Relationship between triglyceride-glucose index and carotid artery plaques in ischemic stroke patients: Based on blood pressure status, sex, and age.

BACKGROUND: Numerous studies have shown that the triglyceride-glucose (TyG) index is a reliable substitute marker for insulin resistance. Nevertheless, its correlation with carotid artery plaques (CAPs) among patients with ischemic stroke (IS) remains to be elucidated. METHODS: 9248 IS patients hospitalized at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine were grouped according to the quartiles of TyG index. Patients were further stratified by blood pressure status, sex, age and hypertension control status. Employing logistic regression to examine the connection between the TyG index and CAPs.Additionally, analyzing the receiver operating characteristic (ROC) curve to evaluate the predictive value of the TyG index for CAPs. RESULTS: Participants with an elevated TyG index had an increased prevalence of CAPs. The TyG index was positively correlated with CAPs (OR: 1.26, CI: 1.14-1.40, P<0.001). Compared with normal blood pressure and prehypertensive patients, the TyG index was markedly correlated with CAPs among hypertensive patients (OR: 1.29, 95% CI: 1.15-1.44, P<0.001). Females had a higher OR value than males(OR: 1.31, 95% CI: 1.11-1.54, P=0.001 versus OR: 1.24, 95% CI: 1.09-1.41, P=0.001). Older patients (>60 years) had a higher OR value than their middle-aged counterparts (≤60 years) (OR: 1.35; 95% CI: 1.16-1.58, P<0.001 versus OR: 1.20; 95% CI: 1.05-1.37, P=0.007). Patients with poorly-controlled hypertension had a higher OR value than patients with well-controlled hypertension(OR: 1.36; 95% CI: 1.14-1.63, P=0.001 versus OR: 1.24; 95% CI: 1.07-1.44, P=0.003). After adjusting for potential confounding factors, the area under the ROC curve (AUC) value in the overall population, sex-stratified group, hypertensive patients and hypertension control status-stratified group were all above 0.7 (P<0.01), demonstrating good forecasting capability. CONCLUSIONS: In IS patients, the TyG index was significantly associated with CAPs. Additionally, this correlation was more pronounced in hypertensive patients, females, older individuals and patients with poorly-controlled hypertension.

Prognostic significance of diffuse increased fluorine-18-fluorodeoxyglucose (18F-FDG) uptake within the reticuloendothelial system in lymphoma patients.

Background: As constituents of the reticuloendothelial system, the spleen and bone marrow (BM) have been recognized as integral components of the systemic inflammatory response in cancer contexts, thereby serving as predictive indicators for assessing cancer prognosis. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has attained widespread utilization for staging, assessing treatment response, and prognostication in lymphoma patients. Several investigations have proposed that focal increased 18F-FDG uptake in the BM or spleen may correlate with malignant involvement in lymphoma. However, scant data exist regarding the implications of diffuse BM and splenic uptake. This study aimed to explore the relationships between metabolic parameters of the spleen and BM on 18F-FDG PET/CT and inflammatory markers, and to assess their prognostic value in patients with lymphoma. Methods: A retrospective analysis was conducted on 118 patients newly diagnosed with malignant lymphoma, who underwent 18F-FDG PET/CT and exhibited diffuse increased splenic or BM uptake in 18F-FDG PET/CT imaging. The mean standardized uptake value (SUV) of the spleen, BM, and liver was calculated. The association between metabolic variables and systemic inflammatory markers was investigated, and the prognostic significance of clinicopathological and PET parameters was assessed using overall survival (OS) and progression-free survival (PFS). Results: A statistically significant correlation was found between the spleen-to-liver SUV ratio (SLR) and inflammatory markers such as C-reactive protein (r=0.264, P=0.007) and platelet-to-lymphocyte ratio (r=0.227, P=0.021). No significant correlation was observed between BM-to-liver SUV ratio (BLR) and hematologic parameters, while concordance analysis revealed a fair agreement between BLR and bone marrow biopsy (BMB) (Cohen's Kappa-κ =0.271, P=0.002). In patients with aggressive non-Hodgkin lymphoma, both SLR [P=0.017, HR 2.715, 95% confidence interval (CI): 0.875-8.428] and BLR (P=0.044, HR 0.795, 95% CI: 0.348-1.813) were significantly linked to OS, while SLR (P=0.019, HR 2.223, 95% CI: 1.139-4.342) emerged as a significant prognostic factor for PFS. Conclusions: This study highlighted that diffuse increased splenic 18F-FDG uptake in lymphoma patients was closely associated with inflammation, whereas diffuse BM uptake was likely attributable to BM infiltration rather than inflammatory changes. Furthermore, both parameters held promise as prognostic indicators for patients with aggressive lymphoma.

