabilitation robot training for balance and lower limb function in sub-acute stroke patients: a pilot, randomized controlled trial.

PURPOSE: This pilot study aimed to investigate the effects of REX exoskeleton rehabilitation robot training on the balance and lower limb function in patients with sub-acute stroke. METHODS: This was a pilot, single-blind, randomized controlled trial. Twenty-four patients with sub-acute stroke (with the course of disease ranging from 3 weeks to 3 months) were randomized into two groups, including a robot group and a control group. Patients in control group received upright bed rehabilitation (n = 12) and those in robot group received exoskeleton rehabilitation robot training (n = 12). The frequency of training in both groups was once a day (60 min each) for 5 days a week for a total of 4 weeks. Besides, the two groups were evaluated before, 2 weeks after and 4 weeks after the intervention, respectively. The primary assessment index was the Berg Balance Scale (BBS), whereas the secondary assessment indexes included the Fugl-Meyer Lower Extremity Motor Function Scale (FMA-LE), the Posture Assessment Scale for Stroke Patients (PASS), the Activities of Daily Living Scale (Modified Barthel Index, MBI), the Tecnobody Balance Tester, and lower extremity muscle surface electromyography (sEMG). RESULTS: The robot group showed significant improvements (P < 0.05) in the primary efficacy index BBS, as well as the secondary efficacy indexes PASS, FMA-LE, MBI, Tecnobody Balance Tester, and sEMG of the lower limb muscles. Besides, there were a significant differences in BBS, PASS, static eye-opening area or dynamic stability limit evaluation indexes between the robotic and control groups (P < 0.05). CONCLUSIONS: This is the first study to investigate the effectiveness of the REX exoskeleton rehabilitation robot in the rehabilitation of patients with stroke. According to our results, the REX exoskeleton rehabilitation robot demonstrated superior potential efficacy in promoting the early recovery of balance and motor functions in patients with sub-acute stroke. Future large-scale randomized controlled studies and follow-up assessments are needed to validate the current findings. CLINICAL TRIALS REGISTRATION: URL: https://www.chictr.org.cn/index.html.Unique identifier: ChiCTR2300068398.

The Association of High Arousal Threshold with Hypertension and Diabetes in Obstructive Sleep Apnea.

Objective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea-hypopnea index (AHI). Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR). Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07-1.62, P < 0.01) and 1.45 (95% CI = 1.01-2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02-3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes. Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.

ß-Cyclodextrin/carbon dots-grafted cellulose nanofibrils hydrogel for enhanced adsorption and fluorescence detection of levofloxacin.

In this study, a novel hydrogel, ß-cyclodextrin/carbon dots-grafted cellulose nanofibrils hydrogel (ßCCH), was fabricated for removal and fluorescence determination of levofloxacin (LEV). A comprehensive analysis was performed to characterize its physicochemical properties. Batch adsorption experiments were conducted, revealing that ßCCH reached a maximum adsorption capacity of 1376.9 mg/g, consistent with both Langmuir and pseudo-second-order models, suggesting that the adsorption process of LEV on ßCCH was primarily driven by chemical adsorption. The removal efficiency of ßCCH was 99.2 % under the fixed conditions (pH: 6, initial concentration: 20 mg/L, contact time: 300 min, temperature: 25 °C). The removal efficiency of ßCCH for LEV still achieved 97.3 % after five adsorption-desorption cycles. By using ßCCH as a fluorescent probe for LEV, a fast and sensitive method was established with linear ranges of 1-120 mg/L and 0.2-1.0 µg/L and a limit of detection (LOD) as low as 0.09 µg/L. The viability of ßCCH was estimated based on the economic analysis of the synthesis process and the removal of LEV, demonstrating that ßCCH was more cost-effective than commercial activated carbon. This study provides a novel approach for preparing a promising antibiotic detection and adsorption material with the advantages of stability, and cost-effectiveness.

Preliminary analysis on the characteristics of light absorption coefficients in typical rivers of different river basins across China.

As a vital constituent of water's optical properties, the absorption coefficients influence the distribution of underwater light field, consequently impacting the structures and functional patterns of riverine ecosystems. In this study, the light absorption of non-algal particulates (ad(λ), m-1), phytoplankton (aph(λ), m-1) and CDOM (ag(λ), m-1) of 380 water samples collected from 133 rivers in eight external river basins across China from 2013 to 2023 were examined to determine the optical absorption characteristics. Results showed significant differences in ad(λ), aph(λ) and ag(λ) across different basins. ① The water bodies of eight basins can be categorized into 5 dominant types of absorption coefficients. ② In eastern China, ag(440) exhibited a northeast-high and southwest-low spatial distribution pattern. The Songliao River Basin had the highest ag(440) than other basins. The higher slope S of ag(λ) in rivers compared to lakes and reservoirs confirm river water primarily derive CDOM from external sources, distinguishing them from lakes and reservoirs. ③ The Huaihe and Haihe River Basins had higher ad(440) and aph(440) values, primarily due to lower terrain and human activities, leading to the accumulation of suspended particles and nutrients. And soil erosion from the Loess Plateau caused significant differences in ad(440) between the upper and middle reaches of the Yellow River Basin. These findings hold significant implications for understanding the optical characteristics of rivers in China.

A highly sensitive fluorescence sensor for tobacco mosaic virus RNA based on DSN cycle and ARGET ATRP double signal amplification.

