Association of Plasma Metal Levels with Outcomes of Assisted Reproduction in Polycystic Ovary Syndrome.

The objective of this study is to explore the correlation of metal levels with assisted reproductive technology (ART) outcomes in polycystic ovary syndrome (PCOS) patients. The individuals were recruited who met the research criteria, only tubal factor or male infertility served as the control group (n = 40) and patient group was PCOS patients (n = 35). Individuals (n = 75) were divided into PCOS group (n = 35) and control group (n = 40). The normal body mass index (BMI) group (control) includes women with BMI < 25 kg/m2 in PCOS group (n = 24) and control group (n = 33), and BMI ≥ 25 kg/m2 in PCOS group (n = 11) and control group (n = 7). We performed an analysis of insulin resistance (IR) (n = 15) group and without insulin resistance (NIR) group (n = 20) in PCOS patient and control patients. Comparing difference demographic data, ART outcomes and the metal levels in every group respectively, the correlation of metal levels and ART outcomes in control participants and PCOS patients were analyzed by the Spearman correlation analysis, and multiple linear regression model was used to examine the association between the concentration of 19 metals and ART outcomes in PCOS group and control group. Plasma manganese (Mn), titanium (Ti), sodium (Na), magnesium (Mg), copper (Cu), calcium (Ca)/Mg ratio, and Cu/zinc (Zn) ratio levels in PCOS patients were higher than that in control, while Zn and Ca levels were lower in PCOS patients than that in control. The Mg levels had a positive connection with the number of eggs recovered, and the iron (Fe) levels were positively associated with the number of transplanted embryos in PCOS-IR. In PCOS-NIR, Mn levels positively correlated with the number of follicles and the number of good embryos. Silver (Ag) levels were negatively correlated with the number of follicles, and aluminum (Al) levels were negatively related with the normal fertilization and the number of good embryos. The Spearman analysis in PCOS-BMI ≥ 25 group exhibited that nickel (Ni) levels were negatively associated with the number of follicles. The plasma metal levels seem to affect the clinical manifestations and in vitro fertilization outcomes in assisted reproduction.

The complete chloroplast genome sequence of Calanthe sieboldii (orchidaceae).

Calanthe sieboldii Decne. ex Regel is a terrestrial orchid with high ornamental and commercial value. In the present study, the chloroplast genome of C. sieboldii was characterized using Illumina technology. The chloroplast genome is 158,345 bp in length with a total AT content of 63.28%. There are 127 genes, comprising 37 tRNA genes, 82 protein-coding genes, and 8 rRNA genes. Phylogenetic relationship analysis was performed using common protein-coding genes extracted from 13 chloroplast genomes of Orchidaceae. It was revealed that C. sieboldi was sister to C. hancockii and closely clustered with C. aristulifera and C. henryi. These findings provide valuable genomic resources that are helpful for further phylogenetic and evolutionary studies of Calanthe.

Effects of bone marrow mesenchymal stromal cells-derived therapies for experimental traumatic brain injury： A meta-analysis.

Background: Bone-marrow-derived mesenchymal stromal (stem) cells [also called MSC(M)] and their extracellular vesicles (EVs) are considered a potentially innovative form of therapy for traumatic brain injury (TBI). Nevertheless, their application to TBI particularly remains preclinical, and the effects of these cells remain unclear and controversial. Therefore, an updated meta-analysis of preclinical studies is necessary to assess the effectiveness of MSC(M) and MSC(M) derived EVs in clinical trials. Methods: The following databases were searched (to December 2022): PubMed, Web of Science, and Embase. In this study, we measured functional outcomes based on the modified neurological severity score (mNSS), cognitive outcomes based on the Morris water maze (MWM), and histopathological outcomes based on lesion volume. A random effects meta-analysis was conducted to evaluate the effect of mNSS, MWM, and lesion volume. Results: A total of 2163 unique records were identified from our search, with Fifty-five full-text articles satisfying inclusion criteria. A mean score of 5.75 was assigned to the studies' quality scores, ranging from 4 to 7. MSC(M) and MSC(M) derived EVs had an overall positive effect on the mNSS score and MWM with SMDs -2.57 (95 % CI -3.26; -1.88; p < 0.01) and - 2.98 (95 % CI -4.21; -1.70; p < 0.01), respectively. As well, MSC(M) derived EVs were effective in reducing lesion volume by an SMD of - 0.80 (95 % CI -1.20; -0.40; p < 0.01). It was observed that there was significant variation among the studies, but further analyses could not determine the cause of this heterogeneity. Conclusions: MSC(M) and MSC(M) derived EVs are promising treatments for TBI in pre-clinical studies, and translation to the clinical domain appears warranted. Besides, large-scale trials in animals and humans are required to support further research due to the limited sample size of MSC(M) derived EVs.

