FUBP3 mediates the amyloid-ß-induced neuronal NLRP3 expression.

JOURNAL/nrgr/04.03/01300535-202507000-00028/figure1/v/2024-09-09T124005Z/r/image-tiff Alzheimer's disease is characterized by deposition of amyloid-ß, which forms extracellular neuritic plaques, and accumulation of hyperphosphorylated tau, which aggregates to form intraneuronal neurofibrillary tangles, in the brain. The NLRP3 inflammasome may play a role in the transition from amyloid-ß deposition to tau phosphorylation and aggregation. Because NLRP3 is primarily found in brain microglia, and tau is predominantly located in neurons, it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines. Here, we found that neurons also express NLRP3 in vitro and in vivo, and that neuronal NLRP3 regulates tau phosphorylation. Using biochemical methods, we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons. In primary neurons and the neuroblastoma cell line Neuro2A, FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-ß is present. In the brains of aged wild-type mice and a mouse model of Alzheimer's disease, FUBP3 expression was markedly increased in cortical neurons. Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses. We also found that FUBP3 trimmed the 5' end of DNA fragments that it bound, implying that FUBP3 functions in stress-induced responses. These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-ß-to-phospho-tau transition than microglial NLRP3, and that amyloid-ß fundamentally alters the regulatory mechanism of NLRP3 expression in neurons. Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice, FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder.

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

Analysis of ZNF208 Polymorphisms on the Clinicopathologic Characteristics of Asian Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), a major form of liver cancer, is characterized by high lethality and a multifactorial etiology that includes hepatitis virus infections, lifestyle factors, and genetic predispositions. This study aimed to explore the impact of ZNF208 gene polymorphisms on the clinicopathological features of Taiwanese HCC patients, focusing on three specific single nucleotide polymorphisms (SNPs): rs2188971, rs2188972, and rs8105767. Our cohort consisted of 438 HCC patients and 1193 control individuals. Clinical staging was determined using the tumor/node/metastasis (TNM) system, and various clinical indicators were collected. Our analysis revealed a statistically significant increase in ZNF208 expression in HCC patients compared to controls, indicating a potential role in HCC progression. Although no substantial association was observed between ZNF208 SNPs and increased HCC risk, specific clinical features such as distant metastasis and vascular invasion showed significant associations with these SNPs, suggesting their influence on disease aggressiveness. Demographic analyses highlighted the importance of factors like alcohol consumption and viral hepatitis markers in HCC. Our study underscores the complexity of genetic influences on HCC, with ZNF208 polymorphisms potentially affecting tumor progression and patient outcomes.

Sinonasal teratocarcinosarcoma involving the nasal cavity, unilateral paranasal sinuses, and intracranial invasion: A case report.

BACKGROUND: Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly invasive neoplasm originating from the nasal cavity and sinuses. Typically, it exhibits an invasive behavior towards adjacent structures; however, in exceptional instances, it may infiltrate the intracranial compartment. Due to the tumor's rarity and lack of distinctive features on computed tomography (CT) and magnetic resonance imaging (MRI) images, SNTCS is often misdiagnosed. CASE SUMMARY: In this study, we present a case of SNTCS in a 56-year-old patient who exhibited unexplained cognitive impairment before admission. CT and MRI scans revealed the presence of a mass in the right nasal cavity, with lesions extending to the right ethmoid sinus and right frontal region. Subsequently, the patient underwent pathological examination for confirmation and received surgical intervention to excise the tumor. The future advancement in our understanding of this disease will significantly contribute to the precise diagnosis and treatment of SNTCS. CONCLUSION: SNTCS is an exceptionally rare malignant tumor that originates from the nasal cavity and paranasal sinuses, presenting a diagnostic challenge due to its non-specific imaging findings. MRI accurately delineates the location, morphological characteristics, size, internal structure, extent of surrounding involvement, and metabolic information of the lesion. These aspects play a pivotal role in the precise localization and qualitative assessment of SNTCS. Nevertheless, a definitive diagnosis still requires a pathological biopsy.

