Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury.

BACKGROUND: Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage. METHODS: Vimentin gene knockout (vim-/-) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim-/- and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection. RESULTS: Compared to the immunocompetent WT sv129 mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8+ T cells and the secretion of interferon-gamma. CONCLUSION: Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection.

Enhancing Oxygen Evolution Reaction Performance of Metal-Organic Frameworks through Cathode Activation.

Due to their abundant active sites and porous structures, metal-organic frameworks (MOFs) have garnered significant interest as oxygen evolution reaction (OER) electrocatalysts. Nevertheless, the development of MOF-based electrocatalysts with efficient OER activity and excellent stability simultaneously still faces challenges. Herein, a cathodic activation strategy was used to enhance the OER electrocatalytic performance of M-HHTP for the first time, where M refers to Ni, Cu, Co, Fe, while HHTP denotes 2, 3, 6, 7, 10, 11-hexahydroxytriphenylene. As a prototype, the activated Ni-HHTP (HA-Ni-HHTP) demonstrates outstanding OER performance, with an overpotential as low as 140 mV at 20 mA cm-2 and a small Tafel slope of 78.7 mV-1, surpassing commercial RuO2 and rivaling state-of-the-art MOFs-based electrocatalysts. Characterizations and density functional theory calculations reveal that the superior performance of HA-Ni-HHTP is primarily ascribed to changes in semiconductor type, contact angle, and oxygen vacancy content induced by cathodic activation. Electrochemical impedance spectroscopy analysis using the transmission line model confirms that cathodic activation accelerates charge transport, enhancing the OER process. Furthermore, the cathodic activation strategy holds promise for improving the water oxidation performance of other MOFs such as Fe-HHTP, Co-HHTP, and Cu-HHTP.

Antibacterial sequential growth factor delivery from alginate/gelatin methacryloyl microspheres for bone regeneration.

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.

Differences in the risk of immune-related pneumonitis between PD-1 and PD-L1 inhibitors: a meta-analysis according to the new mirror-principle and PRISMA guidelines.

PURPOSE: To compare the risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors, the meta-analysis was designed. METHOD: The difference in risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors was assessed by two different meta-analysis methods, the Mirror-pairing and the PRISMA guidelines. RESULTS: A total of eighty-eight reports were used for meta-analysis, while thirty-two studies were used for the Mirror-pairing. Both PD-1 and PD-L1 inhibitors (used alone or combined with chemotherapy) increased the risk of developing immune-related pneumonitis (P < 0.00001; P < 0.00001). Based on indirect analyses results (subgroup analyses), the risk of PD-L1-induced pneumonitis was weaker than that of PD-1 inhibitors when the control group was chemotherapy (OR = 3.33 vs. 5.43) or placebo (OR = 2.53 vs. 3.19), while no obvious significant differences were found (P = 0.17; P = 0.53). For the Mirror-pairing-based meta-analysis, the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors (OR = 1.46, 95%CI [1.08, 1.98], I2 = 0%, Z = 2.47 (P = 0.01)). However, this difference was not significant, when they were combined with chemotherapy (OR = 1.05, 95%CI [0.68, 1.60], I2 = 38%, Z = 0.21 (P = 0.84)). CONCLUSION: Both PD-1 and PD-L1 inhibitors increased the risk of immune-related pneumonitis, while the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors.

The Angiogenic Repertoire of Stem Cell Extracellular Vesicles: Demystifying the Molecular Underpinnings for Wound Healing Applications.

Stem cells-derived extracellular vesicles (SC-EVs) have emerged as promising therapeutic agents for wound repair, recapitulating the biological effects of parent cells while mitigating immunogenic and tumorigenic risks. These EVs orchestrate wound healing processes, notably through modulating angiogenesis-a critical event in tissue revascularization and regeneration. This study provides a comprehensive overview of the multifaceted mechanisms underpinning the pro-angiogenic capacity of EVs from various stem cell sources within the wound microenvironment. By elucidating the molecular intricacies governing their angiogenic prowess, we aim to unravel the mechanistic repertoire underlying their remarkable potential to accelerate wound healing. Additionally, methods to enhance the angiogenic effects of SC-EVs, current limitations, and future perspectives are highlighted, emphasizing the significant potential of this rapidly advancing field in revolutionizing wound healing strategies.

Twin-Field Quantum Key Distribution with Local Frequency Reference.

