Transcriptomic responses of cumulus granulosa cells to SARS-CoV-2 infection during controlled ovarian stimulation.

Cumulus granulosa cells (CGCs) play a crucial role in follicular development, but so far, no research has explored the impact of SARS-CoV-2 infection on ovarian function from the perspective of CGCs. In the present study, we compared the cycle outcomes between infected and uninfected female patients undergoing controlled ovarian stimulation, performed bulk RNA-sequencing of collected CGCs, and used bioinformatic methods to explore transcriptomic changes. The results showed that women with SARS-CoV-2 infection during stimulation had significantly lower number of oocytes retrieved and follicle-oocyte index, while subsequent fertilization and embryo development were similar. CGCs were not directly infected by SARS-CoV-2, but exhibited dramatic differences in gene expression (156 up-regulated and 65 down-regulated). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses demonstrated a high enrichment in antiviral, immune and inflammatory responses with necroptosis. In addition, the pathways related to telomere organization and double strand break repair were significantly affected by infection in gene set enrichment analysis. Further weighted gene co-expression network analysis identified a key module associated with ovarian response traits, which was mainly enriched as a decrease of leukocyte chemotaxis and migration in CGCs. For the first time, our study describes how SARS-CoV-2 infection indirectly affects CGCs at the transcriptional level, which may impair oocyte-CGC crosstalk and consequently lead to poor ovarian response during fertility treatment.

Dysregulation of ferroptosis-related genes in granulosa cells associates with impaired oocyte quality in polycystic ovary syndrome.

Background: Poor oocyte quality remains one of the major challenges for polycystic ovary syndrome (PCOS) patients during in vitro fertilization (IVF) treatment. Granulosa cells (GCs) in PCOS display altered functions and could cause an unfavorable microenvironment for oocyte growth and maturation. Ferroptosis is a new form of programmed cell death, but its role in PCOS has been largely unclarified. Methods: Ferroptosis-related differentially expressed genes (DEGs) of GCs in women with PCOS were identified by bioinformatic analyses of GSE155489 and GSE168404 datasets. Functional enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Core ferroptosis-related genes were further screened by random forest, and evaluated for diagnostic value by receiver operating characteristic curve analyses. Gene expression was validated by real-time quantitative polymerase chain reaction of collected GC samples, and analyzed for association with oocyte quality. In addition, gene regulatory network was constructed based on predicted RNA interactions and transcription factors, while potential therapeutic compounds were screened through molecular docking with crystallographic protein structures. Results: A total of 14 ferroptosis-related DEGs were identified. These DEGs were mainly enriched in reactive oxygen species metabolic process, mitochondrial outer membrane, antioxidant activity as well as ferroptosis and adipocytokine signaling pathways. Eight core ferroptosis-related genes (ATF3, BNIP3, DDIT4, LPIN1, NOS2, NQO1, SLC2A1 and SLC2A6) were further selected in random forest model, which showed high diagnostic performance for PCOS. Seven of them were validated in GC samples, and five were found to be significantly and positively correlated with one or more oocyte quality parameters in PCOS patients, including oocyte retrieval rate, mature oocyte rate, normal fertilization rate, and good-quality embryo rate. Gene regulatory network revealed JUN and HMGA1 as two important transcription factors, while dicoumarol and flavin adenine dinucleotide were predicted as small molecules with therapeutic potential. Conclusions: This is the first comprehensive report to study the differential expression of ferroptosis-related genes in GCs of PCOS and their clinical relevance with oocyte quality. Our findings could provide novel insights on the potential role of GC ferroptosis in PCOS pathogenesis, diagnosis, and targeted treatment.

High-resolution maps show that rubber causes substantial deforestation.

Understanding the effects of cash crop expansion on natural forest is of fundamental importance. However, for most crops there are no remotely sensed global maps1, and global deforestation impacts are estimated using models and extrapolations. Natural rubber is an example of a principal commodity for which deforestation impacts have been highly uncertain, with estimates differing more than fivefold1-4. Here we harnessed Earth observation satellite data and cloud computing5 to produce high-resolution maps of rubber (10 m pixel size) and associated deforestation (30 m pixel size) for Southeast Asia. Our maps indicate that rubber-related forest loss has been substantially underestimated in policy, by the public and in recent reports6-8. Our direct remotely sensed observations show that deforestation for rubber is at least twofold to threefold higher than suggested by figures now widely used for setting policy4. With more than 4 million hectares of forest loss for rubber since 1993 (at least 2 million hectares since 2000) and more than 1 million hectares of rubber plantations established in Key Biodiversity Areas, the effects of rubber on biodiversity and ecosystem services in Southeast Asia could be extensive. Thus, rubber deserves more attention in domestic policy, within trade agreements and in incoming due-diligence legislation.

