MYBL2 is a Novel Independent Prognostic Biomarker and Correlated with TMB in pancreatic cancer.

Background: Pancreatic cancer continues to pose a significant threat due to its high mortality rate. While MYB family genes have been identified as oncogenes in certain cancer types, their role in pancreatic cancer remains largely unexplored. Methods: The mRNA and protein expression of MYB family genes in pancreatic cancer samples was analyzed using TNMplot, HPA, and TISBID online bioinformatics tools, sourced from the TCGA and GETx databases. The relationship between MYB family gene expression and survival time was assessed through Kaplan-Meier analysis, while the prognostic impact of MYB family gene expression was evaluated using the Cox proportional hazards model. Additionally, Spearman's correlation analysis was employed to investigate the correlation between MYB family genes and TMB/MSI. Results: The integration of data from various databases demonstrated that all MYB family genes exhibited dysregulated expression in pancreatic cancer. However, only the expression of the MYBL2 gene displayed a notable association with the grade and stage of pancreatic cancer. Furthermore, the MYBL2 gene exhibited significant variations in both univariate and multivariate factor analyses.Subsequent functional analyses revealed a significant correlation between MYBL2 expression in pancreatic cancers and various biological processes, such as DNA replication, tumor proliferation, G2M checkpoint regulation, pyrimidine metabolism, and the P53 pathway. Additionally, a notable positive association was observed between MYBL2 expression and tumor mutational burden (TMB), a predictive indicator for response to PD1 antibody treatment. Conclusion: MYBL2 may be a double marker for independent diagnosis and PD1 antibody response prediction of pancreatic cancer patients.

Optimal Oxophilicity at the Fe-Nx Interface Enhances the Generation of Singlet Oxygen for Efficient Fenton-Like Catalysis.

In the pursuit of efficient singlet oxygen generation in Fenton-like catalysis, the utilization of single-atom catalysts (SACs) emerges as a highly desired strategy. Here, a discovery is reported that the single-atom Fe coordinated with five N-atoms on N-doped porous carbon, denoted as Fe-N5/NC, outperform its counterparts, those coordinated with four (Fe-N4/NC) or six N-atoms (Fe-N6/NC), as well as state-of-the-art SACs comprising other transition metals. Thus, Fe-N5/NC exhibits exceptional efficacy in activating peroxymonosulfate for the degradation of organic pollutants. The coordination number of N-atoms can be readily adjusted by pyrolysis of pre-assembly structures consisting of Fe3+ and various isomers of phenylenediamine. Fe-N5/NC displayed outstanding tolerance to environmental disturbances and minimal iron leaching when incorporated into a membrane reactor. A mechanistic study reveals that the axial ligand N reduces the contribution of Fe-3d orbitals in LUMO and increases the LUMO energy of Fe-N5/NC. This, in turn, reduces the oxophilicity of the Fe center, promoting the reactivity of *OO intermediate-a pivotal step for yielding singlet oxygen and the rate-determining step. These findings unveil the significance of manipulating the oxophilicity of metal atoms in single-atom catalysis and highlight the potential to augment Fenton-like catalysis performance using Fe-SACs.

WaterBiSeg-Net: An underwater bilateral segmentation network for marine debris segmentation.

The cleanup of marine debris is an urgent problem in marine environmental protection. AUVs with visual recognition technology have gradually become a central research issue. However, existing recognition algorithms have slow inference speeds and high computational overhead. They are also affected by blurred images and interference information. To solve these problems, a real-time semantic segmentation network is proposed, called WaterBiSeg-Net. First, we propose the Multi-scale Information Enhancement Module to solve the impact of low-definition and blurred images. Then, to suppress the interference of background information, the Gated Aggregation Layer is proposed. In addition, we propose a method that can extract boundary information directly. Finally, extensive experiments on SUIM and TrashCan datasets show that WaterBiSeg-Net can better complete the task of marine debris segmentation and provide accurate segmentation results for AUVs in real-time. This research offers a low computational cost and real-time solution for AUVs to identify marine debris.

High-sensitivity THz-ATR imaging of cerebral ischemia in a rat model.

