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1.
Angew Chem Int Ed Engl ; 62(32): e202307447, 2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37316685

ABSTRACT

Asymmetric cross-couplings based on 1,2-carbon migration from B-ate complexes have been developed efficiently to access valuable organoboronates. However, enantioselective reactions triggered by 1,2-boron shift have remained to be unaddressed synthetic challenge. Here, Ir-catalyzed asymmetric allylic alkylation enabled by 1,2-boron shift was developed. In this reaction, we disclosed that excellent enantioselectivities were achieved through an interesting dynamic kinetic resolution (DKR) process of allylic carbonates at the elevated temperature. Notably, the highly valuable (bis-boryl)alkenes have enabled an array of diversifications to access versatile molecules. Extensive experimental and computational studies were conducted to elucidate the reaction mechanism of DKR process and clarify the origin of excellent enantioselectivities.

2.
Proc Natl Acad Sci U S A ; 120(5): e2214684120, 2023 01 31.
Article in English | MEDLINE | ID: mdl-36693099

ABSTRACT

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.


Subject(s)
Progesterone , Receptors, Progesterone , Female , Mice , Humans , Animals , Progesterone/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Embryo Implantation/genetics , Uterus/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Mice, Knockout , RNA, Messenger/metabolism
3.
Medicine (Baltimore) ; 100(41): e27249, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34731102

ABSTRACT

BACKGROUND: Temporal lobe epilepsy is a group of neurological diseases caused by the repeated abnormal discharge of brain neurons. Patients with this disease are often accompanied with cognitive impairment. However, the pathogenesis of the cognitive impairment remains unclear. Resting state functional magnetic resonance imaging is a kind of magnetic resonance imaging method based on blood oxygen level dependence. This can reflect the spontaneous brain functional activity of a human brain in the resting state. In recent years, a number of researchers have used resting state functional magnetic resonance imaging to study the changes in resting spontaneous brain function in patients with temporal lobe epilepsy with cognitive impairment (TLE-CI). However, due to the differences in sample and methodology, the results of these studies were inconsistent. Therefore, the present study aimed to investigate the characteristics of the resting spontaneous brain function in patients with TLE-CI through a meta-analysis. METHODS: A search was conducted on electronic databases, including PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, WANGFANG DATA and Chinese Biomedical Literature Database, and Baidu scholar Database, from the establishment of the database to April 20, 2021. Randomized controlled trials that employed amplitude of low-frequency fluctuations/regional homogeneity to investigate the changes in resting spontaneous brain function in patients with TLE-CI were selected. Anisotropic effect size version of signed differential mapping was applied to perform the data analysis. RESULTS: The study summarized the changes in spontaneous brain function in patients with TLE-CI. CONCLUSION: The conclusion for the functional cerebral alterations based on the latest studies will be provided.


Subject(s)
Brain/physiopathology , Cognitive Dysfunction/diagnostic imaging , Epilepsy, Temporal Lobe/diagnostic imaging , Brain/diagnostic imaging , Cognitive Dysfunction/complications , Epilepsy, Temporal Lobe/complications , Humans , Magnetic Resonance Imaging/methods , Meta-Analysis as Topic , Systematic Reviews as Topic
4.
Medicine (Baltimore) ; 100(6): e24573, 2021 Feb 12.
Article in English | MEDLINE | ID: mdl-33578555

ABSTRACT

BACKGROUND: Diabetic neurogenic bladder (DNB) is one of the common complications of diabetes mellitus, which has a high prevalence rate. Some research suggested that acupuncture can improve the clinical symptoms of diabetic neurogenic bladder patients, but there is no systematic review or meta-analysis to assess this therapy. Therefore, this study aims to explore the effectiveness and safety of acupuncture for patients with DNB. METHODS: In this study, we will search for electronic databases including the Cochrane Library, Web of Science, PubMed, MEDLINE, EMBASE,China National Knowledge Infrastructure (CNKI), Wan-Fang, and Baidu Scholar Database from inception to December 2020. We will select randomized controlled trials that have been published in English or Chinese related to acupuncture for DNB. Selection of study, extraction of data, and assessment of study quality will be performed independently by 2 researchers, and we will use Revman 5.3 software which is provided by Cochrane assistance network, to perform the data analysis. RESULTS: This study will provide evidence of the effectiveness and safety of acupuncture for DNB. CONCLUSION: This study will clarify whether acupuncture is an effective treatment for DNB, and will also provide a reference for clinical practice and guidelines development.


