The relationship between mentally active sedentary behavior and cognitive function across different educational levels.

INTRODUCTION: How education affects the relationship between sedentary behavior and cognitive function remains unclear. The aim of this study was to investigate the relationship between mentally active sedentary behavior and cognitive function in rural older Chinese across different levels of education. METHODS: Data from 517 participants aged 60 years and older in rural China at baseline, 4 weeks, 8 weeks, 6 months, 12 months, and 24 months were analyzed. Univariate analysis was carried out using descriptive statistical techniques and bivariate analysis was performed using Linear mixed effects models. RESULTS: Total mentally active sedentary behavior time and playing cards/mahjong time were significantly associated with global cognition (0.27 points (95% CI, 0.15 to 0.39), P＜0.001; 0.30 points (95% CI, 0.18 to 0.41), P＜0.001, respectively), the attention dimension (0.08 points (95% CI, 0.02 to 0.14), P = 0.005; 0.10 points (95% CI, 0.04 to 0.16), P = 0.001, respectively), and the memory dimension (0.18 points (95% CI, 0.05 to 0.31), P < 0.001; 0.19 points (95% CI, 0.13 to 0.25), P＜0.001, respectively). Such associations were more pronounced in illiterate participants. CONCLUSION: Our study suggested a positive association between mentally active sedentary behavior and cognitive function, with the association being more pronounced among illiterate older adults compared to the relatively well-educated. Future cognitive interventions should focus more on mentally active behavior. In addition, education-specific intervention strategy may be considered in cognitive interventions.

Context-dependent T-BOX transcription factor family: from biology to targeted therapy.

T-BOX factors belong to an evolutionarily conserved family of transcription factors. T-BOX factors not only play key roles in growth and development but are also involved in immunity, cancer initiation, and progression. Moreover, the same T-BOX molecule exhibits different or even opposite effects in various developmental processes and tumor microenvironments. Understanding the multiple roles of context-dependent T-BOX factors in malignancies is vital for uncovering the potential of T-BOX-targeted cancer therapy. We summarize the physiological roles of T-BOX factors in different developmental processes and their pathological roles observed when their expression is dysregulated. We also discuss their regulatory roles in tumor immune microenvironment (TIME) and the newly arising questions that remain unresolved. This review will help in systematically and comprehensively understanding the vital role of the T-BOX transcription factor family in tumor physiology, pathology, and immunity. The intention is to provide valuable information to support the development of T-BOX-targeted therapy.

Reversal of Platinum-based Chemotherapy Resistance in Ovarian Cancer by Naringin Through Modulation of The Gut Microbiota in a Humanized Nude Mouse Model.

As a chemotherapy agent, cisplatin (DDP) is often associated with drug resistance and gastrointestinal toxicity, factors that severely limit therapeutic efficacy in patients with ovarian cancer (OC). Naringin has been shown to increase sensitivity to cisplatin, but whether the intestinal microbiota is associated with this effect has not been reported so far. In this study, we applied a humanized mouse model for the first time to evaluate the reversal of cisplatin resistance by naringin, as well as naringin combined with the microbiota in ovarian cancer. The results showed that naringin combined with Bifidobacterium animalis subsp. lactis NCU-01 had an inhibitory effect on the tumor, significantly reducing tumor size (p<0.05), as well as the concentrations of serum tumor markers CA125 and HE4, increased the relative abundance of Bifidobacterium and Bacteroides, inhibit Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)-induced intestinal inflammation and increase the expression of intestinal permeability-associated proteins ZO-1 (p<0.001) and occludin (p<0.01). In conclusion, the above data demonstrate how naringin combined with Bifidobacterium animalis subsp. lactis NCU-01 reverses cisplatin resistance in ovarian cancer by modulating the intestinal microbiota, inhibiting the TLR4/NF-κB signaling pathway and modulating the p38MAPK signaling pathway.

Auxiliary Rather Than Dominant. The Role of Direct Dy-S Coordination in Single-Molecule Magnet Unveiled via ab initio Study.

