Excitonic topological order in imbalanced electron-hole bilayers.

Correlation and frustration play essential roles in physics, giving rise to novel quantum phases1-6. A typical frustrated system is correlated bosons on moat bands, which could host topological orders with long-range quantum entanglement4. However, the realization of moat-band physics is still challenging. Here, we explore moat-band phenomena in shallowly inverted InAs/GaSb quantum wells, where we observe an unconventional time-reversal-symmetry breaking excitonic ground state under imbalanced electron and hole densities. We find that a large bulk gap exists, encompassing a broad range of density imbalances at zero magnetic field (B), accompanied by edge channels that resemble helical transport. Under an increasing perpendicular B, the bulk gap persists, and an anomalous plateau of Hall signals appears, which demonstrates an evolution from helical-like to chiral-like edge transport with a Hall conductance approximately equal to e2/h at 35 tesla, where e is the elementary charge and h is Planck's constant. Theoretically, we show that strong frustration from density imbalance leads to a moat band for excitons, resulting in a time-reversal-symmetry breaking excitonic topological order, which explains all our experimental observations. Our work opens up a new direction for research on topological and correlated bosonic systems in solid states beyond the framework of symmetry-protected topological phases, including but not limited to the bosonic fractional quantum Hall effect.

In Vivo Fluorescent Labeling of Foam Cell-Derived Extracellular Vesicles as Circulating Biomarkers for In Vitro Detection of Atherosclerosis.

Real-time monitoring of the development of atherosclerosis (AS) is key to the management of cardiovascular disease (CVD). However, existing laboratory approaches lack sensitivity and specificity, mostly due to the dearth of reliable AS biomarkers. Herein, we developed an in vivo fluorescent labeling strategy that allows specific staining of the foam cell-derived extracellular vesicles (EVs) in atherosclerotic plaques, which are released into the blood as circulating biomarkers for in vitro detection of AS. This strategy relies on a self-assembled nanoprobe that could recognize foam cells specifically, where the probe is degraded by the intracellular HClO to produce a trifluoromethyl-bearing boron-dipyrromethene fluorophore (termed B-CF3), a lipophilic dye that can be transferred to the exosomal membranes. These circulating B-CF3-stained EVs can be detected directly on a fluorescence spectrometer or microplate reader without resorting to any sophisticated analytical method. This liquid-biopsy format enables early detection and real-time differentiation of lesion vulnerability during AS progression, facilitating effective CVD management.

Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives.

BACKGROUND: Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear. METHODS: Transcriptome and clinical data of PTC patients were obtained from The Cancer Genome Atlas. The expression patterns of PRGs were identified by consensus clustering. A prognostic model for predicting the thyroid cancer-free interval (TCFi) employed five machine learning methods. Enrichment and immune-related analyses were performed to elucidate the role of pyroptosis. The responses to radioactive iodine (RAI), immune checkpoint inhibitors (ICIs), molecular targeted therapy (MTT), and chemotherapy (CTx) were predicted based on pyroptosis-derived features. Additionally, the expression of prognostic PRGs was validated via six external datasets, 16 cell lines, and 20 pairs of clinical samples. RESULTS: PTC patients were classified into three PyroClusters, C1 exhibited BRFA-like tumors with the highest invasiveness and the worst prognosis, C2 presented RAS-like tumors, and C3 was characterized by gene fusion. Nine PRGs (CXCL8, GJA1, H2BC8, IFI27, PRDM1, PYCARD, SEZ6L2, SIGLEC15, TRAF6) were filtered out to construct a PyroScore prognostic model. A derived nomogram demonstrated superior predictive performance than four clinical staging systems. A strong correlation between pyroptosis and tumor immune microenvironment (TIME) remodeling was observed in mechanistic analyses. Patients with a high PyroScore exhibited "hot" tumor immunophenotypes and had a poorer prognosis but could benefit more from ICIs and CTx (such as paclitaxel). Patients with a low PyroScore were more sensitive to RAI and MTT (such as pazopanib and sorafenib). CONCLUSIONS: PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients.

Palmatine attenuates LPS-induced neuroinflammation through the PI3K/Akt/NF-κB pathway.

