Evaluating the Prognostic Significance of Cystatin C Level Variations Pre- and Post-Radiofrequency Catheter Ablation in the Recurrence of Persistent Atrial Fibrillation.

OBJECTIVE: To investigate the correlation between persistent atrial fibrillation (AF) recurrence and alterations in cystatin C levels pre- and post-radiofrequency catheter ablation (RFCA). METHODS: This study encompassed 114 patients diagnosed with persistent AF. Their serum cystatin C levels were assessed both prior to and 3 months after undergoing an RFCA procedure. The variance in cystatin C levels before and after RFCA is represented as ΔCystatin C. Subsequently, we compared these values between two groups: patients who did not experience a recurrence of AF (n = 79) and those who did experience a recurrence (n = 35). RESULTS: A significant reduction in cystatin C levels post-RFCA in both groups, with a more pronounced decrease observed in the non-recurrence group. Moreover, the recurrence group exhibited larger left atrial diameter and volume before RFCA compared to the non-recurrence group. Cox regression analysis indicated that smaller reductions in serum cystatin C levels and greater left atrial volumes before RFCA were associated with an increased risk of recurrence, after adjusting for covariates. The receiver operating characteristic curve indicated an elevated probability of clinical recurrence of AF post-RFCA in patients with a cystatin C decline < 0.08 mg/L (AUC 0.64). The Kaplan-Meier survival analysis revealed that patients with a cystatin C decline > 0.08 mg/L exhibited significantly higher rates of remaining free from recurrence following RFCA across a 24-month follow-up period (Log-rank test p = 0.003). CONCLUSIONS: Alterations in ΔCystatin C levels pre and post-RFCA in the initial phase could independently predict the recurrence of AF.

Label-free and ultrasensitive electrochemical detection of nucleic acids based on an exonuclease III-assisted target recycling amplification strategy using a heated gold disk electrode.

The present work demonstrates a label-free, rapid and ultrasensitive electrochemical sensor for specific DNA detection with an exonuclease III (Exo III)-assisted target recycling amplification strategy and elevated electrode temperature at a heated gold disk electrode (HAuDE). The proposed electrochemical DNA (E-DNA) sensor was designed such that in the presence of the target DNA, the electrode self-assembled capture probe hybridizes with the target DNA to form a duplex structure, which triggers Exo III to specifically recognize this structure and selectively digest the capture probe, while the released target DNA underwent recycling to hybridize with a new capture probe, leading to the gradual digestion of a large amount of capture probes. It was found that during the digestion period, the activity of Exo III could be significantly improved by elevating electrode temperature, thus promoting the digestion reaction and improving the sensitivity for target DNA detection. Furthermore, an electrochemical indicator ([Ru(NH3)6]3+) was electrostatically bound to the capture probe, leading to a significant square wave voltammetry (SWV) response, which directly related to the amount and length of the capture probes remaining in the electrode and provided a quantitative measure for target DNA detection. The proposed strategy realized the highly sensitive detection of the target DNA with a detection limit of 26 aM (S/N = 3) at an electrode temperature of 40 °C during the digestion period, which was about two magnitudes lower than that at 24 °C.

Investigation of cold-resistance mechanisms in cryophylactic yeast Metschnikowia pulcherrima based on comparative transcriptome analysis.

Introduction: Low temperature inhibits the growth of most microorganisms. However, some microbes can grow well in a low temperature, even a freezing temperature. Methods: In this study, the mechanisms conferring cold resistance in the cryophylactic yeast Metschnikowia (M.) pulcherrima MS612, an isolate of the epidermis of ice grapes, were investigated based on comparative transcriptome analysis. Results: A total of 6018 genes and 374 differentially expressed genes (> 2-fold, p < 0.05) were identified using RNA-Seq. The differentially expressed genes were mainly involved in carbohydrate and energy metabolism, transport mechanisms, antifreeze protection, lipid synthesis, and signal transduction. M. pulcherrima MS612 maintained normal growth at low temperature (5°C) by enhancing energy metabolism, sterol synthesis, metal ion homeostasis, amino acid and MDR transport, while increased synthesis of glycerol and proline transport to improve its resistance to the freezing temperature (-5°C). Furthermore, cAMP-PKA and ERAD signaling pathways contribute to resist the low temperature and the freezing temperature, respectively. Conclusion: This study provides new insights into cold resistance in cryophylactic microorganisms for maneuvering various metabolism to resist different cold environment.