Selective HDAC6 inhibition protects against blood-brain barrier dysfunction after intracerebral hemorrhage.

BACKGROUNDS: Blood-brain barrier (BBB) disruption after intracerebral hemorrhage (ICH) significantly induces neurological impairment. Previous studies showed that HDAC6 knockdown or TubA can protect the TNF-induced endothelial dysfunction. However, the role of HDAC6 inhibition on ICH-induced BBB disruption remains unknown. METHODS: Hemin-induced human brain microvascular endothelial cells (HBMECs) and collagenase-induced rats were employed to investigated the underlying impact of the HDAC6 inhibition in BBB lesion and neuronal dysfunction after ICH. RESULTS: We found a significant decrease in acetylated α-tubulin during early phase of ICH. Both 25 or 40 mg/kg of TubA could relieve neurological deficits, perihematomal cell apoptosis, and ipsilateral brain edema in ICH animal model. TubA or specific siRNA of HDAC6 inhibited apoptosis and reduced the endothelial permeability of HBMECs. HDAC6 inhibition rescued the degradation of TJ proteins and repaired TJs collapses after ICH induction. Finally, the results suggested that the protective effects on BBB after ICH induction were exerted via upregulating the acetylated α-tubulin and reducing stress fiber formation. CONCLUSIONS: Inhibition of HDAC6 expression showed beneficial effects against BBB disruption after experimental ICH, which suggested that HDAC6 could be a novel and promising target for ICH treatment.

Research progress on the fibrinolytic enzymes produced from traditional fermented foods.

Cardiovascular diseases (CVDs) are a global health problem and leading cause of death worldwide. Thrombus formation, one of the CVDs, is essentially the formation of fibrin clots. The existing thrombolytic agents have the disadvantages of high price, short half-life, and high bleeding risk; hence, there is an urgent need to find the alternative thrombolytic agents. In recent years, traditional fermented foods have been widely investigated for their outstanding effects in the prevention and treatment of thrombus formation. In this review, we have focused on fibrinolytic enzymes produced by microorganisms during the fermentation of traditional fermented foods and their potential use for treating CVDs. First, we discussed about the sources of fibrinolytic enzymes and microbial strains that produce those enzymes followed by the optimization of fermentation process, purification, and physicochemical properties of fibrinolytic enzymes. Finally, we have summarized the thrombolytic effects of fibrinolytic enzymes in humans and mice. Fibrinolytic enzymes produced by microorganisms during the fermentation of traditional fermented foods not only lyse thrombi but also acts as anti-atherosclerotic, anti-hyperlipidemia, and neuroprotection agents. Therefore, fibrinolytic enzymes from traditional fermented foods have great potential for the prevention and treatment of CVDs.

Advances in investigating microcystin-induced liver toxicity and underlying mechanisms.

