Oxidative stress and neurodegenerative diseases: a bidirectional Mendelian randomization study.

INTRODUCTION: Oxidative stress (OS) has been linked to neurodegenerative diseases in numerous epidemiological studies; however, whether it is a pathogenesis or a downstream factor remains controversial. METHODS: A two-sample bidirectional Mendelian randomization (MR) analysis was implemented to examine evidence of causality of 15 OS injury markers with 3 major neurodegenerative diseases using available genome-wide association studies statistics. As a main approach, inverse-variance weighted (IVW) analysis was performed. The weighted-median (WM) analysis was used to validate the relationship. In order to investigate the existence of horizontal pleiotropy and correct the IVW estimate, the Radial MR approach was applied. To gauge the consistency and robustness of the findings, several sensitivity and pleiotropy analyses were used. For this analysis, p < 0.05 indicates a nominally causal association; according to the Bonferroni correction test, p < 0.0011 indicates a statistically significant causal association. RESULTS: Via IVW and WM, in directional MR, it was genetically predicted that zinc was nominally causally correlated with the risk of Parkinson's disease but not after Bonferroni correction test; alpha-tocopherol was nominally causally correlated with the risk of Amyotrophic lateral sclerosis (ALS) but not after Bonferroni correction test; furthermore, in reverse MR, it was genetically predicted that Alzheimer's disease was causally correlated with uric acid but not after Bonferroni correction test. These above findings were stable across sensitivity and pleiotropy analyses. CONCLUSIONS: Based on the current study, there is no authentic genetic causal association between OS biomarkers and neurodegenerative diseases. The complex relationship is required to be confirmed in future experimental research.

Effects of Chemical Composition and Cross-Linking Degree on the Thermo-Mechanical Properties of Bio-Based Thermosetting Resins: A Molecular Dynamics Simulation Study.

Bio-based epoxy resins have received significant attention in terms of concerns regarding carbon emission. Epoxidized soybean oil (ESO) derived from sustainable feedstock has been widely used to blend with traditional diglycidyl ether of bisphenol-A (DGEBA) to replace some of the petroleum-based components. In this work, molecular dynamics (MD) simulations were applied to track the network formation and predict the performance of methyl hexahydrophthalic anhydride (MHHPA)-cured ESO/DGEBA blend systems. The effects of ESO content and cross-linking degree on the mass density, volumetric shrinkage, glass transition temperature (Tg), coefficient of thermal expansion (CTE), Young's modulus, yield strength, and Poisson's ratio of the epoxy resin were systematically investigated. The results show that systems with high ESO content achieve gelation at low cross-linking degree. The Tg value, Young's modulus, and yield strength increase with the increase in cross-linking degree, but the CTE at the glassy state and Poisson's ratio decrease. The comparison results between the simulated and experimental data demonstrated that the MD simulations can accurately predict the thermal and mechanical properties of ESO-based thermosets. This study gains insight into the variation in thermo-mechanical properties of anhydride-cured ESO/DGEBA-based epoxy resins during the cross-linking process and provides a rational strategy for optimizing bio-based epoxy resins.

New G-Triplex DNA Dramatically Activates the Fluorescence of Thioflavin T and Acts as a Turn-On Fluorescent Sensor for Uracil-DNA Glycosylase Activity Detection.

G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.

A broadly applicable protein-polymer adjuvant system for antiviral vaccines.

Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and cellular immunity and the need for vaccine adjuvants and delivery system. Herein, we assess a vaccine adjuvant system comprising Quillaja Saponaria-21(QS-21) and cobalt porphyrin polymeric micelles that enabling the display of His-tagged antigen on its surface. The nanoscale micelles promote antigen uptake and dendritic cell activation to induce robust cytotoxic T lymphocyte response and germinal center formation. Using the recombinant protein antigens from influenza A and rabies virus, the micelle adjuvant system elicited robust antiviral responses and protected mice from lethal challenge. In addition, this system could be combined with other antigens to induce high titers of neutralizing antibodies in models of three highly pathogenic viral pathogens: Ebola virus, Marburg virus, and Nipah virus. Collectively, our results demonstrate this polymeric micelle adjuvant system can be used as a potent nanoplatform for developing antiviral vaccine countermeasures that promote humoral and cellular immunity.

TLR9 promotes monocytic myeloid-derived suppressor cell induction during JEV infection.