Vision-Related Quality of Life in Primary Angle-Closure Glaucoma Patients with or without Visual Field Dysfunction.

Purpose: To evaluate the association between visual-related quality of life (VRQoL) and visual field (VF) loss in patients with primary angle-closure glaucoma (PACG). Methods: In this case-control study, a total of 79 patients with PACG (with or without VF detects) and 35 healthy controls were included. The patients underwent the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), clinical examination, and VF testing. VF defects were identified by simplified Hodapp's classification. NEI VFQ-25 scores were compared between the three groups. Results: No significant differences were found in gender, VFQ rating for "composite score" and "color vision" between the three groups. PACG patients with VF loss were most likely to be older and had lower best corrected visual acuity (BCVA), spherical equivalent (SE), mean deviation (MD), and visual field index (VFI), but higher pattern standard deviation (PSD) (all P < 0.05). Furthermore, patients with VF loss had significantly lower NVE-VFQ-25 subscale scores for general health, general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, and peripheral vision than PACG patients without VF loss and healthy controls (all P < 0.05). VFI (ß = 1.498, P=0.003) and MD (ß = -3.891, P=0.016) were significantly correlated with Role Difficulties scores. Additionally, PSD was significantly correlated with Peripheral Vision scores (ß = -1.346, P=0.003). Conclusions: PACG patients with VF loss reported lower NEI VFQ-25 composite and subscale scores. VF indices including VFI, MD, and PSD were strongly correlated with VRQoL as assessed by NEI VFQ-25; thus, VRQoL may be significantly impacted by glaucomatous VF defects.

Isoliquiritigenin induces oxidative stress and immune response in zebrafish embryos.

Isoliquiritigenin (ISL) is used in many households' personal hygiene and medicinal products, and the average human daily ISL exposure is 1-2 mg/kg. However, the molecular mechanisms of ISL toxicity in zebrafish embryos have not been fully elucidated. We investigated whether exposure to ISL induces oxidative stress and inflammatory responses in zebrafish. And exposure to ISL significantly affects the expression of immune response-related genes in zebrafish embryos following oxidative stress and the release of pro-inflammatory mediators through Toll-like receptor signaling.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis.

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

[The new progress and significance of new ultrasound technology in the diagnosis of azoospermia].

The diagnosis and treatment of azoospermia rely heavily on auxiliary ex-amination technology. Compared with CT and MRI, ultrasound has more practical value in the diagnosis of azoospermia.Currently, the main ultrasonic technologies are contrast-enhanced ultrasound, real-time ultrasound elastography and ultrasound tar-geted puncture. This article aims to summarize and prospect the application of new ultrasound technology in azoospermia.Real-time ultrasound elastography is widely used in breast diseases and is expected to play a greater role in azoospermia. Ultra-sound targeted puncture can greatly reduce the damage of testicular spermatogenic function, but its application is still not widely used.The combined application of new technologies can make up for their respective shortcomings and improve the accuracy of azoospermia diagnosis.Therefore, further research on new ultrasound technology in the diagnosis of azoospermia will play a greater role.

Sensory Description and Consumer Hedonic Perception of Ultra-High Temperature (UHT) Milk.

Sensory characteristics of products play an essential role on the consumer' s acceptability, preference and consuming behavior choice. The sensory profiles and consumer hedonic perception for 14 UHT milk products using sensory quantitatively descriptive analysis and a 9-point hedonic scale were investigated in this study. There were significant differences in the sensory attributes intensity and liking scores among the organic whole milk, ordinary whole milk, low-fat milk, and skimmed milk (p < 0.05). Skimmed milk samples had lowest intensity scores of typical milk aroma, taste flavor and texture attributes, as well as had the lowest overall liking scores. Whole milk samples had higher sensory intensity scores than low-fat milk samples, even though no significant differences of overall liking scores were observed between whole milk and low-fat milk. Furthermore, the relationship between the sensory attribute and overall liking was demonstrated according to correlation analysis and partial least squares regression (PLSR) analysis. Overall liking increased significantly with the increasing of sweet, after milk aroma, protein-like, mellow and thick, while decreased significantly with the enhancement of cowy, cooked and whey (p < 0.05). These findings presented a potential strategy for identifying the key sensory attributes responsible for liking score differences among different kinds of UHT milk products.