Microcystins (MCs) are a class of biologically active cyclic heptapeptide pollutants produced by the freshwater alga Microcystis aeruginosa. With increased environmental pollution, MCs have become a popular research topic. In recent years, the hepatotoxicity of MCs and associated effects and mechanisms have been studied extensively. Current epidemiological data indicate that long-term human exposure to MCs can lead to severe liver toxicity, acute toxicity, and death. In addition, current toxicological studies on the liver, a vital target organ of MCs, indicate that MC contamination is associated with the development of liver cancer, nonalcoholic fatty liver, and liver fibrosis. MCs produce hepatotoxicity that affects the metabolic homeostasis of the liver, induces apoptosis, and acts as a pro-cancer factor, leading to liver lesions. MCs mainly mediate the activation of signaling pathways, such as the ERK/JNK/p38 MAPK and IL-6-STAT3 pathways, which leads to oxidative damage and even carcinogenesis. Moreover, MCs can act synergistically with other pollutants to produce combined toxicity. However, few systematic reviews have been performed on these new findings. This review systematically summarizes the toxic effects and mechanisms of MCs on the liver and discusses the combined liver toxicity effects of MCs and other pollutants to provide reference for subsequent research. The toxicity of different MC isomers deserves further study. The detection methods and limit standards of MCs in agricultural and aquatic products will represent important research directions in the future. Standard protocols for fish sampling during harmful algal blooms or to evaluate the degree of MC toxicity in nature are lacking. In future, bioinformatics can be applied to offer insights into MC toxicology research and potential drug development for MC poisoning. Further research is essential to understand the molecular mechanisms of liver function damage in combined-exposure toxicology studies to establish treatment for MC-induced liver damage.

Strontium alleviated the growth inhibition and toxicity caused by cadmium in rice seedlings.

Cadmium (Cd) contamination of rice is an urgent ecological and agricultural problem. Strontium (Sr) has been shown to promote plant growth. However, the effect of Sr on rice seedlings under Cd stress is currently unclear. In this work hydroponic experiments were used to assess the impact of Sr on rice seedling growth under Cd stress. The findings demonstrated that foliar application of 0.5 mg L-1 Sr had no discernible impact on the development of rice seedlings. However, Sr significantly alleviated growth inhibition and toxicity in rice seedlings when threatened by Cd. Compared with the Cd treatment (Cd, 2.5 mg L-1), the root length, shoot height, and whole plant length of rice seedlings in the Cd + Sr treatment (Cd, 2.5 mg L-1; Sr, 0.5 mg L-1) increased by 4.96 %, 12.47 % and 9.60 %, respectively. The content of Cd in rice decreased by 23.34 % (roots) and 5.79 % (shoots). Sr lessened the degree of membrane lipid peroxidation damage (lower MDA concentration) among the seedlings of rice under Cd stress by controlling the activities of antioxidant enzymes and GSH content. By changing the expression of antioxidant enzyme-encoding genes and downregulating the heavy metal transporter gene (OsNramp5), Sr reduced accumulation and the detrimental effects of Cd on rice seedlings. Our study provides a new solution to the problem of Cd contamination in rice, which may promote the safe production of rice and benefit human health.

Selective HDAC6 inhibitor TubA offers neuroprotection after intracerebral hemorrhage via inhibiting neuronal apoptosis.

A large body of evidence has demonstrated that neuronal apoptosis is involved in the pathological process of secondary brain injury following intracerebral hemorrhage (ICH). Additionally, our previous studies determined that the inhibition of HDAC6 activity by tubacin or specific shRNA can attenuate neuronal apoptosis in an oxygen-glucose deprivation reperfusion model. However, whether the pharmacological inhibition of HDAC6-attenuated neuronal apoptosis in ICH remains unclear. In this study, we used hemin-induced SH-SY5Y cells to simulate a hemorrhage state in vitro and adopted a collagenase-induced ICH rat model in vivo to assess the effect of the HDAC6 inhibition. We found a significant increase in HDAC6 during the early stages of ICH. As expected, the acetylated α-tubulin significantly decreased in correlation with the expression of HDAC6. Medium and high doses (25, 40 mg/kg) of TubA, a selective inhibitor of HDAC6, both reduced neurological impairments, histological impairments, and ipsilateral brain edema in vivo. TubA or HDAC6 siRNA both alleviated neuronal apoptosis in vivo and in vitro. Finally, HDAC6 inhibition increased the level of acetylated α-tubulin and Bcl-2 and lowered the expression of Bax and cleaved caspase-3 post-ICH. In general, these results suggested that the pharmacological inhibition of HDAC6 may act as a novel and promising therapeutic target for ICH therapy by up-regulating acetylated α-tubulin and reducing neuronal apoptosis.

FTO: a critical role in obesity and obesity-related diseases.