Subject(s)
Acupuncture Therapy , Diabetes Complications/therapy , Urinary Bladder, Neurogenic/therapy , Humans , Meta-Analysis as Topic , Systematic Reviews as Topic
5.
J Int Med Res ; 48(11): 300060520974927, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33259238

ABSTRACT

OBJECTIVE: To determine the level and influencing factors of informal caregiver burden in gynaecological oncology inpatients receiving chemotherapy. METHODS: This cross-sectional study enrolled gynaecological oncology patients and their informal caregivers between May 2018 and November 2018 and measured the caregivers' burden using the Caregiver Burden Inventory. The influencing factors were evaluated with univariate regression analysis and multivariate linear stepwise regression analysis. RESULTS: A total of 138 patients and their informal caregivers completed the questionnaire. The mean ± SD total informal caregiver burden score was 53.18 ± 10.97. The highest mean ± SD score was recorded in the dimension of time-dependent burden (14.28 ± 2.74), followed by developmental burden (13.65 ± 2.15), physical burden (10.52 ± 2.07), social burden (7.61 ± 2.58) and emotional burden (7.12 ± 1.43). Multivariate analysis showed that the informal caregiver's sex, relationship to the patient, daily duration of care, presence of chronic health problems and the duration of the patient's disease were factors influencing the level of caregiver burden. CONCLUSIONS: The informal caregivers of gynaecological cancer patients hospitalized for chemotherapy experience a moderate level of burden. Nursing measures should be considered to reduce informal caregiver burden and improve the quality of lives of both patients and their caregivers.


Subject(s)
Caregiver Burden , Caregivers , Cross-Sectional Studies , Emotions , Female , Humans , Surveys and Questionnaires
6.
RSC Adv ; 9(11): 5995-6002, 2019 Feb 18.
Article in English | MEDLINE | ID: mdl-35517262

ABSTRACT

A series of AuPd/C catalysts were prepared and tested for the first time for active and stable dehydrogenation of a formic acid-ammonium formate (FA-AF) mixture. The catalysts with different Au-to-Pd molar ratios were prepared using a facile simultaneous reduction method and characterized using transmission electron microscopy (TEM), high-resolution TEM, energy dispersive X-ray spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. It was found that the catalytic activity and stability of the Au3Pd1/C catalyst was the best. The initial turnover frequency for the dehydrogenation of the FA-AF mixture over the Au3Pd1/C catalyst can reach 407.5 h-1 at 365 K. The reaction order with respect to FA and AF is 0.25 and 0.55, respectively. The apparent activation energy of dehydrogenation is 23.3 ± 1.3 kJ mol-1. The catalytic activity of the Au3Pd1/C catalyst remains ca. 88.0% after 4 runs, which is much better than the single Pd/C catalyst. The mechanism for the dehydrogenation is also discussed.

7.
Yao Xue Xue Bao ; 51(6): 843-52, 2016 06.
Article in Chinese | MEDLINE | ID: mdl-29878736

ABSTRACT

The international cooperated research projects of the Human Microbiome Project (HMP) and Metagenomics of The Human Intestinal Tract (MetaHIT) were officially launched in 2007, which indicated the era of metagenomics research of microorganisms in human gastrointestinal tract had been coming. Each human body is a superorganism which is composed of 90% commensal microorganisms, especially the intestinal microorganisms. The intestinal microorganisms play an important role on health maintenance since they are involved in the absorption and metabolism of nutrients in the human bodies. Herein, we review the research progress in the mechanism of intestinal microorganisms in human diseases. Our purpose is to provide novel ideas on human health and therapeutic targets of diseases.


