Neurotoxicity of manganese via ferroptosis induced by redox imbalance and iron overload.

Manganese (Mn) is an essential trace element for maintaining bodily functions. Excessive exposure to Mn can pose serious health risks to humans and animals, particularly to the nervous system. While Mn has been implicated as a neurotoxin, the exact mechanism of its toxicity remains unclear. Ferroptosis is a form of programmed cell death that results from iron-dependent lipid peroxidation. It plays a role in various physiological and pathological cellular processes and may be closely related to Mn-induced neurotoxicity. However, the mechanism of ferroptosis in Mn-induced neurotoxicity has not been thoroughly investigated. Therefore, this study aims to investigate the role and mechanism of ferroptosis in Mn-induced neurotoxicity. Using bioinformatics, we identified significant changes in genes associated with ferroptosis in Mn-exposed animal and cellular models. We then evaluated the role of ferroptosis in Mn-induced neurotoxicity at both the animal and cellular levels. Our findings suggest that Mn exposure causes weight loss and nervous system damage in mice. In vitro and in vivo experiments have shown that exposure to Mn increases malondialdehyde, reactive oxygen species, and ferrous iron, while decreasing glutathione and adenosine triphosphate. These findings suggest that Mn exposure leads to a significant increase in lipid peroxidation and disrupts iron metabolism, resulting in oxidative stress injury and ferroptosis. Furthermore, we assessed the expression levels of proteins and mRNAs related to ferroptosis, confirming its significant involvement in Mn-induced neurotoxicity.

Hypoxia enhances autophagy level of human sperms.

The relationship between oxygen sensing and autophagy in human sperms was explored in this study. Health semen and asthenozoospermia (astheno) semen were incubated with hypoxia-inducible factor-1α (HIF-1α) interferents, i.e., lificiguat (YC-1) or cobalt chloride (CoCl2), respectively. Label-free quantitative proteomic technology was used to identify the differentially expressed proteins in human semen under the hypoxia condition. Selected proteins were detected with ELISA. It was found that the autophagy levels of sperm in the YC-1 + health group or CoCl2 + astheno group increased while the vitality decreased. A total of 17, 34 and 35 differentially expressed proteins were observed in the Astheno group, the YC-1 + health group and the CoCl2 + astheno group, respectively. These proteins were primarily associated with protein processing in endoplasmic reticulum, Th17 cell differentiation, progesterone-mediated oocyte maturation, glycolysis/gluconeogenesis, HIF-1 signaling pathway, biosynthesis of amino acids, and carbon metabolism. The expression levels of protein HIF-1α, LC3B, histone H4, cathepsin L and ENO1 changed significantly in the groups. The study suggests that hypoxia can increase sperm autophagy level and reduce their vitality through HIF-1 signaling pathway and glycolysis/gluconeogenesis signaling pathway. Furthermore, proteins histone H4, cathepsin L, glutathione synthetase and ENO1 are proposed as potential biomarkers of autophagy and vitality in asthenozoospermia sperm.

DNA methylation-mediated Rbpjk suppression protects against fracture nonunion caused by systemic inflammation.

Challenging skeletal repairs are frequently seen in patients experiencing systemic inflammation. To tackle the complexity and heterogeneity of the skeletal repair process, we performed single-cell RNA sequencing and revealed that progenitor cells were one of the major lineages responsive to elevated inflammation and this response adversely affected progenitor differentiation by upregulation of Rbpjk in fracture nonunion. We then validated the interplay between inflammation (via constitutive activation of Ikk2, Ikk2ca) and Rbpjk specifically in progenitors by using genetic animal models. Focusing on epigenetic regulation, we identified Rbpjk as a direct target of Dnmt3b. Mechanistically, inflammation decreased Dnmt3b expression in progenitor cells, consequently leading to Rbpjk upregulation via hypomethylation within its promoter region. We also showed that Dnmt3b loss-of-function mice phenotypically recapitulated the fracture repair defects observed in Ikk2ca-transgenic mice, whereas Dnmt3b-transgenic mice alleviated fracture repair defects induced by Ikk2ca. Moreover, Rbpjk ablation restored fracture repair in both Ikk2ca mice and Dnmt3b loss-of-function mice. Altogether, this work elucidates a common mechanism involving a NF-κB/Dnmt3b/Rbpjk axis within the context of inflamed bone regeneration. Building on this mechanistic insight, we applied local treatment with epigenetically modified progenitor cells in a previously established mouse model of inflammation-mediated fracture nonunion and showed a functional restoration of bone regeneration under inflammatory conditions through an increase in progenitor differentiation potential.