In recent years, obesity is a growing pandemic in the world and has likely contributed to increasing the incidence of obesity-related diseases. Fat mass and obesity-associated gene (FTO) is the first gene discovered which has a close connection with fat. Recent studies suggested that FTO gene has played an important role in the molecular mechanisms of many diseases. Obesity is considered to be a hereditary disease and can evoke many kinds of diseases, including polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), cancer, etc., whose exact possible molecular mechanisms responsible for the effect of FTO on obesity and obesity-related diseases remain largely unknown. In this review, we comprehensively discuss the correlation between FTO gene and obesity, cancer, PCOS, T2DM, as well as the molecular mechanism involved in these diseases.

The role of zinc in follicular development.

Follicles consist of specialized somatic cells that encase a single oocyte. Follicle development is a process regulated by a variety of endocrine, paracrine, and secretory factors that work together to select follicles for ovulation. Zinc is an essential nutrient for the human body and is involved in many physiological processes, such as follicle development, immune response, homeostasis, oxidative stress, cell cycle progression, DNA replication, DNA damage repair, apoptosis, and aging. Zinc deficiency can lead to blocked oocyte meiotic process, cumulus expansion, and follicle ovulation. In this mini-review, we summarize the the role of zinc in follicular development.

Pyroptosis in diabetes and diabetic nephropathy.

Pyroptosis is identified as a pro-inflammatory programmed cell death, mediated by gasdermins (GSDMs) family of proteins accompanied by pro-inflammatory signals release. As essential players in innate immunity, inflammasomes are intracellular protein complexes which cleave gasdermin D (GSDMD), forming structurally stable pores in the cell membrane, subsequently inducing pyroptosis. Extensive evidence indicates that inflammasomes and pyroptosis contributes to tumors, nerve injury, inflammatory diseases and metabolic disorders. As a metabolic disorder, diabetes is characterized with hyperglycemia, insulin resistance and chronic inflammation. Meanwhile, aberrant pyroptosis exerts a key role in the occurrence and progression of diabetes and its common complication, diabetic nephropathy (DN). Furthermore, evidence has shown that DN patients and animal models exhibit increased circulating IL-1ß and inflammasome, while decreasing the expression of key components of the inflammasome mitigates kidney damage and delays progression. Current research has reported that non-coding RNAs (ncRNAs) are involved in activation of inflammasomes and play a crucial role in the control of pyroptosis in DN pathogenesis. In addition, studies have indicated that some natural plant compounds have therapeutic potential via regulation of inflammasomes and pyroptosis to prevent and potentially treat DN. This mini-review examines the molecular mechanism of inflammasome activation and pyroptosis, highlights the critical roles of ncRNA and explores potential therapeutics to regulate pyroptosis in DN.

Living fossils unearthed by blasting human chromosomes with Neanderthal mtDNA / 数字中医药（英文）

@#The successful retrieval of ancient mitochondrial DNA (mtDNA) from Neanderthals provides powerful experimental evidence that clarifies the arguments between the out-of-Africa and multiregional models of evolution. However, the lack of nuclear DNA from Neanderthal fossils and mtDNA of early modern human fossils dating back to approximately the same time in the Pleistocene constitutes a limitation that may compromise the significance of mtDNA phylogenetic analysis. In this report, we introduce a mitochromic analysis using Neanderthal mtDNA as a foreign transgene and humans as a naturally occurring transgenic species. Forty Neanderthal mtDNA retrievable nuclear fragments were identified by blasting human genome data with Neanderthal mtDNA. Five of the 40 fragments exhibited higher correlation with Neanderthal mtDNA than those with modern human mtDNA. Furthermore, these five nuclear fragments harbor Neanderthal mtDNA-unique haplotypes. Based on the 98%+ identity between Neanderthal and modern human mtDNA when compared by groups, we suggest that some of the modern human nuclear fragments retrieved using Neanderthal mtDNA may aid in decoding Neanderthal genetic information, and also may simultaneously demonstrate a close genetic evolutionary relationship between modern humans and Neanderthals.

Efficacy of Melatonin in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Stratified Meta-Analysis.

