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The irreversibility and low utilization of Zn anode stemming from the corrosion and dendrite growth have largely limited the commercialization of aqueous zinc batteries. Here, a carbonyl-rich polymer interphase of zinc polyacrylate (ZPAA) is spontaneously in-situ constructed on Zn anode to address the above-mentioned dilemmas. The ZPAA interlayer enables fast transport kinetics of Zn2+ and tailors the interfacial electric field for realizing the uniform Zn deposition due to superior zincophilicity, high Zn2+ transference number and inherent ion-diffusion channel. Importantly, acting as a buffer interphase with strong adhesion and isolation of electrolytes, this functional layer effectively protects the Zn electrode against the water-induced erosion and passivation. Remarkably, the ZPAA@Zn electrode realizes an enhanced Coulombic efficiency of 99.71 % within 2200 cycles, delivers an ultra-long cycling stability over 7660 h (>319 days, 1 mA cm-2) and 2460 h (5 mA cm-2) with lower voltage hysteresis. Also, the ZPAA@Zn/MnO2 full cell maintains a high capacity of 114 mAh/g after 2000 cycles, much better that of untreated Zn/MnO2 cell (25 mAh/g). This concept of in-situ fabricating ion-sieve-like polymer interphase provides a facile approach to stabilize Zn anode and further paves a way for high-performance aqueous batteries.
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The advancement of interface engineering has demonstrated remarkable efficacy in overcoming the primary impediment associated with sluggish reaction kinetics in supercapacitor electrodes. In this investigation, we employed a facile co-precipitation method to synthesize NiCoMoO4/MXene heterostructures utilizing Ti3C2Tx MXene nanosheets as carriers. This heterostructure inhibits the restacking of MXene nanosheets and simultaneously enhances the exposure of electrochemically active sites in NiCoMoO4 nanorods, thereby mitigating the reduction in specific capacitance resulting from volumetric fluctuations. The NiCoMoO4/MXene electrode, possessing pseudo-capacitance properties, demonstrates an impressive level of specific capacitance, exceptional performance across various charging rates, and consistent behavior throughout repeated cycles. By optimizing the mass ratio, this electrode achieves a specific capacity of 1900 F/g under a current density of 1 A/g. Even after enduring 10,000 cycles at a significantly higher current density of 5 A/g, it still maintains an impressive retention rate of 94.73 %. Our density functional theory (DFT) calculations indicate that the enhanced electrochemical performance can be attributed to the improved electronic coupling within the NiCoMoO4/MXene heterostructure. The integration of NiCoMoO4/MXene cathode and activated carbon (AC) anode with an alkaline gel electrolyte containing potassium ferricyanide in flexible quasi-solid-state supercapacitors (FSSCs) results in exceptional electrochemical performance and flexibility. These FSSCs demonstrate a maximum energy density of 72.89 Wh kg-1 at a power density of 850 W kg-1, while maintaining an impressive power output of 16,780 W kg-1 with an energy density of 37.28 Wh kg-1. Based on these outstanding properties, it is evident that the NiCoMoO4/MXene heterojunction possesses significant advantages as electrode material for supercapacitors, and the fabricated FSSCs devices pave a new pathway for flexible electronic devices.
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JOURNAL/nrgr/04.03/01300535-202507000-00029/figure1/v/2024-09-09T124005Z/r/image-tiff Autografting is the gold standard for surgical repair of nerve defects > 5 mm in length; however, autografting is associated with potential complications at the nerve donor site. As an alternative, nerve guidance conduits may be used. The ideal conduit should be flexible, resistant to kinks and lumen collapse, and provide physical cues to guide nerve regeneration. We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them. Subsequently, we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen. The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers. The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability. Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model, suggesting that it has potential for clinical use in human nerve injuries.
