Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

CD4+CD57+ senescent T cells as promoters of systemic lupus erythematosus pathogenesis and the therapeutic potential of senolytic BCL-2 inhibitor.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by persistent activation of immune cells and overproduction of autoantibodies. The accumulation of senescent T and B cells has been observed in SLE and other immune-mediated diseases. However, the exact mechanistic pathways contributing to this process in SLE remain incompletely understood. In this study, we found that in SLE patients: (1) the frequency of CD4+CD57+ senescent T cells was significantly elevated and positively correlated with disease activity; (2) the expression levels of B-lymphoma-2 (BCL-2) family and interferon-induced genes (ISGs) were significantly upregulated; and (3) in vitro, the cytokine IL-15 stimulation increased the frequency of senescent CD4+ T cells and upregulated the expression of BCL-2 family and ISGs. Further, treatment with ABT-263 (a senolytic BCL-2 inhibitor) in MRL/lpr mice resulted in decreased: (1) frequency of CD4+CD44hiCD62L-PD-1+CD153+ senescent CD4+ T cells; (2) frequency of CD19+CD11c+T-bet+ age-related B cells; (3) level of serum antinuclear antibody; (4) proteinuria; (5) frequency of Tfh cells; and (6) renal histopathological abnormalities. Collectively, these results indicated a dominant role for CD4+CD57+ senescent CD4+ T cells in the pathogenesis of SLE and senolytic BCL-2 inhibitor ABT-263 may be the potential treatment in ameliorating lupus phenotypes.

Clinical report and genetic analysis of a novel variant in ZMIZ1 causing neurodevelopmental disorder with dysmorphic factors and distal skeletal anomalies in a Chinese family.

BACKGROUND: Neurodevelopmental disorder with dysmorphic factors and distal skeletal anomalies (NEDDFSA) is a rare and phenotypically variable disorder. The zinc finger MIZ-type containing 1 gene (ZMIZ1) is a causative gene of NEDDFSA that encodes a protein inhibitor of the activated STAT-like family transcriptional regulator. Given the rarity of reported NEDDFSA cases, new phenotypes and genotypes of this disorder are still being discovered. OBJECTIVE: This study describes the phenotype characteristics of a Chinese NEDDFSA family caused by a novel ZMIZ1 variant. METHODS: We reviewed the clinical phenotype of a Chinese patient with NEDDFSA and performed whole-exome sequencing (WES) of the patient's family. We simulated the potential biological harmfulness of the mutant protein. Plasmids were constructed and used for western blot and immunofluorescence assays to analyze protein expression levels. RESULTS: The patient was a 6-month-old male infant who exhibited dysmorphic facial features, neurodevelopmental abnormalities, congenital heart disease, and previously unreported genitourinary system anomalies. WES revealed a non-frameshift deletion variant in ZMIZ1 (NM_020338.4: c.858_875del, p.Val288_Ala293del), resulting in a structural alteration in the protein's alanine-rich domain. Western blot and immunofluorescence assays indicated a significant decrease in the expression level of the mutant ZMIZ1 protein compared to the wild-type protein. CONCLUSION: The clinical manifestations of this patient may be associated with the ZMIZ1 variant, and the structural alteration in the alanine-rich domain of the ZMIZ1 protein may contribute to a more complex disease phenotype. These results expand the genotype-phenotype correlation of ZMIZ1.

3D Wood Microfilter for Fast and Efficient Removal of Heavy Metal Ions from Water.

Adsorption is an effective method for the treatment of heavy metal ions in water; however, the existing adsorbents are complicated to prepare, and costly and difficult to recover. In this work, a 3D wood microfilter was prepared by modifying wood for the removal of heavy metal contaminants from water. First, a green deep eutectic solvent was used to remove lignin from beech wood. Then citric acid and l-cysteine were sequentially used to graft carboxyl and sulfhydryl groups (-SHs) on the surface of cellulose. Finally, a three-dimensional wood microfilter with an abundant porous structure and adsorption sites was formed. The adsorption kinetics and adsorption isotherms of heavy metal ions on the 3D wood microfilter were systematically investigated using Cu2+ and Cd2+ as model species. The results showed that the 3D wood microfilter had a fast adsorption rate and high saturation capacity for both Cu2+ and Cd2+. Based on the advantages of easy processing and multilayer assembly and stacking, a three-layer wood microfilter was designed to achieve high flux rate (1.53 × 103 L m-2 h-1) and high efficiency (>98%) for the removal of heavy metal ions in water. The enhancement mechanism of the adsorption process of Cu2+ and Cd2+ by the 3D wood microfilter was investigated using SEM and EDS, FTIR, and XPS characterization. The simple synthesis method and high adsorption efficiency of this wood microfilter provide a new strategy for the preparation of cheap, efficient, and recyclable adsorbents for heavy metal ions in water.