Background and Purpose: Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported as a potential neuroprotective agent of SAH. It provides protective effects through the anti-inflammatory effects or the autophagy pathway. Our systematic review aims to evaluate the efficacy of melatonin administration on experimental SAH animals and offer support for the future clinical trial design of the melatonin treatment following SAH. Methods: The following online databases were searched for experimentally controlled studies of the effect of melatonin on SAH models: PubMed, Web of Knowledge, Embase, and China National Knowledge Infrastructure (all until March 2021). The melatonin effect on the brain water content (BWC) and neurological score (NS) were compared between the treatment and control groups using the standardized mean difference (SMD). Results: Our literature identified 160 possible articles, and most of them were excluded due to duplication (n = 69) and failure to meet the inclusion criteria (n = 56). After screening the remaining 35 articles in detail, we excluded half of them because of no relevant outcome measures (n = 16), no relevant interventions (n = 3), review articles (n = 1), duplicated publications (n = 1), and studies on humans or cells (n = 2). Finally, this systematic review contained 12 studies between 2008 and 2018. All studies were written in English except for one study in Chinese, and all of them showed the effect of melatonin on BWC and NS in SAH models. Conclusion: Our research shows that melatonin can significantly improve the behavior and pathological results of SAH animal models. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether melatonin can be used in the adjuvant treatment of clinical SAH patients.

A novel genotyping technique for discriminating LVAS-associated high-frequency variants in SLC26A4 gene.

An increasing number of biological and epidemiological evidence suggests that c.919-2A > G and c.2168A > G variants of solute carrier family 26, member 4 (SLC26A4) gene play a critical role in the development of large vestibular aqueduct syndrome (LVAS). In this study, we developed a rapid genotyping method for discriminating LVAS-associated high-frequency variants in SLC26A4 gene. The genotyping technique consists of 3' terminal exonuclease-resistant phosphorothioate-modified allele specific primer extension mediated by exo+ polymerase. In PCR amplification by Pfu polymerase, allelic specific primers perfectly matching wild type allele were extended while no specific products were yielded from primers targeting variant allele. Similarly, allelic specific primers perfectly matching variant allele were extended and no specific products were observed from primers targeting wild type allele. The clinical application of 3' terminal phosphorothioate-modified allele specific primer extension mediated by Pfu polymerase identified both homozygous for SLC26A4 gene c.919-2A > G variant in two patients clinically diagnosed as LVAS by temporal bone CT scan. The genetic results from this method are consistent with that of DNA sequencing. The data suggest that exo+ polymerase-mediated 3' terminal phosphorothioate-modified primer extension is reliable in the identification of SLC26A4 gene high-frequency variant prior to high-resolution CT scan. The method is extremely suitable for quickly molecular etiologic screening and early diagnosis and aggressive prevention therapy of LVAS.

Adjuvant radiotherapy and chemotherapy in early-stage diffuse large B cell lymphoma of head and neck with extranodal involvement.

Objectives: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous lymphoma with a variety of presentations and treatment modalities. With the introduction of immunotherapy as an addition to chemotherapy (CT), there is ongoing debate about the role of radiotherapy (RT) in treatment and a need to clarify differences by specific anatomic locations.Methods: We identified a cohort of 1929 individuals with limited stage (stage I and II) head and neck DLBCL with extranodal involvement from the National Cancer Data Base. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and propensity score-matched analysis.Results: Multi-agent CT plus RT was associated with longer OS (HR, 0.763; 95% CI, 0.614 to 0.948; p = 0.015) when compared with multi-agent CT alone on multivariate analysis. After propensity score matching to account for confounding variables, multi-agent CT plus RT was associated with longer OS than those who received multi-agent CT alone (HR = 0.769; 95% CI, 0.609-0.971; p = 0.027). The survival benefit persisted in patients over the age of 60 years and those who received RT within 180 days of CT. However, there was no significant difference in OS between the two groups in subgroup analysis of patients who received immunotherapy.Conclusion: The addition of RT to CT resulted in longer OS in patients with limited stage head and neck DLBCL with extranodal involvement.

The first complete chloroplast genome of Liparis nervosa and its phylogenetic position within Orchidaceae.

