High-fat diet led to testicular inflammation and ferroptosis via dysbiosis of gut microbes.

The disorder of gut microbiota has negative impact on male reproductive, and testicular damage is associated with obesity. However, the detailed mechanism of gut microbiota on the obesity-induced testis injury are still unknown. Therefore, we constructed a mouse model to investigate the effects of obesity on testis injury. In this study, we found that HFD-induced obesity could disorder gut microbiota homeostasis, which increased the abundance of Brevundimonas, Desulfovibrionaceae_unclassified and Ralstonia, ultimately leading to the overproduction of lipopolysaccharides (LPS). Meanwhile, HFD-feeding promoted intestinal permeability via inhibiting expression of tight junction proteins (ZO-1, Occludin and Claudin) and reducing excretion of mucus, leading to translocation of LPS. The over-accumulation of LPS in the bloodstream triggered an inflammatory response by activating TLR4/NF-κB pathway in testis. On the other hand, the gut microbiota produced-LPS also could induce ferroptosis in testis, as reflected by enhancing iron content and lipid peroxidation (MDA), as well as decreasing ferroptosis-related proteins, including GPX4, FTH1 and SLC1A11. Moreover, inhibition of LPS ligand (TLR4) with Resatorvid (TAK-242) alleviated obesity-induced testis injury through suppression of inflammation and ferroptosis. In conclusion, this study provides novel insights into the underlying mechanisms of obesity-related testis injury induced by gut microbiota disorder via the gut-testis axis, thus offering potential targets to counteract obesity-induced male reproductive disorder.

Enhanced delivery of CRISPR/Cas9 system based on biomimetic nanoparticles for hepatitis B virus therapy.

The persistent presence of covalently closed circular DNA (cccDNA) in hepatocyte nuclei poses a significant obstacle to achieving a comprehensive cure for hepatitis B virus (HBV). Current applications of CRISPR/Cas9 for targeting and eliminating cccDNA have been confined to in vitro studies due to challenges in stable cccDNA expression in animal models and the limited non-immunogenicity of delivery systems. This study addresses these limitations by introducing a novel non-viral gene delivery system utilizing Gemini Surfactant (GS). The developed system creates stable and targeted CRISPR/Cas9 nanodrugs with a negatively charged surface through modification with red blood cell membranes (RBCM) or hepatocyte membranes (HCM), resulting in GS-pDNA@Cas9-CMs complexes. These GS-pDNA complexes demonstrated complete formation at a 4:1 w/w ratio. The in vitro transfection efficiency of GS-pDNA-HCM reached 54.61%, showing homotypic targeting and excellent safety. Additionally, the study identified the most effective single-guide RNA (sgRNA) from six sequences delivered by GS-pDNA@Cas9-HCM. Using GS-pDNA@Cas9-HCM, a significant reduction of 96.47% in in vitro HBV cccDNA and a 52.34% reduction in in vivo HBV cccDNA were observed, along with a notable decrease in other HBV-related markers. The investigation of GS complex uptake by AML-12 cells under varied time and temperature conditions revealed clathrin-mediated endocytosis (CME) for GS-pDNA and caveolin-mediated endocytosis (CVME) for GS-pDNA-HCM and GS-pDNA-RBCM. In summary, this research presents biomimetic gene-editing nanovectors based on GS (GS-pDNA@Cas9-CMs) and explores their precise and targeted clearance of cccDNA using CRISPR/Cas9, demonstrating good biocompatibility both in vitro and in vivo. This innovative approach provides a promising therapeutic strategy for advancing the cure of HBV.

Construction and evaluation of liposomal drug delivery system for an ALK/HDACs dual-targeted inhibitor with sustained release and enhanced antitumor effect.

