Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction.

Aerobic glycolysis regulates T cell function. However, whether and how primary cancer alters T cell glycolytic metabolism and affects tumor immunity in cancer patients remains a question. Here we found that ovarian cancers imposed glucose restriction on T cells and dampened their function via maintaining high expression of microRNAs miR-101 and miR-26a, which constrained expression of the methyltransferase EZH2. EZH2 activated the Notch pathway by suppressing Notch repressors Numb and Fbxw7 via trimethylation of histone H3 at Lys27 and, consequently, stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling. Moreover, small hairpin RNA-mediated knockdown of human EZH2 in T cells elicited poor antitumor immunity. EZH2(+)CD8(+) T cells were associated with improved survival in patients. Together, these data unveil a metabolic target and mechanism of cancer immune evasion.

RNA molecular recording with an engineered RNA deaminase.

RNA deaminases are powerful tools for base editing and RNA molecular recording. However, the enzymes used in currently available RNA molecular recorders such as TRIBE, DART or STAMP have limitations due to RNA structure and sequence dependence. We designed a platform for directed evolution of RNA molecular recorders. We engineered an RNA A-to-I deaminase (an RNA adenosine base editor, rABE) that has high activity, low bias and low background. Using rABE, we present REMORA (RNA-encoded molecular recording in adenosines), wherein deamination by rABE writes a molecular record of RNA-protein interactions. By combining rABE with the C-to-U deaminase APOBEC1 and long-read RNA sequencing, we measured binding by two RNA-binding proteins on single messenger RNAs. Orthogonal RNA molecular recording of mammalian Pumilio proteins PUM1 and PUM2 shows that PUM1 competes with PUM2 for a subset of sites in cells. Furthermore, we identify transcript isoform-specific RNA-protein interactions driven by isoform changes distal to the binding site. The genetically encodable RNA deaminase rABE enables single-molecule identification of RNA-protein interactions with cell type specificity.

Individual variability in functional connectivity of human auditory cortex.

Individual variability in functional connectivity underlies individual differences in cognition and behaviors, yet its association with functional specialization in the auditory cortex remains elusive. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, this study was designed to investigate the spatial distribution of auditory cortex individual variability in its whole-brain functional network architecture. An inherent hierarchical axis of the variability was discerned, which radiates from the medial to lateral orientation, with the left auditory cortex demonstrating more pronounced variations than the right. This variability exhibited a significant correlation with the variations in structural and functional metrics in the auditory cortex. Four auditory cortex subregions, which were identified from a clustering analysis based on this variability, exhibited unique connectional fingerprints and cognitive maps, with certain subregions showing specificity to speech perception functional activation. Moreover, the lateralization of the connectional fingerprint exhibited a U-shaped trajectory across the subregions. These findings emphasize the role of individual variability in functional connectivity in understanding cortical functional organization, as well as in revealing its association with functional specialization from the activation, connectome, and cognition perspectives.

Revealing the Optical Transition Properties of Interlayer Excitons in Defective WS2/WSe2 Heterobilayers.

Manipulation of physical properties in multidimensional tunable moiré superlattice systems is a key focus in nanophotonics, especially for interlayer excitons (IXs) in two-dimensional materials. However, the impact of defects on IXs remains unclear. Here, we thoroughly study the optical properties of WS2/WSe2 heterobilayers with varying defect densities. Low-temperature photoluminescence (PL) characterizations reveal that the low-energy IXs are more susceptible to defects compared to the high-energy IXs. The low-energy IXs also show much faster PL quenching rate with temperature, faster peak width broadening rate with laser power, shorter lifetime, and lower circular polarization compared to the low-energy IXs in the region with fewer defects. These effects are attributed to the combined effects of increased electron scattering, exciton-phonon interactions, and nonradiative channels introduced by the defects. Our findings aid in optimizing moiré superlattice structures.

The enhancing effects of selenomethionine on harmine in attenuating pathological cardiac hypertrophy via glycolysis metabolism.

