Using regression tree analysis to examine demographic and geographic characteristics of COVID-19 vaccination trends over time, United States, May 2021-April 2022, National Immunization Survey Adult COVID Module.

Using data from the nationally representative National Immunization Survey (NIS), we applied conditional linear regression tree methodology to examine relationships between demographic and geographic factors and propensity of receiving various doses of COVID-19 vaccine over time; these analyses identified temporal changes in these relationships that heretofore had not been identified using conventional logistical regression methodologies. Three regression tree models were built using an R package, Recursive Partitioning for Modeling Survey (rpms), to examine propensities over time of receiving a (1) first dose of a two-dose COVID-19 mRNA primary vaccination series or single dose of the Janssen vaccine (vaccine initiation), (2) primary series completion, and (3) monovalent booster dose, using a conditional linear effect model. Persons ≥50 years were more likely to complete a primary series and receive a first booster dose; persons reporting having received non-COVID-19 vaccines recently were more likely to initiate vaccination, complete the primary series, and get a first booster dose; persons reporting having work or school requirements were more likely to complete the primary series. Persons not reporting having received non-COVID-19 vaccines in 2 years but reporting having work or school vaccination requirements were more likely to initiate vaccination than those without work/school requirements. Among persons not reporting having received non-COVID-19 vaccines in 2 years and not reporting having work or school vaccination requirements, those aged ≥50 years were more likely to initiate vaccination than were younger adults. Propensity of receiving various doses was correlated with age, having recently received non-COVID 19 vaccines, and having vaccination requirements at work or school. Regression tree methodology enabled modeling of different COVID-19 vaccination dose propensities as a linear effect of time, revealed changes in relationships over time between demographic factors and propensity of receipt of different doses, and identified populations that may benefit from vaccination outreach efforts.

Xenotransplanted human organoids identify transepithelial zinc transport as a key mediator of intestinal adaptation.

Short bowel syndrome (SBS) leads to severe morbidity and mortality. Intestinal adaptation is crucial in improving outcomes. To understand the human gene pathways associated with adaptation, we perform single-cell transcriptomic analysis of human small intestinal organoids explanted from mice with experimental SBS. We show that transmembrane ion pathways, specifically the transepithelial zinc transport pathway genes SLC39A4 and SLC39A5, are upregulated in SBS. This discovery is corroborated by an external dataset, bulk RT-qPCR, and Western blots. Oral zinc supplementation is shown to improve survival and weight gain of SBS mice and increase the proliferation of intestinal crypt cells in vitro. Finally, we identify the upregulation of SLC39A5 and associated transcription factor KLF5 in biopsied intestinal tissue specimens from patients with SBS. Thus, we identify zinc supplementation as a potential therapy for SBS and describe a xenotransplantation model that provides a platform for discovery in other intestinal diseases.

Impact of an enhanced recovery after surgery program integrating cardiopulmonary rehabilitation on post-operative prognosis of patients treated with CABG: protocol of the ERAS-CaRe randomized controlled trial.

BACKGROUND: Coronary artery bypass grafting is associated with a high occurrence of postoperative cardiopulmonary complications. Preliminary evidence suggested that enhanced recovery after surgery can effectively reduce the occurrence of postoperative cardiopulmonary complications. However, enhanced recovery after surgery with systematic integration of cardiopulmonary rehabilitation (ERAS-CaRe) into for Coronary artery bypass grafting has not been evaluated so far. We thus design the ERAS-CaRe randomized-controlled trial to evaluate possible superiority of embedding cardiopulmonary rehabilitation in ERAS over ERAS alone as well as to investigate effects of differential timing of cardiopulmonary rehabilitation within enhanced recovery after surgery (pre-, post-, perio-operative) on post-operative cardiopulmonary complications following Coronary artery bypass grafting surgery. METHODS: ERAS-CaRe is a pragmatic, randomized-controlled, parallel four-arm, clinical trial. Three hundred sixty patients scheduled for Coronary artery bypass grafting in two Chinese hospitals will be grouped randomly into (i) Standard enhanced recovery after surgery or (ii) pre-operative ERAS-CaRe or (iii) post-operative ERAS-CaRe or (iv) perio-operative ERAS-CaRe. Primary outcome is the occurrence of cardiopulmonary complications at 10 days after Coronary artery bypass grafting. Secondary outcomes include the occurrence of other individual complications including cardiac, pulmonary, stroke, acute kidney injury, gastrointestinal event, ICU delirium rate, reintubation rate, early drainage tube removal rate, unplanned revascularization rate, all-cause mortality, ICU readmission rate, plasma concentration of myocardial infarction-related key biomarkers etc. DISCUSSION: The trial is designed to evaluate the hypothesis that a cardiopulmonary rehabilitation based enhanced recovery after surgery program reduces the occurrence of cardiopulmonary complications following Coronary artery bypass grafting and to determine optimal timing of cardiopulmonary rehabilitation within enhanced recovery after surgery. The project will contribute to increasing the currently limited knowledge base in the field as well as devising clinical recommendations. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry on 25 August 2023 (ChiCTR2300075125; date recorded: 25/8/2023, https://www.chictr.org.cn/ ).

