Epigallocatechin-3-gallate attenuates the sulfamethoxazole-induced immunotoxicity and reduces SMZ residues in Procambarus clarkii.

Sulfamethoxazole (SMZ) is a commonly used antibiotic in aquaculture, and its residues in water bodies pose a significant threat to aquatic organisms in the water environment. In the present study, epigallocatechin-3-gallate (EGCG), a catecholamine, was used to mitigate the immunotoxicity caused by SMZ exposure in Procambarus clarkii. EGCG reduced the apoptosis rate, which was elevated by SMZ exposure, and increased the total hemocyte count. Simultaneously, EGCG enhanced the activities of enzymes related to antibacterial and antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), lysozyme (LZM), acid phosphatase (ACP), and GSH, which were decreased following SMZ exposure. Hepatopancreatic histology confirmed that EGCG ameliorated SMZ-induced tissue damage caused by SMZ exposure. In addition to EGCG attenuating SMZ-induced immunotoxicity in crayfish, we determined that EGCG can effectively reduce SMZ residues in crayfish exposed to SMZ. In addition, at the genetic level, the expression levels of genes related to the immune response in hemocytes were disrupted after SMZ exposure, and EGCG promoted their recovery and stimulated an increase in the expression levels of metabolism-related transcripts in hemocytes. The transcriptome analysis was conducted, and "phagosome" and "apoptosis" pathways were shown to be highlighted using Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. To the best of our knowledge, this is the first study to confirm that EGCG attenuates SMZ-induced immunotoxicity in aquatic animals and reduces SMZ residues in aquatic animals exposed to SMZ. Our study contributes to the understanding of the mechanisms by which EGCG reduces the immunotoxicity of antibiotic residues in aquatic animals.

Immune checkpoint activity exacerbate renal interstitial fibrosis progression by enhancing PD-L1 expression in renal tubular epithelial cells.

Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse. PD-L1 was significantly overexpressed in HK-2 cells with upregulated collagen and α-SMA when stimulated by inflammation or hypoxia in vitro. Additionally, matrix metalloproteinases (MMP-2) could increase the level of sPD-1 in culture supernatant when added in co-culture system of HK-2 and jurkat cells, which implied serum sPD-1 of IgAN might be cleaved by MMP-2 from T cells infiltrated into the tubulointerstitial inflammatory microenvironment. Crucially, injection of PD-L1 fusion protein, the blocker of sPD-1, could ameliorate kidney fibrosis in UUO mice by increasing T cell coinhibition and exhaustion, suggesting the therapeutic potential of PD-L1 fusion targeting for renal fibrosis. Take together, it reveals a novel causal role of sPD-1 in serum and PD-L1 of renal interstitial tissues in the development of renal fibrosis of IgAN, and targeting sPD-1 in serum by PD-L1 fusion protein is a potential therapeutic approach to prevent renal fibrosis of IgAN.

PIEZO2 expression is an independent biomarker prognostic for gastric cancer and represents a potential therapeutic target.

Gastric cancer (GC) is one of the most prevalent malignant tumors of the gastrointestinal system in the globe. The effect of PIEZO2 on the immune function and pathological features of gastric cancer remains to be explored. The Online database of cancer genes and GSE54129 have been used to analyze the clinical characteristics of PIEZO2 expression. We looked at the relationship between PIEZO2 and the immune systems of GC patients. The TIDE algorithm was used to explore the value of PIEZO2 in immunotherapy. Investigated the enrichment of PIEZO2 gene ontology and associated signal pathways using Online gene databases. The results show that overexpression of PIEZO2 was identified as an independent risk factor for patients with GC who had poor overall survival. Individuals may have a better prognosis if they had poorly differentiated GC and increased PIEZO2 expression (P < 0.05). We demonstrated a strong correlation between PIEZO2 and immune cells. The majority of immune checkpoint and immunological-related genes were associated with PIEZO2 expression. And PIEZO2 might be used as an immunotherapy target. Finally, the differential PIEZO2 genes in GC were mostly implicated in the processes of inflammation, immunological response, and tumor metastasis, according to functional analysis. PIEZO2 has a negative correlation with cell stemness and mutation levels in patients with GC and a positive correlation with immune cell infiltration and gene expression in the tumor microenvironment. These findings point to PIEZO2 as a potential new immunotherapy target of GC.