Frequency offset estimation for nonlinear frequency division multiplexing with continuous spectrum modulation.

Carrier frequency offset (CFO) estimation is very important for the optical fiber communications and has been studied widely in linear coherent systems, while only a few works have been reported for nonlinear Fourier transform (NFT) based systems. In continuous spectrum (CS) modulation nonlinear frequency division multiplexing (CS-NFDM) systems, frequency offset (FO) has a great influence on its performance, requiring an improved frequency offset estimation (FOE) method. We found that the oversampling rate R0 adopted in NFDM to ensure the accuracy of the NFT and inverse NFT (INFT) calculations, would cause the estimation accuracy of the traditional FFT-FOE method to decrease by R0 times. Moreover, CS-NFDM signals with higher baud rate require more subcarriers and then result in an oversampling factor greater than 16. This makes the traditional FFT-FOE method be ineffective to use the common training sequence (TS) overhead to meet the FOE error requirement of CS-NFDM system. Therefore, a modified FOE method based on FFT assisted by TS and autocorrelation has been proposed. The theoretical analysis and simulation results show that the proposed method is applicable to CS-NFDM system, no matter what modulation format is used. For 512 subcarriers, with a high rate of 70GBaud and the TS length of 8192, the proposed method can obtain a minimum FO estimation error about 0.1 MHz, which is better than the other two typical FFT-FOE and Schmidl & Cox methods. In addition, the proposed method can save at least 87.5% and 50% overhead. Thus, the proposed method has obvious improvement for CS-NFDM system with requiring high oversampling rate.

2.4-Tb/s/λ*km fundamental mode transmission over OM2 fiber employing Kramers-Kronig receiver.

We propose a digital-carrier Kramers-Kronig (DC-KK) scheme based high-speed multimode fiber short-reach optical interconnect system with fundamental mode transmission. After optimization of the parameters, including the roll-off factor of the root-raised-cosine (RRC) filter, and the guard interval (GI) between signal and carrier tone, as well as the carrier signal power ratio (CSPR), 200-Gb/s 32-quadrature amplitude modulation (32QAM) signal transmission over 12-km OM2 fiber has been experimentally demonstrated with a bit error ratio (BER) below the soft-decision forward error correction (SD-FEC) threshold of 4 × 10-2. To the best of our knowledge, this is the highest experimental record of single lambda bitrate-distance-product (SLBDP) achieved by direct-detection (DD)-based transmission over a standard multimode fiber (MMF). The proposed scheme has potential to improve the system performance without replacing massive deployed legacy MMFs for future large-capacity data center interconnects (DCIs).

Steroid-resistant nephrotic syndrome associated with certain SGPL1 variants in a family: Case report and literature review.

Objectives: Steroid-resistant nephrotic syndrome (SRNS) is a clinical syndrome characterized by the lack of response to standard steroid therapy, usually progressing to end-stage renal disease. We reported two cases of female identical twins with SRNS caused by SGPL1 variants in one family, reviewed the relevant literature, and summarized their clinical phenotypes, pathological types, and genotypic characteristics. Methods: Two cases of nephrotic syndrome caused by SGPL1 variants were admitted to Tongji Hospital, affiliated with Tongji Medical College of Huazhong University of Science and Technology. Their clinical data were retrospectively collected, and the peripheral blood genomic DNA was captured and sequenced by whole exome sequencing. Related literature published in PubMed, CNKI, and Wan fang databases was reviewed. Results: We described two Chinese identical twin girls with isolated SRNS due to compound heterozygous variants in the SGPL1 (intron4 c.261 + 1G > A and intron12 c.1298 + 6T > C). The patients were followed up for 60.0 months and 53.0 months, respectively, having no extra-renal manifestations. They all died due to renal failure. A total of 31 children with SGPL1 variants causing nephrotic syndrome (including the reported two cases) were identified through a literature review. Conclusions: These two female identical twins were the first reported cases of isolated SRNS caused by SGPL1 variants. Almost all homozygous and compound heterozygous variants of SGPL1 had extra-renal manifestations, but compound heterozygous variants in the intron of SGPL1 may have no obvious extra-renal manifestations. Additionally, a negative genetic testing result does not completely rule out genetic SRNS because the Human Gene Mutation Database or ClinVar is constantly being updated.