The fast label-free detection of the extent and degree of cerebral ischemia has been the difficulty and hotspot for precise and accurate neurosurgery. We experimentally demonstrated that the fresh cerebral tissues at different ischemic stages within 24 hours can be well distinguished from the normal tissues using terahertz (THz) attenuated total reflection (ATR) imaging system. It was indicated that the total reflectivity of THz wave for ischemic cerebral tissues was lower than that for normal tissues. Especially, compared to the images stained with 2,3,5-triphenyl tetrazolium chloride (TTC), the ischemic tissues can be detected using THz wave with high sensitivity as early as the ischemic time of 2.5 hours, where THz images showed the ischemic areas became larger and diffused as the ischemic time increasing. Furthermore, the THz spectroscopy of cerebral ischemic tissues at different ischemic times was obtained in the range of 0.5-2.0 THz. The absorption coefficient of ischemic tissue increased with the increase of ischemic time, whereas the refractive index decreased with prolonging the ischemic time. Additionally, it was found from hematoxylin and eosin (H&E) staining microscopic images that, with the ischemic time increasing, the cell size and cell density of the ischemic tissues decreased, whereas the intercellular substance of the ischemic tissues increased. The result showed that THz recognition mechanism of the ischemia is mainly based on the increase of intercellular substance, especially water content, which has a stronger impact on absorption of THz wave than that of cell density. Thus, THz imaging has great potential for recognition of cerebral ischemia and it may become a new method for intraoperative real-time guidance, recognition in situ, and precise excision.

The Highly Sensitive Refractive Index Sensing of Seawater Based on a Large Lateral Offset Mach-Zehnder Interferometer.

A novel fiber sensor for the refractive index sensing of seawater based on a Mach-Zehnder interferometer has been demonstrated. The sensor consisted of a single-mode fiber (SMF)-no-core fiber (NCF)-single-mode fiber structure (shortened to an SNS structure) with a large lateral offset spliced between the two sections of a multimode fiber (MMF). Optimization studies of the multimode fiber length, offset SNS length, and vertical axial offset distance were performed to improve the coupling efficiency of interference light and achieve the best extinction ratio. In the experiment, a large lateral offset sensor was prepared to detect the refractive index of various ratios of saltwater, which were used to simulate seawater environments. The sensor's sensitivity was up to -13,703.63 nm/RIU and -13,160 nm/RIU in the refractive index range of 1.3370 to 1.3410 based on the shift of the interference spectrum. Moreover, the sensor showed a good linear response and high stability, with an RSD of only 0.0089% for the trough of the interference in air over 1 h.

Echistatin/BYL-719 impedes epithelial-mesenchymal transition in pulmonary fibrosis induced by silica through modulation of the Integrin ß1/ILK/PI3K signaling pathway.

Silicosis is a chronic fibroproliferative lung disease caused by long-term inhalation of crystalline silica dust, characterized by the proliferation of fibroblasts and pulmonary interstitial fibrosis. Currently, there are no effective treatments available. Recent research suggests that the Integrin ß1/ILK/PI3K signaling pathway may be associated with the pathogenesis of silicosis fibrosis. In this study, we investigated the effects of Echistatin (Integrin ß1 inhibitor) and BYL-719 (PI3K inhibitor) on silicosis rats at 28 and 56 days after silica exposure. Histopathological analysis of rat lung tissue was performed using H&E staining and Masson staining. Immunohistochemistry, Western blotting, and qRT-PCR were employed to assess the expression of markers associated with epithelial-mesenchymal transition (EMT), fibrosis, and the Integrin ß1/ILK/PI3K pathway in lung tissue. The results showed that Echistatin, BYL 719 or their combination up-regulated the expression of E-cadherin and down-regulated the expression of Vimentin and extracellular matrix (ECM) components, including type I and type III collagen. The increase of Snail, AKT and ß-catenin in the downstream Integrin ß1/ILK/PI3K pathway was inhibited. These results indicate that Echistatin and BYL 719 can inhibit EMT and pulmonary fibrosis by blocking different stages of Integrinß1 /ILK/PI3K signaling pathway. This indicates that the Integrin ß1/ILK/PI3K signaling pathway is associated with silica-induced EMT and may serve as a potential therapeutic target for silicosis.