A novel multi-channel applicator with a U-shaped channel for vaginal intracavity brachytherapy.

BACKGROUND: Endometrial cancer is one of the most common gynecological malignancies in the world. Vaginal brachytherapy is an important postoperative adjuvant treatment for endometrial cancer. However, a common problem with existing applicators is insufficient dose at the vaginal apex. PURPOSE: This study describes the Hangzhou (HZ) cylinder, a novel 3D printed vaginal intracavity brachytherapy applicator, detailing its characteristics, dose distribution, and clinical applications. METHODS AND MATERIALS: The HZ cylinder is distinguished by its unique structure: a U-shaped channel with a 2 mm diameter, a straight central axis channel of the same diameter, and 10 parallel straight channels. For comparison, standard plans were employed, designed to ensure that a minimum of 95% of the prescribed dose reached 5 mm beneath the mucosal surface. We conducted comparative analyses of mucosal surface doses and doses at a 5 mm depth below the mucosa between the HZ cylinder and a conventional single-channel cylinder across various treatment schemes. Additionally, the study examined dose differences in target volume and organs at risk (OARs) between actual HZ cylinder plans and hypothetical single-channel plans. RESULTS: In the standard plans, mucosal surface doses at the apex of the vagina were 209.32% and 200.61% of the prescribed dose with the HZ and single-channel cylinders, respectively. The doses on the left and right wall mucosal surfaces varied from 149.26% to 178.13% and 142.98% to 180.75% of the prescribed dose, and on the anterior and posterior wall mucosal surfaces varied from 128.87% to 138.50% and 142.98% to 180.75% of the prescribed dose. Analysis of 24 actual treatment plans revealed that when the vaginal tissue volume dose covering 98% (vaginal D98%) was comparable between the HZ cylinder and virtual single-channel plans (6.74 ± 0.07 Gy vs. 6.69 ± 0.10 Gy, p = 0.24), rectum doses of HZ cylinder plans were significantly lower than those of single-channel plans (D1cc, 5.96 ± 0.56 Gy vs. 6.26 ± 0.71 Gy, p = 0.02 and D2cc, 5.26 ± 0.52 Gy vs. 5.56 ± 0.62 Gy, p = 0.02). CONCLUSIONS: The HZ cylinder demonstrates a reduction in dose to the rectum and bladder while maintaining adequate target volume coverage. Its mucosal surface dose is comparable to that of the traditional single-channel cylinder. These findings suggest that the HZ cylinder is a viable and potentially safer alternative for vaginal brachytherapy, warranting further investigation with larger sample sizes.

The Role of Frustrated Lewis Pair in Catalytic Transfer Hydrogenation of Furfural using Nickel Single-Atom Catalysts: A Theoretical Study.

The burgeoning field of frustrated Lewis pair (FLP) heterogeneous catalysts has garnered significant interest in recent years, primarily due to their inherent ability to activate H-source molecules, such as H2, thereby facilitating hydrogenation reactions. However, the application of single metal atom catalysts incorporating FLP sites has been relatively under-explored. In this study, non-precious transition metal atoms were anchored onto a C2N framework with an intrinsic cavity and a defective N-C sheet. Theoretical calculations substantiated energy barriers as low as 0.10 eV for isopropanol activation, thereby positioning these catalysts as highly promising candidates for catalytic transfer hydrogenation of furfural. Electronic structure analyses revealed that the H-O bond breakage in isopropanol molecules was significantly facilitated by the presence of FLP sites within the catalysts. Notably, both Ni-C2N and Ni-N6-C demonstrated exceptional potential as selective catalysts for the hydrogenation of furfural into furfuryl alcohol, exhibiting remarkably low barriers of only 0.65-0.72 eV for the rate-determining steps, which are notably lower than those observed in many traditional catalysts. Theoretical investigations strongly imply that the construction of single atom catalysts with FLP sites could significantly enhance the activity and selectivity for hydrogenation reactions, thus stimulating the experimental synthesis of such catalysts.

