Kui-Jie-Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota.

BACKGROUND AND AIM: Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS). METHODS: Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7 days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0 g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0 g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments. RESULTS: The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis. CONCLUSION: These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.

Classification System for Predicting Emergent Epilepsy Phenotype in the Intra-amygdala Kainic Acid Mouse Model of Epilepsy.

OBJECTIVE: Animal models of drug-resistant epilepsy represent an important resource for discovering new drug targets and testing experimental medicines. Intra-amygdala microinjection of kainic acid in mice is one of the most widely regarded models of drug-resistant epilepsy. Mice develop acute status epilepticus, which diminishes after a few hours and then, within a few days, mice display spontaneous seizures (epilepsy). The frequency of spontaneous seizures varies between mice, with some developing low or high seizure rates. The ability to predict soon after status epilepticus, which mice will go on to develop a normal frequency of seizures, would enable a significant reduction in resources and EEG reviewing time and lead to humane early end-points for the mice with low or high seizure rates. METHOD: In this study, we developed two machine learning models, a feature-based and transfer learning-based approach, for predicting the emergent spontaneous seizure rates in the intra-amygdala kainic acid model based on the acute EEGs recorded in mice during status epilepticus lasting 40 minutes. The method was trained on data from 28 mice and subsequently tested on data from 16 mice. RESULTS: The feature-based and transfer learning-based models achieved accuracies of 69% and 75%, respectively on the test set in classifying emergent epilepsy as normal or outlier (i.e. low-frequency or high-frequency seizure rate). CONCLUSION: A limitation of the intra-amygdala kainic acid model has been the loss of time and resources from generating mice with low or high rates of spontaneous seizures. To date, no other research has attempted to predict emergent spontaneous seizure rates. The feature-based and transfer learning-based models will assist researchers in identifying mice with a normal frequency of seizures before the onset of spontaneous seizures. SIGNIFICANCE: We have implemented this approach as a web server, which can potentially reduce the time and resources spent analysing the EEGs of mice who develop low-frequency or high-frequency seizure rates. This will enable the early humane endpoint of outlier mice, which aligns with the principles of the responsible use of animals in research and simultaneously speeds up preclinical anti-epilepsy drug discovery.

Transvaginal posterior levatorplasty and perineoplasty for female primary stress urinary incontinence: 12-month follow-up and technical presentation.

OBJECTIVE: To investigate the feasibility of transvaginal posterior levatorplasty combined with perineoplasty (TPLP) for women with primary stress urinary incontinence and demonstrate the surgical technique with step-by-step procedures. METHODS: A prospective, non-randomised study was conducted using technique of TPLP to treat female primary SUI from January 2019 to December 2021. Patient follow-up was performed at 3 and 12 months posteroperatively. A series of validated questionnaires were used to evaluate the improvement of symptom severity, sexual function and quality of life. In addition, 4-D ultrasonography was used to measure the anatomic changes of pelvic structures. RESULTS: A total of 47 patients were enrolled in this study with a mean age of 43.6 years. Mean operative time was 78.7 min. Median estimated intraoperative blood loss was 80.2 ml. Objective cure and subjective cure rates were 87.2% and 91.5%, respectively. Compared with baseline, scores of quality of life, symptom severity and sexual function improved after surgery. Meanwhile, mobility of the urethra and bladder neck and areas of levator hiatus were decreased after surgery. Mild coitus pain was reported in 15.4% (6/39) patients at the initial several times of intercourse after resuming sexual activity. CONCLUSIONS: This study shows that transvaginal posterior levatorplasty combined with perineoplasty appears to be an effective surgical method for selected women with primary stress urinary incontinence.

Patterned Hybrid Surfaces for Efficient Dew Harvesting.