To investigate the key molecular mechanisms of palmatine for the treatment of neuroinflammation through modulation of a pathway using molecular docking, molecular dynamics (MD) simulation combined with network pharmacology, and animal experiments. Five alkaloid components were obtained from the traditional Chinese medicine Huangteng through literature mining. Molecular docking and MD simulation with acetylcholinesterase were used to screen palmatine. At the animal level, mice were injected with LPS intracerebrally to cause a neuroinflammatory model, and the Morris water maze experiment was performed to examine the learning memory of mice. Anxiety levels were tested using the autonomous activity behavior experiment with the open field and elevated behavior experiments. HE staining and Niss staining were performed on brain tissue sections to observe morphological lesions and apoptosis; serum was examined for inflammatory factors TNF-α, IL-6, and IL-1ß; Western blot was performed to detect the protein expression. The expression of PI3K/AKT/NFkB signaling pathway-related proteins was examined by Western blot. The results of network pharmacology showed that the screening of palmatine activation containing the PI3K/Akt/NFkB signaling pathway exerts antineuroinflammatory effects. Results from behavioral experiments showed that Pal enhanced learning memory in model mice, improved anxiety behavior, and significantly improved brain damage caused by neuroinflammation. The results of HE staining and Niss staining of brain tissue sections showed that palmatine could alleviate morphological lesions and nucleus damage in brain tissue. Palmatine improved the levels of serum inflammatory factors TNF-α, IL-6, and IL-1ß. SOD, MDA, CAT, ACH, and ACHE in the hippocampus were improved. Western blot results showed that palmatine administration ameliorated LPS-induced neuroinflammation through the PI3K/Akt/NFkB pathway.

The Structure of Hypersexuality and Its Relation to Impulsivity.

Among the multiple controversies surrounding hypersexuality is the important issue of whether it constitutes a univocal construct. Although an initial study supported its homogeneity, more resent research has identified two separate subcomponents-problematic sexuality and sexual drive. The present survey study addressed this issue in a sample that included both in-person tested college students (n = 69) and online respondents (n = 339). A factor analysis of scales attempting to capture the indicators of each subcomponent of hypersexuality yielded two correlated, but separate factors. Whereas Problematic Sexuality (PS) comprised scales measuring sexual compulsivity, using sex as a coping mechanism, and the negative consequences of sexual behavior, Sexual Drive (SD) was defined by frequent sexual activity, preoccupation with sexual fantasies, a predilection for impersonal sexual behavior, and facile sexual arousal. These two subcomponents of hypersexuality were found to covary with different types of impulsivity, further supporting their discrimination and providing external validation for their differentiation. Contrary to a priori hypotheses, however, PS correlated highly with Callous/Manipulative/Risk-Taking as well as with a predicted Affective Instability/Behavioral Disinhibition factor, suggesting that PS may constitute an equifinality of separate developmental trajectories for those high on both subtypes of hypersexuality.

Establishment of a real-time fluorescent quantitative PCR detection method and phylogenetic analysis of BoAHV-1.

BACKGROUND: Infectious bovine rhinotracheitis (IBR), caused by Bovine alphaherpesvirus-1 (BoAHV-1), is an acute, highly contagious disease primarily characterized by respiratory tract lesions in infected cattle. Due to its severe pathological damage and extensive transmission, it results in significant economic losses in the cattle industry. Accurate detection of BoAHV-1 is of paramount importance. In this study, we developed a real-time fluorescent quantitative PCR detection method for detecting BoAHV-1 infections. Utilizing this method, we tested clinical samples and successfully identified and isolated a strain of BoAHV-1.1 from positive samples. Subsequently, we conducted a genetic evolution analysis on the isolate strain's gC, TK, gG, gD, and gE genes. RESULTS: The study developed a real-time quantitative PCR detection method using SYBR Green II, achieving a detection limit of 7.8 × 101 DNA copies/µL. Specificity and repeatability analyses demonstrated no cross-reactivity with other related pathogens, highlighting excellent repeatability. Using this method, 15 out of 86 clinical nasal swab samples from cattle were found to be positive (17.44%), which was higher than the results obtained from conventional PCR detection (13.95%, 12/86). The homology analysis and phylogenetic tree analysis of the gC, TK, gG, gD, and gE genes of the isolated strain indicate that the JL5 strain shares high homology with the BoAHV-1.1 reference strains. Amino acid sequence analysis revealed that gC, gE, and gG each had two amino acid mutations, while the TK gene had one synonymous mutation and one H to Y mutation, with no amino acid mutations observed in the gD gene. Phylogenetic tree analysis indicated that the JL5 strain belongs to the BoAHV-1.1 genotype and is closely related to American strains such as C33, C14, and C28. CONCLUSIONS: The established real-time fluorescent quantitative PCR detection method exhibits good repeatability, specificity, and sensitivity. Furthermore, genetic evolution analysis of the isolated BoAHV-1 JL-5 strain indicates that it belongs to the BoAHV-1.1 subtype. These findings provide a foundation and data for the detection, prevention, and control Infectious Bovine Rhinotracheitis.

