Photoswitchable dynamics and RNAi synergist with tailored interface and controlled release reprogramming tumor immunosuppressive niche.

Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.

Serum calcium improves the relationship between fluoride exposure and hypothalamic-pituitary-testicular axis hormones levels in males-a cross-sectional study on farmers in the lower reaches of the Yellow River.

Numerous studies have reported the toxicity of fluoride to the male reproductive system, but epidemiological evidence is limited. We conducted a cross-sectional study in Kaifeng City, Henan Province in 2011 to explore the association between fluoride exposure and hypothalamic-pituitary-testicular (HPT) axis hormones in men. Morning urinary fluoride (UF), serum HPT axis hormones and serum calcium (SC) concentrations were detected. Percent changes and 95% confidence intervals in HPT axis hormones associated with UF were estimated using adjusted linear regression models, and performed subgroup analysis based on SC levels. The restricted cubic spline model was used to fit nonlinear relationships. For every 10% increase in UF, the concentrations of serum GnRH, T, SHBG and TSI decreased by 2.13%, 2.39%, 2.19% and 1.96%, while E2 and FEI increased by 1.11% and 3.33%. Subgroup analysis showed that for every 10% increase in UF, the levels of GnRH, T, TSI and FTI decreased by approximately 3.15%, 5.49%, 4.47% and 5.14%, while the E2 level increased by 2.92% in low-serum-calcium group (LCG). The levels of GnRH and T decreased by approximately 2.97% and 1.82% in medium-serum-calcium group (MCG). In high-serum-calcium group (HCG), serum SHBG levels decreased by 4.70%, while FTI and FEI levels increased by 4.93% and 4.20% as UF concentration increased (P < 0.05, respectively). The non-linear relationship between serum GnRH and UF concentrations presented an approximately inverted U-shaped curve, with a turning point UF concentration of 1.164 mg/L (P < 0.001), and their nonlinear relationship in LCG and MCG were similar to that in the overall subjects. In conclusion, excessive exposure to fluoride can interfere with male serum HPT axis hormones, and a moderate increase in SC alleviates the effect of fluoride. Prospective cohort studies are essential to confirm the causality.

Naringin alleviates fluoride-induced neurological impairment: A focus on the regulation of energy metabolism mediated by mitochondrial permeability transition pore.

The neurological impairment induced by fluoride is associated with mitochondrial dysfunction. Normal mitochondrial permeability transition pore (mPTP) opening plays a pivotal role in mitochondrial function. However, it remains unclear whether p53-dependent mPTP-related mitochondrial apoptosis is associated with fluoride-induced neurological impairment, and the alleviation of naringin on those. In vivo, NaF-treated rats had impaired learning and memory abilities, damaged hippocampal structure, and higher respiratory exchange rates (RER). In vitro, the increased apoptosis rates, excessive opening of mPTP, and decreased mitochondrial membrane potential (MMP) were observed in PC12 cells treated with NaF. The protein expressions of p53, CytoC, and cleaved caspase 3 were significantly increased in hippocampi of rats treated with 50 mg/L and 100 mg/L NaF and in 40 mg/L and 80 mg/L NaF-treated PC12 cells, while the protein expression of CypD remains stable. And the changes of p53 and CypD were also confirmed by the immunofluorescence staining in vivo. After inhibiting the expression of p53 with pifithrin-α and p53-siRNA, the decreased apoptosis rates and mPTP opening, increased MMP, and decreased protein expressions of p53, CytoC, and cleaved caspase 3 were observed in NaF-treated PC12 cells. Rats, treated with NaF and naringin, had alleviated impaired neurological function, and had lower RER than rats treated with NaF alone. And compared with those in the NaF group, the decreased apoptosis rates and mPTP opening, and increased MMP were also found in PC12 cells treated with NaF and naringin. Furthermore, hippocampi of rats and PC12 cells treated with NaF and naringin had decreased protein expressions of p53, CytoC, and cleaved caspase 3. Our results indicate that fluoride activates the p53-dependent mPTP-related mitochondrial apoptosis, which then affects energy metabolism, resulting in neurological impairment. Additionally, naringin can alleviate this damage, and further studies on the potential health benefits of naringin are needed.