Silencing miR-146a-5p Protects against Injury-Induced Osteoarthritis in Mice.

Osteoarthritis (OA), the most prevalent joint disease and the leading cause of disability, remains an incurable disease largely because the etiology and pathogenesis underlying this degenerative process are poorly understood. Low-grade inflammation within joints is a well-established factor that disturbs joint homeostasis and leads to an imbalance between anabolic and catabolic processes in articular cartilage; however, the complexity of the network between inflammatory factors that often involves positive and negative feedback loops makes current anti-cytokine therapy ineffective. MicroRNAs (miRNAs) have emerged as key regulators to control inflammation, and aberrant miRNAs expression has recently been linked to OA pathophysiology. In the present study, we characterized transcriptomic profiles of miRNAs in primary murine articular chondrocytes in response to a proinflammatory cytokine, IL-1ß, and identified miR-146a-5p as the most responsive miRNA to IL-1ß. miR-146a-5p was also found to be upregulated in human OA cartilage. We further demonstrated that knockdown of miR-146a-5p antagonized IL-1ß-mediated inflammatory responses and IL-1ß-induced catabolism in vitro, and silencing of miR-146a in chondrocytes ameliorated articular cartilage destruction and reduced OA-evoked pain in an injury-induced murine OA model. Moreover, parallel RNA sequencing revealed that differentially expressed genes in response to IL-1ß were enriched in pathways related to inflammatory processes, cartilage matrix homeostasis, and cell metabolism. Bioinformatic analyses of putative miR-146a-5p gene targets and following prediction of protein-protein interactions suggest a functional role of miR-146a-5p in mediating inflammatory processes and regulation of cartilage homeostasis. Our genetic and transcriptomic data define a crucial role of miR-146a-5p in OA pathogenesis and implicate modulation of miR-146a-5p in articular chondrocytes as a potential therapeutic strategy to alleviate OA.

Feasibility of contrast-enhanced ultrasonography (CEUS) in evaluating renal microvascular perfusion in pediatric patients.

BACKGROUND: Changes in renal microvascular perfusion are involved in several kidney diseases. Contrast-enhanced ultrasonography (CEUS) quantitative analysis can enable the estimation of renal microvascular perfusion non-invasively. However, to date, few pediatric patients with renal disease have been subjected to CEUS quantitative analysis. This study aimed to explore the feasibility of CEUS in evaluating renal microvascular perfusion in pediatric patients and paving its way to clinical practice. METHODS: Seventeen pediatric patients with chronic kidney disease (CKD) and five children without kidney disease were consecutively examined using CEUS. Quantitative analysis of CEUS images based on time-intensity curve (TIC) fittings was performed using specialized software. Quantitative parameters of wash-in microvascular blood flow, including A, k, B, and TtoPk, were generated from three regions of interest (ROIs) each in the cortex and medulla of each kidney. RESULTS: CEUS was performed in all children successfully and safely without the use of sedatives. All parameters (A, B, k, and TtoPk) demonstrated no statistical differences among the three sampling ROIs in the renal cortex and medulla. All parameters (A, B, k, and TtoPk) showed no statistical differences between the left and right sides of kidneys both in cortices and medullas. Comparing with patients with CKD stage 3-5, both control group and patients with CKD stage 1-2 had significantly higher values of parameter A in the renal cortex (p = 0.025 and p = 0.031, respectively). In control group and patients stage 1-2, the values of parameters k in the renal cortices were significantly higher than that in the renal medullas, while in patients with CKD stage 3-5, parameter k showed no statistically significant differences between the renal cortex and medulla (p = 0.173). CONCLUSION: CEUS is safe and practicable in pediatric patients with chronic kidney disease. Renal microvascular perfusion estimated by CEUS could be a robust approach in the evaluation of pediatric renal diseases. Parameters A and k derived from CEUS quantitative analysis can provide great potential in non-invasive assessment of renal microvascular perfusion impairment in pediatric CKD.

RNAi and CRISPR-Cas silencing E3-RING ubiquitin ligase AIP2 enhances soybean seed protein content.