Ultrathin 2D-2D MXene-LDH Interlayer with High Polysulfide Adsorption Ability for Advanced Li-S Batteries.

Lithium-sulfur (Li-S) batteries are considered as promising energy storage systems due to the high energy density of 2600 W h kg-1. However, the practical application of Li-S batteries is hindered by the inadequate conductivity of sulfur and Li2S, as well as the shuttle effect caused by polysulfides during the charge-discharge process. Introducing a conductive interlayer between the cathode and the separator to physically resist polysulfides represents an effective and straightforward approach to mitigate the shuttle effect in Li-S batteries. In this paper, an ultrathin (<1 µm) 2D-2D MXene-LDH interlayer with high polysulfide adsorption ability was introduced to Li-S batteries. The synergistic effect between MXene and layered double hydroxide greatly improved the adsorption effect of the interlayers: the conductive Ti3C2Tx MXene chemically adsorbs polysulfides and promotes their fast transfer, and the NiCo-LDH alleviates the restack of MXene and facilitates Li+ diffusion. After inserting the MXene-LDH interlayer, the Li-S batteries exhibit an enhanced specific capacity of 1137.6 mA h g-1 at 0.1 C and retain 622.6 mA h g-1 after 100 cycles. The ultrathin 2D-2D interlayer offers a feasible way for the development of highly efficient and lightweight interlayers in Li-S batteries.

Stenotrophomonas maltophilia uses a c-di-GMP module to sense the mammalian body temperature during infection.

The body temperature of Warm-blooded hosts impedes and informs responses of bacteria accustomed to cooler environments. The second messenger c-di-GMP modulates bacterial behavior in response to diverse, yet largely undiscovered, stimuli. A long-standing debate persists regarding whether a local or a global c-di-GMP pool plays a critical role. Our research on a Stenotrophomonas maltophilia strain thriving at around 28°C, showcases BtsD as a thermosensor, diguanylate cyclase, and effector. It detects 37°C and diminishes c-di-GMP synthesis, resulting in a responsive sequence: the periplasmic c-di-GMP level is decreased, the N-terminal region of BtsD disengages from c-di-GMP, activates the two-component signal transduction system BtsKR, and amplifies sod1-3 transcription, thereby strengthening the bacterium's pathogenicity and adaptation during infections in 37°C warm Galleria mellonella larvae. This revelation of a single-protein c-di-GMP module introduces unrecognized dimensions to the functional and structural paradigms of c-di-GMP modules and reshapes our understanding of bacterial adaptation and pathogenicity in hosts with a body temperature around 37°C. Furthermore, the discovery of a periplasmic c-di-GMP pool governing BtsD-BtsK interactions supports the critical role of a local c-di-GMP pool.

Construction of ion/electron transfer multi-channels for the composite film electrode from GO and cellulose derived porous carbon in supercapacitor.