Prediction of Spread Through Air Spaces (STAS) By Intraoperative Frozen Section for Patients with cT1N0M0 Invasive Lung Adenocarcinoma: A Multi-Center Observational Study (ECTOP-1016).

OBJECTIVE: To investigate the value of intraoperative assessment of spread through air spaces (STAS) on frozen sections (FS) in peripheral small-sized lung adenocarcinoma. BACKGROUND: Surgical decision-making based on FS diagnosis of STAS may be useful to prevent local control failure after sublobar resection. METHODS: We conducted a multicenter prospective observational study of consecutive patients with cT1N0M0 invasive lung adenocarcinoma to evaluate the accuracy of FS for the intraoperative detection of STAS. The final pathology (FP) diagnosis of STAS was based on corresponding permanent paraffin sections. RESULTS: This study included 878 patients with cT1N0M0 invasive lung adenocarcinoma. A total of 833 cases (95%) were assessable for STAS on FS. 26.4% of the cases evaluated positive for STAS on FP, whereas 18.2% on FS. The accuracy, sensitivity, and specificity of FS diagnosis of STAS were 85.1%, 56.4%, and 95.4%, respectively, with moderate agreement (κ=0.575). Inter-observer agreement was substantial (κ=0.756) among the three pathologists. Subgroup analysis based on tumor size or consolidation-to-tumor ratio all showed moderate agreement for concordance. After rigorous reassessment of false-positive cases, the presence of artifacts may be the main cause of interpretation errors. Additionally, true positive cases showed more high-grade histological patterns and more advanced p-TNM stages than false negative cases. CONCLUSIONS: This is the largest prospective observational study to evaluate STAS on FS in patients with cT1N0M0 invasive lung adenocarcinoma. FS is highly specific with moderate agreement, but is not sensitive for STAS detection. While appropriately reporting STAS on FS may provide surgeons with valuable information for intraoperative decision-making, better approaches are needed.

Open-shell Poly(3,4-dioxythiophene) Radical for Highly Efficient Photothermal Conversion.

Open-shell organic radical semiconductor materials have received increasing attention in recent years due to their distinctive properties compared to the traditional materials with closed-shell singlet ground state. However, their poor chemical and photothermal stability in ambient conditions remains a significant challenge, primarily owing to their high reactivity with oxygen. Herein, a novel open-shell poly(3,4-dioxythiophene) radical PTTO2 is designed and readily synthesized for the first time using low-cost raw material via a straightforward BBr3-demethylation of the copolymer PTTOMe2 precursor. The open-shell character of PTTO2 is carefully studied and confirmed via the signal-silent 1H nuclear magnetic resonance spectrum, highly enhanced electron spin resonance signal compared with PTTOMe2, as well as the ultra-wide ultraviolet-visible-near nfraredUV-vis-NIR absorption and other technologies. Interestingly, the powder of PTTO2 exhibits an extraordinary absorption range spanning from 300 to 2500 nm and can reach 274 °C under the irradiation of 1.2 W cm-2, substantially higher than the 108 °C achieved by PTTOMe2. The low-cost PTTO2 stands as one of the best photothermal conversion materials among the pure organic photothermal materials and provides a new scaffold for the design of stable non-doped open-shell polymers.

The landscape of miRNA-mRNA regulatory network and cellular sources in inflammatory bowel diseases: insights from text mining and single cell RNA sequencing analysis.