Dew harvesting, minimally influenced by climate and geographical locations, is an ideal method for addressing water shortage problems. Superhydrophilic surfaces, characterized by their highest affinity for water, are particularly attractive for this purpose as they can attract more water molecules via condensation. However, a significant challenge arises from the high surface capillary force that impedes water from sliding down and being effectively collected. The resulting water film on the superhydrophilic surface tends to stay around the edge of the water collection surface, leading to evaporation loss and reduced collection efficacy. To overcome this problem, triangular patterns with low surface adhesion to water were introduced at the edge of superhydrophilic surfaces. This modification, achieved through a wet chemical method and masked oxygen plasma treatment, has significantly improved the efficiency of water collection. Results indicate that the hybrid surface reduced the time for the first water droplet to slide down by half and increased water collection efficiency by 78% compared to uniform superhydrophilic surfaces and by 536% compared to uniform superhydrophobic surfaces under a relative humidity of 55% with a temperature difference of 15 °C. The underlying principles were elucidated through computational simulations, and the mechanisms driving the enhancement in collection efficiency were explained.

Traces of Bronze Age globalization in East Asia: Insights from a revised phylogeography of the Y-chromosome haplogroup Q1a1a-M120.

OBJECTIVE: In this study, we aim to explore the genetic imprint of Bronze Age globalization in East Asia from a phylogeographic perspective by examining the Y-chromosome haplogroup Q1a1a-M120, and to identify key demographic processes involved in the formation of early China and the ancient Huaxia people. METHODS: Over the past few decades, we have collected the sequences of 347 Y chromosomes from the haplogroup Q1a1a-M120. These sequences were utilized to analyze and reconstruct a highly revised phylogenetic tree with age estimates. And we analyzed the geographical distribution and spatial autocorrelation of nine major sub-branches of Q1a1a-M120. Finally, we observed the expansion of Q1a1a-M120 from the beginning of the Bronze Age in East Asia, along with the continuous dissemination of its sub-lineages among East Asian populations. RESULTS: We suggest that certain sub-lineages played a significant role in the formation of states and early civilizations in China, as well as in the development of the ancient Huaxia people, who are the direct ancestors of the Han population. Overall, we propose that haplogroup Q-M120 played a role in the introduction of Bronze Age culture to the central region of East Asia. Therefore, it is haplogroup Q-M120, rather than the Western Eurasian paternal lineage, that expanded and contributed to the gene pool of the East Asian population. CONCLUSION: In summary, the globalization of the Bronze Age led to large-scale population replacement and admixture across various regions of Eurasia; our findings highlight the unique demographic processes that occurred in East Asia during this period.

KDM4A promotes malignant progression of breast cancer by down-regulating BMP9 inducing consequent enhancement of glutamine metabolism.

BACKGROUND: Recent studies have found that histone-modified genes play an increasingly important role in tumor progression. Lysine(K) specific demethylase 4A (KDM4A) is a histone lysine-specific demethylase highly expressed in a variety of malignant tumors, data showed that KDM4A was negatively correlated with the Bone Morphogenetic Protein 9 (BMP9) in breast cancer. And previous experiments have demonstrated that exogenous BMP9 significantly inhibits breast cancer development. MATERIALS AND METHODS: We detected the expression of KDM4A in breast cancer and the relationship between KDM4A and BMP9 using real-time quantitative PCR (RT-qPCR) and Western blot, and verified the interaction between KDM4A and BMP9 by ChIP experiments. At the same time, we also detected whether KDM4A had effects on the RNA and protein stability of BMP9 using actinomycin D and cycloheximide. Measurement of alpha-ketoglutarate (α-KG) level by ELISA to observe the effect of BMP9 on glutamine metabolism in breast cancer cells. Nucleoplasmic distribution of KDM4A after exogenous BMP9 treatment in breast cancer cells were observed by immunofluorescence staining and Western blot. A subcutaneous xenograft tumor model in nude mice was used to study the therapeutic effects of exogenous BMP9 and KDM4A inhibitor (JIB-04) in breast cancer. CCK-8, conoly formation, Transwell, wound healing, and immunohistochemistry were used to monitor the growth of tumor and cell function. RESULTS: We found that KDM4A was abnormally highly expressed in breast cancer, and silenced BMP9 expression by removing histone methyl groups from the BMP9 gene region. Meanwhile, KDM4A could also reduce the stability of BMP9 protein. BMP9 inhibit glutamine metabolism in breast cancer, resulting in a decrease in its product α-KG, is confirmed by ELISA. Altered nucleoplasmic distribution of KDM4A due to decreased α-KG was confirmed by immunofluorescence staining and Western blot. Animal experiments confirm that the combination of exogenous BMP9 and JIB-04 shows significantly better results in breast cancer. CONCLUSIONS: KDM4A silences BMP9 expression by removing histone methyl groups from the BMP9 gene region, leading to further enhancement of glutamine metabolism, which contributes to malignant tumor progression. In addition, using JIB-04 in combination with exogenous BMP9 could inhibit the malignant progression of breast cancer cells and the growth of tumors more significantly.

