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Purpose Our study aimed to investigate the potential of radiomics with DCE-MRI for predicting Ki-67 expression in invasive ductal breast cancer. Method We conducted a retrospective study including 223 patients diagnosed with invasive ductal breast cancer. Radiomics features were extracted from DCE-MRI using 3D-Slicer software. Two Ki-67 expression cutoff values (20% and 29%) were examined. Patients were divided into training (70%) and test (30%) sets. The Elastic Net method selected relevant features, and five machine-learning models were established. Radiomics models were created from intratumoral, peritumoral, and combined regions. Performance was assessed using ROC curves, accuracy, sensitivity, and specificity. Result For a Ki-67 cutoff value of 20%, the combined model exhibited the highest performance, with area under the curve (AUC) values of 0.838 (95% confidence interval (CI): 0.774–0.897) for the training set and 0.863 (95% CI: 0.764–0.949) for the test set. The AUC values for the tumor model were 0.816 (95% CI: 0.745–0.880) and 0.830 (95% CI: 0.724–0.916), and for the peritumor model were 0.790 (95% CI: 0.711–0.857) and 0.808 (95% CI: 0.682–0.910). When the Ki-67 cutoff value was set at 29%, the combined model also demonstrated superior predictive ability in both training set (AUC: 0.796; 95% CI: 0.724–0.862) and the test set (AUC: 0.823; 95% CI: 0.723–0.911). The AUC values for the tumor model were 0.785 (95% CI: 0.708–0.861) and 0.784 (95% CI: 0.663–0.882), and for the peritumor model were 0.773 (95% CI: 0.690–0.844) and 0.729 (95% CI: 0.603–0.847). Conclusion Radiomics with DCE-MRI can predict Ki-67 expression in invasive ductal breast cancer. Integrating radiomics features from intratumoral and peritumoral regions yields a dependable prognostic model, facilitating pre-surgical detection and treatment decisions. This holds potential for commercial diagnostic tools.

Throughout pregnancy, maternal thyroid-related hormones are transported to the fetus via the placenta to allow normal fetal growth and development and are particularly important in the first and second trimesters of pregnancy. During maternal-fetal transport, in addition to thyroid-related hormones, thyroid-stimulating hormone receptor antibodies and antithyroid drugs can enter the fetus and interfere with development of the fetal thyroid gland and endocrine function, potentially leading to hyperthyroidism or hypothyroidism in the fetus or newborn. Several basic studies have been performed to demonstrate the important role of thyroid-related hormones in fetal and neonatal bone development. Ultrasound can assess neonatal skeletal maturity and bone development safely, rapidly, and effectively. This review aims to communicate the latest knowledge about maternal and fetal thyroid function in both normal and pathological pregnancies and summarize the latest advances in the potential effects of abnormal maternal thyroid function on bone development in the fetus and neonate. Finally, it discusses recent advances in research on ultrasound in the assessment of fetal and neonatal bone development.

Malignant tumors have become a significant risk factor for human mortality. Although there have been notable advancements in the treatment of tumors, patient prognosis remains poor. In recent years, gene diagnosis and gene therapy have brought great benefits to patients. Deoxythymidine kinase (DTYMK) is a highly promising biomarker, has been studied by many scholars, and plays a crucial role in the occurrence and development of various types of cancer. The abnormal expression of DTYMK is involved in tumor occurrence and development, and may also serve as a biomarker for tumor diagnosis, treatment, and prognosis. Several experimental studies have shown that DTYMK can impact tumor progression by regulating mechanisms such as cell cycle, tumor microenvironment, immune infiltration, and signaling pathways. Therefore, this article focuses on clarifying the mechanism of DTYMK in tumors and exploring its clinical application value to help patients prolong their survival cycle and improve their quality of life.

Background The aim of this study was to develop and validate a prediction model for predicting the risk of preoperative asymptomatic lower extremity venous thrombosis (LEVT) in patients with knee osteoarthritis (KOA). Methods Patients with KOA diagnosed at our hospital between March 2022 and July 2023 were included in this study. Five factors were identified as independent risk factors for the development of preoperative asymptomatic LEVT in patients with KOA by univariate and multivariate logistic regression analysis and a prediction model was constructed by analyzing the results. The performance of the model was evaluated using receiver operating characteristic (ROC) curves. The accuracy of the model and its predictive ability were evaluated using calibration curves. The clinical application value of the prediction model was evaluated using decision curve analysis (DCA). Results A total of 354 patients diagnosed with KOA were included in the study. Multivariate logistic regression analysis revealed HDL 0.55 mg/L ( P = 0.049 ) were the independent risk factors for the occurrence of preoperative asymptomatic LEVT in patients with KOA. The combined-variable ROC curve suggested greater predictability and accuracy (AUC = 0.843, specificity = 90.3%, sensitivity = 71.4%). The calibration curve showed good model agreement and DCA suggested good clinical value of the model. Conclusion Low HDL, high LDL, Na + , Ca 2+ , and D-dimer levels can be used as independent risk factors for the preoperative prediction of asymptomatic LEVT in patients with KOA, and the present study also provides a simple prediction model for clinicians and patients.