Sirtuin 1 overexpression contributes to the expansion of follicular helper T cells in Systemic lupus erythematosus and serves as an easy-to-intervene therapeutic target.

OBJECTIVE: SIRT1, an NAD+-dependent deacetylase, is up-regulated in CD4+ T cells from SLE patients and MRL/lpr lupus-like mice. This study aimed to explore the role of SIRT1 in Tfh cell expansion and its potential value as a therapeutic target for SLE. METHODS: Frequencies of CD4+CXCR5+PD-1+ Tfh cells in peripheral blood from SLE patients and their expression of SIRT1 and BCL-6 were determined with flow cytometry. Naïve CD4+ T cells were transfected with SIRT1-expressing lentivirus and small interfering RNA (siRNA) targeting SIRT1, respectively, and then cultured in a Tfh-polarizing condition to study the impact of SIRT1 on Tfh cell differentiation. This impact was also evaluated in both CD4+ T cells and naïve CD4+ T cells by treatment with SIRT1 inhibitors (EX527 and nicotinamide) in vitro. MRL/lpr mice and pristane-induced lupus mice were treated with continuous daily intake of nicotinamide, and their lupus phenotypes including skin rash, arthritis, proteinuria and serum anti-dsDNA autoantibodies were compared with controls. RESULTS: Expression of SIRT1 was elevated in Tfh cells from SLE patients and positively correlated with Tfh cell frequencies. SIRT1 expression gradually increased during Tfh cell differentiation. Overexpression of SIRT1 by lentiviral vectors significantly promoted Tfh cell differentiation/proliferation. Reciprocally, suppressing expression of SIRT1 by siRNA and inhibiting SIRT1 activity by EX-527 or nicotinamide hindered Tfh cell expansion. Continuous daily intake of nicotinamide alleviated lupus-like phenotypes and decreased serum CXCL13 in the two mouse models. CONCLUSION: SIRT1 overexpression contributes to the expansion of Tfh cells in SLE and may serve as a potential target for treatment.

Consecutive injections of low-dose interleukin-2 improve symptoms and disease control in patients with chronic spontaneous urticaria.

PURPOSE: To describe the effectiveness and tolerability of low-dose interleukin (IL)-2 in treating patients with chronic spontaneous urticaria (CSU) refractory to H1-antihistamines. METHODS: This retrospective study included CSU patients who received treatment with at least one cycle of IL-2, injected intramuscularly at a dose of 1.0 million international units daily for 7 consecutive days, after failing treatment with H1-antihistamines. Patients were followed up for ≥12 weeks. RESULTS: Of the 15 patients, 7 (46.7%) and 11 (73.3%) achieved complete response at Week 2 and Week 12, respectively. The mean change of urticaria control test (UCT) and weekly urticaria activity score (UAS7) from baseline was 6.6 (95% CI, 4.2 to 8.9) and - 16.9 (95% CI, -24.0 to -9.8), respectively, at Week 12. Local injection-site reactions were the most common adverse events. No serious adverse events were reported. CONCLUSION: Low-dose IL-2 treatment improves symptoms and disease control for CSU patients refractory to H1-antihistamines.

Does electricity price reduction bring a sustainable development of business: Evidence from fine-grained industrial electricity consumption data in China.

This paper studies the impact of electricity price reduction policy on the economic activities and carbon emissions of different industries. Since 2018, the Chinese government has advocated reducing electricity price for industrial customers in order to alleviate the non-tax burden on businesses. Using monthly electricity consumption and user data from 2016 to 2019, we find that the electricity price reduction has significantly increased the industrial electricity consumption and users. Heterogeneity analyses show that the effect is greater in heavy polluted industries and industries in low and medium GDP regions. The results of threshold impact analysis show that the threshold value of heavy pollution industries was lower than that of general industry and commerce, while heavy pollution industries are more sensitive to electricity prices than general industries. Moreover, the reduction of electricity prices results in a higher percentage of carbon emissions growth in heavy pollution industries. Our result can also help the policymakers access the costs and benefits of electricity price reduction for industrial customers more accurately.