Estrogen Status Influences Whole-Body Vibration Training-Induced Improvements on Muscle Mass and Strength in Female Ovariectomized Mice.

Estradiol (E2) deficiency arising from menopause is closely related to changes in body composition and declines of muscle mass and strength in elderly women. Whole-body vibration training (WBV) is an emerging approach expected to improve muscle mass and strength of older person, but the underlying mechanisms remain unclear. The balance between protein synthesis and degradation is a determining factor for muscle mass and strength, which is regulated by Akt-mTOR and FoxO1 signal pathway, respectively. In the present study, we firstly determined whether the effects of WBV on muscle mass and strength in ovariectomized female mice was affected by estrogen level, then investigated whether this was associated with Akt-mTOR and FoxO1 signal pathways. We found that (1) WBV, E2 supplementation (E) and WBV combined with E2 supplementation (WBV+E) significantly increased serum estradiol content, quadriceps muscle mass and grip strength in ovariectomized mice, accompanied with alterations of body composition (reducing fat content, increasing lean body mass and lean percent), furthermore, the altered degrees of these indicators by WBV+E were greater than WBV alone; (2) WBV, E and WBV+E remarkably increased the activities of Akt and mTOR and decreased FoxO1 activity, and the changed degrees by WBV+E were greater than WBV alone; (3) Pearson correlation coefficient revealed that serum estradiol content was positively correlated with Akt and mTOR activities, while inversely associated with FoxO1 activity. We concluded that WBV could significantly increase muscle mass and strength in ovariectomized mice, which might achieve through activating Akt-mTOR and suppressing FoxO1 signal pathways, and the improving effect of WBV on muscle mass and strength was better when in the presence of estrogen.

Apoptosis and Inflammation Involved with Fluoride-Induced Bone Injuries.

BACKGROUND: Excessive fluoride exposure induces skeletal fluorosis, but the specific mechanism responsible is still unclear. Therefore, this study aimed to identify the pathogenesis of fluoride-induced bone injuries. METHODS: We systematically searched fluoride-induced bone injury-related genes from five databases. Then, these genes were subjected to enrichment analyses. A TF (transcription factor)-mRNA-miRNA network and protein-protein interaction (PPI) network were constructed using Cytoscape, and the Human Protein Atlas (HPA) database was used to screen the expression of key proteins. The candidate pharmacological targets were predicted using the Drug Signature Database. RESULTS: A total of 85 studies were included in this study, and 112 osteoblast-, 35 osteoclast-, and 41 chondrocyte-related differential expression genes (DEGs) were identified. Functional enrichment analyses showed that the Atf4, Bcl2, Col1a1, Fgf21, Fgfr1 and Il6 genes were significantly enriched in the PI3K-Akt signaling pathway of osteoblasts, Mmp9 and Mmp13 genes were enriched in the IL-17 signaling pathway of osteoclasts, and Bmp2 and Bmp7 genes were enriched in the TGF-beta signaling pathway of chondrocytes. With the use of the TF-mRNA-miRNA network, the Col1a1, Bcl2, Fgfr1, Mmp9, Mmp13, Bmp2, and Bmp7 genes were identified as the key regulatory factors. Selenium methyl cysteine, CGS-27023A, and calcium phosphate were predicted to be the potential drugs for skeletal fluorosis. CONCLUSIONS: These results suggested that the PI3K-Akt signaling pathway being involved in the apoptosis of osteoblasts, with the IL-17 and the TGF-beta signaling pathways being involved in the inflammation of osteoclasts and chondrocytes in fluoride-induced bone injuries.

CTDSPL2 promotes the progression of non-small lung cancer through PI3K/AKT signaling via JAK1.