Endophytic Streptomyces sp. NEAU-DD186 from Moss with Broad-Spectrum Antimicrobial Activity: Biocontrol Potential Against Soilborne Diseases and Bioactive Components.

Soilborne diseases cause significant economic losses in agricultural production around the world. They are difficult to control because a host plant is invaded by multiple pathogens, and chemical control often does not work well. In this study, we isolated and identified an endophytic Streptomyces sp. NEAU-DD186 from moss, which showed broad-spectrum antifungal activity against 17 soilborne phytopathogenic fungi, with Bipolaris sorokiniana being the most prominent. The strain also exhibited strong antibacterial activity against soilborne phytopathogenic bacteria Ralstonia solanacearum. To evaluate its biocontrol potential, the strain was prepared into biofertilizer by solid-state fermentation. Response surface methodology was employed to optimize the fermentation conditions for maximizing spore production and revealed that the 1:1 ratio of vermicompost to wheat bran, a temperature of 28°C, and 50% water content with an inoculation amount of 15% represented the optimal parameters. Pot experiments showed that the application of biofertilizer with a spore concentration of 108 CFU/g soil could effectively suppress the occurrence of tomato bacterial wilt caused by R. solanacearum and wheat root rot caused by B. sorokiniana, and the biocontrol efficacy was 81.2 and 72.2%, respectively. Chemical analysis of strain NEAU-DD186 extracts using nuclear magnetic resonance spectrometry and mass analysis indicated that 25-O-malonylguanidylfungin A and 23-O-malonylguanidylfungin A were the main active constituents, which showed high activity against R. solanacearum (EC50 of 2.46 and 2.58 µg ml-1) and B. sorokiniana (EC50 of 3.92 and 3.95 µg ml-1). In conclusion, this study demonstrates that Streptomyces sp. NEAU-DD186 can be developed as biofertilizer to control soilborne diseases.

Progression of enlarged perivascular spaces contributes to occurrence of silent lacunar infarction in the elderly.

INTRODUCTION: This study aims to assess the effect of enlarged perivascular spaces (EPVS) in patients using the methods of scale score and 3D volume quantification and to determine whether EPVS progression is related to the occurrence of silent lacunar infarction (SLI). METHOD: Three hundred sixty-seven elderly patients with EPVS were screened by MRI on the day of admission and 2 years later; 295 patients were included in the final study, among which 136 patients had EPVS with SLI (EL); and 159 patients had EPVS without SLI (EOL). Both scale score and 3D volume quantification method were used to evaluate EPVS. The 295 patients were divided into three groups based on EPVS progression state: Group 1 (no progression), Group 2 (0-50% EPVS progression), and Group 3 (≥ 50% EPVS progression). Multiple logistic regression analysis was used to analyze the risk of occurrence of SLI. RESULTS: The EPVS scores and ΔEPVS scores were not significantly different between the EL and EOL groups (p > 0.05). EPVS volumes and their progression were significantly higher in EL compared with EOL (p < 0.001). The incidence of SLI was increased in Groups 2 and 3 compared with those in Group 1, and the trend test showed statistically significant (p = 0.032). Multiple logistic regression analysis showed that the risk of occurrence of SLI was significantly increased in Group 2 (OR 2.24; p = 0.024) and Group 3 (OR 3.31; p = 0.037) versus that in Group 1. CONCLUSION: 3D volume quantification allows for a more sensitive assessment of EPVS changes, and the progression of EPVS volume may contribute to the occurrence of SLI.

