[Association of serum irisin levels with glucose and lipid metabolism among adolescents in Yinchuan City from 2017 to 2020].

OBJECTIVE: To explore the relationship between serum irisin levels and glucose and lipid metabolism among adolescents in Yinchuan City. METHODS: From 2017 to 2020, a conbination of convenient sampling and stratified cluster random sampling method were used to select 1219 adolescents aged 12 to 18 years old in Yinchuan City as research subjects. The height and weight were measured using the height and sitting height meter and the bioelectrical impedance analyzer. Blood indicators such as fasting plasma glucose(FPG), totalcholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were measured using fully automatic biochemical analyzer. Serum irisin levels were measured by enzyme-linked immunosorbent assay(ELISA). Binary logistic regression was used to analyze the correlation between irisin and abnormal glucose and lipid metabolism. RESULTS: The FPG, TC, HDL-C and LDL-C levels of subjects in the highest tertile of irisin levels were significantly lower than those of subjects in the lowest tertile of irisin levels(F values were 5.13, 3.15, 3.07 and 5.01, P<0.05), and the differences were statistically significant(all P<0.05). The serum irisin levels in the hyperglycemia group(t=2.87, P<0.01), hypercholesterolemia group(t=2.36, P=0.02) and hyperLDL-Cemia group(t=2.34, P=0.02) were significantly lower than those in the normoglycemia group, normal TC group and normal LDL-C group. Meanwhile, the irisin level in the low HDL-Cemia group(t=-2.57, P=0.01) was significantly higher than that in the normal HDL-C group, and the differences were statistically significant(P<0.05). Participants in the highest tertile of irisin had 0.51, 0.49 and 0.50 times the risk of hyperglycemia(OR=0.51, 95%CI 0.29-0.87), hypercholesterolemia(OR=0.49, 95%CI 0.27-0.89) and hyperLDL-cemia(OR=0.50, 95%CI 0.25-0.99) compared with those in the lowest tertile. CONCLUSION: Low levels of irisin are associated with the occurrence of hyperglycemia, hypercholesterolemia, and hyperLDL-Cemia in adolescents.

The significance of extensive HPV genotyping for cervical high-grade neoplasia among women with atypical glandular cells.

OBJECTIVES: To examine the associated risk of cervical intraepithelial neoplasm grade 3+ (CIN3+) lesions in patients with AGC and extensive human papillomavirus (HPV) genotyping. METHODS: Cases with atypical glandular cell (AGC) interpretation on a Papanicolaou (Pap) test were identified along with associated extensive HPV genotyping and histologic follow-up results. RESULTS: Within this cohort of 469,694 Pap tests, 0.4% were diagnosed as AGCs. In total, 1267 cases had concurrent high-risk HPV (hrHPV) genotyping, and 40.3% were hrHPV positive. The percentage of AGC cases with cervical CIN3+ on histologic follow-up was 52.2% when hrHPV was positive, whereas it was 4.9% with a negative hrHPV result. The top 5 hrHPV genotypes associated with cervical CIN3+ in this cohort were HPV16, HPV18, HPV58, HPV52, and HPV33. Indeed, 92.8% of the hrHPV-associated CIN3+ lesions identified in this cohort were positive for at least one of these HPV genotypes. The sensitivity of detecting cervical CIN3+ lesions was 85.6% with the top 5 hrHPV genotypes (HPV16/18/58/52/33) and only increased to 89.0% when the additional 12 genotypes were included. CONCLUSIONS: In patients with an AGC Pap, the risk of having a cervical CIN3+ lesion is greatly increased by positivity for hrHPV types 16, 18, 58, 52, and/or 33. Incorporating comprehensive HPV genotyping into AGC cytology allows for refined risk stratification and more tailored management strategies.

Supplementation of diethyl aminoethyl hexanoate for enhancing antibiotics removal by different microalgae-based system.

