[The Value of Clinical Characteristics and Hematological Parameters for Prognostic Assessment of Pancreatic Cancer Patients Undergoing Radical Resection]. / ä¸€èˆ¬ä¸´åºŠç‰¹å¾ä¸Žè¡€æ¶²å­¦å‚æ•°åœ¨èƒ°è ºå¯¼ç®¡è ºç™Œæ ¹æ²»æ€§åˆ‡é™¤æœ¯æ‚£è€ ä¸­çš„é¢„åŽä»·å€¼ç ”ç©¶.

Objective: To explore the relationship between baseline clinical characteristics and hematological parameters of patients undergoing radical resection for pancreatic ductal adenocarcinoma (PDAC) and their prognosis, and to provide references for stratifying the patients' clinical risks. Methods: We retrospectively collected clinical data from 445 patients who underwent radical surgical treatment for PDAC at West China Hospital, Sichuan University between January 2010 and February 2019. Then, we conducted retrospective clinical analysis with the collected data. Data on patients' basic clinical characteristics, routine blood test results, and tumor indicators were collected to explore their effects on the postoperative overall survival (OS) of PDAC patients. Cox proportional hazards regression was used to identify factors affecting OS. Statistical analysis was performed using the SPSS 23.0 software package. Results: The postoperative median overall survival (mOS) was 17.0 months (95% CI: 15.0-19.0). The 1, 2, 3, 4, and 5-year survival rates of the patients included in the study were 60.6%, 33.4%, 19.1%, 12.7%, and 9.6%, respectively. The multivariate Cox proportional hazards model analysis demonstrated that a number of factors independently affect postoperative survival in PDAC patients. These factors include tumor location (hazards ratio [HR]=1.574, 95% CI: 1.233-2.011), degree of tumor cell differentiation (HR=0.687, 95% CI: 0.542-0.870), presence of neural invasion (HR=0.686, 95% CI: 0.538-0.876), TNM staging (HR=1.572, 95% CI: 1.252-1.974), postoperative adjuvant therapy (HR=1.799, 95% CI: 1.390-2.328), preoperative drinking history (HR=0.744, 95% CI: 0.588-0.943), and high serum CA199 levels prior to the surgery (HR=0.742, 95% CI: 0.563-0.977). Conclusion: In PDAC patients, having tumors located in the head of the pancreas, moderate and high degrees of differentiated, being free from local neurovascular invasion, being in TNM stage Ⅰ, undergoing postoperative adjuvant therapy, no history of alcohol consumption prior to the surgery, and preoperative serum CA199 being less than or equal to 37 U/mL are significantly associated with a better prognosis.

Machine learning on longitudinal multi-modal data enables the understanding and prognosis of Alzheimer's disease progression.

Alzheimer's disease (AD) is a complex pathophysiological disease. Allowing for heterogeneity, not only in disease manifestations but also in different progression patterns, is critical for developing effective disease models that can be used in clinical and research settings. We introduce a machine learning model for identifying underlying patterns in Alzheimer's disease (AD) trajectory using longitudinal multi-modal data from the ADNI cohort and the AIBL cohort. Ten biologically and clinically meaningful disease-related states were identified from data, which constitute three non-overlapping stages (i.e., neocortical atrophy [NCA], medial temporal atrophy [MTA], and whole brain atrophy [WBA]) and two distinct disease progression patterns (i.e., NCA → WBA and MTA → WBA). The index of disease-related states provided a remarkable performance in predicting the time to conversion to AD dementia (C-Index: 0.923 ± 0.007). Our model shows potential for promoting the understanding of heterogeneous disease progression and early predicting the conversion time to AD dementia.

Enhancing COVID-19 booster vaccination among the elderly through text message reminders.