Background: Inflammatory Bowel Diseases (IBDs), encompassing Ulcerative Colitis (UC) and Crohn's Disease (CD), are chronic, recurrent inflammatory conditions of the gastrointestinal tract. The microRNA (miRNA) -mRNA regulatory network is pivotal in the initiation and progression of IBDs. Although individual studies provide valuable insights into miRNA mechanisms in IBDs, they often have limited scope due to constraints in population diversity, sample size, sequencing platform variability, batch effects, and potential researcher bias. Our study aimed to construct comprehensive miRNA-mRNA regulatory networks and determine the cellular sources and functions of key miRNAs in IBD pathogenesis. Methods: To minimize potential bias from individual studies, we utilized a text mining-based approach on published scientific literature from PubMed and PMC databases to identify miRNAs and mRNAs associated with IBDs and their subtypes. We constructed miRNA-mRNA regulatory networks by integrating both predicted and experimentally validated results from DIANA, Targetscan, PicTar, Miranda, miRDB, and miRTarBase (all of which are databases for miRNA target annotation). The functions of miRNAs were determined through gene enrichment analysis of their target mRNAs. Additionally, we used two large-scale single-cell RNA sequencing datasets to identify the cellular sources of miRNAs and the association of their expression levels with clinical status, molecular and functional alternation in CD and UC. Results: Our analysis systematically summarized IBD-related genes using text-mining methodologies. We constructed three comprehensive miRNA-mRNA regulatory networks specific to IBD, CD, and UC. Through cross-analysis with two large-scale scRNA-seq datasets, we determined the cellular sources of the identified miRNAs. Despite originating from different cell types, hsa-miR-142, hsa-miR-145, and hsa-miR-146a were common to both CD and UC. Notably, hsa-miR-145 was identified as myofibroblast-specific in both CD and UC. Furthermore, we found that higher tissue repair and enhanced glucose and lipid metabolism were associated with hsa-miR-145 in myofibroblasts in both CD and UC contexts. Conclusion: This comprehensive approach revealed common and distinct miRNA-mRNA regulatory networks in CD and UC, identified cell-specific miRNA expressions (notably hsa-miR-145 in myofibroblasts), and linked miRNA expression to functional alterations in IBD. These findings not only enhance our understanding of IBD pathogenesis but also offer promising diagnostic biomarkers and therapeutic targets for clinical practice in managing IBDs.

[Advances in Imaging-Based Evaluation of Solid Tumors Treated With Immune Checkpoint Inhibitors].

Immune checkpoint inhibitors have shown remarkable benefits in the treatment of solid tumors,while the occurrence of atypical response patterns and immune-related adverse events during treatment challenges the accuracy of therapeutic evaluation.Medical imaging is crucial for the evaluation of immunotherapy.It enables the assessment of treatment efficacy via both morphological and functional ways and offers unique a predictive value when being combined with artificial intelligence.Here we review the recent research progress in imaging-based evaluation of solid tumors treated with immune checkpoint inhibitors.

ß-hydroxybutyrate and mitochondria mediate the association between medium-chain fatty acids, DHA and mild cognitive impairment: a nested case-control study.

BACKGROUND: Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). ß-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms. METHODS: This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship. RESULTS: Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk. CONCLUSION: Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly.

Concordance between four PD-L1 immunohistochemical assays and 22C3 pharmDx assay in esophageal squamous cell carcinoma in a multicenter study.

Background: The prediction of response to immunotherapy mostly depends on the programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status, and the 22C3 pharmDx assay has been approved in esophageal squamous cell carcinoma (ESCC). However, the widespread use of the 22C3 pharmDx assay is limited due to its availability. Thus, alternative PD-L1 assays are needed. We aimed to investigate the analytical and clinical diagnostic performances of four PD-L1 assays and to compare their concordances with the 22C3 pharmDx assay. Methods: The PD-L1 22C3 pharmDx assay was performed on the Dako Autostainer Link 48 platform, three testing assays (PD-L1 E1L3N XP antibody [Ab], PD-L1 BP6099 Ab and PD-L1 CST E1L3N Ab) on the Leica BOND-MAX/III platform, and one testing assay (PD-L1 MXR006 Ab) on the Roche VENTANA Benchmark Ultra platform. A total of 218 ESCC cases from four centers were included in this retrospective study. Professionals from each center stained and read the IHC slides independently and determined the combined positive score (CPS) and the tumor proportion score (TPS). Results: Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ > 0.8 for all four assays). Regarding diagnostic performance (CPS ≥ 10 was used as the cutoff), the four testing assays showed moderate concordances with the 22C3 pharmDx assay (kappa > 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %. Conclusion: This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