Subject(s)
Gastrointestinal Microbiome , Intestines/microbiology , Metagenomics , Humans , Symbiosis
8.
Zhongguo Zhong Yao Za Zhi ; 41(10): 1766-1772, 2016 May.
Article in Chinese | MEDLINE | ID: mdl-28895319

ABSTRACT

A large number and wide varieties of microorganisms colonize in the human gastrointestinal tract. They construct an intestinal microecological system in the intestinal environment. The intestinal symbiotic flora regulates a series of life actions, including digestion and absorption of nutrient, immune response, biological antagonism, and is closely associated with the occurrence and development of many diseases. Therefore, it is greatly essential for the host's health status to maintain the equilibrium of intestinal microecological environment. After effective compositions of traditional Chinese medicines are metabolized or biotransformed by human intestinal bacteria, their metabolites can be absorbed more easily, and can even decrease or increase toxicity and then exhibit significant different biological effects. Meanwhile, traditional Chinese medicines can also regulate the composition of the intestinal flora and protect the function of intestinal mucosal barrier to restore the homeostasis of intestinal microecology. The relevant literatures in recent 15 years about the interactive relationship between traditional Chinese medicines and gut microbiota have been collected in this review, in order to study the classification of gut microflora, the relationship between intestinal dysbacteriosis and diseases, the important roles of gut microflora in intestinal bacterial metabolism in effective ingredients of traditional Chinese medicines and bioactivities, as well as the modulation effects of Chinese medicine on intestinal dysbacteriosis. In addition, it also makes a future prospect for the research strategies to study the mechanism of action of traditional Chinese medicines based on multi-omics techniques.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Gastrointestinal Microbiome/drug effects , Medicine, Chinese Traditional , Dysbiosis/drug therapy , Humans , Intestinal Mucosa/drug effects , Intestines/microbiology
9.
Chin J Nat Med ; 13(1): 3-21, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25660284

ABSTRACT

In the post-genomic era, biological studies are characterized by the rapid development and wide application of a series of "omics" technologies, including genomics, proteomics, metabolomics, transcriptomics, lipidomics, cytomics, metallomics, ionomics, interactomics, and phenomics. These "omics" are often based on global analyses of biological samples using high through-put analytical approaches and bioinformatics and may provide new insights into biological phenomena. In this paper, the development and advances in these omics made in the past decades are reviewed, especially genomics, transcriptomics, proteomics and metabolomics; the applications of omics technologies in pharmaceutical research are then summarized in the fields of drug target discovery, toxicity evaluation, personalized medicine, and traditional Chinese medicine; and finally, the limitations of omics are discussed, along with the future challenges associated with the multi-omics data processing, dynamics omics analysis, and analytical approaches, as well as amenable solutions and future prospects.


Subject(s)
Biomedical Research/methods , Genomics , Metabolomics , Pharmacology , Proteomics , Gene Expression Profiling
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(8): 2092-5, 2013 Aug.
Article in Chinese | MEDLINE | ID: mdl-24159853

ABSTRACT

The wool and cashmere samples (n = 130) from different areas of Gansu province were identified by visible and near-infrared reflectance spectroscopy (Vis/NIRs). The result shows that principal component-mahalanobis distance pattern can identify the wool and cashmere, and the boundary between two categories was clear; The calibration set samples were used to establish calibration qualitative model using PCR combined with the best pretreatment of the spectra and math, including multivariate scattering correction (MSC), first derivative, eight for the best principal component factor, one for uncertainty factor, this calibration model of the predicted was the best, and the result of the external validation was correct completely. Results from this experiment indicate that Vis/NIRs can be utilized to identify the wool and cashmere.


Subject(s)
Spectroscopy, Near-Infrared/methods , Wool/chemistry , Animals , Calibration , Goats , Principal Component Analysis , Quality Control , Sheep
11.
Burns ; 36(7): 992-8, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20537801

ABSTRACT

INTRODUCTION: Early diagnosis and treatment for thermal injury with septic complications continue to be a serious clinical problem. In this study, plasma biomarkers of rats in the burn and/or septic models were investigated with a metabolomic method. METHODS: Rat plasma samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Multivariate analysis, the principal components analysis (PCA), was used to validate metabolic changes. In addition, another multivariate method, the orthogonal partial least-squares analysis (OPLS), was used to profile potential biomarkers in models. RESULTS: Nine characteristic metabolites, including hypoxanthine, indoxyl sufate, glucuronic acid, gluconic acid, proline, uracil, nitrotyrosine, uric acid, and trihydroxy cholanoic acid were identified in models of thermal injury and/or sepsis. CONCLUSION: These biomarkers were mainly involved in oxidative stress and tissue damage, and might supply evidence for distinguishing burned septic patients from non-septic ones.