Increased viperin expression induced by avian infectious bronchitis virus inhibits viral replication by restricting cholesterol synthesis: an in vitro study.

With the emergence of new variant strains resulting from high mutation rates and genome recombination, avian infectious bronchitis virus (IBV) has caused significant economic losses to the poultry industry worldwide. Little is known about the underlying mechanisms of IBV-host interactions, particularly how IBV utilizes host metabolic pathways for efficient viral replication and transmission. In the present study, the effects of the cell membrane, viral envelope membrane, and viperin-mediated cholesterol synthesis on IBV replication were explored. Our results revealed significant increase in cholesterol levels and the expression of viperin after IBV infection. Acute cholesterol depletion in the cell membrane and viral envelope membrane by treating cells with methyl-ß-cyclodextrin (MßCD) obviously inhibited IBV replication; thereafter, replenishment of the cell membrane with cholesterol successfully restored viral replication, and direct addition of exogenous cholesterol to the cell membrane significantly promoted IBV infection during the early stages of infection. In addition, overexpression of viperin effectively suppressed cholesterol synthesis, as well as IBV replication, whereas knockdown of viperin (gene silencing with siRNA targeting viperin, siViperin) significantly increased IBV replication and cholesterol levels, whereas supplementation with exogenous cholesterol to viperin-transfected cells markedly restored viral replication. In conclusion, the increase in viperin induced by IBV infection plays an important role in IBV replication by affecting cholesterol production, providing a theoretical basis for understanding the pathogenesis of IBV and discovering new potential antiviral targets.

Prevalence and Trends of Transfusion-Transmissible HBV Infection Among Blood Donors in Southwestern China: A Six-Year Retrospective Study.

Objective: Hepatitis B virus (HBV) infection is a significant global public health concern, with variable prevalence rates across regions. The prevalence of transfusion-transmitted HBV infection (TT-HBV) via donated blood necessitates an evaluation of blood safety and potential risks to the population. This study assessed the prevalence of HBV infection among blood donors in Southwestern China over 6 years. Methods: We analyzed 903,023 blood donations from a central blood center in Southwestern China between January 2017 and December 2022. The prevalence of HBV in donations was determined for one-time and repeat donors, considering birth cohorts and covariates. Demographic characteristics, donation frequency, and anti-HBV antibody status were analyzed to estimate the incidence of TT-HBV. Results: One-time donors provided 47.78% of the samples, and 52.22% were from repeat donors. The HBV prevalence decreased from 1.0% in 2017 to 0.87% in 2022 in one-time donors and from 0.30% to 0.09%, respectively, in repeat donors. A significantly lower HBV prevalence was identified in the post-1992 birth cohort (0.33%) than in the pre-1992 birth cohort (1.67%). The estimated incidences of TT-HBV occurring from one-time donors, repeat donors, post-1992 birth cohort donors, and pre-1992 birth cohort donors were 20.76, 13.84, 0.82, and 20.98 per 104 person-years, respectively. Conclusion: Our findings indicate a decreasing trend in HBV prevalence among blood donors in Southwestern China over the 6-year study period. This decline may be attributed to the widespread administration of HBV vaccinations and stringent screening measures implemented by blood donation centers. Continuous monitoring for HBV among blood donors is necessary to evaluate the effectiveness of preventive measures and inform future strategies to reduce transmission.