ALK/HDACs dual target inhibitor (PT-54) was a 2,4-pyrimidinediamine derivative synthesized based on the pharmacophore merged strategy that inhibits both anaplastic lymphoma kinase (ALK) and histone deacetylases (HDACs), which has demonstrated significant efficacy in treating multiple cancers. However, its poor solubility in water limited its clinical application. In this study, we prepared PT-54 liposomes (PT-54-LPs) by the membrane hydration method to overcome this defect. The encapsulation efficiency (EE) and particle size were used as evaluation indicators to explore the preparation conditions of PT-54-LPs. The morphology, particle size, EE, drug loading content (DLC), drug release properties, and stability of PT-54-LPs were further investigated. In vitro drug release studies showed that PT-54-LPs exhibited significant slow-release properties compared with free PT-54. PT-54-LPs also showed better tumor inhibitory effects than free PT-54 without significant adverse effects. These results suggested that PT-54-LPs displayed sustained drug release and significantly improved the tumor selectivity of PT-54. Thus, PT-54-LPs showed significant promise in enhancing anticancer efficiency.

Identification of antimicrobial-susceptible Pseudomonas aeruginosa RpoA variant strains through positional conservation pattern.

BACKGROUND: Bacterial RNA polymerase (RNAP) is a promising target for antimicrobial chemotherapy due to its indispensable role in bacterial growth and survival. Among its components, only the rpoB gene encoding the ß-subunit is known for its association with rifampicin resistance. We recently identified a variant of the RNAP α-subunit (RpoA) in Pseudomonas aeruginosa, conferring heightened bacterial susceptibility to antimicrobials. This susceptibility was attributed to the specific down-regulation of the MexEF-OprN efflux pump. OBJECTIVES: We asked how to distinguish antimicrobial-susceptible variant strains from clinical isolates. METHODS: In this study, we identified various P. aeruginosa RpoA variants from clinical sources. Using the sequence alignment of different bacterial RpoA species, we computed the positional conservation of substitutions in RpoA variants using Shannon Entropy. RESULTS: Our findings revealed that selective RpoA variant strains exhibited distinct profiles of antimicrobial susceptibility. Notably, RpoA variant strains, containing single-substitutions in the C-terminal domain (α-CTD) but not the N-terminal domain (α-NTD), showed attenuated MexEF-OprN expression and increased susceptibility to MexEF-OprN-specific antibiotics. Furthermore, we observed a close correlation between the susceptibility of these α-CTD RpoA variant strains to antibiotics and the conservation degrees of positional substitutions. CONCLUSIONS: Our findings demonstrate the prevalence of antimicrobial-susceptible RpoA variant strains among P. aeruginosa clinical isolates. The identified positional conservation pattern in our study facilitates the rapid classification of RpoA variant strains with distinct drug resistances. Given the high conservation of RNAP across bacterial species, our findings open a new therapeutic perspective for precisely and efficiently combating pathogenic RpoA variant strains with specific antimicrobials.

Isorhamnetin Improves Oocyte Maturation by Activating the Pi3k/Akt Signaling Pathway.

SCOPE: Isorhamnetin is a natural flavonoid with various pharmacological activities, which can be widely and continuously ingested by humans and animals through their daily diet. The aim of this study is to explore the benefits and molecular mechanisms of isorhamnetin on oocyte maturation. METHODS AND RESULTS: Oocytes are incubated with isorhamnetin (5, 10, 20, and 30 µM) for 44 h. Isorhamnetin (10 µM) increases the polar body extrusion rate of oocytes. Furthermore, isorhamnetin alleviates oxidative stress by inhibiting reactive oxygen species levels and stimulating SOD2 protein expression. The changes in intracellular mitochondrial autophagy and apoptosis-related proteins (Bcl-2, Bax/Bcl-2, and C-Casp3) indicate that isorhamnetin inhibits oocyte apoptosis. Isorhamnetin inhibits endoplasmic reticulum stress by reducing the protein expression of CHOP and GRP78 and improving the normal distribution rate of endoplasmic reticulum. Mechanistic studies show that isorhamnetin activates the PI3K/Akt signaling pathway. CONCLUSION: Isorhamnetin promotes oocyte maturation by inhibiting oxidative stress, mitochondrial dysregulation, apoptosis, and endoplasmic reticulum stress, which have important potential for improving oocyte quality and treating female infertility.

Diquat causes mouse testis injury through inducing heme oxygenase-1-mediated ferroptosis in spermatogonia.