Crowd-sourced machine learning prediction of long COVID using data from the National COVID Cohort Collaborative.

BACKGROUND: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. METHODS: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). FINDINGS: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. INTERPRETATION: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. FUNDING: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

Visualizing Mitochondrial Membrane Potential with FRET Probes: Integrating Fluorescence Intensity Ratio and Lifetime Imaging.

Mitochondrial membrane potential (MMP) is crucial for mitochondrial function and serves as a key indicator of cellular health and metabolic activity. Traditional lipophilic cationic fluorescence intensity probes are unavoidably influenced by probe concentration, laser intensity, and photobleaching, limiting their accuracy. To address these issues, we designed and synthesized a pair of fluorescence molecules, OR-C8 and SiR-BA, based on the Förster Resonance Energy Transfer (FRET) mechanism, for dual-modality visualization of MMP. OR-C8 anchors to the inner mitochondrial membrane through strong hydrophobic interactions, while SiR-BA is expelled from mitochondria when MMP decreases, thereby regulating the FRET process. During MMP reduction, the fluorescence intensity and lifetime of OR-C8 increase, while the fluorescence intensity of SiR-BA decreases. By combining changes in fluorescence intensity ratio and fluorescence lifetime, dual-modality visualization of MMP was achieved. This method not only accurately reflects MMP changes but also provides a novel tool for in-depth studies of mitochondrial function and related disease mechanisms, offering significant potential for advancing mitochondrial research and therapeutic development.

Advances in targeted delivery of mRNA into immune cells for enhanced cancer therapy.

Messenger RNA (mRNA) therapy has been applied to the treatment of various human diseases including malignant tumors. Increasing evidences have shown that mRNA can enhance the efficacy of cancer immunotherapy by modulating the functions of immune cells and stimulating their activity. However, mRNA is a type of negatively charged biomacromolecules that are susceptible to serum nucleases and cannot readily cross the cell membrane. In the past few decades, various nanoparticles (NPs)-based delivery systems have been rationally designed and developed to facilitate the intracellular uptake and cytosolic delivery of mRNA. More importantly, by means of the specific recognition between the targeting ligands decorated on NP surface and receptors specifically expressed on immune cells, these mRNA delivery systems could be functionalized to target immune cells to further enhance the mRNA-based cancer immunotherapy. In this review, we briefly introduced the advancements of mRNA in cancer therapy, discussed the challenges faced by mRNA delivery, and systematically summarized the recent development in NPs-based mRNA delivery systems targeting various types of immune cells for cancer immunotherapy. The future development of NPs-mediated targeted mRNA delivery and their challenges in clinical translation are also discussed.

Nanoparticles (NPs)-mediated lncMALAT1 silencing to reverse cisplatin resistance for effective hepatocellular carcinoma therapy.