Twin-field quantum key distribution (TFQKD) overcomes the linear rate-loss limit, which promises a boost of secure key rate over long distance. However, the complexity of eliminating the frequency differences between the independent laser sources hinders its practical application. We analyzed and determined the frequency stability requirements for implementing TFQKD using frequency-stabilized lasers. Based on this analysis, we proposed and demonstrated a simple and practical approach that utilizes the saturated absorption spectroscopy of acetylene as an absolute reference, eliminating the need for fast frequency locking to achieve TFQKD. Adopting the 4-intensity sending-or-not-sending TFQKD protocol, we experimentally demonstrated the TFQKD over 502, 301, and 201 km ultralow-loss optical fiber, respectively. We expect this high-performance scheme will find widespread usage in future intercity and free-space quantum communication networks.

Large-scale parameters framework with large convolutional kernel for encoding visual fMRI activity information.

Visual encoding models often use deep neural networks to describe the brain's visual cortex response to external stimuli. Inspired by biological findings, researchers found that large receptive fields built with large convolutional kernels improve convolutional encoding model performance. Inspired by scaling laws in recent years, this article investigates the performance of large convolutional kernel encoding models on larger parameter scales. This paper proposes a large-scale parameters framework with a sizeable convolutional kernel for encoding visual functional magnetic resonance imaging activity information. The proposed framework consists of three parts: First, the stimulus image feature extraction module is constructed using a large-kernel convolutional network while increasing channel numbers to expand the parameter size of the framework. Second, enlarging the input data during the training stage through the multi-subject fusion module to accommodate the increase in parameters. Third, the voxel mapping module maps from stimulus image features to functional magnetic resonance imaging signals. Compared to sizeable convolutional kernel visual encoding networks with base parameter scale, our visual encoding framework improves by approximately 7% on the Natural Scenes Dataset, the dedicated dataset for the Algonauts 2023 Challenge. We further analyze that our encoding framework made a trade-off between encoding performance and trainability. This paper confirms that expanding parameters in visual coding can bring performance improvements.

Highly-efficient low-cost polarization-sensitive organic photodetectors based on laminated self-assembly planar and bulk heterojunctions.

To overcome the severe problems arising from the insufficient light absorption of ultrathin self-assembly active layers and the high cost use of atomic force deposition (ALD)-grown low-leakage-current transport layers, we successfully developed a low-cost, simple and facile strategy of floating-film transfer and multilayer lamination (FFTML) for constructing highly-efficient ALD-free broadband polarization-sensitive organic photodetectors (OPDs) with the two commonly used structures of donor/acceptor planar heterojunction (PHJ) and donor:acceptor multilayer bulk heterojunction (BHJ). It was found that the PHJ-based polarization-sensitive OPD by FFTML possesses a low dark current due to the high carrier injection barrier, indicating it is more suitable to be applied in low polarized light detection scenarios. In contrast, the BHJ-based device by FFTML has a higher spectral responsivity in the whole wavelength due to more photo-excitons transferred to the donor:acceptor interface and dissociated into photoexcited carrirers. Furthermore, the film thickness, which is tuned by increasing lamination number of BHJ layers, has a big effect on the polarization-sensitive photodetection performance. The polarization-sensitive 4-BHJ OPD by FFTML finally achieved a high specific detectivity of 8.33 × 1010Jones, which was much higher than 2.72 × 1010Jones for the 2-BHJ device at 0 V. This work demonstrates that layer-by-layer lamination of self-assembly films can effectively improve the polarized-light detection performance, contributing significantly to the rapid development of the field.

Performance evaluation and clinical application of the UA-5600 automatic dry chemistry urine analyzer in renal diseases.