PM2.5 exposure promotes the progression of acute kidney injury by activating NLRP3-mediated macrophage inflammatory response.

AIM: We reveal the mechanism of action whereby ambient PM2.5 promotes kidney injury. METHODS: Using C57BL/6 mice, the effects of PM2.5 exposure on the acute kidney injury (AKI) were investigated, including renal function changes, expression of inflammatory cytokines, histopathological changes, as well as activation of nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3（NLRP3）. The effects of PM2.5 on renal injury after NLRP3 inhibition were explored using NLRP3 inhibitor (MCC950) and NLRP3 knockout mice. The effects of PM2.5 on the inflammatory response of renal macrophages were investigated at the cellular level. RESULTS: PM2.5 exposure could promote kidney injury, NLRP3 activation and inflammatory response in mice. After using MCC950 and NLRP3 knockout mice, the effects of PM2.5 and the kidney injury could be inhibited. The cellular-level results also suggested that MCC950 could inhibit the effects of PM2.5. CONCLUSION: PM2.5 can promote the progression of AKI and aggravate tissue inflammation through NLRP3, which is an important environmental toxicological mechanism of PM2.5.

Atractylenolide I improves behaviors in mice with depression-like phenotype by modulating neurotransmitter balance via 5-HT2A.

To explore the antidepressant effects and targets of atractylenolide I (ATR) through a network pharmacological approach. Relevant targets of ATR and depression analyzed by network pharmacology were scored (identifying 5-HT2A targets). Through elevated plus maze, open field, tail suspension, and forced swimming tests, the behavioral changes of mice with depression (chronic unpredictable mild stress [CUMS]) were examined, and the levels of neurotransmitters including serotonin, dopamine, and norepinephrine (5-HT, DA, and NE) were determined. The binding of ATR to 5-HT2A was verified by small molecular-protein docking. ATR improved the behaviors of CUMS mice, elevated their levels of neurotransmitters 5-HT, DA, and NE, and exerted a protective effect on their nerve cell injury. After 5-HT2A knockout, ATR failed to further improve the CUMS behaviors. According to the results of small molecular-protein docking and network pharmacological analysis, ATR acted as an inhibitor by binding to 5-HT2A. ATR can improve the behaviors and modulate the neurotransmitters of CUMS mice by targeting 5-HT2A.

Analysis of the mechanism of fibrauretine alleviating Alzheimer's disease based on transcriptomics and proteomics.

The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aß1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of Aß and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.

NiS/Cd0.6 Zn0.4 S Schottky Junction Bifunctional Photocatalyst for Sunlight-Driven Highly Selective Catalytic Oxidation of Vanillyl Alcohol Towards Vanillin Coupled with Hydrogen Evolution Reaction.

Selective oxidation of biomass-based molecules to high-value chemicals in conjunction with hydrogen evolution reaction (HER) is an innovative photocatalysis strategy. The key challenge is to design bifunctional photocatalysts with suitable band structures, which can achieve highly efficient generation of high-value chemicals and hydrogen. Herein, NiS/Cd0.6 Zn0.4 S Schottky junction bifunctional catalysts are constructed for sunlight-driven catalytic vanillyl alcohol (VAL) selective oxidation towards vanillin (VN) coupling HER. At optimal conditions, the 8% NiS/Cd0.6 Zn0.4 S photocatalyst achieves high activity of VN production (3.75 mmol g-1 h-1 ) and HER (3.84 mmol g-1 h-1 ). It also exhibits remarkable VAL conversion (66.9%), VN yield (52.1%), and selectivity (77.8%). The photocatalytic oxidation of VAL proceeds a carbon-centered radical mechanism via the cleavage of αC-H bond. Experimental results and theoretical calculations show that NiS with metallic properties enhances the electron transfer capability. Importantly, a Ni-S-Cd "electron bridge" formed at the interface of NiS/Cd0.6 Zn0.4 S further improves the separation/transfer of electrone/h+ pairs and also furnishes HER active sites due to its smaller the |ΔGH* | value, thereby resulting in a remarkably HER activity. This work sheds new light on the selective catalytic oxidation VAL to VN coupling HER, with a new pathway towards achieving its efficient HER efficiency.