Detection of Muscular Metastasis in a Case of Parathyroid Carcinoma Using 18 F-FAPI-04 PET/CT.

ABSTRACT: A 46-year-old woman underwent surgery for parathyroid carcinoma 2 years ago. During follow-up, the patient presented with elevated parathyroid hormone (127.50 pg/mL; normal, 15-65). No abnormal uptake of 18 F-FDG or 11 C-choline was observed on 18 F-FDG and 11 C-choline PET/CT imaging. The patient was enrolled in a clinical trial for 18 F-FAPI PET/CT imaging, revealing a lesion with intense focal uptake within the left sternocleidomastoid muscle. The patient underwent surgery. Postoperative pathology and immunohistochemical analysis confirmed parathyroid carcinoma metastasis.

Transcriptomics Reveals the Pathway for Increasing Brassica chinensis L. Yield under Foliar Application of Titanium Oxide Nanoparticles.

In this study, Brassica chinensis L seedlings after 6 weeks of soil cultivation were treated with foliar application of TiO2 NPs (20 mg/L) for different times. Transcriptomics analysis was employed to investigate the impact of TiO2 NPs on the physiology, growth, and yield of B. chinensis L. Results showed that TiO2 NPs' exposure significantly increased the biomass, total phosphorus, and catalase enzyme activity by 23.60, 23.72, and 44.01%, respectively, compared to the untreated ones (not bulk or ion).TiO2 NPs increased the leaf chlorophyll content by 4.9% and photosynthetic rate by 16.62%, which was attributed to the upregulated expression of seven genes (PetH, PetF, PsaF, PsbA, PsbB, PsbD, and Lhcb) associated with electron transport in photosystem I and light-harvesting in leaves. The water balance of B. chinensis was improved correlating with the altered expressions of 19 aquaporin genes (e.g., PIP2;1 and NIP6;1). The expressions of 58 genes related to plant hormone signaling and growth were dysregulated, with notable downregulations in GA20, SnRK2, and PP2C and upregulations of DELLAs, SAM, and ETR. Moreover, the 11 tricarboxylic acid cycle genes and 13 glycolysis genes appear to stimulate pathways involved in promoting the growth and physiology of B. chinensis. This research contributes valuable insights into new strategies for increasing the yield of B. chinensis.

Predictive Machine Learning Model to Assess the Adsorption Efficiency of Biochar-Heavy Metals for Effective Remediation of Soil-Plant Environment.

Biochar is crucial for agricultural output and plays a significant role in effectively eliminating heavy metals (HMs) from the soil, which is essential for maintaining a soil-plant environment. This work aimed to assess machine learning models to analyze the impact of soil parameters on the transformation of HMs in biochar-soil-plant environments, considering the intricate non-linear relationships involved. A total of 211 datasets from pot or field experiments were evaluated. Fourteen factors were taken into account to assess the efficiency and bioavailability of HM-biochar amendment immobilization. Four predictive models, namely linear regression (LR), partial least squares (PLS), support vector regression (SVR), and random forest (RF), were compared to predict the immobilization efficiency of biochar-HM. The findings revealed that the RF model was created using 5-fold cross-validation, which exhibited a more reliable prediction performance. The results indicated that soil features accounted for 79.7% of the absorption of HM by crops, followed by biochar properties at 17.1% and crop properties at 3.2%. The main elements that influenced the result have been determined as the characteristics of the soil (including the presence of different HM species and the amount of clay) and the quantity and attributes of the biochar (such as the temperature at which it was produced by pyrolysis). Furthermore, the RF model was further developed to predict bioaccumulation factors (BAF) and variations in crop uptake (CCU). The R2 values were found to be 0.7338 and 0.6997, respectively. Thus, machine learning (ML) models could be useful in understanding the behavior of HMs in soil-plant ecosystems by employing biochar additions.