Background: Urine testing as a routine screening programme, abnormal test results can be suggestive to clinicians but can sometimes be overlooked, and the establishment of a diagnostic model can better assist clinicians in identifying potential problems. BLD (blood), LEU (leukocyte), PRO (protein) and GLU (glucose) are the four most important parameters in urine testing, and the accuracy of their results is a key concern for clinicians, so it is essential to verify the accuracy of their results. In this study, we evaluated the analytical and clinical performance of Mindray's automatic urine dry chemistry analyzer, the UA-5600 (Hereinafter referred to as the (UA-5600), and the test strips configured with the instrument, and developed a machine-learning (ML) model for kidney disease screening from the results of 11 parameters output from the UA-5600 with the aim of detecting abnormal urine test results. Methods: Urine samples from outpatients and inpatients at The First Affiliated Hospital of Sun Yat-sen University were collected from August to September 2022 to evaluate the performance of the Mindray UA-5600 dry chemistry analyzer and test strips. The evaluation of the UA-5600 and its test strips focused on the agreement of the urine BLD and LEU readings with the RBC (red blood cell) and WBC (white blood cell) counts obtained by the Mindray EH-2090 urine formed element analyzer. We also compared the PRO and GLU readings with the results of the Mindray BS-2800M biochemistry analyzer. Urine samples from outpatients and inpatients were retrospectively analysed and grouped according to LIS diagnosis. Additionally, eight ML models for kidney disease screening were developed using 11 parameters measured by the UA-5600. And the model was validated by the validation set. Results: The UA-5600 had an 89.55% concordance rate for BLD and a 91.04% concordance rate for LEU compared to the EH-2090 analyzer. When benchmarked against the BS-2800M, the concordance rates for PRO and GLU were 94.14% and 95.20%, respectively. A total of 1,691 samples were used for the construction of the ML models, of which 346 patients (135 males and 211 females, age range: 18 to 98 years) diagnosed with renal disease, and 1,345 patients (397 males and 948 females, age range: 18 to 92 years) with non-renal disease diagnosed with other conditions. Notably, the Naïve Bayes (NB) model, which was built from the UA-5600 parameters, demonstrated superior predictive capabilities for renal disease, with an area under the receiver operating characteristic curve of 0.9470, a sensitivity of 0.7767, and a specificity of 0.9457. Conclusions: The Mindray UA-5600 demonstrates robust detection abilities for both BLD and LEU, and its results for PRO and GLU align closely with those obtained from the chemistry analyzer. The NB model has a good screening ability and shows promise as an effective screening tool.

Antiferromagnetic phase transition in a 3D fermionic Hubbard model.

The fermionic Hubbard model (FHM)1 describes a wide range of physical phenomena resulting from strong electron-electron correlations, including conjectured mechanisms for unconventional superconductivity. Resolving its low-temperature physics is, however, challenging theoretically or numerically. Ultracold fermions in optical lattices2,3 provide a clean and well-controlled platform offering a path to simulate the FHM. Doping the antiferromagnetic ground state of a FHM simulator at half-filling is expected to yield various exotic phases, including stripe order4, pseudogap5, and d-wave superfluid6, offering valuable insights into high-temperature superconductivity7-9. Although the observation of antiferromagnetic correlations over short10 and extended distances11 has been obtained, the antiferromagnetic phase has yet to be realized as it requires sufficiently low temperatures in a large and uniform quantum simulator. Here we report the observation of the antiferromagnetic phase transition in a three-dimensional fermionic Hubbard system comprising lithium-6 atoms in a uniform optical lattice with approximately 800,000 sites. When the interaction strength, temperature and doping concentration are finely tuned to approach their respective critical values, a sharp increase in the spin structure factor is observed. These observations can be well described by a power-law divergence, with a critical exponent of 1.396 from the Heisenberg universality class12. At half-filling and with optimal interaction strength, the measured spin structure factor reaches 123(8), signifying the establishment of an antiferromagnetic phase. Our results provide opportunities for exploring the low-temperature phase diagram of the FHM.

Genetic Characteristics of Non B Cell-Derived Immunoglobulin Genes.

It is widely acknowledged that immunoglobulins (Igs) are produced solely by B-lineage cells. The Ig gene is created by the rearrangement of a group of gene segments [variable (V), diversity (D), and joining (J) segments rearrangement, or V(D)J recombination], which results in the vast diversity of B cell-derived Ig responsible for recognising various antigens. Ig subsequently undergoes somatic hypermutation (SHM) and class switch recombination (CSR) after exposure to antigens, thus converting the low-affinity IgM to IgG, IgA, or IgE antibodies. IgM and IgD are primarily expressed in naïve B cells that have not been exposed to antigens, they do not undergo somatic hypermutation; hence, their variable region sequences remain the same as those in the germline. In contrast, IgG, IgA, and IgE are expressed in antigen-stimulated memory B cells or plasma cells, and thus, they often possess high-frequency mutations in their variable region sequences. Since the discovery that Ig can be produced by non-B cells, Qiu's group has investigated and compared the genetic characteristics of B cell-derived Ig and non-B cell-derived Ig. These findings demonstrated that non-B cell-derived Ig shares certain similarities with B cell-derived Ig in that the sequence of its constant region is identical to that of B cell-derived Ig, and its variable region is also strictly dependent on the rearrangement of V, D, and J gene segments. Moreover, akin to B cell-derived Ig, the V regions of IgM and IgD are rarely mutated, while IgG, IgA, and IgE produced by cancer cells are frequently mutated. However, the non-B cell-derived Ig V region sequence displays unique characteristics. (1) Unlike the vast diversity of B cell-derived Igs, non-B cell-derived Igs exhibit restricted diversity; cells from the same lineage always select the same V(D)J recombination patterns; (2) Both mRNA and proteins of RAG1/RAG2 recombinase have been detected in Ig positive cancer cell lines and normal tissues. But Ig recombination could also be found in RAG1-/- and RAG2-/- mice, suggesting that they are not necessary for the rearrangement of non-B cell-derived Igs. These features of non-B cell-derived Igs suggest a potentially undiscovered mechanism of V(D)J recombination, ligation, and SHM in non-B cells, which necessitates further investigation with advanced technology in molecular biology.