What role does PDL1 play in EMT changes in tumors and fibrosis?

Epithelial-mesenchymal transformation (EMT) plays a pivotal role in embryonic development, tissue fibrosis, repair, and tumor invasiveness. Emerging studies have highlighted the close association between EMT and immune checkpoint molecules, particularly programmed cell death ligand 1 (PDL1). PDL1 exerts its influence on EMT through bidirectional regulation. EMT-associated factors, such as YB1, enhance PDL1 expression by directly binding to its promoter. Conversely, PDL1 signaling triggers downstream pathways like PI3K/AKT and MAPK, promoting EMT and facilitating cancer cell migration and invasion. Targeting PDL1 holds promise as a therapeutic strategy for EMT-related diseases, including cancer and fibrosis. Indeed, PDL1 inhibitors, such as pembrolizumab and nivolumab, have shown promising results in clinical trials for various cancers. Recent research has also indicated their potential benefit in fibrosis treatment in reducing fibroblast activation and extracellular matrix deposition, thereby addressing fibrosis. In this review, we examine the multifaceted role of PDL1 in immunomodulation, growth, and fibrosis promotion. We discuss the challenges, mechanisms, and clinical observations related to PDL1, including the limitations of the PD1/PDL1 axis in treatment and PD1-independent intrinsic PDL1 signaling. Our study highlights the dynamic changes in PDL1 expression during the EMT process across various tumor types. Through interplay between PDL1 and EMT, we uncover co-directional alterations, regulatory pathways, and diverse changes resulting from PDL1 intervention in oncology. Additionally, our findings emphasize the dual role of PDL1 in promoting fibrosis and modulating immune responses across multiple diseases, with potential implications for therapeutic approaches. We particularly investigate the therapeutic potential of targeting PDL1 in type II EMT fibrosis: strike balance between fibrosis modulation and immune response regulation. This analysis provides valuable insights into the multifaceted functions of PDL1 and contributes to our understanding of its complex mechanisms and therapeutic implications.

Coordination of growth and drought responses by GA-ABA signaling in rice.

The drought caused by global warming seriously affects the crop growth and agricultural production. Plants have evolved distinct strategies to cope with the drought environment. Under drought stress, energy and resources should be diverted from growth toward stress management. However, the molecular mechanism underlying coordination of growth and drought response remains largely elusive. Here, we discovered that most of the gibberellin (GA) metabolic genes were regulated by water scarcity in rice, leading to the lower GA contents and hence inhibited plant growth. Low GA contents resulted in the accumulation of more GA signaling negative regulator SLENDER RICE 1, which inhibited the degradation of abscisic acid (ABA) receptor PYL10 by competitively binding to the co-activator of anaphase-promoting complex TAD1, resulting in the enhanced ABA response and drought tolerance. These results elucidate the synergistic regulation of crop growth inhibition and promotion of drought tolerance and survival, and provide useful genetic resource in breeding improvement of crop drought resistance.

Therapeutic Strategies for Postherpetic Neuralgia: Mechanisms, Treatments, and Perspectives.

PURPOSE OF REVIEW: Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and interventional treatments for postherpetic neuralgia and updates the research on the efficacy, thereby providing doctors with more treatment options. The adverse effects and effective doses of its various treatments are also presented so that the therapy can be prescribed according to their concrete physical conditions. In a word, this review is dedicated to providing a comprehensive overview of the treatment options for postherpetic neuralgia and offering patients more choices. RECENT FINDINGS: Combinational therapy is more excellent than monotherapy. The local anesthesia and gabapentin comprised outstanding compatibility. In addition, two therapeutic tools for PHN patients, especially for the intractable ones, electroacupuncture (EA), and osteopathic manipulative treatment (OMT), show their efficacy and become potential options to alleviate pain. In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). And drug efficacy can be limited by adverse effects and tolerated doses. Interventional treatments, with their invasiveness and operational difficulty, are usually considered for intractable patients. Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture.