MLH1 Gene Expression in Peripheral Blood in Colon Cancer Patients and Their Association with Colon Cancer.

MutL homolog 1 (MLH1) is a component of the heterodimeric complex MutLα that detects and fixes base-base mismatches and insertion/deletion loops caused by nucleotide misincorporation. In the absence of MLH1 protein, the frequency of non-repaired mismatches increases, resulting in organ cancer. The current study sought to quantify MLH1 gene expression and its relationship with tumor invasion (T) and lymph node invasion (N) in blood samples from patients with colorectal cancer (CRC). Blood samples were obtained from 36 CRC patients. RNA was extracted, and cDNA was synthesized using a kit. The primers were built using the exon-exon junction approach, and MLH1 and ß-actin genes were tested 3x using real-time polymerase chain reaction (Real-Time PCR). Gene expression analysis software was used to analyze the data, and a t-test was used to examine the expression of MLH1 and its connection with T and N variables. In this study, 36 patients with colorectal cancer, including 15 (41.6%) women and 21 (58.4%) men, with a mean age of 57.35 ± 4.22 years and in the age range of 26-87 years, were included. The results showed that the ratio of MLH1 gene expression in patients decreased compared to that in healthy individuals, and the decrease in gene expression at different stages of the disease was significant. The results of this study showed that the reduction of MLH1 gene expression has an effective role in the development of CRC.

Nomogram for prediction of severe postoperative complications in elective hepato-pancreato-biliary surgery after COVID-19 breakthrough infection: A large multicenter study.

BACKGROUND: Currently, there is a deficiency in a strong risk prediction framework for precisely evaluating the likelihood of severe postoperative complications in patients undergoing elective hepato-pancreato-biliary surgery subsequent to experiencing breakthrough infection of coronavirus disease 2019 (COVID-19). This study aimed to find factors predicting postoperative complications and construct an innovative nomogram to pinpoint patients who were susceptible to developing severe complications following breakthrough infection of COVID-19 after undergoing elective hepato-pancreato-biliary surgery. METHODS: This multicenter retrospective cohort study included consecutive patients who underwent elective hepato-pancreato-biliary surgeries between January 3 and April 1, 2023 from four hospitals in China. All of these patients had experienced breakthrough infection of COVID-19 prior to their surgeries. Additionally, two groups of patients without preoperative COVID-19 infection were included as comparative controls. Surgical complications were meticulously documented and evaluated using the comprehensive complication index (CCI), which ranged from 0 (uneventful course) to 100 (death). A CCI value of 20.9 was identified as the threshold for defining severe complications. RESULTS: Among 2636 patients who were included in this study, 873 were included in the reference group I, 941 in the reference group II, 389 in the internal cohort, and 433 in the external validation cohort. Multivariate logistic regression analysis revealed that completing a full course of COVID-19 vaccination > 6 months before surgery, undergoing surgery within 4 weeks of diagnosis of COVID-19 breakthrough infection, operation duration of 4 h or longer, cancer-related surgery, and major surgical procedures were significantly linked to a CCI > 20.9. A nomogram model was constructed utilizing CCI > 20.9 in the training cohort [area under the curve (AUC): 0.919, 95% confidence interval (CI): 0.881-0.957], the internal validation cohort (AUC: 0.910, 95% CI: 0.847-0.973), and the external validation cohort (AUC: 0.841, 95% CI: 0.799-0.883). The calibration curve for the probability of CCI > 20.9 demonstrated good agreement between the predictions made by the nomogram and the actual observations. CONCLUSIONS: The developed model holds significant potential in aiding clinicians with clinical decision-making and risk stratification for patients who have experienced breakthrough infection of COVID-19 prior to undergoing elective hepato-pancreato-biliary surgery.