Diquat dibromide (DQ) is a globally used herbicide in agriculture, and its overuse poses an important public health issue, including male reproductive toxicity in mammals. However, the effects and molecular mechanisms of DQ on testes are limited. In vivo experiments, mice were intraperitoneally injected with 8 or 10 mg/kg/ day of DQ for 28 days. It has been found that heme oxygenase-1 (HO-1) mediates DQ-induced ferroptosis in mouse spermatogonia, thereby damaging testicular development and spermatogenesis. Histopathologically, we found that DQ exposure caused seminiferous tubule disorders, reduced germ cells, and increased sperm malformation, in mice. Reactive oxygen species (ROS) staining of frozen section and transmission electron microscopy (TEM) displayed DQ promoted ROS generation and mitochondrial morphology alterations in mouse testes, suggesting that DQ treatment induced testicular oxidative stress. Subsequent RNA-sequencing further showed that DQ treatment might trigger ferroptosis pathway, attributed to disturbed glutathione metabolism and iron homeostasis in spermatogonia cells in vitro. Consistently, results of western blotting, measurements of MDA and ferrous iron, and ROS staining confirmed that DQ increased oxidative stress and lipid peroxidation, and accelerated ferrous iron accumulation both in vitro and in vivo. Moreover, inhibition of ferroptosis by deferoxamine (DFO) markedly ameliorated DQ-induced cell death and dysfunction. By RNA-sequencing, we found that the expression of HO-1 was significantly upregulated in DQ-treated spermatogonia, while ZnPP (a specific inhibitor of HO-1) blocked spermatogonia ferroptosis by balancing intracellular iron homeostasis. In mice, administration of the ferroptosis inhibitor ferrostatin-1 effectively restored the increase of HO-1 levels in the spermatogonia, prevented spermatogonia death, and alleviated the spermatogenesis disorders induced by DQ. Overall, these findings suggest that HO-1 mediates DQ-induced spermatogonia ferroptosis in mouse testes, and targeting HO-1 may be an effective protective strategy against male reproductive disorders induced by pesticides in agriculture.

Uncovering a hidden functional role of the XRE-cupin protein PsdR as a novel quorum-sensing regulator in Pseudomonas aeruginosa.

XRE-cupin family proteins containing an DNA-binding domain and a cupin signal-sensing domain are widely distributed in bacteria. In Pseudomonas aeruginosa, XRE-cupin transcription factors have long been recognized as regulators exclusively controlling cellular metabolism pathways. However, their potential functional roles beyond metabolism regulation remain unknown. PsdR, a typical XRE-cupin transcriptional regulator, was previously characterized as a local repressor involved solely in dipeptide metabolism. Here, by measuring quorum-sensing (QS) activities and QS-controlled metabolites, we uncover that PsdR is a new QS regulator in P. aeruginosa. Our RNA-seq analysis showed that rather than a local regulator, PsdR controls a large regulon, including genes associated with both the QS circuit and non-QS pathways. To unveil the underlying mechanism of PsdR in modulating QS, we developed a comparative transcriptome approach named "transcriptome profile similarity analysis" (TPSA). Using this TPSA method, we revealed that PsdR expression causes a QS-null-like transcriptome profile, resulting in QS-inactive phenotypes. Based on the results of TPSA, we further demonstrate that PsdR directly binds to the promoter for the gene encoding the QS master transcription factor LasR, thereby negatively regulating its expression and influencing QS activation. Moreover, our results showed that PsdR functions as a negative virulence regulator, as inactivation of PsdR enhanced bacterial cytotoxicity on host cells. In conclusion, we report on a new QS regulation role for PsdR, providing insights into its role in manipulating QS-controlled virulence. Most importantly, our findings open the door for a further discovery of untapped functions for other XRE-Cupin family proteins.

Preparation of etoposide liposomes for enhancing antitumor efficacy on small cell lung cancer and reducing hematotoxicity of drugs.

