Identification of autophagy-related genes ATG18 subfamily genes in potato (Solanum tuberosum L.) and the role of StATG18a gene in heat stress.

Autophagy is a highly conserved process in eukaryotes that is used to recycle the cellular components from the cytoplasm. It plays a crucial function in responding to both biotic and abiotic stress, as well as in the growth and development of plants. Autophagy-related genes (ATG) and their functions have been identified in numerous crop species. However, their specific tasks in potatoes (Solanum tuberosum L.), are still not well understood. This work is the first to identify and characterize the potato StATG18 subfamily gene at the whole-genome level, resulting in a total of 6 potential StATG18 subfamily genes. We analyzed the phylogenetic relationships, chromosome distribution and gene replication, conserved motifs and gene structure, interspecific collinearity relationship, and cis-regulatory elements of the ATG18 subfamily members using bioinformatics approaches. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) analysis suggested that StATG18 subfamily genes exhibit differential expression in various tissues and organs of potato plants. When exposed to heat stress, their expression pattern was observed in the root, stem, and leaf. Based on a higher expression profile, the StATG18a gene was further analyzed under heat stress in potatoes. The subcellular localization analysis of StATG18a revealed its presence in both the cytoplasm and nucleus. In addition, StATG18a altered the growth indicators, physiological characteristics, and photosynthesis of potato plants under heat stresses. In conclusion, this work offers a thorough assessment of StATG18 subfamily genes and provides essential recommendations for additional functional investigation of autophagy-associated genes in potato plants. Moreover, these results also contribute to our understanding of the potential mechanism and functional validation of the StATG18a gene's persistent tolerance to heat stress in potato plants.

Visceral Adiposity and Neutralizing Antibody Expression: An Adult-Based Cross-Sectional Study.

Purpose: Visceral adiposity is a significant risk factor for severe COVID-19. However, the impact of the Chinese visceral adiposity index (CVAI) on the efficacy of SARS-CoV-2 vaccines remains poorly understood. This study aims to explore the impact of CVAI on the production of neutralizing antibodies (NAb) in inactivated SARS-CoV-2 vaccines and the potential mechanism, thereby optimizing vaccination guidance. Methods: In this cross-sectional study, 206 health workers (completed two SARS-CoV-2 vaccination on February 8th and March 10th, 2021, respectively) were recruited. All baseline anthropometric parameters of the participants were collected, and venous blood samples were obtained 6 weeks later to measure peripheral innate immune cells, inflammatory cytokines, and NAb titers against SARS-CoV-2. CVAI were calculated according to the formula and divided participants into two groups depending on CVAI median. Results: The median NAb titer among healthcare workers was 12.94 AU/mL, with an efficacy of 87.86% for the SARS-CoV-2 vaccine. NAb titers were lower in the CVAI dysfunction group than in the CVAI reference group (median: 11.40 AU/mL vs 15.57 AU/mL), the hsCRP levels (median: 0.50 mg/L vs 0.30 mg/L) and peripheral monocyte count (mean: 0.47 × 109/L vs 0.42 × 109/L) in the CVAI dysfunction group were higher than in the CVAI reference group. Additionally, CVAI showed positive correlations with hsCRP, monocytes, lymphocytes, and B-lymphocytes, and a negative correlation with NAb titers. Conclusion: CVAI may inhibit SARS-CoV-2 neutralizing antibody expression through inducing immune dysfunction and chronic inflammation. Thus, more attention should be paid to the vaccination for high CVAI population to improve the effectiveness of vaccination, which could provide more robust support for COVID-19 epidemic prevention and control.

Application of Odd-Order Derivatives in Fourier Transform Nuclear Magnetic Resonance Spectroscopy toward Quantitative Deconvolution.

