Genome-wide association study of image-based trait reveals the genetic architecture of dark-induced leaf senescence in rice.

Darkness is often used as an effective measure to induce leaf senescence. Although many senescence-related genes in rice have been reported, the genome-wide genetic architecture underlying leaf senescence remains poorly understood. In our study, indica and japonica rice showed contrasting responses to dark-induced leaf senescence (DILS). Genome-wide association studies (GWAS) combined with transcriptomic analyses revealed 57, 97, and 48 loci involved in the regulation of the onset, progression, and ending of DILS, respectively. Haplotype analyses showed that the senescence-related loci differentially accumulated in indica and japonica accessions and functioned additively to regulate DILS. A total of 357 candidate genes were identified that are involved in various senescence-related processes such as lipid and amino acid catabolism, photosynthesis, response to reactive oxygen species, and regulation of defense response. In addition, functional analyses of the two candidate genes, OsMYB21 and OsSUB1B, revealed that OsMYB21 positively regulates the onset of DILS, while OsSUB1B negatively regulates its progression. Thus, our results provide new insights into the genetic regulation of DILS in rice.

Dietary apigenin ameliorates obesity-related hypertension through TRPV4-dependent vasorelaxation and TRPV4-independent adiponectin secretion.

BACKGROUND: Obesity-related hypertension is a major cardiovascular risk factor. Apigenin, a natural flavonoid in celery, induces vascular dilation via endothelial transient receptor potential channel vanilla 4 (TRPV4) channels. This study aimed to explore apigenin's potential to alleviate obesity-related hypertension in mice and its underlying mechanisms. METHODS: The C57BL/6 and TRPV4 knockout mice were fed a high-fat diet and subjected to dietary intervention with apigenin. Body weight and tail blood pressure of the mice were measured during the feeding. Vascular reactivity was assessed through a DMT wire myograph systems in vitro. The distribution and expression of adiponectin and pro-inflammatory markers in brown fat were detected. Injecting adeno-associated eight (AAV8) viruses into brown adipose tissue (BAT) to determine whether adiponectin is indispensable for the therapeutic effect of apigenin. Palmitic acid (PA) was used in mouse brown adipocytes to examine the detailed mechanisms regulating adiponectin secretion. RESULTS: Apigenin improved vasodilation and reduced blood pressure in obese mice, effects partly blocked in TRPV4 knockout. It also reduced weight gain independently of TRPV4. Apigenin increased adiponectin secretion from BAT; knockdown of adiponectin weakened its benefits. Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing adiponectin expression. CONCLUSIONS: Our study indicates that dietary apigenin is suitable as a nonpharmaceutical intervention for obesity-related hypertension. In mechanism, in addition to improving vascular relaxation through the activation of endothelial TRPV4 channels, apigenin also directly alleviated adipose inflammation and increased adiponectin levels by inhibiting CD38.

Triphenodioxazine Diimides: Design, Synthesis, and Properties.

To increase solubility and decrease the lowest unoccupied molecular orbital (LUMO) energy levels of triphenodioxazine (TPDO), a novel series of imide-fused TPDO derivatives (TPDODIs) were designed, synthesized, and investigated. The introduction of alkyl diimide groups endows TPDODIs with high solubility and LUMO energy levels below -3.90 eV. TPDODIs also show strong absorption in the visible region with high maximum molar extinction coefficients and high fluorescence quantum yields (0.67 and 0.71, respectively). Moreover, TPDODIs display thermotropic liquid-crystalline behavior as indicated by spindly nematic or dendritic textures. Their high solubility and low LUMO levels suggest these materials are well-suited for solution-processable n-type electronic devices.

Revisiting the activity origin of the PtAu24(SR)18 nanocluster for enhanced electrocatalytic hydrogen evolution by combining first-principles simulations with the experimental in situ FTIR technique.

Thiolate-protected metal nanoclusters (NCs) have been widely used in various electrocatalytic reactions, yet the dynamic evolution of metal NCs during electrocatalysis has been rarely explored and the activity origin remains largely ambiguous. Herein, using a PtAu24(SCH3)18 NC as a prototype model, we combined advanced first-principles calculations and attenuated total reflection surface-enhanced infrared spectroscopy (ATR-SEIRAS) to re-examine its active site and reaction dynamics in the hydrogen evolution reaction (HER). It has been previously assumed that the central Pt is the only catalytic center. However, differently, we observed the spontaneous desorption of thiolate ligands under moderate potential, and the dethiolated PtAu24 exhibits excellent HER activity, which is contributed not only by the central Pt atom but also by the exposed bridged Au sites. Particularly, the exposed Au exhibits high activity even comparable to Pt, and the synergistic effect between them makes dethiolated PtAu24 an extraordinary HER electrocatalyst, even surpassing the commercial Pt/C catalyst. Our predictions are further verified by electrochemical activation experiments and in situ FTIR (ATR-SEIRAS) characterization, where evident adsorption of Au-H* and Pt-H* bonds is monitored. This work detected, for the first time, the Au-S interfacial dynamics of the PtAu24 nanocluster in electrocatalytic processes, and quantitatively evaluated the essential catalytic role of the exposed Au sites that has been largely overlooked in previous studies.