Pathological cardiac hypertrophy, a common feature in various cardiovascular diseases, can be more effectively managed through combination therapies using natural compounds. Harmine, a ß-carboline alkaloid found in plants, possesses numerous pharmacological functions, including alleviating cardiac hypertrophy. Similarly, Selenomethionine (SE), a primary organic selenium source, has been shown to mitigate cardiac autophagy and alleviate injury. To explores the therapeutic potential of combining Harmine with SE to treat cardiac hypertrophy. The synergistic effects of SE and harmine against cardiac hypertrophy were assessed in vitro with angiotensin II (AngII)-induced hypertrophy and in vivo using a Myh6R404Q mouse model. Co-administration of SE and harmine significantly reduced hypertrophy-related markers, outperforming monotherapies. Transcriptomic and metabolic profiling revealed substantial alterations in key metabolic and signalling pathways, particularly those involved in energy metabolism. Notably, the combination therapy led to a marked reduction in the activity of key glycolytic enzymes. Importantly, the addition of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) did not further potentiate these effects, suggesting that the antihypertrophic action is predominantly mediated through glycolytic inhibition. These findings highlight the potential of SE and harmine as a promising combination therapy for the treatment of cardiac hypertrophy.

Two Birds with One Stone: Impedance-Voltage Dual-Mode Low Humidity Sensor Based on LiBr-MOF-801 with High Response.

Dual-mode humidity sensors have received wide attention in recent years due to their great potential in multifunction applications. Herein, following a "two birds with one stone" strategy, a dual-mode and self-powered low humidity sensor based on LiBr-MOF-801 with high response and power generation is proposed. The optimized LiBr-MOF-801-based sensor exhibits impedance-voltage dual-mode sensitivity in the low humidity range of 0-23% relative humidity (RH) with high response (57.1 and 0.61 V), small hysteresis (0.3% RH) and good long-term stability at room temperature (20 °C). Moreover, an integrated humidity power generator is obtained by series connection of the self-powered humidity sensor within 15 cm2, and the output voltage reaches 2.6 V with an output power density of 110 nW cm-2, and can be used as energy, supplying power to commercial electronic equipment even in low humidity. This work provides a new sight for fabricating high-performance, dual-mode, and self-powered low-humidity sensors.

Electron Transport Layer Engineering Induced Carrier Dynamics Optimization for Efficient Cd-Free Sb2 Se3 Thin-Film Solar Cells.

Antimony selenide (Sb2 Se3 ) is a highly promising photovoltaic material thanks to its outstanding optoelectronic properties, as well as its cost-effective and eco-friendly merits. However, toxic CdS is widely used as an electron transport layer (ETL) in efficient Sb2 Se3 solar cells, which largely limit their development toward market commercialization. Herein, an effective green Cd-free ETL of SnOx is introduced and deposited by atomic layer deposition method. Additionally, an important post-annealing treatment is designed to further optimize the functional layers and the heterojunction interface properties. Such engineering strategy can optimize SnOx ETL with higher nano-crystallinity, higher carrier density, and less defect groups, modify Sb2 Se3 /SnOx heterojunction with better interface performance and much desirable "spike-like" band alignment, and also improve the Sb2 Se3 light absorber layer quality with passivated bulk defects and prolonged carrier lifetime, and therefore to enhance carrier separation and transport while suppressing non-radiative recombination. Finally, the as-fabricated Cd-free Mo/Sb2 Se3 /SnOx /ITO/Ag thin-film solar cell exhibits a stimulating efficiency of 7.39%, contributing a record value for Cd-free substrate structured Sb2 Se3 solar cells reported to date. This work provides a viable strategy for developing and broadening practical applications of environmental-friendly Sb2 Se3 photovoltaic devices.

Mpox patients' experience from infection to treatment and implications for prevention and control: A multicenter qualitative study in China.