Molecular dissection of the parental contribution in Paeonia Itoh hybrids.

Hybrid breeding between herbaceous peonies (the maternal parent) and tree peonies (the paternal parent) results in Paeonia Itoh hybrids (Itoh peonies), a triploid species that combines advantageous traits from both parental species, thus offering great economic value. However, the exact genetic contribution of the two parents is unclear. In this study, we introduce a straightforward approach utilizing heterozygous SNPs and Sanger sequencing of targeted gene fragments to trace the original bases back to their parents in Itoh peonies. Our results indicate that in triploid Itoh peonies, only one set of genes are derived from herbaceous peonies, and two sets of genes are derived from the tree peonies. Notably, the presence of three distinct bases of heterozygous SNPs across multiple Itoh cultivars suggests that the gametes from the paternal parents carry two sets of heterozygous homologous chromosomes, which could be due to meiosis I failure during gamete formation. To validate our method's effectiveness in parentage determination, we analyzed two Itoh hybrids and their parents, confirming its practical utility. This research presents a method to reveal the parental genetic contribution in Itoh peonies, which could enhance the efficiency and precision of hybrid breeding programs of triploids in Paeonia and other plant species.

Analysis of hepatitis B Virus Test results among blood donors in Chongqing, China.

BACKGROUND: Hepatitis B virus (HBV) infection is a major concern regarding blood safety in countries with a high HBV prevalence, such as China. We aimed to understand the prevalence of HBV infection among blood donors in Chongqing and provide an important basis for developing appropriate blood screening strategies. METHODS: Dual enzyme-linked immunosorbent assays (ELISAs) for hepatitis B surface antigen (HBsAg) were conducted in parallel with nucleic acid testing (NAT) of donors. All HBsAg-reactive and/or HBV DNA-positive blood samples were tested for HBsAg and hepatitis B DNA levels. RESULTS: A total of 117,927 blood donor samples were collected from the Chongqing Blood Center between April 2020 and November 2020. In total, 473 HBV-ineligible samples were retained for HBsAg and DNA confirmation. A total of 272 samples were confirmed to be HBsAg+, including 2 HBV DNA - and 270 HBV DNA + samples. A total of 201 donations were HBsAg-, including 72 HBV DNA - samples. The rate of HBV infection was 65.33% (309/473) in men, which was significantly higher than that in women (p < 0.001). The HBV failure rate was higher among the first-time donors (p < 0.05). Of the 182 NAT R/HBsAg N/N samples (Nucleic acid test reactivity/2 anti-HBsAg tests negative), 37.91% (69/182) were false positives. The proportion of hepatitis B infections in the 18 NAT R/HBsAg N/R (Nucleic acid test reactivity/1 anti-HBsAg tests negative) samples was 94.44% (17/18), of which 50% (9/18) were occult HBV infection. A total of 95.83% (69/72) of the false positives were from the NAT R/HBsAg N/N group, and 58.33% (42/72) were first-time donors. CONCLUSION: Our data showed a strikingly high HBV infection rate among blood donors in Chongqing. Double ELISA and single NAT can effectively prevent HBV leakage and improve blood safety. First-time donors have a high rate of HBV transplant failure; therefore, donors should be retained and recruited from low-risk groups.

Oral administration of osthole mitigates maladaptive behaviors through PPARα activation in mice subjected to repeated social defeat stress.

