Relationship Between Work-Related Noise Exposure and Cognitive Impairment: A Cross-Sectional Study in China.

Background: Noise exposure and the risk of cognitive impairment are currently major public health issues. Objective: This study aimed to analyze the relationship between noise exposure and early impairment of cognitive function from the perspective of occupational epidemiology and to provide evidence for the long-term prevention and treatment of dementia in the context of aging. Methods: This study was conducted in China between May and August 2021. The independent variables were the type of hazardous factors, duration of noise exposure, perceived noise intensity, and cumulative noise exposure (CNE). The dependent variable was cognitive function, which was measured using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Multiple linear and logistic regression were used to analyze the relationship between noise exposure and cognitive function and to establish an effect curve. Results: The detection rates of cognitive dysfunction using the MMSE and MoCA were 1.1% and 36.2%, respectively. The predicted MMSE and MoCA scores showed a downward trend within the CNE value ranging from 90-140 dB.time. Each unit increase in CNE decreased cognitive function scores by 0.025 (0.037, 0.013) and 0.020 (0.037, 0.003) points,respectively. Conclusions: From the perspective of occupational epidemiology, these findings reveal a potential link between long-term noise exposure and early cognitive impairment.

Transcriptomic and metabolomic dissection of skeletal muscle of crossbred Chongming white goats with different meat production performance.

BACKGROUND: The transcriptome and metabolome dissection of the skeletal muscle of high- and low- growing individuals from a crossbred population of the indigenous Chongming white goat and the Boer goat were performed to discover the potential functional differentially expressed genes (DEGs) and differential expression metabolites (DEMs). RESULTS: A total of 2812 DEGs were detected in 6 groups at three time stages (3,6,12 Month) in skeletal muscle using the RNA-seq method. A DEGs set containing seven muscle function related genes (TNNT1, TNNC1, TNNI1, MYBPC2, MYL2, MHY7, and CSRP3) was discovered, and their expression tended to increase as goat muscle development progressed. Seven DEGs (TNNT1, FABP3, TPM3, DES, PPP1R27, RCAN1, LMOD2) in the skeletal muscle of goats in the fast-growing and slow-growing groups was verified their expression difference by reverse transcription-quantitative polymerase chain reaction. Further, through the Liquid chromatography-mass spectrometry (LC-MS) approach, a total of 183 DEMs in various groups of the muscle samples and these DEMs such as Queuine and Keto-PGF1α, which demonstrated different abundance between the goat fast-growing group and slow-growing group. Through weighted correlation network analysis (WGCNA), the study correlated the DEGs with the DEMs and identified 4 DEGs modules associated with 18 metabolites. CONCLUSION: This study benefits to dissection candidate genes and regulatory networks related to goat meat production performance, and the joint analysis of transcriptomic and metabolomic data provided insights into the study of goat muscle development.

Evaluation of Dry Ice for Short-Term Storage and Transportation of Frozen Boar Semen.

To address the safety problems posed by the transportation of boar semen using LN, this study was conducted on the short-term storage of frozen boar semen in dry ice (-79 °C). Boar semen frozen in LN was transferred to dry ice, kept for 1 day, 3 days, 5 days, 7 days, or 8 days, and then moved back to LN. The quality of frozen semen stored in LN or dry ice was determined to evaluate the feasibility of short-distance transportation with dry ice. The results showed that 60 °C for 8 s was the best condition for thawing frozen semen stored in dry ice. No significant differences in spermatozoa motility, plasma membrane integrity, or acrosome integrity were observed in semen after short-term storage in dry ice compared to LN (p > 0.05). There were no significant changes in antioxidant properties between storage groups either (p > 0.05). In conclusion, dry ice could be used as a cold source for the short-term transportation of frozen boar semen for at least 7 days, without affecting sperm motility, morphological integrity, or antioxidant indices.

LRRK2 regulates ferroptosis through the system Xc-GSH-GPX4 pathway in the neuroinflammatory mechanism of Parkinson's disease.