Myeloid-derived suppressor cells (MDSCs) are a group of heterologous populations of immature bone marrow cells consisting of progenitor cells of macrophages, dendritic cells and granulocytes. Recent studies have revealed that the accumulation of MDSCs in the mouse spleen plays a pivotal role in suppressing the immune response following JEV infection. However, the mechanisms by which JEV induces MDSCs are poorly understood. Here, it was found that JEV infection induces mitochondrial damage and the release of mitochondrial DNA (mtDNA), which further leads to the activation of TLR9. TLR9 deficiency decreases the M-MDSCs population and their suppressive function both in vitro and in vivo. Moreover, the increase of MHCⅡ expression on antigen-presenting cells and CD28 expression on T cells in TLR9-/- mice was positively correlated with M-MDSCs reduction. Accordingly, the survival rate of TLR9-/- mice dramatically increased after JEV infection. These findings reveal the connections of mitochondrial damage and TLR9 activation to the induction of M-MDSCs during JEV infection.

Transcriptomic Insights into Different Stimulation Intensity of Electroacupuncture in Treating COPD in Rat Models.

Background: Electroacupuncture (EA), with varying stimulation intensities, has demonstrated therapeutic potentials in both animal and clinical studies for the treatment of chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of the intensity-related effects, particularly 1mA and 3mA of EA, and the underlying mechanisms remains lacking. Methods: A COPD rat model was established by prolonged exposure to cigarette smoke and intermittent intratracheal instillation of lipopolysaccharide. EA treatment was administered at acupoints BL13 (Feishu) and ST36 (Zusanli), 20 minutes daily for 2 weeks, with intensities of 1mA and 3mA. EA effectiveness was evaluated by pulmonary function, histopathological change, serum level of inflammatory cytokines, and level of oxidative stress markers in serum and lung tissues. Transcriptome profiling and weighted gene co-expression network analysis (WGCNA) were performed to reveal gene expression patterns and identify hub genes. Real-time quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect the mRNA and protein expression levels, respectively. Results: EA at both 1mA and 3mA exerted differing therapeutic effects by improving lung function and reducing inflammation and oxidative stress in COPD rats. Transcriptome analysis revealed distinct expression patterns between the two groups, functionally corresponding to shared and intensity-specific (1mA and 3mA) enriched pathways. Eight candidate genes were identified, including Aqp9, Trem1, Mrc1, and Gpnmb that were downregulated by EA and upregulated in COPD. Notably, Msr1 and Slc26a4 exclusively downregulated in EA-1mA, while Pde3a and Bmp6 upregulated solely in EA-3mA. WGCNA constructed 5 key modules and elucidated the module-trait relationship, with the aforementioned 8 genes being highlighted. Additionally, their mRNA and protein levels were validated by RT-qPCR and WB. Conclusion: Our results demonstrated that 1mA and 3mA intensities induce distinct gene expression patterns at the transcriptional level, associated with shared and 1mA vs 3mA-specific enriched pathways. Genes Mrc1, Gpnmb, Trem1, and Aqp9 emerge as promising targets, and further studies are needed to elucidate their functional consequences in COPD.

A prospective study of sleep status, anxiety, and depression levels of college students at a university in Shandong Province, China.

Objective: To investigate the changes in sleep conditions, anxiety, and depression levels among college students before and after entering the university. Methods: Utilizing a random sampling method, 692 new students from a college in Shandong province were selected in September 2019, and relevant indices were statistically analyzed in September 2021 following a comprehensive follow-up. Sleep status, anxiety, and depression levels were assessed using the Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Gender, passive smoking, exercise, intake of fruits, and intake of seafood were identified as significant influencing factors on college students' sleep status, anxiety, and depression levels (p < 0.05). A substantial difference was observed in the sleep quality of college students between the early enrollment stage and the follow-up stage (p < 0.05). Moreover, a significant positive correlation was found between PSQI scores and the levels of anxiety and depression (p < 0.05), cumulatively explaining approximately 10% of the variance in anxiety and depression levels. Conclusion: The sleep quality of college students exhibited significant improvement after enrollment compared to the early enrollment period. Engaging in appropriate exercise and consuming fruits and seafood demonstrated a positive impact on sleep conditions, anxiety, and depression levels. These findings underscore the importance of fostering healthy lifestyle habits for promoting overall well-being among college students.