The BOOST (Booster promotion for older outpatients using SMS text reminders) program at Taipei Veterans General Hospital assessed the effectiveness of text message reminders in enhancing COVID-19 booster vaccination rates among the elderly, guided by the Health Belief Model (HBM). Targeting patients aged 65 and above, eligible yet unvaccinated for a COVID-19 booster, this cohort study sent personalized reminders a week prior to their scheduled appointments between April 18, 2022, and May 12, 2022, acting as cues to action to enhance vaccination uptake by overcoming perceived barriers and raising awareness of benefits. Over 5 weeks, the study observed a 38% increase in vaccination rate among 3,500 eligible patients, markedly surpassing the concurrent national rate increase of 4% for the same demographic. The majority of vaccinations occurred within two weeks after the reminder, illustrating the effectiveness of the strategy. Cox regression analysis identified age and time since last vaccination as significant predictors of responsiveness, with those aged 65-74 and 75-84 showing higher uptake, particularly when reminders were sent within 4 months after the last dose. A single reminder proved to be effective. The findings of this study demonstrate the potential of SMS reminders to promote COVID-19 vaccination among the elderly through the strategic use of HBM principles, suggesting a feasible and effective approach to public health communication.

Frontoparietal and salience network synchronizations during nonsymbolic magnitude processing predict brain age and mathematical performance in youth.

The development and refinement of functional brain circuits crucial to human cognition is a continuous process that spans from childhood to adulthood. Research increasingly focuses on mapping these evolving configurations, with the aim to identify markers for functional impairments and atypical development. Among human cognitive systems, nonsymbolic magnitude representations serve as a foundational building block for future success in mathematical learning and achievement for individuals. Using task-based frontoparietal (FPN) and salience network (SN) features during nonsymbolic magnitude processing alongside machine learning algorithms, we developed a framework to construct brain age prediction models for participants aged 7-30. Our study revealed differential developmental profiles in the synchronization within and between FPN and SN networks. Specifically, we observed a linear increase in FPN connectivity, concomitant with a decline in SN connectivity across the age span. A nonlinear U-shaped trajectory in the connectivity between the FPN and SN was discerned, revealing reduced FPN-SN synchronization among adolescents compared to both pediatric and adult cohorts. Leveraging the Gradient Boosting machine learning algorithm and nested fivefold stratified cross-validation with independent training datasets, we demonstrated that functional connectivity measures of the FPN and SN nodes predict chronological age, with a correlation coefficient of .727 and a mean absolute error of 2.944 between actual and predicted ages. Notably, connectivity within the FPN emerged as the most contributing feature for age prediction. Critically, a more matured brain age estimate is associated with better arithmetic performance. Our findings shed light on the intricate developmental changes occurring in the neural networks supporting magnitude representations. We emphasize brain age estimation as a potent tool for understanding cognitive development and its relationship to mathematical abilities across the critical developmental period of youth. PRACTITIONER POINTS: This study investigated the prolonged changes in the brain's architecture across childhood, adolescence, and adulthood, with a focus on task-state frontoparietal and salience networks. Distinct developmental pathways were identified: frontoparietal synchronization strengthens consistently throughout development, while salience network connectivity diminishes with age. Furthermore, adolescents show a unique dip in connectivity between these networks. Leveraging advanced machine learning methods, we accurately predicted individuals' ages based on these brain circuits, with a more mature estimated brain age correlating with better math skills.

Dissociation of focal and large-scale inhibitory functions in the older adults: A multimodal MRI study.