Monkeypox (mpox), a viral zoonotic disease, is spreading worldwide. However, evidence that informs prevention and control strategies in the Asia Pacific Region is very limited. Our study aims to investigate the experiences of mpox patients from infection to treatment to provide scientific basis for the prevention and control. A multicenter qualitative design was used. A total of 15 mpox patients were recruited between July 6 and July 25, 2023, from six cities in China. Semistructured interviews were conducted by telephone and analyzed using the thematic analysis. The interview was divided into two sections: patients' experiences (prediagnosis experience, treatment-seeking experience, and quarantine experience) and advice. Prediagnosis experience was summarized into three themes: symptoms, possible routes of infection, and knowledge of mpox. Treatment-seeking experience was summarized into three themes: time of visit to hospital, diagnostic difficulties, and attitude toward diagnosis. Quarantine experience was summarized into three themes: body and mind reactions, reluctance to self-disclose infection status, and factors facilitating recovery. Themes identified from patients' advice were as follows: (1) Increase in testing channels and methods, (2) Development and introduction of vaccines, (3) Adjustment of quarantine program, (4) Improvement of treatment measures, and (5) Improvement of publicity and education. To effectively curb the mpox epidemic, structured measures are urgently needed to address the mpox-related stigma and discrimination. Targeted health education should be provided to MSM, focusing on the prevention, detection, and treatment services. Hospitals should enhance the training of clinicians in key departments including infectious disease and dermatology, to improve diagnostic capability and sensitivity. Furthermore, given the absence of specific antiviral medications, supervised home quarantine may be a good option.

Two-Year Outcomes and Biomarker Analysis of Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma After Neoadjuvant Chemotherapy and Immunotherapy from the Phase II WuhanUHGI001 Trial.

BACKGROUND: This study reports the 2-year outcomes and biomarker analysis results of patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma who received neoadjuvant chemotherapy and immunotherapy in a phase II WuhanUHGI001 trial. METHODS: Eligible patients with cT3/4aN+M0 locally advanced G/GEJ adenocarcinoma were screened, enrolled, and treated with 3 cycles of neoadjuvant tislelizumab and SOX followed by D2 gastrectomy and another 5 cycles of postoperative adjuvant SOX. The primary endpoint was major pathological response. RESULTS: Of the 49 included patients, 24 (49.0%) achieved major pathological response and 13 (26.5%) achieved pathological complete response. During a median follow-up of 26.8 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 69.4% and 81.2%, respectively. Grade 3-4 adverse events occurred in six patients (12.2%) during the neoadjuvant period, eight patients (17.0%) during the postoperative period, and seven patients (15.2%) during the adjuvant period. Biomarker analysis revealed that the pathological complete response showed no association with 2-year PFS and OS. Major pathological response showed a potentially strong association with improved 2-year PFS and OS rates. In addition, preoperative circulating tumor cells combined with pathological responses are helpful in prognosis assessment. In addition, our results showed that T downstaging, lymphocyte-to-monocyte ratio, and CD3+ T cells were independent factors that affect PFS. The signet ring cell component (SRCC), T downstaging, and neutrophil-to-lymphocyte ratio were independent factors affecting OS. Prognostic nomograms of PFS and OS constructed based on the multivariate Cox regression results demonstrated suitable calibration and discrimination ability. CONCLUSIONS: Neoadjuvant tislelizumab plus SOX exhibits promising efficacy and acceptable toxicity in patients with locally advanced G/GEJ adenocarcinoma. In addition, our study established a prognostic risk signature and nomograms based on clinicopathological characteristics, which can accurately predict patient outcomes and aid in personalized treatment planning.