Background Gamma delta (γδ) T cells play dual roles in human tumors, with both antitumor and tumor-promoting functions. However, the role of γδT cells in HPV-infected cervical cancer is still undetermined. Therefore, we aimed to identify γδT cell-related prognostic signatures in the cervical tumor microenvironment. Methods Single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data, and corresponding clinical information of cervical cancer patients were obtained from the TCGA and GEO databases. The Seurat R package was used for single-cell analysis, and machine learning algorithms were used to screen and construct a γδT cell-related prognostic signature. Real-time quantitative PCR (RT-qPCR) was performed to detect the expression of prognostic signature genes. Results Single-cell analysis indicated distinct populations of γδT cells between HPV-positive (HPV+) and HPV-negative (HPV-) cervical cancers. A trajectory analysis indicated γδT cells clustered into differential clusters with the pseudotime. High-dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) identified the key γδT cell-related gene modules. Bulk RNA-seq analysis also demonstrated the heterogeneity of immune cells, and the γδT-score was positively associated with inflammatory response and negatively associated with MYC stemness. Eight γδT cell-related hub genes (GTRGs), including ITGAE, IKZF3, LSP1, NEDD9, CLEC2D, RBPJ, TRBC2, and OXNAD1, were selected and validated as a prognostic signature for cervical cancer. Conclusion We identified γδT cell-related prognostic signatures that can be considered independent factors for survival prediction in cervical cancer.

Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan–Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% ( P = .042), and the 3-year DFS rates were 70.4% and 47.4% ( P = .003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS ( P = .033, .003, .042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS ( P = .015, .003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5 cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients ( P = .046, .006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C.

Background: Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID. Method: This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis. Result: The RR of high-grade diarrhea and all-grade diarrhea were 0.31 ( I 2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 ( I 2 = 65%, 95% CI: 0.62-0.93; P

Background: Siwu Decoction (SWD) is a well-known classical TCM formula that has been shown to be effective as a basis for preventing and reducing liver metastases (LM). However, the active ingredients and potential molecular mechanisms remain unclear. Objective: This study aimed to systematically analyze the active ingredients and potential molecular mechanisms of SWD on LM and validate mechanisms involved. Materials and methods: The active ingredients in SWD were extracted by UHPLC-MS/MS in a latest study. Protox II was retrieved to obtain toxicological parameters to detect safety. Swiss Target Prediction database was exploited to harvest SWD targets. Five databases, Gene Cards, DisGeNET, Drugbank, OMIM, and TTD, were employed to filter pathogenic targets of LM. STRING database was utilized to construct the protein–protein interaction network for therapeutic targets, followed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. GEPIA database and the Human Protein Atlas were taken to observe the expression of core genes and proteins. ImmuCellAI algorithm was applied to analyze the immune microenvironment and survival relevant to core genes. Molecular docking was performed to verify the affinity of SWD effective ingredients to core targets. In vivo experiments were carried out to validate the anti-LM efficacy of SWD and verify the pivotal mechanisms of action. Results: Eighteen main bioactive phytochemicals identified were all non-hepatotoxic. PPI network acquired 118 therapeutic targets, of which VEGFA, CASP3, STAT3, etc. were identified as core targets. KEGG analysis revealed that HIF-1 pathway and others were critical. After tandem targets and pathways, HIF-1/VEGF was regarded as the greatest potential pathway. VEGFA and HIF-1 were expressed differently in various stages of cancer and normal tissues. There was a negative regulation of immunoreactive cells by VEGFA, which was influential for prognosis. Molecular docking confirmed the tight binding to VEGFA. This study revealed the exact effect of SWD against LM, and identified significant inhibition the expression of HIF-1α, VEGF, and CD31 in the liver microenvironment. Conclusion: This study clarified the active ingredients of SWD, the therapeutic targets of LM and potential molecular mechanisms. SWD may protect against LM through suppressing HIF-1/VEGF pathway.

We present a unique case of left atrial (LA) dissection in a 46-year-old man following aortic dissection surgery. The LA dissection was attributed to coronary sinus catheter–related injury. This report highlights the importance of recognizing this rare complication and the crucial role of transesophageal echocardiography in its diagnosis. We discuss the pathogenesis, diagnostic criteria, and management strategies for LA dissection.

To identify key factors affecting all-cause mortality in the elderly aged 80 years and above. Data from Chinese Longitudinal Healthy Longevity Survey (2011-2018) were utilized ( N = 3993). A healthy lifestyle score was obtained by assigning 8 factors: smoking, drinking, exercise, sleep duration, social activity, waist circumference, BMI, and healthful plant-based diet index. Cox regression and decision tree model were used to identify factors influencing the mortality risk. Lifestyle and activities of daily living (ADL) were 2 of the most important modifiable factors influencing the mortality risk of the oldest seniors. A higher healthy lifestyle score was associated with lower mortality risk. The HR (95% CI ) of death risk in Q2, Q3, and Q4 groups were 0.91 (0.81-1.01), 0.78 (0.71-0.86), and 0.64 (0.58-0.71), respectively, when compared with the Q1 group of healthy lifestyle score. Elderly with ADL disability had a higher mortality rate than those without ADL disability. When the elderly already have ADL disability, the healthier the lifestyle, the lower the mortality rate. Among individuals aged 80 to 89 years with ADL disability, the mortality rate was higher in the healthy lifestyle score Q1-Q2 groups (92.1%) than that in the Q3-Q4 groups (71.6%). Similar results were observed among subjects aged 90 to 99 years with ADL disability (Q1-Q2: 97.9%, Q3-Q4: 92.1%). For centenarians without ADL disability, maintaining a healthy lifestyle significantly reduced mortality (Q1-Q3: 90.5%, Q4: 75.5%). Caregivers should prioritize the consideration of lifestyle and ADL in their healthcare practices of the oldest old.