Early and sensitive detection of tobacco mosaic virus (TMV) is of great significance for improving crop yield and protecting germplasm resources. Herein, we constructed a novel fluorescence sensor to detect TMV RNA (tRNA) through double strand specific nuclease (DSN) cycle and activator regenerative electron transfer atom transfer radical polymerization (ARGET ATRP) dual signal amplification strategy. The hairpin DNA complementarily paired with tRNA was used as a recognition unit to specifically capture tRNA. By the double-stranded DNA hydrolyzed with DSN, tRNA is released to open more hairpin DNA, and more complementary DNA (cDNA) is bound to the surface of the magnetic beads (MBs) to achieve the first amplification. After binding with the initiator, the cDNA employed ARGET ATRP to attach more fluorescent signal molecules to the surface of MBs, thus achieving the second signal amplification. Under the optimal experimental conditions, the logarithm of fluorescence intensity versus tRNA concentration showed a good linear relationship in the range of 0.01-100 pM, with a detection limit of 1.03 fM. The limit of detection (LOD) was calculated according to LOD = 3 N/S. Besides, the sensor showed good reproducibility and stability, which present provided new method for early and highly sensitive detection for plant viruses.

Increased risk of hearing loss associated with MT-RNR1 gene mutations: a real-world investigation among Han Taiwanese Population.

BACKGROUND: Previous studies have implicated inherited mutations in mitochondrial DNA (mtDNA) in sensorineural hearing loss (SNHL). However, the definitive association between mitochondrial 12S rRNA (MT-RNR1) variants and hearing loss in the population has not been well established, particularly in Asia. The objective of this retrospective cohort study was to assess the association between MT-RNR1 variants and the risk of SNHL in patients in Taiwan. METHODS: The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups. RESULTS: The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21-47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32-26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p < 0.05). CONCLUSION: This study highlights the increased risk of hearing loss in patients carrying MT-RNR1 variants, particularly those with diabetes mellitus. Future research that integrates genetic and clinical data is crucial for developing more precise interventions to monitor and treat hearing loss in this vulnerable population.

[The expression and secretion of human lactoferrin in Bacillus subtilis].

Human lactoferrin (HLF), an essential nutrient found in breast milk, possesses antibacterial, anti-inflammatory, and immune-enhancing properties. In this study, the effects of three constitutive promoters (P21, P43, and Pveg) and three inducible promoters (Pgrac100, PxylA, and Ptet*) on the expression of HLF were compared using Bacillus subtilis G601 as the host strain. The results showed that the highest expression of HLF, reaching 651.57 µg/L, was achieved when regulated by the Ptet* promoter. Furthermore, the combinational optimization of ribosome binding site (RBS) and signal peptides was investigated, and the optimal combination of RBS6 and SPyycP resulted in increased HLF expression to 1 099.87 µg/L, with 498.68 µg/L being secreted extracellularly. To further enhance HLF secretion, the metal cations-related gene dltD was knocked out, leading to an extracellular HLF level of 637.28 µg/L. This study successfully demonstrated the secretory expression of HLF in B. subtilis through the selection and optimization of expression elements, laying the foundation for the development of efficient B. subtilis cell factories for lactoprotein synthesis.

High-glucose conditions attenuate the response of macrophages to Legionella pneumophila infection by inhibiting NOD1 and MAPK signaling.

BACKGROUND: Patients with diabetes are particularly susceptible to Legionella pneumophila (LP) infection, but the exact pathogenesis of LP infection in diabetic patients is still not fully understood. Herein, we investigated the effect of diabetes on immune function during LP infection in vitro and in vivo. METHODS: The time course of LP infection in macrophages under normal and high-glucose (HG) conditions was examined in vitro. Western blot was used to determine nucleotide-binding oligomerization domain 1 (NOD1), kinase 1/2 (ERK1/2), mitogen-activated protein kinase p38 (MAPK p38), and c-Jun N-terminal kinases (JNK). Enzyme-linked immunosorbent assay (ELISA) was used to assess the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Cell Counting Kit-8 (CCK8) assay assessed U937 cell viability after treating cells with different concentrations of high sugar medium and ML130 (NOD1 inhibitor). For the in vivo study, normal and streptozocin-induced diabetic guinea pigs were infected with LP for 6, 24, and 72 h, after which NOD1, MAPK-related signals, TNF-α, and IL-6 expression in lung tissues were assessed using immunohistochemistry, western blot, and RT-PCR. RESULTS: HG attenuated the upregulation of NOD1 expression and reduced TNF-α and IL-6 secretion caused by LP compared with LP-infected cells exposed to normal glucose levels (all p < 0.05). In diabetic guinea pigs, HG inhibited the upregulation of NOD1 expression in lung tissues and the activation of p38, ERK1/2, and cJNK caused by LP infection compared to control pigs (all p < 0.05). CONCLUSION: HG attenuates the response of macrophages to LP infection by inhibiting NOD1 upregulation and the activation of MAPK signaling.

The competition of heavy metals between hyporheic sediments and microplastics of driving factors in the Beiluo River Basin.

Both sediments and microplastics (MPs) are medias of heavy metals (HMs) in river ecosystems. This study investigated HMs (Mn, Cr, V, As, Cu, Co, Cd, Pb, and Ni) concentration and driving factors for competitive enrichment between hyporheic sediments versus MPs. The medias basic characteristics indicated that the sediments were mostly sand and rich in Fe2O3; three polymer types were identified, with blue, fragment, less than 500 µm being the main types of MPs. The results have shown that the average content of extracted HMs in MPs was much higher than that of the same metals accumulated in sediments. HMs in sediments and MPs reached heavily polluted at some points, among which As and Cd were ecological risks. Electrostatic adsorption and surface complexation, and biofilm-mediated and organic matter complexation were the interaction mechanism of HMs with sediments and MPs. Further, the driving factors affecting the distribution of HMs in the two carriers were analyzed by multivariate statistical analysis. The results demonstrated that carrier characteristics, hydrochemical factors, and the inherent metal load of MPs were the main causes of the high HMs content. These findings improved our understanding of HMs fate and environmental risks across multiple medias.