[Asthma management and asthma control level in children]. / å„¿ç«¥å“®å–˜ç®¡ç†ä¸Žå“®å–˜æŽ§åˆ¶æ°´å¹³çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To investigate the influencing factors for asthma management and asthma control level in children. METHODS: A total of 202 children with a confirmed diagnosis of asthma were enrolled. The questionnaire of asthma control level and family management was used to investigate the influencing factors for asthma control level and the indicators of family management. The awareness of childhood asthma and its management was analyzed among the parents, as well as the influence on asthma control level in children, and the association between them was analyzed. RESULTS: Compared with the non-complete control group, the complete control group had significantly longer course of asthma and treatment time (P<0.05). The proportions of asthma attacks ≥3 times and aerosol treatment for asthma attacks >3 times in one year in the complete control group were significantly lower than those in the non-complete control group (P<0.05). The complete control group had a significantly lower proportion of children with frequent respiratory infection, wheezing during respiratory infection, or a family history of allergic diseases (P<0.05). The parents in the complete control group had significantly stronger awareness of short-term escalation to asthma medication after respiratory infection and significantly enhanced management of maintenance medication (P<0.05). Compared with the complete control group, the non-complete control group had a significantly higher proportion of children with abnormal pulmonary function at the initial stage (P<0.05). The level of asthma control in children was associated with short-term escalation to asthma medication during respiratory infection and initial lung function (P<0.05). CONCLUSIONS: The level of asthma control in children is closely associated with the severity of asthma and the comprehensive management of childhood asthma. Early treatment and family management, especially escalation to asthma medication during the early stage of respiratory infection, are of great importance in asthma control. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(1): 73-79.

Extended use of rh-endostatin improves prognosis in patients with advanced non-small cell lung cancer: an analysis of retrospective study.

Background: Rh-endostatin is a potent inhibitor of angiogenesis approved and widely used for advanced non-small cell lung cancer (NSCLC) in China. While the efficacy and safety of extended use of rh-endostatin with platinum-based chemotherapy during induced and maintenance therapy are still not very clear, and whether extended use of rh-endostatin can improve survival needs further investigation. Methods: We performed a retrospective analysis of chemotherapy-naïve patients with stage IIIB-IV or recurrent NSCLC who had been treated with first-line chemotherapy plus rh-endostatin between January 2008 and June 2018. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Cox proportional hazards regression model was used to assess the prognostic importance of risk factors (age, gender, smoking status, Eastern Cooperative Oncology Group (ECOG) performance score, stage, pathology, previous thoracic surgery, and rh-endostatin treatment cycles). Results: A total of 105 patients, with a median of 4 cycles of chemotherapy with rh-endostatin, were eligible for analysis. The median [95% confidence interval (CI)] PFS and OS for patients with extended use of rh-endostatin (≥4 cycles) and nonextended use were 8.2 (4.2-12.3) vs. 3.2 (1.3-5.0) months [hazard ratio (HR) =0.50, P=0.002] and 25.1 (20.5-29.7) vs. 14.0 (9.2-18.8) months (HR =0.50, P=0.003), respectively. The objective response rate (ORR) and disease control rate (DCR) were 23.2% and 92.9%, respectively. Extended use of rh-endostatin (≥4 cycles) was significantly correlated with better PFS and OS in multivariate analysis. Patients with squamous cell cancers significantly benefited from the extended use of rh-endostatin (≥4 cycles) (n=56, P=0.001) but not adenocarcinoma (n=49, P=0.378). Hematologic and gastrointestinal toxicities occurred more frequently in the extended group compared with those in the nonextended group but without any significant differences. Conclusions: In patients with advanced NSCLC, the extended use of rh-endostatin (≥4 cycles) could provide additional survival benefits and satisfactory toxicity profiles, especially for those with squamous cell cancer, which merits further evaluation in a prospective randomized study in the future.

2, 5-dichloro-1, 4-benuinone exposure to zebrafish embryos/larvae causes neurodevelopmental toxicity.

2, 5-dichloro-1, 4-benuinone (2, 5-DCBQ) is an emerging disinfection by-product belonging to the class of halobenzoquinones (HBQs). However, there is limited evidence regarding the neurotoxic effects of 2, 5-DCBQ. To better understand the toxicological mechanisms of aquatic organisms, zebrafish embryos were exposed to 0.2 mg/L, 0.4 mg/L, and 0.6 mg/L of 2, 5-DCBQ from 4 h post-fertilization (hpf) to 120 hpf. Developmental defects, such as reduced body length, decreased heart rate, decreased pigmentation, and abnormal motor axon structure was observed. In particular, the locomotor activity of zebrafish larvae reduced with exposure to increasing 2, 5-DCBQ concentrations, and this effect was more pronounced under dark stimulation. The results indicated that the genes associated with neuronal development (gfap, mbp, syn2a, elavl3, ache, and a1-tubulin) were significantly downregulated after treatment with 2, 5-DCBQ. Furthermore, the KEGG result showed the neuroactive ligand-receptor interaction and apoptosis pathways were visibly disrupted, and we found acetylcholinesterase activity was also affected. In summary, the disinfection by-product, 2, 5-DCBQ, exhibits neurodevelopmental toxicity in zebrafish embryos, providing novel evidence for comprehensive analyses of its toxicity.