Synthesis of chiral α-amino acids via Pd(ii)-catalyzed enantioselective C-H arylation of α-aminoisobutyric acid.

Non-natural chiral α,α-disubstituted α-amino acids (α,α-AAs) constitute an attractive α-aminoisobutyric acid (Aib) replacement for improving bioavailability of linear peptides as therapeutics due to the ability of these amino acids to induce the peptides to form helical structures. Enantioselective ß-C(sp3)-H arylation of Aib could potentially provide a versatile one-step strategy for accessing diverse α,α-AAs, but the installation and removal of external directing groups was found in our previously reported work to reduce the efficiency of this approach. Herein we report a Pd(ii)-catalyzed enantioselective C-H arylation of N-phthalyl-protected Aib enabled by a N-2,6-difluorobenzoyl aminoethyl phenyl thioether (MPAThio) ligand, affording α,α-AAs with up to 72% yield and 98% ee. Use of this newly developed chiral catalyst has also significantly improved enantioselective C(sp3)-H arylation of cyclopropanecarboxylic acids by expanding the substrate scope to heterocyclic coupling partners and increasing enantioselectivity to 99% ee.

Norm Emergence through Conflict-Blocking Interactions in Industrial Internet of Things Environments.

Norms have been effectively utilized to facilitate smooth interactions among agents. Norms are usually the global data that agents cannot directly access in complex environments; instead, norms can only be indirectly accessed by agents via maintaining their own beliefs about norms. Establishing norms using decentralized interaction-based methods has attracted much attention. However, the current methods overlook Industrial Internet of Things (IIoT) environments. In IIoT, there is a prevalent feature called "conflict-blocking", where agents' conflicting action strategies can block an interaction from being completed or even cause danger. To facilitate norm emergence in IIoT, we propose a framework to support agent decisions in conflict-blocking interactions. The framework aids in achieving system scalability by integrating the fusion of agent beliefs about norms. We prove that the proposed framework guarantees norm emergence. We also theoretically and experimentally analyze the time required for norm emergence under the influence of various factors, such as the number of agents. A vehicle movement simulator is also developed to vividly illustrate the process of norm emergence.

Disparities in COVID-19 vaccine uptake, attitudes, and experiences between food system and non-food system essential workers.

The COVID-19 pandemic has disproportionately affected the health of food system (FS) essential workers compared with other essential and non-essential workers. Even greater disparity exists for workers in certain FS work settings and for certain FS worker subpopulations. We analyzed essential worker respondents (n = 151,789) in May-November 2021 data from the National Immunization Survey Adult COVID Module (NIS-ACM) to assess and characterize COVID-19 vaccination uptake (≥1 dose) and intent (reachable, reluctant), attitudes about COVID-19 and the vaccine, and experiences and difficulties getting the vaccine. We compared rates, overall and by certain characteristics, between workers of the same group, and between FS (n = 17,414) and non-food system (NFS) worker groups (n = 134,375), to determine if differences exist. FS worker groups were classified as "agriculture, forestry, fishing, or hunting" (AFFH; n = 2,730); "food manufacturing facility" (FMF; n = 3,495); and "food and beverage store" (FBS; n = 11,189). Compared with NFS workers, significantly lower percentages of FS workers reported ≥1 dose of COVID-19 vaccine or vaccine requirements at work or school, but overall vaccine experiences and difficulties among vaccinated FS workers were statistically similar to NFS workers. When we examined intent regarding COVID-19 vaccination among unvaccinated FS workers compared with NFS counterparts, we found a higher percentage of FMF and FBS workers were reachable whereas a higher percentage of AFFH workers were reluctant about vaccination, with differences by sociodemographic characteristics. Overall, results showed differences in uptake, intent, and attitudes between worker groups and by some sociodemographic characteristics. The findings reflect the diversity of FS workers and underscore the importance of collecting occupational data to assess health inequalities and of tailoring efforts to worker groups to improve confidence and uptake of vaccinations for infectious diseases such as COVID-19. The findings can inform future research, adult infectious disease interventions, and emergency management planning.