BACKGROUND: The decline of inhibitory in cognitive aging is linked to reduced cognitive and mental capacities in older adults. However, this decline often shows inconsistent clinical presentations, suggesting varied impacts on different inhibition-related tasks. Inhibitory control, a multifaceted construct, involves various types of inhibition. Understanding these components is crucial for comprehending how aging affects inhibitory functions. Our research investigates the influences of aging on large-scale and focal-scale inhibitory and examines the relationship with brain markers. METHODS: We examined the impact of aging on inhibitory in 18 younger (20-35 years) and 17 older adults (65-85 years) using focal and large-scale inhibition tasks. The Gabor task assessed focal-scale inhibition, while the Stop Signal Task (SST) evaluated large-scale inhibition. Participants underwent neuropsychological assessments and MRI scans, including magnetic resonance spectroscopy (MRS) and structural and resting fMRI. RESULTS: Older adults exhibited a marked decline in inhibitory function, with slower SST responses indicating compromised large-scale inhibition. Conversely, the Gabor task showed no significant age-related changes. MRS findings revealed decreased levels of GABA, glutamate, glutamine, and NAA in the pre-SMA, correlating with observed large-scale inhibition in older adults. Additionally, pre-SMA seed-based functional connectivity analysis showed reduced brain network connections in older adults, potentially contributing to inhibitory control deficits. CONCLUSIONS: Our study elucidates the differential effects of aging on inhibitory functions. While large-scale inhibition is more vulnerable to aging, focal-scale inhibition is relatively preserved. These findings highlight the importance of targeted cognitive interventions and underscore the necessity of a multifaceted approach in aging research.

Direct Current Pulse Atmospheric Pressure Plasma Jet Treatment on Electrochemically Deposited NiFe/Carbon Paper and Its Potential Application in an Anion-Exchange Membrane Water Electrolyzer.

An atmospheric pressure plasma jet (APPJ) is used to process electrochemically deposited NiFe on carbon paper (NiFe/CP). The reactive oxygen and nitrogen species (RONs) of the APPJ modify the surface properties, chemical bonding types, and oxidation states of the material at the self-sustained temperature of the APPJ. The APPJ treatment further enhances the hydrophilicity and creates a higher disorder level in the carbon material. Moreover, the metal carbide bonds of NiFe/CP formed in the electrochemical deposition (ED) process are converted to metal oxide bonds after APPJ processing. The potential application of APPJ treatment on NiFe/CP in alkaline water electrolysis is demonstrated. With more oxygen-containing species and better hydrophilicity after APPJ treatment, APPJ-treated NiFe/CP is applied as the electrocatalyst for the oxygen evolution reaction (OER) in alkaline water electrolysis. APPJ-treated NiFe/CP is also used in a custom-made anion-exchange membrane water electrolyzer (AEMWE); this should contribute toward realizing the practical large-scale application of AEM for hydrogen production.

Valorization of Food Waste: Utilizing Natural Porous Materials Derived from Pomelo-Peel Biomass to Develop Triboelectric Nanogenerators for Energy Harvesting and Self-Powered Sensing.

Food waste is an enormous challenge, with implications for the environment, society, and economy. Every year around the world, 1.3 billion tons of food are wasted or lost, and food waste-associated costs are around $2.6 trillion. Waste upcycling has been shown to mitigate these negative impacts. This study's optimized pomelo-peel biomass-derived porous material-based triboelectric nanogenerator (PP-TENG) had an open circuit voltage of 58 V and a peak power density of 254.8 mW/m2. As porous structures enable such triboelectric devices to respond sensitively to external mechanical stimuli, we tested our optimized PP-TENG's ability to serve as a self-powered sensor of biomechanical motions. As well as successfully harvesting sufficient mechanical energy to power light-emitting diodes and portable electronics, our PP-TENGs successfully monitored joint motions, neck movements, and gait patterns, suggesting their strong potential for use in healthcare monitoring and physical rehabilitation, among other applications. As such, the present work opens up various new possibilities for transforming a prolific type of food waste into value-added products and thus could enhance long-term sustainability while reducing such waste.

Improved camptothecin encapsulation and efficacy by environmentally sensitive block copolymer/chitosan/fucoidan nanoparticles for targeting lung cancer cells.