Due to excellent flexibility and dispersibility, 2D graphene oxide (GO) is regarded as one of the prospective materials for preparing self-supporting electrode material. Nevertheless, the self-stacking characteristic of GO significantly restricts the ion transmission and accessibility in GO-based electrodes, especially in the direction perpendicular to the electrode surface. Herein, a novel composite film was fabricated from GO and 3D porous carbon (PC) through vacuum filtration combined with thermal reduction strategy. The combination of GO and PC not only avoids the self-stacking of GO, but also exposes more active sites for ions in the inner. A massive released nitrogen and oxygen-containing gases during the thermal reduction endows the reduced graphene oxide (RGO) with abundant porous and CC, which contributes to the energy storage in the direction perpendicular to the electrode surface. Besides, the high specific surface area of the prepared composite film is favorable for the storage and release of charge on the electrode surface. Benefiting from the above characteristics, the electrode assembled by the as-prepared film exhibits ultrahigh areal/volumetric specific capacitance in supercapacitor and ZIHCs (Zinc ion hybrid capacitors). This work provides a promising approach for the development of advanced self-supported electrode materials with desirable electrochemical properties.

Effective Detection of Hoechst Side Population Cells by Flow Cytometry.

The side population (SP) cells are identified through Hoechst 33342 staining and analyzed using flow cytometry (FCM). The Hoechst SP method is utilized for the isolation of stem cells based on the dye efflux properties of ATP-binding cassette (ABC) transporters. The method was initially employed for the identification and isolation of hematopoietic stem cells (HSCs), but it has now evolved to primarily focus on the identification and isolation of cancer stem cells (CSCs). The traditional detection method of FCM uses a 355 nm laser to excite the dye to detect SP cells. Through this study, we have successfully identified alternative approaches for dye excitation that can effectively replace the detection of SP cells using a 355 nm laser. This is achieved through the utilization of high-power 375 nm or 405 nm lasers. This allows us to exercise enhanced selectivity in the detection of SP cells rather than being solely limited to the 355 nm laser flow cytometry.

Robust and predictive 3D-QSAR models for predicting the activities of novel oxadiazole derivatives as multifunctional anti-Alzheimer agents.

In recent years, Alzheimer disease (AD) as a neurodegenerative disorder has been increasing annually with the aging of the global population, therefore, development of novel anti-AD drugs is imperative. Studies have proven that glycogen synthase kinase-3ß (GSK-3ß) is a pivotal factor in the development of AD. Therefore, GSK-3ß inhibitors would provide powerful means to treat the disorders, such as AD. To in-depth study the structure-activity relationship of a series of oxadiazole derivatives as multifunctional anti-Alzheimer agents, computational three dimensional quantitative structure-activity relationship (3D-QSAR) studies, molecular docking and molecular dynamics were conducted. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were conducted to build up the 3D-QSAR models, and exhibited significant results (R cv 2 = 0.692, R pred 2 = 0.6885/CoMFA, R cv 2 = 0.696, R pred 2 = 0.6887/CoMSIA). The accuracy of the 3D-QSAR models was validated by external validation and applicability domain analysis. The derived contour maps provided structural information for designing novel compounds to improve the inhibitory activities. Additionally, molecular docking and molecular dynamics were also employed to investigate the bonding interactions and stability of this series of inhibitors in the active site of GSK-3ß, and the results revealed that the importance of residues Ile62, Asn64 Val70, Tyr128, Val129 and Leu182 for ligand binding to the receptor GSK-3ß. All the results would be of great help for the discovery of new GSK-3ß agents that can solve the problem of AD.

Impact of short-term proton pump inhibitors vs. histamine-2 receptor antagonists on gut microbiota in patients with acute coronary syndrome: A multicenter randomized trial.

BACKGROUND: Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs has been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients. METHODS: The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI (n = 40), H2RA (n = 31), or control group (n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S rRNA gene sequencing. RESULTS: There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group. CONCLUSIONS: PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs. REGISTRATION: www.chictr.org.cn/ (ChiCTR2000029552).

Effect of Sitting Baduanjin exercise on early rehabilitation of sepsis patients with non-invasive ventilation : a randomized controlled trial.