Psychological stress induces neuroinflammatory responses, which are associated with the pathogenesis of various psychiatric disorders, such as posttraumatic stress disorder and anxiety. Osthole-a natural coumarin isolated from the seeds of the Chinese herb Cnidium monnieri-exerts anti-inflammatory and antioxidative effects on the central nervous system. However, the therapeutic benefits of osthole against psychiatric disorders remain largely unknown. We previously demonstrated that mice subjected to repeated social defeat stress (RSDS) in the presence of aggressor mice exhibited symptoms of posttraumatic stress disorder, such as social avoidance and anxiety-like behaviors. In this study, we investigated the therapeutic effects of osthole and the underlying molecular mechanisms. Osthole exerted therapeutic effects on cognitive behaviors, mitigating anxiety-like behaviors and social avoidance in a mouse model of RSDS. The anti-inflammatory response induced by the oral administration of osthole was strengthened through the upregulation of heme oxygenase-1 expression. The expression of PPARα was inhibited in mice subjected to RSDS. Nonetheless, osthole treatment reversed the inhibition of PPARα expression. We identified a positive correlation between heme oxygenase-1 expression and PPARα expression in osthole-treated mice. In conclusion, osthole has potential as a Chinese herbal medicine for anxiety disorders. When designing novel drugs for psychiatric disorders, researchers should consider targeting the activation of PPARα.

High-Efficiency Photo-Fenton-like Catalyst of FeOOH/g-C3N4 for the Degradation of PNP: Characterization, Catalytic Performance and Mechanism Exploration.

The composite photocatalyst FeOOH/g-C3N4 was prepared through thermal polycondensation and co-precipitation methods, followed by XRD, SEM and UV-vis characterization. The stability of FeOOH/g-C3N4 was explored by the recycling test. The active species in the reaction system were investigated by the capture experiment. The results indicated that the optimal preparation condition for g-C3N4 involved calcination at 600 °C for 4 h. XRD analysis revealed that g-C3N4 exhibits a high-purity phase, and Fe in FeOOH/g-C3N4 exists in a highly dispersed amorphous state. SEM analysis showed that FeOOH/g-C3N4 has a rough surface with an irregular layered structure. Element composition analysis confirmed that the content of elements in the prepared catalyst is consistent with the theoretical calculation. FeOOH/g-C3N4 possesses the largest specific surface area of 143.2 m2/g and a suitable pore distribution. UV-vis DRS analysis showed that the absorption intensity of FeOOH/g-C3N4 is stronger than that of g-C3N4. When the catalyst dosage was 1.0 g/L, the H2O2 dosage was 4 mmol/L, the PNP initial concentration was 10 mg/L and the initial pH value was 5, the PNP removal could reach 92% in 120 min. Even after 5 cycles, the efficiency of PNP removal by FeOOH/g-C3N4 remains nearly 80%. The capture experiment indicated that both •OH and •O2- play roles in the photocatalytic degradation of PNP, with •OH being more significant. These findings affirm that FeOOH has been successfully incorporated into g-C3N4, resulting in a conspicuous catalytic effect on the degradation of PNP in the visible light-assisted Fenton-like reaction.

Biochar Blended with Alkaline Mineral Can Better Inhibit Lead and Cadmium Uptake and Promote the Growth of Vegetables.