In this study, thermo-sensitive poly(N-isopropyl acrylamide) (PNP) was polymerized with pH-sensitive poly(acrylic acid) (PAA) to prepare a PAA-b-PNP block copolymer. Above its cloud point, the block copolymer self-assembled into nanoparticles (NPs), encapsulating the anticancer drug camptothecin (CPT) in situ. Chitosan (CS) and fucoidan (Fu) further modified these NPs, forming Fu-CPT-NPs to enhance biocompatibility, drug encapsulation efficiency (EE), and loading content (LC), crucially facilitating P-selectin targeting of lung cancer cells through a pulmonary drug delivery system. The EE and LC reached 82 % and 3.5 %, respectively. According to transmission electron microscope observation, these Fu-CPT-NPs had uniform spherical shapes with an average diameter of ca. 250 nm. They could maintain their stability in a pH range of 5.0-6.8. In vitro experimental results revealed that the Fu-CPT-NPs exhibited good biocompatibility and had anticancer activity after encapsulating CPT. It could deliver CPT to cancer cells by targeting P-selectin, effectively increasing cell uptake and inducing cell apoptosis. Animal study results showed that the Fu-CPT-NPs inhibited lung tumor growth by increasing tumor cell apoptosis without causing significant tissue damage related to generating reactive oxygen species in lung cancer cells. This system can effectively improve drug-delivery efficiency and treatment effects and has great potential for treating lung cancer.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Lysine L-lactylation is the dominant lactylation isomer induced by glycolysis.

Lysine L-lactylation (Kl-la) is a novel protein posttranslational modification (PTM) driven by L-lactate. This PTM has three isomers: Kl-la, N-ε-(carboxyethyl)-lysine (Kce) and D-lactyl-lysine (Kd-la), which are often confused in the context of the Warburg effect and nuclear presence. Here we introduce two methods to differentiate these isomers: a chemical derivatization and high-performance liquid chromatography analysis for efficient separation, and isomer-specific antibodies for high-selectivity identification. We demonstrated that Kl-la is the primary lactylation isomer on histones and dynamically regulated by glycolysis, not Kd-la or Kce, which are observed when the glyoxalase system was incomplete. The study also reveals that lactyl-coenzyme A, a precursor in L-lactylation, correlates positively with Kl-la levels. This work not only provides a methodology for distinguishing other PTM isomers, but also highlights Kl-la as the primary responder to glycolysis and the Warburg effect.

MicroRNA-195-5p Attenuates Intracerebral-Hemorrhage-Induced Brain Damage by Inhibiting MMP-9/MMP-2 Expression.

Intracerebral hemorrhage (ICH) remains a devastating disease with high mortality, and there is a lack of effective strategies to improve functional outcomes. The primary injury of ICH is mechanical damage to brain tissue caused by the hematoma. Secondary injury, resulting from inflammation, red cell lysis, and thrombin production, presents a potential target for therapeutic intervention. Inflammation, crucial in secondary brain injury, involves both cellular and molecular components. MicroRNAs (miRNAs) are vital regulators of cell growth, differentiation, and apoptosis. Their deregulation may lead to diseases, and modulating miRNA expression has shown therapeutic potential, especially in cancer. Recent studies have implicated miRNAs in the pathogenesis of stroke, affecting endothelial dysfunction, neurovascular integrity, edema, apoptosis, inflammation, and extracellular matrix remodeling. Preclinical and human studies support the use of miRNA-directed gene modulation as a therapeutic strategy for ICH. Our study focused on the effects of miR-195 in ICH models. Neurological tests, including the corner turn and grip tests, indicated that miR-195 treatment led to improvements in motor function impairments caused by ICH. Furthermore, miR-195-5p significantly reduced brain edema in the ipsilateral hemisphere and restored blood-brain barrier (BBB) integrity, as shown by reduced Evans blue dye extravasation. These results suggest miR-195-5p's potential in attenuating ICH-induced apoptosis, possibly related to its influence on MMP-9 and MMP-2 expression, enzymes associated with secondary brain injury. The anti-apoptotic effects of miR-195-5p, demonstrated through TUNEL assays, further underscore its therapeutic promise in addressing the secondary brain injury and apoptosis associated with ICH. In conclusion, miR-195-5p demonstrates a significant neuroprotective effect against ICH-induced neural damage, brain edema, and BBB disruption, primarily through the downregulation of MMP-9 and MMP-2. Our findings indicate that miR-195-5p holds therapeutic potential in managing cerebral cell death following ICH.