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In recent years, core-shell structured Prussian Blue Analogues (PBAs) have been considered as highly promising cathode materials for sodium-ion batteries. Reducing production costs and simplifying the preparation method for core-shell PBAs have also become crucial considerations. This paper presents a novel approach for the first time: by acid-treating the as-synthesized solution from a simple coprecipitation reaction, a high-crystallinity, sodium-rich Mn2+-doped iron hexacyanoferrate (Fe/MnHCF) shell material is self-grown on the surface of manganese hexacyanoferrate (MnHCF). This method significantly improves the electrochemical properties of the MnHCF material. The core-shell structured PBA exhibits excellent cycling performance (with a capacity retention of 95.5 % for 400 cycles at 1 A/g) and high rate performance (134.2mAh/g@10 mA/g, 95.2mAh/g@1 A/g). In this article, we explore the growth mechanism of the high-sodium content, high-crystallinity shell structure and introduce a green chelating agent that is better suited for the crystallization of Mn and Fe-type PBA systems. Our study demonstrates that Mn2+ doping enhances the conductivity of the shell material. Meanwhile, the heterojunction structure of MnHCF@Fe/MnHCF conducive to charge separation and migration. This straightforward synthesis strategy offers a novel approach for fabricating high-performance core-shell structured Prussian Blue Analogue materials.
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Transition metal sulfides have emerged as compelling anode materials for sodium-ion batteries (SIBs), leveraging their abundant elemental reserves and high theoretical capacities. However, the reaction of sulfur with Na ions is usually accompanied by significant volume dilation, which hinders their further development and application. Hence, constructing bimetallic sulfide (FeSn)/S for SIBs anode material greatly alleviates the circulation attenuation caused by volume expansion. Through constructing bimetallic heterojunction materials from nanocube precursors, the (FeSn)/S anode material retains a high specific capacity of 578 mAh/g at an intense current density of 2 A/g after 1000 cycles, and exhibits an great rate capability, delivering 796 mAh/g at 100 mA/g. The excellent electrochemical performance of the heterojunction material presents a promising solution to the enduring quest for enhanced anode material for SIBs.
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Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that â¼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.
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Proliferação de Células , MicroRNAs , Infarto do Miocárdio , Miócitos Cardíacos , Estresse Oxidativo , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Suínos , Hidrogéis/química , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismoRESUMO
Alzheimer's disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis. The Alzheimer's disease brain tends to be hyperexcitable and hypersynchronized, thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life, leaving patients incapacitated. Repetitive transcranial magnetic stimulation is a cost-effective, neuro-modulatory technique used for multiple neurological conditions. Over the past two decades, it has been widely used to predict cognitive decline; identify pathophysiological markers; promote neuroplasticity; and assess brain excitability, plasticity, and connectivity. It has also been applied to patients with dementia, because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult. However, its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies. This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment, evaluate its effects on synaptic plasticity, and identify the associated mechanisms. This review essentially focuses on changes in the pathology, amyloidogenesis, and clearance pathways, given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer's disease. Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription, which are closely related to the neural regeneration process, are also highlighted. Finally, we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation, with the aim to highlight future directions for better clinical translations.
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Objective: LncRNA plays a significant role in regulating feed efficiency. This study aims to explore the key long non-coding RNAs, associated genes, and pathways in pigs with extreme feed efficiencies. Methods: We screened pigs with extremely high and low RFI through a 12-week animal growth trial and then conducted transcriptome analysis on their liver and ileum tissues. We analyzed the differential expressed lncRNAs, miRNAs, and mRNAs through target gene prediction and functional analysis. And we identified key lncRNAs and their potential regulatory genes associated with feed efficiency through the construction of competitive endogenous RNA network. Results: Differentially expressed lncRNAs were pinpointed in the liver, revealing 23 crucial target genes primarily associated with GTP metabolism and glycolipid biosynthesis. In the ileum, a screening identified 92 pivotal target genes, mainly linked to lipid and small molecule metabolism. Moreover, LOC106504303 and LOC102160805 emerged as potentially significant lncRNAs respectively, playing roles in mitochondrial oxidative phosphorylation in the liver, and lipid and cholesterol metabolism in the ileum. Conclusion: The lncRNAs regulate energy metabolism and biosynthesis in the liver, and the digestive absorption capacity in the small intestine, affecting the feed efficiency of pigs.