Parkinson's disease (PD) is the most prevalent neurodegenerative disorder. Neuroinflammation mediated by activated microglia and apoptosis of dopaminergic (DA) neurons in the midbrain are its primary pathological manifestations. Leucine-rich repeat protein kinase 2 (LRRK2) kinase has been observed to increase expression during neuroinflammation, however, the effect of LRRK2 on microglia activation remains poorly understood. In this study, we have established lipopolysaccharide (LPS) treated BV2 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models for both in vivo and in vitro investigation. Our data in vivo reveal that LRRK2 can promote microglia activation by regulating ferroptosis and activating nuclear factor-κB. Inhibition of LRRK2 expression effectively suppressed the LPS-induced pro-inflammatory cytokines and facilitated the secretion of neuroprotective factors. Importantly, by co-overexpressing LRRK2 and glutathione peroxidase 4 (GPX4), we identified the system Xc-GSH-GPX4 pathway as a crucial component in LRRK2-mediated microglial ferroptosis and inflammatory responses. Using a microglial culture supernatant (MCS) transfer model, we found that inhibiting LRRK2 or downregulating ferroptosis in BV2 cells prevented SH-SY5Y cell apoptosis. Additionally, we observed abundant expression of LRRK2 and P-P65 in the midbrain, which was elevated in the MPTP-induced PD model, along with microglia activation. LRRK2 and P-P65 expression inhibition with PF-06447475 attenuated microglia activation in the nigrostriatal dense part of MPTP-treated mice. Based on our findings, it is evident that LRRK2 plays a critical role in promoting the neuroinflammatory response during the pathogenesis of PD by regulating the system Xc-GSH-GPX4 pathway. Taken together, our data highlights the potential research and therapeutic value of targeting LRRK2 to regulate neuroinflammatory response in PD through ferroptosis.

Subcortical structure alteration in patients with drug-induced parkinsonism: Evidence from neuroimaging.

Parkinson's Disease (PD) and Drug-induced parkinsonism (DIP) are the most common subtypes of parkinsonism, yet no studies have reported that the subcortical volume alterations in DIP patients. This study aimed to identify specific alterations of subcortical structures volume in DIP patients, and investigate association between the subcortical structure modifications and clinical symptoms. We recruited 27 PD patients, 25 DIP patients and 30 healthy controls (HCs). The clinical symptom-related parameters (Unified Parkinson's Disease Rating Scale, UPDRS) were evaluated. Structural imaging was performed on a 3.0 T scanner, and volumes of subcortical structures were obtained using FreeSurfer software. Analysis of covariance (ANCOVA) and partial correlation analysis were performed. DIP group had significantly smaller volume of the thalamus, pallidum, hippocampus and amygdala compared to HCs. ROC curve analysis demonstrated that the highest area under curve (AUC) value was in the right pallidum (AUC = 0.831) for evaluating the diagnostic efficacy in DIP from HCs. Moreover, the volumes of the putamen, hippocampus and amygdala were negatively correlated with UPDRSII in the DIP patients. The volume of the amygdala was negatively correlated with UPDRSIII. The present study provides novel information regarding neuroanatomical alteration of subcortical nuclei in DIP patients, suggesting that these methods might provide the basis for early diagnosis and differential diagnosis of DIP.

Daytime napping, biological aging and cognitive function among middle-aged and older Chinese: insights from the China health and retirement longitudinal study.