Etoposide (VP16) is commonly used in the treatment of small cell lung cancer (SCLC) in clinical practice. However, severe adverse reactions such as bone marrow suppression toxicity limit its clinical application. Although several studies on VP16 liposomes were reported, no significant improvement in bone marrow suppression toxicity has been found, and there was a lack of validation of animal models for in vivo antitumor effects. Therefore, we attempted to develop a PEGylated liposomal formulation that effectively encapsulated VP16 (VP16-LPs) and evaluated its therapeutic effect and toxicity at the cellular level and in animal models. First, we optimized the preparation process of VP16-LPs using an orthogonal experimental design and further prepared them into freeze-dried powder to improve storage stability of the product. Results showed that VP16-LPs freeze-dried powder exhibited good dispersibility and stability after redispersion. In addition, compared to marketed VP16 injection, VP16-LPs exhibited sustained drug release characteristics. At the cellular level, VP16-LPs enhanced the cellular uptake of drugs and exhibited strong cytotoxic activity. In animal models, VP16-LPs could target and aggregate in tumors and exhibit a higher anti-tumor effect than VP16-injection after intravenous injection. Most importantly, hematological analysis results showed that VP16-LPs significantly alleviated the bone marrow suppression toxicity of drug. In summary, our study confirmed that PEGylated liposomes could enhance therapeutic efficacy and reduce toxicity of VP16, which demonstrated that VP16-LPs had enormous clinical application potential.

Comparative study of reactive oxygen species and tetracycline degradation pathways in catalytic peroxodisulfate activation by asymmetric mesoporous TiO2 and the corresponding controlled-release materials.

The removal of trace amounts of antibiotics from water environments while simultaneously avoiding potential environmental hazards during the treatment is still a challenge. In this work, green, harmless, and novel asymmetric mesoporous TiO2 (A-mTiO2) was combined with peroxodisulfate (PDS) as active components in a controlled-release material (CRM) system for the degradation of tetracycline (TC) in the dark. The formation of reactive oxygen species (ROS) and the degradation pathways of TC during catalytic PDS activation by A-mTiO2 powder catalysts and the CRMs were thoroughly studied. Due to its asymmetric mesoporous structure, there were abundant Ti3+/Ti4+ couples and oxygen vacancies in A-mTiO2, resulting in excellent activity in the activation of PDS for TC degradation, with a mineralization rate of 78.6%. In CRMs, ROS could first form during PDS activation by A-mTiO2 and subsequently dissolve from the CRMs to degrade TC in groundwater. Due to the excellent performance and good stability of A-mTiO2, the resulting constructed CRMs could effectively degrade TC in simulated groundwater over a long period (more than 20 days). From electron paramagnetic resonance analysis and TC degradation experiments, it was interesting to find that the ROS formed during PDS activation by A-mTiO2 powder catalysts and CRMs were different, but the degradation pathways for TC were indeed similar in the two systems. In PDS activation by A-mTiO2, besides the free hydroxyl radical (·OH), singlet oxygen (1O2) worked as a major ROS participating in TC degradation. For CRMs, the immobilization of A-mTiO2 inside CRMs made it difficult to capture superoxide radicals (·O2-), and continuously generate 1O2. In addition, the formation of sulfate radicals (·SO4-), and ·OH during the release process of CRMs was consistent with PDS activation by the A-mTiO2 powder catalyst. The eco-friendly CRMs had a promising potential for practical application in the remediation of organic pollutants from groundwater.

Sulforaphane reduces adipose tissue fibrosis via promoting M2 macrophages polarization in HFD fed-mice.

Adipose tissue fibrosis has been identified as a novel contributor to the pathomechanism of obesity associated metabolic disorders. Sulforaphane (SFN) has been shown to have an anti-obesity effect. However, the impact of SFN on adipose tissue fibrosis is still not well understood. In this study, obese mice induced by high-fat diets (HFD) were used to examine the effects of SFN on adipose tissue fibrosis. According to the current findings, SFN dramatically enhanced glucose tolerance and decreased body weight in diet-induced-obesity (DIO) mice. Additionally, SFN therapy significantly reduced extracellular matrix (ECM) deposition and altered the expression of genes related to fibrosis. Furthermore, SFN also reduced inflammation and promoted macrophages polarization towards to M2 phenotype in adipose tissue, which protected adipose tissue from fibrosis. Notably, SFN-mediated nuclear factor E2-related factor 2 (Nrf2) activation was crucial in decreasing adipose tissue fibrosis. These results implied that SFN had favorable benefits in adipose tissue fibrosis, which consequently ameliorates obesity-related metabolic problems. Our research provides new treatment strategies for obesity and associated metabolic disorders.