With the growth of the aquaculture industry, antibiotic residues in treated wastewater have become a serious ecological threat. The effects of supplementation with diethyl aminoethyl hexanoate (DA-6) on the removal of tetracycline (TC), ciprofloxacin (CPFX), and sulfamonomethoxine (SMM) from aquaculture wastewater by different microalgae-based systems were examined and systematically analyzed. The results demonstrated that C. vulgaris -S395-2-C. rosea symbiont performed best under 0.2 mg L-1 antibiotic treatment for antibiotic removal. At 10-7 M, DA-6 significantly enhanced C. vulgaris-S395-2-C. rosea symbiont removal of CPFX and SMM at 0.20 mg L-1. The removal of TC, CPFX and SMM by this strain under optimal conditions was 99.2 ± 0.4 %, 86.3 ± 6.3 %, and 91.3 ± 5.7 %, respectively. These results suggest that DA-6 may act on microalgae-bacteria-fungi three-phase symbionts for the removal of multiple antibiotics from aquaculture wastewater.

The regulatory role of m6A modification in the maintenance and differentiation of embryonic stem cells.

As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs, N 6-methyladenosine (m6A) post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes. m6A modification is regulated by m6A writers, erasers, and readers. Emerging evidence suggests that m6A modification plays essential roles in modulating the cell-fate transition of embryonic stem cells. Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development, which is also the premise for the application of embryonic stem cells in regenerative medicine. This review highlights the current knowledge of m6A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.

Dyadic effects of financial toxicity and social support on the fear of cancer recurrence in breast cancer patients and caregivers: an actor-partner interdependence mediation model.

PURPOSE: In this study, the actor-partner interdependence mediation model (APIMeM) was applied to breast cancer patients and their caregivers to assess the factors that affect the fear of cancer recurrence. In particular, the purpose of this study was to evaluate the mediating effect of social support on financial toxicity and the fear of cancer recurrence, providing an effective basis for developing plans to reduce the level of fear of cancer recurrence. METHODS: This study employed a cross-sectional design, and 405 dyads of breast cancer patients and their caregivers were enrolled. Financial toxicity, social support, and fear of cancer recurrence were assessed by computing comprehensive scores for financial toxicity based on patient-reported outcome measures, the Social Support Rating Scale, and the Fear of Cancer Recurrence Inventory Short Form, respectively. The data were analysed using SPSS 24.0 and AMOS 23.0. RESULTS: The results showed that the fear of cancer recurrence of breast cancer patients and their caregivers was significantly related to dyadic financial toxicity and social support. In addition, the financial toxicity of breast cancer patients and their caregivers had significant actor effects and partner effects on the fear of cancer recurrence through dyadic social support. CONCLUSIONS: The financial toxicity of breast cancer patients and their caregivers could produce actor and partner effects on the fear of cancer recurrence through the mediation of social support, which provided empirical support for improving reducing the level of fear of cancer recurrence among patients and caregivers at the dyadic level.

Impact of high fat and low lean mass phenotype on bone mineral content: A cross-sectional study of Chinese adolescent population.