Objective: The complicated association of daytime napping, biological aging and cognitive function remains inconclusive. We aimed to evaluate the cross-sectional and longitudinal associations of daytime napping and two aging measures with cognition and to examine whether napping affects cognition through a more advanced state of aging. Methods: Data was collected from the China Health and Retirement Longitudinal Study. Napping was self-reported. We calculated two published biological aging measures: Klemera and Doubal biological age (KDM-BA) and physiological dysregulation (PD), which derived information from clinical biomarkers. Cognitive z-scores were calculated at each wave. Linear mixed models were used to explore the longitudinal association between napping, two aging measures, and cognitive decline. Mediation analyses were performed to assess the mediating effects of biological age acceleration on the association between napping and cognition. Results: Participants aged over 45 years were included in the analyses. Non-nappers had greater KDM-BA and PD [LS means (LSM) = 0.255, p = 0.007; LSM = 0.085, p = 0.011] and faster cognitive decline (LSM = -0.061, p = 0.005)compared to moderate nappers (30-90 min/nap). KDM-BA (ß = -0.007, p = 0.018) and PD (ß = -0.034, p < 0.001) showed a negative association with overall cognitive z scores. KDM-BA and PD partially mediated the effect of napping on cognition. Conclusion: In middle-aged and older Chinese, compared to moderate nappers, non-nappers seem to experience a more advanced state of aging and increased rates of cognitive decline. The aging status possibly mediates the association between napping and cognition. Moderate napping shows promise in promoting healthy aging and reducing the burden of cognitive decline in Chinese middle-aged and older adults.

Genomic Dissection through Whole-Genome Resequencing of Five Local Pig Breeds from Shanghai, China.

China has rich genetic resources of local pig breeds. In this study, whole-genome resequencing was performed on five Shanghai local pig breeds, aiming to analyze their population genetic structure and unique genomic characteristics. Tens of millions of single nucleotide variants were obtained through the resequencing of a total of 150 individual pigs from five local pig breeds (Meishan, Fengjing, Shawutou, Pudong White, and Shanghai White) after mapping them with the pig reference genome of Sus scrofa 11.1. The results of admixture structure analysis also clearly demonstrated the genetic differences between the Shanghai local pig breeds and the three commercial pig breeds (Duroc, Landrace, and Yorkshire). The genetic infiltration of Landrace and Yorkshire pig breeds in the SHW breed was detected, which is consistent with the early history of crossbreeding in this breed. Selective sweep analysis between four indigenous Shanghai pig breed populations and three commercial pig breed populations identified 270 and 224 genes with selective signatures in the commercial and indigenous Shanghai pig populations, respectively. Six genes (TGS1, PLAG1, CHCHD7, LCORL, TMEM68, and TMEM8B) were found to be associated with animal growth in the commercial pig population through gene enrichment and protein-protein interaction analysis. In contrast, the MSRB3 gene in the indigenous Shanghai pig population was significantly under selection, which correlated with the long pendulous ear phenotype of the indigenous Shanghai pig population. In conclusion, this study is the first genomic profiling of five representative local pig breeds in Shanghai, which provides molecular genetic data and foundations for better conservation and utilization of local pig breed resources in Shanghai, China.

Ultrasound-Guided Percutaneous Transhepatic Cholangioscopic Lithotripsy for the Treatment of Common Bile Duct Stones and Analysis of Risk Factors for Recurrence.

BACKGROUND: As a minimally invasive treatment for common bile duct (CBD) stones, ultrasound-guided percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) is gaining attention and recognition from the medical community. METHODS: A retrospective analysis was conducted on patients with CBD stones treated in our hospital from January 2016 to April 2022. Patients were divided into three groups: 77 treated with PTCSL, 93 with endoscopic retrograde cholangiopancreatography (ERCP), and 103 with laparoscopic common bile duct exploration (LCBDE). Their clinical data, perioperative indicators, and complications were analyzed comparatively. Then, risk factors for the post-PTCSL recurrence of CBD stones were analyzed by logistic regressions. Finally, the receiver operating characteristic curve was drawn. RESULTS: All perioperative indicators of the PTCSL group were better than the LCBDE group (P < 0.001). The incidences of cholangitis, hemobilia, and incisional infection after surgery were lower in the PTCSL group than in the LCBDE group (P < 0.05). Pancreatitis, reflux esophagitis, and papillary stenosis occurred less frequently in the PTCSL group than in the ERCP group (P < 0.05). Logistic regression analysis indicated that gallstones and family history were independent risk factors. The AUC for recurrent CBD stones predicted by multi-indicators was 0.895 (95% CI 0.792-0.999, P < 0.001) with a sensitivity of 96.7% and specificity of 68.8%. CONCLUSIONS: Ultrasound-guided PTCSL is a safe and effective treatment for CBD stones. Patients recovered quickly with fewer postoperative complications. It can be a first-line treatment for CBD stones. Gallstones and family history are independent risk factors for recurrent CBD stones, which provide a reference for clinicians in identifying the high-risk population needing close follow-up.