Carboxy-terminal domain small phosphatase like 2 (CTDSPL2), one of the haloacid dehalogenase phosphatases, is associated with several diseases including cancer. However, the role of CTDSPL2 and its regulatory mechanism in lung cancer remain unclear. Here, we aimed to explore the clinical implications, biological functions, and molecular mechanisms of CTDSPL2 in non-small cell lung cancer (NSCLC). CTDSPL2 was identified as a novel target of the tumor suppressor miR-193a-3p. CTDSPL2 expression was significantly elevated in NSCLC tissues. Database analysis showed that CTDSPL2 expression was negatively correlated with patient survival. Depletion of CTDSPL2 inhibited the proliferation, migration, and invasion of NSCLC cells, as well as tumor growth and metastasis in mouse models. Additionally, silencing of CTDSPL2 enhanced CD4+ T cell infiltration into tumors. Moreover, CTDSPL2 interacted with JAK1 and positively regulated JAK1 expression. Subsequent experiments indicated that CTDSPL2 activated the PI3K/AKT signaling pathway through the upregulation of JAK1, thereby promoting the progression of NSCLC. In conclusion, CTDSPL2 may play an oncogenic role in NSCLC progression by activating PI3K/AKT signaling via JAK1. These findings may provide a potential target for the diagnosis and treatment of NSCLC.

Preconception mitochondrial DNA copy number plays a crucial role in linking prenatal air pollution with the risk of preterm birth.

The relationship between maternal peripheral blood mitochondrial DNA and adverse pregnancy outcomes, specifically preterm birth (PTB), remains uncertain. To investigate the effects of preconception mitochondrial DNA copy number (mtDNAcn) on the association between prenatal air pollutants exposure and PTB risk, a total of 1871 expectant mothers from six regions in Henan Province were recruited. Information regarding air pollutants was obtained from 151 environmental monitoring sites, and relative mtDNAcn was evaluated using real-time PCR analysis. After adjusting for potential confounding variables, it was determined that the risk of PTB increased with elevated levels of inhalable particulate matter (PM10), fine particulate matter (PM2.5), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3) exposure (P < 0.05) but decreased with higher nitrogen dioxide (NO2) exposure (0.05 < P < 0.10) during the entire pregnancy. Additionally, the preconception relative mtDNAcn was lower in the PTB group (0.82 ± 0.23) compared to the term group (0.92 ± 0.29). Furthermore, for each 0.1-unit increase in preconception mtDNAcn, the risk of PTB decreased by 14.8%. Stratified analyses revealed that the risk of PTB rose with increasing O3 concentrations, regardless of the relative mtDNAcn. Moreover, the study found a significant association between PTB risk and prenatal exposure to elevated PM10, PM2.5, SO2, and CO, particularly in mothers with low mtDNAcn (≤0.88) (P < 0.05). Conversely, a decrease in the PTB risk was observed with elevated NO2 exposure in mothers with high mtDNAcn (>0.88). Interaction analysis revealed that exposure to PM10, PM2.5, SO2, NO2, and CO interacted with mtDNAcn, respectively, affecting PTB risk (P-interaction<0.05). These findings indicate a noteworthy association between PTB risk and prenatal air pollutants exposure, which is influenced by the preconception mtDNAcn.

Association between fluoride exposure and psychiatric disorders in adults.

To explore the association between fluoride exposure and depression / anxiety in adults, the 1,169 participants were recruited. The demographic information of participants was obtained through questionnaire survey and physical measurements. Morning urine samples were collected, and urinary fluoride (UF) level was determined. Changes in depression and anxiety levels were evaluated using the Patient Health Questionnaire-2 and General Anxiety Disorder-2 scales. The association between psychiatric disorders and UF levels was analyzed. In the total population, the prevalence of depression and anxiety were 3.17% and 4.19%, respectively. These results showed no significant association between depression / anxiety scale scores and UF levels. Logistic regression suggested no significant association between depression / anxiety levels, and UF levels, but there was an interaction between UF and income on depression. Our findings highlighted the interaction between fluoride exposure and monthly income, which may affect depression in adults.