Objective We investigated the potential of dual-energy computed tomography (DECT) radiomics in assessing cancer-associated fibroblasts in clear cell renal carcinoma (ccRCC). Methods A retrospective analysis was conducted on 132 patients with ccRCC. The arterial and venous phase iodine-based material decomposition images (IMDIs), virtual non-contrast images, 70 keV, 100 keV, and 150 keV virtual monoenergetic images, and mixed energy images (MEIs) were obtained from the DECT datasets. On the Radcloud platform, radiomics feature extraction, feature selection, and model establishment were performed. Seven radiomics models were established using the support vector machine. The predictive performance was evaluated by utilizing receiver operating characteristic and the area under the curve (AUC) was calculated. Nomograms were constructed. Results The combined model demonstrated high efficiency in evaluating pseudocapsule thickness with AUC, specificity, and sensitivity of 0.833, 0.870, and 0.750, respectively in the validation set, surpassing those of other models. The precision, F1-score, and Youden index were also higher for the combined model. For evaluating the number of collagen fibers, the combined model exhibited the highest AUC (0.741) among all models, with a specificity of 0.830 and a sensitivity of 0.330. The AUC in the 150 kv model and IMDI model were slightly lower than those in the combined model (0.728 and 0.710, respectively), with corresponding sensitivity and specificity of 0.560/0.780 and 0.670/0.830. The nomogram exhibited that Rad-score had good prediction efficiency. Conclusion DECT radiomics features have significant value in evaluating the interstitial fibers of ccRCC. The combined model of IMDI + MEI exhibits superior performance in assessing the thickness of the pseudocapsule, while the combined, 150 keV, and IMDI models demonstrate higher efficacy in evaluating collagen fiber number. Radiomics, combined with imaging features and clinical features, has excellent predictive performance. These findings offer crucial support for the clinical diagnosis, treatment, and prognosis of ccRCC and provide valuable insights into the application of DECT.

Exostosis (also known as osteochondroma) is the most common benign bony lump of young people, usually arising at the distal femur. Vascular complications associated with exostoses are rare and include true aneurysm or pseudoaneurysm formation, deep vein thrombosis, arteriovenous fistula, and arterial insufficiency of the limbs. Few case reports describe pseudoaneurysms resulting from exostoses in mature adults, and no consensus has been reached regarding the optimal therapy. We report the case of a 51-year-old male patient complaining of persistent right thigh pain with a pulsatile mass and right calf swelling, without a history of trauma or hereditary multiple exostoses. The diagnosis was confirmed by computed tomography angiography, which showed a pseudoaneurysm of the popliteal artery resulting from an exostosis on the lateral aspect of the distal femur. A Doppler ultrasound examination confirmed popliteal vein thrombosis caused by the compression of the pseudoaneurysm. Surgical treatment consisted of removing the exostosis, excision of the pseudoaneurysm, and an end-to-end anastomosis. The deep vein thrombosis was treated with rivaroxaban for 3 months. The patient was discharged after 6 days and followed up for 6 months with satisfactory results.

We aimed to explore the relationship between pulmonary artery distensibility obtained from computed tomography pulmonary angiography (CTPA) and short-term adverse clinical outcomes in patients with acute pulmonary embolism (APE). We included patients who underwent retrospective electrocardiogram-gated CTPA and were subsequently diagnosed with APE. Patients were categorized into good and poor outcome groups based on short-term clinical outcomes. Pulmonary artery distensibility (AD), right ventricle/left ventricle (RV/LV) ratio, and pulmonary artery obstruction index (PAOI) were measured, and the receiver operating characteristic curves were constructed. Sixty-four patients with APE (good outcome, 46; poor outcome, 18) were enrolled. AD, RV/LV ratio, and PAOI differed significantly between groups (P

Background: Chronic respiratory diseases (CRDs) pose a significant global health burden. Antioxidant-rich diets have been associated with improved lung health, but the specific relationship with CRDs remains unclear. Methods: This study examined the relationship between dietary antioxidant intakes and CRDs using data from the 2001–2018 National Health and Nutrition Examination Survey (NHANES). Information on dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoid, were collected from the 2 24-h recall interviews to calculate composite dietary antioxidant index (CDAI). CRDs were determined based on self-reported physician diagnoses. To examine the relationship between CDAI and CRDs, multivariate logistic regression was used. To study potential non-linear correlations within these associations, restricted cubic spline (RCS) regression was performed. Results: The study involved 40 557 individuals. The median CDAI was −0.09 (−2.05, 2.25). We discovered those who were in the fourth quartile of CDAI scores had a 19% lower prevalence than those in the first quartile (OR = 0.81 [0.72–0.91], Ptrend < 0.01) after adjusting for all relevant covariates. The fourth quartile of CDAI was linked with a lower prevalence of emphysema (OR = 0.57 [0.40–0.81], Ptrend < 0.01) and chronic bronchitis (OR = 0.74 [0.62–0.88], Ptrend < 0.01). RCS regression showed that CDAI was non-linearly related to the prevalence of CRDs, with inflection points of 3.20 (P for non-linearity

The quality control of herbal medicines is key to their clinical efficacy. The multi-component and multi-effect characteristics of herbal medicines have prompted scholars to clarify various factors related to quality evaluation through various methods. Nevertheless, the relationship between chemical properties and their associated clinical efficacy is little reflected in the quality control techniques currently in use. To address the issue, a novel herbal quality standard system based on the efficacy-oriented Q-marker of the effect-constituent index (ECI) is promoted in this study, using Scutellariae Radix (SR), a widely used herbal medicine with anti-inflammation, anti-tumor, anti-viral and other therapeutic effects, as a case study. Combined with chromatographic analysis and bioassay, four Q-markers including baicalin, baicalein, wogonin and oroxylin A were selected based on the anti-inflammatory efficacy of SR. The ECI model of SR was constructed by combining the content determination of the Q-markers via ultra-high-performance liquid chromatography-triple quadrupole mass spectroscopy (UHPLC-QqQ-MS/MS) with the corresponding biological potency obtained from the anti-inflammatory effects on tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. Correlation analysis showed that the ECI was significantly correlated with the measured anti-inflammatory activity ( p < 0.01). The ECI exhibited a good ability to determine and predict the bioeffect-based quality grade for SR. Overall, the construction and application of the ECI for SR in this study provides a beneficial reference for quality evaluation methods of other herbs with distinct effects and active ingredients.