Autophagy-amplifying nanoparticles evoke immunogenic cell death combined with anti-PD-1/PD-L1 for residual tumors immunotherapy after RFA.

Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.

Effects of white matter hyperintensity on cognitive function in PD patients: a meta-analysis.

Background: Parkinson's disease (PD) is often accompanied by cognitive dysfunction, which imposes a heavy burden on patients, their families, and society. Early identification and intervention are particularly important, but reliable biomarkers for identifying PD-related cognitive impairment at an early stage are currently lacking. Although numerous clinical studies have investigated the association between brain white matter hyperintensity (WMH) and cognitive decline, the findings regarding the relationships between WMH and cognitive dysfunction in PD patients have been inconsistent. Therefore, this study aims to conduct a meta-analysis of the effect of WMH on PD cognitive function. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We systematically searched relevant literature from databases such as PubMed, Web of Science, EMBASE, CNKI, and CBM. The retrieval time was limited to database records created up until December 31, 2022. Additionally, we manually retrieved references for full-text reading. Statistical data analysis was performed using RevMan 5.3 and Stata 15.0 software. Results: This study encompassed 23 individual studies and involved 2,429 patients with PD. The group of PD with mild cognitive impairment (PD-MCI) exhibited a significantly higher overall level of WMH than the group of PD with normal cognitive function (PD-NC) (SMD = 0.37, 95% CI: 0.21-0.52, p < 0.01). This finding was consistent across subgroup analyses based on different ethnicities (Asian or Caucasian), WMH assessment methods (visual rating scale or volumetry), and age matching. In addition to the overall differences in WMH load between the PD-MCI and PD-NC groups, the study found that specific brain regions, including periventricular white matter hyperintensity (PVH) and deep white matter hyperintensity (DWMH), had significantly higher WMH load in the PD-MCI group compared to the PD-NC group. The study also conducted a meta-analysis of WMH load data for PD with dementia (PDD) and PD without dementia (PDND), revealing that the overall WMH load in the PDD group was significantly higher than that in the PDND group (SMD = 0.98, 95% CI: 0.56-1.41, p < 0.01). This finding was consistent across subgroup analyses based on different ethnicities and age matching. Moreover, regarding specific brain regions (PVH or DWMH), the study found that the PDD group had significantly higher WMH load than the PDND group (p < 0.01). Conclusion: WMH was associated with PD cognitive dysfunction. The early appearance of WMH may indicate PD with MCI.

Suture Interface Inspired Self-Recovery Architected Structures for Reusable Energy Absorption.

Designing materials and structures with high energy absorption and self-recoverability remains a challenge for reusable energy absorption, particularly in aerospace engineering applications (i.e., planetary landers). While the prevalent design methods of reusable energy absorbers mainly use the mechanical instability of tilted and curved beams, the limited energy absorption capabilities and low strength of tilted or curved beams limit performance improvement. In nature, Phlorodes diabolicus has evolved extreme impact resistance, in which the suture interface structure plays a key role. Herein, we propose a convex interface slide design strategy for reusability and energy absorption through friction interface, geometry, and bending elasticity, inspired by the elytra of Phlorodes diabolicus. Convex interfaces slide to achieve a more than 270% higher energy absorption capacity per unit volume than the curved beams. The convex interface slide design can be easily integrated with other structures to achieve multiple functions, such as various shapes and self-recoverability. Furthermore, we developed a theoretical model to predict the mechanical behavior and energy absorption performance. Our strategy opens up a new design space for creating reusable energy-absorbing structures.

DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA.