A comprehensive study of the colloidal properties, biocompatibility, and synergistic antioxidant actions of Antarctic krill phospholipids.

Excipient selection is crucial to address the oxidation and solubility challenges of bioactive substances, impacting their safety and efficacy. AKPL, a novel ω-3 polyunsaturated fatty acids (PUFAs) esterified phospholipid derived from Antarctic krill, demonstrates unique antioxidant capabilities and synergistic effects. It exhibits pronounced surface activity and electronegativity at physiological pH, as evidenced by a critical micelle concentration (CMC) of 0.15 g/L and ζ-potential of -49.9 mV. In aqueous environments, AKPL self-assembles into liposomal structures, offering high biocompatibility and promoting cell proliferation. Its polyunsaturated bond-rich structure provides additional oxidation sites, imparting antioxidant properties superior to other phospholipids like DSPC and DOPC. Additionally, AKPL augments the efficacy of lipophilic antioxidants, such as alpha-tocopherol and curcumin, in aqueous media through both intermolecular and intramolecular interactions. In sum, AKPL emerges as an innovative unsaturated phospholipid, offering new strategies for encapsulating and delivering oxygen-sensitive agents.

Chemical Structures, Biological Activities, and Biosynthetic Analysis of Secondary Metabolites from Agaricus Mushrooms: A Review.

Agaricus mushrooms are an important genus in the Agaricaceae family, belonging to the order Agaricales of the class Basidiomycota. Among them, Agaricus bisporus is a common mushroom for mass consumption, which is not only nutritious but also possesses significant medicinal properties such as anticancer, antibacterial, antioxidant, and immunomodulatory properties. The rare edible mushroom, Agaricus blazei, contains unique agaricol compounds with significant anticancer activity against liver cancer. Agaricus blazei is believed to expel wind and cold, i.e., the pathogenic factors of wind and cold from the body, and is an important formula in traditional Chinese medicine. Despite its nutritional richness and outstanding medicinal value, Agaricus mushrooms have not been systematically compiled and summarized. Therefore, the present review compiles and classifies 70 natural products extracted from Agaricus mushrooms over the past six decades. These compounds exhibit diverse biological and pharmacological activities, with particular emphasis on antitumor and antioxidant properties. While A. blazei and A. bisporus are the primary producers of these compounds, studies on secondary metabolites from other Agaricus species remain limited. Further research is needed to explore and understand the anticancer and nutritional properties of Agaricus mushrooms. This review contributes to the understanding of the structure, bioactivity, and biosynthetic pathways of Agaricus compounds and provides insights for the development of functional foods using these mushrooms.

Does environmental public interest litigation improve the urban land green use efficiency?-Evidence from a quasi-natural experiment in China.

Environmental public interest litigation (EPIL) is a significant part of the judicial system; it is aimed at strengthening judicial protections and safeguarding public interests. Based on the quasi-natural experimental setting of China's EPIL pilot project, this study examines the impact of EPIL on the country's urban land green use efficiency (ULGUE). The findings show that effectively implementing EPIL enhances ULGUE. Specifically, this policy has led to a 6.6% increase in ULGUE in pilot cities, and its impact has grown stronger over time. Mechanism analysis results show that EPIL mainly enhances ULGUE by strengthening environmental supervision and law enforcement, by increasing public participation in environmental governance, and by promoting green innovation and industrial structure upgrades. Furthermore, heterogeneity analysis revealed that the positive effects of this policy implementation are more pronounced in resource-based cities, cities with open environmental information, and cities with high marketization. This paper provides empirical evidence for the effectiveness of environmental governance via EPIL.

Modulation of host lipid metabolism by virus infection leads to exoskeleton damage in shrimp.

The arthropod exoskeleton provides protection and support and is vital for survival and adaption. The integrity and mechanical properties of the exoskeleton are often impaired after pathogenic infection; however, the detailed mechanism by which infection affects the exoskeleton remains largely unknown. Here, we report that the damage to the shrimp exoskeleton is caused by modulation of host lipid profiles after infection with white spot syndrome virus (WSSV). WSSV infection disrupts the mechanical performance of the exoskeleton by inducing the expression of a chitinase (Chi2) in the sub-cuticle epidermis and decreasing the cuticle chitin content. The induction of Chi2 expression is mediated by a nuclear receptor that can be activated by certain enriched long-chain saturated fatty acids after infection. The damage to the exoskeleton, an aftereffect of the induction of host lipogenesis by WSSV, significantly impairs the motor ability of shrimp. Blocking the WSSV-caused lipogenesis restored the mechanical performance of the cuticle and improved the motor ability of infected shrimp. Therefore, this study reveals a mechanism by which WSSV infection modulates shrimp internal metabolism resulting in phenotypic impairment, and provides new insights into the interactions between the arthropod host and virus.