BACKGROUND AND OBJECTIVE: Research on body composition phenotypes and bone health in adolescents is limited. Hence, this study aimed to analyze the relationship between different body composition phenotypes, bone mineral content, and bone metabolism markers in Chinese adolescents. METHODS: In this cross-sectional study, 1852 adolescents aged 12 to 18 years were selected from six schools in Yinchuan City between 2017 and 2020 using stratified cluster random sampling. The participant's body composition and bone mineral content (BMC) were measured using bioelectrical impedance analysis (BIA). Serum bone metabolic markers (OC, CTX, and Ca) were measured. Based on their FMI and LMI, individuals were categorized into four body composition phenotypes: low fat mass-low lean mass (LFMI-LLMI), low fat mass-high lean mass (LFMI-HLMI), high fat mass-high lean mass (HFMI-HLMI), high fat mass-low lean mass (HFMI-LLMI). RESULTS: There was a statistically significant difference between the four different body composition phenotypes with BMC, CTX and Ca in boys (all P < 0.05), similar conclusions were found in girls, except the OC and CTX. After adjusting for age, gender, smoking, drinking, and others, compared with the LFMI-HLMI reference group, the two high FMI groups (HFMI-LLMI and HFMI-HLMI) had a greater negative correlation with BMC, while the low BMC risk of the HFMI-LLMI group was the highest (OR = 33.28; 95%CI: 11.12-99.63; P < 0.001). The correlation between BMC of different body composition phenotypes in boys was greater than that in girls. HFMI-HLMI is a risk phenotype negatively associated with Ca content (ß = -0.12; 95%CI: -0.19 to -0.04; P < 0.05). Regardless of body composition level, BMC was always negatively correlated with fat mass (LLMI: ß = -0.27; 95%CI: -0.32-0.21; HLMI: ß = -0.52, 95%CI: -0.65-0.40) and positively correlated with lean mass (LFMI: ß =0.24; 95%CI: 0.20-0.28; HFMI: ß =0.23, 95%CI:0.13-0.33) (all P < 0.001). The fat mass showed different correlations with OC and CTX in girls and boys based on LLMI or HLMI (all P < 0.05). CONCLUSION: HFMI-LLMI is a risk phenotype of low BMC in Chinese adolescents, and the relationship between fat mass and bone metabolism markers is affected by lean body mass and gender.

Microfluidic Mechanoporation: Current Progress and Applications in Stem Cells.

Intracellular delivery, the process of transporting substances into cells, is crucial for various applications, such as drug delivery, gene therapy, cell imaging, and regenerative medicine. Among the different approaches of intracellular delivery, mechanoporation stands out by utilizing mechanical forces to create temporary pores on cell membranes, enabling the entry of substances into cells. This method is promising due to its minimal contamination and is especially vital for stem cells intended for clinical therapy. In this review, we explore various mechanoporation technologies, including microinjection, micro-nano needle arrays, cell squeezing through physical confinement, and cell squeezing using hydrodynamic forces. Additionally, we highlight recent research efforts utilizing mechanoporation for stem cell studies. Furthermore, we discuss the integration of mechanoporation techniques into microfluidic platforms for high-throughput intracellular delivery with enhanced transfection efficiency. This advancement holds potential in addressing the challenge of low transfection efficiency, benefiting both basic research and clinical applications of stem cells. Ultimately, the combination of microfluidics and mechanoporation presents new opportunities for creating comprehensive systems for stem cell processing.

Prediction of high-level fear of cancer recurrence in breast cancer survivors: An integrative approach utilizing random forest algorithm and visual nomogram.

PURPOSE: This study is the first attempt to use a combination of regression analysis and random forest algorithm to predict the risk factors for high-level fear of cancer recurrence and develop a predictive nomogram to guide clinicians and nurses in identifying high-risk populations for high-level fear of cancer recurrence. METHODS: After receiving various recruitment strategies, a total of 781 survivors who had undergone breast cancer resection within 5 years in four Grade-A hospitals in China were included. Besides demographic and clinical characteristics, variables were also selected from the perspectives of somatic, cognitive, psychological, social and economic factors, all of which were measured using a scale with high reliability and validity. This study established univariate regression analysis and random forest model to screen for risk factors for high-level fear of cancer recurrence. Based on the results of the multi-variable regression model, a nomogram was constructed to visualize risk prediction. RESULTS: Fatigue, social constraints, maladaptive cognitive emotion regulation strategies, meta-cognition and age were identified as risk factors. Based on the predictive model, a nomogram was constructed, and the area under the curve was 0.949, indicating strong discrimination and calibration. CONCLUSIONS: The integration of two models enhances the credibility of the prediction outcomes. The nomogram effectively transformed intricate regression equations into a visual representation, enhancing the readability and accessibility of the prediction model's results. It aids clinicians and nurses in swiftly and precisely identifying high-risk individuals for high-level fear of cancer recurrence, enabling the development of timely, predictable, and personalized intervention programs for high-risk patients.