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Polyimide (PI) coated with atomic layer deposition (ALD) thin films shows promising potential for applications in extreme environments. To achieve a high quality ultrathin ALD coating on the PI surface, Al-doped ALD-TiO2 (ATO) films were deposited on the alkaline hydrothermally activated PI surfaces. The nucleation and growth of ATO films were studied by XPS monitoring and SEM observation. The incorporation of aluminum introduced additional active sites that acted as a seed layer, promoting the adsorption and growth of titanium oxide. This effectively compensated for the defects in the TiO2 film, resulting in the formation of a continuously growing conformal film on the PI surface. After 200 ALD cycles, the ATO film deposited on PI exhibits excellent water vapor barrier properties and significant resistance to atomic oxygen (AO) erosion. When exposed to an AO flux of 1.4 × 1022 atom per cm2, the erosion yield of the PI coated with 200 ALD cycles of ATO film was as low as 2.4 × 10-26 cm3 per atom, which is two orders less than that of the standard polyimide-ref Kapton® film.
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Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.
The combination of transarterial chemoembolization, lenvatinib, and PD-1 inhibitor is an efficacious conversion therapy for uHCC. In this multicenter retrospective study, we discovered that PR was associated with the prognosis of patients who underwent conversion surgery. Predictors of MPR included neutrophil-to-lymphocyte ratio and alpha-fetoprotein levels.
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AIM: To describe the distribution of ocular biometrics and to evaluate its associations with refractive error and to assess the contribution from ocular parameters to refractive error among Chinese myopic children. METHODS: This cross-sectional study evaluated subjects aged 8-12y. Keratometry, ocular biometry, and cycloplegic autorefraction were performed on each subject. Spherical equivalent refraction (SER) and ocular biometrics were assessed as a function of age and gender. The Pearson correlation analysis between SER and ocular biometrics was carried out. Multiple linear regression was performed to analyze the association between SER and ocular parameters. RESULTS: A total of 689 out of 735 participants (321 boys, 48.1%) were analyzed, with a mean SER of -2.98±1.47 diopter (D). Axial length (AL), anterior chamber depth (ACD), corneal radius of curvature (CR), horizontal visible iris diameter (HVID), central corneal thickness (CCT) and lens power (LP) showed normal distribution. The AL, AL/CR ratio, ACD and CR increased from 8 to 12y of age, while SER and LP decreased, HVID and CCT remained stable. There was no difference in gender. SER decreased by 0.929 D for every 1 mm increase in AL and decreased by 1.144 D for every 0.1 increase in AL/CR ratio. The Pearson correlation coefficient between SER and AL was -0.538 (P<0.01) and -0.747 (P<0.01) between SER and AL/CR ratio. For the SER variance, AL explained 29.0%, AL/CR ratio explained 55.7%, while AL, CR, ACD and LP explained 99.3% after adjusting for age and gender. CONCLUSION: The AL, CR, ACD and LP are the most important determinants of myopic refractive error during myopia progression.
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Background and Aims: Metabolic syndrome (MetS) is associated with the development of several diseases. However, the correlation between MetS and size of renal cysts remains unclear. This research aims to explore the potential connection between them, offering theoretical guidance for clinical prevention and treatment of renal cysts. Methods: A total of 467 patients diagnosed with renal cysts and admitted to Sir Run Run Hospital, Nanjing Medical University from September 2019 to September 2020 were eventually included in this study. They were divided into the small cyst group (cyst volume≤1.5cm³) and the large cyst group (cyst volume>1.5cm³) based on the median value of cyst volume. Multivariate logistic regression analysis was used to evaluate the association between MetS and size of renal cysts. Results: Our results indicated that MetS (OR 1.941, 95% CI 1.286-2.927, P=0.002) was positively associated with the size of renal cysts. Additionally, multiple renal cysts (OR 2.259, 95% CI 1.402-3.640, P=0.001) and serum globulin (OR 0.945, 95% CI 0.905-0.987, P=0.011) were positively and negatively related to size of renal cysts, respectively. Conclusion: Our study reveals the association between MetS and the size of renal cysts. Patients with MetS are more likely to have larger renal cysts. The administration of MetS may help limit the development of renal cysts. Further prospective studies are needed to explore the causal relationship between MetS and renal cysts.