Glutamine metabolism in fluorosis: Integrated metabolomics and transcriptomics analysis.

OBJECTIVE: To identify the potential metabolic biomarkers of fluorosis and the pathogenesis of fluorosis. METHODS: Sprague Dawley rats in this study were randomly divided into fluoride exposure and control groups. In the fluoride exposure group, six offspring rats without dental fluorosis were defined as group A, and six offspring rats with dental fluorosis were defined as group C. Eight offspring rats in the control group were defined as group B. The metabolites in plasma were determined using GC-MS, with differential metabolites (DMs) identified using VIP > 1, and P < 0.05. Cluster analysis, KEGG pathway enrichment analysis and Receiver Operating Characteristic (ROC) analysis were subsequently performed. The DMs which were caused by fluoride exposure in the previous study were used to verify our results. The GSE70719 from GEO database were used to support this research at the mRNA level and in vitro experiment were selected to verify above results. RESULTS: The 13 up-regulated and 4 down-regulated DMs were identified in the group A + C, the 18 up-regulated and 4 down-regulated DMs were identified in group A, and the 12 up-regulated and 2 down-regulated DMs were identified in group C. All groups showed enrichment in Aminoacyl-tRNA synthesis, D-glutamine and D-glutamate metabolism, Nitrogen metabolism, and Purine metabolism pathways. ROC analysis revealed that L-glutamine had excellent diagnostic ability for fluorosis (AUC > 0.85, P < 0.05). Changes in major DMs (L-glutamine, 4-hydroxyproline and L-alanine) were consistent with previous findings. Transcriptomic results showed the significant alteration of GLS gene in the fluoride exposure group. In vitro experiments confirmed decreased GLS and SLC1A5 genes expression. CONCLUSION: L-glutamine emerges as a potential biomarker for fluorosis. Glutamine metabolism was involved in the pathogenesis of fluorosis.

Comparative analysis of bioaerosol emissions: Seasonal dynamics and exposure risks in hospital vs. municipal wastewater treatment systems.

Hospital wastewater is known to contain various pathogenic microorganisms and harmful substances. During the hospital wastewater treatment process, the bioaerosols released may encapsulate these pathogens, leading to human infection. This study undertook an investigation to compare the dispersion characteristics and seasonal variations of bioaerosols from hospital and municipal sewage. The results indicated that the airborne bacterial concentration from hospital sewage (119 ± 118 CFU/m3) was higher than municipal sewage (46 ± 19 CFU/m3), with the highest concentration observed in summer. The dominant bacterial genera present in bioaerosols from both sewages were alike, with the proportions varied by sewage types and the structure mainly influenced by seasonal factors. Bacteroides, Escherichia-Shigella and Streptococcus were identified as the most prevalent pathogenic genera in spring, summer and winter bioaerosols, respectively, while Pseudomonas and Acinetobacter were abundant in autumn. Although the non-carcinogenic risk associated with bioaerosols was low (<1), the presence of pathogenic species and their potential synergistic interactions elevated the overall exposure risk. The diffusion modeling results demonstrated that bioaerosol emissions from the surface of hospital sewage can reach up to 10570 CFU/m3 in summer and can spread more than 300 m downwind. The potential pathogenicity of bioaerosols was also highest in summer, which may pose a health hazard to populations located downwind. Therefore, the management and control of bioaerosols from sewage should be strengthened, especially in summer.

Combined healthy lifestyles and risk of depressive symptoms: A baseline survey in China.

BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.

Impaired neurogenesis induced by fluoride via the Notch1 signaling and effects of carvacrol intervention.