BACKGROUND: For patients with sepsis receiving non-invasive ventilation (NIV), early rehabilitation is crucial. The Sitting Baduanjin (SBE) is an efficient early rehabilitation exercise suitable for bed patients. There is no consensus about the effect of SBE on the early rehabilitation of septic patients with NIV. This study focused on how the SBE affected the early rehabilitation of sepsis patients with NIV. METHODS: 96 sepsis patients with NIV were randomly assigned to either an Baduanjin group that received the SBE based on the routine rehabilitation exercise (n = 48) or a control group (n = 48) that received routine rehabilitation exercise. The primary outcome was the Medical Research Council(MRC)score, and the Barthel Index score, the duration of NIV, length of ICU stay, length of total stay, hospitalization expense as secondary outcomes. RESULTS: A total of 245 sepsis patients were screened, with 96 randomly assigned. The study was completed by 90 patients out of the 96 participants.Results revealed that the MRC score increased in both groups, but the improvement of muscle strength in Baduanjin group was more obvious, with statistical significance (p < 0.001).There was statistically significantly difference between the two groups in Barthel Index at the day of transfer out of ICU(P = 0.028).The patients in the Baduanjin group had an average reduction of 24.09 h in the duration of NIV and 3.35 days in total length of hospital stay compared with the control group (p < 0.05).Of note, the Baduanjin group had significantly reduction the total hospitalization expense. No serious adverse events occurred during the intervention period. CONCLUSIONS: In patients with sepsis, the SBE appears to improve muscle strength and activities of daily living (ADL), and lowed the duration of NIV, the length of the total stay, and the hospitalization expense. TRIAL REGISTRATION: The study registered on the Chinese Clinical Trial Registry ( www.chictr.org.cn ), Clinical Trials identifier ChiCTR1800015011 (28/02/2018).

Clinical concentration of sevoflurane had no short-term effect on the myelin sheath in prefrontal cortex of aged marmosets.

Introduction: The fragile brain includes both the developing brain in childhood and the deteriorating brain in elderly. While the effects of general anesthesia on the myelin sheath of developing brain have been well-documented, limited research has explored its impact on degenerating brain in elderly individuals. Methods: In our study, aged marmosets in control group were only anesthetized with 6-8% sevoflurane and 100% oxygen (2 L/min) for 1-2 min for anesthesia induction. In addition to anesthesia induction, the anesthesia group was exposed to a clinical concentration of sevoflurane (1.5-2%) for 6 h to maintain anesthesia. After anesthesia, scanning electron microscopy (SEM) and artificial intelligence-assisted image analysis were utilized to observe the effects of general anesthesia on the myelin sheath in prefrontal cortex (PFC) of aged marmosets. Results: Compared with the control group, our findings revealed no evidence that 6 h of sevoflurane general anesthesia altered the thickness of myelin sheath, the diameter of myelinated axons, and the g-ratio in prefrontal cortex of aged marmosets. Conclusion: Clinical concentration of sevoflurane may have no short-term effect on the myelin sheath in prefrontal cortex of aged marmosets.

No QTc prolongation with CDK 4/6 inhibitor FCN-437c: results of a concentration-QTc analysis from a dedicated study in adult healthy subjects.

Cardiotoxicity and QT interval prolongation have been a common cause of withdrawal of drugs from the market. FCN-437c is an oral, second-generation, potent, and selective CDK4/6 inhibitor for the treatment of patients with HR+/HER2- metastatic breast cancer. A single-center, double-blind, randomized, and placebo-controlled clinical study in healthy subjects was conducted to investigate the QTc prolongation potential of FCN-437c utilizing Concentration-QTc (C-QTc) modeling approach. FCN-437c was administered at doses of 300, and 400 mg with single oral administration, along with placebo, in 18 healthy subjects. Electrocardiograms (ECGs) through 24 h holter monitor and blood samples were collected. The Cmax of 400 mg single dose in healthy subjects is similar to that from therapeutic dose 200 mg QD at steady state in patients with cancer. The 90% CI upper limit of ΔΔQTcF at the Cmax geometric mean in both dose groups were <10 ms. It is concluded that FCN-437c has low risk of prolonging the QT interval at therapeutic dose. Systematic Review Registration: https://clinicaltrials.gov/study/NCT06290466?term=NCT06290466&rank=1, identifier [NCT06290466].