Photodynamic Therapy Using RGD-Functionalized Quantum Dots Elicit a Potent Immune Response in a Syngeneic Mouse Model of Pancreatic Cancer.

Purpose: Photodynamic therapy (PDT) induces anti-tumor immune responses by triggering immunogenic cell death in tumor cells. Previously, we demonstrated that novel QDs-RGD nanoparticles exhibited high efficiency as photosensitizers in the treatment of pancreatic cancer. However, the underlying mechanism of the anti-tumor immune effects induced by the photosensitizer remains unknown. This study assessed the anticancer immune effect of QDs-RGD, as well as the conventional photosensitizer chlorine derivative, YLG-1, for comparison, against pancreatic cancer in support of superior therapeutic efficacy. Methods: The pancreatic cancer cell line, Panc02, was used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies to assess the anti-tumor effects of QDs-RGD-PDT and YLG-1-PDT. The immunostimulatory ability of both photosensitizers was examined by measuring the expression of damage-associated molecular patterns (DAMP), such as calreticulin (CRT), assessing dendritic cell (DC) maturation, and analyzing cytokine expression. The specific immunity of QDs-RGD and YLG-1-PDT on distant tumor were determined by combining PDT with anti-CTLA-4 antibody. Results: QDs-RGD-PDT and YLG-1-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. While both photosensitizers significantly promoted CRT release, DC maturation, and interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) expression, QDs-RGD exerted a stronger immunostimulatory effect than YLG-1. Combination treatment with QDs-RGD and CTLA-4 blockade was able to significantly inhibit the growth of distant tumors. Conclusion: QDs-RGD is a novel and effective PDT strategy for treating pancreatic tumors by inducing anti-tumor immune responses.

Alterations in liver triglyceride profiles in CCl4-induced liver regeneration.

Lipid metabolism, particularly triglyceride (TG) metabolism, is crucial for liver regeneration. During the early phase of liver regeneration, the liver temporarily accumulates a substantial amount of TG-dominated lipids. However, the specific composition of the TG profile during this phase is not yet fully understood. Here, we showed that the TG molecular composition in the liver was significantly altered during liver regeneration following carbon tetrachloride (CCl4)-induced liver injury. Lipid accumulation in livers was observed as early as 12 hours after CCl4 treatment, with transient regeneration-associated steatosis (TRAS) lasting until 24 hours. Hepatocyte proliferation began only after liver lipid levels returned to baseline at 48 hours. Furthermore, the profile of TG species changed significantly during liver regeneration. During the TRAS period, the accumulated TGs in the liver were mainly long-chain triglycerides, with most of the fatty acids constituting these triglycerides having fewer than 20 carbon atoms. In the proliferation phase, the fatty acid composition of these triglycerides shifted from long-chain to ultra-long-chain fatty acids. Our results suggest a significant TRAS-related change in the TG lipid profile of the liver during liver regeneration.

Optimized terahertz generation in BNA organic crystals with chirped Ti:sapphire laser pulses.

We report on the efficient generation of intense terahertz radiation from the organic crystal N-benzyl-2-methyl-4-nitroaniline pumped by chirped Ti:sapphire femtosecond laser pulses. The THz energy and spectrum as a function of the pump fluence and duration of the chirped laser pulses are studied systematically. For the appropriate positively chirped pump pulses, a significant boost in the THz generation efficiency by a factor of around 2.5 is achieved, and the enhancement of high-frequency components (>1 THz) shortens the THz pulse duration. Via complete characterization of THz properties and transmitted laser spectra, this nonlinear behavior is attributed to the extended effective interaction length for phase matching as a result of the self-phase modulation of the intense pump laser pulses. Numerical calculations well reproduce the experimental observation. Our results demonstrate a robust, efficient, strong-field (up to several MV/cm) THz source using the common sub-10 mJ and sub-100 fs Ti:sapphire laser systems without optical parametric amplifiers.

Associations between first-trimester screening biomarkers and maternal characteristics with gestational diabetes mellitus in Chinese women.