The negative regulation on neurogenesis has been implicated in fluoride neurotoxicity, while the evidence is limited. To explore whether fluoride interferes with neurogenesis via the Notch1 signaling and the potential alleviation effects of carvacrol (CAR), we conducted in vivo and in vitro experiments, as well as epidemiological analyses in this study. The results showed that urinary fluoride levels and circulating Notch1 levels were associated with IQ levels in boys. NaF-treated rats had fewer neurons, lower densities of dendritic spines, depressed neurogenesis, and impaired learning and memory abilities. In vitro experiments using undifferentiated PC12 cells mimicking neurogenesis revealed that NaF suppressed differentiation and neurite outgrowth. Besides, Notch1 signaling activation was detected in vivo and in vitro. The latter was confirmed using an in vitro model supplemented with DAPT, a potent Notch1 inhibitor. Furthermore, CAR supplementation negatively regulated NICD1 and Hes1 expressions and promoted hippocampal neurogenesis, thereby improving neurological functions in NaF-treated rats. These findings indicated that the inhibition of neurogenesis in hippocampi induced by fluoride via Notch1 signaling activation may be one of the underlying mechanisms of its neurotoxicity, and that CAR significantly alleviated the neurotoxicity of NaF via the Notch1 signaling.

Efficacy and Postoperative Infection following Super Mini Percutaneous Nephrolithotomy vs Flexible Ureteroscopy for Diabetic Nephrolithiasis: A Comparative Analysis and Risk Factors for Postoperative Infectious Complications.

Objective: To compare the efficacy and postoperative infection rate of super mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopic lithotripsy (FURL) in patients with diabetic nephrolithiasis and to explore the risk factors associated with postoperative infection following these two procedures. Methods: The medical history and surgery details of 252 patients with diabetic nephrolithiasis who underwent lithotripsy in our hospital between January 2018 and May 2023, including 144 SMP and 108 FURL, were reviewed and compared. Perioperative outcomes were compared between the two groups. Logistic regression was performed to identify the significant risk factors for infection after each procedure. Results: SMP achieved a higher stone-free rate (SFR) on postoperative day 1 and postoperative day 30 compared with FURL (p < 0.05). The mean operative time was shorter in SMP (p < 0.01). FURL was associated with less hemoglobin drop (p < 0.01) and shorter length of stay (p < 0.01). The incident rate of systemic inflammatory response syndrome (SIRS) was higher after SMP (p = 0.019), while the incident rate of urinary tract infection (UTI) was higher after FURL (p = 0.021). Overall postoperative infection and sepsis rates were similar between the two procedures. Logistic regression analysis revealed that gender odds ratio [OR]: 0.225, 95% confidence interval [CI]: 0.079-0.639), HbA1c (OR: 3.516, 95% CI: 1.841-6.716), and operation time (OR: 1.037, 95% CI: 1.008-1.066) were independent risk factors for infection after FURL, while operation time (OR: 1.063, 95% CI: 1.022-1.106) and HbA1c (OR: 7.443, 95% CI: 2.956-18.742) significantly predicted SMP-associated infections. Conclusion: In diabetic patients, SMP demonstrated higher SFR and shorter operation time, whereas FURL was associated with less bleeding and shorter hospitalization. SMP had a higher incident rate of SIRS and FURL had a higher incident rate of UTI. Elevated HbA1c and prolonged operative duration increased infection risk after both procedures, while female gender was an additional risk factor for FURL-related infections.

Mediation of mitochondrial DNA copy number and oxidative stress in fluoride-related bone mineral density alteration in Chinese farmers.