LncRNA RASAL2-AS1 promotes METTL14-mediated m6A methylation in the proliferation and progression of head and neck squamous cell carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) are key regulators of the 6-methyladenosine (m6A) epigenetic modification, playing a role in the initiation and progression of tumors. However, the regulatory mechanisms in head and neck squamous cell carcinoma (HNSCC) remain elusive. In this study, we investigated the molecular regulatory mechanisms of the lncRNA RASAL2-AS1 in the occurrence and development of HNSCC tumors. METHODS: A bioinformatics analysis was conducted to analyze the expression level of RASAL2-AS1 in HNSCC and normal tissues. RASAL2-AS1 mRNA and protein levels were detected using RT-PCR and Western blotting. Wound healing, transwell assays, flow cytometry, M6A dot blot, and RNA immunoprecipitation experiments were conducted to explore the regulatory role of the RASAL2-AS1 and downstream targets METTL14/LIS1 signaling pathway in HNSCC. Immunohistochemical examination was conducted to evaluate the expression of METTL14 and LIS1 in HNSCC and normal tissues. A tumor xenograft model of BALB/c nude mice was established to assess the impact of RASAL2-AS1 on cell proliferation and growth. RESULTS: RASAL2-AS1 high expression in HNSCC and cells deteriorated with survival rates of HNSCC. RASAL2-AS1 overexpression in HNSCC accelerated cell migration, colony formation, cell proliferation, cell cycle in S stage, while RASAL2-AS1 knockdown in HNSC cells inhibited cell cycle in G1 stage. After silencing METTL14, the above effects induced by overexpression of the RASAL2-AS1 were reversed. RASAL2-AS1 overexpression prompted LIS1 expression, whereas RASAL2-AS1 silencing reduced LIS1 levels in HNSCC cells, which was confirmed by immunohistological staining. Results demonstrated elevated expression of METTL14 or LIS1 in tongue cancer tissues. Overexpression of RASAL2-AS1 promoted tumor weight and tumor volume, which was counteracted by pcDNA3.1 RASAL2-AS1 plus silencing METTL14 and METTL14 and LIS1 were significantly decreased. CONCLUSION: Our study highlights the functional importance of the LncRNA RASAL2-AS1 in HNSCC and might assist in the development of a prognostic stratification and therapeutic approach. Which regulates HNSCC with the dependence of m6a manner.

Efficacy of Double-Lumen Biliary-Enteric Tube in Enteral Nutrition for Patients with Malignant Obstructive Jaundice.

OBJECTIVE: This study aimed to evaluate the efficacy of a double-lumen biliary-enteric tube (DBET) for enteral nutrition (EN) in individuals with malignant obstructive jaundice (MOJ). METHODS: A retrospective cohort study was conducted using data from a prospectively maintained single-center database, including patients with MOJ. In the intervention group, DBET placement was performed concurrently with percutaneous transhepatic cholangiodrainage and biliary stenting, followed by postoperative EN (DBET-EN). In the control group, deep vein catheterization was undertaken after endoscopic biliary stenting, and parenteral nutrition (PN) was provided. A multivariable generalized linear model was used to assess the association between DBET-EN and 6-month mortality. RESULTS: A total of 74 patients were included in this study, comprising 28 patients in the intervention group (DBET-EN group) and 46 patients in the control group (PN group). Within the 6-month follow-up, 5 patients (17.9%) in the DBET-EN group and 20 (43.5%) in the PN group died. The multivariable generalized linear model demonstrated a significantly reduced 6-month mortality in the DBET-EN group compared to the PN group (adjusted odds ratio [OR]: 0.25, 95% CI: 0.08-0.81, P = 0.020). Secondary outcomes indicated that patients in the DBET-EN group had lower 9-month mortality rates and longer tube retention durations compared to the PN group (all adjusted P < 0.05). Postoperative liver function improved similarly in both groups. At 3, 6, and 9 months postoperatively, patient-generated subjective global assessment (PG-SGA) scores and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scores were significantly higher in the DBET-EN group than in the PN group (P < 0.05). CONCLUSION: The implementation of DBET for EN in patients in the advanced stage of MOJ proved to be a minimally invasive and safe intervention. It significantly improved patients' nutritional status and quality of life while reducing mortality.

Identification of potential biomarkers for atrial fibrillation and stable coronary artery disease based on WGCNA and machine algorithms.