Failure Diagnosis for Dental Air Turbine Handpiece with Payload Using Feature Engineering and Temporal Convolution Network.

The internal mechanisms of dental air turbine handpieces (DATHs) have become increasingly intricate over time. To enhance the operational reliability of dental procedures and guarantee patient safety, this study formulated temporal convolution network (TCN) prediction models with the functions of causality in time sequence, transmitting memory, learning, storing, and fast convergence for monitoring the health and diagnosing the rotor and collet failure of DATHs. A handpiece mimicking a dentist's hand load of 100 g was employed to repeatedly mill a glass porcelain block back and forth for cutting. An accelerometer was employed to capture vibration signals during free-running of unrestrained operation of the handpiece, aiming to discern the characteristic features of these vibrations. These data were then utilized to create a diagnostic health classification (DHC) for further developing a TCN, a 1D convolutional neural network (CNN), and long short-term memory (LSTM) prediction models. The three frameworks were used and compared for machine learning to establish DHC prediction models for the DATH. The experimental results indicate that, in terms of DHC predicted for the experimental dataset, the square categorical cross-entropy loss function error of the TCN framework was generally lower than that of the 1D CNN, which did not have a memory framework or the drawback of the vanishing gradient problem. In addition, the TCN framework outperformed the LSTM model, which required a longer history to provide sufficient diagnostic ability. Still, high accuracies were achieved both in the direction of feed-drive milling and in the gravity of the handpiece through vibration signals. In general, the failure classification prediction model could accurately predict the health and failure mode of the dental handpiece before the use of the DATH when an embedded sensor was available. Therefore, this model could prove to be a beneficial tool for predicting the deterioration patterns of real dental handpieces in their remaining useful life.

Increasing DNA damage sensitivity through corylin-mediated inhibition of homologous recombination.

BACKGROUND: DNA repair allows the survival of cancer cells. Therefore, the development of DNA repair inhibitors is a critical need for sensitizing cancers to chemoradiation. Sae2CtIP has specific functions in initiating DNA end resection, as well as coordinating cell cycle checkpoints, and it also greatly interacts with the DDR at different levels. RESULTS: In this study, we demonstrated that corylin, a potential sensitizer, causes deficiencies in DNA repair and DNA damage checkpoints in yeast cells. More specifically, corylin increases DNA damage sensitivity through the Sae2-dependent pathway and impairs the activation of Mec1-Ddc2, Rad53-p and γ-H2A. In breast cancer cells, corylin increases apoptosis and reduces proliferation following Dox treatment by inhibiting CtIP. Xenograft assays showed that treatment with corylin combined with Dox significantly reduced tumor growth in vivo. CONCLUSIONS: Our findings herein delineate the mechanisms of action of corylin in regulating DNA repair and indicate that corylin has potential long-term clinical utility as a DDR inhibitor.

Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair.

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.

Mitigating fungal contamination of cereals: The efficacy of microplasma-based far-UVC lamps against Aspergillus flavus and Fusarium graminearum.

Fungal contaminations of cereal grains are a profound food-safety and food-security concern worldwide, threatening consumers' and animals' health and causing enormous economic burdens. Because far-ultraviolet C (far-UVC) light at 222 nm has recently been shown to be human-safe, we investigated its efficacy as an alternative to thermal, chemical, and conventional 254 nm UVC anti-fungal treatments. Our microplasma-based far-UVC lamp system achieved a 5.21-log reduction in the conidia of Aspergillus flavus suspended in buffer with a dose of 1032.0 mJ/cm2, and a 5.11-log reduction of Fusarium graminearum conidia in suspension with a dose of 619.2 mJ/cm2. We further observed that far-UVC treatments could induce fungal-cell apoptosis, alter mitochondrial membrane potential, lead to the accumulation of intracellular reactive oxygen species, cause lipid peroxidation, and result in cell-membrane damage. The lamp system also exhibited a potent ability to inhibit the mycelial growth of both A. flavus and F. graminearum. On potato dextrose agar plates, such growth was completely inhibited after doses of 576.0 mJ/cm2 and 460.8 mJ/cm2, respectively. To test our approach's efficacy at decontaminating actual cereal grains, we designed a cubical 3D treatment chamber fitted with six lamps. At a dose of 780.0 mJ/cm2 on each side, the chamber achieved a 1.88-log reduction of A. flavus on dried yellow corn kernels and a 1.11-log reduction of F. graminearum on wheat grains, without significant moisture loss to either cereal type (p > 0.05). The treatment did not cause significant changes in the propensity of wheat grains to germinate in the week following treatment (p > 0.05). However, it increased the germination propensity of corn kernels by more than 71% in the same timeframe (p < 0.05). Collectively, our results demonstrate that 222 nm far-UVC radiation can effectively inactivate fungal growth in liquid, on solid surfaces, and on cereal grains. If scalable, its emergence as a safe, cost-effective alternative tool for reducing fungi-related post-harvest cereal losses could have important positive implications for the fight against world hunger and food insecurity.