Excessive fluoride can adversely affect bone mineral density (BMD). Oxidative stress and mitochondrial dysfunction are crucial mechanisms of health damage induced by fluoride. Here, a cross-sectional survey involving 907 Chinese farmers (aged 18-60) was carried out in Tongxu County in 2017, aiming to investigate the significance of mitochondrial DNA copy number (mtDNAcn) and oxidative stress in fluoride-related BMD change. Concentrations of urinary fluoride (UF), serum oxidative stress biomarkers, including total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), as well as relative mtDNAcn in peripheral blood were determined. The multivariable linear model and mediation analysis were performed to assess associations between UF, oxidative stress, and relative mtDNAcn with BMD. Results showed that GSH-Px levels increased by 6.98 U/mL [95% confidence interval (CI) 3.41-10.56)] with each 1.0 mg/L increment of UF. After stratification, the T-AOC, relative mtDNAcn, and BMD decreased by 0.04 mmol/L (-0.08 ~ -0.01), 0.29-unit (-0.55 ~ -0.04), and 0.18-unit (-0.33 ~ -0.03) with every 1.0 mg/L elevation of UF in the excessive fluoride group (EFG, adults with UF > 1.6 mg/L), respectively. Furthermore, T-AOC and relative mtDNAcn were favorably related to the BMD in the EFG (ß = 0.82, 95%CI 0.16-1.48 for T-AOC; ß = 0.11, 95%CI 0.02-0.19 for relative mtDNAcn). Mediation analysis showed that relative mtDNAcn and T-AOC mediated 15.4% and 17.1% of the connection between excessive fluoride and reduced BMD, respectively. Findings suggested that excessive fluoride was related to lower BMD in adults, and the decrement of T-AOC and relative mtDNAcn partially mediate this relationship.

Environmentally related microcystin-LR-induced ovarian dysfunction via the CCL2-CCR10 axis in mice ameliorated by dietary mulberry.

Microcystin-LR (MC-LR) is a reproductive toxin produced by cyanobacteria in the aquatic environment and can be ingested by humans through drinking water and the food chain, posing a threat to human reproductive health. However, the toxic mechanisms and prospective interventions for MC-LR-induced ovarian dysfunction at environmental doses are unknown. The mulberry fruit is a traditional natural product of plant origin, with various pharmacological effects, such as antioxidant and anti-inflammatory effects. Here, mice were exposed to MC-LR (10, 100 µg/L) in drinking water for 90 days, during which mice were gavage 600 mg/kg/week of mulberry fruit extract (MFE). It was found that MC-LR can accumulate in mouse ovaries, causing sexual hormone disturbance, inflammatory infiltration, and ovarian pathological damage. Results from RNA-seq were shown that CCL2, a chemokine associated with inflammatory response, was significantly increased in mouse ovary after MC-LR exposure. Further investigation revealed that MC-LR exposure aggravates apoptosis of granulosa cells via the CCL2-CCR10 axis-mediated Jak/Stat pathway. Importantly, MFE can significantly ameliorate these ovarian dysfunction phenotypes by inhibiting the activation of the CCL2-CCR10 axis. This study broadened new insights into the ovarian toxicity of MC-LR and clarified the pharmacological effects of mulberry fruit on ovarian function protection.

Change characteristics, bacteria host, and spread risks of bioaerosol ARGs/MGEs from different stages in sewage and sludge treatment process.

The spread of antibiotic resistance genes (ARGs) in the atmospheric environment has seriously threatened human health. Wastewater treatment plants (WWTPs) are an important source of aerosol ARGs. A large WWTP, including sewage treatment process (SWP) and sludge treatment process (SDP), was selected in North China for sampling in this study. The content of ARGs, mobile genetic elements (MGEs), and bacterial genera in sewage/sludge and aerosols from different process stages was detected. The possible correlation between ARGs/ MGEs and bacteria was analyzed. The risk of antibiotic-resistant bacteria was evaluated and the diffusion of ARGs/MGEs was simulated. The results showed that the concentration of ARGs/MGEs varied as the process progressed, and which in the aeration tank was relatively high. The ARGs/MGEs content in SWP aerosol (8.35-163.27 copies/m3) was higher than that in SDP (5.52-16.36 copies/m3). The main ARGs/MGEs detected in SWP aerosol were tnpA-05, tnpA-04, and ermF, while the main ARGs/MGEs detected in SDP aerosol were sul1, ermF, and blaPAO. ARGs were positively correlated with most bacteria and Escherichia coli with ARGs carries higher cytotoxicity. ARGs/MGEs mainly diffused towards the southeast, which may cause harm to urban residents with the diffusion of aerosols. This study provides clues and theoretical basis for preventing the hazards of ARGs from WWTP sources.