BACKGROUND: Patients with atrial fibrillation (AF) often have coronary artery disease (CAD), but the biological link between them remains unclear. This study aims to explore the common pathogenesis of AF and CAD and identify common biomarkers. METHODS: Gene expression profiles for AF and stable CAD were downloaded from the Gene Expression Omnibus database. Overlapping genes related to both diseases were identified using weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. Hub genes were then identified using the machine learning algorithm. Immune cell infiltration and correlations with hub genes were explored, followed by drug predictions. Hub gene expression in AF and CAD patients was validated by real-time qPCR. RESULTS: We obtained 28 common overlapping genes in AF and stable CAD, mainly enriched in the PI3K-Akt, ECM-receptor interaction, and relaxin signaling pathway. Two hub genes, COL6A3 and FKBP10, were positively correlated with the abundance of MDSC, plasmacytoid dendritic cells, and regulatory T cells in AF and negatively correlated with the abundance of CD56dim natural killer cells in CAD. The AUCs of COL6A3 and FKBP10 were all above or close to 0.7. Drug prediction suggested that collagenase clostridium histolyticum and ocriplasmin, which target COL6A3, may be potential drugs for AF and stable CAD. Additionally, COL6A3 and FKBP10 were upregulated in patients with AF and CAD. CONCLUSION: COL6A3 and FKBP10 may be key biomarkers for AF and CAD, providing new insights into the diagnosis and treatment of this disease.

Lymph node metastasis diagnosis of postoperative OSCC patients by analyzing extracellular vesicles in drainage fluid based on microfluidic isolation.

Lymph node metastasis (LNM) is a typical marker in oral squamous cell carcinoma (OSCC) indicating poor prognosis. Pathological examination by artificial image acquisition and analysis, as the main diagnostic method for LNM, often takes a week or longer which may cause great anxiety of the patient and also retard timely treatment. However, there are few efficient fast LNM diagnosis methods in clinical applications currently. Our previous study profiled the proteomics of extracellular vesicles (EVs) derived from postoperative drainage fluid (PDF) and showed the potential of detecting specific EVs that expressed aspartate ß-hydroxylase (ASPH) for LNM diagnosis in OSCC patients. Considering that the analysis of ASPH+ PDF-EVs is challenging due to their low abundance (counting less than 10% of total EVs in PDF) and the complex EV isolation process of ultra-centrifugation, we developed a facile platform containing two microfluidic chips filled with antibody-modified microbeads to isolate ASPH+ PDF-EVs, with both the capture and retrieval rate reaching around 90%. Clinical sample analysis based on our method revealed that a mean of 6 × 106 /mL ASPH+ PDF-EVs could be isolated from LNM+ OSCC patients compared to 2.5 × 106 /mL in LNM- OSCC ones. When combined with enzyme-linked immunosorbent assay (ELISA) technique that was commonly used in clinical laboratories in hospitals, this microfluidic platform could precisely distinguish postoperative OSCC patients with LNM or not in several hours, which were validated by a double-blind test containing 6 OSCC patients. We believe this strategy has promise for early diagnosis of LNM in postoperative OSCC patients and finally helps guiding timely and reasonable treatment in clinic.

Microglia contribute to nociception via CSF-1R signaling pathway in rat orofacial carcinoma.

OBJECTIVE: Cancer-induced pain is the most common complication of the head and neck cancer. The microglia colony-stimulating factor receptor 1 (CSF1R) plays a crucial role in the inflammation and neuropathic pain. However, the effect of CSF1R on orofacial cancer-induced pain is unclear. Here, we aimed to determine the role of CSF1R in orofacial pain caused by cancer. METHODS: We established an animal model of cancer-induced orofacial pain with Walker 256B cells. Von Frey filament test and laser-intensity pain tester were used to evaluate tumor-induced mechanical and thermal hypersensitivity. Minocycline and PLX3397 were used to alter tumor-induced mechanical and thermal hyperalgesia. Additionally, we evaluated the effect of PLX3397 on immunoinflammatory mediators and neuronal activation within the trigeminal spinal subnucleus caudalis (Vc). RESULTS: Walker 256B cell-induced tumor growth resulted in mechanical and thermal hyperalgesia, accompanying by microglia activation and CSF1R upregulation. Treatment with minocycline or PLX3397 reversed the associated nocifensive behaviors and microglia activation triggered by tumor. As a result of PLX3397 treatment, tumor-induced increases in pro-inflammatory cytokine expression and neuronal activation of the Vc were significantly inhibited. CONCLUSIONS: The results of our study showed that blocking microglial activation via CSF1R may help prevent cancer-induced orofacial pain.