The majority of plant protein in the world's food supply is derived from soybean (Glycine max). Soybean is a key protein source for global animal feed and is incorporated into plant-based foods for people, including meat alternatives. Soybean protein content is genetically variable and is usually inversely related to seed oil content. ABI3-interacting protein 2 (AIP2) is an E3-RING ubiquitin ligase that targets the seed-specific transcription factor ABI3. Silencing both soybean AIP2 genes (AIP2a and AIP2b) by RNAi enhanced seed protein content by up to seven percentage points, with no significant decrease in seed oil content. The protein content enhancement did not alter the composition of the seed storage proteins. Inactivation of either AIP2a or AIP2b by a CRISPR-Cas9-mediated mutation increased seed protein content, and this effect was greater when both genes were inactivated. Transactivation assays in transfected soybean hypocotyl protoplasts indicated that ABI3 changes the expression of glycinin, conglycinin, 2S albumin, and oleosin genes, indicating that AIP2 depletion increased seed protein content by regulating activity of the ABI3 transcription factor protein. These results provide an example of a gene-editing prototype directed to improve global food security and protein availability in soybean that may also be applicable to other protein-source crops.

Ultrasound-Guided Modified Seldinger Placement of Tenckhoff Catheters in Pediatric Patients Undergoing Peritoneal Dialysis: Single Center Experience.

Minimally invasive peritoneal dialysis (PD) catheterization is increasingly common, and percutaneous PD catheters may be placed using a trocar or the Seldinger technique. There are few reports of pediatric percutaneous PD catheter insertion. We retrospectively compared the outcomes from percutaneous placement of Tenckhoff catheters using a modified Seldinger technique with catheter placement by open surgery. This single-center retrospective study compared 14 pediatric patients who received percutaneous PD catheter insertion using an ultrasound-guided modified Seldinger technique (August 2018-February 2021) with 10 patients who received open-surgical PD catheter insertion (2015-2018). Complications and catheter survival were evaluated. The overall technical success rate was 100%, but the Seldinger technique required less time (30 vs. 45 min) and smaller incisions (1.1 vs. 4.4 cm). The early complications in the Seldinger and control groups were bleeding (1 vs. 0), catheter dysfunction (1 vs. 1), abdominal pain (3 vs. 7), and exit leakage (0 vs. 1). In the Seldinger group, the median time from insertion to first use was 3 days, and the minimum follow-up was 6 months. Catheter survival at 6 months was 93% (Seldinger group) and 90% (open surgery group). The adoption of this technique at our institution led to a significant increase in the percentage of new pediatric dialysis patients commencing PD rather than hemodialysis. Collectively, the modified Seldinger technique described here was safe and feasible in pediatric patients. This approach is simpler and more rapid than open surgery, and reduces early complications and increases PD uptake.

Clinical and Renal Histology Findings and Different Responses to Induction Treatment Affecting the Long-Term Renal Outcomes of Children With ANCA-Associated Vasculitis: a Single-Center Cohort Analysis.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is relatively rare in children. This article aimed to analyze clinical and renal histology findings and different responses to induction treatment associated with the long-term renal outcomes in children with AAV in a single center. Methods: All pediatric patients with AAV admitted to Tongji Hospital from January 2002 to January 2021 were included in the study. The demographic, clinical, pathological, laboratory, and treatment data and outcomes were collected and analyzed to identify predictors associated with response to induction treatment and progression to end-stage renal disease (ESRD). Results: In total, 48 children with AAV were included in this cohort; 81.25% of them were women, and 91.7% were microscopic polyangiitis (MPA). Kidney involvement was found in 45 patients (93.75%). The most common histopathological subtype was crescentic form in this cohort according to Berden's classification. In total, 34 patients (70.8%) showed eGFR <60 ml/min/1.73 m2 at the time of diagnosis. Complete and partial remission was achieved in 8 patients (16.7%) and 19 patients (39.6%), respectively, following 6-month induction treatment. Half of the patients eventually progressed to ESRD at a mean time of (13.04 ± 15.83) months after diagnosis. The independent predictors of nonremission following induction treatment and progression to ESRD were baseline eGFR <60 ml/min/1.73 m2 and hypertension at diagnosis. Renal survival significantly decreased over time in patients with renal sclerotic subtypes or those with nonremission following induction treatment by Kaplan-Meier curve estimation. Conclusions: Our study demonstrates that women, MPA, and crescentic subtypes are predominant in pediatric AAV in China. Initial renal failure (eGFR <60 ml/min/1.73 m2), hypertension, sclerotic pathological subtype, and nonremission following induction treatment are predictive of long-term renal outcomes.