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BACKGROUND: Amyotrophic lateral sclerosis (ALS) is linked to ageing and genetic and environmental risk factors, yet underlying mechanisms are incompletely understood. We aimed to evaluate epigenetic age acceleration (EAA), i.e., DNA methylation (DNAm) age acceleration, and its association with ALS case status and survival. METHODS: In this study, we included 428 ALS and 288 control samples collected between 2011 and 2021. We calculated EAA using the GrimAge residual method from ALS and control blood samples and grouped participants with ALS into three ageing groups (fast, normal, slow). We associated EAA with ALS case status and survival, stratified by sex, and correlated it with environmental and biological factors through occupational exposure assessments, immune cell proportions, and transcriptome changes. FINDINGS: Participants with ALS had higher average EAA by 1.80 ± 0.30 years (p < 0.0001) versus controls. Participants with ALS in the fast ageing group had a hazard ratio of 1.52 (95% confidence interval 1.16-2.00, p = 0.0028) referenced to the normal ageing group. In males, this hazard ratio was 1.55 (95% confidence interval 1.11-2.17, p = 0.010), and EAA was positively correlated with high-risk occupational exposures including particulate matter (adj.p < 0.0001) and metals (adj.p = 0.0087). Also, in male participants with ALS, EAA was positively correlated with neutrophil proportions and was negatively correlated with CD4+ T cell proportions. Pathways dysregulated in participants with ALS with fast ageing included spliceosome, nucleocytoplasmic transport, axon guidance, and interferons. INTERPRETATION: EAA was associated with ALS case status and, at least in males, with shorter survival after diagnosis. The effect of EAA on ALS was partially explained by occupational exposures and immune cell proportions in a sex-dependent manner. These findings highlight the complex interactions of ageing and exposures in ALS. FUNDING: NIH, CDC/National ALS Registry, ALS Association, Dr. Randall Whitcomb Fund for ALS Genetics, Peter Clark Fund for ALS Research, Sinai Medical Staff Foundation, Scott L. Pranger ALS Clinic Fund, NeuroNetwork Therapeutic Discovery Fund, NeuroNetwork for Emerging Therapies.
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Viscosity is closely associated with physiological and pathological processes, as well as food quality. Herein, a novel fluorescent molecular rotor, BMCY-V, was presented and applied for detection of viscosity. BMCY-V contained a benzoindole unit as electron donor and a malononitrile group as acceptor. In low-viscous solvents, the rotor can freely rotate, leading to dissipation of excited-state energy. In high-viscous media, however, the free rotation of the rotor is severely restricted, thus reducing non-radiative transition and resulting in significantly enhanced fluorescence intensity. BMCY-V is extremely sensitive to viscosity, showing about 3968 times increase of fluorescence intensity at 728 nm from water to 95 % glycerol. Due to the excellent photophysical property such as near-infrared emission, BMCY-V was successfully used to visualize viscosity in live cells and in liver tissues. In addition, BMCY-V can also evaluate the thickening effect of various thickeners and visualize the changes of viscosity during deterioration of fluid drinks.
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The short-term risks associated with atmospheric trace gases, particularly carbon monoxide (CO), are critical for ecological security and human health. Traditional statistical methods, which still dominate the assessment of these risks, limit the potential for enhanced accuracy and reliability. This study evaluates the performance of traditional models (ARIMA), machine learning models (LightGBM, ConvLSTM2D), and optimized machine learning solutions (Bayes residual optimization ConvLSTM2D LightGBM, Bayes_CL) in predicting Sentinel 5P columnar CO levels. This study findings demonstrate that machine learning models and their optimized versions significantly outperform traditional ARIMA models in cross-validation (CV), visualization, and overall prediction performance. Notably, machine learning model based on Bayes and residual optimization (Bayes_CL) achieved the highest CV score (Bayes_CL R2 = 0.8, LightGBM R2 = 0.79, ConvLSTM2D R2 = 0.75, ARIMA R2 = 0.61), along with superior visualization and other metrics. Using Bayes_CL, we effectively quantified a 2.4% increase in columnar CO levels in mainland China in the second half of 2023, following the complete lifting of COVID-19 lockdowns. This study confirms that machine learning models can effectively replace traditional methods for short-term risk assessment of Sentinel 5P columnar CO. This transition holds significant implications for policy formulation, greenhouse effect assessment, and population health risk evaluation, especially in uncertain situations where human activities are severely disrupted, thereby affecting environmental safety.
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Fibroblast growth factor 18 (FGF18) emerges as a promising therapeutic target for osteoarthritis (OA). In this study, a novel articular cavity-localized lipid nanoparticle (LNP) named WG-PL14 is developed. This optimized formulation has a nearly 30-fold increase in mRNA expression as well as better articular cavity enrichment compared to commercial lipids MC3 when performing intra-articular injection. Then, a mRNA sequence encoding recombinant human FGF18 (rhFGF18) for potential mRNA therapy in OA is optimized. In vitro assays confirm the translation of rhFGF18 mRNA into functional proteins within rat and human chondrocytes, promoting cell proliferation and extracellular matrix (ECM) synthesis. Subsequently, the therapeutic efficacy of the LNP-rhFGF18 mRNA complex is systematically assessed in a mouse OA model. The administration exhibits several positive outcomes, including an improved pain response, upregulation of ECM-related genes (e.g., AGRN and HAS2), and remodeling of subchondral bone homeostasis compared to a control group. Taken together, these findings underscore the potential of localized LNP-rhFGF18 mRNA therapy in promoting the regeneration of cartilage tissue and mitigating the progression of OA.
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Objective: To evaluate belimumabf's efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response. Methods: In this single-arm retrospective study, we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment. Results: Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70-1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001). Conclusion: Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.
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Background: Sanda, a martial art that primarily involves punching, kicking, and throwing techniques, requires athletes to maintain high levels of concentration during combat. Sanda principally involves striking the opponent to secure victory, with trauma frequently occurring to the head; however, it remains unclear whether prolonged training enhances or impairs the athletes' attentional capacities. This study aimed to investigate the impact of Sanda training on athletes' attention by employing attention network tests. Methods: A retrospective analysis was conducted on 37 professional Sanda athletes from a certain sports academy; 38 college students from the same institution majoring in physical education were recruited as the control group. Control participants had no prior experience in Sanda training, and the Sanda and control groups were matched in terms of sex, age, and education level. The Attention Network Test (ANT) was administered to both groups to compare differences in efficiency across the alerting, orienting, and executive control networks. Results: Compared to the control group, the Sanda athletes exhibited significantly higher executive control network efficiency values and executive control network efficiency ratios (P < 0.05). There were no significant differences between the Sanda group and the control group regarding the efficiency values of the alerting and orienting networks (P > 0.05). Additionally, total accuracy and total reaction time between the Sanda athletes and control participants showed no statistically significant differences (P > 0.05). Conclusion: Sanda practice has detrimental effects on attention, including a decrease in the efficiency of the executive control network and a prolongation of the total reaction time. Therefore, athletes should improve attention training and use head protection to prevent frequent head impacts during training.