Dose-response relationship between serum N-glycan markers and liver fibrosis in chronic hepatitis B.

BACKGROUND: Evaluation of liver fibrosis played a monumental role in the diagnosis and monitoring of chronic hepatitis B (CHB). We aimed to explore the value of serum N-glycan markers in liver fibrosis. METHODS: This multi-center (33 hospitals) study recruited 760 treatment-naïve CHB patients who underwent liver biopsy. Serum N-glycan markers were analyzed by DNA sequencer-assisted fluorophore-assisted with capillary electrophoresis (DSA-FACE) technology. First, we explore the relationship between 12 serum N-glycan markers and the fibrosis stage. Then, we developed a Px score for diagnosing significant fibrosis using the LASSO regression. Next, we compared the diagnostic performances between Px, LSM, APRI, and FIB-4. Finally, we explored the relationships between glycosyltransferase gene and liver fibrosis with RNA-transcriptome sequencing. RESULTS: We included 622 CHB participants: male-dominated (69.6%); median age 42.0 (IQR 34.0-50.0); 287 with normal ALT; 73.0% with significant fibrosis. P5(NA2), P8(NA3), and P10(NA4) were opposite to the degree of fibrosis, while other profiles (except for P0[NGA2]) increased with the degree of fibrosis. Seven profiles (P1[NGA2F], P2[NGA2FB], P3[NG1A2F], P4[NG1A2F], P7[NA2FB], P8[NA3], and P9[NA3Fb]) were selected into Px score. Px score was associated with an increased risk of significant fibrosis (for per Px score increase, the risk of significant fibrosis was increased by 3.54 times (OR = 4.54 [2.63-7.82]) in the fully-adjusted generalized linear model. p for trend was <0.001. The diagnostic performance of the Px score was superior to others. Glycosyltransferase genes were overexpressed in liver fibrosis, and glycosylation and glycosyltransferase-related pathways were significantly enriched. CONCLUSIONS: Serum N-glycan markers were positively correlated with liver fibrosis. Px score had good performance in distinguishing significant fibrosis.

FADD regulates adipose inflammation, adipogenesis, and adipocyte survival.

Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/-) mice did not show any significant changes in body weight or composition. However, Fadd+/- mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/- mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

Evaluation of artificial intelligence-assisted morphological analysis for platelet count estimation.

INTRODUCTION: This study aims to assess the performance of the platelet count estimation using artificial intelligence technology on the MC-80 digital morphology analyzer. METHODS: Digital morphology analyzer uses two different computational principles for platelet count estimation: based on PLT/RBC ratio (PLT-M1) and estimate factor (PLT-M2). 977 samples with various platelet counts (low, median, and high) were collected. Out of these, 271 samples were immunoassayed using CD61 and CD41 antibodies. The platelet counts obtained from the hematology analyzer (PLT-I and PLT-O), digital morphology analyzer (PLT-M1 and PLT-M2), and flow cytometry (PLT-IRM) were compared. RESULTS: There was no significant deviation observed before and after verification for both PLT-M1 and PLT-M2 across the analysis range (average bias: -0.845/-0.682, 95% limit of agreement (LOA): -28.675-26.985/-29.420-28.056). When platelet alarms appeared, PLT-M1/PLT-M2 showed the strongest correlation with PLT-IRM than PLT-I with PLT-IRM (r: 0.9814/0.9796 > 0.9601). The correlation between PLT-M1/PLT-M2 and PLT-IRM was strong for samples with interference, such as large platelets or RBC fragments, but relatively weak in small RBCs. The deviation between PLT-M1 and PLT-M2 is related to the number of RBCs. Compared with PLT-I, PLT-M1/PLT-M2 showed higher accuracy for platelet transfusion decisions, especially for samples with low-value PLT. CONCLUSION: The novel platelet count estimation on the MC-80 digital morphology analyzer provides high accuracy, especially the reviewed result, which can effectively confirm suspicious platelet count.