Diagnostic value of one-stop CT energy spectrum and perfusion for angiogenesis in colon and rectum cancer.

OBJECTIVE: Evaluation of the predictive value of one-stop energy spectrum and perfusion CT parameters for microvessel density (MVD) in colorectal cancer cancer foci. METHODS: Clinical and CT data of 82 patients with colorectal cancer confirmed by preoperative colonoscopy or surgical pathology in our hospital from September 2019 to November 2022 were collected and analyzed retrospectively. Energy spectrum CT images were measured using the Protocols general module of the GSI Viewer software of the GE AW 4.7 post-processing workstation to measure the CT values of the arterial and venous phase lesions and the neighboring normal intestinal wall in a single energy range of 40 kev∼140 kev, and the slopes of the energy spectrum curves (λ) were calculated between 40 kev-90 kev; Iodine concentration (IC), Water concentration (WC), Effective-Z (Eff-Z) and Normalized iodine concentration (NIC) were measured by placing a region of interest (ROI) on the iodine concentration map and water concentration map at the lesion and adjacent to the normal intestinal wall.Perfusion CT images were scanned continuously and dynamically using GSI Perfusion software and analyzed by applying CT Perfusion 4.0 software.Blood volume (BV), blood flow (BF), surface permeability (PS), time to peak (TTP), and mean transit time (MTT) were measured respectively in the lesion and adjacent normal colorectal wall. Based on the pathological findings, the tumors were divided into a low MVD group (MVD < 35/field of view, n = 52 cases) and a high MVD group (MVD ≥ 35/field of view, n = 30 cases) using a median of 35/field of view as the MVD grouping criterion. The collected data were statistically analyzed, the subjects' operating characteristic curve (ROC) was plotted, and the area under curve (AUC), sensitivity, specificity, and Yoden index were calculated for the predicted efficacy of each parameter of the energy spectrum and perfusion CT and the combined parameters. RESULTS: The CT values, IC, NIC, λ, Eff-Z of 40kev∼140kev single energy in the arterial and venous phase of colorectal cancer in the high MVD group were higher than those in the low MVD group, and the differences were all statistically significant (p < 0.05). The AUC of each single-energy CT value in the arterial phase from 40 kev to 120 kev for determining the high or low MVD of colorectal cancer was greater than 0.8, indicating that arterial stage has a good predictive value for high or low MVD in colorectal cancer; AUC for arterial IC, NIC and IC + NIC were all greater than 0.9, indicating that in arterial colorectal cancer, both single and combined parameters of spectral CT are highly effective in predicting the level of MVD. The AUC of 40 kev to 90 kev single-energy CT values in the intravenous phase was greater than 0.9, and its diagnostic efficacy was more representative; The AUC of IC and NIC in venous stage were greater than 0.8, which indicating that the IC and NIC energy spectrum parameters in venous stage colorectal cancer have a very good predictive value for the difference between high and low MVDs, with the greatest diagnostic efficacy in IC.The values of BV and BF in the high MVD group were higher than those in the low MVD group, and the differences were statistically significant (P < 0.05), and the AUC of BF, BV, and BV + BF were 0.991, 0.733, and 0.997, respectively, with the highest diagnostic efficacy for determining the level of MVD in colorectal cancer by BV + BF. CONCLUSION: One-stop CT energy spectrum and perfusion imaging technology can accurately reflect the MVD in living tumor tissues, which in turn reflects the tumor angiogenesis, and to a certain extent helps to determine the malignancy, invasion and metastasis of living colorectal cancer tumor tissues based on CT energy spectrum and perfusion parameters.

ATP6V1B1 regulates ovarian cancer progression and cisplatin sensitivity through the mTOR/autophagy pathway.