BACKGROUND: The DEAD-box family is essential for tumorigenesis and embryogenesis. Previously, we linked the malfunction of DDX (DEAD-box RNA helicase)-24 to a special type of vascular malformation. Here, we aim to investigate the function of DDX24 in vascular smooth muscle cells (VSMCs) and embryonic vascular development. METHODS: Cardiomyocyte (CMC) and VSMC-specific Ddx24 knockout mice were generated by crossing Tagln-Cre mice with Ddx24flox/flox transgenic mice. The development of blood vessels was explored by stereomicroscope photography and immunofluorescence staining. Flow cytometry and cell proliferation assays were used to verify the regulation of DDX24 on the function of VSMCs. RNA sequencing and RNA immunoprecipitation coupled with quantitative real-time polymerase chain reaction were combined to investigate DDX24 downstream regulatory molecules. RNA pull-down and RNA stability experiments were performed to explore the regulation mechanism of DDX24. RESULTS: CMC/VSMC-specific Ddx24 knockout mice died before embryonic day 13.5 with defects in vessel formation and abnormal vascular remodeling in extraembryonic tissues. Ddx24 knockdown suppressed VSMC proliferation via cell cycle arrest, likely due to increased DNA damage. DDX24 protein bound to and stabilized the mRNA of FANCA (FA complementation group A) that responded to DNA damage. Consistent with the function of DDX24, depletion of FANCA also impacted cell cycle and DNA repair of VSMCs. Overexpression of FANCA was able to rescue the alterations caused by DDX24 deficiency. CONCLUSIONS: Our study unveiled a critical role of DDX24 in VSMC-mediated vascular development, highlighting a potential therapeutic target for VSMC-related pathological conditions.

Effect of Poria cocos Mushroom Polysaccharides (PCPs) on the Quality and DNA Methylation of Cryopreserved Shanghai White Pig Spermatozoa.

In this study, we explore the effects of Poria cocos mushroom polysaccharides (PCPs) on the quality and DNA methylation of the cryopreserved spermatozoa of Shanghai white pigs. A total of 24 ejaculates (three ejaculate samples per boar) from eight Shanghai white pigs were manually collected. The pooled semen was diluted with a based extender supplemented with different concentrations of PCPs (0, 300, 600, 900, 1200, and 1500 µg/mL). Once thawed, the quality of the spermatozoa and their antioxidant function were assessed. In the meantime, the effect of spermatozoa DNA methylation was also analyzed. The results show that compared with the control group, 600 µg/mL of PCPs significantly improves the spermatozoa viability (p < 0.05). The motility and plasma membrane integrity of the frozen-thawed spermatozoa are significantly higher after treatment with 600, 900, and 1200 µg/mL of PCPs compared with the control group (p < 0.05). In comparison with the control group, the percentages of acrosome integrity and mitochondrial activity are significantly enhanced after the application of 600 and 900 µg/mL PCPs (p < 0.05). The reactive oxygen species (ROS), the malondialdehyde (MDA) levels, and the glutathione peroxidase (GSH-Px) activity, in comparison with the control group, are significantly decreased in all groups with PCPs (all p < 0.05). The enzymatic activity of superoxide dismutase (SOD) in spermatozoa is significantly higher in the treatment with 600 µg/mL of PCPs than in the other groups (p < 0.05). As compared with the control group, a significant increase in the catalase (CAT) level is found in the groups with PCPs at 300, 600, 900, and 1200 µg/mL (all p < 0.05). In comparison with the control group, the 5-methylcytosine (5-mC) levels are significantly decreased in all groups with PCPs (all p < 0.05). As a result of these findings, a certain amount of PCPs (600-900 µg/mL) added to the cryodiluent can significantly improve the quality of Shanghai white pig spermatozoa and can also reduce the methylation of spermatozoa DNA caused by cryopreservation. This treatment strategy may establish a foundation for the cryopreservation of semen from pigs.

Effects of morphological characteristics of patent foramen ovale by transesophageal echocardiography on minimalist transcatheter closure in southern China.