Efficacy of autologous blood patch injection for pneumothorax rate after CT-guided percutaneous transthoracic lung biopsy: a systematic review and meta-analysis.

BACKGROUND: Pneumothorax is the most frequent complication after CT-guided percutaneous transthoracic lung biopsy (CT-PTLB). Many studies reported that injection of autologous blood patch (ABP) during biopsy needle withdrawal could reduce the pneumothorax and chest tube insertion rate after CT-PTLB, but the result is debatable. The aim of this systematic review and meta-analysis is to synthesize evidence regarding the efficacy of ABP procedure in patients receiving CT-PTLB. METHODS: Eligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between ABP and the pneumothorax and/or chest tube insertion rate after CT-PTLB. Subgroup analyses according to study type, emphysema status and ABP technique applied were also conducted. Odds ratio (OR) with 95% confidence interval (CI) were calculated to examine the risk association. RESULTS: A total of 10 studies including 3874 patients were qualified for analysis. Our analysis suggested that ABP reduced the pneumothorax (incidence: 20.0% vs. 27.9%, OR = 0.67, 95% CI = 0.48-0.66, P < 0.001) and chest tube insertion rate (incidence: 4.0% vs. 8.0%, OR = 0.47, 95% CI = 0.34-0.65, P < 0.001) after CT-PTLB. Subgroup analysis according to study type (RCT or retrospective study), emphysema status (with or without emphysema), and ABP technique applied (clotted or non-clotted ABP) were also performed and we found ABP reduced the pneumothorax and chest tube insertion rate in all subgroups. CONCLUSIONS: Our study indicated that the use of ABP was effective technique in reducing the pneumothorax and chest tube insertion rate after CT-PTLB.

Negatively charged nanodiscs for the reduction of toxicity and enhanced efficacy of polymyxin B against Acinetobacter baumannii sepsis.

The treatment of sepsis caused by multidrug-resistant (MDR) Gram-negative bacterial infections remains challenging. With these pathogens exhibiting resistance to carbapenems and new generation cephalosporins, the traditional antibiotic polymyxin B (PMB) has reemerged as a critical treatment option. However, its severe neurotoxicity and nephrotoxicity greatly limit the clinical application. Therefore, we designed negatively charged high-density lipoprotein (HDL) mimicking nanodiscs as a PMB delivery system, which can simultaneously reduce toxicity and enhance drug efficacy. The negative charge prevented the PMB release in physiological conditions and binding to cell membranes, significantly reducing toxicity in mammalian cells and mice. Notably, nanodisc-PMB exhibits superior efficacy than free PMB in sepsis induced by carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Nanodisc-PMB shows promise as a treatment for carbapenem-resistant Gram-negative bacterial sepsis, especially caused by Acinetobacter baumannii, and the nanodiscs could be repurposed for other toxic antibiotics as an innovative delivery system. STATEMENT OF SIGNIFICANCE: Multidrug-resistant Gram-negative bacteria, notably carbapenem-resistant Acinetobacter baumannii, currently pose a substantial challenge due to the scarcity of effective treatments, rendering Polymyxins a last-resort antibiotic option. However, their therapeutic application is significantly limited by severe neurotoxic and nephrotoxic side effects. Prevailing polymyxin delivery systems focus on either reducing toxicity or enhancing bioavailability yet fail to simultaneously achieve both. In this scenario, we have developed a distinctive HDL-mimicking nanodisc for polymyxin B, which not only significantly reduces toxicity but also improves efficacy against Gram-negative bacteria, especially in sepsis caused by CRAB. This research offers an innovative drug delivery system for polymyxin B. Such advancement could notably improve the therapeutic landscape and make a significant contribution to the arsenal against these notorious pathogens.

Activation of Sirtuin3 by honokiol ameliorates alveolar epithelial cell senescence in experimental silicosis via the cGAS-STING pathway.