Three successive vegetable pot experiments were conducted to assess the effects on the long-term immobilization of heavy metals in soil and crop yield improvement after the addition of peanut shell biochar and an alkaline mineral to an acidic soil contaminated with lead and cadmium. Compared with the CK treatment, the change rates of biomass in the edible parts of the three types of vegetables treated with B0.3, B1, B3, B9, R0.2 and B1R0.2 were -15.43%~123.30%, 35.10%~269.09%, 40.77%~929.31%, -26.08%~711.99%, 44.14%~1067.12% and 53.09%~1139.06%, respectively. The cadmium contents in the edible parts of the three vegetables treated with these six additives reduced by 2.08%~13.21%, 9.56%~24.78%, 9.96%~35.61%, 41.96%~78.42%, -4.19%~57.07% and 12.43%~65.92%, respectively, while the lead contents in the edible parts reduced by -15.70%~59.47%, 6.55%~70.75%, 3.40%~80.10%, 55.26%~89.79%, 11.05%~70.15% and 50.35%~79.25%, respectively. Due to the increases in soil pH, soil cation-exchange capacity and soil organic carbon content, the accumulation of Cd and Pb in the vegetables was most notably reduced with a high dosage of 9% peanut shell biochar alone, followed by the addition of a low dosage of 1% peanut shell biochar blended with 0.2% alkaline mineral. Therefore, the addition of a low dosage of 1% peanut shell biochar blended with 0.2% alkaline mineral was the best additive in increasing the vegetable biomass, whereas the addition of 9% peanut shell biochar alone was the worst. Evidently, the addition of 0.2% alkaline mineral can significantly reduce the amount of peanut shell needed for passivating heavy metals in soil, while it also achieves the effect of increasing the vegetable yield.

Repetitive Administration of Low-Dose Lipopolysaccharide Improves Repeated Social Defeat Stress-Induced Behavioral Abnormalities and Aberrant Immune Response.

Repetitive exposure of innate immune cells to a subthreshold dosage of endotoxin components may modulate inflammatory responses. However, the regulatory mechanisms in the interactions between the central nervous system (CNS) and the immune system remain unclear. This study aimed to investigate the effects of lipopolysaccharide (LPS) preconditioning in repeated social defeat stress (RSDS)-induced abnormal immune responses and behavioral impairments. This study aimed to elucidate the mechanisms that underlie the protective effects of repeated administration of a subthreshold dose LPS on behavioral impairments using the RSDS paradigm. LPS preconditioning improved abnormal behaviors in RSDS-defeated mice, accompanied by decreased monoamine oxidases and increased glucocorticoid receptor expression in the hippocampus. In addition, pre-treated with LPS significantly decreased the recruited peripheral myeloid cells (CD11b+CD45hi), mainly circulating inflammatory monocytes (CD11b+CD45hiLy6ChiCCR2+) into the brain in response to RSDS challenge. Importantly, we found that LPS preconditioning exerts its protective properties by regulating lipocalin-2 (LCN2) expression in microglia, which subsequently induces expressions of chemokine CCL2 and pro-inflammatory cytokine. Subsequently, LPS-preconditioning lessened the resident microglia population (CD11b+CD45intCCL2+) in the brains of the RSDS-defeated mice. Moreover, RSDS-associated expressions of leukocytes (CD11b+CD45+CCR2+) and neutrophils (CD11b+CD45+Ly6G+) in the bone marrow, spleen, and blood were also attenuated by LPS-preconditioning. In particular, LPS preconditioning also promoted the expression of endogenous antioxidants and anti-inflammatory proteins in the hippocampus. Our results demonstrate that LPS preconditioning ameliorates lipocalin 2-associated microglial activation and aberrant immune response and promotes the expression of endogenous antioxidants and anti-inflammatory protein, thereby maintaining the homeostasis of pro-inflammation/anti-inflammation in both the brain and immune system, ultimately protecting the mice from RSDS-induced aberrant immune response and behavioral changes.

Integrated metabolomics and network pharmacology approach to exploring the anti-inflammatory mechanisms of Chuanwang xiaoyan capsules.