The Role of ICG-Guided Fluorescent Mode in Boosting the Learning Curve of Laparoscopic Cholecystectomy.

Background: The most common therapy for gallstones is laparoscopic cholecystectomy (LC). How to help young residents avoid bile duct injuries (BDI) during surgery and grasp LC seems to be a paradox. Methods: We retrospectively reviewed 145 cases of LC operated by two residents under indocyanine green (ICG)-guided mode or normal LC procedures to illustrate the role of ICG mode in boosting the LC learning curve. The clinic data were analyzed by logistic regression, receiver operator curve tests, Cumulative Sum (CUSUM), and Risk-Adjusted Cumulative Sum (RA-CUSUM) analysis. Results: The operation failure rate is similar. However, operation time under ICG mode is shorter than that under normal mode. The peak at the 49th case represented the normal resident's complete mastery of the surgery, while the peak point of ICG mode appeared at the 36th case in the fitting curve. The most significant cumulative risk (peak point) of operation failure of LC was at the 35th case in ICG LC mode, while it appeared in the 49th in normal LC mode. Conclusions: Owing to the advantage of real-time imaging and the stable success rate of cholangiography, ICG-guided LC helps residents shorten the operation time, boost the learning curve, and manage to control the operation failure rate.

Structure-Guided Discovery of a Potent Inhibitor of the Ferric Citrate Binding Protein FecB in Vibrio Bacteria.

Infections caused by Gram-negative bacteria present a significant risk to human health worldwide. Novel strategies are needed to deal with the challenge caused by drug-resistant bacteria. Here, we report a new approach to combat infections by targeting iron-binding proteins to suppress bacterial growth. We investigated the function of the conserved periplasmic binding protein FecB from Vibrio alginolyticus. FecB was known to play a crucial role in the bacterial growth and to relate with biofilm formation. We then solved the crystal structures and elucidated the binding mechanism of FecB with ferric ion chelated by citrate. The results indicated that FecB binds weakly to one citrate molecule and strongly to the Fe3+-(citrate)2 complex. Based on these results, a structure-based virtual screening approach was conducted against FecB to identify small molecules that block ferric-citrate uptake. Further evaluations in vivo and in vitro demonstrated that salvianolic acid C significantly suppressed bacterial growth, indicating that targeting bacterial nutrient absorption is a promising strategy for identifying potential antibacterial drugs.

Effect of mixed probiotics on pulmonary flora in patients with mechanical ventilation: an exploratory randomized intervention study.

OBJECTIVE: The study objective was to investigate the effect of mixed probiotics on the diversity of the pulmonary flora in critically ill patients requiring mechanical ventilation by analysing the changes in lung microbes. METHODS: 24 adult critically ill patients who needed mechanical ventilation in our hospital were randomly divided into a probiotic group and a control group. Then, the probiotic group was given Live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules, Oral (Bifico) by nasal feeding within 24 h after mechanical ventilation. Bronchoalveolar lavage fluid (BALF) and venous blood were collected within 24 h after mechanical ventilation and on the 5th day after mechanical ventilation, and the treatment status of patients (mechanical ventilation time, 28-day survival), measured cytokine levels (IL-1 ß, IL-6, IL-8, IL-17A) and changes in pulmonary microorganisms were observed. RESULTS: The microbial diversity of BALF samples decreased in the control group, and there was no significant difference in the probiotic group. Species difference analysis showed that among the three probiotics (Bifidobacterium, Lactobacillus, Enterococcus) used for intervention, Lactobacillus caused significant differences in BALF in the control group. Clinical factor association analysis displayed significant associations with IL-17A levels in both blood and BALF. CONCLUSION: Mechanical ventilation can cause a decline in pulmonary microbial diversity, which can be improved by administering mixed probiotics.

Associations between blood nickel and lung function in young Chinese: An observational study combining epidemiology and metabolomics.