Gene expression profiles to clarify the effect of low-dose benzo(a)pyrene on crystalline silica induced acute lung injury in mice.

Published evidences have suggested that air pollutant benzo(a)pyrene (BaP) may modify the toxicity and adverse effects produced by other toxicants. However, the precise role of short-term exposure to low-dose BaP on acute lung injury (ALI) induced by crystalline silica (CS) and the underlying mechanisms remain to be clarified. To investigate this issue, a mouse co-exposure model was established by intratracheal instillation of 2.5 mg CS and BaP alone or in combination. Our data found that CS exposure resulted in ALI as evidenced by lung histological changes, elevated lactate dehydrogenase activity, increased level of pro-inflammatory markers and enhanced oxidative damage. Although exposure to BaP alone had little effect on the pathological changes of mice lung tissues except for occasionally mild inflammation, it could aggravate the CS-induced ALI in a dose-dependent manner. Bioinformatic analysis of transcriptome sequencing suggested that the expression changes of significantly differentially expressed genes were closely related to the severity of ALI. The joined analysis of STC and WGCNA found that "NOD-like receptor signaling pathway", "toll-like receptor signaling pathway", "TNF signaling pathway", and "NF-kappa B signaling pathway" associated with immune and inflammatory response were the most prominent significant pathways. TLR2/9 and Nod2 might be the key inflammation-related genes that were differentially expressed in the combined lung toxicity induced by CS and BaP exposure. All these findings suggest that co-exposure of CS and low-dose BaP can cause more severe lung inflammation and oxidative damage in mice than exposure alone, which may be useful in the management and prevention of silicosis. The roles of TLR2/9 and Nod2 as candidate targets in the combined toxicity need further exploration.

Exploring the effects of environmentally relevant concentrations of tris(2-chloroethyl) phosphate on tadpole health: A comprehensive analysis of intestinal microbiota and hepatic transcriptome.

Tris(2-chloroethyl) phosphate (TCEP), a chlorinated organophosphate ester, is commonly found in aquatic environments. Due to its various toxic effects, it may pose a risk to the health of aquatic organisms. However, the potential impacts of TCEP exposure on the intestinal microbiota and hepatic function in amphibians have not been reported. This study investigated the impact of long-term exposure to environmentally relevant concentrations of TCEP (0, 3, and 90 µg/L) on the intestinal microbiota and hepatic transcriptome of Polypedates megacephalus tadpoles. The results showed that the body size of the tadpoles decreased significantly with an increase in TCEP concentration. Additionally, TCEP exposure affected the diversity and composition of the intestinal microbiota in tadpoles, leading to significant changes in the relative abundance of certain bacterial groups (the genera Aeromonas decreased and Citrobacter increased) and potentially promoting a more even distribution of microbial species, as indicated by a significant increase in the Simpson index. Moreover, the impact of TCEP on hepatic gene expression profiles in tadpoles was significant, with the majority of differentially expressed genes (DEGs) (709 out of 906 total DEGs in 3 µg/L of TCEP versus control, and 344 out of 387 DEGs in 90 µg/L of TCEP versus control) being significantly down-regulated, which were primarily related to immune response and immune system process. Notably, exposure to TCEP significantly reduced the relative abundance of the genera Aeromonas and Cetobacterium in the tadpole intestine. This reduction was positively correlated with the down-regulated expression of immune-related genes in the liver of corresponding tadpoles. In summary, these findings provide empirical evidence of the potential health risks to tadpoles exposed to TCEP at environmentally relevant concentrations.

Current treatment for male infertility: an umbrella review of systematic reviews and meta-analyses.

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration (n = 36), sperm morphology (n = 26), and sperm motility (n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% (n = 48), 25.6% (n = 23), and 21.1% (n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.

Photocurrent polarity switching photoelectrochemical aptasensor for oxytetracycline based on BiOBr/Ag2S/PDA//CuO: CuO-induced II-type to dual Z-scheme system.