A proactive crash risk prediction framework for lane-changing behavior incorporating individual driving styles.

Driving style may have an important effect on traffic safety. Proactive crash risk prediction for lane-changing behaviors incorporating individual driving styles can help drivers make safe lane-changing decisions. However, the interaction between driving styles and lane-changing risk is still not fully understood, making it difficult for advanced driver-assistance systems (ADASs) to provide personalized lane-changing risk information services. This paper proposes a personalized risk lane-changing prediction framework that considers driving style. Several driving volatility indices based on vehicle interactive features have been proposed, and a dynamic clustering method is developed to determine the best identification time window and methods of driving style. The Light Gradient Boosting Machine (LightGBM) based on Shapley additive explanation is used to predict lane-changing risk for cautious, normal, and aggressive drivers and to analyze their risk factors. The highD trajectory dataset is used to evaluate the proposed framework. The obtained results show that i) spectral clustering and a time window of 3 s can accurately identify driving styles during the lane-changing intention process; ii) the LightGBM algorithm outperforms other machine learning methods in personalized lane-changing risk prediction; iii) aggressive drivers seek more individual driving freedom than cautious and normal drivers and tend to ignore the state of the car behind them in the target lane, with a greater lane-changing risk. The research conclusion can provide basic support for the development and application of personalized lane-changing warning systems in ADASs.

Hybridization alters the gut microbial and metabolic profile concurrent with modifying intestinal functions in Tunchang pigs.

Introduction: Hybridization has been widely used among Chinese wild boars to improve their growth performance and maintain meat quality. Most studies have focused on the genetic basis for such variation. However, the differences in the gut environment between hybrid and purebred boars, which can have significant impacts on their health and productivity, have been poorly understood. Methods: In the current study, metagenomics was used to detect the gut microbial diversity and composition in hybrid Batun (BT, Berkshire × Tunchang) pigs and purebred Tunchang (TC) pigs. Additionally, untargeted metabolomic analysis was used to detect differences in gut metabolic pathways. Furthermore, multiple molecular experiments were conducted to demonstrate differences in intestinal functions. Results: As a result of hybridization in TC pigs, a microbial change was observed, especially in Prevotella and Lactobacillus. Significant differences were found in gut metabolites, including fatty acyls, steroids, and steroid derivatives. Furthermore, the function of the intestinal barrier was decreased by hybridization, while the function of nutrient metabolism was increased. Discussion: Evidences were shown that hybridization changed the gut microbiome, gut metabolome, and intestinal functions of TC pigs. These findings supported our hypothesis that hybridization altered the gut microbial composition, thereby modifying the intestinal functions, even the host phenotypes. Overall, our study highlights the importance of considering the gut microbiome as a key factor in the evaluation of animal health and productivity, particularly in the context of genetic selection and breeding programs.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Fei Jin Sheng Formula in the Treatment of Lung Cancer.

BACKGROUND: Fei Jin Sheng Formula (FJSF) is widely used in clinical treatment of lung cancer. But the underlying active ingredients and mechanisms are unclear. OBJECTIVE: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro. RESULTS: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona, quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage I patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate (MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2. CONCLUSION: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer.

RBM3 suppresses stemness remodeling of prostate cancer in bone microenvironment by modulating N6-methyladenosine on CTNNB1 mRNA.