Succession of the Gut Microbiome in the Tibetan Population of Minjiang River Basin.

Tibetans are one of the oldest ethnic groups in China and South Asia. Based on the analysis of 1,059 Tibetans in the Minjiang River basin at an altitude of 500-4,001 m, we found that the dominant phyla of the Tibetan population were Bacteroidota and Firmicutes, and the main genera were Prevotella and Bacteroides, which were mostly in consistent with other nationalities. We further evaluated in total 115 parameters of seven categories, and results showed that altitude was the most important factor affecting the variation in the microbial community. In the process of emigration from high altitudes to the plain, the gut microbial composition of late emigrants was similar to that of plateau aborigines. In addition, regarding immigration from low altitude to high altitude, the microbial community became more similar to that of high altitude population with the increase of immigration time. Changes in these microbes are related to the metabolism, disease incidence and cell functions of the Tibetan population. The results of other two cohorts (AGP and Z208) also showed the impact of altitude on the microbial community. Our study demonstrated that altitude of habitation is an important factor affecting the enterotype of the microflora in the Tibetan population and the study also provided a basis to explore the interaction of impact parameters with gut microbiome for host health and diseases.

Joint effect between bisphenol A and alcohol consumption on benign prostatic hyperplasia: A case-control study in Hong Kong Chinese males.

BACKGROUND: Whether bisphenol A (BPA) exposure is a contributing factor to benign prostatic hyperplasia (BPH) remains unclear. This study evaluated the association between chronic BPA exposure and BPH risk, and explored whether this association was modified by alcohol drinking. METHODS: This study included a total of 650 BPH cases and 650 controls recruited from the same hospital in Hong Kong during 2011-2016. Chronic BPA exposure level was estimated by a validated cumulative BPA exposure index (CBPAI). We performed unconditional logistic regression model to examine the association of BPH risk with potential sources of BPA exposure via oral intake and CBPAI. We further tested the interactions between CBPAI and alcohol consumption habits on BPH risk. RESULTS: A positive exposure-response relationship was observed between CBPAI and BPH risk. Frequent BPA exposure via oral intake of foods heated in a plastic box/bag (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.51-8.22), cooling water in a plastic bottle (OR = 2.65, 95% CI: 1.33-5.27), or using a plastic cup to contain hot water (OR = 4.14, 95% CI: 1.02-16.89), was significantly associated with increased BPH risk. Compared with nonalcohol drinkers, alcohol drinkers was insignificantly associated with BPH risk (OR = 1.10, 95% CI: 0.77-1.57), but it demonstrated a more remarkable positive gradient between CBPAI exposure and BPH risk among alcohol drinkers, indicating an additive interaction between CBPAI and alcohol on BPH risk (synergy index = 4.24, 95% CI: 1.21-14.94). CONCLUSIONS: Chronic oral BPA exposure increased BPH risk with a positive exposure-response relationship among Hong Kong Chinese, and alcohol drinking amplified the effect of BPA on BPH. Hence, minimizations of containing food or water/beverage in plastic containers and drinking alcohol are recommended in the community to mitigate BPH risk. Future larger and designated studies are warranted.

Potential role of CFTR in bisphenol A-induced malignant transformation of prostate cells via mitochondrial apoptosis.

Bisphenol A (BPA) is an environmental endocrine disruptor and a risk factor for prostate cancer. The cystic fibrosis transmembrane conductance regulator (CFTR) is proposed to be a prostate cancer suppressor in some recent researches. However, the potential role and mechanism of CFTR in BPA-induced prostate cancer cells has not been well identified. In this study, BPA decreased the viability of human normal prostate RWPE-1 cells detected with a CCK-8 kit. The capacity of the cell line on soft agar colony formation, wound healing, and transwell invasion indicated malignant transformation induced by BPA. Western blot analysis demonstrated that the levels of CFTR and Bcl-2 decreased, whereas Bax level increased, and ELISA detection showed a decreased ATP level in BPA-exposed cells. Cell apoptosis was analyzed with Annexin V-FITC Detection Kit by flow cytometry. However, no significant difference was observed in cell viability and apoptosis rates compared to normal RWPE-1 cells. Our research revealed a potential role of CFTR in BPA-induced malignant transformation via mitochondrial apoptosis of normal prostate cells.