BACKGROUND: As a broad-spectrum tetracycline antibiotic, Oxytetracycline (OTC) was widely used in a variety of applications. But, the overuse of OTC had led to the detection of it in food, water and soil, which could present significance risk to human health and cause damage to ecosystem. It was of great significance to develop sensitive detection methods for OTC. Herein, an environmentally friendly photoelectrochemical (PEC) aptasensor was constructed for the sensitive detection of OTC based on CuO-induced BiOBr/Ag2S/PDA (Polydopamine) photocurrent polarity reversal. RESULTS: BiOBr/Ag2S/PDA composites modified electrode not only produced stable initial anodic photocurrent but also provided attachment sites for the aptamer S1 of OTC by the strong adhesion of PDA. On the other hand, CuO loaded OTC aptamer S2 (Cu-S2) was got through Cu-S bonds. After the target OTC was identified on the electrode surface, CuO was introduced to the surface of ITO/BiOBr/Ag2S/PDA through the specific binding of OTC to S2. This identification process formed dual Z-type heterojunctions and resulted in a remarkable reversal of photocurrent polarity from anodic to cathodic. Under optimization conditions, the PEC aptasensor showed a wide linear range (50 fM âˆ¼ 100 nM), low detection limit (1.9 fM), excellent selectivity, stability and reproducibility for the detection of OTC. Moreover, it was successfully used for the analysis of OTC in real samples of tap water, milk and honey, and had the potential for practical application. SIGNIFICANCE: This work developed an environmentally friendly photocurrent-polarity-switching PEC aptasensor with excellent selectivity, reproducibility, stability, low LOD and wide linear range for OTC detection. This sensitive system, which was including BiOBr, Ag2S, PDA and CuO were low toxicity, not only reduced the risk of traditional toxic semiconductors to operators and the environment, but can also be used for the detection of real samples, broadening the wider range of applications for BiOBr, Ag2S, PDA and CuO.

FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells.

Male ageing is always accompanied by decreased fertility. The forkhead O (FOXO) transcription factor FOXO4 is reported to be highly expressed in senescent cells. Upon activation, it binds p53 in the nucleus, preventing senescent cell apoptosis and maintaining senescent cells in situ. Leydig cells play key roles in assisting spermatogenesis. Leydig cell senescence leads to deterioration of the microenvironment of the testes and impairs spermatogenesis. In this study, we observed that FOXO4-DRI, a specific FOXO4- p53 binding blocker, induced apoptosis in senescent Leydig cells, reduced the secretion of certain Senescence-Associated Secretory Phenotype and improved the proliferation of cocultured GC-1 SPG cells. In naturally aged mice, FOXO4-DRI-treated aged mice exhibited increased sperm quality and improved spermatogenesis.

Alpha-Synuclein Interaction with UBL3 Is Upregulated by Microsomal Glutathione S-Transferase 3, Leading to Increased Extracellular Transport of the Alpha-Synuclein under Oxidative Stress.

Aberrant aggregation of misfolded alpha-synuclein (α-syn), a major pathological hallmark of related neurodegenerative diseases such as Parkinson's disease (PD), can translocate between cells. Ubiquitin-like 3 (UBL3) is a membrane-anchored ubiquitin-fold protein and post-translational modifier. UBL3 promotes protein sorting into small extracellular vesicles (sEVs) and thereby mediates intercellular communication. Our recent studies have shown that α-syn interacts with UBL3 and that this interaction is downregulated after silencing microsomal glutathione S-transferase 3 (MGST3). However, how MGST3 regulates the interaction of α-syn and UBL3 remains unclear. In the present study, we further explored this by overexpressing MGST3. In the split Gaussia luciferase complementation assay, we found that the interaction between α-syn and UBL3 was upregulated by MGST3. While Western blot and RT-qPCR analyses showed that silencing or overexpression of MGST3 did not significantly alter the expression of α-syn and UBL3, the immunocytochemical staining analysis indicated that MGST3 increased the co-localization of α-syn and UBL3. We suggested roles for the anti-oxidative stress function of MGST3 and found that the effect of MGST3 overexpression on the interaction between α-syn with UBL3 was significantly rescued under excess oxidative stress and promoted intracellular α-syn to extracellular transport. In conclusion, our results demonstrate that MGST3 upregulates the interaction between α-syn with UBL3 and promotes the interaction to translocate intracellular α-syn to the extracellular. Overall, our findings provide new insights and ideas for promoting the modulation of UBL3 as a therapeutic agent for the treatment of synucleinopathy-associated neurodegenerative diseases.