Bone metastasis is the most happened metastatic event in prostate cancer (PCa) and needs a large effort in treatment. When PCa metastasizes to the bone, the new microenvironment can induce the epigenome reprogramming and stemness remodeling of cancer cells, thereby increasing the adaptability of cancer cells to the bone microenvironment, and this even leads to the occurrence of secondary tumor metastasis. Our group has previously found that RNA binding motif 3 (RBM3) affects the stem cell-like properties of PCa by interfering with alternative splicing of CD44. However, whether RBM3, as a stress-response protein, can resist microenvironmental remodeling of PCa particularly in bone metastasis remains unknown. By co-culturing PCa cells with osteoblasts to mimic PCa bone metastases, we found that RBM3 upregulates the N6-methyladenosine (m6A) methylation on the mRNA of catenin beta 1 (CTNNB1) in a manner dependent on methyltransferase 3 (METTL3), an N6-adenosine-methyltransferase complex catalytic subunit. Consequently, this modification results in a decreased stability of CTNNB1 mRNA and a followed inactivation of Wnt signaling, which ultimately inhibits the stemness remodeling of PCa cells by osteoblasts. Thus, the present study may extend our understanding of the inhibitory role of RBM3 on particularly bone metastasis of PCa.

Natural peptides for immunological regulation in cancer therapy: Mechanism, facts and perspectives.

Cancer incidence and mortality rates are increasing annually. Treatment with surgery, chemotherapy and radiation therapy (RT) is unsatisfactory because many patients have advanced disease at the initial diagnosis. However, the emergence of immunotherapy promises to be an effective strategy to improve the outcome of advanced tumors. Immune checkpoint antibodies, which are at the forefront of immunotherapy, have had significant success but still leave some cancer patients without benefit. For more cancer patients to benefit from immunotherapy, it is necessary to find new drugs and combination therapeutic strategies to improve the outcome of advanced cancer patients and achieve long-term tumor control or even eradication. Peptides are promising choices for tumor immunotherapy drugs because they have the advantages of low production cost, high sequence selectivity, high tissue permeability, low toxicity and low immunogenicity etc., and the adjuvant matching and technologies like nanotechnology can further optimize the effects of peptides. In this review, we present the current status and mechanisms of research on peptides targeting multiple immune cells (T cells, natural killer (NK) cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), regulatory T cells (Tregs)) and immune checkpoints in tumor immunotherapy; and we summarize the current status of research on peptide-based tumor immunotherapy in combination with other therapies including RT, chemotherapy, surgery, targeted therapy, cytokine therapy, adoptive cell therapy (ACT) and cancer vaccines. Finally, we discuss the current status of peptide applications in mRNA vaccine delivery.

Association between glycemic traits and melanoma: a mendelian randomization analysis.

Background: The causation of Glycemic Traits and risks of Melanoma remains unknown. We used Mendelian Randomization (MR) to assess the links between Glycemic Traits and Melanoma. Method: Pooled data from Genome-Wide Association Studies (GWAS) were utilized to examine the relationships that exist between Fasting Insulin (n = 26), 2-h Glucose (n = 10), Fasting Glucose (n = 47), HbA1c (n = 68), and Type-2 Diabetes (n = 105) and Melanoma. We evaluated the correlation of these variations with melanoma risk using Two-Samples MR. Result: In the IVW model, Fasting Glucose (OR = 0.99, 95%CI = 0.993-0.998, p < 0.05, IVW), Type-2 Diabetes (OR = 0.998, 95%CI = 0.998-0.999, p < 0.01, IVW) and HbA1c (OR = 0.19, 95%CI = 0.0415-0.8788, p < 0.05, IVW) was causally associated with a lower risk of Melanoma. In all models analyzed, there was no apparent causal relationship between Fasting Insulin and Melanoma risk. There was no obvious causal difference in the IVW analysis of 2-h Glucose and Melanoma, but its p < 0.05 in MR Egger (OR = 0.99, 95%CI = 0.9883-0.9984, p < 0.05, MR Egger), and the direction was consistent in other MR analyses, suggesting that there may be a causal relationship. Conclusion: The results of this study suggest that a higher risk of Fasting Glucose, Type-2 Diabetes, 2-h Glucose, and HbA1c may be associated with a lower risk of Melanoma. However, no causal relationship between fasting insulin and melanoma was found. These results suggest that pharmacological or lifestyle interventions that regulate plasma glucose levels in the body may be beneficial in the prevention of melanoma.

When to Pre-Train Graph Neural Networks? From Data Generation Perspective!