Platinum-based chemotherapy has been widely used for clinical cancer treatment, but drug resistance is the main barrier to induce the poor prognosis of cancer patients. Long non-coding RNAs (lncRNAs) have been recognized as a type of new cancer therapeutic targets due to their important role in regulating cancer progression such as drug resistance. However, it is still challenged to effectively intervene the expression of lncRNAs as they are usually located at various subcellular organelles (e.g., nucleus, mitochondrion, and endoplasmic reticulum). We herein developed an endosomal pH-responsive nanoparticle (NP) platform for small interfering RNA (siRNA) and cisplatin prodrug co-delivery and effective cisplatin-resistant hepatocellular carcinoma (HCC) therapy. This co-delivery nanoplatform is comprised of a hydrophilic polyethylene glycol (PEG) shell and a hydrophobic poly (2-(diisopropylamino)ethyl methacrylate) (PDPA) core, in which cisplatin prodrug and electrostatic complexes of nucleus-targeting amphiphilic peptide (NTPA) and siRNA are encapsulated. After intravenous injection and then uptake by tumor cells, the endosomal pH could trigger the dissociation of nanoplatform and enhance the endosomal escape of loaded cisplatin prodrug and NTPA/siRNA complexes via the "proton sponge" effect. Subsequently, the NTPA/siRNA complexes could specifically transport siRNA into the nucleus and efficiently reverse cisplatin resistance via silencing the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncMALAT1) mainly localized in the nucleus, ultimately inhibiting the growth of cisplatin-resistant HCC tumor.

The activities of daily living partially mediate the relationship between rapid eye movement sleep behavior disorder and depressive symptoms in Parkinson's disease.

Objective: A longitudinal study was conducted to investigate whether rapid eye movement sleep behavior disorder affect depression in patients with Parkinson's disease through activities of daily living. Methods: A total of 387 Parkinson's disease patients' six-year follow-up data (one follow-up per year) were obtained from the Parkinson's Progression Markers Initiative. To allow causal effects to manifest, this study increased the lag period and divided the data from the six follow-ups into two groups: wave 1 (wave refers to time points), wave 3, and wave 5 as one group, and wave 2, wave 4, and wave6 as the other group. The time interval between two time points in each group was two years. To comprehensively and deeply analyze the dynamic relationships between variables, accurately infer causal relationships, control for individual differences, and detect the stability of these relationships, this study constructed the fixed effects cross-lagged panel model (CLPM), the random effects CLPM (RE-CLPM) model, and the Equating CLPM and Equating RE-CLPM models with applied restriction conditions. Additionally, a reverse path was added to verify the reverse prediction effect. The most suitable data analysis model was selected to explore the relationships between the study variables. Furthermore, the longitudinal mediating effect of daily living activities between rapid eye movement sleep behavior disorder and depression was investigated. Results: In the models, Equating cross-lagged panel model was the best. The lag effect was positive and significant. In wave 1, 3, 5, activities of daily living mediated 11.82% on the path from rapid eye movement sleep behavior disorder to depression; in wave 2, 4, 6, it mediated 13.13%. Therefore, attention should be paid to the treatment of activities of daily living. Conclusion: Longitudinal changes in activities of daily living have indirect effects on the relationship between rapid eye movement sleep behavior disorder and depression, which highlights the importance of changes in activities of daily living ability in Parkinson's disease patients with rapid eye movement sleep behavior disorder.

COVID-19 prevention and control effect of non-pharmaceutical interventions-fuzzy-sets qualitative comparative analysis based on 69 countries in the world.

Introduction: Coronavirus disease 2019 occurred unexpectedly in late December 2019, it was difficult to immediately develop an effective vaccine or propose targeted medical interventions in the early stages of the outbreak. At this point, non-pharmaceutical interventions (NPIs) are essential components of the public health response to COVID-19. How to combine different NPIs in the early stages of an outbreak to control the spread of epidemics and ensure that the policy combination does not incur high socio-economic costs became the focus of this study. Methods: We mainly used the fuzzy set qualitative comparative analysis to assess the impact of different combinations of NPIs on the effectiveness of control in the COVID-19 pandemic early stage, using open datasets containing case numbers, country populations and policy responses. Results: We showed that the configuration of high morbidity results includes one, which is the combination of non-strict face covering, social isolation and travel restrictions. The configuration of non-high morbidity results includes three, one is strict mask wearing measures, which alone constitute sufficient conditions for interpreting the results; the second is strict testing and contact tracing, social isolation; the third is strict testing and contact tracing, travel restriction. The results of the robustness test showed that the number, components and consistency of the configurations have not changed after changing the minimum case frequency, which proved that the analysis results are reliable. Conclusion: In the early stages of the epidemic, the causes of high morbidity are not symmetrical with the causes of non-high morbidity. Strict face covering is the most basic measure required to prevent and control epidemics, and the combination of non-strict face covering and containment is the most important factor leading to poor prevention and control, and the combination of strict containment and proactive pursuit is the way to achieve superior prevention and control, timely and proactive containment strategies have better prevention and control, and should mobilize the public to cooperate.