When Fourier transform (FT) spectrum peaks are overlapped, primary maxima of odd-order derivatives can be used to evaluate their independent intensities. We studied the feasibility of higher odd-order derivatives on Lorentzian peak shape and magnitude peak shape. Simulation studies for FT nuclear magnetic resonance (NMR) spectroscopy demonstrated good results toward quantitative deconvolution of overlapping FT spectrum peaks. Although it is not so desirable to deconvolute special line shapes such as Gaussian, Voigt, and Tsallis profiles, the odd-order derivatives exhibit a bright future compared to even-order derivatives. An application example of practical NMR spectroscopy with ethylbenzene isomers is presented. White Gaussian noises were added to the simulated spectra at two different signal-to-noise ratios (20 and 40). Kauppinen's denoising and smoothing algorithms can effectively remove interference of the noise and help to have good deconvoluting results using the odd-order derivatives. We compared features of our approach with popular deconvolution sharpening algorithms and conducted a comparison study with Kauppinen's Fourier self-deconvolution. Our approach has a better dynamic range of peak intensities and is not sensitive to the sampling rates. Other common deconvolution methods are also discussed briefly.

From hate to harmony: Leveraging large language models for safer speech in times of COVID-19 crisis.

This study investigates the rampant spread of offensive and derogatory language during the COVID-19 pandemic and aims to mitigate it through machine learning. Employing advanced Large Language Models (LLMs), the research develops a sophisticated framework adept at detecting and transforming abusive and hateful speech. The project begins by meticulously compiling a dataset, focusing specifically on Chinese language abuse and hate speech. It incorporates an extensive list of 30 pandemic-related terms, significantly enriching the resources available for this type of research. A two-tier detection model is then introduced, achieving a remarkable accuracy of 94.42 % in its first phase and an impressive 81.48 % in the second. Furthermore, the study enhances paraphrasing efficiency by integrating generative AI techniques, primarily Large Language Models, with a Latent Dirichlet Allocation (LDA) topic model. This combination allows for a thorough analysis of language before and after modification. The results highlight the transformative power of these methods. They show that the rephrased statements not only reduce the initial hostility but also preserve the essential themes and meanings. This breakthrough offers users effective rephrasing suggestions to prevent the spread of hate speech, contributing to more positive and constructive public discourse.

A functional variant rs912304 for late-onset T1D risk contributes to islet dysfunction by regulating proinflammatory cytokine-responsive gene STXBP6 expression.

BACKGROUND: Our previous genome­wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated. METHODS: We assessed the association between variant rs912304 and T1D, as well as islet autoimmunity and islet function, stratified by the diagnosed age of 12. We used epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to prioritize the most likely functional variant and potential causal gene. We also performed functional experiments to evaluate the role of the causal gene on islet function and its related mechanisms. RESULTS: We identified rs912304 as a risk variant for T1D subgroups with diagnosed age ≥ 12 but not < 12. This variant is associated with residual islet function but not islet-specific autoantibody positivity in T1D individuals. Bioinformatics analysis indicated that rs912304 is a functional variant exhibiting spatial overlaps with enhancer active histone marks (H3K27ac and H3K4me1) and open chromatin status (ATAC-seq) in the human pancreas and islet tissues. Luciferase reporter gene assays and eQTL analyses demonstrated that the biallelic sites of rs912304 had differential allele-specific enhancer activity in beta cell lines and regulated STXBP6 expression, which was defined as the most putative causal gene based on Open Targets Genetics, GTEx v8 and Tiger database. Moreover, Stxbp6 was upregulated by T1D-related proinflammatory cytokines but not high glucose/fat. Notably, Stxbp6 over-expressed INS-1E cells exhibited decreasing insulin secretion and increasing cell apoptosis through Glut1 and Gadd45ß, respectively. CONCLUSIONS: This study expanded the genomic landscape regarding late-onset T1D risk and supported islet function mechanistically connected to T1D pathogenesis.

Association between pre-stroke frailty status and stroke risk and impact on outcomes: a systematic review and meta-analysis of 1,660,328 participants.