Vision-Related Quality of Life and Association Between Retinal Parameters in Patients with Non-Arteritic Anterior Ischemic Optic Neuropathy.

Purpose: To evaluate visual-related quality of life (VR-QoL) and its association with optic nerve head microvasculature in individuals with nonarteritic anterior ischemic optic neuropathy (NAION) evaluated at the acute stage. Methods: In this retrospective case-control study, 23 NAION eyes at the acute stage and 25 age and gender matched healthy eyes were included, respectively. All included eyes underwent a complete ophthalmic examination including optical coherence tomography (OCT) and OCT angiography (OCTA). The Chinese version of the National Eye Institute Visual Function Questionnaire-25 (CHI-NEI-VFQ-25) was applied to assess VR-QoL in individuals consecutively visited at an ophthalmic center. Descriptive and analytic statistics were employed. Results: There were no significant differences on age, gender, socioeconomic and education level (P > 0.05), but best-corrected visual acuity (BCVA) differences were reported between cases and controls (P < 0.05). Each peripapillary retinal nerve fiber layer (RNFL) thickness was higher but peripapillary vessel density (VD) and VR-QoL scores for all subscales were significantly lower in cases when compared with controls, respectively (P < 0.05). Particularly, pearson's partial correlation analysis restricted to eyes with NAION revealed stronger correlations between peripapillary RNFL measurements, VD and VR-QoL. Conclusion: NAION at the acute stage affects VR-QoL in Chinese individuals. Some peripapillary RNFL measurements and VD correlated with VR-QoL. Retinal anatomic and blood flow examinations and inventions in patients with NAION are necessary to facilitate VR-QoL and disease control.

Quantification of peripapillary vessel density in non-arteritic anterior ischemic optic neuropathy patients with optical coherence tomography angiography.

BACKGROUND: Quantitative assessments based on optical coherence tomographic angiography (OCTA) may have potential promising value in the early detection of non-arteritic anterior ischemic optic neuropathy (NA-AION), but there is limited information on the ability of OCTA to distinguish eyes with NA-AION. This study was conducted to evaluate the ability of measurements of peripapillary perfusion using OCTA to distinguish healthy eyes from eyes with NA-AION. METHODS: In this retrospective case-control study, newly diagnosed NA-AION patients and healthy controls matched at a ratio of 1:3 by gender and age (±5 years) were enrolled from 1 September 2020 to 30 June 2021. Peripapillary vessel density (pVD) was examined based on the area of vessels by means of a 4.5 mm OCTA scan. In addition, peripapillary retinal nerve fiber layer (pRNFL) thickness was obtained from structural optical coherence tomography (OCT), as was the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 29 eyes from 28 cases with NA-AION and 99 healthy eyes from 68 participants were imaged. All participants were Chinese. The NA-AION group showed a significant reduction of the pVD (P<0.001), while all subregions of pRNFL thickness were prominent in all 8 quadrants (P>0.05). The pVD of the optic disc in the superior temporal (ST) region showed better diagnostic accuracy (AUC =0.86) in discriminating the NA-AION group from healthy controls. After adjusting for confounders, ST was independently associated with the presence of NA-AION [odds ratio (OR) =0.971, 95% confidence interval (CI): 0.943-0.990, P=0.048]. CONCLUSIONS: Decreased pVD was detected by non-invasive measurements of OCTA in the eyes of NA-AION patients. This finding may reveal an association between the ST region and the presence of NA-AION. The pVD may have potential diagnostic ability and may serve as an additional biomarker in the management of the disease.

Risk factors for peripheral venous catheter failure: A prospective cohort study of 5345 patients.