In recent years, graph pre-training has gained significant attention, focusing on acquiring transferable knowledge from unlabeled graph data to improve downstream performance. Despite these recent endeavors, the problem of negative transfer remains a major concern when utilizing graph pre-trained models to downstream tasks. Previous studies made great efforts on the issue of what to pre-train and how to pre-train by designing a variety of graph pre-training and fine-tuning strategies. However, there are cases where even the most advanced "pre-train and fine-tune" paradigms fail to yield distinct benefits. This paper introduces a generic framework W2PGNN to answer the crucial question of when to pre-train (i.e., in what situations could we take advantage of graph pre-training) before performing effortful pre-training or fine-tuning. We start from a new perspective to explore the complex generative mechanisms from the pre-training data to downstream data. In particular, W2PGNN first fits the pre-training data into graphon bases, each element of graphon basis (i.e., a graphon) identifies a fundamental transferable pattern shared by a collection of pre-training graphs. All convex combinations of graphon bases give rise to a generator space, from which graphs generated form the solution space for those downstream data that can benefit from pre-training. In this manner, the feasibility of pre-training can be quantified as the generation probability of the downstream data from any generator in the generator space. W2PGNN offers three broad applications: providing the application scope of graph pre-trained models, quantifying the feasibility of pre-training, and assistance in selecting pre-training data to enhance downstream performance. We provide a theoretically sound solution for the first application and extensive empirical justifications for the latter two applications.

Environmental Factors Affecting Freshwater Snail Intermediate Hosts in Shenzhen and Adjacent Region, South China.

Sound knowledge of the local distribution and diversity of freshwater snail intermediate hosts and the factors driving the occurrence and abundance of them is crucial to understanding snail-borne parasitic disease transmission and to setting up effective interventions in endemic areas. In this study, we investigated the freshwater snails, water quality parameters, physical characteristics of habitats, predators and competitors, and human activity variables at 102 sites during December 2018 and August 2019 in Shenzhen and adjacent areas in China. We used decision tree models and canonical correspondence analysis to identify the main environmental and biotic factors affecting the occurrence and abundance of snail species. A total of nine species of snail were collected throughout the study area, with Biomphalaria straminea, Sinotaia quadrata, and Physella acuta being the most predominant species. Our study showed that the most important variables affecting the abundance and occurrence of snail species were the presence of predators and competitors, macrophyte cover, chlorophyll-a, substrate type, river depth, and water velocity. In terms of human activities, snail species occurred more frequently and in larger numbers in water bodies affected by human disturbances, especially for sewage discharge, which may reduce the occurrence and abundance of snail predators and competitors. These findings suggest that proper management of water bodies to reduce water pollution may increase the abundance of snail predators and competitors, and should be considered in integrated snail control strategies in the study area.

Kidney diseases and long non-coding RNAs in the limelight.

The most extensively and well-investigated sequences in the human genome are protein-coding genes, while large numbers of non-coding sequences exist in the human body and are even more diverse with more potential roles than coding sequences. With the unveiling of non-coding RNA research, long-stranded non-coding RNAs (lncRNAs), a class of transcripts >200 nucleotides in length primarily expressed in the nucleus and rarely in the cytoplasm, have drawn our attention. LncRNAs are involved in various levels of gene regulatory processes, including but not limited to promoter activity, epigenetics, translation and transcription efficiency, and intracellular transport. They are also dysregulated in various pathophysiological processes, especially in diseases and cancers involving genomic imprinting. In recent years, numerous studies have linked lncRNAs to the pathophysiology of various kidney diseases. This review summarizes the molecular mechanisms involved in lncRNAs, their impact on kidney diseases, and associated complications, as well as the value of lncRNAs as emerging biomarkers for the prevention and prognosis of kidney diseases, suggesting their potential as new therapeutic tools.