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Background: Fruquintinib is a third-line and subsequent targeted therapy for patients with metastatic colorectal cancer (mCRC). Identifying survival predictors after fruquintinib is crucial for optimizing the clinical use of this medication. Objectives: We aimed to identify factors influencing the prognosis of patients with mCRC treated with fruquintinib and to leverage these insights to develop a nomogram model for estimating survival rates in this patient population. Design: Multicenter retrospective observational study. Methods: We collected patient data from January 2019 to October 2023, with one healthcare institution's data serving as the training cohort and the other three hospitals' data serving as the multicenter validation cohort. The nomogram for overall survival was calculated from Cox regression models, and variable selection was screened using the univariate Cox regression analysis with additional variables based on clinical experience. Model performance was measured by the concordance index (C-index), calibration curves, decision curve analyses (DCA), and utility (patient stratification into low-risk vs high-risk groups). Results: Data were ultimately collected on 240 patients, with 144 patients included in the training cohort and 96 included in the multicenter validation cohort. Predictors included in the nomogram were CA199, body mass index, T stage, the primary site of the tumor, and other metastatic and pathological differentiation. The C-index of the nomogram in the training set and multicenter validation was 0.714 and 0.729, respectively. The models were fully calibrated and their predictions aligned closely with the observed data. DCA curves indicated the promising clinical benefits of the predictive model. Finally, the reliability of the model was also verified through the risk classification using the nomogram. Conclusions: We constructed a nomogram for mCRC treated with fruquintinib based on six variables that may be used to assist in personalizing the use of the drug.
A nomogram for predicting OS after application of fruquintinib in patients with mCRC The prognostic predictors of fruquintinib as a third-line and subsequent treatment agent for patients with mCRC have not been established. In this study, we explored possible factors influencing its prognosis and developed a nomogram model for estimating survival rates in this patient population. The nomogram, based on six key variables including CA199, BMI, T stage, primary tumor site, other metastatic sites, and pathological differentiation, was validated through a rigorous multicenter validation process. The nomogram has the potential to help clinicians personalize the use of fruquintinib for mCRC patients.
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The microbial communities associated with sponges contribute to the adaptation of hosts to environments, which are essential for the trophic transformation of benthic-marine coupling. However, little is known about the symbiotic microbial community interactions and adaptative strategies of high- and low-microbial abundance (HMA and LMA) sponges, which represent two typical ecological phenotypes. Here, we compared the 1-year dynamic patterns of microbiomes with the HMA sponge Spongia officinalis and two LMA sponge species Tedania sp. and Haliclona simulans widespread on the coast of China. Symbiotic bacterial communities with the characteristic HMA-LMA dichotomy presented higher diversity and stability in S. officinalis than in Tedania sp. and H. simulans, while archaeal communities showed consistent diversity across all sponges throughout the year. Dissolved oxygen, dissolved inorganic phosphorus, dissolved organic phosphorus, and especially temperature were the major factors affecting the seasonal changes in sponge microbial communities. S. officinalis-associated microbiome had higher diversity, stronger stability, and closer interaction, which adopted a relatively isolated strategy to cope with environmental changes, while Tedania sp. and H. simulans were more susceptible and shared more bacterial Amplicon Sequence Variants (ASVs) with surrounding waters, with an open way facing the uncertainty of the environment. Meta-analysis of the microbiome in composition, diversity, and ecological function from 13 marine sponges further supported that bacterial communities associated with HMA and LMA sponges have evolved two distinct environmental adaptation strategies. We propose that the different adaptive ways of sponges responding to the environment may be responsible for their successful evolution and their competence in global ocean change. IMPORTANCE: During long-term evolution, sponge holobionts, among the oldest symbiotic relationships between microbes and metazoans, developed two distinct phenotypes with high- and low-microbial abundance (HMA and LMA). Despite sporadic studies indicating that the characteristic microbial assemblages present in HMA and LMA sponges, the adaptation strategies of symbionts responding to environments are still unclear. This deficiency limits our understanding of the selection of symbionts and the ecological functions during the evolutionary history and the adaptative assessment of HMA and LMA sponges in variable environments. Here, we explored symbiotic communities with two distinct phenotypes in a 1-year dynamic environment and combined with the meta-analysis of 13 sponges. The different strategies of symbionts in adapting to the environment were basically drawn: microbes with LMA were more acclimated to environmental changes, forming relatively loose-connected communities, while HMA developed relatively tight-connected and more similar communities beyond the divergence of species and geographical location.