Polysaccharide from Boletus aereus ameliorates DSS-induced colitis in mice by regulating the MANF/MUC2 signaling and gut microbiota.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions characterized by disruptions in the colonic mucus barrier and gut microbiota. In this study, a novel soluble polysaccharide obtained from Boletus aereus (BAP) through water extraction was examined for its structure. The protective effects of BAP on colitis were investigated using a DSS-induced mice model. BAP was found to promote the expression of intestinal mucosal and tight junction proteins, restore the compromised mucus barrier, and suppress the activation of inflammatory signaling. Moreover, BAP reshape the gut microbiota and had a positive impact on the composition of the gut microbiota by reducing inflammation-related microbes. Additionally, BAP decreased cytokine levels through the MANF-BATF2 signaling pathway. Correlation analysis revealed that MANF was negatively correlated with the DAI and the level of cytokines. Furthermore, the depletion of gut microbiota using antibiotic partially inhabited the effect of BAP on the activation of MANF and Muc2, indicating the role of gut microbiota in its protective effect against colitis. In conclusion, BAP had an obvious activation on MANF under gut inflammation. This provides new insights into the prospective use of BAP as a functional food to enhance intestinal health.

Lipidomic and transcriptomic analysis of the increase in eicosapentaenoic acid under cobalamin deficiency of Schizochytrium sp.

Schizochytrium sp. is a heterotrophic microorganism capable of accumulating polyunsaturated fatty acids and has achieved industrial production of docosahexaenoic acid (DHA). It also has the potential for eicosapentaenoic acid (EPA) production. In this study, it was found that the cell growth, lipid synthesis and fatty acid composition of Schizochytrium sp. were significantly affected by the level of cobalamin in the medium, especially with regard to the content of EPA in the fatty acids. The content of EPA in the fatty acids increased 17.91 times, reaching 12.00%, but cell growth and lipid synthesis were significantly inhibited under cobalamin deficiency. The response mechanism for this phenomenon was revealed through combined lipidomic and transcriptomic analysis. Although cell growth was inhibited under cobalamin deficiency, the genes encoding key enzymes in central carbon metabolism were still up-regulated to provide precursors (Acetyl-CoA) and reducing power (NADPH) for the synthesis and accumulation of fatty acids. Moreover, the main lipid subclasses observed during cobalamin deficiency were glycerolipids (including glycerophospholipids), with EPA primarily distributed in them. The genes involved in the biosynthesis of these lipid subclasses were significantly up-regulated, such as the key enzymes in the Kennedy pathway for the synthesis of triglycerides. Thus, this study provided insights into the specific response of Schizochytrium sp. to cobalamin deficiency and identified a subset of new genes that can be engineered for modification.

Anti-inflammatory activity of Boletus aereus polysaccharides: Involvement of digestion and gut microbiota fermentation.

Boletus aereus, an edible mushroom, has gained popularity as a medicinal and functional food. This study aimed to investigate the digestive characteristics of B. aereus polysaccharide (BAP) and its effects on gut microbiota. In vitro digestion results indicated partial degradation of BAP. Furthermore, the digested BAP displayed significantly enhanced antioxidant ability. The 16S rRNA sequencing data revealed that BAP positively influenced the abundance of Phascolarctobacterium, Prevotella, and Bifidobacterium in the gut microbiota. Additionally, BAP promoted the production of short-chain fatty acids (SCFAs). Metabolites of BAP utilized by the gut microbiota effectively reduced the concentration of TNF-α, IL-1ß, and NO in an LPS-stimulated RAW 264.7 cell inflammation model. Mantel tests demonstrated a strong correlation among fermentation indicators, gut microbiome composition, SCFAs, and inflammatory cytokines. Overall, this research revealed the underlying digestive and fermentation mechanisms of BAP and provided new insights into the usage of edible mushroom polysaccharides in functional food.