BACKGROUND: Silicosis, characterized by interstitial lung inflammation and fibrosis, poses a significant health threat. ATII cells play a crucial role in alveolar epithelial repair and structural integrity maintenance. Inhibiting ATII cell senescence has shown promise in silicosis treatment. However, the mechanism behind silica-induced senescence remains elusive. METHODS: The study employed male C57BL/6 N mice and A549 human alveolar epithelial cells to investigate silicosis and its potential treatment. Silicosis was induced in mice via intratracheal instillation of crystalline silica particles, with honokiol administered intraperitoneally for 14 days. Silica-induced senescence in A549 cells was confirmed, and SIRT3 knockout and overexpression cell lines were generated. Various analyses were conducted, including immunoblotting, qRT-PCR, histology, and transmission electron microscopy. Statistical significance was determined using one-way ANOVA with Tukey's post-hoc test. RESULTS: This study elucidates how silica induces ATII cell senescence, emphasizing mtDNA damage. Notably, honokiol (HKL) emerges as a promising anti-senescence and anti-fibrosis agent, acting through sirt3. honokiol effectively attenuated senescence in ATII cells, dependent on sirt3 expression, while mitigating mtDNA damage. Sirt3, a class III histone deacetylase, regulates senescence and mitochondrial stress. HKL activates sirt3, protecting against pulmonary fibrosis and mitochondrial damage. Additionally, HKL downregulated cGAS expression in senescent ATII cells induced by silica, suggesting sirt3's role as an upstream regulator of the cGAS/STING signaling pathway. Moreover, honokiol treatment inhibited the activation of the NF-κB signaling pathway, associated with reduced oxidative stress and mtDNA damage. Notably, HKL enhanced the activity of SOD2, crucial for mitochondrial function, through sirt3-mediated deacetylation. Additionally, HKL promoted the deacetylation activity of sirt3, further safeguarding mtDNA integrity. CONCLUSIONS: This study uncovers a natural compound, HKL, with significant anti-fibrotic properties through activating sirt3, shedding light on silicosis pathogenesis and treatment avenues.

Association between untreated and treated blood pressure levels and cognitive decline in community-dwelling middle-aged and older adults in China: a longitudinal study.

BACKGROUND: Optimal blood pressure (BP) levels to reduce the long-term risk of cognitive decline remains controversial. We aimed to investigate the association between BP and anti-hypertensive treatment status with cognitive decline in older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study. Cognitive function was assessed at year 2011, 2013, 2015, and 2018. Global cognitive Z-score was calculated as the average score of episodic memory and mental intactness. BP were measured at the first and second wave. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Cumulative BP was calculated as the area under the curve using BP measurements from 2011 to 2013. Linear mixed models were used to assess the longitudinal association between BP-related measurements and cognitive decline. RESULTS: We included 11,671 participants (47.3% men and mean age 58.6 years). Individual with BP > 140/90 mm Hg or taking anti-hypertensive medication were independently associated with accelerated cognitive decline (ß=-0.014, 95% CI: -0.020 to -0.007). Individuals with anti-hypertensive medication use, but with controlled SBP to less than 120 mm Hg did not have a significantly increased risk of cognitive decline compared with normotension (ß=-0.003, 95% CI: -0.021 to 0.014). Individuals on anti-hypertensive treatment with PP of more than 70 mm Hg had a significantly higher risk of cognitive decline (ß=-0.033, 95% CI: -0.045 to -0.020). Regardless of anti-hypertensive treatment status, both elevated baseline and cumulative SBP and PP were found to be independently associated with accelerated cognitive decline. CONCLUSIONS: Cumulatively elevated SBP, PP and uncontrolled BP were associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment may be able to preserve cognitive decline in older adults.

Electromagnetohydrodynamic (EMHD) flow of Jeffrey fluid through a rough circular microchannel with surface charge-dependent slip.