The role of Dy-S coordination in a single-molecule magnet (SMM) is investigated via an ab initio study in a group of mononuclear structures. The SMM performance of this group is well interpreted via a concise criterion consisting of long quantum tunneling of magnetization (QTM) time τQTM and high effective barrier for magnetic reversal Ueff. The best SMMs in the selected group, i.e., 1Dy (CCDC refcode: PUKFAF) and 2Dy (CCDC refcode: NIKSEJ), are just those holding the longest τQTM and the highest Ueff simultaneously. Further analysis based on the crystal field model and ab initio magneto-structural exploration indicates that the influence of Dy-S coordination on the SMM performance of 1Dy is weaker than that of axial Dy-O coordination. Thus, Dy-S coordination is more likely to play an auxiliary role rather than a dominant one. However, if placed at the suitable equatorial position, Dy-S coordination could provide important support for good SMM performance. Consequently, starting from 1Dy, we built two new structures where Dy-S coordination only exists at the equatorial position and two axial positions are occupied by strong Dy-O/Dy-F coordination. Compared to 1Dy and 2Dy, these new ones are predicted to have significantly longer τQTM and higher Ueff, as well as a nearly doubled blocking temperature TB. Thus, they are probable candidates of SMM having clearly improved performance.

Effectiveness of Psychobiotic Bifidobacterium breve BB05 in Managing Psychosomatic Diarrhea in College Students by Regulating Gut Microbiota: A Randomized, Double-Blind, Placebo-Controlled Trial.

Diarrhea of college students (DCS) is a prevalent issue among college students, affecting their daily lives and academic performance. This study aims to explore the potential effect of Bifidobacterium breve BB05 supplements on the DCS. Initially, fifty healthy and fifty diarrheal students were recruited in the observational experiment and allocated into control and diarrhea groups, respectively. Subsequently, one hundred diarrheal students were newly recruited in the intervention experiment and randomly allocated into placebo and probiotic groups, both treated for 2 weeks. Questionnaires (BSS, HAMA-14, and HDRS-17) were performed to assess the students' diarrheal states and mental health at baseline and post-treatment. Fecal samples underwent 16S rRNA sequencing and Enzyme-Linked Immunosorbent Assay to evaluate gut microbiota and fecal metabolite alternations. Results indicated that B. breve BB05 supplementation significantly enriched (p < 0.05) the reduced gut microbial diversity caused by diarrhea. Diarrhea resulted in notable alterations in gut microbiota composition, as exhibited by elevated Collinsella and Streptococcus, alongside substantially decreased Bifidobacterium, Bacteroides, and Prevotella, while B. breve BB05 supplementation partially restored the compromised gut microbiota at both the phylum and genus levels, particularly by increasing Bifidobacterium and Roseburia (p < 0.05). Importantly, questionnaire results suggested that B. breve BB05 administration achieved superior efficacy in relieving diarrhea symptoms and the associated anxiety and depression in college students. An increased fecal concentration of 5-hydroxytryptamine (5-HT) was also observed in the probiotic group, while Acetylcholine (ACH), Epinephrine (EPI), and Noradrenaline/Norepinephrine (NANE) reduced, revealing the potential of B. breve BB05 in alleviating anxiety and depression via modulating the microbiota-gut-brain axis. Furthermore, correlation analysis suggested that the altered microbiota and fecal neurotransmitters were closely associated with the mental symptoms. These results endorse B. breve BB05 intervention as a promising and innovative approach to alleviate both diarrhea and mental health conditions among college students.

Pollen identification of three notorious illicit drug plants and its potential applications in forensic practice.

Opium poppy, coca and cannabis are raw materials for three notorious illicit drugs. For a long time, drug lords have been growing and smuggling these drugs in a variety of ways and channels and are continually finding new ways of trafficking their wares, which has led to the increasing difficulty of global drug enforcement. In the present paper, we propose an innovative pollen identification system for these important drug plants, which provides a tool for screening and detection of the drugs to aid in drug enforcement. By utilizing the characteristics of these fine particles, their abundant production, and high resistance to decay, we believe this tool could be applied in the following scenarios: detecting and dynamically monitoring drug cultivation activities; determining whether a suspect has been to fields of drug plants and determining whether the site has ever been planted with a drug plant and/or was involved in drug production. In the future, combined with microscope automatic image acquisition technology and intelligent image recognition technology, this pollen identification system is expected to be used to screen three notorious illicit drug plants, thus enhancing the efficiency of drug related crime investigations.

Association between blood urea nitrogen to serum albumin ratio and in-hospital mortality in critical patients with diabetic ketoacidosis: a retrospective analysis of the eICU database.