[Relationship of triglyceride-glucose index and its derivatives with blood pressure abnormalities in adolescents: an analysis based on a restricted cubic spline model]. / åŸºäºŽé™åˆ¶æ€§ç«‹æ–¹æ ·æ¡æ¨¡åž‹åˆ†æžé’å°‘å¹´ä¸‰é °ç”˜æ²¹-è‘¡è„ç³–æŒ‡æ•°åŠå ¶è¡ç”ŸæŒ‡æ•°ä¸Žè¡€åŽ‹å¼‚å¸¸çš„å ³ç³».

OBJECTIVES: To explore the relationship of triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), and triglyceride-glucose-waist circumference index (TyG-WC) with blood pressure abnormalities in adolescents, providing theoretical basis for the prevention and control of hypertension in adolescents. METHODS: A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys, physical measurements, and laboratory tests. Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG, TyG-BMI, and TyG-WC with blood pressure abnormalities in adolescents. RESULTS: Multivariable logistic regression analysis revealed that after adjusting for confounding factors, the groups with the highest quartile of TyG, TyG-BMI, and TyG-WC had 1.48 times (95%CI: 1.07-2.04), 3.71 times (95%CI: 2.67-5.15), and 4.07 times (95%CI: 2.89-5.73) higher risks of blood pressure abnormalities compared to the groups with the lowest quartile, respectively. Moreover, as the levels of TyG, TyG-BMI, and TyG-WC increased, the risk of blood pressure abnormalities gradually increased (P<0.05). A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.002). Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearit =0.232), and between TyG-WC and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.224). CONCLUSIONS: Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents, with linear or non-linear dose-response relationships.

Metabolite profiling and antioxidant capacity of natural Ophiocordyceps gracilis and its cultures using LC-MS/MS-based metabolomics: Comparison with Ophiocordyceps sinensis.

INTRODUCTION: Ophiocordyceps gracilis is an entomopathogenic fungus and a precious traditional Chinese medicine with similar medicinal properties to Ophiocordyceps sinensis. However, information on the metabolite profiles of natural O. gracilis and its cultures is lacking, which limits their utilization. OBJECTIVE: The metabolic variations and antioxidant activities of O. gracilis cultures and natural O. gracilis were analyzed to evaluate the nutritional and medicinal value of O. gracilis and its cultures. METHOD: The metabolite profiles of O. gracilis cultures (fruiting bodies and aerial mycelia), natural O. gracilis, and natural O. sinensis were compared by LC-MS/MS coupled with multivariate data analysis. Furthermore, their antioxidant activities were evaluated based on their DPPH• , ABTS•+ , and • OH scavenging abilities. RESULTS: A total of 612 metabolites were identified, and the metabolic compositions of the four Cordyceps samples were similar, with differences observed in the levels of some metabolites. There were 126 differential metabolites between natural O. gracilis and natural O. sinensis, among which fatty acids, carbohydrates, and secondary metabolites are predominant in natural O. gracilis. Furthermore, 116 differential metabolites between O. gracilis cultures and natural Cordyceps were identified, with generally higher levels in O. gracilis cultures than in natural Cordyceps. O. gracilis cultivated fruiting bodies exhibited the strongest antioxidant capacity among Cordyceps samples. Additionally, 46 primary and 24 secondary differential metabolites contribute to antioxidant activities. CONCLUSION: This study provides a reference for the application of natural O. gracilis and its cultures in functional food and medicine from the perspective of metabolites and antioxidant capacity.