Performance of field demonstration nanoscale zero-valent iron in groundwater remediation: A review.

Nanoscale zero-valent iron (nZVI) has gained widespread usage in groundwater remediation due to its exceptional reactivity. Since its initial deployment in field demonstrations in 2001, nZVI has proven to be an effective nanomaterial for addressing groundwater contaminants. Subsequent research has highlighted the versatility of nZVI, showcasing its potential to overcome critical limitations associated with conventional remediation technologies. The effectiveness of nZVI in remediation varies, contingent on factors such as the type of nZVI, contaminant nature, site conditions, and injection methodologies employed. This review aims to present a comprehensive progress report on the field application of nZVI spanning 22 years across eight countries. Drawing from a database encompassing 32 pilot or full-scale remediation sites, the study delineates the various types of nZVI, modification methods, demonstration sites, and primary contaminants targeted in field tests. Specific attention is given to the application effects and mechanisms of unmodified nZVI, Pd, surfactants, and carbon-modified nZVI in diverse field demonstrations. An analysis of the key factors influencing their performance is provided, and potential future applications of nZVI in groundwater remediation are discussed.

Polypeptides as alternatives to PEGylation of therapeutic agents.

INTRODUCTION: Due to the concerns raised by the extensive application of PEGylation, polypeptides have stood out as excellent candidates with adequate biocompatibility and biodegradability with tunable hydrophilicity. AREAS COVERED: In this review, polypeptides with the potential to replace PEGylation have been summarized and their application has been reviewed, including XTEN, PASylation, polysarcosine, zwitterion polypeptides, ELPylation, etc. Besides their strengths, the remaining challenges have also been discussed and the future perspectives have been provided. EXPERT OPINION: Polypeptides have been applied in the designing of peptide/protein drugs as well as nanomedicines, and some of the pharmaceutics have made it into the clinical trials and got approved. These polypeptides showed similar hydrophilic properties to PEGylation, which increased the hydrodynamic volumes of protein drugs, reduced kidney elimination, decreased protein-polymer interaction and potentially improved the drug delivery efficiency due to the extended circulation time in the system. Moreover, they demonstrated superior biodegradability and biocompatibility, compensating for the deficiencies for polymers such as PEG.

Construction and evaluation of a phospholipid-based phase transition in situ gel system for brexpiprazole.

The objective of this study was to develop phospholipid-based injectable phase transition in situ gels (PTIGs) for the sustained release of Brexpiprazole (Brex). Phospholipid (Lipoid S100, S100) and stearic acid (SA) were used as the gel matrix which was dissolved in biocompatible solvent medium-chain triglyceride (MCT), N-methyl pyrrolidone (NMP), and ethanol to obtain PTIGs solution. The Brex PTIG showed a solution condition of low viscosity in vitro and was gelatinized in situ in vivo after subcutaneous injection. Both in vitro release assay and in vivo pharmacokinetics study in SD rats displayed that Brex in PTIGs could achieve a sustained release, compared with brexpiprazole solution (Brex-Sol) or brexpiprazole suspension (Brex-Sus). The Brex-PTIGs had good degradability and biocompatibility in vivo with rare inflammation at the injection site. Among the three Brex-PTIG formulations, Brex-PTIG-3 with the SA in the formulation had the greatest gelation viscosity, the lowest initial release rate, and the most stable release profile with sustained release of up to 60 days. The above results indicated that, as a novel drug delivery system, the Brex-PTIGs offered a new option for the clinical treatment of patients with schizophrenia.

Construction and evaluation of an antioxidant synergistic system containing vitamin C and vitamin E.