Early detection and effective chemotherapy for ovarian cancer, a serious gynecological malignancy, require further progress. This study aimed to investigate the molecular mechanism of ATPase H+-Transporting V1 Subunit B1 (ATP6V1B1) in ovarian cancer development and chemoresistance. Our data show that ATP6V1B1 is upregulated in ovarian cancer and correlated with decreased progression-free survival. Gain- and loss-of-function experiments demonstrated that ATP6V1B1 promotes the proliferation, migration, and invasion of ovarian cancer cells in vitro, while ATP6V1B1 knockout inhibits tumor growth in vivo. In addition, knocking down ATP6V1B1 increases the sensitivity of ovarian cancer cells to cisplatin. Mechanistic studies showed that ATP6V1B1 regulates the activation of the mTOR/autophagy pathway. Overall, our study confirmed the oncogenic role of ATP6V1B1 in ovarian cancer and revealed that ATP6V1B1 promotes ovarian cancer progression via the mTOR/autophagy axis.

Increased intestinal bile acid absorption contributes to age-related cognitive impairment.

Cognitive impairment in the elderly is associated with alterations in bile acid (BA) metabolism. In this study, we observe elevated levels of serum conjugated primary bile acids (CPBAs) and ammonia in elderly individuals, mild cognitive impairment, Alzheimer's disease, and aging rodents, with a more pronounced change in females. These changes are correlated with increased expression of the ileal apical sodium-bile acid transporter (ASBT), hippocampal synapse loss, and elevated brain CPBA and ammonia levels in rodents. In vitro experiments confirm that a CPBA, taurocholic acid, and ammonia induced synaptic loss. Manipulating intestinal BA transport using ASBT activators or inhibitors demonstrates the impact on brain CPBA and ammonia levels as well as cognitive decline in rodents. Additionally, administration of an intestinal BA sequestrant, cholestyramine, alleviates cognitive impairment, normalizing CPBAs and ammonia in aging mice. These findings highlight the potential of targeting intestinal BA absorption as a therapeutic strategy for age-related cognitive impairment.

Interfacial Spinel Local Interlocking Strategy Toward Structural Integrity in P3 Oxide Cathodes.

P3-layered transition oxide cathodes have garnered considerable attention owing to their high initial capacity, rapid Na+ kinetics, and less energy consumption during the synthesis process. Despite these merits, their practical application is hindered by the substantial capacity degradation resulting from unfavorable structural transformations, Mn dissolution and migration. In this study, we systematically investigated the failure mechanisms of P3 cathodes, encompassing Mn dissolution, migration, and the irreversible P3-O3' phase transition, culminating in severe structural collapse. To address these challenges, we proposed an interfacial spinel local interlocking strategy utilizing P3/spinel intergrowth oxide as a proof-of-concept material. As a result, P3/spinel intergrowth oxide cathodes demonstrated enhanced cycling performance. The effectiveness of suppressing Mn migration and maintaining local structure of interfacial spinel local interlocking strategy was validated through depth-etching X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and in situ synchrotron-based X-ray diffraction. This interfacial spinel local interlocking engineering strategy presents a promising avenue for the development of advanced cathode materials for sodium-ion batteries.

Pegylated-interferon alpha (PEG-IFNα)-induced interstitial lung disease in a patient with chronic hepatitis B: A case report and literature review.

OBJECTIVES: Interferon (IFN)-induced lung injury is a rare but severe complication. Studies are needed to elucidate the demographic characteristics, clinical manifestations, and prognostic features of IFN-induced interstitial lung disease (ILD). CASE REPORT: We report a patient with chronic hepatitis who developed ILD after interferon monotherapy. To further clarify the clinical characteristics of such patients, we searched for cases in which lung injury was documented as a side effect of hepatitis treatment and systematically analyzed all case reports for clinical manifestations, type of treatment, and outcomes. RESULTS: This is a 61-year-old male with a previous medical history of chronic hepatitis B. After 2 months of pegylated-interferon alpha (PEG-IFNα) application, he gradually developed cough and exertional dyspnea. Repeated chest images suggested progressive ILD, and lung biopsy revealed subacute lung injury. The diagnosis of PEG-IFNα-induced ILD was made. Including our case, 35 articles containing 45 patients were involved in our review. IFN-induced ILDs, often with a subacute onset, are characterized by nonproductive cough, dyspnea, and pulmonary infiltrates on chest radiograph. Most patients(62%, 28/45) required additional systemic steroid, and 5 (11%) patients who were co-administered ribavirin died of ILD progression despite steroid treatment. CONCLUSION: Although rare, IFN-induced ILD can lead to decreased lung function, and sometimes become fatal despite intensive treatment. Most previously reported cases were with chronic hepatitis C, and most of the medication was in combination with ribavirin. IFN-induced ILD should be monitored during IFN therapy, and appropriate steroid is recommended in patients with progressive manifestations.