Manganese induced nervous injury by α-synuclein accumulation via ATP-sensitive K(+) channels and GABA receptors.

Manganese (Mn) is an environmental pollutant having a toxic effect on Parkinson's disease, with significant damage seen in the neurons of basal ganglia. Hence, Mn pollution is a public health concern. A Sprague-Dawley rat model was used to determine the damage to basal nuclei, and the effect of Mn intake was detected using the Morris water maze test and transmission electron microscopy. The SH-SY5Y cell line was exposed to Mn, and downstream signaling was assessed to determine the mechanism of toxicity. Mn exposure injured neurons, repressing GABAAR receptors and inducing GABABR receptors. The synergistic effect of the GABABR receptor and Kir6.1-SUR1 or Kir6.2-SUR1 was found to be one of the potential factors for the secretion of α-synuclein. The accumulation of α-synuclein regulated downstream factors calmodulin (CAM) cAMP response element-binding protein (CREB), thereby impairing learning and memory. Other genes downstream of CREB, rather than the feedback regulation of CREB, and brain-derived neurotrophic factor might also be involved.

Variation of diagnostic criteria in women with chronic endometritis and its effect on reproductive outcomes: A systematic review and meta-analysis.

This meta-analysis aimed to evaluate the variation in the diagnostic criteria for chronic endometritis (CE) and its effect on reproductive outcomes. A search of the academic literature was conducted in various databases including PubMed, Embase, Cochrane Library, and Chinese National Knowledge Internet. Studies published in English or Chinese prior to October 1, 2019, were included in the primary screen. Data on the CE incidence rate, cure rate after antibiotic therapy, clinical pregnancy rate, miscarriage rate, and live birth rate were extracted and analyzed. Twelve eligible studies involving 1879 patients were included in this meta-analysis. Compared with strict diagnostic criteria, studies that used broad diagnostic criteria to identify CE reported a higher incidence rate (odds radio [OR] = 2.96, 95% confidence interval [CI]: 1.13-6.44), clinical pregnancy rate (OR = 1.83, 95 % CI: 1.18-2.8), and live birth rate (OR = 2.08, 95 % CI: 1.43-3.02). Compared with a short treatment course, a longer course of antibiotic treatment significantly improved the cure rate of CE (OR = 0.29, 95% CI: 0.18-0.47). Based on these findings, variation in the diagnostic criteria may alter the incidence rate, clinical pregnancy rate, and live birth rate of women with CE. A consensus on the diagnostic criteria must be established to obtain a better understanding of and additional information about CE.

Liver Function of Male Rats Exposed to Manganese at Different Time Points.

As an essential trace element in the human body, manganese (Mn) is involved in many important biochemical reactions. However, excessive exposure to manganese can cause multiple systematic damages to the body. This study aims to investigate the effects of manganese exposure on serum hepatic enzymes in male rats at different time points. After adaptive feeding for 7 days, male Sprague-Dawley (SD) rats were injected intraperitoneally with 30 mg/kg MnCl2·4H2O once a day for 21 days at zeitgeber time point 2 (ZT2), ZT8, ZT14, and ZT20, respectively. We found that short-term repeated exposure to manganese caused slower body weight gain and increased relative liver and spleen weight index in male rats at different time points. Moreover, serum total bile acid (TBA) increased while aspartate aminotransferase (AST) decreased at ZT2, ZT8, and ZT20. Cholinesterase (ChE) decreased at ZT2 and ZT20, lactic dehydrogenase (LDH) decreased at ZT2, ZT14, and ZT20, and acid phosphatase (ACP) decreased at ZT2 and ZT14. Alkaline phosphatase (ALP) decreased at ZT2, ZT14, and ZT20, but increased at ZT8. Alanine amino transferase (ALT) decreased at ZT2 and ZT20, but increased at ZT8. There was a negative correlation between relative liver weight index with AST, ACP, ALP, and LDH, while a positive correlation with TBA. However, relative spleen weight index had a positive correlation with relative liver weight index and TBA, while a negative correlation with ALT, AST, ACP, ALP, LDH, and ChE. Our study shows that the injury of liver function is caused by short-term repeated manganese exposure at different time points. The time effect should be considered in manganese toxicity evaluation.