Non-rigid Multi-Modal Medical Image Registration Based on Improved Maximum Mutual Information PV Image Interpolation Method.

With the continuous improvement of medical imaging equipment, CT, MRI and PET images can obtain accurate anatomical information of the same patient site. However, due to the fuzziness of medical image physiological evaluation and the unhealthy understanding of objects, the registration effect of many methods is not ideal. Therefore, based on the medical image registration model of Partial Volume (PV) image interpolation method and rigid medical image registration method, this paper established the non-rigid registration model of maximum mutual information Novel Partial Volume (NPV) image interpolation method. The proposed NPV interpolation method uses the Davidon-Fletcher-Powell algorithm (DFP) algorithm optimization method to solve the transformation parameter matrix and realize the accurate transformation of the floating image. In addition, the cubic B-spline is used as the kernel function to improve the image interpolation, which effectively improves the accuracy of the registration image. Finally, the proposed NPV method is compared with the PV interpolation method through the human brain CT-MRI-PET image to obtain a clear CT-MRI-PET image. The results show that the proposed NPV method has higher accuracy, better robustness, and easier realization. The model should also have guiding significance in face recognition and fingerprint recognition.

Molecular mechanism of ethylparaben on zebrafish embryo cardiotoxicity based on transcriptome analyses.

Ethylparaben (EP), one of the parabens, a ubiquitous food and cosmetic preservatives, has caused widespread concern due to its health risks. Recently, studies have found that parabens exposure during pregnancy is negatively correlated with fetal and early childhood development. However, studies about EP on embryo development are few. In this study, the cardiotoxicity effects of EP concentrations ranging from 0 to 20 mg/L on zebrafish embryo development were explored. Results showed that EP exposure induce abnormal cardiac function and morphology, mainly manifested as pericardial effusion and abnormal heart rate in early-stage development of zebrafish embryos. Through transcriptome sequencing followed by Gene Ontology enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we further confirmed that EP exposure ultimately leads to cardiac morphologic abnormalities via the following three mechanisms: 1. Disruption of the retinoic acid signaling pathway related to original cardiac catheter development; 2. Inhibition of gene expression related to myocardial contraction; 3. Orientation development disturbance of heart tube. Moreover, O-Dianisidine staining, whole-mount in situ hybridization at 30 and 48 hours post fertilization (hpf) and hematoxylin-eosin staining results all confirmed the decreased heart's return blood volume, misoriented heart tubes toward either the right or the middle side, and heart loop defects. For the first time, we explored the mechanism by which EP exposure causes abnormal heart development in zebrafish embryos, laying the foundation for further revealing of the EP toxicity on embryonic development.

Abnormalities in Gut Microbiota and Metabolism in Patients With Chronic Spontaneous Urticaria.

Background: Increasing evidence suggests that the gut microbiome plays a role in the pathogenesis of allergy and autoimmunity. The association between abnormalities in the gut microbiota and chronic spontaneous urticaria (CSU) remains largely undefined. Methods: Fecal samples were obtained from 39 patients with CSU and 40 healthy controls (HCs). 16S ribosomal RNA (rRNA) gene sequencing (39 patients with CSU and 40 HCs) and untargeted metabolomics (12 patients with CSU and 12 HCs) were performed to analyze the compositional and metabolic alterations of the gut microbiome in CSU patients and HCs. Results: The 16S rRNA gene sequencing results showed a significant difference in the ß-diversity of the gut microbiota, presented as the Jaccard distance, between CSU patients and HCs. No significant differences were found in the α-diversity of the gut microbiota between patients and HCs. At the phylum level, the major bacteria in the gut microbiome of patients with CSU were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. At the genus level, Lactobacillus, Turicibacter, and Lachnobacterium were significantly increased and Phascolarctobacterium was decreased in patients with CSU. PICRUSt and correlation analysis indicated that Lactobacillus, Turicibacter, and Phascolarctobacterium were positively related to G protein-coupled receptors. Metabolomic analysis showed that α-mangostin and glycyrrhizic acid were upregulated and that 3-indolepropionic acid, xanthine, and isobutyric acid were downregulated in patients with CSU. Correlation analysis between the intestinal microbiota and metabolites suggested that there was a positive correlation between Lachnobacterium and α-mangostin. Conclusions: This study suggests that disturbances in the gut microbiome composition and metabolites and their crosstalk or interaction may participate in the pathogenesis of CSU.