Background: This study aimed to investigate the association between blood urea nitrogen to serum albumin ratio (BAR) and the risk of in-hospital mortality in patients with diabetic ketoacidosis. Methods: A total of 3,962 diabetic ketoacidosis patients from the eICU Collaborative Research Database were included in this analysis. The primary outcome was in-hospital death. Results: Over a median length of hospital stay of 3.1 days, 86 in-hospital deaths were identified. One unit increase in LnBAR was positively associated with the risk of in-hospital death (hazard ratio [HR], 1.82 [95% CI, 1.42-2.34]). Furthermore, a nonlinear, consistently increasing correlation between elevated BAR and in-hospital mortality was observed (P for trend =0.005 after multiple-adjusted). When BAR was categorized into quartiles, the higher risk of in-hospital death (multiple-adjusted HR, 1.99 [95% CI, (1.1-3.6)]) was found in participants in quartiles 3 to 4 (BAR≥6.28) compared with those in quartiles 1 to 2 (BAR<6.28). In the subgroup analysis, the LnBAR-hospital death association was significantly stronger in participants without kidney insufficiency (yes versus no, P-interaction=0.023). Conclusion: There was a significant and positive association between BAR and the risk of in-hospital death in patients with diabetic ketoacidosis. Notably, the strength of this association was intensified among those without kidney insufficiency.

Development of a diagnostic nomogram for alpha-fetoprotein-negative hepatocellular carcinoma based on serological biomarkers.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Serum biomarkers play an important role in the early diagnosis and prognosis of HCC. Because a certain percentage of HCC patients are negative for alpha-fetoprotein (AFP), the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC. AIM: To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers. METHODS: A total of 180 HCC patients were enrolled in this study. The expression levels of GP73, des-γ-carboxyprothrombin (DCP), CK18-M65, and CK18-M30 were detected by a fully automated chemiluminescence analyser. The variables were selected by logistic regression analysis. Several models were constructed using stepwise backward logistic regression. The performance of the models was compared using the C statistic, integrated discrimination improvement, net reclassification improvement, and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: The results showed that the expression levels of GP73, DCP, CK18-M65, and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls (P < 0.001). Multivariate logistic regression analysis revealed that GP73, DCP, and CK18-M65 were independent factors for diagnosing AFP-negative HCC. By comparing the diagnostic performance of multiple models, we included GP73 and CK18-M65 as the model variables, and the model had good discrimination ability (area under the curve = 0.946) and good goodness of fit. The DCA curves indicated the good clinical utility of the nomogram. CONCLUSION: Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC. The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

Tailored Cis-Trans Isomeric Metal-Covalent Organic Frameworks for Coordination Configuration-Dependent Electrochemiluminescence.

Precise manipulation of the coordination configuration within substances can modulate the band structure and catalytic properties of the target material. Metal-covalent organic frameworks (MCOFs), a crystal material amalgamating the benefits of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), can integrate a predetermined coordination environment into the frameworks for amplifying the catalytic effect. In this study, we delicately synthesize isomeric MCOFs using bis(glycinato)copper as the aminoligand via kinetically and thermodynamically favorable pathways to yield cis-MCOF and trans-MCOF products, respectively, thereby introducing a cis-trans isomeric coordination field into the framework. Moreover, the twisted skeleton derived from the flexibility of amino acid and ß-ketoenamine linkages endows trans-MCOF with surprising water dispersibility. Compared to cis-MCOF, the trans isomerism displays a significant enhancement in cathodic electrochemiluminescence via the catalysis of Cu nodes toward K2S2O8. The density of states analysis shows that the d-band center of trans-MCOF is closer to the Fermi level, leading to more stable adsorption binding to promote the catalysis. This study is the first report on constructing predesign coordination configuration MCOFs via an easy-handling method, which gives the guidelines for the design of amino acid-based MCOF materials.

Loss-tailoring single-mode high-power supersymmetric lasers.

Diode lasers with high beam quality and high power have many promising applications. However, high beam quality is always in conflict with high power. In this Letter, we theoretically and experimentally confirm the mode instability property of supersymmetric structures at higher operating currents. Meanwhile, we propose a loss-tailoring diode laser based on a supersymmetric structure, which enables the higher-order lateral modes to obtain higher losses, raises the excitation threshold of the higher-order lateral modes, and achieves a stable fundamental-lateral-mode output at higher current operation. The device obtained a quasi-single-lobe lateral far-field distribution with the full width at half maximum (FWHM) of 7.58° at 350 mA under room temperature, which is a 65% reduction compared to the traditional Fabry-Perot (FP) diode lasers. Moreover, the M2 of 2.181@350 mA has an improvement of about 37% over traditional FP and supersymmetric structure lasers.

Proangiogenic Azaphilones from the Marine-Derived Fungus Neopestalotiopsis sp. HN-1-6.