Prior research has explored the relationship between occupational exposure to nickel and lung function. Nonetheless, there is limited research examining the correlation between blood nickel levels and lung function among young adults in the general population. The metabolomic changes associated with nickel exposure have not been well elucidated. On August 23, 2019, we enrolled 257 undergraduate participants from the Chinese Undergraduates Cohort to undergo measurements of blood nickel levels and lung function. The follow-up study was conducted in May 2021. A linear mixed-effects model was employed to assess the relationship between blood nickel levels and lung function. We also conducted stratified analyses by home address. In addition, in order to explore the biological mechanism of lung function damage caused by nickel exposure, we performed metabolomic analyses of baseline serum samples (N = 251). Both analysis of variance and mixed linear effect models were utilized to assess the impact of blood nickel exposure on metabolism. Our findings from cross-sectional and cohort analyses revealed a significant association between blood nickel levels and decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) among young adults in the general population. Furthermore, we found stronger associations in urban areas. In metabolomics analysis, a total of nine metabolites were significantly changed under blood nickel exposure. The changed metabolites were mainly enriched in six pathways including carbohydrate, amino acid, and cofactor vitamin metabolism. These metabolic pathways involve inflammation and oxidative stress, indicating that high concentrations of nickel exposure can cause inflammation and oxidative stress by disrupting the above metabolism of the body.

Associations between soft drinks intake and primary dysmenorrhea among Chinese undergraduate female students.

Primary dysmenorrhea (PD) is a common global health concern. However, limited studies explored the association between soft drinks intake and PD among female undergraduates in China. To determine the association between soft drinks (carbonated soft drinks, etc.) as well coffee intake and the incidence/severity of PD among female undergraduates in China. We performed a cross-sectional study among 1809 female undergraduates in China from September 29, 2020 to October 22, 2020. The demographic information and menstrual information of the participants were collected by a self-administrated questionnaire. Chi-square test, ANOVA test, and logistic regression test were used to investigate the association between soft drinks intake and the incidence/severity of PD. We also conducted stratification analysis among different locations (rural or urban). The prevalence of PD was 47.1% (n = 852). There were 221 (25.9%) participants suffered from severe pain. In the participants with PD, the OR of carbonated soft drinks intake was 1.244 (95% CI 1.010-1.533). Among the participants with PD from rural areas, the OR of carbonated soft drinks intake was 1.402 (95% CI 1.045-1.881), compared with the non-carbonated soft drink group. In the participants with moderate and severe PD, the OR of coffee intake was 0.451 (95% CI 0.228-0.892), compared with the non-coffee-drinking group. There was a significant association between carbonated soft drinks intake frequency and the severity of PD (P < 0.05). Our study showed that carbonated soft drinks intake is a risk factor for PD, especially in participants from rural areas. Coffee intake is a protective factor for the severity of PD. Periodical awareness programs about adverse effects of excessive soft drink consumption should be introduced to reduce the prevalence and exacerbation of PD. Coffee intake might be helpful to relieve the severity of PD.

USP22 promotes gefitinib resistance and inhibits ferroptosis in non-small cell lung cancer by deubiquitination of MDM2.

BACKGROUND: The emergence of chemoresistance markedly compromised the treatment efficiency of human cancer, including non-small cell lung cancer (NSCLC). In the present study, we aimed to explore the effects of ubiquitin-specific peptidase 22 (USP22) and murine double minute 2 (MDM2) in gefitinib resistance in NSCLC. METHODS: Immunohistochemistry (IHC) assay, quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were carried out to determine the expression of USP22 and MDM2. Transwell assay and flow cytometry analysis were performed to evaluate cell migration and apoptosis. Cell Counting Kit-8 (CCK-8) assay was employed to assess gefitinib resistance. The phenomenon of ferroptosis was estimated by related commercial kits. The oxidized C11-BODIPY fluorescence intensity by C11-BODIPY staining. The relation between USP22 and MDM2 was analyzed by ubiquitination assay and co-immunoprecipitation (Co-IP) assay. RESULTS: USP22 was abnormally upregulated in NSCLC tissues and cells, and USP22 silencing markedly repressed NSCLC cell migration and facilitated apoptosis and ferroptosis. Moreover, our results indicated that ferroptosis could enhance the suppressive effect of gefitinib on NSCLC cells. Besides, USP22 overexpression enhanced gefitinib resistance and ferroptosis protection in NSCLC cells. Mechanically, USP22 stabilized MDM2 and regulated MDM2 expression through deubiquitination of MDM2. MDM2 deficiency partially restored the effects of USP22 on gefitinib resistance and ferroptosis in NSCLC cells. Of note, we validated the promotional effect of USP22 on gefitinib resistance in NSCLC in vivo through establishing the murine xenograft model. CONCLUSION: USP22/MDM2 promoted gefitinib resistance and inhibited ferroptosis in NSCLC, which might offer a novel strategy for overcoming gefitinib resistance in NSCLC.