Children's tendency to prefer rich to poor people and to view wealthy individuals more positively has been well-documented, but little is known about (a) the mechanisms underlying this "pro-wealth" bias and (b) the extent to which it holds across various social domains (e.g., friendships vs. school project partners). Using a mixed-methods approach, we examined the development of status-based social preferences in a socioeconomically diverse sample of children from Chinese American immigrant families ( N = 169; 7-11 years; M Age = 9.16 years, SD ± 1.05; 87 male, 82 female). We examined the development of these preferences in middle childhood, a period during which aspects of group membership and social stratification are salient, particularly for children of immigrants. Children exhibited preferences for a high-status child over a low-status child across three social domains (friendship, playdate, and school project). Children's open-ended responses explaining their preferences most commonly referenced status-based stereotypes (e.g., "He's more educated, he might know more about the topic") and personal loss or gain (e.g., "I'll get to play with his stuff"). Children higher in parent-rated effortful control exhibited fewer status-based preferences and were less likely to reference status-based stereotypes and personal loss or gain in their explanations. Together, these findings shed light on the complexity and nuance of children's pro-wealth bias, as well as the underlying forces that drive these social preferences. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Plants bearing double flowers have long been cultivated as ornamental plants. Hose-in-hose flowers, bearing 2-whorled corolla tubes in whorls 1 and 2, are uncommon but recur in Sinningia (Gesnerioideae, Gesneriaceae). In this study, we selected 15 hose-in-hose cultivars as materials to explore the underlying molecular and genetic mechanisms of this floral architecture. We found that they originated from different hybridization events within the Dircaea clade. Three B-class MADS-box genes were globally expressed in all floral whorls, but only GLOBOSA1 (GLO1) has accumulated a dominant mutation, i.e., the insertion of a hAT-like miniature inverted-repeat transposable element (MITE) into its promoter, that co-segregated with the hose-in-hose phenotype. In addition, all 15 hose-in-hose cultivars contained the same dominant GLO1 allele. Transient gene expression assays confirmed the role of this MITE insertion in up-regulating the promoter activity of GLO1 by providing several cis-regulatory elements. Genetic transformation in heterologous Chirita pumila (Didymocarpoideae, Gesneriaceae) verified that this dominant GLO1 allele is sufficient to confer the hose-in-hose phenotype. We further demonstrated that both the GLO1 allele and the hAT-like MITE descended from wild S. cardinalis with single flowers. This study highlights the significance of wide hybridization in frequent gains of the dominant GLO1 allele and thereafter repeated occurrence of hose-in-hose flowers in Sinningia., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Heat stress (HS) has become a common stressor, owing to the increasing frequency of extreme high-temperature weather triggered by global warming, which has seriously affected the reproductive capacity of important livestock such as sheep. However, little is known about whether HS reduces sperm motility by inducing circadian rhythm disorders in rumen microorganisms and metabolites in sheep. In this study, the year-round reproduction of two-year-old Hu rams was selected, and the samples were collected in May and July 2022 at average environmental temperatures between 18.71 °C and 33.58 °C, respectively. The experiment revealed that the mean temperature-humidity index was 86.34 in July, indicating that Hu rams suffered from HS. Our research revealed that HS significantly decreased sperm motility in Hu rams. Microbiome analysis further revealed that HS reshaped the composition and circadian rhythm of rumen microorganisms, leading to the circadian disruption of microorganisms that drive cortisol and testosterone synthesis. Serum indicators further confirmed that HS significantly increased the concentrations of cortisol during the daytime and decreased the testosterone concentration at the highest body temperature. Untargeted metabolomics analysis revealed that the circadian rhythm of rumen fluid metabolites in the HS group was enriched by the cortisol and steroid synthesis pathways. Moreover, HS downregulated metabolites, such as kaempferol and L-tryptophan in rumen fluid and seminal plasma, which are associated with promotion of spermatogenesis and sperm motility; furthermore, these metabolites were found to be strongly positively correlated with Veillonellaceae&#95;UCG&#95;001 . Overall, this study revealed the relationship between the HS-induced circadian rhythm disruption of rumen microorganisms and metabolites and sperm motility decline. Our findings provide a new perspective for further interventions in enhancing sheep sperm motility with regard to the circadian time scale.

High-intensity lasers require suppression of prepulses and other nonideal temporal structure to avoid target disruption before the arrival of the main pulse. To address this, we demonstrate that ionization gratings act as a controllable optical switch for high-power light with a temporal contrast improvement of at least 3×10^{5} and a switching time less than 500 fs. We also show that a grating system can run for hours at 10 Hz without degradation. The contrast improvement from an ionization grating compares favorably to that achievable with plasma mirrors.