Leaves, seeds and exocarp of Ginkgo biloba L. (Ginkgoaceae): A Comprehensive Review of Traditional Uses, phytochemistry, pharmacology, resource utilization and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. (Ginkgoaceae) is a treasure species with high medicinal value. The Ming Dynasty "Compendium of Materia Medica" and Qing Dynasty "Bencao Fengyuan" in China recorded this herbal medicine can reduce phlegm, clear poison, treat diarrhea and frequent urination, etc. AIM OF THE STUDY: Until now, there is no painstakingly summarized review on leaves, seeds and exocarp of G. biloba simultaneously. This review will systematically summarize and compare current knowledge of G. biloba. MATERIALS AND METHODS: Ample original publications related to traditional uses, phytochemistry, pharmacology, resource utilization and toxicity of G. biloba leaves, seeds and exocarp till the end of 2021 were searched and collected by using various literature databases, including China National Knowledge Infrastructure, PubMed, Elsevier, Springer, Google Scholar and Web of Science database. RESULTS: According to classical Chinese herbal books and Chinese Pharmacopoeia, relieving cough, reducing phlegm, clearing poison and relieving diarrhea are the main pharmacological effects of G. biloba. The common chemical ingredients in different parts of G. biloba are flavonoids, terpenoids, phenolic acids, polysaccharides and endotoxin, etc. Among them, flavonoids and terpenoids are the main bioactive compounds in G. biloba leaves. Phenolic acids are the main bioactive compounds in G. biloba exocarp. G. biloba seeds are rich in nutritional ingredients, such as starch, adipose, protein, etc. Modern pharmacological studies showed that the crude extracts or compounds of G. biloba leaves, seeds and exocarp can be used for treating cardiovascular and cerebrovascular diseases, Alzheimer's disease, atherosclerosis, cancer, asthma, non-alcoholic fatty liver, diabetic complications and other diseases. In daily life, G. biloba seeds were usually used as raw material or additives for commodities, healthy food, drinks, even insecticides and antibacterial agents, etc. G. biloba leaves and seeds have been mainly applied for treating cardiovascular and cerebrovascular diseases, cough and asthma in clinical. However, endotoxins and ginkgolic acids have been identified as the dominating toxic ingredients in different parts of G. biloba. Besides, flavonoids and ginkgolides also have been proved to have toxicity recently. CONCLUSIONS: This review systematically sums up and compares the traditional uses, phytochemistry, pharmacology, resource utilization and toxicity research progress of G. biloba leaves, seeds and exocarp for the first time. It will provide some comprehensive reference data and suggestions for future research on this herbal medicine.

The Role of Extracellular Vesicles in Embryo Implantation.

Extracellular vesicles (EVs) are membrane-coating nanoparticles derived from cells. The effect of cell-to-cell communication mediated by EVs has been investigated in different fields of physio-logical as well as pathological process in recent years. Reproduction, regarded as a definitive characteristic of organisms, has been a focus in both animal and medical sciences. It is well agreed that implantation is a critical event during early pregnancy in viviparous animals, and a proper implantation is essential for the establishment and maintenance of normal pregnancy. However, successful implantation requires the synchronized development of both the uterus and the embryo, therefore, in which well communication and opportune regulation are necessary. This review focuses on the progression of studies that reveal the role of EVs in early pregnancy, especially during implantation. Based on current evidence, EVs are produced and exist in the environment for implantation. It has been proved that EVs of different origins such as endometrium and embryo, have positive influences on embryo implantation. With their cargos of proteins and nucleic acids (especially microRNAs), EVs exert their effects including information transportation, immune stimulation and regulation of gene expression.

Level, source, and distribution of organochlorine pesticides (OCPs) in agricultural soils of Tanzania.

