Based on the genomic information of Emericella sp. 1454, in conjunction with literature analysis of its secondary metabolite emestrin, this study identified the biosynthetic precursors of emestrin and enhanced its production by supplementing the culture medium with these precursors. In this study, it was found for the first time that the addition of biosynthetic precursor, reduced glutathione, to the culture medium significantly increased emestrin yield. By incorporating 1.5 g of reduced glutathione into 50 g of rice culture medium and fermenting for 15 days, a yield of 30.82 mg of emestrin was obtained, which marked an 11.71-fold increase compared to the original fermentation approach. The method is both simple and cost-effective, establishing a solid foundation for the efficient synthesis of emestrin and similar compounds. Additionally, it serves as an important reference for enhancing the production of other epipolythiodioxopiperazine compounds.

The phenylpropanoid pathway is one of the important pathways for synthesizing plant secondary metabolites, which can produce lignin, flavonoid, and sinapoylmalate. These compounds can not only affect the plant growth, development, and stress response, but also be used to produce perfume, pesticide, dye, medicine, feed, and biomass energy. R2R3-MYBs play important roles in regulating plant secondary metabolism, organ development, and in responding to environmental stresses. Wheat (Triticum aestivum L.) is an important food crop, but lots of straw will be produced accompanied by grain yields. Therefore, elucidating the function and regulatory mechanism of R2R3 MYBs of wheat is crucial for the effective utilization of the wheat straw. RT-PCR results showed that TaMYB1A was highly expressed in the wheat stems, and the GFP-TaMYB1A fusion protein was mainly localized in the nucleus of the N. benthamiana epidermal cells. TaMYB1A has transcriptional repressive activity in yeast cells. In this study, TaMYB1A-overexpressed transgenic Arabidopsis lines were generated to elucidate the effect of overexpression of TaMYB1A on the biosynthesis of lignin and flavonoid. Our results suggested that overexpression of TaMYB1A inhibited the plant height (P < 0. 05) and decreased the lignin (P < 0. 05) and flavonoid (P < 0. 05) biosynthesis of the transgenic Arabidopsis plants significantly. TaMYB1A could bind to the promoters of the Arabidopsis At4CL1, AtC4H, AtC3H, and AtCHS as well as the wheat Ta4CL1 and TaC4H1 revealed by yeast one-hybrid (Y1H) assasy, the transcriptional repressive effect of TaMYB1A on At4CL1, AtC4H, AtC3H, and AtCHS was confirmed by dual-luciferase reporter systems and also on Ta4CL1 and TaC4H1 by a genetic approach. Gene chip and quantitative RT-PCR (qRT-PCR) results showed that overexpression of TaMYB1A down-regulated the expression of most of the key genes involved in the phenylpropanoid metabolism and decreased the 4CL activity (P < 0. 05) of the transgenic Arabidopsis plants significantly. As suggested above, the wheat TaMYB1A belongs to the subgroup 4 R2R3 MYB transcription factors. TaMYB1A could bind to the promoters of the key genes involved in phenylpropanoid metabolism, repress their expression and negatively regulate the phenylpropanoid metabolism pathway and plant height.

Objective To explore the risk factors for renal injury in tumors patients treated with programmed death receptor-1(PD-1)inhibitor,and further construct a column chart model to predict the likelihood of renal injury in patients.Methods The present study is a single center retrospective analysis.447 patients with tumors treated with PD-1 inhibitors in the Third Affiliated Hospital of Soochow University between January 2018 and January 2021 were included and followed up until January 2022.Kidney injury was defined as acute kidney disease(AKD).All patients were divided into AKD group(n=71)and non-AKD group(n=376 according to whether PD-1 inhibitor associated with AKD development at the end of follow-up.Basic information,disease and medication situation,laboratory indicators,and the incidence of extrarenal immune related adverse events(irAEs)during follow-up period were compared between the two groups.Univariate and multivariate logistic regression models were used to identify independent risk factors for PD-1 inhibitor associated AKD.The present study randomly divided all samples(n=447)into training set(n=313)and validation set(n=134)in a 7:3 ratio,built nomogram prediction models in the training set according to the screened independent risk factors,drawn the receiver operating characteristic(ROC)curves to evaluate the discrimination of the models,drawn calibration curves to evaluate the calibration of the models,and drawn clinical decision curve analysis(DCA)to explore the clinical validity and benefit rate of the models.Results The combination of antibiotics,diabetes,hypertension,extrarenal irAEs and cystatin C(Cys C)in AKD group were significantly higher than those in non-AKD group(P<0.05),but hemoglobin(Hb)was significantly lower than that in non-AKD group(P<0.05).Single factor logistic regression analysis showed that combination of antibiotics,diabetes,hypertension,extrarenal irAEs,lower Hb,estimated glomerular filtration rate(eGFR),higher blood urea nitrogen(BUN),serum creatinine(SCr),Cys C,fasting blood glucose(FBG),and alanine transaminase(ALT)were risk factors for PD-1 inhibitor related AKD(P<0.05).Multivariate logistic regression analysis showed that concomitant extrarenal irAEs,lower Hb,higher SCr,and direct bilirubin(DBIL)were independent risk factors for PD-1 inhibitor associated AKD(P<0.05).Based on the independent risk factors mentioned above,a column chart prediction model was further established and validated.The results showed that the area under the ROC curve(AUC)of the training and validation sets of the model were 0.703(95%CI 0.628-0.777)and 0.791(95%CI 0.671-0.911),respectively,indicating good discrimination.The calibration curves of both the training and validation sets hover around the ideal line of 45°,indicating that the model has good calibration.DCA shows that the constructed model curve is far away from the two polar lines(the curve with a net benefit of 0 and the curve with all samples being positive),indicating that the model has good clinical benefits.Conclusion The combination of extrarenal irAEs,lower Hb,higher SCr,and higher DBIL are independent risk factors for the occurrence of PD-1 inhibitor related AKD;The established column chart model has good discrimination and calibration,which can provide guidance for clinical practice.