Objective: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants., Methods: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection (BTI) following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals., Results: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 BTI, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 BTI following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 BTI after primary vaccination., Conclusions: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pattern recognition receptors are an essential part of the immune system, which detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and help shape both innate and adaptive immune responses. When dsDNA is present, cyclic GMP-AMP Synthase (cGAS) produces a second messenger called cyclic GMP-AMP (cGAMP), which then triggers an adaptor protein called STING, and eventually activates the expression of type I interferon (IFN) and pro-inflammatory cytokines in immune cells. The cGAS-STING signaling pathway has been receiving a lot of attention lately as a key immune-surveillance mediator. In this review, we summarize the present circumstances of the cGAS-STING signaling pathway in viral infections and inflammatory diseases, as well as autoimmune diseases. Modulation of the cGAS-STING signaling pathway provides potential strategies for treating viral infections, inflammatory diseases, and autoimmune diseases., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Introduction: An increasing number of early-stage lung adenocarcinoma (LUAD) are detected as lung nodules. The radiological features related to LUAD progression remain further investigation. Exploration is required to bridge the gap between radiomics features and molecular characteristics of lung nodules., Methods: Consensus clustering was applied to the radiomics features of 1,212 patients to establish stable clustering. Clusters were illustrated using clinicopathological and next-generation sequencing (NGS). A classifier was constructed to further investigate the molecular characteristic in patients with paired CT and RNA-seq data., Results: Patients were clustered into 4 clusters. Cluster 1 was associated with a low consolidation-to-tumor ratio (CTR), pre-invasion, grade I disease and good prognosis. Clusters 2 and 3 showed increasing malignancy with higher CTR, higher pathological grade and poor prognosis. Cluster 2 possessed more spread through air spaces (STAS) and cluster 3 showed higher proportion of pleural invasion. Cluster 4 had similar clinicopathological features with cluster 1 except higher proportion of grade II disease. RNA-seq indicated that cluster 1 represented nodules with indolent growth and good differentiation, whereas cluster 4 showed progression in cell development but still had low proliferative activity. Nodules with high proliferation were classified into clusters 2 and 3. Additionally, the radiomics classifier distinguished cluster 2 as nodules harboring an activated immune environment, while cluster 3 represented nodules with a suppressive immune environment. Furthermore, gene signatures associated with the prognosis of early-stage LUAD were validated in external datasets., Conclusion: Radiomics features can manifest molecular events driving progression of lung adenocarcinoma. Our study provides a molecular insight into radiomics features and assists in the diagnosis and treatment of early stage LUAD., (Copyright © 2024. Published by Elsevier Inc.)

A new sterol, aspersterol E ( 1 ), a newly discovered alkaloid, asperginine A ( 2 ), and five known compounds ( 3-7 ) were obtained from the endophytic fungus Aspergillus sp. S3 of Hibiscus tiliaceus Linn. The compounds were extracted from their fermentation products using silica gel, ODS C18, and semi-preparative HPLC. The structure of each compound was determined through spectroscopic analysis. All the obtained compounds ( 1-7 ) were evaluated for their cytotoxic activity against the mouse pre-gastric cancer cell line MFC by using the MTT assay. The IC 50 values of compounds 1 , 2 , 3, and 5 were found to be 153.43 μM, 61.25 μM, 73.19 μM, and 181.69 μM respectively.

Background: Hemiptera is the fifth species-rich order of insects and the most species-rich order of hemimetabolous insects, including numerous insect species that are of agricultural or medical significance. Despite much effort and recent advance in inferring the Hemiptera phylogeny, some high-level relationships among superfamilies remain controversial., Results: We sequenced the genomes of 64 hemipteran species from 15 superfamilies and the transcriptomes of two additional scale insect species, integrating them with existing genomic and transcriptomic data to conduct a comprehensive phylogenetic analysis of Hemiptera. Our datasets comprise an average of 1625 nuclear loci of 315 species across 27 superfamilies of Hemiptera. Our analyses supported Cicadoidea and Cercopoidea as sister groups, with Membracoidea typically positioned as the sister to Cicadoidea + Cercopoidea. In most analyses, Aleyrodoidea was recovered as the sister group of all other Sternorrhyncha. A sister-group relationship was supported between Coccoidea and Aphidoidea + Phylloxeroidea. These relationships were further supported by four-cluster likelihood mapping analyses across diverse datasets. Our ancestral state reconstruction indicates phytophagy as the primary feeding strategy for Hemiptera as a whole. However, predation likely represents an ancestral state for Heteroptera, with several phytophagous lineages having evolved from predatory ancestors. Certain lineages, like Lygaeoidea, have undergone a reversal transition from phytophagy to predation. Our divergence time estimation placed the diversification of hemipterans to be between 60 and 150 million years ago., Conclusions: By expanding phylogenomic taxon sampling, we clarified the superfamily relationships within the infraorder Cicadomorpha. Our phylogenetic analyses supported the sister-group relationship between the superfamilies Cicadoidea and Cercopoidea, and the superfamily Membracoidea as the sister to Cicadoidea + Cercopoidea. Our divergence time estimation supported the close association of hemipteran diversification with the evolutionary success and adaptive radiation of angiosperms during the Cretaceous period., (© 2024. The Author(s).)

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy, with a rising incidence worldwide. Accurate prognostic models are essential for effective patient management. This study evaluates the prognostic value of various lymph node staging systems in DTC using a competing risks model. We used SEER database records (1998-2016) of 16,527 DTC patients, analyzing N stage, positive lymph node numbers (PLNNs), metastatic lymph node ratio (MLNR), log odds of positive lymph nodes (LODDS), and log odds of the negative lymph node (NLN)/T stage ratio (LONT). Univariate and multivariate analyses in a competing risks model were performed, along with subgroup analyses based on demographic and clinical characteristics. In this study of 16,527 patients with DTC, different lymph node staging systems showed different prognostic correlations in univariate and multivariate analyses. In particular, PLNNs showed significant prognostic correlations in several subgroups. Additionally, PLNNs were more suitable as a lymph node staging system for DTC than LODDS and MLNR in N1 stage subgroups, with an optimal cut-off of 13. Receiver operating characteristic curves, calibration curves and nomograms improved the clinical utility of the prognostic model based on PLNNs. Using competing risks model and subgroup analyses, we found that PLNNs had the best prognostic discriminatory efficacy for patients with DTC, especially those with N1 stage disease, and had an optimal cut-off value of 13., (© 2024. Italian Society of Surgery (SIC).)