Combined treatment with Aronia berry extract and oligomeric proanthocyanidins exhibit a synergistic anticancer efficacy through LMNB1-AKT signaling pathways in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent and highly recurrent malignancies worldwide and currently ranks as the second leading cause of cancer-related deaths. The high degree of morbidity and mortality associated with CRC is primarily attributed to the limited effectiveness of current therapeutic approaches and the emergence of chemoresistance to standard treatment modalities. Recent research indicates that several natural products, including Aronia berry extracts (ABE) and oligomeric proanthocyanidins (OPCs), might offer a safe, cost-effective, and multitargeted adjunctive role to cancer treatment. Herein, we hypothesized a combined treatment with ABE and OPCs could synergistically modulate multiple oncogenic pathways in CRC, thereby enhancing their anticancer activity. We initially conducted a series of in vitro experiments to assess the synergistic anticancer effects of ABE and OPCs on CRC cell lines. We demonstrate that these two compounds exhibited a superior synergistic anticancer potential versus individual treatments in enhancing the ability to inhibit cell viability, suppress colony formation, and induce apoptosis (p < 0.05). Consistent with our in vitro findings, we validated this combinatorial anticancer effect in tumor-derived 3D organoids (PDOs; p < 0.01). Using genome-wide transcriptomic profiling, we identified that a specific gene, LMNB1, associated with the cell apoptosis pathway, was found to play a crucial role in exhibiting anticancer effects with these two products. Furthermore, the combined treatment of ABE and OPCs significantly impacted the expression of key proteins involved in apoptosis, including suppressed expression levels of LMNB1 in CRC cell lines (p < 0.05), which resulted in inhibiting downstream AKT phosphorylation. In conclusion, our study provides novel evidence of the synergistic anticancer effects of ABE and OPCs in CRC cells, partially mediated through the regulation of apoptosis and the oncogene LMNB1 within the AKT signaling pathway. These findings have the potential to better appreciate the anticancer potential of natural products in CRC and help improve treatment outcomes in this malignancy.

Distribution and control mechanism of pCO2 and water-air CO2 efflux in the Pearl River Estuary.

Estuaries are generally considered to be important sources of atmospheric CO2. However, the differences between estuaries, and inadequate observations of partial pressure of CO2 in estuarine water (pCO2water) hamper global estuarine CO2 budgeting. In this study, the longitudinal distribution of CO2 in the waters of Modaomen (MSE) and Lingdingyang (LSE), two sub-estuaries of the Pearl River Estuary (PRE), and its influencing mechanism are studied. The change in the distribution of pCO2water along the distance from the upstream estuary to the ocean between LSE and MSE was significantly different. pCO2water at the LSE ranges from 238 to 7267 µatm, whereas the MSE ranges from 406 to 3078 µatm. Stronger microbial respiration and relatively long water retention times were the main influences that led to higher pCO2water at LSE than at MSE. Seasonally, the increase of soil CO2 into the water in the upstream basin caused by precipitation is the potential influencing factor that the water pCO2water in the flood season is higher than in the dry season. PRE was a net source of atmospheric CO2 with an average annual water-air flux of 41.2 ± 33.3 mmol m-2 day-1. Our results suggest that the differences in longitudinal gradients of pCO2water between estuaries in the same region and the effects of different gas transport velocity models on CO2 emission estimates need to be considered in estuarine CO2 emission budgeting.

Improving Memory through Better Sleep in Community-dwelling Older Adults: A Tai Chi Intervention Study.