Relationship between new surrogate marks of insulin resistance and bone mineral content in adolescents / 中国学校卫生

Objective@#To analyze the relationship between new surrogate marks of insulin resistance (IR) and bone mineral content (BMC) in adolescents, and predictive value of the new surrogate marks on low bone mass, so as to provide scientific basis for early identification and prevention of skeletal related diseases in adolescents.@*Methods@#A total of 1 594 adolescents aged 12-18 years in Yinchuan City were selected by convenience sampling and stratified cluster random sampling from September 2017 to September 2020, and triglyceride and glucose index (TyG), triglyceride glucose-body mass index (TyG-BMI) and triglyceride/high density lipoprotein cholesterol (TG/HDL-C) were calculated as new simplified IR index. The correlation between different simplified IR indexes and BMC level was analyzed by partial correlation. Binary Logistic regression was used to analyze the relationship between IR index and low bone mass, and receiver operating characteristic (ROC) curve was constructed to analyze its evaluation effect on low bone mass.@*Results@#After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, systolic blood pressure (SBP) and diastolic blood pressure (DBP), the new surrogate marks of IR were positively correlated with BMC level (TyG: r =0.11, TyG-BMI: r =0.58, TG/HDL-C: r =0.21, P <0.01). After further adjustment of body mass index (BMI), fat mass (FM) and lean mass (LM), the relationship between IR indexes and BMC turned into negative correlation (TyG: r =-0.20, TyG-BMI: r =-0.18, TG/HDL-C: r=-0.14, P <0.01). After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, SBP and DBP, Logistic regression results showed that the increase of TyG, TyG-BMI and TG/HDL-C levels reduced the possibility of low bone mass in adolescents (TyG: OR=0.63, 95%CI = 0.40-0.98, TyG-BMI: OR=0.94, 95%CI =0.93-0.96, TG/HDL-C: OR=0.31, 95%CI=0.17-0.58, P <0.01). After adjusting BMI, FM and LM, the above results were completely reversed. Girls with high TyG and TG/HDL-C levels were 4.95 and 4.38 times more likely to have low bone mass than those with low TyG and TG/HDL-C levels (TyG: OR=4.95, 95%CI =1.29- 18.95 , TG/HDL-C: OR=4.38, 95%CI=1.04-18.50, P <0.05). ROC curve showed that TyG-BMI had the best predictive value on low bone mass (AUC=0.80, 95% CI=0.77-0.83, P <0.01).@*Conclusion@#The new surrogate marks of IR in adolescents are negatively correlated with adolescent BMC, of which TyG-BMI is the best for assessing of low bone mass and can serving as a reliable indicator for early identification of low bone mass.

A Neutral Polysaccharide from Spores of Ophiocordyceps gracilis Regulates Oxidative Stress via NRF2/FNIP1 Pathway.

Ophiocordyceps gracilis (O. gracilis) is a parasitic fungus used in traditional Chinese medicine and functional foods. In this study, a neutral heteropolysaccharide (GSP-1a) was isolated from spores of O. gracilis, and its structure and antioxidant capacities were investigated. GSP-1a was found to have a molecular weight of 72.8 kDa and primarily consisted of mannose (42.28%), galactose (35.7%), and glucose (22.02%). The backbone of GSP-1a was composed of various sugar residues, including →6)-α-D-Manp-(1→, →2,6)-α-D-Manp-(1→, →2,4,6)-α-D-Manp-(1→, →6)-α-D-Glcp-(1→, and →3,6)-α-D-Glcp-(1→, with some branches consisting of →6)-α-D-Manp-(1→ and α-D-Gal-(1→. In vitro, antioxidant activity assays demonstrated that GSP-1a exhibited scavenging effects on hydroxyl radical (•OH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS•+), and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•). Moreover, GSP-1a was found to alleviate H2O2-induced oxidative stress in HepG2 cells by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing the activities of superoxide dismutase (SOD). Furthermore, GSP-1a upregulated the mRNA expression of antioxidant enzymes such as Ho-1, Gclm, and Nqo1, and regulated the NRF2/KEAP1 and FNIP1/FEM1B pathways. The findings elucidated the structural types of GSP-1a and provided a reliable theoretical basis for its usage as a natural antioxidant in functional foods or medicine.