Syngeneic mesenchymal stem cells loaded with telomerase-dependent oncolytic adenoviruses enhance anti-metastatic efficacy.

Oncolytic adenoviruses have emerged as a promising therapeutic approach for cancer therapy. However, systemic delivery of the viruses to metastatic tumors remains a major challenge. Mesenchymal stem cells (MSCs) possess tumor tropism property and can be used as cellular vehicles for delivering oncolytic adenoviruses to tumor sites. Since telomerase activity is found in ~90% of human carcinomas, but undetected in normal adult cells, the human telomerase reverse transcriptase gene (TERT) promoter can be exploited for regulating the replication of oncolytic adenoviruses. Here, we evaluated the antitumor effects of syngeneic murine MSCs loaded with the luciferase-expressing, telomerase-dependent oncolytic adenovirus Ad.GS2 (MSC-Ad.GS2) and Ad.GS2 alone on metastatic MBT-2 bladder tumors. MSCs supported a low degree of Ad.GS2 replication, which could be augmented by coculture with MBT-2 cells or tumor-conditioned medium (TCM), suggesting that viral replication is increased when MSC-Ad.GS2 migrates to tumor sites. MBT-2 cells and TCM enhanced viral replication in Ad.GS2-infected MSCs. SDF-1 is a stem cell homing factor. Our results suggest that the SDF-1/STAT3/TERT signaling axis in MSCs in response to the tumor microenvironment may contribute to the enhanced replication of Ad.GS2 carried by MSCs. Notably, we demonstrate the potent therapeutic efficacy of systemically delivered MSC-Ad.GS2 in pleural disseminated tumor and experimental metastasis models using intrapleural and tail vein injection of MBT-2 cells, respectively. Treatment with MSC-Ad.GS2 significantly reduced tumor growth and prolonged the survival of mice bearing metastatic bladder tumors. Since telomerase is expressed in a broad spectrum of cancers, this therapeutic strategy may be broadly applicable.

Fabrication of a decellularized liver matrix-based hepatic patch for the repair of CCl4-induced liver injury.

This article primarily introduces a new treatment for liver fibrosis/cirrhosis. We developed a hepatic patch by combining decellularized liver matrix (DLM) with the hepatocyte growth factor (HGF)/heparin-complex and evaluated its restorative efficacy. In vitro prophylactic results, the HGF/heparin-DLM patches effectively mitigated CCl4-induced hepatocyte toxicity and restored the cytotoxicity levels to the baseline levels by day 5. Furthermore, these patches restored albumin synthesis of injured hepatocytes to more than 70% of the normal levels within 5 days. In vitro therapeutic results, the urea synthesis of the injured hepatocytes reached 91% of the normal levels after 10 days of culture, indicating successful restoration of hepatic function by the HGF/heparin-DLM patches in both prophylactic and therapeutic models. In vivo results, HGF/heparin-DLM patches attached to the liver and gut exhibited a significant decrease in collagen content (4.44 times and 2.77 times, respectively) and an increase in glycogen content (1.19 times and 1.12 times, respectively) compared to the fibrosis group after 1 week, separately. In summary, liver function was restored and inflammation was inhibited through the combined effects of DLM and the HGF/heparin-complex in fibrotic liver. The newly designed hepatic patch holds promise for both in vitro and in vivo regeneration therapy and preventive health care for liver tissue engineering.