AIMS: The aim of this study is to develop a liposome that could exert unparalleled antioxidant effects. In the present study, a vitamin C (VC)/vitamin E (VE)-co-loaded multivesicular liposome (VCVE-MVL) was constructed. METHODS: Vitamins were encapsulated in soybean phosphatidylcholine (SPC) and cholesterol (CHO) by multi-emulsification method. The concentration of VC was determined by Fast Blue method. The concentration of VE was determined by high performance liquid chromatography (HPLC). Vitamin antioxidant capacity in vitro and in vivo was determined using ß-carotene bleaching. RESULTS: VCVE-MVL with particle diameter of 848.55 ± 0.29 nm and SPAN of 0.16 ± 0.11 were obtained. The encapsulation efficiency of VC reached 48.51% (w/w)±0.15. Compared with VC/VE solution, VCVE-MVL had a higher permeation efficiency. In addition, the in vitro and ex-vivo antioxidant tests verified the adequate antioxidant activity of VCVE-MVL. CONCLUSIONS: In conclusion, the antioxidant synergistic system we constructed and demonstrated its potential applications in the cosmetics industry.

Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway.

BACKGROUND: Zearalenone (ZEA) widely exists in moldy grains, which seriously destroys the fertility of females. Isorhamnetin, a natural flavonoid, has extensive of pharmacological activities. However, the beneficial effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced porcine oocyte damage have not been investigated. METHODS: Oocytes were treated with different concentrations of ZEA (3, 5, 8 and 10 µmol/L) and isorhamnetin (5, 10, 20 and 30 µmol/L) for 44 h at 39 â„ƒ. ZEA (5 µmol/L) and isorhamnetin (10 µmol/L) were selected for subsequent studies. Polar body exclusion rate, apoptosis rate and apoptosis related proteins, ROS levels and SOD2 protein, mitochondrial membrane potential and distribution, endoplasmic reticulum distribution and proteins expression, and PI3K, Akt and p-Akt proteins expression of oocytes were detected. In addition, the effect of PI3K antagonist (LY294002) on oocyte nuclear maturation and apoptosis were used to determine the involvement of PI3K/Akt signaling pathway. RESULTS: Our findings showed that ZEA exposure damaged oocytes and isorhamnetin therapy restored the developmental capability of porcine oocytes. Isorhamnetin promoted polar body extrusion rate to rescue ZEA-induced meiotic arrest in porcine oocytes. Isorhamnetin alleviated ZEA-induced oxidative stress by stimulating SOD2 protein expression and inhibiting ROS production. Moreover, isorhamnetin enhanced normal mitochondrial distribution and mitochondrial membrane potential to prevent mitochondrial dysfunction induced by ZEA. Changing the expression of endoplasmic reticulum stress-related marker proteins (CHOP, GRP78) and the distribution rate of normal endoplasmic reticulum showed that isorhamnetin relieved ZEA-caused endoplasmic reticulum stress. Mechanistically, isorhamnetin decreased Bax/Bcl-2 protein expression and inhibited ZEA-induced apoptosis through PI3K/Akt signaling pathway. CONCLUSIONS: Collectively, these results suggest that isorhamnetin protects oocytes from ZEA-caused damage through PI3K/Akt signaling pathway, which enhances meiotic maturation and mitochondrial function, and inhibits early apoptosis, oxidative stress and endoplasmic reticulum stress in porcine oocytes. Our study provides a new strategy for solving the reproductive toxicity induced by ZEA and treating woman infertility. A possible mechanism by which isorhamnetin protected porcine oocytes from ZEA-induced damage. Isorhamnetin inhibited meiosis arrest and apoptosis of porcine oocytes induced by ZEA through the PI3K/Akt signaling pathway. Moreover, isorhamnetin repaired ZEA-induced oocyte damage by alleviating oxidative stress, mitochondrial dysfunction and ER stress.

Melatonin Ameliorates Diquat-Induced Testicular Toxicity via Reducing Oxidative Stress, Inhibiting Apoptosis, and Maintaining the Integrity of Blood-Testis Barrier in Mice.