OBJECTIVES: Transcatheter closure has become one of the main treatment methods for patent foramen ovale (PFO). However, the population in southern China is generally thin and the size of PFO is small, so the application of minimalist surgery is challenging. This study aimed to analyze the morphological characteristics of PFOs in southern China by transesophageal echocardiography (TEE), and to explore the influence on minimalist transcatheter closure. METHODS: About 110 patients with PFO closure in our hospital were selected. All cases were examined by TEE including the PFO size, length, septum secundum thickness, color characteristic and surrounding structures, and morphologically classified. During the operation, the procedure time, number of times for the guidewire attempting to pass the interatrial septum and the success rate of simply using J guidewire to cross the interatrial septum were recorded. RESULTS: About 110 cases of PFO were classified into two categories and four subtypes, including 55 cases with Uniform Channel Type (UCT, 50.0%), 16 cases with Irregular Channel Type (ICT, 14.6%), 15 cases with Right Funnel Type (RFT, 13.6%), and 24 cases with Left Funnel Type (LFT, 21.8%). According to the complexity of the procedure, they were divided into simple procedure (n = 73) and complex procedure (n = 37). Multivariate logistic regression showed that the anatomical types of PFO, the tunnel entrance size, and the tunnel entrance size <2 mm were independent factors affecting the complexity of procedure [OR = 2.819, 95% CI (1.124, 7.066), p = .027; OR = .027, 95% CI (.004, .208), p = .001; OR = 4.715, 95% CI (1.028, 21.619), p = .046]. With ICT and LFT groups, the procedure duration was relatively long (p < .001), number of times for the guidewire attempting to pass the interatrial septum was significantly increased (p < .001), and the success rate of simply using J guidewire to cross the interatrial septum was relatively low (p < .001). CONCLUSIONS: The PFO size in southern China was relatively small and characterized by large tunnel tension. It was concluded that TEE could clearly show the morphological characteristics of PFO, which could provide guidance for making more reasonable surgical plans in clinical practice, shorten the procedure time and improve the success rate of PFO closure.

Screening Discriminating SNPs for Chinese Indigenous Pig Breeds Identification Using a Random Forests Algorithm.

Chinese indigenous pig breeds have unique genetic characteristics and a rich diversity; however, effective breed identification methods have not yet been well established. In this study, a genotype file of 62,822 single-nucleotide polymorphisms (SNPs), which were obtained from 1059 individuals of 18 Chinese indigenous pig breeds and 5 cosmopolitan breeds, were used to screen the discriminating SNPs for pig breed identification. After linkage disequilibrium (LD) pruning filtering, this study excluded 396 SNPs on non-constant chromosomes and retained 20.92~-27.84% of SNPs for each of the 18 autosomes, leaving a total of 14,823 SNPs. The principal component analysis (PCA) showed the largest differences between cosmopolitan and Chinese pig breeds (PC1 = 10.452%), while relatively small differences were found among the 18 indigenous pig breeds from the Yangtze River Delta region of China. Next, a random forest (RF) algorithm was used to filter these SNPs and obtain the optimal number of decision trees (ntree = 1000) using corresponding out-of-bag (OOB) error rates. By comparing two different SNP ranking methods in the RF analysis, the mean decreasing accuracy (MDA) and mean decreasing Gini index (MDG), the effects of panels with different numbers of SNPs on the assignment accuracy, and the statistics of SNP distribution on each chromosome in the panels, a panel of 1000 of the most breed-discriminative tagged SNPs were finally selected based on the MDA screening method. A high accuracy (>99.3%) was obtained by the breed prediction of 318 samples in the RF test set; thus, a machine learning classification method was established for the multi-breed identification of Chinese indigenous pigs based on a low-density panel of SNPs.