Single and Multiple High-Risk Human Papillomavirus Infections in Histopathologically Confirmed Cervical Squamous Lesions: Incidences, Distribution, and Associated Detection Rates for Precancerous and Cancerous Lesions.

Coinfection with multiple high-risk human papillomavirus (hrHPV) is frequently observed in cervical specimens; however, the clinical significance of concomitant multiple hrHPV infections is poorly understood, and the published results remain inconsistent. A retrospective study at a tertiary care institution was performed, evaluating Tellgenplex human papillomavirus (HPV) 27 genotyping or YanengBio HPV 23 genotyping results and immediate cervical histologic diagnosis (within 6 months after HPV genotyping), between November 2015 and October 2022. Among 49,299 cases with hrHPV genotyping and histologic diagnosis, 24,361 cases were diagnosed as cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma. Among women with cervical squamous lesions, 86.5% (21,070/24,361) had hrHPV infections, and concomitant multiple hrHPV infections accounted for 24.7% of hrHPV-positive cases (5210/21,070). The hrHPV-positive rates in these cervical squamous lesions increased progressively with disease severity; however, the percentages of concomitant multiple hrHPV infection rates among hrHPV-positive cases decreased significantly with increasing degree of squamous abnormalities. There was no increased detection rate of CIN3+ (CIN3 and squamous cell carcinoma) in cases with concomitant 2 or 3 hrHPV genotype infections when compared with those with corresponding single hrHPV infections. Conversely, some combinations of multiple hrHPV infections demonstrated a decrease in the detection rates of CIN3+ lesions. In this large cohort, our results demonstrated that multiple hrHPV infections do not carry an increased risk for developing CIN3+ lesions when compared to the corresponding single-genotype infection. The reduced risk of CIN3+ in women infected with some combinations of hrHPV genotypes compared to those with single-genotype infections supports the concept of intergenotypic competition of hrHPV genotypes in cervical squamous lesions.

Development of a novel microplate for high-throughput screening and optimization of DHA producing strains based on CFD technology.

Microtiter plates are suitable for screening and process development of most microorganisms. They are currently the container of choice for high-throughput and small-scale microbial culture, but require optimization for specific work. In this research, a novel type of microtiter plate was developed using computational fluid dynamics (CFD) technology. The new plate provided high oxygen supply and optimal mixing effects for the fermentation culture of docosahexaenoic acid (DHA) producing strains, surpassing the conventional method of strain screening with shake flasks, which was insufficient. The shape of the microtiter plate was modified, and baffles were introduced to improve mass transfer and oxygen supply effects in the vibrating bioreactor. CFD technology was used to model the new plate's characteristics, establishing the superiority of hexagonal microtiter plates with six baffles. Parameters in the incubation process, such as vibration frequency and liquid load, were optimized, and the final result achieved an oxygen transfer coefficient (KL a) of 0.61 s-1 and a volume power input of 2364 w m-3 , which was four to five times better than the original 96-well plate. The culture results optimized by the model were also verified. Therefore, this new microtiter plate provides a powerful tool for future high-throughput screening of strains.

Integration of Physiological, Transcriptomic and Metabolomic Reveals Molecular Mechanism of Paraisaria dubia Response to Zn2+ Stress.