Diquat is a fast, potent, and widely used bipyridine herbicide in agriculture and it induces oxidative stress in several animal models. However, its genotoxic effects on the male reproductive system remain unclear. Melatonin is an effective free-radical scavenger, which has antioxidant and anti-apoptotic properties and can protect the testes against oxidative damage. This study aimed to investigate the therapeutic effects of melatonin on diquat-induced testicular injury in mice. The results showed melatonin treatment alleviated diquat-induced testicular injury, including inhibited spermatogenesis, increased sperm malformations, declined testosterone level and decreased fertility. Specifically, melatonin therapy countered diquat-induced oxidative stress by increasing production of the antioxidant enzymes GPX1 and SOD1. Melatonin treatment also attenuated diquat-induced spermatogonia apoptosis in vivo and in vitro by modulating the expression of apoptosis-related proteins, including P53, Cleaved-Caspase3, and Bax/Bcl2. Moreover, melatonin restored the blood-testicular barrier by promoting the expression of Sertoli cell junction proteins and maintaining the ordered distribution of ZO-1. These findings indicate that melatonin protects the testes against diquat-induced damage by reducing oxidative stress, inhibiting apoptosis, and maintaining the integrity of the blood-testis barrier in mice. This study provides a theoretical basis for further research to protect male reproductive health from agricultural pesticides.

The prevalence and risk factors of Trichomonas vaginalis in Wuhan and the Tibetan area, China: a two-center study.

Trichomonas vaginalis (T. vaginalis) infection is one of the most common sexually transmitted infections worldwide and is associated with several complications. However, the paucity of research regarding the prevalence of T. vaginalis infection in the Tibetan area limits control efforts. We aimed to evaluate the prevalence of T. vaginalis infection in the Tibetan area by a comparison with the prevalence of T. vaginalis in Wuhan city and to unveil the potential risk factors in the Tibetan area. This descriptive, cross-sectional study was conducted among adult women attending gynecology outpatient clinics in two public hospitals (one in Shannan city of Tibet and one in Wuhan city) in China in 2020. Data were retrieved from the medical record system and laboratory information management system, including T. vaginalis infection, bacterial vaginosis, and vulvovaginal candidiasis by wet mount microscopy or nucleic acid hybridization of vaginal secretions from patients. The associations of variables associated with T. vaginalis prevalence were quantified by odds ratios with 95% confidence intervals. The overall prevalence rates of T. vaginalis infection in the Tibetan area and Wuhan city were 20.94% and 2.84%, respectively. The statistically significant factors for the higher prevalence of T. vaginalis infection in the Tibetan area included tertiary educational status (AOR: 0.36 [95% CI: 0.16-0.81]), yearly family income > ¥100,000 (AOR: 0.48 [95% CI: 0.26-0.91]), clinical symptoms (AOR: 4.58[95% CI: 2.32-9.04]), and III-IV grade vaginal cleanliness (AOR: 29.71 [95% CI: 3.95-223.56]) in the multivariate logistic analysis. Interventions targeting improved living standards as well as women's educational level and promoting reproductive hygiene habits are recommended to contribute to the reduction in T. vaginalis infection in the Tibetan area.

Isorhamnetin protects zearalenone-induced damage via the PI3K/Akt signaling pathway in porcine ovarian granulosa cells.