Developing novel, safe, and efficient proangiogenic drugs is an important approach for the prevention and treatment of cardiovascular diseases. In this study, 4 new compounds, including 3 azaphilones (1-3) and 1 dihydroisocoumarin (4), as well as 13 known compounds (5-17), were isolated from the sea-mud-derived fungus Neopestalotiopsis sp. HN-1-6 from the Beibu Gulf of China. The structures of the new compounds were determined by NMR, MS, ECD, and NMR calculations. Compounds 3, 5, and 7 exhibited noteworthy proangiogenic activities in a zebrafish model at a concentration of 40 µM, without displaying cytotoxicity toward five human cell lines. In addition, some compounds demonstrated antibacterial effects against Staphylococcus aureus, Escherichia coli, and Candida albicans, with MIC values ranging from 64 µg/mL to 256 µg/mL.

Up-regulation of miR-10a-5p expression inhibits the proliferation and differentiation of neural stem cells by targeting Chl1.

Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like ( Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p ( Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.

Reticular Ratchets for Directing Electrochemiluminescence.

Electrochemiluminescence (ECL) involves charge transfer between electrochemical redox intermediates to produce an excited state for light emission. Ensuring precise control of charge transfer is essential for decoding ECL fundamentals, yet guidelines on how to achieve this for conventional emitters remain unexplored. Molecular ratchets offer a potential solution, as they enable the directional transfer of energy or chemicals while impeding the reverse movement. Herein, we designed 10 pairs of imine-based covalent organic frameworks as reticular ratchets to delicately manipulate the intrareticular charge transfer for directing ECL transduction from electric and chemical energies. Aligning the donor and acceptor (D-A) directions with the imine dipole effectively facilitates charge migration, whereas reversing the D-A direction impedes it. Notably, the ratchet effect of charge transfer directionality intensified with increasing D-A contrast, resulting in a remarkable 680-fold improvement in the ECL efficiency. Furthermore, dipole-controlled exciton binding energy, electron/hole decay kinetics, and femtosecond transient absorption spectra identified the electron transfer tendency from the N-end toward the C-end of reticular ratchets during ECL transduction. An exponential correlation between the ECL efficiency and the dipole difference was discovered. Our work provides a general approach to manipulate charge transfer and design next-generation electrochemical devices.

Clinical outcomes and predictive factors of stent grafts treatment for symptomatic central venous obstruction in end stage kidney disease patients with arteriovenous access.

To assess the efficacy of stent grafts (SGs) in managing central venous obstruction disease (CVOD) in hemodialysis (HD) patients with arteriovenous (AV) access, and to identify predictive factors influencing the SG treatment outcomes. HD subjects with CVOD who underwent SGs placement at our center between August 2018 and June 2022 were enrolled. Survival curve analysis using the Kaplan-Meier method and log-rank test was performed. Cox proportional hazards regression analysis was employed to identify predictive factors associated with outcomes. A total of 59 SG implantation procedures for CVOD were analyzed, comprising 30 cases of stenosis and 29 cases of occlusion. The access circuit primary patency (ACPP) at 6, 12, and 24 months post-SG placement were 80.9%, 53.8%, and 31.4%, respectively, while, the target lesion primary patency (TLPP) were 91.3%, 67.6%, and 44.5%, respectively. Subgroup analysis revealed higher TLPP in the stenosis group compared to the occlusion group, although the difference was not statistically significant (P = 0.165). The TLPP was significantly improved by SG placement in those who had antecedent balloon dilations (P < 0.001). Cox proportional hazards regression identified target lesion length ≥ 30 mm and procedure defects as independent predictors of lower TLPP after SG treatment for CVOD in HD patients. SG placement demonstrates safety and efficacy in managing CVOD among HD patients, leading to improved TLPP of endovascular therapy (EVT) for CVOD. Notably, long target lesions (≥ 30 mm) and procedure defects emerged as predictive factors influencing TLPP.

Lysosome-Targeting Bacterial Outer Membrane Vesicles for Tumor Specific Degradation of PD-L1.