The prevalence of frailty is increasing, and it is associated with increased risk of diseases and adverse outcomes. Although substantial research has focused on post-stroke frailty, understanding of pre-stroke frailty remains limited. Our aim was to synthesize literature on pre-stroke frailty and stroke risk to explore their relationship and impact on prognosis. A systematic search of multiple databases was conducted to identify cohort studies published until October 28, 2023. Meta-analysis was conducted using a random effects model. Heterogeneity was assessed with the I² statistic, and publication bias was evaluated using Begg's test. Finally, we included 11 studies (n = 1,660,328 participants). The pooled hazard ratios (HRs) for stroke risk associated with pre-stroke frailty compared to non-frail individuals was 1.72 (95% confidence interval, CI: 1.46-2.02, p = 0.002, I2 = 69.2%, Begg's test: p = 0.536). The pooled HRs for mortality and the pooled relative risk (RRs) modified Rankin Scale (mRs) associated with pre-stroke frailty were 1.68 (95% CI: 1.10-2.56, p = 0.136, I2 = 49.9%, Begg's test: p = 0.296) and 3.11 (95% CI: 1.77-5.46, p = 0.192, I2 = 39.4%, Begg's test: p = 1.000), respectively. In conclusion, pre-stroke frailty is strongly associated with stroke risk and impacts its prognosis, irrespective of the measurement method. Future research should focus on prospective studies to assess the effects of early intervention for frailty. This has significant implications for primary healthcare services and frailty management.

Strong coupling of an epsilon-near-zero mode to a chiral plasmon.

The reconfigurable chiroptical effect is highly desirable for spin photonics, chiral spectroscopy, and photocatalysis due to its merits for dynamic and broadband applications. The coupling of an epsilon-near-zero (ENZ) mode to a chiral plasmon is expected to enable active and effective manipulation of the chiroptical effect but remains unexplored. Here we, for the first time to our knowledge, propose and demonstrate the strong coupling of an ENZ mode to a chiral plasmon by using a hybrid system composed of two identical vertically placed gold nanorods and an in-between ENZ film. An analytical three-oscillator model combined with numerical simulations is established to study the coupling mechanism, which predicts a Rabi splitting up to 240 meV with an ENZ film thickness of 60 nm in circular dichroism.

Cascaded partitioned phase modulation for cross-connection of orbital angular momentum mode and polarization multiplexing channels.

Multi-dimensional orbital angular momentum (OAM) mode multiplexing provides a promising route for enlarging communication capacity and establishing comprehensive networks. While multi-dimensional multiplexing has gained advancements, the cross-connection of these multiplexed channels, especially involving modes and polarizations, remains challenging due to the needs for multi-mode interconversion and on-demand polarization control. Herein, we propose an OAM mode-polarization cross-transformation solution via cascaded partitioned phase modulation, which enables the divergently separated OAM modes to be independently phase-imposed within distinct spatial regions, leading to the synergistic conversion operation of mode and polarization channels. In demonstrations, we implemented the cross-connection of three OAM modes and two polarization multiplexed channels, achieving the mode purity that exceeds 0.951 and polarization contrast up to 0.947. The measured mode insertion losses and polarization conversion losses are below 3.42 and 3.54 dB, respectively. Consequently, 1.2 Tbit/s quadrature phase shift keying signals were successfully exchanged, yielding the bit-error-rates close to 10-6. Incorporating with increased partitioned phase treatments, this approach shows promise in accommodating massive mode-polarization multiplexed channels, which hold the potential to augment networking capability of large-scale OAM mode multiplexing communication networks.

Muscle Mass Adjusted by Body Height is not Correlated with Mobility of Middle-Aged and Older Adults.