Prohibitin 2 deficiency in photoreceptors leads to progressive Retinal Degeneration and facilitated Müller glia engulfing microglia debris.

Müller glia and microglia are capable of phagocytosing fragments of retinal cells in response to retinal injury or degeneration. However, the direct evidence for their mutual interactions between Müller glia and microglia in the progression of Retinal Degeneration (RD) remains largely unclear. This study aims to construct a progressive RD mouse model and investigate the activated pattern of Müller glia and the interplay between Müller glia and microglia in the early stage or progression of RD. A Prohibitin 2 (Phb2) photoreceptor-specific knockout (RKO) mouse model was generated by crossing Phb2flox/flox mice with Rhodopsin-Cre mice. Optical Coherence Tomography (OCT), histological staining, and Electroretinography (ERG) assessed retinal structure and function, and RKO mice exhibited progressive RD from six weeks of age. In detail, six-week-old RKO mice showed no significant retinal impairment, but severe vision dysfunction and retina thinning were shown in ten-week-old RKO mice. Furthermore, RKO mice were sensitive to Light Damage (LD) and showed severe RD at an early age after light exposure. Bulk retina RNA-seq analysis from six-week-old control (Ctrl) and RKO mice showed reactive retinal glia in RKO mice. The activated pattern of Müller glia and the interplay between Müller glia and microglia was visualized by immunohistology and 3D reconstruction. In six-week-old RKO mice or light-exposed Ctrl mice, Müller glia was initially activated at the edge of the retina. Moreover, in ten-week-old RKO mice or light-exposed six-week-old RKO mice with severe photoreceptor degeneration, abundant Müller glia was activated across the whole retinas. With the progression of RD, phagocytosis of microglia debris by activated Müller glia was remarkably increased. Altogether, our study establishes a Phb2 photoreceptor-specific knockout mouse model, which is a novel mouse model of RD and can well demonstrate the phenotype of progressive RD. We also report that Müller glia in the peripheral retina is more sensitive to the early damage of photoreceptors. Our study provides more direct evidence for Müller glia engulfing microglia debris in the progression of RD due to photoreceptor Phb2 deficiency.

Transcriptome analysis of pigeon pituitary gland: expression changes of genes encoding protein and peptide hormones at different breeding stages.

Unlike other poultry, parent pigeons produce "pigeon milk" in their crops to nurture their squabs, which is mainly controlled by prolactin (PRL). Exception for PRL, the pituitary gland may also release various other peptide and protein hormones. However, whether these hormones change during pigeon crop lactation and their potential physiological functions remain unclear. Here, to identify potential peptide or protein hormone genes that regulate crop lactation, we conducted transcriptome analysis of pigeon pituitary glands at 3 different breeding stages (the ceased stage-nonincubation and non-nurturing stage, the 11th d of the incubation, and the 1st d of the nurturing stage) using RNA sequencing (RNA-Seq). Our analysis identified a total of 15,191 mRNAs and screened out 297 differentially expressed genes (DEG), including PRL, VIP, etc. The expression abundance of PRL mRNA on the 1st d of the nurturing stage was respectively 4.93 and 3.62 folds higher when compared to the ceased stage and the 11th d of the incubation stage. Additionally, the expression abundance of VIP is higher in the 1st d of the nurturing stage than in the ceased stage. Protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) analysis identified several vital DEGs (e.g., GHRHR, VIP, etc.), being closely linked with hormone and enriched in neuropeptide signaling pathway and response to the hormone. Expression pattern analysis revealed that these DEGs exhibited 4 distinct expression patterns (profile 10, 16, 18, 19). Genes in profile 10 and 19 presented a trend with the highest expression level on 1st d of the nurturing stage, and functional enrichment analysis indicated that these genes are involved in neuropeptide hormone activity, receptor-ligand activity, and the extracellular matrix, etc. Taken together, being consistent with PRL, some genes encoding peptide and protein hormones (e.g., VIP) presented differentially expressed in different breeding stages. It suggests that these hormones may be involved in regulation of the crop lactation process or corresponding behavior in domestic pigeons. The results of this study help to gain new insights into the role of pituitary gland in regulating pigeon lactation.