OBJECTIVES: The relationship between sleep and memory has been well documented. However, it remains unclear whether a mind-body exercise, i.e., Tai Chi exercise, can improve memory performance in older adults by improving their subjective and objective sleep. METHOD: A randomized controlled trial was conducted with participants (M = 67.36, 56-79 years) randomly assigned to Tai Chi and control groups. The primary outcomes were sleep, both subjectively reported and objectively assessed by actigraphy, and memory performance, as well as the mediating role of sleep in memory improvement with Tai Chi practice. RESULTS: Tai Chi exercise led to improvements in subjective sleep, as indicated by ISI (p < 0.001, Cohen's d = 0.62) and daytime dysfunction of the PSQI (p = 0.02, Cohen's d = 0.80), and in actigraphy-assessed sleep onset latency (p < 0.01, Cohen's d = 0.61), as well as improved memory performance on digit span forward (p < 0.001, Cohen's d = 1.20) and visual spatial memory tasks (p < 0.01, Cohen's d = 0.83) compared to the control group. Importantly, Tai Chi practice improved digit span forward memory performance through parallel mediation of both subjective sleep (i.e., daytime dysfunction of the PSQI) and objective sleep (i.e., sleep onset latency; b = 0.29, p < 0.01). DISCUSSION: Our findings uncovered the potential benefits of Tai Chi exercise in relation to both subjective and objective sleep in older adults, in turn, how sleep changes played a role in the link between Tai Chi exercise and memory changes in older adults.

Enhancing intracranial efficacy prediction of osimertinib in non-small cell lung cancer: a novel approach through brain MRI radiomics.

Introduction: Osimertinib, a third-generation EGFR-TKI, is known for its high efficacy against brain metastases (BM) in non-small cell lung cancer (NSCLC) due to its ability to penetrate the blood-brain barrier. This study aims to evaluate the use of brain MRI radiomics in predicting the intracranial efficacy to osimertinib in NSCLC patients with BM. Materials and methods: This study analyzed 115 brain metastases from NSCLC patients with the EGFR-T790M mutation treated with second-line osimertinib. The primary endpoint was intracranial response, and the secondary endpoint was intracranial progression-free survival (iPFS). We performed tumor delineation, image preprocessing, and radiomics feature extraction. Using a 5-fold cross-validation strategy, we built radiomic models with eight feature selectors and eight machine learning classifiers. The models' performance was evaluated by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis. Results: The dataset of 115 brain metastases was divided into training and validation sets in a 7:3 ratio. The radiomic model utilizing the mRMR feature selector and stepwise logistic regression classifier showed the highest predictive accuracy, with AUCs of 0.879 for the training cohort and 0.786 for the validation cohort. This model outperformed a clinical-MRI morphological model, which included age, ring enhancement, and peritumoral edema (AUC: 0.794 for the training cohort and 0.697 for the validation cohort). The radiomic model also showed strong performance in calibration and decision curve analyses. Using a radiomic-score threshold of 199, patients were classified into two groups with significantly different median iPFS (3.0 months vs. 15.4 months, p < 0.001). Conclusion: This study demonstrates that MRI radiomics can effectively predict the intracranial efficacy of osimertinib in NSCLC patients with brain metastases. This approach holds promise for assisting clinicians in personalizing treatment strategies.

Navigating the Landscape of Coronary Microvascular Research: Trends, Triumphs, and Challenges Ahead.

Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the microcirculation that impair myocardial perfusion. CMD plays a pivotal role in numerous cardiovascular diseases, including myocardial ischemia with non-obstructive coronary arteries, heart failure, and acute coronary syndromes. This review summarizes recent advances in CMD pathophysiology, assessment, and treatment strategies, as well as ongoing challenges and future research directions. Signaling pathways implicated in CMD pathogenesis include adenosine monophosphate-activated protein kinase/Krüppel-like factor 2/endothelial nitric oxide synthase (AMPK/KLF2/eNOS), nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), Angiotensin II (Ang II), endothelin-1 (ET-1), RhoA/Rho kinase, and insulin signaling. Dysregulation of these pathways leads to endothelial dysfunction, the hallmark of CMD. Treatment strategies aim to reduce myocardial oxygen demand, improve microcirculatory function, and restore endothelial homeostasis through mechanisms including vasodilation, anti-inflammation, and antioxidant effects. Traditional Chinese medicine (TCM) compounds exhibit therapeutic potential through multi-targeted actions. Small molecules and regenerative approaches offer precision therapies. However, challenges remain in translating findings to clinical practice and developing effective pharmacotherapies. Integration of engineering with medicine through microfabrication, tissue engineering and AI presents opportunities to advance the diagnosis, prediction, and treatment of CMD.