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.
Drugs, Chinese Herbal ; Analytic Hierarchy Process ; Berberine ; Entropy ; Water

BACKGROUND: Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis. METHODS: Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists. RESULTS: A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%). CONCLUSION The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.
Humans ; Female ; Male ; Arthritis, Psoriatic/epidemiology* ; Rheumatologists ; Prevalence ; East Asian People ; Psoriasis/epidemiology*

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Objective To explore whether metformin preconditioning can protect brain injury after cardiac arrest/cardiopulmonary resuscitation(CA/CPR)and its possible mechanisms and signaling pathways.Methods Constructed a CA model by using electrical stimulation.Rats were randomly divided into the sham group(0.9％NaCl gavage daily for 14 days,without inducing CA),model group(CA model was induced after 0.9％NaCl gavage daily for 14 days),experimental group(CA model was induced after 200 mg·kg-1 Met+0.9％NaCl gavage daily for 14 days),Cc group[200 mg·kg-1 Met+0.9％NaCl gavage daily for 14 days,adenosine 5'-monophosphate kinase-activated protein(AMPK)inhibitor Compoud C(Cc)was injected intraperitoneally at 1 hour before modeling],chloroquine(CQ)group(daily 200 mg·kg-1 Met+0.9％NaCl gavage for 14 days,intraperitoneal injection of autophagy inhibitor CQ at 1 hour before modeling)and AICAR group(continuous daily 200 mg·kg-1 Met+0.9％NaCl gavage for 14 days,intraperitoneal injection of AMPK agonist AICAR at 1 hour before modeling).The 7-day survival rate after CA/CPR via using survival curves was recorded;the neurological function 7-days after CA/CPR was scored by using the neurological disability scale;the protein malondialdehyde(MDA)level were measured using the Coomassie Brilliant Blue method;detection of reactive oxygen species(ROS)levels in brain tissue by using ROS fluorescent probe DHE;Western blotting was used to determine the expression levels of related proteins such as AMPK,p-AMPK,microtubule associated protein 1 light chain 3 Ⅰ(LC3 Ⅰ),LC3 Ⅱ,and p62 in brain tissue.Results The 7-day survival rates of sham,model,experimental,Cc,CQ and AICAR groups rats were 100％,40％,70％,40％,40％and 65％,respectively;the 7-day neurological function scores were 78.35±1.65,46.50±4.41,67.93±4.64,49.50±3.53,52.00±2.83 and 68.33±1.53,respectively;the ROS levels were(417.60±8.37),(748.60±36.05),(575.80±10.73),(713.80±18.85),(668.20±9.58)and(566.00±24.48)U·mg-1,respectively;the MDA levels were(4.38±0.33),(8.06±0.76),(5.50±0.48),(7.18±0.29),(6.82±0.31)and(5.20±0.34)nmol·mg-1,respectively;the brain tissue p-AMPK/AMPK were 0.74±0.04,0.87±0.01,1.61±0.01,0.55±0.05,1.09±0.09 and 1.27±0.07,respectively;the p62 values were 0.42±0.02,0.86±0.05,0.61±0.04,0.98±0.04 and 0.78±0.03,respectively;the LC3 Ⅱ/LC3 1 were 0.29±0.32,0.37±0.26,0.96±0.78,0.58±0.26,0.43±0.03 and 1.40±0.10,respectively.Compared with the model group,the differences of above indexes in the experimental group,AICAR group were statistically significant(all P＜0.05);compared with the experimental group,the differences of above indexes in the Cc group,CQ group were statistically significant(all P＜0.05).Conclusion Metformin preconditioning can play a protective role in brain injury after cardiac arrest/cardiopulmonary resuscitationin in rats by activating the AMPK signaling pathway,regulating mitochondrial energy metabolism and promoting autophagy.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases