Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Constructing a Cr-Substituted Co-Free Li-Rich Ternary Cathode with a Spinel-Layered Biphase Interface.

Lithium-rich manganese-based layered oxides (LRMOs) have recently attracted enormous attention on account of their remarkably big capacity and high working voltage. However, some inevitable inherent drawbacks impede their wide-scale commercial application. Herein, a kind of Cr-containing Co-free LRMO with a topical spinel phase (Li1.2Mn0.54Ni0.13Cr0.13O2) has been put forward. It has been found that the high valence of Cr6+ can reduce the Li+ ion content and induce the formation of a local spinel phase by combining more Li+ ions, which is beneficial to eliminate the phase boundary between the spinel phase and the bulk phase of the LRMO material, thus dramatically avoiding phase separation during the cycling process. In addition, the introduction of Cr can also expand the layer spacing and construct a stronger Cr-O bond compared with Mn-O, which enables to combine the transition metal (TM) slab to prevent the migration of TM ions and the transformation of the bulk phase to the spinel phase. Simultaneously, the synergistic effect of the successfully constructed spinel-layered biphase interface and the strong Cr-O bond can effectively impede the escape of lattice oxygen during the initial activation process of Li2MnO3 and provide the fast diffusion path for Li+ ion transmission, thus further reinforcing the configurable stability. Besides, Cr-LRMO presents an ultrahigh first discharge specific capacity of 310 mAh g-1, an initial Coulombic efficiency of as high as 92.09%, a good cycling stability (a capacity retention of 94.70% after 100 cycles at 1C), and a small voltage decay (3.655 mV per cycle), as well as a good rate capacity (up to 165.88 mAh g-1 at 5C).

Association Among Vitamin D Supplementation, Serum 25(OH)D Concentrations, and Mortality Risk: A Prospective Cohort Study Using NHANES 2007-2018 Data.

BACKGROUND: To determine the associations among self-reported vitamin D (VD) supplementation, measured serum 25-hydroxyvitamin D (25[OH]D) concentrations, and all-cause and cause-specific mortality risks. METHODS: Self-reported VD supplementation, serum 25(OH)D concentration, and all-cause and cause-specific mortality data from the National Health and Nutrition Examination Survey 2007-2018 were examined for 10,793 adults ≥20 years from the United States. VD dosage was categorized as <800 or ≥800 IU/d. The mortality status and causes of mortality up to 2019 were determined using the National Death Index. The relationships among VD, 25(OH)D levels, and mortality were analyzed using Cox regression before and after propensity score matching (PSM). RESULTS: Over a median of 6.6 years, 915 deaths were recorded, 230 because of cardiovascular disease (CVD), 240 because of cancer, and 445 because of other specific causes. Mortality risk did not differ between VD <800 IU/d and ≥800 IU/d before or after PSM. However, serum 25(OH)D concentrations were statistically different before and after PSM. The upper 2 quartiles of 25(OH)D levels were associated with lower all-cause mortality, and the fourth quartile was associated with reduced other-specific mortality before and after PSM. No correlation was found between the 25(OH)D concentration and CVD- or cancer-specific mortality after PSM. The inverse 25(OH)D-mortality relationship was consistent across subgroups. CONCLUSIONS: Based on this large cohort study, higher 25(OH)D levels are robustly associated with reduced all-cause and other specific mortality but not CVD- or cancer-specific mortality. These findings support the benefits of maintaining adequate VD status for longevity. Further research is required to elucidate these mechanisms and define the optimal VD concentration to reduce mortality. These results underscore the importance of public health strategies for preventing VD deficiency.

Discovery of Phenylpyrazole Derivatives as a New Class of Selective Inhibitors of MCL-1 with Antitumor Activity.

MCL-1, an antiapoptotic member of the BCL-2 family, is dysregulated and overexpressed in various tumors. In tumors with MCL-1 overexpression, selective inhibitors of MCL-1 are expected to overcome the drug resistance caused by BCL-2 inhibitors currently used in clinical treatment. Here, we employed docking-based virtual screening to identify an active hit, LC126, with binding affinity around 10 µM for MCL-1 and BCL-2. Under the guidance of structure-based design, we obtained a few selective inhibitors of MCL-1 after three rounds of structural optimization. The representative compound GQN-B37-E exhibited binding affinity for MCL-1 at the submicromolar range (K i = 0.6 µM) without apparent binding to BCL-2 or BCL-XL. 15N-heteronuclear single-quantum coherence NMR spectra suggested that this compound binds to the BH3-domain-binding pocket in the MCL-1 surface. Cellular assays revealed that GQN-B37-Me, the precursor of GQN-B37-E, is effective particularly on leukemia cells (such as H929 and MV-4-11) to induce caspase-dependent apoptosis. Its interaction with MCL-1 in cells was confirmed by coimmunoprecipitation. Administration of GQN-B37-Me to MV-4-11 xenograft mice at 50 mg/kg every 2 days for 20 days led to 43% tumor growth inhibition. GQN-B37-Me also exhibited reasonable in vitro stability in GSH and liver microsomes from several species. This new class of MCL-1 inhibitor may have potential to be further developed into a preclinical candidate for treating leukemia.

Factors linked to prognosis in children with provisional tic disorder: a prospective cohort study.

The purpose of the present study was to estimate the factors linked to the prognosis of children with provisional tic disorder (PTD). We conducted a prospective cohort study enrolled children with PTD who were subsequently followed-up at three-month intervals for 1 year post-enrolment. A total of 259 PTD patients were included in the final analysis. At the end of the follow-up period, 77 (30%) of the patients had achieved clinical remission. Result of the LASSO logistic regression analysis revealed that a disease duration >3 months (OR=4.20, 95% CI 1.20-14.73), moderate/severe tic severity (OR=5.57, 95% CI 2.26-13.76), and comorbid behavioral problems (OR=2.78, 95% CI 1.15-6.69) were significant factors linked to remission in the PTD patients. The path analysis model showed that comorbid behavioral problems and recurrence partially mediated the association between tic severity and remission, with a mediating effect of 37%. Conclusions: We have identified several significant factors linked to prognosis in children with PTD, including comorbid behavioral problems and recurrence, which were found to be important mediators. These findings provide new insights for the clinical management of patients with PTD.

Validation of the Center for Neurologic Study Bulbar Function Scale-Chinese version in a population with amyotrophic lateral sclerosis.

OBJECTIVE: The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. METHODS: A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5-10 days after the first evaluation. RESULTS: The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p < 0.001). The CNS-BFSC total score and sialorrhea and speech scores were significantly correlated with the ALSFRS-R bulbar subscore (p < 0.001). The CNS-BFSC total score and ALSFRS-R bulbar subscale score were highly predictive of a clinician diagnosis of impaired bulbar function (area under the receiver operating characteristic curve, 0.947 and 0.911, respectively; p < 0.001). A cutoff value for the CNS-BFSC total score was selected by maximizing Youden's index; this cutoff score was 33, with 86.4% sensitivity and 93.3% specificity. The CNS-BFSC total score and the sialorrhea, speech and swallowing subscores had good-retest reliability (p > 0.05). The Cronbach's α of the CNS-BFSC was 0.972. CONCLUSION: The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

Molecular and morphological evidence supports the resurrection of Chrysospleniumguangxiense H.G.Ye & Gui C.Zhang (Saxifragaceae).

Chrysospleniumguangxiense H.G.Ye & Gui C.Zhang was first described as a new species in 1994 but later synonymized in the Flora of China treatment with C.glossophyllum H.Hara. Plastid genomes and nrDNA sequences were used to infer the phylogenetic relationships of selected taxa in Chrysosplenium. Our phylogenetic analyses revealed that C.guangxiense belongs to sect. Alternifolia, is closely related to Chrysospleniumhydrocotylifolium H.Lév. & Vaniot but distant from C.glossophyllum. Morphologically, C.guangxiense could be easily distinguished from C.glossophyllum by having robust rhizomes, basal leaves with a long cuneate base and fewer teeth in the margin, curled sepal margins, and red, larger seeds. It could also be easily distinguished from C.hydrocotylifolium by possessing long elliptic leaves and a long cuneate leaf base. Along with the phylogenetic studies, the complete plastid genome of C.guangxiense was also reported. The plastid genome was 154,004 bp in length and comprised two inverted repeats (IRs) of 28,120 bp, separated by a large single-copy of 80,646 bp and a small single-copy of 17,118 bp. A total of 111 functional genes were discovered, comprising 78 protein-coding genes, 29 tRNA genes, and four rRNA genes. Based on assessment of morphological and molecular data Chrysospleniumguangxiense H.G.Ye & Gui C.Zhang is resurrected from C.glossophyllum H.Hara at species level. A global conservation assessment classifies C.guangxiense as Vulnerable (VU).

Operative Mortality After Type A Aortic Dissection Surgery: Differences Based on Sex and Age.

Background: There is controversy regarding sex differences in short-term mortality in acute type A aortic dissection (ATAAD). Objectives: This study aimed to investigate the impact of sex differences on 30-day operative mortality after ATAAD surgery and to determine if other covariates modify the association. Methods: Consecutive patients (N = 5670) with surgically repaired ATAAD were identified from the multicenter China 5A study. The primary outcome was operative mortality. The age dependency was modeled using a cubic spline curve. Results: There were 1,503 females (26.5%) and 4,167 males (73.5%). Females were older and had a lower percentage of comorbidities compared with males. Females had higher mortality compared to males (10.2% vs 8.2%, P = 0.019); however, there was no difference after propensity analyses (adjusted OR: 1.334 [95% CI: 0.918-1.938]). There was an interaction with sex and age (P interaction = 0.035): older age was associated with higher odds of operative mortality among females (OR: 1.045 [95% CI: 1.029-1.061]) compared with males (OR: 1.025 [95% CI: 1.016-1.035]). The risk of mortality for males and females appears to diverge at 55 years of age (P interaction = 0.019): females under 55 years of age had similar odds to males (OR: 0.852 [95% CI: 0.603-1.205]) but higher odds when over 55 years (OR: 1.420 [95% CI: 1.096-1.839]) compared to males. Conclusions: Under the age of 55 years, females have similar odds of operative mortality compared with males; however, over the age of 55 years females have higher odds than males. Understanding differences in risk allows for individualized treatment strategies. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy; NCT04398992).

CT-based quantification of intratumoral heterogeneity for predicting pathologic complete response to neoadjuvant immunochemotherapy in non-small cell lung cancer.

Objectives: To investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC) using quantification of intratumoral heterogeneity from pre-treatment CT image. Methods: This retrospective study included 178 patients with NSCLC who underwent NAIC at 4 different centers. The training set comprised 108 patients from center A, while the external validation set consisted of 70 patients from center B, center C, and center D. The traditional radiomics model was contrasted using radiomics features. The radiomics features of each pixel within the tumor region of interest (ROI) were extracted. The optimal division of tumor subregions was determined using the K-means unsupervised clustering method. The internal tumor heterogeneity habitat model was developed using the habitats features from each tumor sub-region. The LR algorithm was employed in this study to construct a machine learning prediction model. The diagnostic performance of the model was evaluated using criteria such as area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). Results: In the training cohort, the traditional radiomics model achieved an AUC of 0.778 [95% confidence interval (CI): 0.688-0.868], while the tumor internal heterogeneity habitat model achieved an AUC of 0.861 (95% CI: 0.789-0.932). The tumor internal heterogeneity habitat model exhibits a higher AUC value. It demonstrates an accuracy of 0.815, surpassing the accuracy of 0.685 achieved by traditional radiomics models. In the external validation cohort, the AUC values of the two models were 0.723 (CI: 0.591-0.855) and 0.781 (95% CI: 0.673-0.889), respectively. The habitat model continues to exhibit higher AUC values. In terms of accuracy evaluation, the tumor heterogeneity habitat model outperforms the traditional radiomics model, achieving a score of 0.743 compared to 0.686. Conclusion: The quantitative analysis of intratumoral heterogeneity using CT to predict pCR in NSCLC patients undergoing NAIC holds the potential to inform clinical decision-making for resectable NSCLC patients, prevent overtreatment, and enable personalized and precise cancer management.

Identification of geographical origins of Gastrodia elata Blume based on multisource data fusion.

INTRODUCTION: Identifying the geographical origin of Gastrodia elata Blume contributes to the scientific and rational utilization of medicinal materials. In this study, infrared spectroscopy was combined with machine learning algorithms to distinguish the origin of G. elata BI. OBJECTIVE: Realization of rapid and accurate identification of the origin of G. elata BI. MATERIALS AND METHODS: Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectra and Fourier transform near-infrared (FT-NIR) spectra were collected for 306 samples of G. elata BI. SAMPLES: Firstly, a support vector machine (SVM) model was established based on the single-spectrum and the full-spectrum fusion data. To investigate whether feature-level fusion strategy can enhance the model's performance, the sequential and orthogonalized partial least squares discriminant analysis (SO-PLS-DA) model was established to extract and combine two types of spectral features. Next, six algorithms were employed to extract feature variables, SVM model was established based on the feature-level fusion data. To avoid complicated preprocessing and feature extraction processes, a residual convolutional neural network (ResNet) model was established after converting the raw spectral data into spectral images. RESULTS: The accuracy of the feature-level fusion model is better as compared to the single-spectrum model and the fusion model with full-spectrum, and SO-PLS-DA is simpler than feature-level fusion based on the SVM model. The ResNet model performs well in classification but requires more data to enhance its generalization capability and training effectiveness. CONCLUSION: Sequential and orthogonalized data fusion approaches and ResNet models are powerful solutions for identifying the geographic origin of G. elata BI.

The Non-Denatured Processing of Brasenia schreberi Mucilage-Characteristics of Hydrodynamic Properties and the Effect on In Vivo Functions.

Food non-denatured processes, such as freeze-drying and grinding, are commonly applied to raw materials with good bioactive functions. Although the functional components are maintained, whether structural and physical changes impact the in vivo function is often ignored in practical situations. Brasenia schreberi mucilage (BSM) has a significant alleviation effect on DSS-induced colitis. This work focused on the influence of non-denatured manufacture on the colonic benefits of BSM-based products. First, three forms of products including fresh mucilage (FM), freeze-dried products (FS), and freeze-dried powder (FP) were prepared. Then, their in vitro physiochemical properties were compared, analyzing their influence on the gut inflammation degree, microbial composition, and SCFA production in mice. The results suggested that the water retention rate of FS and FP was decreased to 34.59 ± 3.85%, and 9.93 ± 1.76%. The viscosity of FM, FS, and FP was 20.14 Pa∙s, 4.92 Pa∙s, and 0.41 Pa∙s, respectively. The freeze-drying and grinding process also damaged the lamellar microstructure of BSM. Then, animal tests showed that colitis mice intervened with FM, FS, and FP had disease activity scores of 2.03, 3.95, and 4.62. Meanwhile, FM notably changed the gut microbial composition and significantly increased propionate and butyrate levels. It seemed that the distinct colitis alleviation efficacy of BSM-based products is attributed to different hydrodynamic properties in the gut. FM had relatively higher viscosity and correspondingly high nutritional density in the gut lumen, which stimulates Firmicutes growth and promotes butyrate production, and thereby exhibited the best efficiency on protecting from colitis.

Intraocular pressure control efficacy and safety of HA-Mg glaucoma drainage plate implantation in the anterior chamber of rabbit eyes.

The current clinical application of glaucoma drainage devices is made of non-degradable materials. These non-degradable drainage devices often trigger inflammatory responses and scar proliferation, possibly leading to surgical failure. We developed a biodegradable material hydroxyapatite-coated magnesium (HA-Mg) as a glaucoma drainage device. Twelve New Zealand white rabbits were randomly assigned to three groups: HA-Mg drainage plate group (6 right eyes), trabeculectomy group (6 right eyes), and control group (12 left eyes). Results showed that all HA-Mg drainage plates were completely degraded ~4 months postoperatively. At the 5th month postoperatively, there was no statistical difference in the corneal endothelium density between the HA-Mg drainage plate group and the control group (p = 0.857). The intraocular pressure (IOP) level in the HA-Mg drainage plate implantation group was lower than in the other two groups. The trypan blue dye still drained from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation. HE staining revealed the scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded, with no obvious infiltration with the inflammatory cells. This study showed the safety and efficacy of HA-Mg glaucoma drainage plate in controlling IOP after implantation into the anterior chamber of rabbit eyes.

Factors influencing fatigue, mental workload and burnout among Chinese health care workers during public emergencies: an online cross-sectional study.

OBJECTIVES: The purpose of this study was to investigate fatigue, mental workload, and burnout among health care workers (HCWs) and explore the possible underlying factors. MATERIALS AND METHODS: An online cross-sectional survey design was used to collect data from HCWs in Chongqing, China. The online survey included the Fatigue Severity Scale, NASA Task Load Index, and Chinese version of the Maslach Burnout Inventory-General Survey to assess fatigue, mental workload, and burnout, respectively, and was conducted from February 1 to March 1, 2023. RESULTS: In this study, the incidence of fatigue and burnout among HCWs was 76.40% and 89.14%, respectively, and the incidence of moderate to intolerable mental workloads was 90.26%. Work-family conflict, current symptoms, number of days of COVID-19 positivity, mental workload, burnout and reduced personal accomplishment were significantly associated with fatigue. Mental workload was affected by fatigue and reduced personal accomplishment. Furthermore, burnout was influenced by marital status and fatigue. Moreover, there was a correlation among mental workload, fatigue, and burnout. CONCLUSIONS: Fatigue, mental workload and burnout had a high incidence and were influenced by multiple factors during COVID-19 public emergencies in China.

Exploring the Mechanism of Zhishi-Xiebai-Guizhi Decoction for the Treatment of Hypoxic Pulmonary Hypertension Based on Network Pharmacology and Experimental Analyses.

BACKGROUND: Hypoxic Pulmonary Hypertension (HPH), a prevalent disease in highland areas, is a crucial factor in various complex highland diseases with high mortality rates. Zhishi-Xiebai-Guizhi Decoction (ZXGD), traditional Chinese medicine with a long history of use in treating heart and lung diseases, lacks a clear understanding of its pharmacological mechanism. OBJECTIVE: This study aimed to investigate the pharmacological effects and mechanisms of ZXGD on HPH. METHODS: We conducted a network pharmacological prediction analysis and molecular docking to predict the effects, which were verified through in vivo experiments. RESULTS: Network pharmacological analysis revealed 51 active compounds of ZXGD and 701 corresponding target genes. Additionally, there are 2,116 target genes for HPH, 311 drug-disease co-target genes, and 17 core target genes. GO functional annotation analysis revealed that the core target genes primarily participate in biological processes such as apoptosis and cellular response to hypoxia. Furthermore, KEGG pathway enrichment analysis demonstrated that the core targets are involved in several pathways, including the phosphatidylinositol- 3 kinase/protein kinase B (PI3K/Akt) signaling pathway and Hypoxia Inducible Factor 1 (HIF1) signaling pathway. In vivo experiments, the continuous administration of ZXGD demonstrated a significant improvement in pulmonary artery pressure, right heart function, pulmonary vascular remodeling, and pulmonary vascular fibrosis in HPH rats. Furthermore, ZXGD was found to inhibit the expression of PI3K, Akt, and HIF1α proteins in rat lung tissue. CONCLUSION: In summary, this study confirmed the beneficial effects and mechanism of ZXGD on HPH through a combination of network pharmacology and in vivo experiments. These findings provided a new insight for further research on HPH in the field of traditional Chinese medicine.

Electromagnetic Cellularized Patch with Wirelessly Electrical Stimulation for Promoting Neuronal Differentiation and Spinal Cord Injury Repair.

Although stem cell therapy holds promise for the treatment of spinal cord injury (SCI), its practical applications are limited by the low degree of neural differentiation. Electrical stimulation is one of the most effective ways to promote the differentiation of stem cells into neurons, but conventional wired electrical stimulation may cause secondary injuries, inflammation, pain, and infection. Here, based on the high conductivity of graphite and the electromagnetic induction effect, graphite nanosheets with neural stem cells (NSCs) are proposed as an electromagnetic cellularized patch to generate in situ wirelessly pulsed electric signals under a rotating magnetic field for regulating neuronal differentiation of NSCs to treat SCI. The strength and frequency of the induced voltage can be controlled by adjusting the rotation speed of the magnetic field. The generated pulsed electrical signals promote the differentiation of NSCs into functional mature neurons and increase the proportion of neurons from 12.5% to 33.7%. When implanted in the subarachnoid region of the injured spinal cord, the electromagnetic cellularized patch improves the behavioral performance of the hind limbs and the repair of spinal cord tissue in SCI mice. This work opens a new avenue for remote treatment of SCI and other nervous system diseases.

Cell-free DNA methylation patterns in aging and their association with inflamm-aging.

Aim: Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Methods: Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. Results: It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. Conclusion: These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.

Our bodies undergo many changes as we age, some of which might affect our health. To better understand these changes, scientists study something called 'cell-free DNA' (cfDNA) in our blood. This cfDNA can give us clues about our health and the risk of diseases like cancer or heart conditions.In our research, we analyzed cfDNA from the blood of 35 people to identify patterns associated with aging. We discovered that approximately 2000 specific spots in our DNA change in a way that's linked to aging. These changes might help us figure out someone's biological age ­ essentially, how old their body seems based on various health factors, which can differ from their actual age.We also found that these DNA changes could indicate how aging might make the body's defense system ­ which fights off diseases ­ react more intensely. Understanding this could be crucial for managing health as we get older.Our study suggests that cfDNA could be a useful marker for aging, offering a new approach to understanding and possibly managing the health effects associated with growing older.

Transmissibility of the variant of concern for SARS-CoV-2 in six regions.

Introduction: Differences in transmissibility of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) in different districts are hard to assess. To address this, our study focused on calculating the Real-time reproduction number (R t ) for these variants in different regions. Methods: According to the criteria defined by the World Health Organization (WHO), the global landscape was categorized into six distinct regions. In each region, the predominant SARS-CoV-2 variant was first identified based on the proportion of variant sequencing analysis results. Then, using serial interval (SI) parameters, we calculated R t for the relevant Variant of Concern (VOC) in each region. This approach enabled us to compare the R t values of the same variant across different regions and analyze the transmissibility of each region's variant in relation to the overall situation in that region. Results: The progression of VOC for SARS-CoV-2 shows regional variations. However, a common sequence of evolution is observed: Wild-type → Alpha → Beta → Delta → Omicron. Moreover, an increasing trend is discerned within diverse regions where the shift in R t of distinct VOC corresponds with the overarching R t route of SARS-CoV-2 in specific regions. Conclusion: As the COVID-19 pandemic advances, regional epidemiological trends are aligning, likely due to similar virus mutations and shared public health strategies, suggesting opportunities for standardized global responses.

Effect of microplastics on sodium hypochlorite disinfection and changes in its toxicity on zebrafish.

The presence of microplastics (MPs) in water may affect the efficacy of the disinfection process and induce toxicity changes to MPs themselves during disinfection. Therefore, this study evaluated the two-way effects of polyethylene microplastic (MP) particles in water and wastewater during sodium hypochlorite (NaClO) disinfection. On the one hand, it has been confirmed that the presence of MPs reduced the disinfection efficiency of NaClO. The required CT (concentration of the disinfection × contact time) for a 2-4-log inactivation of Escherichia coli (E. coli) in different water samples was in the order of deionized water < turbid water (1 NTU) < water with MPs (1 mg/L) < turbid water (10 NTU). On the other hand, although exposure to MPs did induce significant changes in the activities of superoxide dismutase and glutathione, compared to pristine MPs, the MPs treated by NaClO at current conditions (0.3 and 3.0 mg/L for 30 min) did not show significant changes in their toxicity on zebrafish, at an MP exposure concentration of 1 mg/L. There was no significant difference in the survival rate and weight growth rate, neither as in the activities of the oxidative stress-related enzymes (superoxide dismutase, catalase, glutathione, glutathione peroxidase, and glutathione s-transferase) in both gut and muscle tissues of the zebrafish, between exposure to the pristine and NaClO-treated MPs. It is indicated that NaClO disinfection commonly applied for water and wastewater treatment would not pose a serious concern to effluent safety in the presence of mild levels of MPs.

Preparation of Controlled Multicompartmental Gel Microcarriers Based on Aqueous Two-Phase Emulsions for 3D Partitioned Cell Coculture In Vitro.

A facile method was proposed for preparing controllable multicompartment gel microcarriers using an aqueous two-phase emulsion system. By leveraging the density difference between the upper polyethylene glycol solution and the lower dextran-calcium chloride (CaCl2) solution in the collection solution and the high viscosity of the lower solution, controllable fusion of core-shell droplets made by coextrusion devices was achieved at the water/water (w/w) interface to fabricate microcarriers with separated core compartments. By adjusting the sodium alginate concentration, collected solution composition, and number of fused liquid droplets, the pore size, shape, and number of compartments could be controlled. Caco-2 and HepG2 cells were encapsulated in different compartments to establish gut-liver coculture models, exhibiting higher viability and proliferation compared to monoculture models. Notably, significant differences in cytokine expression and functional proteins were observed between the coculture and monoculture models. This method provides new possibilities for preparing complex and functional three-dimensional coculture materials.