Simultaneous detection of multiple urinary biomarkers in patients with early-stage diabetic kidney disease using Luminex liquid suspension chip technology.

Background: Several urinary biomarkers have good diagnostic value for diabetic kidney disease (DKD); however, the predictive value is limited with the use of single biomarkers. We investigated the clinical value of Luminex liquid suspension chip detection of several urinary biomarkers simultaneously. Methods: The study included 737 patients: 585 with diabetes mellitus (DM) and 152 with DKD. Propensity score matching (PSM) of demographic and medical characteristics identified a subset of 78 patients (DM = 39, DKD = 39). Two Luminex liquid suspension chips were used to detect 11 urinary biomarkers according to their molecular weight and concentration. The biomarkers, including cystatin C (CysC), nephrin, epidermal growth factor (EGF), kidney injury molecule-1 (KIM-1), retinol-binding protein4 (RBP4), α1-microglobulin (α1-MG), ß2-microglobulin (ß2-MG), vitamin D binding protein (VDBP), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor receptor-1 (TNFR-1), and tumor necrosis factor receptor-2 (TNFR-2) were compared in the DM and DKD groups. The diagnostic values of single biomarkers and various biomarker combinations for early diagnosis of DKD were assessed using receiver operating characteristic (ROC) curve analysis. Results: Urinary levels of VDBP, RBP4, and KIM-1 were markedly higher in the DKD group than in the DM group (p < 0.05), whereas the TIMP-1, TNFR-1, TNFR-2, α1-MG, ß2-MG, CysC, nephrin, and EGF levels were not significantly different between the groups. RBP4, KIM-1, TNFR-2, and VDBP reached p < 0.01 in univariate analysis and were entered into the final analysis. VDBP had the highest AUC (0.780, p < 0.01), followed by RBP4 (0.711, p < 0.01), KIM-1 (0.640, p = 0.044), and TNFR-2 (0.615, p = 0.081). However, a combination of these four urinary biomarkers had the highest AUC (0.812), with a sensitivity of 0.742 and a specificity of 0.760. Conclusions: The urinary levels of VDBP, RBP4, KIM-1, and TNFR-2 can be detected simultaneously using Luminex liquid suspension chip technology. The combination of these biomarkers, which reflect different mechanisms of kidney damage, had the highest diagnostic value for DKD. However, this finding should be explored further to understand the synergistic effects of these biomarkers.

PM2.5-mediated cardiovascular disease in aging: Cardiometabolic risks, molecular mechanisms and potential interventions.

Air pollution, particularly fine particulate matter (PM2.5) with <2.5 µm in diameter, is a major public health concern. Studies have consistently linked PM2.5 exposure to a heightened risk of cardiovascular diseases (CVDs) such as ischemic heart disease (IHD), heart failure (HF), and cardiac arrhythmias. Notably, individuals with pre-existing age-related cardiometabolic conditions appear more susceptible. However, the specific impact of PM2.5 on CVDs susceptibility in older adults remains unclear. Therefore, this review addresses this gap by discussing the factors that make the elderly more vulnerable to PM2.5-induced CVDs. Accordingly, we focused on physiological aging, increased susceptibility, cardiometabolic risk factors, CVDs, and biological mechanisms. This review concludes by examining potential interventions to reduce exposure and the adverse health effects of PM2.5 in the elderly population. The latter includes dietary modifications, medications, and exploration of the potential benefits of supplements. By comprehensively analyzing these factors, this review aims to provide a deeper understanding of the detrimental effects of PM2.5 on cardiovascular health in older adults. This knowledge can inform future research and guide strategies to protect vulnerable populations from the adverse effects of air pollution.

Intelligent identification of picking periods of Lu'an Guapian tea by an indicator displacement colorimetric sensor array combined with machine learning.