Subject(s)
Burns/blood , Sepsis/blood , Amino Acids/blood , Animals , Biomarkers/blood , Carboxylic Acids/blood , Chromatography, High Pressure Liquid/methods , Disease Models, Animal , Heterocyclic Compounds/blood , Male , Mass Spectrometry , Metabolomics/methods , Rats , Rats, Sprague-Dawley , Sepsis/diagnosis
12.
Int J Cancer ; 127(12): 2841-50, 2010 Dec 15.
Article in English | MEDLINE | ID: mdl-21351263

ABSTRACT

The prediction of chemosensitivity is a challenging problem in the management of cancer. In the present study, a metabonomic approach was proposed to assess the feasibility of chemosensitivity prediction in a human xenograft model of gastric cancer. BALB/c-nu/nu mice were transplanted with MKN-45 cell line to establish the xenograft model. The mice were then randomized into treatment group (cisplatin and 5-fluorouracil) and control group (0.9% sodium chloride), and their plasma were collected before treatment. Metabolic profiles of all plasma samples were acquired by using high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer (HPLC/Q-TOF-MS). Based on the data of metabolic profiles and k-Nearest Neighbor algorithm, a prediction model for chemosensitivity was developed and an average accuracy of 90.4% was achieved. In addition, a series of endogenous metabolites, including 1-acyl-lysophosphatidycholines, polyunsaturated fatty acids and their derivatives, were determined as potential indicators of chemosensitivity. In conclusion, our results suggest that the proposed metabonomic approach allows effective chemosensitivity prediction in human xenograft model of gastric cancer. The approach presents a new concept in the chemosensitivtiy prediction of cancer and is expected to be developed as a powerful tool in the personalized cancer therapy.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Drug Resistance, Neoplasm/drug effects , Metabolomics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Adenocarcinoma/pathology , Animals , Biomarkers, Tumor/metabolism , Cisplatin/administration & dosage , Fluorouracil/administration & dosage , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Stomach Neoplasms/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
13.
Bioorg Med Chem ; 18(2): 744-54, 2010 Jan 15.
Article in English | MEDLINE | ID: mdl-20022253

ABSTRACT

Twenty-five new (abiesadines A-Y, 1-25) and 29 known (26-54) diterpenes were isolated from the aerial parts of Abies georgei. Abiesadine A (1) is a novel 8,14-seco-abietane, while abiesadine B (2) is a novel 9,10-seco-abietane. The structures of the new compounds were established on the basis of spectroscopic data analysis. Manool (52) showed the strongest effect against LPS-induced NO production in RAW264.7 macrophages with the IC(50) value of 11.0microg/mL. In another anti-inflammatory assay against TNFalpha-triggered NF-kappaB activity, (12R,13R)-8,12-epoxy-14-labden-13-ol (54) exhibited the strongest effect (IC(50)=8.7microg/mL). For antitumor assays, pomiferin A (26) and 8,11,13-abietatriene-7alpha,18-diol (29) both showed the most significant activity against LOVO cells (IC(50)=9.2microg/mL). While 7-oxocallitrisic acid (46) exhibited significant cytotoxicity against QGY-7703 tumor cells (IC(50)=10.2microg/mL).


Subject(s)
Abies/chemistry , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Diterpenes/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Diterpenes/chemistry , Diterpenes/isolation & purification , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Stereoisomerism , Structure-Activity Relationship
14.
Eur J Pharmacol ; 615(1-3): 61-5, 2009 Aug 01.
Article in English | MEDLINE | ID: mdl-19358840

ABSTRACT

Peripheral nerve injury, which gives rise to persistent chronic pain, has become an area of intense research activity, largely because it represents a disorder with a high unmet medical need. In this study, serum biomarkers of the spinal nerve ligation model were successfully investigated with the metabolomic method. The regulatory effect of gabapentin, a novel clinical antineuralgia drug, on biomarker levels in serum was also investigated. Rat serum extract samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A method of supervised multivariate analysis, the partial least squares-discrimination analysis (PLS-DA), was used to validate metabolic changes. In addition, another multivariate method, the orthogonal partial least-squares analysis (OPLS), was used to monitor the real biological variability and to detect potential biomarkers in the spinal nerve ligation model. The results demonstrated that the spinal nerve ligation model had several discriminating ions compared with the control model. Among the detectable metabolites, levels of norepinephrine were increased in the spinal nerve ligation model and were decreased to control levels by gabapentin.