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1ß pathway.

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.

Pipette-tip solid-phase extraction coupled with matrix-assisted laser desorption/ionization mass spectrometry enables rapid and high-throughput analysis of antidepressants in rat serum.

Therapeutic drug monitoring is essential for ensuring the efficacy and safety of medications. This study introduces a streamlined approach that combines pipette-tip solid-phase extraction (PT-SPE) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), facilitating rapid and high-throughput monitoring of drug concentrations. As a demonstration, this method was applied to the extraction and quantification of antidepressants in serum. Utilizing Zip-Tip C18, the method enabled the extraction of antidepressants from complex biological matrices in less than 2 min, with the subsequent MALDI-MS analysis yielding results in just 1 min. Optimal extraction recoveries were achieved using a sampling solution at pH 9.0 and a 10 µL ethanol desorption solution containing 0.1% phosphoric acid. For MALDI analysis, 2,5-dihydroxybenzoic acid was identified as the most effective matrix for producing the highest signal intensity. The quantification strategy exhibited robust linearities (R2 ≥ 0.997) and satisfactory limits of quantification, ranging from 0.05 to 0.5 µg/mL for a suite of antidepressants. The application for monitoring dynamic concentration changes of antidepressants in rat serum emphasized the method's efficacy. This strategy offers the advantages of high throughput, minimal sample usage, environmental sustainability, and simplicity, providing ideas and a reference basis for the subsequent development of methods for therapeutic drug monitoring.

Enhanced Lithium Storage Performance: Dual-Modified Electrospun Si@MnO@CNFs Composites for Advanced Anodes.

Due to its many benefits, including high specific capacity, low voltage plateau, and plentiful supplies, silicon-based anode materials are a strong contender to replace graphite anodes. However, silicon has drawbacks such as poor electrical conductivity, abrupt volume changes during the discharge process, and continuous growth of the solid electrolyte interfacial (SEI) film during cycling, which would cause the electrode capacity to degrade quickly. Coating the silicon's exterior with carbon or metal oxide is a popular method to resolve the above-mentioned problems. In light of those above, the liquid-phase approach and electrostatic spinning technique were used in this work to create Si@MnO@CNFs bilayer-coated silicon-based anode materials. Because of the well-thought-out design, MnO and C bilaterally coat the silicon nanoparticles, significantly reducing their volume effect during cycling. Furthermore, manganese oxide has outstanding electrochemical kinetics and an excellent theoretical capacity. The carbon nanofibers' outermost layer increases the material's conductivity and stabilizes the composite material's structure, reducing the volume effect. After 1100 cycles at 2 A g-1, the composite anode material prepared in this work can still maintain a high capacity of 994.4 mAh g-1. This study offers an unusual combination of silicon and MnO that might set the way for the application of silicon-based composites in lithium-ion batteries.

The Optimal Cut-off Value of Upper Arm Circumference and Calf Circumference for Assessing Sarcopenia Among Chinese Community-Dwelling Older Adults.