Chronic Urticaria: Advances in Understanding of the Disease and Clinical Management.

Chronic urticaria (CU) is a common skin condition characterized by the recurrence of wheals, with or without angioedema, which lasts for at least 6 weeks. Owing to its pruritus and incurability, this disease adversely affects the patients' physical and mental health and diminishes the quality of life. CU is generally classified into two subtypes based on the relevance of eliciting factors: chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), the latter of which is further divided into several subtypes. To improve the understanding and clinical management of this highly heterogeneous disorder, the EAACI/GA2LEN/EDF/WAO guideline was developed and published in 2018 based on evidence and expert consensus. The diagnostic and treatment algorithms proposed by the guideline have largely facilitated dermatologists in clinical practice. However, several questions remained unsolved and have been widely investigated in the recent years. First, a better understanding of the association between chronic urticaria and its potential underlying causes or eliciting factors such as autoimmunity, infections, coagulation aberrance, and vitamin D deficiency is warranted. This would lead to updates in the diagnostic and treatment procedures of different subtypes of chronic urticaria. Secondly, treatment for recalcitrant cases, especially those resistant to or intolerant of second-generation antihistamines and (or) omalizumab, calls for novel therapeutic measures or strategies. In the present review, we summarized recent advances in the understanding and management of both CSU and CIndU, with special emphasis on their underlying causes or eliciting factors, pathogenic mechanisms, potential targets for intervention, and advances in treatment strategies.

Cardiac developmental toxicity and transcriptome analyses of zebrafish (Danio rerio) embryos exposed to Mancozeb.

Mancozeb (MZ), an antibacterial pesticide, has been linked to reproductive toxicity, neurotoxicity, and endocrine disruption. However, whether MZ has cardiactoxicity is unclear. In this study, the cardiotoxic effects of exposure to environment-related MZ concentrations ranging from 1.88 µM to 7.52 µM were evaluated at the larval stage of zebrafish. Transcriptome sequencing predicted the mechanism of MZ-induced cardiac developmental toxicity in zebrafish by enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Consistent with morphological changes, the osm, pfkfb3, foxh1, stc1, and nrarpb genes may effect normal development of zebrafish heart by activating NOTCH signaling pathways, resulting in pericardial edema, myocardial fibrosis, and congestion in the heart area. Moreover, differential gene expression analysis indicated that cyp-related genes (cyp1c2 and cyp3c3) were significantly upregulated after MZ treatment, which may be related to apoptosis of myocardial cells. These results were verified by real-time quantitative RT-qPCR and acridine orange staining. Our findings suggest that MZ-mediated cardiotoxic development of zebrafish larvae may be related to the activation of Notch and apoptosis-related signaling pathways.

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.

Iridium(iii) complexes as mitochondrial topoisomerase inhibitors against cisplatin-resistant cancer cells.

Herein, we developed the first metal-based mitochondrial topoisomerase inhibitors to achieve an effective therapeutic outcome for the therapy of cisplatin-resistant tumour cells.

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.

Evaluation of 3,4,4,9-trichlorocarbanilide to zebrafish developmental toxicity based on transcriptomics analysis.

Triclocarban (TCC), considered an endocrine-disrupting, persistent, and bioaccumulating organic matter, has attracted a great deal of attention for its pollution and health risks. However, studies on its toxicological mechanism, especially for embryo development are limited. This article explores the cardiac developmental toxicity induced in zebrafish embryos after exposure to different TCC concentrations. First, liquid chromatography-tandem mass spectrometry was used in detecting TCC in embryos in vivo after exposure to various TCC. Results showed that embryonic TCC content reached 9.23 ng after exposure to 300 µg/L TCC, the heart rates of the embryos markedly decreased, heart abnormalities significantly increased. In addition, obvious pericardial effusion was observed in the larvae. Through transcriptome sequencing, 200 differential gene expression (DGE) patterns were detected in the TCC (300 µg/L) experimental and control groups. The results of GO function analysis and KEGG pathway of DGE showed that aryl hydrocarbon receptor (AhR) activation and cyp-related genes (cyp1a, cyp1b1 and cyp1c) were significantly up-regulated. these affected the normal development of zebrafish embryonic heart, tissue edema, and hemorrhage. TCC exhibited strong cardiac teratogenic effects and developmental toxicity, which is partly related to AhR activation. Transcriptome-based results are helpful in precisely determining the risk of TCC exposure. The potential mechanism between TCC and AhR should be further investigated.