Subject(s)
Amines/pharmacology , Analgesics/pharmacology , Biomarkers/blood , Cyclohexanecarboxylic Acids/pharmacology , Peripheral Nervous System Diseases/blood , Spinal Nerves/injuries , gamma-Aminobutyric Acid/pharmacology , Animals , Chromatography, High Pressure Liquid , Disease Models, Animal , Gabapentin , Injections, Intraperitoneal , Ligation , Male , Metabolomics , Multivariate Analysis , Norepinephrine/blood , Peripheral Nervous System Diseases/etiology , Rats , Rats, Sprague-Dawley , Serum , Tandem Mass Spectrometry
15.
NMR Biomed ; 22(6): 601-8, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19322815

ABSTRACT

This study proposes an NMR-based metabonomic approach to early prognostic evaluation of sepsis. Forty septic rats receiving cecal ligation and puncture (CLP) were divided into the surviving group and nonsurviving group on day 6, while 20 sham-operated rats served as the control group. Serum samples were collected from septic and sham-operated rats at 12 h after surgery and analyzed using (1)H NMR spectroscopy. Orthogonal partial least squares (OPLS) were applied and showed clustering according to predefined groups, indicating that NMR-based metabolic profiling could reveal pathologic characteristics in the serum of sham-operated, surviving, and nonsurviving septic rats. In addition, six characteristic metabolites including lactate, alanine, acetate, acetoacetate, hydroxybutyrate, and formate, which are mainly involved in energy metabolism, changed markedly in septic rats, especially in the nonsurvivors. Using these metabolites, a predictive model for prognostic evaluation of sepsis was constructed using a radial basis function neural network (RBFNN) with a prediction accuracy of about 87% by test samples. The results indicated that the NMR-based metabonomic approach is a potential technique for the early prognostic evaluation of sepsis.


Subject(s)
Metabolomics/methods , Nuclear Magnetic Resonance, Biomolecular , Sepsis , Animals , Humans , Male , Prognosis , Random Allocation , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity , Sepsis/diagnosis , Sepsis/metabolism , Sepsis/physiopathology , Serum/chemistry , Serum/metabolism , Survival Rate
16.
J Infect ; 56(6): 474-81, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18471887

ABSTRACT

OBJECTIVES: Early prognostic evaluation of sepsis is an attractive strategy to decrease the mortality of septic patients, but presently there are no satisfactory approaches. Our goal is to establish an early, rapid and efficient approach for prognostic evaluation of sepsis. METHODS: Forty-five septic rats, induced by cecal ligation and puncture, were divided into surviving (n=23) and nonsurviving group (n=22) on day 6. Serum samples were obtained from septic and sham-operated rats (n=25) at 12h after surgery. HPLC/MS assays were performed to acquire serum metabolic profiles, and radial basis function neural network (RBFNN) was employed to build predictive model for prognostic evaluation of sepsis. RESULTS: Principle component analysis allows a clear discrimination of the pathologic characteristics among rats from surviving, nonsurviving and sham-operated groups. Six metabolites related to the outcome of septic rats were then structurally identified, which included linolenic acid, linoleic acid, oleic acid, stearic acid, docosahexaenoic acid and docosapentaenoic acid. A RBFNN model was built upon the metabolic profile data from rat serum, and a high predictive accuracy over 94% was achieved. CONCLUSIONS: HPLC/MS-based metabonomic approach combined with pattern recognition permits accurate outcome prediction of septic rats in the early stage. The proposed approach has advantages of rapid, low-cost and efficiency, and is expected to be applied in clinical prognostic evaluation of septic patients.


Subject(s)
Metabolism/physiology , Sepsis/metabolism , Animals , Chromatography, High Pressure Liquid , Male , Mass Spectrometry , Principal Component Analysis , Prognosis , Random Allocation , Rats , Rats, Sprague-Dawley , Sepsis/blood , Specific Pathogen-Free Organisms
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