Utilizing mycoremediation is an important direction for managing heavy metal pollution. Zn2+ pollution has gradually become apparent, but there are few reports about its pollution remediation. Here, the Zn2+ remediation potential of Paraisaria dubia, an anamorph of the entomopathogenic fungus Ophiocordyceps gracilis, was explored. There was 60% Zn2+ removed by Paraisaria dubia mycelia from a Zn2+-contaminated medium. To reveal the Zn2+ tolerance mechanism of Paraisaria dubia, transcriptomic and metabolomic were executed. Results showed that Zn2+ caused a series of stress responses, such as energy metabolism inhibition, oxidative stress, antioxidant defense system disruption, autophagy obstruction, and DNA damage. Moreover, metabolomic analyses showed that the biosynthesis of some metabolites was affected against Zn2+ stress. In order to improve the tolerance to Zn2+ stress, the metabolic mechanism of metal ion transport, extracellular polysaccharides (EPS) synthesis, and microcycle conidiation were activated in P. dubia. Remarkably, the formation of microcycle conidiation may be triggered by reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling pathways. This study supplemented the gap of the Zn2+ resistance mechanism of Paraisaria dubia and provided a reference for the application of Paraisaria dubia in the bioremediation of heavy metals pollution.

Comparative metabolic profiling of mycelia, fermentation broth, spore powder and fruiting bodies of Ophiocordyceps gracilis by LC-MS/MS.

INTRODUCTION: Ophiocordyceps gracilis, a type of edible and medicinal fungus, exhibits multiple health-promoting effects. Due to the scarcity of natural O. gracilis, artificial cultures have been developed as its substitutes. However, lacking comprehension of the metabolite composition of cultures limits its utilisation. OBJECTIVE: This research aimed to evaluate the nutritional and medicinal value of four cultures of O. gracilis by analysing their metabolite composition. In addition, metabolic pathways in mycelia and fruiting bodies were analysed to explore fruiting body formation mechanism at metabolic level. METHOD: The mycelia, fermentation broth, spore powder and fruiting bodies of O. gracilis were cultivated in this study. Their metabolite composition was compared using an untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) showed that the four cultures have noticeable differences in metabolite composition. A total of 612 metabolites were identified, among which 159 metabolites showed significant differences, and these differential metabolites were classified into 13 categories. The metabolites in the fruiting bodies were the most abundant compared with other cultures. However, each culture had its own advantages and significantly accumulates some active metabolites respectively. Pearson's correlation analysed the mutual relationship among metabolites. In addition, seven metabolic pathways were closely related to fruiting body formation, such as "Biosynthesis of plant secondary metabolites", "amino acids metabolism", "tricarboxylic acid (TCA) cycle". CONCLUSION: This study offered a reference to mycelia, fermentation broth, spore powder and fruiting bodies of O. gracilis as health-promoting functional foods and medicine.

[Relationship between skeletal muscle mass index and metabolic phenotypes of obesity in adolescents]. / é’å°‘å¹´éª¨éª¼è‚Œè´¨é‡æŒ‡æ•°ä¸Žè‚¥èƒ–ä»£è°¢è¡¨åž‹çš„å ³ç³».

OBJECTIVES: To study the relationship between skeletal muscle mass index (SMI) and metabolic phenotypes of obesity in adolescents, and to provide a basis for the prevention and control of adolescent obesity and related metabolic diseases. METHODS: A total of 1 352 adolescents aged 12 to 18 years were randomly selected by stratified cluster sampling in Yinchuan City from October 2017 to September 2020, and they were surveyed using questionnaires, physical measurements, body composition measurements, and laboratory tests. According to the diagnostic criteria for metabolic abnormalities and the definition of obesity based on the body mass index, the subjects were divided into four metabolic phenotypes: metabolically healthy normal weight, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity. The association between SMI and the metabolic phenotypes was analyzed using multivariate logistic regression. RESULTS: The SMI level in the metabolically unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity groups was lower than that in the metabolically healthy normal weight group (P<0.001). Multivariate logistic regression analysis showed that after adjusting for gender and age, a higher SMI level was a protective factors for adolescents to develop metabolic unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity phenotypes (OR=0.74, 0.60, and 0.54, respectively; P<0.001). CONCLUSIONS: Increasing SMI can reduce the risk of the development of metabolic unhealthy/obesity.