Mechanisms of Autoimmune Cell in DA Neuron Apoptosis of Parkinson's Disease: Recent Advancement.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that manifests as motor and nonmotor symptoms due to the selective loss of midbrain DArgic (DA) neurons. More and more studies have shown that pathological reactions initiated by autoimmune cells play an essential role in the progression of PD. Autoimmune cells exist in the brain parenchyma, cerebrospinal fluid, and meninges; they are considered inducers of neuroinflammation and regulate the immune in the human brain in PD. For example, T cells can recognize α-synuclein presented by antigen-presenting cells to promote neuroinflammation. In addition, B cells will accelerate the apoptosis of DA neurons in the case of PD-related gene mutations. Activation of microglia and damage of DA neurons even form the self-degeneration cycle to deteriorate PD. Numerous autoimmune cells have been considered regulators of apoptosis, α-synuclein misfolding and aggregation, mitochondrial dysfunction, autophagy, and neuroinflammation of DA neurons in PD. The evidence is mounting that autoimmune cells promote DA neuron apoptosis. In this review, we discuss the current knowledge regarding the regulation and function of B cell, T cell, and microglia as well as NK cell in PD pathogenesis, focusing on DA neuron apoptosis to understand the disease better and propose potential target identification for the treatment in the early stages of PD. However, there are still some limitations in our work, for example, the specific mechanism of PD progression caused by autoimmune cells in mitochondrial dysfunction, ferroptosis, and autophagy has not been clarified in detail, which needs to be summarized in further work.

Does Antioxidant Mitoquinone (MitoQ) Ameliorate Oxidative Stress in Frozen-Thawed Rooster Sperm?

In this study, we aimed to determine the benefit of mitoquinone (MitoQ) in rooster semen extenders on sperm quality, motility parameters, antioxidant capacities, and apoptotic changes in post-thawed rooster semen. A total of 85 ejaculates from 18 roosters were collected and then divided into five equal aliquots and cryopreserved in extenders with 1.0% soy lecithin nanoparticles that contained various concentrations of MitoQ (0 nM (M0), 50 nM (M50), 100 nM (M100), 150 nM (M150), and 200 nM (M200)). By using a computer-assisted semen analyzer, sperm motility parameters were assessed after freeze thawing. The M150 group had significantly higher percentages of total motility, progressive motility, viability, acrosome membrane integrity, and mitochondrial activity than the other groups (p < 0.05). Compared to other groups, M100 and M150 groups produced a higher percentage of plasma membrane integrity and ATP contents (p < 0.05). Additionally, the lowest levels of ROS and MDA in spermatozoa were observed in M150 group (p < 0.05), whereas the highest levels of ROS and MDA were observed in sperm in the controls or the M200 group (p < 0.05). Significantly higher values of SOD, GPx, and Cas-3 were found in the M150 group compared to other groups (p < 0.05). Overall, these results demonstrate that MitoQ at 150 nM not only ameliorates post-thawed sperm quality and motility parameters by restoring ATP levels and preventing membrane damage, but also improves redox balance and antiapoptotic activities.

Resveratrol Protects against Zearalenone-Induced Mitochondrial Defects during Porcine Oocyte Maturation via PINK1/Parkin-Mediated Mitophagy.

Mitochondria hold redox homeostasis and energy metabolism as a crucial factor during oocyte maturation, while the exposure of estrogenic mycotoxin zearalenone causes developmental incapacity in porcine oocyte. This study aimed to reveal a potential resistance of phytoalexin resveratrol against zearalenone during porcine oocyte maturation and whether its mechanism was related with PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. Porcine oocytes were exposed to 20 µM zearalenone with or without 2 µM resveratrol during in vitro maturation. As for the results, zearalenone impaired ultrastructure of mitochondria, causing mitochondrial depolarization, oxidative stress, apoptosis and embryonic developmental incapacity, in which mitophagy was induced in response to mitochondrial dysfunction. Phytoalexin resveratrol enhanced mitophagy through PINK1/Parkin in zearalenone-exposed oocytes, manifesting as enhanced mitophagy flux, upregulated PINK1, Parkin, microtubule-associated protein light-chain 3 beta-II (LC3B-II) and downregulated substrates mitofusin 2 (MFN2), voltage-dependent anion channels 1 (VDAC1) and p62 expressions. Resveratrol redressed zearalenone-induced mitochondrial depolarization, oxidative stress and apoptosis, and accelerated mitochondrial DNA copy during maturation, which improved embryonic development. This study offered an antitoxin solution during porcine oocyte maturation and revealed the involvement of PINK1/Parkin-mediated mitophagy, in which resveratrol mitigated zearalenone-induced embryonic developmental incapacity.

Chronic Noise Exposure and Risk of Dementia: A Systematic Review and Dose-Response Meta-Analysis.

Objective: Evidence is scarce about the effect of noise exposure on the risk of dementia. We conducted a systematic review and dose-response meta-analysis, aiming to explore the association between noise exposure and the risk of dementia. Methods: We searched PubMed, EMBASE and the Cochrane Library to collect studies on chronic noise exposure and the risk of dementia from database inception to September 18, 2021 without language limitations. Two authors independently screened the literature, extracted data and assessed the risk of bias of the included studies. A dose-response meta-analysis and subgroup analysis were then conducted to detect the association between noise exposure and the risk of dementia by using Stata 14.0 software. This study is registered on PROSPERO (CRD42021249243). Results: A total of 11 studies were eligible for qualitative synthesis, and nine were eligible for quantitative data synthesis. All of them showed moderate to high quality scores in the assessment of risk of bias. We found a positive linear association between the noise increment and dementia risk (R2 = 0.58). When noise exposure increased 57 dB, the RR of dementia was 1.47 (95% CI: 1.21-1.78). From the outcome subgroup of AD, AD and dementia, VaD and NAD, we also found a positive association (R2 = 0.68, 0.68, 0.58, respectively). When noise exposure increased by 25 dB, the RRs were 1.18 (95% CI: 1.14-1.23), 1.19 (95% CI: 1.14-1.23) and 1.17 (95% CI: 1.06-1.30), respectively. We found a nonlinear association between the noise increment and dementia risk when only cohort studies were included (R2 = 0.58). When noise exposure increased by 25 dB, the RR of dementia was 1.16 (95% CI: 1.12-1.20). From the subgroup of AD, AD and dementia, VaD and NAD of cohort studies, the regression curve showed a nonlinear positive association (R2 = 0.74, 0.71, 0.43, respectively). When noise exposure increased by 25 dB, the RRs were 1.17 (95% CI: 1.12-1.21), 1.17 (95% CI: 1.12-1.22) and 1.13 (95% CI: 0.99-1.28), respectively. Conclusion: Based on the current evidence, exposure to noise may be a specific risk factor for dementia. To better prevent dementia, more rigorously designed studies are needed to explore the etiological mechanism of noise and dementia.

Can adjuvant chemotherapy improve the prognosis of adult ovarian granulosa cell tumors?: A narrative review.

ABSTRACT: Adult granulosa cell tumors (aGCTs) are rare ovarian neoplasms with a relatively favorable prognosis. They follow an indolent course, characterized by a prolonged natural history and a tendency to late recurrences, Around a quarter of patients develop recurrence and More than 70% of women with recurrence die from their disease, The percentage of patients received chemotherapy increases over time, whether adjuvant chemotherapy improve the prognosis of aGCTs is equivocal? The purpose of this review is to summarize the previously published evidence to evaluate whether adjuvant chemotherapy improve the prognosis of aGCTs to provide guidance for clinical practice. EMBASE, PubMed, Web of Science, WanFang Data and Chinese National Knowledge Infrastructure are searched up to December 2020, used the search strategy of ovar* and granulosa cell* and (tumor* or tumour* or malignan* or cancer* or carcinom* or neoplasm*) and chemotherapy. The screening process was conducted strictly based on inclusion and exclusion criteria. Clinical studies based on human including randomized controlled trial, quasi-randomised controlled trials, nonrandomised trials cohort study and case control study were included without restriction of time. The percentage of patients received chemotherapy increases over time, but the benefit of adjuvant chemotherapy is lack of high-grade evidence of prospective study, based on the current retrospective studies, we still do not have the evidence to confirm the survival benefit of adjuvant chemotherapy in early stage, advanced stage or recurrent aGCT with no residual tumor, but for inoperable disseminated disease or disease with suboptimal cytoreduction, adjuvant chemotherapy maybe an Optable options. Multinational prospective randomised controlled trials are urgently needed to validate the role of adjuvant chemotherapy. Further research on molecular mechanisms and developing novel targeted medicines may improve the survival of aGCTs.