This research examines the electromagnetohydrodynamic (EMHD) flow of Jeffrey fluid in a rough circular microchannel while considering the effect of surface charge on slip. The channel wall corrugations are described as periodic sinusoidal waves with small amplitudes. The perturbation method is employed to derive solutions for velocity and volumetric flow rate, and a combination of three-dimensional (3D) and two-dimensional (2D) graphical representations is utilized to effectively illustrate the impacts of relevant parameters on them. The significance of the Reynolds number R e $Re$ in investigations of EMHD flow is particularly emphasized. Furthermore, the effect of wall roughness ε $\varepsilon $ and wave number k $k$ on velocity and the influence of wall roughness ε $\varepsilon $ and surface charge density σ s ${\sigma }_s$ on volumetric flow rate are primarily focused on, respectively, at various Reynolds numbers. The results suggest that increasing the wall roughness leads to a reduction in velocity at low Reynolds numbers ( R e = 1 $Re = 1$ ) and an increment at high Reynolds numbers ( R e = 10 $Re = 10$ ). For any Reynolds number, a roughness with an odd multiple of wave number ( k = 6 , 10 $k = 6,10$ ) will result in a more stable velocity profile compared to one with an even multiple of wave number ( k = 4 , 8 $k = 4,8$ ). Decreasing the relaxation time λ ¯ 1 ${\bar{\lambda }}_1$ while increasing the retardation time λ ¯ 2 ${\bar{\lambda }}_2$ and Hartmann number H a $Ha$ can diminish the impact of wall roughness ε $\varepsilon $ and surface charge density σ s ${\sigma }_s$ on volumetric flow rate, independent of the Reynolds number. Interestingly, in the existence of wall roughness, further consideration of the effect of surface charge on slip leads to a 15% drop in volumetric flow rate at R e = 1 $Re = 1$ and a 32% slippage at R e = 10 $Re = 10$ . However, in the condition where the effect of surface charge on slip is considered, further examination of the presence of wall roughness only results in a 1.4% decline in volumetric flow rate at R e = 1 $Re = 1$ and a 1.6% rise at R e = 10 $Re = 10$ . These findings are crucial for optimizing the EMHD flow models in microchannels.

Synergetic Electrostatic and Steric Effects in α-FAPbI3 Single Crystals For X-Ray Detection and Imaging.

It is still challenging to stabilize α-FAPbI3 perovskite for high performance optoelectrical devices. Herein, a novel strategy is proposed utilizing the synergetic electrostatic and steric effect to stabilize the α-FAPbI3 phase and suppress the ion migration. Dimethylamine (DMA+) cations are chosen as the dopant to fabricate FA0.96DMA0.04PbI3 single crystals (SCs). DFT calculations reveal that DMA+ cations can improve the stability of α-FAPbI3 phase in both thermodynamics (lower Gibbs free energy) and kinetics (higher defect formation and migration energy). The resulting SCs exhibit an environmental stability over 100 days and an extraordinary low dark current drift of 3.7 × 10-7 nA cm-1 s-1 V-1, comparable to 2D perovskite SCs. The X-ray detectors have also achieved the-state-of-the-art performance in X-ray detection and imaging. This work demonstrates the significance of electrostatic and steric effects in improving the phase and operational stability of perovskites.

FL% is associated with the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk and total arch replacement.

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement. Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection. Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe.

Source-specific probabilistic health risk assessment of heavy metals in surface water of the Yangtze River Basin.

The detrimental effects of heavy metal accumulation on both ecosystems and public health have raised widespread concern. Source-specific risk assessment is crucial for developing effective strategies to prevent and control heavy metal contamination in surface water. This study aims to investigate the contamination characteristics of heavy metals in the Yangtze River Basin, identifying the pollution sources, assessing the risk levels, and further evaluating the health risks to humans. The results indicated that the average concentrations of heavy metals were ranked as follows: zinc (Zn) > arsenic (As) > copper (Cu) > chromium (Cr) > cadmium (Cd) > nickel (Ni) > lead (Pb), with average concentrations of 38.02 µg/L, 4.34 µg/L, 2.53 µg/L, 2.10 µg/L, 1.17 µg/L, 0.84 µg/L, and 0.32 µg/L, respectively, all below the WHO 2017 standards for safe drinking water. The distribution trend indicates higher concentrations in the upper and lower reaches and lower concentrations in the mid-reaches of the river. By integrating the Absolute Principal Component Scores-Multiple Linear Regression (APCS-MLR) receptor model and Positive Matrix Factorization (PMF) model, the main sources of heavy metals were identified as industrial activities (APCS-MLR: 41.3 %; PMF: 42.1 %), agricultural activities (APCS-MLR: 30.1 %; PMF: 27.4 %), and unknown mix sources (APCS-MLR: 29.1 %; PMF: 30.4 %). The calculation of the hazard index (HI) for both children and adults was <1, indicating no non-carcinogenic or carcinogenic risks. Based on the source-specific risk assessment, agricultural activities contribute the most to non-carcinogenic risks, while industrial activities pose the greatest contribution to carcinogenic risks. This study offers a reference for monitoring heavy metals and controlling health risks to residents, and provides crucial evidence for the utilization and protection of surface water in the Yangtze River Basin.