Electrocatalytic nitrogen reduction reaction (NRR) is a green and highly efficient way to replace the industrial Haber-Bosch process. Herein, clusters consisting of three transition metal atoms loaded on C 2 N as NRR electrocatalysts are investigated using density functional theory (DFT). Meanwhile, Ca was introduced as a promoter and the role of Ca in NRR was investigated. It was found that Ca anchored to the catalyst can act as an electron donor and effectively promote the activation of N 2 on M 3 . In both M 3 @C 2 N and M 3 Ca@C 2 N (M=Fe, Co, Ni), the limiting potential (U L ) is less negative than that of the Ru(0001) surface and has the ability to suppress the competitive hydrogen evolution reaction (HER). Among them, Fe 3 @C 2 N is suggested to be the most promising candidate for NRR with high thermal stability, strong N 2 adsorption ability, low limiting potential, and good NRR selectivity. The concepts of trimetallic sites and alkaline earth metal promoters in this work provide theoretical guidance for the rational design of atomically active sites in electrocatalytic NRR., (© 2024 Wiley-VCH GmbH.)

Background: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled., Aim: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps., Methods: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t -tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators., Results: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella , Plesiomonas , and Cronobacter , was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones., Conclusion: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

Drug administration law of the People's Republic of China(2019 revised edition), which came into effect on December 1, 2019, proposed that &quot; the state shall establish a pharmacovigilance system&quot;. Pharmacovigilance work of Chinese patent medicines is more difficult, and it is necessary to carry out Pharmacovigilance activities that are in line with the characteristics of Chinese patent medicines. Pharmacovigilance guidelines of Chinese patent medicines(T/CACM 1563. 1-2024), based on the principles of Drug Administration Law of the People's Republic of China(2019 revised edition) and Pharmacovigilance quality management standards(No. 65 of 2021) of the National Medical Products Administration, draws on the EU Pharmacovigilance regulation and the secondary guidelines of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), and it is drafted in accordance with the provisions of Guidelines for standardization work part 1: structure and drafting rules of standardization documents(GB/T1. 1-2020) based on the characteristics of Chinese patent medicines. It serves as a general document for a series of pharmacovigilance guidelines of Chinese patent medicines, such as Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions(T/CACM 1563. 2-2024), Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines(T/CACM 1563. 3-2024), Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections(T/CACM 1563. 4-2024), Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use(T/CACM 1563. 5-2024), and Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration(T/CACM 1563. 6-2024), including four major elements of pharmacovigilance monitoring and reporting of Chinese patent medicines, signal identification, risk evaluation, and risk control, as well as pharmacovigilance activities for Chinese patent medicines, ensuring the safety of public drug use.

Mitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial cellular processes, such as energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled the exploration of mitochondria-targeting treatment as a promising strategy for cancer therapy. Since the groundbreaking discovery of cisplatin, the trajectory of research on the development of metal complexes have been marked by continuous advancement, giving rise to a diverse array of metallodrugs characterized by variations in ligand types, metal center properties, and oxidation states. By specifically targeting mitochondria, these metallodrugs exhibit the remarkable ability to elicit various programmed cell death pathways, encompassing apoptosis, autophagy, and ferroptosis. This review primarily focuses on recent developments in transition metal-based mitochondria-targeting agents, offering a comprehensive exploration of their capacity to induce distinct cell death modes. The aim is not only to disseminate knowledge but also to stimulate an active field of research toward new clinical applications and novel anticancer mechanisms., (© 2024 Wiley-VCH GmbH.)

The electrolysis of seawater for hydrogen production holds promise as a sustainable technology for energy generation. Developing water-splitting catalysts with low overpotential and stable operation in seawater is essential. In this study, we employed a hydrothermal method to synthesize NiMoWO X microrods (NiMoWO X @NF). Subsequently, an annealing process yielded a composite N-doped carbon-coated Ni 3 N/MoO 2 /WO 2 nanorods (NC@Ni 3 N/MoO 2 /WO 2 @NF), preserving the ultrahigh-specific surface area of the original structure. A two-electrode electrolytic cell was assembled using NC@Ni 3 N/MoO 2 /WO 2 @NF as the cathode and NiMoWO X @NF as the anode, demonstrating exceptional performance in seawater splitting. The cell operated at a voltage of 1.51 V with a current density of 100 mA·cm -2 in an alkaline seawater solution. Furthermore, the NC@Ni 3 N/MoO 2 /WO 2 @NF || NiMoWO X @NF electrolytic cell exhibited remarkable stability, running continuously for over 120 h at a current of 1100 mA·cm -2 without any observable delay. These experimental results are corroborated by density functional theory calculations. The NC@Ni 3 N/MoO 2 /WO 2 @NF || NiMoWO X @NF electrolyzer emerges as a promising option for industrial-scale hydrogen production through seawater electrolysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children. However, certain factors influencing local chickenpox outbreaks have not been studied. Here, we examined the relationship between spatial clustering, heterogeneity of chickenpox outbreaks, and socioeconomic factors in Southern China., Methods: We assessed chickenpox outbreak data from Southern China between 2006 and 2021, comprising both relatively fast-growing parts and slower sub-regions, and provides a representative sample of many developing regions. We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics., Results: There were significant spatial heterogeneity in the risk of chickenpox outbreaks, with strong correlations between chickenpox risk and various factors, particularly demographics and living environment. Furthermore, interactive effects among specific are factors, such as population density and per capita residential building area, percentage of households with toilets, percentage of rental housing, exhibited q statistics of 0.28, 0.25, and 0.24, respectively., Conclusion: This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions, revealing the socioeconomic factors affecting disease transmission. These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