Background: Low muscle mass and obesity are associated with mobility disability, cardiometabolic diseases, and loss of independence. Three skeletal muscle indices (SMIs) are proposed to adjust the body size of individuals. However, it is unknown which index is better correlated with mobility. Additionally, it remains unclear whether low muscle mass or abdominal obesity has a greater impact on the mobility and cardiometabolic health of older adults. Objectives: This study explored the association between different SMIs {appendicular skeletal muscle mass [ASM] adjusted by body height [Ht], body weight [Wt], or body mass index [BMI (kg/m2)]} and mobility/cardiometabolic health. The roles of low muscle mass and abdominal obesity in the mobility and cardiometabolic health of individuals were also identified. Methods: Four-hundred and twenty-seven community-dwelling middle-aged and older adults underwent body composition assessments [dual-energy x-ray absorptiometry and waist circumference (WC)], grip strength, and mobility (timed up-and-go test and chair stand test). Spearman's rank correlation coefficient and regression models were used to examine research questions. This study was registered in the Thai Clinical Trials Registry (registration number: TCTR20210521007). Results: All SMIs were positively correlated with the grip strength (ASM/Ht2: r = 0.392; ASM/Wt: r = 0.439; ASM/BMI: r = 0.569). Regarding mobility, only ASM/Ht2 wasn't relevant. After adjusting for age, sex, and WC, ASM/BMI was the only SMI associated with grip strength (ß = 0.274). When age and sex were controlled, WC, but not SMI, was associated with mobility and cardiometabolic health. Conclusions: ASM/Ht2 did not correlate with mobility in middle-aged and older adults, whereas ASM/Wt and ASM/BMI did. Abdominal obesity has a greater impact on mobility and cardiometabolic health than low muscle mass in middle-aged and older adults. We recommend using ASM/BMI to identify the low muscle mass of individuals. In addition, clinicians should note the important role of abdominal obesity when considering mobility in middle-aged and older adults.

Flavopereirine exerts anti-cancer activities in various human thyroid cancer cells.

Thyroid cancer (TC) stands out as the most prevalent endocrine malignancy globally, with a steadily increasing incidence. Its clinical manifestations include enlarged thyroid nodules, dysphagia, enophthalmos, and various other symptoms. While standard treatments such as thyroidectomy and radioiodine therapy effectively manage most cases of differentiated thyroid cancers (DTC), some recurrent cases of DTC or those involving poorly differentiated thyroid cancers (PDTC) require specialized interventions. However, existing drugs primarily address symptom management without offering a curative solution. Therefore, the development of a new therapeutic agent for these challenging cases is of utmost importance. Flavopereirine, derived from Geissospermum vellosii, has demonstrated promise as a potential anti-cancer agent across various human cancers. However, its specific anti-cancer effects on human thyroid cancer (TC) have remained unclear. Therefore, this study aims to investigate the anti-cancer activity of flavopereirine in human TC. The research findings revealed that flavopereirine effectively hinders the growth of human TC cells, induces cell cycle arrest, promotes apoptosis, and modulates autophagy. Moreover, the study delved into the underlying mechanisms by which flavopereirine influenced signaling pathways. To validate these anti-cancer effects, an in vivo zebrafish model was utilized, confirming the efficacy of flavopereirine against human TC cells. In summary, this study establishes that flavopereirine exhibits notable anti-human TC activities, positioning it as a promising therapeutic candidate for the treatment of human thyroid cancer.

Autologous peripheral blood stem cell harvest timing by absolute neutrophil count in children and young adult patients: Single-institute experience.

BACKGROUND: Myeloablative, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) improves outcome in some high-risk malignant solid tumors and lymphomas in children and young adults. METHODS: We performed 16 peripheral blood stem cell (PBSC) harvests in 12 children and 2 young adult patients with a high-risk malignant solid tumor or refractory/relapsed Hodgkin's lymphoma from August 2015 to December 2020. In our chemotherapy mobilization protocol, we used an absolute neutrophil count (ANC) of >1 × 109/L following the nadir after chemotherapy as the criterion for undertaking the apheresis. RESULTS: The median CD34+ cell count per kg body weight of the 33 apheresis products was 4.92 × 106 cells/kg (range, 0.34-22.53 × 106 cells/kg). Thirteen of the 14 patients (93%) had successful PBSC collections that met their goals for PBSCT. Three patients did not receive PBSCT due to disease progression prior to transplantation. Prompt engraftment occurred in all the remaining 11 patients with 17 PBSCTs. CONCLUSION: Our data suggest that ANC can be helpful as a surrogate parameter in clinical decision-making when the peripheral blood CD34+ count is unavailable.

[Determination of 13 perfluorinated and polyfluoroalkyl substances in fishes by QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry].

Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 µg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 µg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 µg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.

Spontaneous Photonic Jammed Packing of Core-Shell Colloids in Conductive Aqueous Inks for Non-Iridescent Structural Coloration.