Sphaerisporangium perillae sp. nov., isolated from the root of Perilla frutescens (Linn.) Britt.

A novel protease-producing actinomycete, designated strain NEAU-ZS1T, was isolated from the root of Perilla frutescens (Linn.) Britt collected from Jiamusi, Heilongjiang, PR China. Comparative 16S rRNA gene sequencing showed that strain NEAU-ZS1T belonged to the genus Sphaerisporangium and was most closely related to 'Sphaerisporangium corydalis' NEAU-YHS15T (99.2%) and Sphaerisporangium cinnabarinum JCM 3291T (99.0%). Phylogenetic tree analysis revealed that strain NEAU-ZS1T formed a monophyletic clade with 'S. corydalis' NEAU-YHS15T. The genome size was 9.3 Mbp with a DNA G+C content of 70.3 mol%. Digital DNA-DNA hybridization, average nucleotide identity and average amino acid identity values between the genome sequence of strain NEAU-ZS1T and those of 'S. corydalis' NEAU-YHS15T (28.6, 83.9 and 79.1 %) and S. cinnabarinum JCM 3291T (18.5, 70.6 and 50.2 %) were below the recommended thresholds for species delineation. The strain formed spherical spore vesicles produced on the aerial hyphae. The cell wall contained meso-diaminopimelic acid and the whole-cell sugars were glucose and madurose. The polar lipids consisted of diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol, an unidentified phospholipid and an unidentified glycolipid. The menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The major fatty acids were iso-C16 : 0, C16 : 1 ω5c, 10-methy C17 : 0 and C17 : 1 ω7c. On the basis of the results of a polyphasic taxonomic study, it is concluded that strain NEAU-ZS1T represents a novel species of the genus Sphaerisporangium, for which the name Sphaerisporangium perillae sp. nov. is proposed. The type strain is NEAU-ZS1T (=CCTCC AA 2021019T= JCM 35655T).

Spatiotemporal Assembly and Immigration of Heterotrophic and Anammox Bacteria Allow a Robust Synergy for High-Rate Nitrogen Removal.

The novel partial denitrification-driven anammox (PD/A) is an energy-efficient method for nitrogen removal from wastewater. However, its stability and efficiency are impeded by the competition between heterotrophic denitrifying bacteria and relatively slow-growing anammox bacteria. In this study, a PD/A granular sludge system was developed, which achieved a nitrogen removal efficiency of 94% with 98% anammox contribution, even as the temperature dropped to 9.6 °C. Analysis of bacterial activity in aggregates of different sizes revealed that the largest granules (>2.0 mm) exhibited the highest anammox activity, 2.8 times that of flocs (<0.2 mm), while the flocs showed significantly higher nitrite production rates of PD, more than six times that of the largest granules. Interestingly, fluorescent in situ hybridization (FISH) combined with confocal laser scanning microscopy (CLSM) revealed a nest-shaped structure of PD/A granules. The Thauera genus, a key contributor to PD, was highly enriched at the outer edge, providing substrate nitrite for anammox bacteria inside the granules. As temperature decreased, the flocs transformed into small granules to efficiently retain anammox bacteria. This study provides multidimensional insights into the spatiotemporal assembly and immigration of heterotrophic and autotrophic bacteria for stable and high-rate nitrogen removal.

Highly Enriched Anammox Bacteria with a Novel Granulation Model Regulated by Epistylis spp. in Domestic Wastewater Treatment.

Anammox granulation is an efficient solution proffered to enrich slow-growing anammox bacteria (AnAOB), but the lack of effective granulation strategies for low-strength domestic wastewater impedes its application. In this study, a novel granulation model regulated by Epistylis spp. for highly enriched AnAOB was revealed for the first time. Notably, anammox granulation was achieved within 65 d of domestic wastewater treatment. The stalks of Epistylis spp. were found to act as the skeleton of granules and provide attachment points for bacterial colonization, and the expanded biomass layer in turn provided more area for the unstalked free-swimming zooids. Additionally, Epistylis spp. exerted much less predation stress on AnAOB than on nitrifying bacteria, and AnAOB tended to grow in aggregates in the interior of granules, thus favoring the growth and retention of AnAOB. Ultimately, the relative abundance of AnAOB reached up to a maximum of 8.2% in granules (doubling time of 9.9 d) compared to 1.1% in flocs (doubling time of 23.1 d), representing the most substantial disparity between granules and flocs. Overall, our findings advance the current understanding of interactions involved in granulation between protozoa and microbial communities and offer new insight into the specific enrichment of AnAOB under the novel granulation model.