Association between oxidative balance score and kidney stones: data from the national health and nutrition examination survey (NHANES).

PURPOSE: Some studies have found that the pathological formation of kidney stones is closely related to injury and inflammatory response. Behaviors such as dietary composition, physical activity, obesity and smoking can all affect the body's oxidative stress levels. In order to evaluate the effects of various diets and lifestyles on the body's oxidative and antioxidant systems, an oxidative balance score was developed. To investigate whether the OBS is associated with the development of kidney stones. METHODS: Data were taken from the National Health and Nutrition Examination Survey (NHANES) from 2007-2018, followed by retrospective observational studies. The association between kidney stones and OBS was analyzed using survey-weighted logistic regression by adjusting for demographics, laboratory tests, and medical comorbidity covariates. The oxidative balance score is calculated by screening 16 nutrients and 4 lifestyle factors, including 5 prooxidants and 15 antioxidants, based on prior information about the relationship between oxidation levels in the body and nutrients or lifestyle factors. RESULTS: A total of 26,786 adult participants were included in the study, of which 2,578, or 9.62%, had a history of nephrolithiasis. Weighted logistic regression analysis found an association between OBS and kidney stones. In the fully tuned model, i.e., model 3, the highest quartile array of OBS was associated with the lowest quartile array of OBS (OR = 0.73 (0.57, 0.92)) with the risk of kidney stone (p = 0.01), and was statistically significant and remained relatively stable in each model. At the same time, the trend test in the model is also statistically significant. With the increase of OBS, the OR value of kidney stones generally tends to decrease. CONCLUSIONS: There is an inverse correlation between OBS and kidney stone disease. At the same time, higher OBS suggests that antioxidant exposure is greater than pro-oxidative exposure in diet and lifestyle, and is associated with a lower risk of kidney stones.

Risk factor analysis and nomogram for predicting poor symptom control in smoking asthmatics.

BACKGROUND: Smoking induces and modifies the airway immune response, accelerating the decline of asthmatics' lung function and severely affecting asthma symptoms' control level. To assess the prognosis of asthmatics who smoke and to provide reasonable recommendations for treatment, we constructed a nomogram prediction model. METHODS: General and clinical data were collected from April to September 2021 from smoking asthmatics aged ≥14 years attending the People's Hospital of Zhengzhou University. Patients were followed up regularly by telephone or outpatient visits, and their medication and follow-up visits were recorded during the 6-months follow-up visit, as well as their asthma control levels after 6 months (asthma control questionnaire-5, ACQ-5). The study employed R4.2.2 software to conduct univariate and multivariate logistic regression analyses to identify independent risk factors for 'poorly controlled asthma' (ACQ>0.75) as the outcome variable. Subsequently, a nomogram prediction model was constructed. Internal validation was used to test the reproducibility of the model. The model efficacy was evaluated using the consistency index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve. RESULTS: Invitations were sent to 231 asthmatics who smoked. A total of 202 participants responded, resulting in a final total of 190 participants included in the model development. The nomogram established five independent risk factors (P<0.05): FEV1%pred, smoking index (100), comorbidities situations, medication regimen, and good or poor medication adherence. The area under curve (AUC) of the modeling set was 0.824(95%CI 0.765-0.884), suggesting that the nomogram has a high ability to distinguish poor asthma control in smoking asthmatics after 6 months. The calibration curve showed a C-index of 0.824 for the modeling set and a C-index of 0.792 for the self-validation set formed by 1000 bootstrap sampling, which means that the prediction probability of the model was consistent with reality. Decision curve analysis (DCA) of the nomogram revealed that the net benefit was higher when the risk threshold probability for poor asthma control was 4.5 - 93.9%. CONCLUSIONS: FEV1%pred, smoking index (100), comorbidities situations, medication regimen, and medication adherence were identified as independent risk factors for poor asthma control after 6 months in smoking asthmatics. The nomogram established based on these findings can effectively predict relevant risk and provide clinicians with a reference to identify the poorly controlled population with smoking asthma as early as possible, and to select a better therapeutic regimen. Meanwhile, it can effectively improve the medication adherence and the degree of attention to complications in smoking asthma patients.