Objective: To explore the cut-off values and health evaluations of upper arm circumference (AC) and calf circumference (CC) on sarcopenia in Chinese community-dwelling older people. Methods: In this cross-sectional study, AC, CC, handgrip strength, muscle mass and gait speed were measured in 1537 Chinese community-dwelling older people in Sub-study 1. Correlation analysis, receiver operator characteristic curve (ROC curve) analysis, and consistency analysis were used for determination of AC and CC cut-off values for sarcopenia diagnosis (sarcopenia-AC and CC). Thereafter, 269 participants accepted additional assessments on physical function, body composition and muscle strength in Sub-study 2. T-test or Mann-Whitney U-test was used to explore the differential effects of sarcopenia-AC and CC on health indicators between sarcopenic and non-sarcopenic participants. Results: In Sub-study 1, the Area Under ROC (AUC) of AC and CC for sarcopenia screening were greater than 0.700 (P<0.05). The cut-off values, sensitivity and specificity of AC and CC on sarcopenia in males were 25.9 cm (86.0%, 83.6%) and 33.7 cm (90.7%, 81.4%) whereas in females were 26.5 cm (70.8%, 69.7%) and 33.0 cm (86.5%, 69.4%), respectively. In Sub-study 2, the participants with sarcopenia-AC or sarcopenia-CC showed lower muscle strength and lower fat and muscle mass than the ones without (P<0.05). Additionally, males instead of females with sarcopenia-AC or sarcopenia-CC showed worse performance in time-up and go test and 6-Minute Walk Test (P<0.05). However, the 30-second chair stand test was not different between participants with and without sarcopenia-AC or sarcopenia-CC in both sexes. Conclusion: We found accurate and Chinese population targeted cut-off values of AC and CC on sarcopenia diagnosis (25.9 cm and 33.7 cm in males; 26.5 cm and 33.0 cm in females) and a good evaluation effect of AC and CC on fat and muscle mass, muscle strength and physical functions in males, not females.

Single-cell sequencing reveals the correlation of aggrephagy signaling and multiple myeloma immune microenvironment composition.

Aggrephagy, a type of autophagy, degrades the aggregation of misfolded protein in cells. However, the role of aggrephagy in multiple myeloma (MM) has not been fully demonstrated. In this study, we first investigated the correlation between aggrephagy signaling, MM immune microenvironment composition and disease prognosis. Single-cell RNA-seq data, including the expression profiles of 12,187 single cells from seven MM bone marrow (BM) and seven healthy BM samples, were analyzed by non-negative matrix factorization for 44 aggrephagy-related genes. Bulk RNA-seq cohorts from the Gene Expression Omnibus database were used to evaluate the prognostic value of aggrephagy-related immune cell subtypes and predict immune checkpoint blockade immunotherapeutic response in MM. Compared with healthy BM, MM BM exhibited different patterns of aggrephagy-related gene expression. In MM BM, macrophages, CD8+ T cells, B cells and natural killer cells could be grouped into four to nine aggrephagy-related subclusters. The signature of aggrephagy signaling molecule expression in the immune cells correlates with the patient's prognosis. Our investigation provides a novel view of aggrephagy signaling in MM tumor microenvironment cells, which might be a prognostic indicator and potential target for MM treatment.

PARK2 suppresses the proliferation of high-grade serous ovarian carcinoma via inducing the proteasomal degradation of ZNF703.

High-grade serous ovarian cancer (HGSC) is an aggressive disease with poor prognosis. The oncoprotein ZNF703 is implicated in driving HGSC pathogenesis, but factors regulating its abundance remain unclear. In this study, we aim to investigate the potential connection between ZNF703 dysregulation and ubiquitin-mediated protein degradation in HGSC. Bioinformatics prediction was performed using BioGRID database. HGSC representative cell lines were utilized for in vitro and in vivo studies. Results showed that ZNF703 protein was stabilized upon proteasome inhibition, suggesting a regulation via ubiquitination. The ubiquitin E3 ligase PARK2 was found to interact with ZNF703 in a dose-dependent manner, promoting its polyubiquitination and subsequent proteasomal degradation. Re-expression of PARK2 in HGSC cells led to reduced ZNF703 levels together with decreased Cyclin D1/E1 abundance and G1 cell cycle arrest. ZNF703 overexpression alone increased S phase cells, Cyclin D1/E1 levels, and xenograft tumor growth, while co-expression with PARK2 mitigated these oncogenic effects. Collectively, our findings identify ZNF703 as a bona fide substrate of PARK2, reveal a tumor suppressive function for PARK2 in attenuating ZNF703-mediated G1/S transition and HGSC growth through instigating its degradation. This study elucidates a pivotal PARK2-ZNF703 axis with therapeutic implications for targeted intervention in HGSC.