Palmatine ameliorates LPS-induced HT-22 cells and mouse models of depression by regulating apoptosis and oxidative stress.

Depression is one of the most common neuropsychiatric disorders that is characterized by low mood, lack of motivation, slow thinking, and recurrent suicidal thoughts. The mechanism of action of palmatine in depression has been rarely reported and remains unclear. The present study examined the neuroprotective effects of palmatine on lipopolysaccharide (LPS)-induced oxidative stress, apoptosis, and depression-like behavior. In this study, cell apoptosis was evaluated by CCK-8, flow cytometry, and Hoechst 33258 staining in LPS-induced HT-22 cells. Meanwhile, reactive oxygen species (ROS) and mitochondrial membrane potential were detected in vitro. In vivo, we investigated depressive-like behaviors in mice by an open field test (OFT) and elevated plus-maze test (EPM). Additionally, the levels of superoxide dismutases (SOD), TNF-α, IL-1ß, and IL-6 were detected by enzyme-linked immunosorbent assay. The hematoxylin-eosin staining and TUNEL staining were used to evaluate the pathology of the hippocampus. The expression of Nrf2/HO-1 and BAX/Bcl-2 pathways in the hippocampus were assessed by Western blot analysis. Palmatine could significantly reduce apoptosis and ROS levels, and improve mitochondrial damage. Moreover, palmatine significantly improves movement time and central square crossing time in OFT, and improves open arms and movement time in EMP. And the levels of SOD, TNF-α, IL-1ß, and IL-6 were significantly decreased after palmatine treatment. More importantly, palmatine improved neuronal apoptosis in the hippocampus, and depression through BAX/Bcl-2 and Nrf2/HO-1 signaling pathways. We provide evidence that palmatine further alleviates the depressive-like behavior of LPS-induced by improving apoptosis and oxidative stress.

Evaluating the effect of ginsenoside Rg1 on CPF-induced brain injury in mice via PI3k/AKT pathway.

Organophosphorus pesticides (OPs) have long been used extensively on agricultural land and can lead to significant improvements in crop yields. Due to occupational exposure, humans are exposed to pesticides through dermal contact, inhalation, and ingestion. The effects of OPs on the organism are currently studied for their effects on livers, kidneys, hearts, blood indicators, neurotoxicity, and teratogenic, carcinogenic, and mutagenic effects, while studies in the direction of brain tissue damage have not been reported in detail. Previous reports have confirmed that ginsenoside Rg1 is a prominent and representative tetracyclic triterpenoid derivative rich in ginseng and has good neuroprotective activity. Considering that, the aim of this study was to establish a mouse model of brain tissue injury by using the OP-type pesticide chlorpyrifos (CPF) and to explore the therapeutic effects and possible molecular mechanisms of Rg1. Mice in the experimental group were pre-protected with Rg1 by gavage for 1 week, and brain tissue damage was induced using CPF (5 mg/kg for 1 week) to assess the effect of Rg1 (80 and 160 mg/kg for 3 weeks) in alleviating brain damage. Morris water maze and histopathological analysis were performed to assess cognitive function and pathological changes in the mouse brain, respectively. Protein expression levels of Bax, Bcl-2, Caspase-3, Cl-Cas-3, Caspase-9, Cl-Cas-9, phosphoinositide 3-kinase (PI3K), phosphorylated-PI3K, protein kinase B (AKT), and phosphorylated-AKT were quantified by protein blotting analysis. Rg1 obviously restored CPF-induced oxidative stress damage in mouse brain tissue, increased the levels of antioxidant parameters (total superoxide dismutase, total antioxidative capacity, and glutathione) in the brain, and significantly reduced the overexpression of apoptosis-related proteins induced by CPF. At the same time, Rg1 also markedly attenuated the histopathological changes in the brain induced by CPF exposure. Mechanistically, Rg1 could effectively activate the phosphorylation of PI3K/AKT. Furthermore, molecular docking studies revealed a stronger binding capacity between Rg1 and PI3K. Rg1 attenuated neurobehavioural alterations and reduced lipid peroxidation in the mouse brain to a great extent. Apart from that, Rg1 administration improved brain histopathology in CPF-induced rats. All results suggest that ginsenoside Rg1 has potential antioxidant effects on CPF-induced oxidative brain injury, and it is evident that Rg1 could be used as a promising therapeutic strategy for the study of brain injury from OP poisoning.