BACKGROUND Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a recently described inflammatory demyelinating disease of the central nervous system (CNS), which needs to be distinguished from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). CASE REPORT A 42-year-old woman presenting with loss of vision due to optic neuritis was admitted to the Naval Medical Center in October 2022. She had optic disc edema, blurred visual margins, optic disc pallor, and deficient visual field in both eyes. Cranial magnetic resonance imaging (MRI) showed bilateral optic nerve thickening, tortuosity, and swelling, especially on the right side. Orbital MRI T2 sequence showed the typical "double track sign" change. The titers of MOG-IgG in CSF and serum were 1: 1 (+) and 1: 32 (+) separately, so MOGAD was diagnosed. The primary treatment was intravenous methylprednisolone for 2 weeks, after which the blurred vision improved and MRI showed the optic nerve lesions disappeared. She was discharged and oral corticosteroids were tapered gradually, and 1 month later, the symptom had vanished without recurrence, cranial MRI was normal, and MOG-IgG in CSF and serum were negative. Low-dose oral corticosteroids were continued for 6 months, with no relapse and normal cranial MRI, so we stopped corticosteroid therapy. At 1-year follow-up, the symptoms had not recurred. CONCLUSIONS A 42-year-old woman presented with loss of vision due to optic neuritis and positive antibody testing for MOG. MOGAD was diagnosed, and timely immunotherapy was effective.

We report herein a direct and practical synthesis of arylsulfonamides from electron-rich aromatic compounds by using in situ generated N -sulfonylamine as the active electrophile. Substrates include derivatives of aniline, indole, pyrrole, furan, styrene and so on. The reaction proceeds under mild conditions and tolerates many sensitive functional groups such as alkyne, acetate, the trifluoromethoxy group or acetoxymethyl ester. Applications of this method for the construction of metal ion sensors and fluorogenic dye have been demonstrated, thus highlighting the potential of this method for probe development., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer, which owned severe resistance to platinum-based anticancer agents. Herein, we report a new metal-arene complex, Ru-TPE-PPh 3 , which can be synthesized in vitro and in living cells with copper catalyzed the cycloaddition reaction of Ru-azide and alkynyl (CuAAC). The complex Ru-TPE-PPh 3 exhibited superior inhibition of the proliferation of TNBC MDA-MB-231 cells with an IC 50 value of 4.0 μM. Ru-TPE-PPh 3 could induce the over production of reactive oxygen species (ROS) to initiate the oxidative stress, and further damage the mitochondria both functionally and morphologically, as loss of mitochondrial membrane potential (MMP) and cutting the supply of adenosine triphosphate (ATP), the disappearance of cristae structure. Moreover, the damaged mitochondria evoked the occurrence of mitophagy with the autophagic flux blockage and cell death. The complex Ru-TPE-PPh 3 also demonstrated excellent anti-proliferative activity in 3D MDA-MB-231 multicellular tumor spheroids (MCTSs), indicating the potential to inhibit solid tumors in living cells. This study not only provided a potent agent for the TNBC treatment, but also demonstrated the universality of the bioorthogonally catalyzed lethality (BCL) strategy through CuAAC reation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Conventional flap repair surgery has several drawbacks, including operational complexity, donor site damage, and high risk. In this case series, the authors explored an alternative approach for repairing exposed tendon wounds caused by trauma using absorbable gelatin sponges (AGSs) and autologous thigh skin grafts. This report presents two cases of lower-extremity skin necrosis with tendon exposure following wound debridement. The treatment approach involved early debridement, negative-pressure wound therapy, and wound irrigation with 0.9% sodium chloride. Upon achieving controlled wound infection, AGSs were applied to the exposed tendon to prevent degeneration and promote wound healing. Subsequently, areas where granulation tissue failed to cover the tendon were repaired using AGSs and 0.25-mm-thick autologous mesh skin grafts harvested from the thigh. Complete wound healing was achieved in both cases, on the 20th and 12th day after skin grafting, respectively. The proposed method proved successful in repairing exposed tendon wounds, effectively preventing infection and necrosis., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Although numerous studies have reported the association between tertiary lymphoid structures (TLSs) and clinical outcomes in cancer patients treated with immune checkpoint inhibitors (ICIs), there remains a lack of a newer and more comprehensive meta-analysis. The main objective of this study is to explore prognostic biomarkers in immunotherapy-related patients, through analyzing the associations between tertiary lymphoid structures (TLSs) and clinical outcomes in cancer patients treated with ICIs, so as to investigate their prognostic value in cancer patients treated with ICIs., Methods: A comprehensive search was conducted until February 2024 across PubMed, Embase, Web of Science, and the Cochrane Library databases to identify relevant studies evaluating the association between tertiary lymphoid structures and clinical outcomes in cancer patients treated with ICIs. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR)., Results: Thirteen studies were incorporated in this meta-analysis, among which nine evaluated the prognostic value of TLSs. The results showed the high levels of TLSs predicted a significantly prolonged OS (pooled HR = 0.35, 95% CI: 0.24-0.53, p < 0.001) and PFS (pooled HR = 0.47, 95% CI: 0.31-0.72, p < 0.001), while lower ORR (pooled OR = 3.78, 95% CI: 2.26-6.33, p < 0.001) in cancer patients treated with ICIs., Conclusion: Our results indicated that high levels of TLSs could predict a favorable prognosis for cancer patients treated with ICIs and have the potential to become a prognostic biomarker of immunotherapy-related patients., Competing Interests: Author PS was employed by Philips Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Guo, Gong, Wang, Wang, Sun, Jiang and Yang.)