Chuanwang xiaoyan capsules (CWXYC) have anti-inflammatory and detoxification effect, are used in the treatment of acute and chronic tonsillitis, pharyngitis and other inflammation-related diseases clinically. However, the anti-inflammatory mechanisms have not been elucidated. This study aimed to investigate the anti-inflammatory mechanisms of CWXYC using cell metabolomics and network pharmacology strategy. Specifically, CWXYC could efficiently reduce the content of nitric oxide (NO), the cytokines Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in LPS-induced RAW264.7 cells. Furthermore, metabolomics was performed to achieve 23 differential metabolites and 9 metabolic pathways containing glutamate metabolism, glutathione metabolism, arginine and proline metabolism, urea cycle, malate-aspartate shuttle, phosphatidylcholine biosynthesis, transfer of acetyl groups into mitochondria, cysteine metabolism and ammonia recycling. The results of network pharmacology showed that CWXYC could treat inflammation through 10 active components, 10 key targets and 55 pathways. Then the results of molecular docking also approved that there existed strong binding energy between the active components and the key targets. Finally, metabolomics and network pharmacology were integrated to get core targets AKT1, SRC and EGFR. Western blot experiments verified that CWXYC could exert anti-inflammatory effect by down-regulating the activated Akt1 and Src proteins. This study demonstrated that CWXYC exerted effects against inflammation, and the potential mechanisms were elucidated. These novel findings will provide an important basis for further mechanism investigations.

Ramelteon protects against social defeat stress-associated abnormal behaviors.

Psychological stress affects the neuroendocrine regulation, which modulates mental status and behaviors. Melatonin, a hormone synthesized primarily by the pineal gland, regulates many brain functions, including circadian rhythms, pain, sleep, and mood. Selective pharmacological melatonin agonist ramelteon has been clinically used to treat mood and sleep disorders. Posttraumatic stress disorder (PTSD) is a psychiatric condition associated with severe trauma; it is generally triggered by traumatic events, which lead to severe anxiety and uncontrollable trauma recall. We recently reported that repeated social defeat stress (RSDS) may induce robust anxiety-like behaviors and social avoidance in mice. In the present study, we investigated whether melatonin receptor activation by melatonin and ramelteon regulates RSDS-induced behavioral changes. Melatonin treatment improved social avoidance and anxiety-like behaviors in RSDS mice. Moreover, treatment of the non-selective MT1/MT2 receptor agonist, ramelteon, markedly ameliorated RSDS-induced social avoidance and anxiety-like behaviors. Moreover, activating melatonin receptors also balanced the expression of monoamine oxidases, glucocorticoid receptors, and endogenous antioxidants in the hippocampus. Taken together, our findings indicate that the activation of both melatonin and ramelteon regulates RSDS-induced anxiety-like behaviors and PTSD symptoms. The current study also showed that the regulatory effects of neuroendocrine mechanisms and cognitive behaviors on melatonin receptor activation in repeated social defeat stress.

A comprehensive study of Chuanwang Xiaoyan capsule based on characterization of chemical constituents in vitro and in vivo using ultra-high-performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry and pharmacokinetic study of multiple components in rats using ultra-high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry.

Chuanwang Xiaoyan (CWXY) capsule is primarily used to treat a variety of acute and chronic inflammations, including acute and chronic pharyngitis and tonsillitis. However, a systematic study of its chemical constituents is still not available. This study evaluated the chemical constituents in vitro and metabolite profiles in vivo of CWXY using ultra-high-performance liquid chromatography (UHPLC) coupled with Q-Exactive Orbitrap mass spectrometry, and the pharmacokinetic behaviors of the nine main components in rats were detected using ultra-high-performance liquid chromatography-triple quadrupole-mass spectrometry (UPLC-QQQ-MS/MS). A total of 92 chemical constituents in CWXY were preliminarily identified in vitro. After oral administration to rats, 56 prototype components and 128 metabolites of CWXY were detected in the biological samples of rat plasma, urine, bile, and feces. Of these prototype components and metabolites, seven new compounds, namely M15, M16, M25, M30, M31, M71, and M128, were detected for the first time. The quantitation method of nine components in rat plasma was developed using a pharmacokinetic study. To the best of our knowledge, this study was the first to investigate the pharmacokinetic behavior of triumbelletin.