Effects of Sub-Acute Manganese Exposure on Thyroid Hormone and Glutamine (Gln)/Glutamate (Glu)-γ- Aminobutyric Acid (GABA) Cycle in Serum of Rats.

Excessive manganese (Mn) exposure may adversely affect the central nervous system, and cause an extrapyramidal disorder known as manganism. The glutamine (Gln)/glutamate (Glu)-γ-aminobutyric acid (GABA) cycle and thyroid hormone system may be involved in Mn-induced neurotoxicity. However, the effect of Mn on the Gln/Glu-GABA cycle in the serum has not been reported. Herein, the present study aimed to investigate the effects of sub-acute Mn exposure on the Gln/Glu-GABA cycle and thyroid hormones levels in the serum of rats, as well as their relationship. The results showed that sub-acute Mn exposure increased serum Mn levels with a correlation coefficient of 0.733. Furthermore, interruption of the Glu/Gln-GABA cycle in serum was found in Mn-exposed rats, as well as thyroid hormone disorder in the serum via increasing serum Glu levels, and decreasing serum Gln, GABA, triiodothyronine (T3) and thyroxine (T4) levels. Additionally, results of partial correlation showed that there was a close relationship between serum Mn levels and the detected indicators accompanied with a positive association between GABA and T3 levels, as well as Gln and T4 levels in the serum of Mn-exposed rats. Unexpectedly, there was no significant correlation between serum Glu and the serum T3 and T4 levels. In conclusion, the results demonstrated that both the Glu/Gln-GABA cycle and thyroid hormone system in the serum may play a potential role in Mn-induced neurotoxicity in rats. Thyroid hormone levels, T3 and T4, have a closer relationship with GABA and Gln levels, respectively, in the serum of rats.

Immunogenicity and Safety of an F-Genotype Attenuated Mumps Vaccine in Healthy 8- to 24-Month-Old Children.

Background: Mumps vaccine immunizations have reduced the incidence of this disease. With the variation of mumps circulating strain, novel vaccine strains are always important. Methods: A 2-center parallel, randomized, double-blind noninferiority trial was performed to compare an F-genotype attenuated mumps vaccine (SP strain) to the A-genotype vaccine (S-79, Jeryl-Lynn strain) in 1080 healthy children aged 8-24 months in Hubei, China. Results: Participants were randomly assigned to receive a high or low dose of the SP or S79 vaccine and then assessed clinically at 30 minutes and 1-28 days postinoculation. No differences in local or systemic reactivity were observed. A similar incidence of severe adverse events associated with the vaccine was observed in the high-dose group and the positive control group. Based on throat swab collections, no viral shedding was present at the 4th and 10th days in any group. Neutralizing and hemagglutination-inhibiting antibody assays with the F- or A-genotype strains showed similar trends in geometric mean titers in the high-dose SP and S79 groups. Increased cytotoxic T lymphocyte responses were observed in all groups. Conclusions: The F-genotype attenuated mumps vaccine is safe, offers immunogenicity against a homologous virus, and is noninferior to the A-genotype vaccine in 8- to 24-month-old children.

A novel role and mechanism of cystic fibrosis transmembrane conductance regulator in bisphenol A-induced prostate cancer.

Bisphenol A (BPA) is a well known environmental endocrine disruptor that may cause human prostate cancer through disturbing cell mitosis, proliferation, and apoptosis. As one of the most important anion channels in organisms, cystic fibrosis transmembrane conductance regulator (CFTR) is proposed as a tumor suppressor in carcinogenesis and development of prostate cancer in recent studies. Whether CFTR plays a role in BPA-induced prostate cancer needs to be further identified. In this study, two prostate cancer cell lines PC-3 and LNCaP were exposed to BPA for detecting the cytotoxic reactions by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and enzyme-linked immunosorbent assays. After the treatment with BPA for 24 hours, the cell viability was decreased significantly with increased cell apoptosis in the two cell lines. Moreover, both PC-3 and LNCaP cells had a reduced expression level of cAMP, CFTR, and adenosine triphosphate upon BPA treatment. In addition, AMPKα kinase was found upregulated to promote cell apoptosis through increasing Bax expression and decreasing Bcl-2 expression. Our study suggests a role and mechanism of CFTR in BPA-induced prostate cancer via cell apoptosis for the first time.