Increased expression of immune check point genes, such as PD-L1, is one of the main reasons for immunosuppression, especially for colon cancer. Development of novel therapeutic strategies is of great importance to improve the prognosis. In this study, outer membrane vesicles (OMV) derived from Gram-negative bacteria are engineered to immune checkpoint blockade nanosystem for efficient elicitation of anti-tumor immunity. Briefly, the OMVs are engineered with Lyp1-Traptavidin (S52G, R53D mutant of streptavidin) fusion protein displayed on the surface. The Lyp-1 endows the OMV with the capacity to target tumor tissues, while the Traptavidin ensures easy decoration of biotinylated anti-PD-L1 and biotinylated M6P (mannose 6-phosphate). The simultaneously anchored anti-PD-L1 and M6P (ligand for cation-independent mannose 6-phosphate receptor) on the engineered OMVs coordinately direct the membrane PD-L1 to lysosome for degradation, and thus unleash the anti-tumor immunity. With syngeneic tumor model, the engineered OMVs are confirmed to boost immunity, inhibit cancer growth, and thus prolong survival. Together, A proposed OMV-based modular nanosystem that enables assembly of biotinylated anti-PD-L1 and M6P on the surface for tumor-targeted immune checkpoint blockade.

Design, synthesis and antiproliferative activity of raloxifene/histone deacetylase inhibitor hybrids in breast cancer.

Antiestrogen/histone deacetylase inhibitor (HDACi) hybrids were designed by merging structures of raloxifene with suberoylanilide hydroxamic acid, incorporating the HDACi unit into the phenolic ring of the antiestrogen. These hybrids were synthesized with a range of HDACi chain lengths and assessed for bifunctionality. Four hybrids, 21 (YW471), 22 (YW490), 27(YW486), and 28 (YW487) showed good potency both as antiestrogens in a BRET assay and in a fluorometric HDACi assay. The antiproliferative activity of the hybrids was demonstrated in both ER+ MCF7 and ER- MDA-MB-231 breast cancer cell lines.

Ultracompact and multifunctional integrated photonic platform.

Realizing a multifunctional integrated photonic platform is one of the goals for future optical information processing, which usually requires large size to realize due to multiple integration challenges. Here, we realize a multifunctional integrated photonic platform with ultracompact footprint based on inverse design. The photonic platform is compact with 86 inverse designed-fixed couplers and 91 phase shifters. The footprint of each coupler is 4 µm by 2 µm, while the whole photonic platform is 3 mm by 0.2 mm-one order of magnitude smaller than previous designs. One-dimensional Floquet Su-Schrieffer-Heeger model and Aubry-André-Harper model are performed with measured fidelities of 97.90 (±0.52) % and 99.34 (±0.44) %, respectively. We also demonstrate a handwritten digits classification task with the test accuracy of 87% using on-chip training. Moreover, the scalability of this platform has been proved by demonstrating more complex computing tasks. This work provides an effective method to realize an ultrasmall integrated photonic platform.

Dynamic changes in the aroma profiles and volatiles of Enshi Yulu tea throughout its industrial processing.

Although Enshi Yulu tea (ESYL) possesses a distinctive fragrance, there is a scarcity of studies focusing on its primary volatiles or aroma genesis. This study aims to elucidate the dynamics in the profiles of aromas and volatiles through aroma profiling analysis and headspace solid-phase microextraction/gas chromatography-mass spectrometry. A total of 10 aroma attributes and 128 volatiles were identified in ESYL, with geraniol and linalool exhibiting the highest levels, and alcohols constituting the predominant proportion. Besides, a relative odor activity value (ROAV) based molecular aroma wheel was constructed, revealing 12 key odorants with ROAVs >1, wherein linalool, ß-ionone, and nonanal ranked highest. Notably, steaming and final drying emerged as critical steps for ESYL aroma development, while the non-enzymatic degradation of fatty acids likely contributed to the formation of its fresh aroma. These findings significantly enhance our comprehension of ESYL aroma formation.

Enabling non-viral DNA delivery using lipid nanoparticles co-loaded with endogenous anti-inflammatory lipids.

Lipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading DNA would provide additional advantages such as long-term expression and availability of promoter sequences. However, here we show that plasmid DNA (pDNA) delivery via LNPs (pDNA-LNPs) induces acute inflammation in naïve mice which we find is primarily driven by the cGAS-STING pathway. Inspired by DNA viruses that inhibit this pathway for replication, we co-loaded endogenous lipids that inhibit STING into pDNA-LNPs. Specifically, loading nitro-oleic acid (NOA) into pDNA-LNPs (NOA-pDNA-LNPs) ameliorates serious inflammatory responses in vivo enabling prolonged transgene expression (at least 1 month). Additionally, we demonstrate the ability to iteratively optimize NOA-pDNA-LNPs' expression by performing a small LNP formulation screen, driving up expression 50-fold in vitro. Thus, NOA-pDNA-LNPs, and pDNA-LNPs co-loaded with other bioactive molecules, will provide a major new tool in the genetic medicine toolbox, leveraging the power of DNA's long-term and promoter-controlled expression.