Humans ; PPAR gamma/metabolism* ; Multiple Sclerosis ; Transcription Factors/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.

Objective:To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis.Methods:Using gene expression profile microarray,we identified highly ex-pressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR,immunohistochemistry,Western blot and immunofluorescence staining,and verified its function and molecular mechanism using bioinformatics analysis,dual-luciferase reporter assay and cell cycle synchronization.Results:The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks(PNW),increased from the 3rd PNW to sexual maturity,localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids,but was absent in the nuclei of mature sperm.Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals.Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation(normalized enrichment score[NES]=1.652,P＜0.01,false discov-ery rate[FDR]=0.153),meiosis(NES=1.960,P＜0.01,FDR=0.001)and formation of microtubule cytoskeleton during mitosis(NES=1.903,P＜0.01,FDR=0.009).Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation.Conclusion:The D930020B18Rik gene is expressed in the mouse testis in a time-and location-specific manner,highly associated with spermiogenesis,mainly localized in the nuclei of germ cells,and may be involved in the meiosis of spermatocytes and spermiogenesis.

Objective:To study the effect of a modified behavioral treatment(MBT)on functional anejaculation and analyze the factors influencing the therapeutic efficacy.Methods:We enrolled in this study 59 men aged 24-45 years visiting the Andrology Clinic of Shanghai First Maternity and Infant Hospital from August 2019 to May 2021 and complaining of aejaculation in sexual inter-course but normally ejaculating during masturbation.Thirty-nine of the patients underwent conventional behavioral treatment(the CBT group)and the other 20 received MBT,namely,changing the masturbation method combined with audiovisual stimulation during sexual intercourse(the MBT group).We compared the therapeutic effects between the two groups of patients,and analyzed the correlation of the outcomes of MBT with age,abstinence duration,use of audiovisual stimulation,change of the sexual position,mean bilateral testis volume and sex hormone levels.Results:After treatment,22(37.29％)of the patients achieved successful ejaculation at least once in sexual intercourse,11(55.00％)in the MBT group,and the other 11(28.21)in the CBT group,with a significantly higher effec-tiveness rate in the former than in the latter(P＜0.05).The effectiveness rate was significantly correlated to the method of standing-position masturbation plus sexual intercourse and reduction in the frequency of masturbation among various strategies of behavioral treat-ment(P＜0.05).Conclusion:MBT has a certain effect on functional anejaculation,and targeting the previous events of the patient is the key to the therapeutic efficacy.Further exploration of more effective strategies of behavioral treatment will become the trend of de-velopment in the management of functional anejaculation.

In mass spectrometry-based proteomics experiments,achieving high-throughput and efficientproteolytic digestion is crucial to ensure optimal protein cleavage and enhance the depth of protein identi-fication (including the number of identified proteins and the coverage of protein amino acid sequences) .Trypsin is the most widely used protease in mass spectrometry-based proteomics due to its ability to spe-cifically cleave the carboxyl terminus of arginine and lysine.However,it was found that Trypsin has some missed enzymatic efficiency for the cleavage of lysine residues.Therefore,in actual proteomics sample preparation,a combination of Trypsin and LysC will be used to ensure adequate cleavage of lysine resi-dues.Our study revealed that the commonly employed LysC-Trypsin tandem cleavage method exerts an impact on the enzymatic cleavage of protein samples by Trypsin due to the subsequent cleavage of Trypsin by initially added LysC.Consequently,we adjusted the order of LysC and Trypsin tandem digestion,with Trypsin cleavage being performed first followed by the addition of LysC to target any missed lysine resi-dues.We comprehensively compared and analyzed three distinct sequential digestion methods,namely Trypsin-Trypsin (T-T),LysC-Trypsin (L-T),and Trypsin-LysC (T-L),in terms of their effects on pro-tein sample preparation quality.The results demonstrated that the Trypsin-LysC sequential digestion ap-proach not only minimizes missed protein lysine/arginine cleavage sites without increasing experimental costs,at the same time yielding peptides with a moderate amino acid sequence length.The use of Tryp-sin-LysC digestion enhances the adsorption and separation of peptide samples in RP-HPLC,as well as improves the depth of protein detection and amino acid sequence coverage during tandem mass spectrome-try analysis.This research work offers a novel technical solution and serves as a valuable reference for proteome sample preparation.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Exosomes are nanoscale extracellular vesicles that are secreted by a variety of cells in the body. They carry particular miRNA, protein molecules, transcription factors, and other information molecules, and they play a role in the pathophysiological regulation of a number of diseases in the body. Exosomes can persist steadily in biological tissues and bodily fluids. Exosomes have quickly advanced in ophthalmology in recent years due to the extensive studies of exosomes in a variety of fields, such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, corneal disease, glaucoma, and other diseases. The number of people who are blind caused by diabetic retinopathy is rising as living standards rise. However, it is still unclear how diabetic retinopathy works. In recent years, many studies have found that exosomes play an important role in diabetic retinopathy. In this paper, the most recent developments in exosome studies as they relate to the pathogenesis and progression of diabetic retinopathy are reviewed.

Shegan Mahuang Decoction has been used in clinical practice for thousands of years, and is a classical formula for treating asthma and other respiratory diseases, with the effects of ventilating lung, dispersing cold, and relieving cough and asthma. This paper summarized the history, clinical application and mechanism of Shegan Mahuang Decoction, and predicted its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggested that irisflorentin, tectoridin, tectorigenin, irigenin, ephedrine, pseudoephedrine, asarinin, methyleugenol, shionone, epifriedelanol, tussilagone, 6-gingerol, trigonelline, cavidine, schizandrin, and schizandrin B could be used as Q-markers of Shegan Mahuang Decoction, which provided a basis for the quality control and subsequent research and development of Shegan Mahuang Decoction.
Humans ; Ephedra sinica ; Drugs, Chinese Herbal/pharmacology* ; Asthma/drug therapy* ; Lung ; Cough/drug therapy*