PURPOSE: The objective of this study was to determine the independent risk factors associated with peripheral venous catheter (PVC) failure and develop a model that can predict PVC failure. METHODS: This prospective, multicenter cohort study was carried out in nine tertiary hospitals in Suzhou, China between December 2017 and February 2018. Adult patients undergoing first-time insertion of a PVC were observed from catheter insertion to removal. Logistic regression was used to identify the independent risk factors predicting PVC failure. RESULTS: This study included 5345 patients. The PVC failure rate was 54.05% (n = 2889/5345), and the most common causes of PVC failure were phlebitis (16.3%) and infiltration/extravasation (13.8%). On multivariate analysis, age (45-59 years: OR, 1.295; 95% CI, 1.074-1.561; 60-74 years: OR, 1.375; 95% CI, 1.143-1.654; ⩾75 years: OR, 1.676; 95% CI, 1.355-2.073); department (surgery OR, 1.229; 95% CI, 1.062-1.423; emergency internal/surgical ward OR, 1.451; 95% CI, 1.082-1.945); history of venous puncture in the last week (OR, 1.298, 95% CI 1.130-1.491); insertion site, number of puncture attempts, irritant fluid infusion, daily infusion time, daily infusion volume, and type of sealing liquid were independent predictors of PVC failure. Receiver operating characteristic curve analysis indicated that a logistic regression model constructed using these variables had moderate accuracy for the prediction of PVC failure (area under the curve, 0.781). The Hosmer-Lemeshow goodness of fit test demonstrated that the model was correctly specified (χ2 = 2.514, p = 0.961). CONCLUSION: This study should raise awareness among healthcare providers of the risk factors for PVC failure. We recommend that healthcare providers use vascular access device selection tools to select a clinically appropriate device and for the timely detection of complications, and have a list of drugs classified as irritants or vesicants so they can monitor patients receiving fluid infusions containing these drugs more frequently.

Studying the mechanism of sperm DNA damage caused by folate deficiency.

Sperm DNA injury is one of the common causes of male infertility. Folic acid deficiency would increase the methylation level of the important genes, including those involved in DNA double-strand break (DSB) repair pathway. In the early stages, we analysed the correlation between seminal plasma folic acid concentration and semen parameters in 157 infertility patients and 91 sperm donor volunteers, and found that there was a significant negative correlation between seminal folic acid concentration and sperm DNA Fragmentation Index (DFI; r = -0.495, p < 0.01). Then through reduced representation bisulphite sequencing, global DNA methylation of sperm of patients in the low folic acid group and the high folic acid group was analysed, it was found that the methylation level in Rad54 promoter region increased in the folic acid deficiency group compared with the normal folic acid group. Meanwhile, the results of animal model and spermatocyte line (GC-2) also found that folic acid deficiency can increase the methylation level in Rad54 promoter region, increased sperm DFI in mice, increased the expression of γ-H2AX, that is, DNA injury marker protein, and increased sensitivity of GC-2 to external damage and stimulation. The study indicates that the expression of Rad54 is downregulated by folic acid deficiency via DNA methylation. This may be one of the mechanisms of sperm DNA damage caused by folate deficiency.

Varicocele-Mediated Male Infertility: From the Perspective of Testicular Immunity and Inflammation.

Background: Varicocele (VC) is present in 35 - 40% of men with infertility. However, current surgical and antioxidant treatments are not completely effective. In addition to oxidative stress, it is likely that other factors such as testicular immune microenvironment disorder contribute to irreversible testicular. Evidence suggests that VC is associated with anti-sperm antibodies (ASAs), spermatogenesis and testosterone secretion abnormalities, and testicular cytokine production. Moreover, inhibition of inflammation can alleviate VC-mediated pathogenesis. The normal function of the testis depends on its immune tolerance mechanism. Testicular immune regulation is complex, and many infectious or non-infectious diseases may damage this precision system. Results: The testicular immune microenvironment is composed of common immune cells and other cells involved in testicular immunity. The former includes testicular macrophages, T cells, dendritic cells (DCs), and mast cells, whereas the latter include Leydig cells and Sertoli cells (SCs). In animal models and in patients with VC, most studies have revealed an abnormal increase in the levels of ASAs and pro-inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha in the seminal plasma, testicular tissue, and even peripheral blood. It is also involved in the activation of potential inflammatory pathways, such as the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing (NLRP)-3 pathway. Finally, the development of VC-mediated infertility (VMI) may be facilitated by abnormal permeability of proteins, such as claudin-11, that constitute the blood-testis barrier (BTB). Conclusions: The testicular immune response, including the production of ASAs and inflammatory factors, activation of inflammatory pathways, and destruction of the BTB may be involved in the pathogenesis of VMI it is necessary to further explore how patient outcomes can be improved through immunotherapy.