Lipid production from corn straw by cellobiohydrolase and delta-6 desaturase engineered Mucor circinelloides strains under solid state fermentation.

Previously, we constructed engineered M. circinelloides strains that can not only utilize cellulose, but also increase the yield of γ-linolenic acid (GLA). In the present study, an in-depth analysis of lipid accumulation by engineered M. circinelloides strains using corn straw was to be explored. When a two-stage temperature control strategy was adopted with adding 1.5% cellulase and 15% inoculum, the engineered strains led to increases in the lipid yield (up to 1.56 g per 100 g dry medium) and GLA yield (up to 274 mg per 100 g dry medium) of 1.8- and 2.3-fold, respectively, compared with the control strain. This study proved the engineered M. circinelloides strains, especially for Mc-C2PD6, possess advantages in using corn straw to produce GLA. This work provided a reference for transformation from agricultural cellulosic waste to functional lipid in one step, which might play a positive role in promoting the sustainable development of biological industry.

Ferumoxytol-Enhanced 5D Multiphase Steady-State Imaging Using Rotating Cartesian K-Space With Low-Rank Reconstruction for Pediatric Congenital Heart Disease.

BACKGROUND: The rotating Cartesian k-space multiphase steady-state imaging with contrast (ROCK-MUSIC) pulse sequence enables acquisition of whole-heart, cardiac phase-resolved images in pediatric congenital heart disease (CHD) without reliance on the ventilator gating signal. Multidimensional reconstruction with low rank tensor (LRT) has shown promise for resolving complex cardiorespiratory motion. PURPOSE: To enhance ROCK-MUSIC by resolving cardiorespiratory phases using LRT reconstruction and to enable semi-automatic hyperparameter tuning by developing an image quality scoring model. STUDY TYPE: Retrospective. POPULATION: Thirty patients (45% female, age 2 days to 6.7 years) with CHD. FIELD STRENGTH/SEQUENCE: 3-T, four-dimensional (4D) spoiled gradient recalled echo sequence. ASSESSMENT: Eigenvector-based iTerative Self-consistent Parallel Imaging Reconstruction (ESPIRiT) served as the reference comparison for LRT reconstruction. A 4-point Likert scale was used for cardiac and vascular image quality scoring based on cardiac chamber definition, lumen signal uniformity, vascular margin clarity, and motion artifact. Ejection fraction and ventricular volumes were assessed in 16 patients. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and edge sharpness were computed. STATISTICAL TESTS: Intraclass correlation coefficients, Wilcoxon signed-rank test, Bland-Altman. A P-value <0.05 was considered statistically significant. RESULTS: Relative to ESPIRiT, LRT images received significantly higher cardiac (2.81 ± 0.57 vs. 3.19 ± 0.54) and vascular (2.81 ± 0.60 vs. 3.36 ± 0.53) image quality scores. Image quality scoring with semi-automated hyperparameter tuning showed strong correlations (R2 = 0.748) among image quality, SNR, and septal sharpness. Comparison of ejection fraction and volumetry derived from ESPIRiT, and LRT showed no significant systematic difference (P = 0.32). DATA CONCLUSION: Integration of low-rank reconstruction with ROCK-MUSIC acquisition may be feasible, and semi-automatic hyperparameter tuning could be effective for generating cardiorespiratory resolved images. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Dual-Modality Imaging with a Zwitterionic Fluorescent Probe for Reversible Monitoring of Mitochondrial Membrane Potential Dynamics.