This study investigated the level, composition, and spatial and vertical distribution of the organochlorine pesticides (OCPs) at 0-2 cm and 2-20 cm in the agricultural surface soils from Southeastern to Central-western Tanzania. Although the most abundant OCPs were DDT with a mean concentration of 2.29 ng/g, dieldrin (1.57 ng/g), and methoxychlor (0.79 ng/g), HCH was the most dominant (with detection frequency of 88%). OCP dominance was in the Southern Highlands, which is the most productive agricultural zone. Though there were indicators of recent inputs for some sites, OCP contamination was mainly historical. DDT contamination was dominated by p,p'-DDE and resulted from both technical DDT and dicofol while HCH contamination was dominated by γ-HCH and resulted from both technical HCH and lindane. Based on depth, the OCPs dominated mainly the upper 2 cm, which was associated with soil and environmental factors rather than recent inputs since most of the detected compounds were historical. Nevertheless, some sites showed exceptional high abundance in the lower soil with more concentration of parent compounds. Therefore, this study recommends the need for further studies on the influence of soil properties on OCPs' transport in the soil, surface water, and air. Besides, detection of recent inputs at some sites calls for more mapping of the OCPs in the country to strengthen their control and prevention of future risks.

Deposition records of polycyclic aromatic hydrocarbons and black carbon in peat core from Dajiuhu, Shennongjia, Central China: human activity imprint since the industrial revolution.

Polycyclic aromatic hydrocarbons (PAHs) are a kind of organic pollutants with carcinogenic, teratogenic, and mutagenic effects. This study aims to assess the effects of changes in China's socio-economic indicators represented by energy consumption and number of motor vehicles, on PAHs and black carbon (BC) deposition. For this, a 50-cm peat core from Dajiuhu peatland, Central China, was collected and divided into 50 subsamples to establish a sedimentary record of about 200 years with radioactive 210Pb. The Σ16PAH concentration ranged from 212.67 to 830.10 ng·g-1, mainly composed of 2- and 3-ring PAHs, and BC ranged from 7.89 to 36.48%. The deposition characteristics of BC first increased and then decreased from the core bottom to the top. The predominant of the carcinogenic PAHs (C-PAHs) was Dibenzo[a,h]anthracene (DBA) before 1949, and then changed to Benzo[b]fluoranthene (BbF). Ratio of Fla/Pyr, (3+4)-ring/(5+6)-ring PAHs, and BaA/(BaA+Chr), IcdP/(IcdP+BghiP) suggested that long-range atmospheric transmission (LRAT) and pyrogenic were the main PAHs sources, but that local PAH emission contribution gradually increased since 1990, and mixed (petroleum and combustion) sources were the dominant since 2000. The high concentration of Phenanthrene (Phe) and Naphthalene (Nap) were likely from plant product. Furthermore, increased concentrations of 4-, 5-, and 6-ring PAHs showed significant correlations with increased coal and petroleum consumption and the number of motor vehicles, respectively, and this influence has strengthened after 2000. These were caused by rapid urbanization and industrialization following the implementation of the reform and opening up policy in 1978, and a new round of urbanization after 2000.

Melatonin Alleviates Glucose and Lipid Metabolism Disorders in Guinea Pigs Caused by Different Artificial Light Rhythms.

Modern lifestyle-associated factors, such as high-calorie intake, high-fat diet (HFD), and excessive artificial light, are risk factors for glucose and lipid metabolism disturbances. Melatonin may be beneficial for managing obesity and diabetes; however, the underlying molecular mechanisms are not well elucidated. We aimed to assess whether melatonin has beneficial effects on constant artificial light-induced fat deposition, lipid metabolism, and insulin resistance. Guinea pigs were randomly divided into five experimental groups: control (C), HFD (H), 12 h light (12HL), 24 h light (24HL), and melatonin (M). The majority of indexes, including insulin resistance and obesity, were measured after 10 weeks. AMP-activated protein kinase α (AMPKα)/peroxisome proliferator-activated receptor-α (PPARα) pathway expression was analyzed by quantitative reverse transcription PCR and western blotting. Although insulin resistance and obesity indexes were higher in the 24HL group than in the 12HL group, they were significantly lower in the M group than in the 24HL group. Melatonin treatment markedly upregulated AMPKα, phosphorylated AMPKα (p-AMPKα), PPARα, and carnitine palmitoyl-CoA transferase 1 A (CPT1A) gene and protein expression. Melatonin may alleviate insulin resistance and obesity caused by persistent artificial light exposure in guinea pigs, likely via activation of the AMPKα/PPARα signaling pathway.