Global Prevalence of Overweight and Obesity in Children and Adolescents: A Systematic Review and Meta-Analysis.

Importance: Overweight and obesity in childhood and adolescence is a global health issue associated with adverse outcomes throughout the life course. Objective: To estimate worldwide prevalence of overweight and obesity in children and adolescents from 2000 to 2023 and to assess potential risk factors for and comorbidities of obesity. Data Sources: MEDLINE, Web of Science, Embase, and Cochrane. Study Selection: The inclusion criteria were: (1) studies provided adequate information, (2) diagnosis based on body mass index cutoffs proposed by accepted references, (3) studies performed on general population between January 2000 and March 2023, (4) participants were younger than 18 years. Data Extraction and Synthesis: The current study was performed in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. DerSimonian-Laird random-effects model with Free-Tukey double arcsine transformation was used for data analysis. Sensitivity analysis, meta-regression, and subgroup analysis of obesity among children and adolescents were conducted. Main Outcomes and Measures: Prevalence of overweight and obesity among children and adolescents assessed by World Health Organization, International Obesity Task Force, the US Centers for Disease Control and Prevention, or other national references. Results: A total of 2033 studies from 154 different countries or regions involving 45 890 555 individuals were included. The overall prevalence of obesity in children and adolescents was 8.5% (95% CI 8.2-8.8). We found that the prevalence varied across countries, ranging from 0.4% (Vanuatu) to 28.4% (Puerto Rico). Higher prevalence of obesity among children and adolescents was reported in countries with Human Development Index scores of 0.8 or greater and high-income countries or regions. Compared to 2000 to 2011, a 1.5-fold increase in the prevalence of obesity was observed in 2012 to 2023. Substantial differences in rates of obesity were noted when stratified by 11 risk factors. Children and adolescents with obesity had a high risk of depression and hypertension. The pooled estimates of overweight and excess weight in children and adolescents were 14.8% (95% CI 14.5-15.1) and 22.2% (95% CI 21.6-22.8), respectively. Conclusions and Relevance: This study's findings indicated 1 of 5 children or adolescents experienced excess weight and that rates of excess weight varied by regional income and Human Development Index. Excess weight among children and adolescents was associated with a mix of inherent, behavioral, environmental, and sociocultural influences that need the attention and committed intervention of primary care professionals, clinicians, health authorities, and the general public.

Serum 25-Hydroxyvitamin D Level Is Positively Associated with Vascular Reactivity Index in Patients with Type 2 Diabetes Mellitus.

Circulating 25-hydroxyvitamin D (25(OH)D) significantly influences endothelial function. This study assessed the correlation between serum 25(OH)D and endothelial function using the vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples from 102 T2DM participants and VRI were assessed. Patients were divided into three categories based on VRI: low (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0). Among these patients, 30 (29.4%) had poor, 39 (38.2%) had intermediate, and 33 (32.4%) exhibited good vascular reactivity. Higher serum fasting glucose (p = 0.019), glycated hemoglobin (p = 0.009), and urinary albumin-to-creatinine ratio (p = 0.006) were associated, while lower prevalence of hypertension (p = 0.029), lower systolic blood pressure (p = 0.027), lower diastolic blood pressure (p < 0.001), and lower circulation 25(OH)D levels (p < 0.001) were associated with poor vascular reactivity. Significant independent associations between diastolic blood pressure (p = 0.002) and serum 25(OH)D level (p < 0.001) and VRI were seen in T2DM patients according to multivariable forward stepwise linear regression analysis. Serum 25(OH)D positively correlated with VRI values, and lower levels of serum 25(OH)D were linked to endothelial dysfunction in T2DM patients.