Liparis nervosa is a plant of the family Orchidaceae and mainly distributed in subtropical and tropical regions of the world. In Chinese traditional medicine, it has been used for the treatment of hemostasis, carbuncle, and furuncle for centuries. The chloroplast (cp) genome of L. nervosa, sequenced based on next-generation platform (NEOSAT), is 157,274 bp in size. The cp genome encodes 130 genes, including eight rRNA genes, 85 protein-coding genes (PCGs), and 37 tRNA genes. Phylogenetic relationship analysis based on complete cp genome sequences exhibited that both of L. nervosa and L. loeselii were phylogenetically closer to Dendrobium officinale.

The complete chloroplast genome of Paris polyphylla var. chinensis, an endemic medicinal herb in China.

Paris polyphylla var. chinensis is a species of flowering herb of the family Liliaceae and widely distributed in 12 provinces in China. It has been used in Chinese traditional medicine for centuries. The chloroplast (cp) genome of P. polyphylla var. chinensis, sequenced based on next-generation platform (NEOSAT), is 164,429 bp in size. The cp genome encodes 133 genes, including eight rRNA genes, 87 protein-coding genes (PCGs), and 38 tRNA genes. Phylogenetic relationship analysis based on complete cp genome sequences exhibited that P. polyphylla var. chinensis was most related to Daiswa forrestii.

Characterization of the complete chloroplast genome sequence of Tinospora sagittata and its phylogenetic implications.

Tinospora sagittata is a perennial vine of the family Menispermaceae and distributed in Hunan, Hubei, Guangxi, and Sichuan province of P. R. China. It has been used in Chinese traditional medicine for centuries. The chloroplast (cp) genome of T. sagittata, characterized using Illumina technology, is 163,662 bp in size. There are a total of 130 genes, coding for 85 proteins, 37 tRNAs, and 8 rRNAs. Phylogenetic relationship analysis based on 16 complete cp genome sequences exhibited that T. sagittata was phylogenetically closer to Menispermum dauricum and Stephania japonica.

A Novel Assay Coupling Dephosphorylation and Blue/White Colony Screening for the G > A Hotspot Mutation at Codon 13 of KRAS Gene.

Development of sensitive assay for detection of hotspot mutations of cancer driving gene is crucial for circulating tumor DNA analysis. This study tested the possibilities of applying restriction enzyme digestion and dephosphorylation coupled with blue/white screening technology for analyzing a hotspot point mutation in codon 13 of KRAS gene. The present study has documented that the combination of PCR with restriction digestion, dephosphorylation, blue/white screening and Sanger's sequencing can identify rare mutations with sensitivities at 0.003%. This novel assay with high sensitivity may have application in the diagnosis of early cancer targeting ctDNAs.

Publication trend, resource utilization, and impact of the US National Cancer Database: A systematic review.

BACKGROUND: The utilization and impact of the studies published using the National Cancer Database (NCDB) is currently unclear. In this study, we aim to characterize the published studies, and identify relatively unexplored areas for future investigations. METHODS: A literature search was performed using PubMed in January 2017 to identify all papers published using NCDB data. Characteristics of the publications were extracted. Citation frequencies were obtained through the Web of Science. RESULTS: Three hundred 2 articles written by 230 first authors met the inclusion criteria. The number of publications grew exponentially since 2013, with 108 articles published in 2016. Articles were published in 86 journals. The majority of the published papers focused on digestive system cancer, while bone and joints, eye and orbit, myeloma, mesothelioma, and Kaposi Sarcoma were never studied. Thirteen institutions in the United States were associated with more than 5 publications. The papers have been cited for a total of 9858 times since the publication of the first paper in 1992. Frequently appearing keywords congregated into 3 clusters: "demographics," "treatments and survival," and "statistical analysis method." Even though the main focuses of the articles captured a extremely wide range, they can be classified into 2 main categories: survival analysis and characterization. Other focuses include database(s) analysis and/or comparison, and hospital reporting. CONCLUSION: The surging interest in the use of NCDB is accompanied by unequal utilization of resources by individuals and institutions. Certain areas were relatively understudied and should be further explored.