Elicitation of effective antitumor immunity following cancer vaccination requires the selective activation of distinct effector cell populations and pathways. Here we report a therapeutic approach for generating potent T cell responses using a modular vaccination platform technology capable of inducing directed immune activation, termed the Protein-like Polymer (PLP). PLPs demonstrate increased proteolytic resistance, high uptake by antigen-presenting cells (APCs), and enhanced payload-specific T cell responses. Key design parameters, namely payload linkage chemistry, degree of polymerization, and side chain composition, were varied to optimize vaccine formulations. Linking antigens to the polymer backbone using an intracellularly cleaved disulfide bond copolymerized with a diluent amount of oligo(ethylene glycol) (OEG) resulted in the highest payload-specific potentiation of antigen immunogenicity, enhancing dendritic cell (DC) activation and antigen-specific T cell responses. Vaccination with PLPs carrying either gp100, E7, or adpgk peptides significantly increased the survival of mice inoculated with B16F10, TC-1, or MC38 tumors, respectively, without the need for adjuvants. B16F10-bearing mice immunized with gp100-carrying PLPs showed increased antitumor CD8 + T cell immunity, suppressed tumor growth, and treatment synergy when paired with two distinct stimulator of interferon gene (STING) agonists. In a human papillomavirus-associated TC-1 model, combination therapy with PLP and 2'3'-cGAMP resulted in 40% of mice completely eliminating implanted tumors while also displaying curative protection from rechallenge, consistent with conferment of lasting immunological memory. Finally, PLPs can be stored long-term in a lyophilized state and are highly tunable, underscoring the unique properties of the platform for use as generalizable cancer vaccines.

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

Dual suppression of oxidative phosphorylation (OXPHOS) and glycolysis can disrupt metabolic adaption of cancer cells, inhibiting energy supply and leading to successful cancer therapy. Herein, we have developed an α-tocopheryl succinate (α-TOS)-functionalized iridium(III) complex Ir2, a highly lipophilic mitochondria targeting anticancer molecule, could inhibit both oxidative phosphorylation (OXPHOS) and glycolysis, resulting in the energy blockage and cancer growth suppression. Mechanistic studies reveal that complex Ir2 induces reactive oxygen species (ROS) elevation and mitochondrial depolarization, and triggers DNA oxidative damage. These damages could evoke the cancer cell death with the mitochondrial-relevant apoptosis and autophagy. 3D tumor spheroids experiment demonstrates that Ir2 owned superior antiproliferation performance, as the potent anticancer agent in vivo. This study not only provided a new path for dual inhibition of both mitochondrial OXPHOS and glycolytic metabolisms with a novel α-TOS-functionalized metallodrug, but also further demonstrated that the mitochondrial-relevant therapy could be effective in enhancing the anticancer performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Although the association between sleep disorders and frailty has been well established, little is known about the cognitive appraisal mechanisms underlying this association. Building on the transactional theory of stress and coping, this study explores the role of self-efficacy and coping style in the association between sleep quality and frailty among community-dwelling older adults., Methods: In this cross-sectional study, 585 community-dwelling older adults were investigated using the Pittsburgh Sleep Quality Index, Tilburg Frailty Indicator, General Self-Efficacy Scale, and Simplified Coping Style Questionnaire. Descriptive statistics and hierarchical regression were performed. A moderated mediation model was established using the PROCESS macro., Results: Poor sleep quality affects frailty directly (B = 0.193, p  < .01) and indirectly via self-efficacy (B = 0.063, p  < .01). The negative impact of poor sleep on frailty through self-efficacy was moderated by both positive and negative coping style (index =  -0.007). The moderating effect was stronger when participants' negative coping tendencies increased., Conclusions: Poor sleep quality indirectly influences frailty by modifying self-efficacy. Effective coping strategies can help attenuate this association., Clinical Implications: Timely sleep assessment and tailored strategies such as psychoeducational programs and targeted coping skills training may be beneficial for preventing frailty in older adults.

In order to characterize and identify the chemical components in different parts of Artemisia argyi(roots, stems, leaves, and seeds), compounds with antioxidant activity were screened. In this study, ultra-performance liquid chromatography-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt-quadrupole time-of-flight-tandem mass spectrometry(UPLC-ABTS-Q-TOF-MS) was used as an online combination technique. Poroshell 120 SB-Aq(3.0 mm×150 mm, 2.7 μm) was used as the column, and acetonitrile(A)-0.2% formic acid water(B) was adopted as the mobile phase to perform gradient elution and was scanned in positive and negative ion modes. MassLynx software was utilized, and combined with reference substances and related literature, the chemical components of different parts of A. argyi were identified and compared. The antioxidant active components were detected by using the online detection system, and the antioxidant activities of active components of different parts of A. argyi were compared and evaluated by scavenging efficiency. As a result, a total of 87 compounds were identified from extracts of different parts of A. argyi, and 38, 72, 85, and 33 components were identified from roots, stems, leaves, and seeds. 22 compounds with antioxidant activity were screened, and 14, 17, 20, and 11 compounds with antioxidant activity were identified from roots, stems, leaves, and seeds. The results show that there are certain differences in chemical components and antioxidant components of different parts of A. argyi, which provides data support for the resource utilization and further research and development of A. argyi.

Background and Purpose: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent μ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid-like side effects were also determined., Experimental Approach: The spinal antinociceptive effects of CEMR-1 and CEMR-2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury-induced neuropathic pain, complete Freund's adjuvant-induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test., Key Results: Spinal administration of CEMR-1 and CEMR-2 produced potent and prolonged antinociceptive effects in acute pain. CEMR-1 and CEMR-2 may produce their antinociception through distinct μ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR-1 showed non-tolerance-forming analgesic properties, while CEMR-2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit., Conclusions and Implications: The present investigation demonstrated that CEMR-1 and CEMR-2 displayed potent and long-lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR-1 and CEMR-2 might serve as promising analgesic compounds with minimal opioid-like side effects., (© 2023 British Pharmacological Society.)