Lu'an Gua Pian (LAGP) tea is one of the most famous green teas in China. The quality of green tea is related to its picking periods, especially the green tea before Qingming Festival (usually April 6th) is highly praised as precious in the market. In this work, a simple and cheap indicator displacement colorimetric sensor array combined with smartphone was developed to rapidly identify LAGP picked during different picking periods. First, the chemical component contents of LAGP picked before and after Qingming Festival were analyzed. Second, a well-designed colorimetric sensor array was proposed based on the tea component contents differences. Finally, machine learning was used to process the array data taken by a smartphone. By comparison, the accuracy of the best model for the prediction set was 97%. Meanwhile, the multi-channel advantages of the sensing array were demonstrated by an ablation experiment. In addition, the method achieved an AGREE analysis score of 0.88, indicating that it was environmental-friendly.

Effectiveness of palliative care interventions on patient-reported outcomes and all-cause mortality in community-dwelling adults with heart failure: A systematic review and meta-analysis.

BACKGROUND: Current evidence that supports palliative care interventions predominantly focuses on individuals with cancer or hospitalized patients. However, the effectiveness of palliative care on patient-reported outcomes and mortality in community-dwelling adults with heart failure has not been evaluated. OBJECTIVE: We aimed to evaluate the effectiveness of palliative care interventions on patient-reported outcomes and all-cause mortality in community-dwelling adults with heart failure. DESIGN: A systematic review and meta-analysis of randomized controlled trials. METHODS: MEDLINE, Embase, Cochrane Library, and CINAHL databases were searched from inception to October 2023. Randomized controlled trials were considered if they compared palliative care interventions with usual care, attention control, or waiting-list control primarily in a community-dwelling heart failure patient population. The primary outcome was patient-reported generic health-related or heart failure-specific quality of life. Secondary outcomes were patient-reported symptom burden, psychological health (anxiety and depression), spiritual well-being, and all-cause mortality. Two independent reviewers screened the retrieved articles and extracted data from the included studies. A random-effects meta-analysis was performed to pool the data, followed by sensitivity analysis, subgroup analysis, and meta-regression. All analyses were performed using R version 4.2.2. RESULTS: Eleven eligible studies were included in this review with a total of 1535 patients. Compared to usual care, palliative care interventions demonstrated statistically significant effects on improving generic health-related quality of life (SMD, 0.30 [95 % CI, 0.12 to 0.48]) and heart failure-specific quality of life (SMD, 0.17 [95 % CI, 0.03 to 0.31]). Palliative care interventions also reduced anxiety (SMD, -0.22 [95 % CI, -0.40 to -0.05]) and depression (SMD, -0.18 [95 % CI, -0.33 to -0.03]), and enhanced spiritual well-being (SMD, 0.43 [95 % CI, 0.05 to 0.81]), without adversely affecting all-cause mortality (RR, 1.00 [95 % CI, 0.76 to 1.33]). Yet, the interventions had no significant effects on symptom burden (SMD, -0.09 [95 % CI, -0.40 to 0.21]). The certainty of evidence across the outcomes ranged from very low to moderate based on the GRADE approach. CONCLUSIONS: Palliative care interventions are beneficial for community-dwelling adults with heart failure in that the interventions improved patient-reported quality of life, psychological health, and spiritual well-being, and importantly, did not lead to higher mortality rates. Findings of this review support the implementation of palliative care for adults with heart failure in community settings. REGISTRATION: CRD42023482495.

Enhancement of Apple Stress Resistance via Proline Elevation by Sugar Substitutes.

Plants encounter numerous adversities during growth, necessitating the identification of common stress activators to bolster their resistance. However, the current understanding of these activators' mechanisms remains limited. This study identified three anti-stress activators applicable to apple trees, all of which elevate plant proline content to enhance resistance against various adversities. The results showed that the application of these sugar substitutes increased apple proline content by two to three times compared to the untreated group. Even at a lower concentration, these activators triggered plant stress resistance without compromising apple fruit quality. Therefore, these three sugar substitutes can be exogenously sprayed on apple trees to augment proline content and fortify stress resistance. Given their effectiveness and low production cost, these activators possess significant application value. Since they have been widely used in the food industry, they hold potential for broader application in plants, fostering apple industry development.