Ag3PO4 enables the generation of long-lived radical cations for visible light-driven [2 + 2] and [4 + 2] pericyclic reactions.

Photocatalytic redox reactions are important for synthesizing fine chemicals from olefins, but the limited lifetime of radical cation intermediates severely restricts semiconductor photocatalysis efficiency. Here, we report that Ag3PO4 can efficiently catalyze intramolecular and intermolecular [2 + 2] and Diels-Alder cycloadditions under visible-light irradiation. The approach is additive-free, catalyst-recyclable. Mechanistic studies indicate that visible-light irradiation on Ag3PO4 generates holes with high oxidation power, which oxidize aromatic alkene adsorbates into radical cations. In photoreduced Ag3PO4, the conduction band electron (eCB-) has low reduction power due to the delocalization among the Ag+-lattices, while the particle surfaces have a strong electrostatic interaction with the radical cations, which considerably stabilize the radical cations against recombination with eCB-. The radical cation on the particle's surfaces has a lifetime of more than 2 ms, 75 times longer than homogeneous systems. Our findings highlight the effectiveness of inorganic semiconductors for challenging radical cation-mediated synthesis driven by sunlight.

Association of chronic conditions and physical multimorbidity with new-onset incontinence in a nationwide prospective cohort study of older adults ≥ 50 years in China.

BACKGROUND: The relationship between multimorbidity (i.e. ≥ 2 chronic conditions) and incontinence (i.e. urinary and/or faecal incontinence) is underexplored. This study investigated the association between multimorbidity and incident incontinence in Chinese adults aged ≥50 years. METHODS: Data from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study were used. The association between 12 chronic conditions, multimorbidity and new-onset incontinence was analysed using weighted logistic regression models. Mediation analysis was conducted to explore the potential mediators (self-reported health, subjective memory, depressive symptoms, disability, cognitive function, handgrip strength, mobility limitations, medications and frailty status) between multimorbidity and incontinence. FINDINGS: Among 9,986 individuals aged ≥50 years who were continent at baseline, 5.3% (n = 521) were newly incontinent 4 years later (incident cases). The risk of incident incontinence increased with physical multimorbidity (OR 2.04, 95% CI 1.62-2.57). Compared to no chronic condition, having 1, 2, 3 and ≥ 4 chronic conditions were associated with incident incontinence with OR (95% CI): 1.41 (1.01-1.97), 1.74 (1.24-2.44), 2.82 (1.93-4.12) and 3.99 (2.29-6.95), respectively. The association between multimorbidity and incontinence was mediated by self-reported health (41.2%), medications (26.6%), mobility limitations (20.9%), depressive symptoms (12.8%), disability (11.6%), subjective memory (8.7%) and frailty status (8.3%). CONCLUSION: This longitudinal study found that physical multimorbidity and specific chronic conditions may increase the risk of new-onset incontinence among Chinese adults aged ≥50 years. Self-reported health, medications and mobility limitations seemed to be important intermediate conditions between multimorbidity and incident incontinence.

Role of long non-coding RNAs in metabolic reprogramming of gastrointestinal cancer cells.