Traditional fluorescence intensity-based probes face challenges in accurately measuring mitochondrial membrane potential (MMP) due to intramolecular fluorescence quenching. In this work, we introduce a novel approach by incorporating quenching moieties within the zwitterionic probe to eliminate self-quenching interference, thus, enabling real-time and precise visualization of reversible MMP changes. We synthesized a zwitterionic fluorescent probe consisting of silicon-rhodamine (SiR) that was hydroxyl-substituted on the bay position of perylene diimides (PDIs) connected via a polyethylene glycol (PEG) linker. The lipophilic cationic SiR facilitates the entry of the PDI into the mitochondria, where the alkaline pH environment (pH = 8.0) ionizes the hydroxyl to a negatively charged species, affecting the quenching efficiency of SiR depending on the distance between the PDI and SiR moieties regulated by the MMP. The rigid aromatic ring of the PDI and strong hydrophobic interactions with the lipid bilayer, along with the inhibitory effect of the negatively charged hydroxyl on internalization, ensure the retention of PDI within the mitochondria. As the MMP decreases, SiR shifts outward, reducing quenching by phenolic anions and restoring fluorescence. Conversely, as the MMP increases, SiR moves inward, intensifying quenching by phenolic ions and reducing fluorescence, enabling reversible visualization monitoring of the MMP. This strategy overcomes the limitations of traditional intensity-based probes, providing a new avenue for reversible monitoring of the MMP.

Which emerging micropollutants deserve more attention in wastewater in the post-COVID-19 pandemic period? Based on distribution, risk, and exposure analysis.

Aggravated accumulation of emerging micropollutants (EMs) in aquatic environments, especially after COVID-19, raised significant attention throughout the world for safety concerns. This article reviews the sources and occurrence of 25 anti-COVID-19 related EMs in wastewater. It should be pointed out that the concentration of anti-COVID-19 related EMs, such as antivirals, plasticizers, antimicrobials, and psychotropic drugs in wastewater increased notably after the pandemic. Furthermore, the ecotoxicity, ecological, and health risks of typical EMs before and after COVID-19 were emphatically compared and analyzed. Based on the environmental health prioritization index method, the priority control sequence of typical EMs related to anti-COVID-19 was identified. Lopinavir (LPV), venlafaxine (VLX), di(2-ethylhexyl) phthalate (DEHP), benzalkonium chloride (BAC), triclocarban (TCC), di-n-butyl phthalate (DBP), citalopram (CIT), diisobutyl phthalate (DIBP), and triclosan (TCS) were identified as the top-priority control EMs in the post-pandemic period. Besides, some insights into the toxicity and risk assessment of EMs were also provided. This review provides direction for proper understanding and controlling the EMs pollution after COVID-19, and is of significance to evaluate objectively the environmental and health impacts induced by COVID-19.

Recent progress on triterpenoid derivatives and their anticancer potential.

Cancer poses a significant global public health challenge, with commonly used adjuvant or neoadjuvant chemotherapy often leading to adverse side effects and drug resistance. Therefore, advancing cancer treatment necessitates the ongoing development of novel anticancer agents with diverse structures and mechanisms of action. Natural products remain crucial in the process of drug discovery, serving as a primary source for pharmaceutical leads and therapeutic advancements. Triterpenoids are particularly compelling due to their complex structures and wide array of biological activities. Recent research has demonstrated that naturally occurring triterpenes and their derivatives have the potential to serve as promising candidates for new drug development. This review aims to comprehensively explore the anticancer properties of triterpenoids and their synthetic analogs, with a focus on recent advancements. Various aspects, such as synthesis, phytochemistry, and molecular simulation for structure-activity relationship analyses, are summarized. It is anticipated that triterpenoid derivatives will emerge as notable anticancer agents following further investigation into their mechanisms of action and in vivo studies.