Network pharmacology and molecular docking analysis on the mechanism of Cordyceps militaris polysaccharide regulating immunity through TLR4/TNF-α pathwayss.

The role of polysaccharide components in the immune system, especially immunomodulatory effects, has received increasing attention. In this context, in this study, network pharmacology was adopted to explore the hypothesis of a multitarget mechanism for immune modulation by Chrysalis polysaccharides. A total of 174 common targets were screened by network pharmacology, with the main ones being TNF, MAPK3, CASP3, VEGFA, and STAT3, mostly enriched in the Toll pathway. The molecular docking results showed that the polysaccharide fraction of Chrysalis binds well to TNF proteins. Besides, in vitro cellular assays were performed to verify the ability of Chrysalis polysaccharides to regulate macrophage polarization and to screen for macrophage surface receptors. Furthermore, in vivo experiments were conducted to prove the activation of TLR4 and TNF-α protein expression in mice by Chrysalis polysaccharide.

Characterization of Immunopathology and Small Airway Remodeling in Constrictive Bronchiolitis.

Rationale: Constrictive bronchiolitis (ConB) is a relatively rare and understudied form of lung disease whose underlying immunopathology remains incompletely defined. Objectives: Our objectives were to quantify specific pathological features that differentiate ConB from other diseases that affect the small airways and to investigate the underlying immune and inflammatory phenotype present in ConB. Methods: We performed a comparative histomorphometric analysis of small airways in lung biopsy samples collected from 50 soldiers with postdeployment ConB, 8 patients with sporadic ConB, 55 patients with chronic obstructive pulmonary disease, and 25 nondiseased control subjects. We measured immune and inflammatory gene expression in lung tissue using the NanoString nCounter Immunology Panel from six control subjects, six soldiers with ConB, and six patients with sporadic ConB. Measurements and Main Results: Compared with control subjects, we found shared pathological changes in small airways from soldiers with postdeployment ConB and patients with sporadic ConB, including increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and lymphocyte infiltration. Using principal-component analysis, we showed that ConB pathology was clearly separable both from control lungs and from small airway disease associated with chronic obstructive pulmonary disease. NanoString gene expression analysis from lung tissue revealed T-cell activation in both groups of patients with ConB with upregulation of proinflammatory pathways, including cytokine-cytokine receptor interactions, NF-κB (nuclear factor-κB) signaling, TLR (Toll-like receptor) signaling, T-cell receptor signaling, and antigen processing and presentation. Conclusions: These findings indicate shared immunopathology among different forms of ConB and suggest that an ongoing T-helper cell type 1-type adaptive immune response underlies airway wall remodeling in ConB.

Quantitative evaluation of anisometropic amblyopia treatment efficacy by coupling multiple visual functions via CRITIC algorithm.

BACKGROUND: The evaluation of amblyopia treatment efficacy is essential for amblyopia prevention, control, and rehabilitation. METHODS: To evaluate the amblyopia treatment efficacy more precisely and quantitatively, this study recorded four visual function examination results, i.e., visual acuity, binocular rivalry balance point, perceptual eye position, and stereopsis before and after amblyopia treatment. RESULTS: We found that all these four results had a significant difference between before and after treatment, and the relationship between visual acuity improvement and the difference of BRBP, PEP, and stereoacuity cannot show a fitting correlation regarding the widely used index of visual acuity as the standard of treatment efficacy. By using the Criteria Importance Through Inter-criteria Correlation (CRITIC) method, a more comprehensive and quantitative index by coupling the selected four indexes with objective weights was obtained for further training efficacy representation, and the validation dataset also showed a good performance. CONCLUSIONS: This study proved that our proposed coupling method based on different visual function examination results via the CRITIC algorithm is a potential means to quantify the amblyopia treatment efficacy.