Evaluation of Latent Tuberculosis Infection Using the ESAT6-CFP10 Skin Test Among International Freshmen With Diverse Skin Tones at a University - Nanjing City, Jiangsu Province, China, September 2023.

Introduction: Newer skin tests, including the ESAT6-CFP10 (EC) skin test, were recommended for diagnosing Mycobacterium tuberculosis (M. tb) infection. However, no data exist assessing the diagnostic performance of the EC skin test among foreign students with different skin tones. Methods: A cohort study at Nanjing Medical University screened incoming foreign freshmen. The EC skin test was used to assess for M. tb infection, and results were read at 24, 48, 72, and 96-hours post-administration. Results: Among 96 participants, M. tb infection rates at 24, 48, 72, and 96-hours post-injection were 3.13%, 7.29%, 13.54%, and 9.38%, respectively. While infection rates were lower among individuals with darker skin tones, the difference was not statistically significant (P=0.186), and variations were consistent across different measurement times. Trajectory analysis revealed 5.3% in the continuous-increasing group, 86.5% in the low-stable group, and 5.2% in the elevated-decreasing group. Notably, participants in the elevated-decreasing group had lighter skin tones, with trajectory patterns consistent across different skin colors. Discussion: The EC skin test is safe, and redness diameter is a more reliable indicator than induration. Results should be collected within 48 to 72 hours, with verification at 72 hours crucial if initial results are negative. Importantly, skin color does not affect EC skin test outcomes.

Description of Short-Range Interactions of Carbon-Based Materials with a Combined AIREBO and ZBL Potential.

An accurate description of short-range interactions among atoms is crucial for simulating irradiation effects in applications related to ion modification techniques. A smooth integration of the Ziegler-Biersack-Littmark (ZBL) potential with the adaptive intermolecular reactive empirical bond-order (AIREBO) potential was achieved to accurately describe the short-range interactions for carbon-based materials. The influence of the ZBL connection on potential energy, force, and various AIREBO components, including reactive empirical bond-order (REBO), Lennard-Jones (LJ), and the torsional component, was examined with configurations of the dimer structure, tetrahedron structure, and monolayer graphene. The REBO component is primarily responsible for the repulsive force, while the LJ component is mainly active in long-range interactions. It is shown that under certain conditions, the torsional energy can lead to a strong repulsive force at short range. Molecular dynamics simulations were performed to study the collision process in configurations of the C-C dimer and bulk graphite. Cascade collisions in graphite with kinetic energies of 1 keV and 10 keV for primary knock-on atoms showed that the short-range description can greatly impact the number of generated defects and their morphology.

A patient-derived cell model for malignant transformation in IDH-mutant glioma.