Inactivated cGAS-STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2- Breast Cancer.

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

Sex differences in the association between Body Mass Index and cognitive function in Parkinson disease: a cross-sectional study.

Objective: This study utilized a binary logistic regression model to explore the relationship between Body Mass Index (BMI) and cognitive function in Parkinson's disease (PD) patients. Methods: In this cross-sectional study, data were obtained from 1,005 Parkinson's patients enrolled in the Parkinson's Progression Markers Initiative (PPMI) from 2010 to 2023, including 378 females and 627 males. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and the correlation between BMI and cognitive function was determined using binary logistic regression. Results: The median age of enrollment was 63.6 (56.2, 69.6) years old, including 378 (37.6%) females and 627 (62.4%) males. In the final adjusted model, a significant positive correlation was found between BMI and the prevalence of cognitive impairment in females (OR = 1.06, 95% CI = 1.01 ~ 1.12, p = 0.022), while no correlation was found in males (OR = 1.03, 95% CI = 0.99 ~ 1.08, p = 0.165). The results after categorizing BMI indicate that, among females, the risk of cognitive impairment increases for both groups with BMI ≥ 30 kg/m2 and those with 25 ≤ BMI < 30 kg/m2 compared to the reference group with BMI < 25 kg/m2, with a p for trend <0.001 indicating a stable and strong association between BMI and cognitive impairment in females. In males, the results were not significant. The trend of linear fitting was consistent with the above results. Conclusion: In female Parkinson's patients, there is a positive correlation between BMI and cognitive impairment, while no correlation was found in male patients. This study provides new evidence of sex differences in the correlation between BMI and cognitive impairment among Parkinson's patients. The role of sex differences in the relationship between BMI and cognitive impairment should be considered in future research.

Emerging Nanotechnology in Preclinical Pancreatic Cancer Immunotherapy: Driving Towards Clinical Applications.

The high malignant degree and poor prognosis of pancreatic cancer (PC) pose severe challenges to the basic research and clinical translation of next-generation therapies. The rise of immunotherapy has improved the treatment of a variety of solid tumors, while the application in PC is highly restricted by the challenge of immunosuppressive tumor microenvironment. The latest progress of nanotechnology as drug delivery platform and immune adjuvant has improved drug delivery in a variety of disease backgrounds and enhanced tumor therapy based on immunotherapy. Based on the immune loop of PC and the status quo of clinical immunotherapy of tumors, this article discussed and critically analyzed the key transformation difficulties of immunotherapy adaptation to the treatment of PC, and then proposed the rational design strategies of new nanocarriers for drug delivery and immune regulation, especially the design of combined immunotherapy. This review also put forward prospective views on future research directions, so as to provide information for the new means of clinical treatment of PC combined with the next generation of nanotechnology and immunotherapy.

Partial Discharge Fault Diagnosis in Power Transformers Based on SGMD Approximate Entropy and Optimized BILSTM.

Partial discharge (PD) fault diagnosis is of great importance for ensuring the safe and stable operation of power transformers. To address the issues of low accuracy in traditional PD fault diagnostic methods, this paper proposes a novel method for the power transformer PD fault diagnosis. It incorporates the approximate entropy (ApEn) of symplectic geometry mode decomposition (SGMD) into the optimized bidirectional long short-term memory (BILSTM) neural network. This method extracts dominant PD features employing SGMD and ApEn. Meanwhile, it improves the diagnostic accuracy with the optimized BILSTM by introducing the golden jackal optimization (GJO). Simulation studies evaluate the performance of FFT, EMD, VMD, and SGMD. The results show that SGMD-ApEn outperforms other methods in extracting dominant PD features. Experimental results verify the effectiveness and superiority of the proposed method by comparing different traditional methods. The proposed method improves PD fault recognition accuracy and provides a diagnostic rate of 98.6%, with lower noise sensitivity.