Integrating structural colors and conductivity into aqueous inks has the potential to revolutionize wearable electronics, providing flexibility, sustainability, and artistic appeal to electronic components. This study aims to introduce bioinspired color engineering to conductive aqueous inks. Our self-assembly approach involves mixing poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with sulfonic acid-modified polystyrene (sPS) colloids to generate non-iridescent structural colors in the inks. This spontaneous structural coloration occurs because PEDOT:PSS and sPS colloids can self-assemble into core-shell structures and reversibly cluster into photonic aggregates of maximally random jammed packing within the aqueous environment, as demonstrated by small-angle X-ray scattering. Dissipative particle dynamics simulation confirms that the self-assembly aggregation of PEDOT:PSS chains and sPS colloids can be manipulated by the polymer-colloid interactions. Utilizing the finite-difference time-domain method, we demonstrate that the photonic aggregates of the core-shell colloids achieve close to maximum jammed packing, making them suitable for producing vivid structural colors. These versatile conductive inks offer adjustable color saturation and conductivity, with conductivity levels reaching 36 S cm-1 through the addition of polyethylene glycol oligomer, while enhanced water resistance and mechanical stability are achieved by doping with a cross-linker, poly(ethylene glycol) diglycidyl ether. With these unique features, the inks can create flexible, patterned circuits through processes like coating, writing, and dyeing on large areas, providing eco-friendly, visually appealing colors for customizable, stylish, comfortable, and wearable electronic devices.

Forecasting hospital discharges for respiratory conditions in Costa Rica using climate and pollution data.

Respiratory diseases represent one of the most significant economic burdens on healthcare systems worldwide. The variation in the increasing number of cases depends greatly on climatic seasonal effects, socioeconomic factors, and pollution. Therefore, understanding these variations and obtaining precise forecasts allows health authorities to make correct decisions regarding the allocation of limited economic and human resources. We aimed to model and forecast weekly hospitalizations due to respiratory conditions in seven regional hospitals in Costa Rica using four statistical learning techniques (Random Forest, XGboost, Facebook's Prophet forecasting model, and an ensemble method combining the above methods), along with 22 climate change indices and aerosol optical depth as an indicator of pollution. Models were trained using data from 2000 to 2018 and were evaluated using data from 2019 as testing data. During the training period, we set up 2-year sliding windows and a 1-year assessment period, along with the grid search method to optimize hyperparameters for each model. The best model for each region was selected using testing data, based on predictive precision and to prevent overfitting. Prediction intervals were then computed using conformal inference. The relative importance of all climatic variables was computed for the best model, and similar patterns in some of the seven regions were observed based on the selected model. Finally, reliable predictions were obtained for each of the seven regional hospitals.

Allopurinol is Associated with an Increased Risk of Cerebral Infarction: A Two-Sample Mendelian Randomization Study.

OBJECTIVE: Previous studies have reported that the inappropriate use of allopurinol may increase the risk of cerebrovascular accidents, but some studies have also confirmed that allopurinol is a protective factor against stroke. To clarify whether there is a relevant causal relationship between allopurinol and cerebral infarction, we conducted a two-sample Mendelian randomization (MR) study. METHODS: Data on single nucleotide polymorphisms (SNPs) associated with allopurinol and genome-wide association studies of cerebral infarction were obtained from the genome-wide association study (GWAS) web site. Five basic MR analyses were performed using MR-Egger regression, weighted median (WM1), inverse variance weighting (IVW), weighted mode (WM2), and simple mode. Sensitivity analysis was subsequently performed to detect horizontal pleiotropy, heterogeneity, and potential outliers. The final analysis results were mainly based on the IVW estimates. RESULTS: A total of 10 SNPs were used as instrumental variables (IVs). MR analysis [(IVW: odds ratio (OR) = 1.053, 95% confidence interval (CI): 1.019-1.088, P = 0.002), (WM1: OR = 1.053, 95% CI: 1.009-1.098, P = 0.017), (WM2: OR = 1.050, 95% CI: 1.008-1.095, P = 0.044), (MR Egger: Q = 4.285, P = 0.830)] showed a positive causal association between allopurinol and the risk of cerebral infarction. Sensitivity analysis such as horizontal pleiotropy and heterogeneity increased the reliability of this result. CONCLUSION: The results of this study provide direct evidence that there is a causal relationship between allopurinol and cerebral infarction and that allopurinol may increase the risk of cerebral infarction.