Metabolic reprogramming, which is recognized as a hallmark of cancer, refers to the phenomenon by which cancer cells change their metabolism to support their increased biosynthetic demands. Tumor cells undergo substantial alterations in metabolic pathways, such as glycolysis, oxidative phosphorylation, pentose phosphate pathway, tricarboxylic acid cycle, fatty acid metabolism, and amino acid metabolism. Latest studies have revealed that long non-coding RNAs (lncRNAs), a group of non-coding RNAs over 200 nucleotides long, mediate metabolic reprogramming in tumor cells by regulating the transcription, translation and post-translational modification of metabolic-related signaling pathways and metabolism-related enzymes through transcriptional, translational, and post-translational modifications of genes. In addition, lncRNAs are closely related to the tumor microenvironment, and they directly or indirectly affect the proliferation and migration of tumor cells, drug resistance and other processes. Here, we review the mechanisms of lncRNA-mediated regulation of glucose, lipid, amino acid metabolism and tumor immunity in gastrointestinal tumors, aiming to provide more information on effective therapeutic targets and drug molecules for gastrointestinal tumors.

Copper Chaperone for Superoxide Dismutase Subtypes as a Prognostic Marker in Luminal B Breast Cancer.

Background: Copper chaperone for superoxide dismutase (CCS) is an essential component of the oxidation-reduction system. In breast cancer cells, CCS expression is highly up-regulated, which contributes to cellular proliferation and migration. Breast cancer is a multifaceted disease with different tumor prognoses and responses to clinical treatments, which may be associated with multiple molecular subtypes of CCS. Methods: The CCS expression patterns in breast cancer were investigated by TNMplot, cBioPortal, and HPA network database. The correlation of CCS expression with clinicopathological parameters was analyzed using the UALCAN database. The Cancer Genome Atlas (TCGA) data set was used to analyze the Clinical characteristics of CCS in luminal B patients. The bc-GenExMiner database was used to analyze the effects of BReast-CAncer susceptibility gene (BRCA)1/2, TP53 mutation status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER) expression on CCS expression. The survival curves and prognostic value of CCS in luminal B breast cancer were performed through Kaplan-Meier curves, univariate and multivariate Cox regression using the PrognoScan, bc-GenExMiner, and Clinical bioinformatics analysis platform. Results: We found that CCS expression was associated with patient age, race, ER, and PR status. We also discovered that BRCA1/2 mutations had an effect on CCS expression. The luminal B subtype had the highest CCS expression, which was linked to poor survival compared with other subtypes. In addition, Kaplan-Meier curve analysis showed that luminal B patients with high CCS mRNA expression showed a poor survival and the CCS gene is an independent predictor of outcome in patients with luminal B breast cancer by univariate and multivariate Cox regression. Conclusions: Our findings emphasize the significant expression of CCS in luminal B breast cancer and its potential as an autonomous prognostic determinant for this specific molecular subtype. These findings suggest that CCS holds promise as a prospective marker for the treatment of luminal B breast cancer.

The Association Between Serum Uric Acid and Cognitive Function Among Middle-Aged and Older Adults Without Hyperuricemia: The Mediating Role of Depressive Symptoms.

BACKGROUND: The association between serum uric acid (SUA) and cognitive function remains unclear, especially among individuals without hyperuricemia. We examined the cross-sectional and longitudinal bidirectional associations between SUA and cognition, as well as the mediating effect of depressive symptoms among Chinese adults. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). SUA (continuous) and cognitive function (based on mental intactness and episodic memory) were measured at Wave 1 and Wave 3. Depressive symptoms (Center for Epidemiologic Studies Depression scale) were assessed at Wave 1. Bivariate latent change score models and mediation analysis were used to investigate these possible associations. RESULTS: A total of 6 236 participants free of hyperuricemia (aged 58.3 ±â€…8.5 years) were included. After controlling for potential confounders, the SUA level was associated with cognition at baseline (standardized r = 0.042; p = .001). Higher baseline SUA level was associated with slower subsequent cognitive decline (standardized ß = 0.026; p = .027), whereas baseline cognition was not significantly associated with subsequent change in SUA (standardized ß = 0.003; p = .817). In mediation analysis, baseline SUA was indirectly associated with subsequent cognition via baseline depressive symptoms (mediation effect 13.3%; p < .001). CONCLUSIONS: Higher baseline SUA level is associated with better baseline cognition and less subsequent cognitive decline among Chinese adults without hyperuricemia. Baseline depressive symptoms may partially mediate the association between baseline SUA and later cognition. Continued research is warranted to verify these findings and elucidate the causality and underlying mechanisms.