Folic acid deficiency damages male reproduction via endoplasmic reticulum stress-associated PERK pathway induced by Caveolin-1 in mice.

Folic acid is critical to maintaining normal male reproductive function. Endoplasmic reticulum (ER) stress plays a crucial role in folic acid deficiency. Studies have shown that Caveolin-1 (Cav-1) is involved in ER stress, but the specific mechanism in male reproduction is still unclear. This study aimed to investigate the effects of folic acid deficiency on spermatogenesis and elucidate the underlying mechanisms. C57BL/6 mice fed with folic acid deficiency induced diet(0.3 mg/kg) were used. A significant decrease in the sperm concentration in the folic acid deficiency group was observed. Meanwhile, folic acid deficiency decreased Cav-1 expression in the testis tissue and increased endoplasmic reticulum stress-related PERK, eIF2α, ATF4, CHOP gene expression. Our results suggest that folic acid deficiency can affect male reproduction through the Cav-1-PERK-eIFα-ATF4-CHOP pathway.Abbreviations: ATF4: activating transcription factor 4; Ca2+: calcium ion; Cav-1: Caveolin-1; CCK-8: cell counting kit-8; CHOP: CCAAT-enhancer-binding protein homologous protein; DNA: Deoxyribonucleic acid; DSB: double strand breakage; eIF2α: eukaryotic Initiation Factor 2 alpha; ER: endoplasmic reticulum; FD: folic acid deficiency; FITC: fluorescein isothiocyanate; HE: hematoxylin and eosin; H3K4me3: histone H3 lysine 4 trimethylation; PERK: protein kinase RNA-like endoplasmic reticulum kinase; PI: propidium iodide; RT-qPCR: quantitative reverse transcription PCR; TUNEL: TdT mediated dUTP Nick End Labeling.

Obesity Causes Abrupt Changes in the Testicular Microbiota and Sperm Motility of Zebrafish.

Background: Obesity is a recognized risk factor for low fertility and is becoming increasingly prevalent in many countries around the world. Obesity changes intestinal microbiota composition, causes inflammation of various organs, and also reduces sperm quality. Several microorganisms are present in the testis. However, whether obesity affects the changes of testicular microbiota and whether these changes are related to reduced fertility in obese men remain to be elucidated. Methods: In the present study, a zebrafish obesity model was established by feeding with egg yolk powder. Sperm motility was measured by the Computer Assisted Sperm Analysis system, testicular microbial communities was assessed via 16s RNA sequencing, the immune response in zebrafish testis was quantified by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, and the testicular tissue structure was detected by electron microscopy and hematoxylin-eosin staining. Results: Compared with the control group, zebrafish sperm motility was dramatically reduced, the expression of testicular proinflammatory cytokines in the testes was upregulated, and the blood-testis barrier structure was disrupted in the obese group. In addition, testicular microbiome composition was clearly altered in the obese group. Conclusion: Obesity alters testicular microbiota composition, and the reason behind the decreased sperm motility in obese zebrafish may be related to changes in the testicular microbial communities.

Severe Acute Respiratory Syndrome Coronavirus 2 and Male Reproduction: Relationship, Explanations, and Clinical Remedies.

Coronavirus disease 2019 (COVID-2019) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been an ongoing pandemic and worldwide public health emergency, having drawn a lot of attention around the world. The pathogenesis of COVID-19 is characterized by infecting angiotensin-converting enzyme 2 (ACE2)-expressing cells, including testis-specific cells, namely, Leydig, Sertoli, and spermatogenic cells, which are closely related to male reproduction. This leads to aberrant hyperactivation of the immune system generating damage to the infected organs. An impairment in testicular function through uncontrolled immune responses alerts more attention to male infertility. Meanwhile, the recent clinical data indicate that the infection of the human testis with SARS-CoV-2 may impair male germ cell development, leading to germ cell loss and higher immune cell infiltration. In this review, we investigated the evidence of male reproductive dysfunction associated with the infection with SARS-CoV-2 and its possible immunological explanations and clinical remedies.

tmbim4 protects against triclocarban-induced embryonic toxicity in zebrafish by regulating autophagy and apoptosis.