Life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study.

BACKGROUND: Previous studies have demonstrated the benefits of ideal cardiovascular health (CVH) in reducing cardiovascular risk. However, its role in subclinical atherosclerosis (SA) progression remains unclear. We aim to examine the association of CVH, estimated by the American Heart Association's new Life's Essential 8 (LE8), with the progression of SA. METHODS: This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for 5.7 years. The LE8 score (range, 0-100) consisted of blood pressure, lipids, glucose, body mass index, smoking status, diet health, physical activity and sleep health was evaluated in 1998 and 2008-2009. Progression of SA was determined by carotid plaque and coronary artery calcification (CAC) in 2008-2009 and 2013-2014. Log-binomial regression model was used to estimate the association of LE8 score with SA progression. RESULTS: Each 10 points increment in LE8 score was associated with 15.2% (RR: 0.848, 95% CI: 0.797-0.902), 17.7% (RR: 0.823, 95% CI: 0.766-0.884) and 12.0% (RR: 0.880, 95% CI: 0.845-0.916) lower risks of carotid plaque, CAC and overall SA progression, respectively. Compared with participants with non-ideal CVH at both visits, the participants with ideal CVH at both visits had 39.1% (RR: 0.609, 95% CI: 0.494-0.752), 41.0% (RR: 0.590, 95% CI: 0.456-0.764) and 29.7% (RR: 0.703, 95% CI: 0.598-0.825) lower risks of carotid plaque, CAC and overall SA progression, respectively. CONCLUSIONS: Higher LE8 scores were associated with lower risks of SA progression. Besides, long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

Screening Privileged Alkyl Guanidinium Motifs under Host-Mimicking Conditions Reveals a Novel Antibiotic with an Unconventional Mode of Action.

Screening large molecule libraries against pathogenic bacteria is often challenged by a low hit rate due to limited uptake, underrepresentation of antibiotic structural motifs, and assays that do not resemble the infection conditions. To address these limitations, we present a screen of a focused library of alkyl guanidinium compounds, a structural motif associated with antibiotic activity and enhanced uptake, under host-mimicking infection conditions against a panel of disease-associated bacteria. Several hit molecules were identified with activities against Gram-positive and Gram-negative bacteria, highlighting the fidelity of the general concept. We selected one compound (L15) for in-depth mode of action studies that exhibited bactericidal activity against methicillin-resistant Staphylococcus aureus USA300 with a minimum inhibitory concentration of 1.5 µM. Structure-activity relationship studies confirmed the necessity of the guanidinium motif for antibiotic activity. The mode of action was investigated using affinity-based protein profiling with an L15 probe and identified the signal peptidase IB (SpsB) as the most promising hit. Validation by activity assays, binding site identification, docking, and molecular dynamics simulations demonstrated SpsB activation by L15, a recently described mechanism leading to the dysregulation of protein secretion and cell death. Overall, this study highlights the need for unconventional screening strategies to identify novel antibiotics.

Pediatric massage therapy in infants and children under 5 years: An umbrella review of systematic reviews.