Zearalenone (ZEA) is widely derived from moldy cereal grain, which has adverse effects on animal reproduction. In particular, pigs are more sensitive to ZEA-induced toxicity than other animals. Isorhamnetin has extensive pharmacological activity. However, the role of isorhamnetin in ZEA-induced cytotoxicity remains unclear. This study was designed to investigate the therapeutic effect of isorhamnetin on ZEA-induced damage in porcine ovarian granulosa cells and elucidate its molecular mechanism. Two experiments were conducted, where a minimum of 3 biological replicates were used for each treatment. In Exp. 1, ovarian granulosa cells were treated with different concentrations of isorhamnetin (1, 5, 10, 20 and 30 µmol/L) and ZEA (0, 10, 30, 60, 90 and 120 µmol/L) for 24 h. Our results indicated that 60 µmol/L ZEA (half-maximal inhibitory concentration value) and 20 µmol/L isorhamnetin (the most effective concentration against ZEA-induced cytotoxicity) were optimum concentrations. In Exp. 2, ovarian granulosa cells were treated with isorhamnetin (20 µmol/L) for 2 h, before treatment with ZEA (60 µmol/L) for 24 h. Apoptosis, endoplasmic reticulum stress, oxidative stress, proliferation and hormone secretion of ovarian granulosa cells were detected. Our findings showed that isorhamnetin suppressed (P < 0.05) ZEA-induced apoptosis by altering mitochondrial membrane potential and apoptosis-related proteins (B-cell lymphoma-2 [Bcl-2], Bcl2-associated x [Bax] and cleaved caspase-3 [C-Casp3]). Changes in intracellular Ca2+ levels and C/EBP homologous protein (CHOP), recombinant activating transcription factor 6 (ATF6), glucose regulated protein78 kD (GRP78) indicated that isorhamnetin rescued (P < 0.05) ZEA-induced endoplasmic reticulum stress. Furthermore, isorhamnetin prevented (P < 0.05) ZEA-induced oxidative stress via the mitogen-activated protein kinase (P38) signaling pathway. Mechanistically, isorhamnetin stimulated (P < 0.05) the expression of proliferating cell nuclear antigen (PCNA) and cyclin D, thereby increasing the ratio of S phase cells in response to ZEA-induced apoptosis via phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway. Isorhamnetin also recovered (P < 0.05) ZEA-induced steroidogenesis disorder by regulating steroidogenic enzyme gene and proteins (follicle-stimulating hormone receptor [FSHR] and cytochrome P450 family 19 subfamily a member 1 [CYP19A1]). Collectively, these findings show that isorhamnetin protects ovarian granulosa cells from ZEA-induced damage, which promotes proliferation, alleviates apoptosis, endoplasmic reticulum stress, oxidative stress, and steroidogenesis disorder.

Polyglycerol fatty acid esters as alternatives to PEGylated lipids for liposome coating.

Background: Polyglycerol (PG) is a type of biocompatible hydrophilic polyether polyol, and it is considered as a potential alternative to polyethylene glycol (PEG) in modifying nanomedicines. Materials & methods: Polyglycerol fatty acid esters (PGFEs) were modified onto liposomes and their serum stability, pharmacokinetics, in vivo distribution and the capacity to induce anti-PEG IgM were compared with PEGylated liposomes (PEG-Lips). Results: Polyglycerol 10-monostearate (PG-10-MS) displayed considerable serum stability and compatibility with mice red blood cells, and it significantly prolonged the blood circulation of liposomes in the pharmacokinetics study compared with the unmodified liposomes, with a similar biodistribution pattern to that of the PEG-Lips. Moreover, PGFE-modified liposomes were less likely to induce the production of anti-PEG IgM. Conclusion: PGFEs could be considered as good candidates to replace PEG lipids for the preparation of liposomes.

Comparative study of the performance of controlled release materials containing mesoporous MnOx in catalytic persulfate activation for the remediation of tetracycline contaminated groundwater.

Controlled release materials (CRMs) are an emerging oxidant delivery technique for in-situ chemical oxidation (ISCO) that solve the problems of contaminant rebound, backflow and wake during groundwater remediation. CRMs were fabricated using ordered mesoporous manganese oxide (O-MnOx) and sodium persulfate (Na2S2O8) as active components, for the removal of antibiotic pollutants from groundwater. In both static and dynamic groundwater environments, persulfate can first be activated by O-MnOx within CRMs to form sulfate radicals and hydroxyl radicals, with these radicals subsequently dissolving out from the CRMs and degrading tetracycline (TC). Due to their excellent persulfate activation performance and good stability, the constructed CRMs could effectively degrade TC in both static and dynamic simulated groundwater systems over a long period (>21 days). The TC removal rate reached >80 %. Changing the added content of O-MnOx and persulfate could effectively regulate the performance of the CRMs during TC degradation in groundwater. The process and products of TC degradation in the dynamic groundwater system were the same as in the static groundwater system. Due to the strong oxidizing properties of sulfate radicals and hydroxyl radicals, TC molecules were completely mineralized within the groundwater systems, resulting in only trace levels of degradation products being detectable, with low- or non-toxicity. Therefore, the CRMs constructed in this study exhibited good potential for practical application in the remediation of organic pollutants from both static and dynamic groundwater environments.