Daidzein protects endothelial cells against high glucose-induced injury through the dual-activation of PPARα and PPARγ.

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARß antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARß. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors.

Efforts made, challenges faced, and recommendations provided by stakeholders involved in mpox prevention and control in China: a qualitative study.

OBJECTIVES: Mpox continues to spread in China, and stakeholders' experiences may help inform prevention and control strategies. STUDY DESIGN: Qualitative study. METHODS: A qualitative study across 14 Chinese cities recruited stakeholders from Centers for Disease Control and Prevention (CDCs), community-based organizations (CBOs), and hospitals involved in curbing mpox. Semi-structured interviews were conducted by telephone and analyzed using Colaizzi's phenomenological method. RESULTS: 15 CBOs workers, 14 CDCs staff, and 13 healthcare workers were recruited. Three theme categories were identified: "Efforts to curb mpox epidemic", including CDCs' epidemic management and health education, hospitals' diagnosis, treatment, and care, CBOs' counseling, publicity, and referrals. "Challenges to curb mpox epidemic", including negative impacts of hospital-based quarantine, lack of specific antiviral drugs, gay identity disclosure concerns, psychological problems, contact tracing difficulties, and inadequate communication and collaboration. "Recommendations for curbing mpox epidemic", including prioritizing supervised home-based quarantine, incorporating HIV-related indicators into hospital quarantine criteria, reducing the cost of hospital quarantine, accelerating the development of vaccines and drugs, enhancing patient privacy protection, psychological training for stakeholders, establishing a task force that comprises personnel who are experienced in contact tracing and strengthening communication and collaboration. CONCLUSIONS: Effective control of mpox spread requires strengthening collaboration with CBOs and community healthcare centers (CHCs) and working out a flexible and contextualized mechanism. It also needs to reinforce patient privacy protection and integrate stigma reduction into strategies. Additionally, it is important to include HIV-related indicators in the quarantine evaluation and provide psychological training for stakeholders to help them manage their mental health and improve counseling skills.

DeepSub: Utilizing Deep Learning for Predicting the Number of Subunits in Homo-Oligomeric Protein Complexes.

The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt, this information is not readily available for most proteins. In this study, we addressed this gap by extracting and curating subunit information from the UniProt database to establish a robust benchmark dataset. Subsequently, we propose a novel model named DeepSub, which leverages the protein language model and Bi-directional Gated Recurrent Unit (GRU), to predict NS in homo-oligomers solely based on protein sequences. DeepSub demonstrates remarkable accuracy, achieving an accuracy rate as high as 0.967, surpassing the performance of QUEEN. To validate the effectiveness of DeepSub, we performed predictions for protein homo-oligomers that have been reported in the literature but are not documented in the UniProt database. Examples include homoserine dehydrogenase from Corynebacterium glutamicum, Matrilin-4 from Mus musculus and Homo sapiens, and the Multimerins protein family from M. musculus and H. sapiens. The predicted results align closely with the reported findings in the literature, underscoring the reliability and utility of DeepSub.

[Clinical and genetic analysis of a patient with short stature due to variant of RPL13 gene].

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene. METHODS: A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c.548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION: Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.