Objective: To systematically evaluate and synthesize quantitative evidence regarding the effects of pediatric massage in infants and children under five years. Review methods: We conducted searches in databases including MEDLINE, Embase, Health Technology Assessment Database, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Allied and Complementary Medicine, Embase, the China National Knowledge Infrastructure, Wanfang Data, SinoMed, and CQVIP up to February 2024. Two reviewers independently screened articles, extracted data, and conducted quality appraisals on the included studies. We focused on systematic reviews with meta-analyses comparing pediatric tuina with a waitlist control, placebo, medication, massage combined with other interventions, and usual care. Outcomes analyzed included physical, psychological, developmental, and safety-related measures for children and their caregivers. Methodological quality was assessed using AMSTAR 2, and evidence quality was evaluated using the GRADE approach. Pooled effect estimates and heterogeneity were extracted for each meta-analyzed outcome. Evidence evaluated as 'high' and 'moderate' quality by GRADEpro with low heterogeneity are presented in the result section. Results: Twenty-two systematic reviews with meta-analysis of 81 outcomes were included. Seven studies (31.8 %) were high quality, and the evidence of 6 (7.4 %) outcomes were evaluated as high quality. The meta-analysis results demonstrate significant benefits of pediatric massage for infants compared to routine care, with increased weight gain (MD 455.07 g; 95 % CI 86.33 to 823.8; I2 = 0 %) based on 2 studies with 157 cases, length growth (MD 1.58 cm; 95 % CI 1.42 to 1.74; I2 = 25 %) from 9 studies with 1294 cases, reduced fussing (MD -0.37 time; 95 % CI -0.53 to -0.21; I2 = 30 %) according to 3 studies with 271 cases, and lower post-intervention bilirubin levels (3 studies/345 cases; MD -31.75 mmol/L; 95 % CI -40.05 to -23.46; I2 = 0 %). Pediatric massage was associated with reduced diarrhea incidence compared to waitlist controls (2 RCTs/310 cases; RR 0.39; 95 % CI 0.2 to 0.76; I2 = 0 %) and improved psychomotor development indices (4 RCTs/466 cases; SMD -0.35; 95 % CI -0.54 to -0.15; I2 = 1.06 %). Additionally, pediatric massage significantly enhanced blood oxygen saturation variation post-procedure for pain management (5 RCTs/355 cases; MD 1.05; 95 % CI 0.51 to 1.58; I2 = 0 %). Conclusions: Pediatric massage significantly enhances mother-child attachment, promotes physical growth, reduces fussing, lowers bilirubin levels, improves motor and psychomotor development, as well as manages digestive conditions and pain in children under 5 years. Future research should improve study quality and comprehensively report adverse events.

Thoracoscopic resection of a giant esophageal schwannoma: A case report and review of literature.

INTRODUCTION: Benign esophageal tumors are uncommon, accounting for approximately 2% of esophageal tumors. Esophageal schwannoma is a much rarer solid tumor with few cases reported in the literature. Open surgery is the surgical approach of choice for the treatment of esophageal tumors. With the advent of thoracoscopy, more and more countries are adopting a thoracoscopic approach to treat esophageal tumors, but there is still no clear surgical standard or modality for the treatment of esophageal tumors. PATIENT CONCERNS: A 50-year-old woman was admitted to our hospital. Over the past 2 months, her clinical presentation has included progressively worse swallowing disorder and weight loss. Gastroscopy showed an elevated lesion with a smooth surface visible 18 cm out from the incisors. An electron circumferential ultrasound endoscopy showed a hemispherical bulge with a smooth surface 18 to 23 cm from the incisor; the bulge originated from the intrinsic muscular layer and showed a heterogeneous mixed moderate ultrasound with a little blood flow signal and blue-green elastography in 1 of the sections measuring approximately 4 cm × 3 cm. Chest computed tomography (CT) showed a mass-like soft tissue shadow in the upper esophagus measuring approximately 39 mm × 34 mm, with a CT The lumen was compressed and narrowed, and the lumen of the upper part of the lesion was dilated, and the adjacent trachea was compressed and displaced to the right. INTERVENTIONS: After completion of the examination, assisted by artificial pneumothorax and thoracoscopic resection of esophageal masses were performed. DIAGNOSIS AND OUTCOMES: Postoperative pathology report: Mesenchymal-derived tumor (esophagus), combined with immunohistochemical staining results and morphologic features supported schwannoma. The patient's postoperative course was calm. The patient's postoperative dysphagia subsided. CONCLUSION: We describe a case of successful treatment of a schwannoma of the upper esophagus using artificial pneumothorax-assisted VATS. The combined use of Sox10 and S100 helps to improve the sensitivity and specificity of schwannoma diagnosis. Damage to the esophageal lining was avoided by mixed thoracoscopic and endoscopic exploration. This approach can also be applied to benign esophageal tumors in the thoracic and subthoracic segments, leading to better minimally invasive results.