Triclocarban (TCC), an antibacterial agent widely used in personal care products, can affect embryonic development. However, the specific molecular mechanism of TCC-induced embryonic developmental damage remains unclear. In this study, TCC exposure was found to increase the expression of tmbim4 gene in zebrafish embryos. The tmbim4 mutant embryos are more susceptible to TCC exposure than wild-type (WT) embryos, with tmbim4 overexpression reducing TCC-induced embryonic death in the former. Exposure of tmbim4 mutant larvae to 400 µg/L TCC substantially increased apoptosis in the hindbrain and eyes. RNA-sequencing of WT and tmbim4 mutant larvae indicated that knockout of the tmbim4 gene in zebrafish affects the autophagy pathway. Abnormalities in autophagy can increase apoptosis and TCC exposure caused abnormal accumulation of autophagosomes in the hindbrain of tmbim4 mutant zebrafish embryos. Pretreatment of TCC-exposed tmbim4 mutant zebrafish embryos with autophagosome formation inhibitors, substantially reduced the mortality of embryos and apoptosis levels. These results indicate that defects in the tmbim4 gene can reduce zebrafish embryo resistance to TCC. Additionally, apoptosis induced by abnormal accumulation of autophagosomes is involved in this process.

Clinical characteristics, rates of blindness, and geographic features of PACD in China.

OBJECTIVE: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China. METHODS: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed. RESULTS: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes. CONCLUSION: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.

Chronic exposure to organic oxygen-demanding pollutants at an environmentally realistic concentration affects sperm motility in zebrafish.

Wastewater and organic oxygen-demanding pollutants (ODPs) are produced by various factories in China, the United States and other countries. However, whether ODP affects reproductive health remains unclear. To investigate the impact of environmental concentrations of ODP exposure on reproductive health, adult male zebrafish were used to evaluated the effects ODP exposure on the fertility in this study. We found that exposure to ODP reduced the sperm motility of adult male zebrafish. Similarly, the testosterone content of the experimental zebrafish was obviously decreased. Transcription of immune response-related genes, including tumor necrosis factor (tnf)-α, il-1ß, and il-8, was upregulated upon exposure to ODP. Mating experiments indicated that the hatching time of the offspring embryos was clearly prolonged upon ODP exposure, but the embryo fertilization rate was not different. These results assumed that exposure to ODP at ambient concentrations visibly affected the sperm motility in adult zebrafish maybe due to the expression of immune response-related genes in the zebrafish male gonads and the release of pro-inflammatory mediators. Therefore, we assumed that the impact of ODP on the reproductive health of aquatic organisms cannot be ignored.

Prokineticin 2 via Calcium-Sensing Receptor Activated NLRP3 Inflammasome Pathway in the Testicular Macrophages of Uropathogenic Escherichia coli-Induced Orchitis.

Reproductive tract infections contribute to the development of testicular inflammatory lesions, leading to male infertility. Previous research shows that the activation of the NLRP3 inflammasome in orchitis promotes the secretion and maturation of IL-1ß and, thus, decreases male fertility. The calcium-sensing receptor (CaSR) is closely related to the secretion of proinflammatory cytokines. An increase in the CaSR level promotes the assembly and activation of the NLRP3 inflammasome. However, the role of CaSRs in orchitis is unknown. We first constructed a uropathogenic Escherichia Coli (UPEC) rat orchitis model and then detected the expression of CaSR and NLRP3 inflammatory pathway proteins in testicular macrophages (TM) through RT-PCR and WB, calcium levels in TM through flow cytometry, and proinflammatory factor IL-1ß through ELISA. In addition, testosterone levels in the serum samples were detected using liquid chromatography-mass spectrometry (LC-MS). Here, we show that CaSR upregulation after infection in TM in a rat model of UPEC induces the activation of the NLRP3 inflammasome pathway and thereby enhances IL-1ß secretion and reduces the testosterone level in the blood. Moreover, CaSR inhibitors can alleviate inflammatory impairment. After UPEC challenge in vitro, CaSR promoted NLRP3 expression and released IL-1ß cleaved from TM into the supernatant. Overall, elevated CaSR levels in TM in testes with UPEC-induced orchitis may impair testosterone synthesis through the activation of the NLRP3 pathway and PK2 is an upstream regulatory protein of CaSR. Our research further shows the underlying mechanisms of inflammation-related male infertility and provides anti-inflammatory therapeutic targets for male infertility.