Malignant transformation (MT) is commonly seen in IDH-mutant gliomas. There has been a growing research interest in revealing its underlying mechanisms and intervening prior to MT at the early stages of the transforming process. Here we established a unique pair of matched 3D cell models: 403L, derived from a low-grade glioma (LGG), and 403H, derived from a high-grade glioma (HGG), by utilizing IDH-mutant astrocytoma samples from the same patient when the tumor was diagnosed as WHO grade 2 (tumor mutational burden (TMB) of 3.96/Mb) and later as grade 4 (TMB of 70.07/Mb), respectively. Both cell models were authenticated to a patient's sample retaining endogenous expression of IDH1 R132H. DNA methylation profiles of the parental tumors referred to LGG and HGG IDH-mutant glioma clusters. The immunopositivity of SOX2, NESTIN, GFAP, OLIG2, and beta 3-Tubulin suggested the multilineage potential of both models. 403H was more prompt to cell invasion and developed infiltrative HGG in vivo. The differentially expressed genes (DEGs) from the RNA sequencing analysis revealed the tumor invasion and aggressiveness related genes exclusively upregulated in the 403H model. Pathway analysis showcased an enrichment of genes associated with epithelial-mesenchymal transition (EMT) and Notch signaling pathways in 403H and 403L, respectively. Mass spectrometry-based targeted metabolomics and hyperpolarized (HP) 1-13C pyruvate in-cell NMR analyses demonstrated significant alterations in the TCA cycle and fatty acid metabolism. Citrate, glutamine, and 2-HG levels were significantly higher in 403H. To our knowledge, this is the first report describing the development of a matched pair of 3D patient-derived cell models representative of MT and temozolomide (TMZ)-induced hypermutator phenotype (HMP) in IDH-mutant glioma, providing insights into genetic and metabolic changes during MT/HMP. This novel in vitro model allows further investigation of the mechanisms of MT at the cellular level.

Splicing of Helix Framework in Modified Nagata Method Stage I for Auricle Reconstruction in Patients With Insufficient 8th Rib Cartilage.

BACKGROUND: The 8th rib cartilage was sometimes insufficient to construct a complete external helix in ear reconstruction for microtia. The aim of this study was to investigate the splicing technique of 8th rib cartilage in modified Nagata method stage I. METHODS: Between September 2022 and May 2023, 231 consecutive patients with microtia underwent auricular reconstruction with modified Nagata method stage I. Thirty-four patients with insufficient 8th rib cartilage were screened out by three-dimensional (3D) computed tomography preoperatively, who were included in the study prospectively. The 8th rib was spliced to create the external helix when fabricating the ear framework in the stage I surgery for the 34 patients. The median duration of follow-up was 12.1 months (8-15 months). RESULTS: There were no perioperative complications in our study. During follow-up, all patients had satisfying outcomes, with no inward collapse, displacement, or absorption of the spliced external helix. The splicing point was not obvious. CONCLUSIONS: It was safe and effective to splice the 8th rib cartilage for external helix of the cartilage framework in ear reconstruction for microtia.

Quantitative assessment methods and qualitative evaluation system for the complementary characteristics of multi-energy.

Assessing and analyzing the complementary characteristics of renewable energy (RE) is crucial for designing, operating, and optimizing multi-energy complementary systems (MECSs). However, unified and precise quantitative descriptions of the complementary and stability characteristics among various energy outputs in MECSs have lacked attention and research. Here, this study innovatively proposed a mathematical model for the multi-energy complementarity index (MECI), which considers the complementarity rates of multiple energy outputs during zero and non-zero output periods, and a mathematical model for the multi-energy volatility index (MEVI), which accounts for fluctuation thresholds and the overall volatility of output processes. An evaluation system for multi-energy complementarity characteristics qualitative analysis has been established. The natural output processes of RE at three MECSs in China were applied in the case calculations and verification. Results show that the hydropower rated discharge (Qrating) has a significant negative correlation with MECI, with the MECI decreasing by an average of 0.0046 for every 5 m³/s increase in Qrating. The relationship between the Qrating and MEVI shows an overall negative correlation with local fluctuations. Notably, The MECI of the BeiPan River MECSs exhibits significant seasonal characteristics, with the MEVI in summer (0.378) and autumn (0.395) higher than those in spring (0.132) and winter (0.160), closely related to the natural seasonal variations of the three energy sources: water, wind, and solar. We believe that the study can assist in evaluating and making decisions on the multi-energy complementarity characteristics of RE bases in the future, making a significant contribution to achieving dual carbon goals.

Eight new dammarane-type triterpenoid saponins from Gynostemma pentaphyllum.

Phytochemical investigation of Gynostemma pentaphyllum led to the purification of five novel dammarane-type triterpene isolates, gypenosides B1 - B5 (1-5). Their structures were determined through comprehensive 1D and 2D NMR spectroscopic analyses and HRESIMS data. Of note, 1-3 are inseparable mixtures of epimers due to their unstable nature, and a total of eight dammarane-type triterpene saponins were identified. Additionally, the protective activities of these new compounds against PC12 cell injury induced by hypoxia were evaluated.