Dissecting causal links between gut microbiota, inflammatory cytokines, and DLBCL: a Mendelian randomization study.

ABSTRACT: Causal relationships between gut microbiota, inflammatory cytokines, and diffuse large B-cell lymphoma (DLBCL) remain elusive. In addressing this gap, our Mendelian randomization (MR) study used data from the MiBioGen consortium encompassing 211 microbiota taxa (n = 18 340), genome-wide association study meta-analyses of 47 inflammatory cytokines, and DLBCL cases and controls from the FinnGen consortium (cases, n = 1010; controls, n = 287 137). Through bidirectional MR analyses, we examined the causal links between gut microbiota and DLBCL and used mediation analyses, including 2-step MR and multivariable MR (MVMR), to identify potential mediating inflammatory cytokines. Our findings revealed that 4 microbiota taxa were causally associated with DLBCL, and conversely, DLBCL influenced the abundance of 20 taxa. Specifically, in the 2-step MR analysis, both the genus Ruminococcaceae UCG-002 (odds ratio [OR], 1.427; 95% confidence interval [CI], 1.011-2.015; P = .043) and the inflammatory cytokine monokine induced by gamma (MIG) (OR, 1.244; 95% CI, 1.034-1.487; P = .020) were found to be causally associated with an increased risk of DLBCL. Additionally, a positive association was observed between genus Ruminococcaceae UCG-002 and MIG (OR, 1.275; 95% CI, 1.069-1.520; P = .007). Furthermore, MVMR analysis indicated that the association between genus Ruminococcaceae UCG-002 and DLBCL was mediated by MIG, contributing to 14.9% of the effect (P = .005). In conclusion, our MR study provides evidence that supports the causal relationship between genus Ruminococcaceae UCG-002 and DLBCL, with a potential mediating role played by the inflammatory cytokine MIG.

Correlations between bone metabolism biomarkers and fluoride exposure in adults and children.

Increased exposure to fluoride, which notably affects bone metabolism, is a global concern. However, the correlations and sensitivity of bone metabolism to fluoride remain controversial. In this cross-sectional study, 549 children (aged 7-12 years) and 504 adults (≥ 18 years old) were recruited in the high-fluoride areas of the Henan Province. Urinary fluoride (UF) level was determined using a fluoride electrode. Fasting venous blood serum was collected to measure bone metabolism biomarkers. The selected bone metabolism biomarkers for children included bone alkaline phosphatase (BALP), serum alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT), parathyroid hormone (PTH), phosphorus (P5+), and calcium (Ca2+). For adults, the biomarkers included ALP, CT, PTH, ß-CrossLaps (ß-CTX), P5+, and Ca2+. The correlations between UF and bone metabolism biomarkers were analyzed using binary logistic regression, a trend test, a generalized additive model, and threshold effect analysis. Regression analysis indicated a significant correlation between serum OCN, PTH, and UF levels in children aged 7-9 years. Serum OCN, PTH, and BALP contents were significantly correlated with UF in boys (P < 0.05). Furthermore, the interaction between age and UF affected serum P5+ and PTH (P < 0.05). The generalized additive model revealed nonlinear dose-response relationships between P5+, BALP, and UF contents in children (P < 0.05). Serum OCN level was linearly correlated with the UF concentration (P < 0.05). Similarly, a significant correlation was observed between ß-CTX and UF levels in adults. In addition, significant correlations were observed between UF-age and serum Ca2+, ß-CTX, and PTH contents. There was a non-linear correlation between serum Ca2+, P5+, and ß- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P5+ levels can serve as sensitive bone metabolism biomarkers in children, while ß-CTX, P5+, and Ca2+ can be considered fluoride-sensitive bone metabolism biomarkers in adults.