Tong-Xie-Yao-Fang strengthens intestinal feedback control of bile acid synthesis to ameliorate irritable bowel syndrome by enhancing bile salt hydrolase-expressing microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: A herbal formula Tong-Xie-Yao-Fang (TXYF) is traditionally used to treat irritable bowel syndrome (IBS), modern pharmacological evidence supports that the formula efficacy is associated with altered gut microbiota. Yet, the mechanistic role of gut microbiota in the therapy of TXYF remains unclear. We previously clarified that gut microbiota-dysregulated bile acid (BA) metabolism contribute to the pathogenesis of IBS, deriving a hypothesis that microbiota-BA metabolic axis might be a potential target of TXYF. AIM OF THE STUDY: We aim to investigate a new gut microbiota-mediated mechanism underlying anti-IBS efficacy of TXYF. MATERIALS AND METHODS: We established an IBS rat model with a combination of stressors, compared the herbal efficacy in models undergone gut bacterial manipulations, also examined BA metabolism-related microbiota, metabolites, genes and proteins by 16S rRNA gene sequencing, targeted metabolomics, qPCR and multiplex immunofluorescence staining. RESULTS: We observed that TXYF attenuated visceral hyperalgesia and diarrhea in IBS rats but not in those underwent gut bacteria depletion. Transferring gut microbiota from TXYF-treated donors also decreased visceral sensitivity and slightly relief diarrhea-like behaviors in IBS recipient rats. Fecal 16S rRNA gene sequencing revealed that TXYF modulated microbial ß-diversity and taxonomic structure of IBS rats, with a significant increase in relative abundance of bile salt hydrolase (BSH)-expressing Bacteroidaceae. qPCR and culturing data validated that TXYF had a promotive effect on the growth and BSH activity of Bacteroides species. TXYF-reshaped microbiota upregulated the expression of intestinal Fgf15, a feedback signal to control BA synthesis in the liver. As a result, the BA synthetic and excretory levels in IBS rats were decreased by TXYF, so as that colonic BA membrane receptor Tgr5 sensing and its mediated Calcitonin gene-related peptide (Cgrp)-positive neuronal response were attenuated. CONCLUSION: This study poses a new microbiota-driven therapeutic action for TXYF, highlighting the potential of developing new anti-IBS strategies from the herbal formula targeting BSH-expressing gut bacteria.

Crucial roles of soil inherent Fe-bearing minerals in enhanced Cr(VI) reduction by biochar: The electronegativity neutralization and electron transfer mediation.

Biochar has been used for soil Cr(VI) remediation in the last decade due to its enriched redox functional groups and good electrochemical properties. However, the role of soil inherent Fe-bearing minerals during the reduction of Cr(VI) has been largely overlooked. In this study, biochar with different electron-donating capacities (EDCs) was produced at 400 °C (BC400) and 700 °C (BC700), and their performance for Cr(VI) reduction in soils with varied properties (e.g., Fe content) was investigated. The addition of BC400 caused around 14.2-36.0 mg g-1 Cr(VI) reduction after two weeks of incubation in red soil, paddy soil, loess soil, and fluvo-aquic soil, while a less Cr(VI) was reduced by BC700 (2.57-16.7 mg g-1) with smaller EDCs. The Cr(VI) reduction by both biochars in different soils was closely related to Fe content (R2 = 0.93-0.98), so red soil with the richest Fe (14.8% > 1.79-3.49%) showed the best reduction capability, and the removal of soil free Fe oxides (e.g., hematite) resulted in 71.9% decrease of Cr(VI) reduction by BC400. On one hand, Fe-bearing minerals could increase the soil acidity, neutralize the surface negative charge of biochar, enhance the contact between Cr(VI) and biochar, and thus facilitate the direct Cr(VI) reduction by biochar in soils. On the other hand, Fe-bearing minerals could also facilitate the indirect Cr(VI) reduction by mediating the electron from biochar to Cr(VI) with the cyclic transformation of Fe(II)/Fe(III). This study demonstrates the key role of soil Fe-bearing minerals in Cr(VI) reduction by biochar, which advances our understanding on the biochar-based remediation mechanism of Cr(VI)-contaminated soils.