Reciprocal regulation of T follicular helper cells and dendritic cells drives colitis development.

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (TFH) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and TFH cells was found within T cell zones of colonic lymphoid follicles. TFH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted TFH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, TFH cells transdifferentiated into long-lived pathogenic TH1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of TFH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.

Cost-Effectiveness Analysis of 6 Tyrosine Kinase Inhibitors as First-Line Treatment for ALK-Positive NSCLC in China.

Background: Lung cancer ranks first in both cancer incidence and mortality in China. The emergence of novel treatments for ALK-positive NSCLC led to an improvement in survival and quality of life for patients with advanced ALK mutation-positive non-small cell lung cancer (NSCLC). This study sought to assess the cost-effectiveness of 6 tyrosine kinase inhibitors (TKIs)-crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib-as first-line treatments for ALK-positive NSCLC from the perspective of the Chinese health care system. Methods: A Markov model was developed to estimate the cost-effectiveness of these 6 TKIs. In this model, ALK-positive NSCLC patients were initially simulated to receive 1 of the 6 TKIs as first-line therapy, followed by different TKIs as subsequent treatment and salvage chemotherapy as last-line treatment. Survival data were sourced from the latest published clinical trials. Costs were derived from recent national health insurance negotiations and hospital information systems of selected health care facilities. Utilities for healthy states and adverse events were obtained from the literature. One-way and probabilistic sensitivity analysis as well as scenario analysis was conducted to assess the robustness of the results. Results: Compared to ensartinib, crizotinib, alectinib, ceritinib, brigatinib, and lorlatinib demonstrated incremental quality-adjusted life years (QALYs) of -1.13, 0.39, -0.58, -0.09, and 0.35, respectively. The corresponding incremental costs were $10 677, $33 501, -$6426, $2672, and $24 358. This resulted in ICERs of -$9449/QALY, $85 900/QALY, $11 079/QALY, $29 689/QALY and $69 594/QALY, respectively. Conclusion: Crizotinib was considered to be absolutely dominated by ensartinib. Under a willingness-to-pay threshold of $38 223/QALY, ceritinib and brigatinib were cost-effective compared with ensartinib, while lorlatinib and alectinib were not cost-effective when compared with ensartinib. Overall, brigatinib emerged as the most cost-effective treatment among all the options considered.

Sedentary Behavior and Risk of Depression in Older Adults: A Systematic Meta-Analysis.

Background: The elderly represents the population group with the highest rate of sedentary behavior. Sedentary behavior has an adverse impact on the elderly, which might be related to depression. Methods: We queried PubMed, EMBASE, Web of Science, and MEDLINE to collect literature data. The odds ratio (OR) and corresponding 95% confidence interval (CI) were adopted for the pooled measurements. Sub-group analyses were conducted through stratified meta-analyses based on study design, depression indicator, adjustment for physical activity, sedentary behavior indicator, and type. Sensitivity analyses were performed to test the robustness of the results, and publication bias was assessed through a funnel plot. Results: Seven cross-sectional studies and five cohort studies were included in our meta-analysis. The overall pooled OR was 1.38 (95%CI: 1.16-1.65; P < 0.01), which indicated that sedentary behavior was positively associated with depression in older adults. Sub-group analysis showed that different study designs, depression indicators, sedentary behavior indicators, adjustment for physical activity, sedentary behavior indicator, and type produced different results. In the cross-sectional studies (OR = 1.45, 95%CI: 1.15-1.84), CES-D scale (OR = 1.54, 95%CI: 1.13-2.10), self-reported (OR = 1.39, 95%CI: 1.04-1.87), watching TV (OR = 1.75, 95%CI: 1.02-3.02), and not adjusted for physical activity (OR = 1.37, 95%CI: 1.14-1.65) groups, there was a strong correlation between sedentary behavior and depression in the elderly. Conclusion: Sedentary behavior is associated with depression in the elderly. As a preventive strategy, we should consider reducing their sedentary time and appropriately increasing physical activity.