Background: Gestational diabetes mellitus (GDM) can result in adverse maternal and neonatal outcomes. Predicting those at high risk of GDM and early interventions can reduce the development of GDM. The aim of this study was to examine the associations between first-trimester prenatal screening biomarkers and maternal characteristics in relation to GDM in Chinese women. Methods: We conducted a retrospective cohort study of singleton pregnant women who received first-trimester aneuploidy and preeclampsia screening between January 2019 and May 2021. First-trimester prenatal screening biomarkers, including pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotropin, and placental growth factor (PLGF), along with maternal characteristics, were collected for analysis in relation to GDM. Receiver operating characteristic (ROC) curve and logistic regression analyses were used to evaluate variables associated with GDM. Results: Of the 1452 pregnant women enrolled, 96 developed GDM. PAPP-A (5.01 vs. 5.73 IU/L, P < 0.001) and PLGF (39.88 vs. 41.81 pg/mL, P = 0.044) were significantly lower in the GDM group than in the non-GDM group. The area under the ROC curve of combined maternal characteristics and biomarkers was 0.73 (95% confidence interval [CI] 0.68-0.79, P < 0.001). The formula for predicting GDM was as follows: P = 1/[1 + exp (-8.148 + 0.057 x age + 0.011 x pregestational body mass index + 1.752 x previous GDM history + 0.95 x previous preeclampsia history + 0.756 x family history of diabetes + 0.025 x chronic hypertension + 0.036 x mean arterial pressure - 0.09 x PAPP-A - 0.001 x PLGF)]. Logistic regression analysis revealed that higher pregestational body mass index (adjusted odds ratio [aOR] 1.03, 95% CI 1.01 - 1.06, P = 0.012), previous GDM history (aOR 9.97, 95% CI 3.92 - 25.37, P < 0.001), family history of diabetes (aOR 2.36, 95% CI 1.39 - 4.02, P = 0.001), higher mean arterial pressure (aOR 1.17, 95% CI 1.07 - 1.27, P < 0.001), and lower PAPP-A level (aOR 0.91, 95% CI 0.83 - 1.00, P = 0.040) were independently associated with the development of GDM. The Hosmer-Lemeshow test demonstrated that the model exhibited an excellent discrimination ability (chi-square = 3.089, df = 8, P = 0.929). Conclusion: Downregulation of first-trimester PAPP-A and PLGF was associated with the development of GDM. Combining first-trimester biomarkers with maternal characteristics could be valuable for predicting the risk of GDM.

Deciphering the mediating role of CXCL10 in hypothyroidism-induced idiopathic pulmonary fibrosis in European ancestry: a Mendelian randomization study.

Background: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by progressive fibrosis, leading to impaired gas exchange and high mortality. The etiology of IPF is complex, with potential links to autoimmune disorders such as hypothyroidism. This study explores the relationship between hypothyroidism and IPF, focusing on the mediating role of plasma proteins. Methods: A two-sample Mendelian randomization (MR) approach was employed to determine the impact of hypothyroidism on IPF and the mediating role of 4,907 plasma proteins, all in individuals of European ancestry. Sensitivity analyses, external validation, and reverse causality tests were conducted to ensure the robustness of the findings. Additionally, the function of causal SNPs was evaluated through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Conclusion: The findings suggest that hypothyroidism, through altered plasma protein expression, particularly CXCL10, may contribute to the pathogenesis of IPF. This novel insight highlights the potential of CXCL10 as a therapeutic target in IPF, especially in patients with hypothyroidism. The study emphasizes the need for further research into the complex interplay between autoimmune disorders and IPF, with a view towards developing targeted interventions for IPF management.

[Regional Difference and Spatial Convergence of Land Use Carbon Emissions in Three Urban Agglomerations of Yangtze River Economic Belt].

It is of great significance to explore the regional differences of land use carbon emission （LUCE） in the Yangtze River Economic Belt and the path of coordinated emission reduction for regional sustainable development. Based on the LUCE estimation method, this study scientifically calculated the LUCE of the three major urban agglomerations of the Yangtze River Economic Belt （Yangtze River Delta, middle reaches of the Yangtze River, and Chengdu-Chongqing urban agglomeration） from 2010 to 2020. Kernel density estimation and the spatial convergence model were used to study the dynamic evolution, regional differences, and convergence characteristics of LUCE. The results showed that： ① The carbon absorption of forest land, water areas, grassland, and unused land were relatively small in terms of carbon emissions from cultivated land and construction land. The carbon emission of construction land increased gradually, whereas the carbon absorption of four carbon sinks fluctuated little during the study period. ② The core density curves of different urban agglomerations showed different distribution patterns, extensibility, and polarization characteristics but generally tended to be balanced. ③ From 2010 to 2020, the LUCE of the Yangtze River Economic Belt as a whole showed the spatio-temporal characteristics of increasing first and then decreasing and high in the east and low in the west. The LUCE of the central cities of the three urban agglomerations were at the highest level steadily, and stable coupling mechanisms had not been established between the economic development level and the ecological environment. ④ The LUCE of the three urban agglomerations in the Yangtze River Economic Belt all had absolute ß convergence and also had conditional ß convergence under the model control variables such as economic development level, urbanization level, industrial structure, population density, and environmental regulation, etc., and the conditional convergence speed was greater than the absolute convergence speed in each region. The convergence speed of the Yangtze River Delta urban agglomeration was the slowest. The above conclusions provide support for the coordinated emission reduction path of the three urban agglomerations in the Yangtze River Economic Belt and are also conducive to actively and steadily promoting the realization of the goals of carbon peak and carbon neutralization.

Green transformation and performance synergy efficiency of china's thermal power enterprises on the basis of the environmental tax burden.

Global climate change and the collection of environmental protection taxes are accelerating the green transformation of thermal power enterprises. This study selected Chinese thermal power listed companies as samples and used a dynamic three-stage (operational, green transformation, and market performance) network DEA model to evaluate their transformation efficiency and corporate performance. This paper incorporates targeted indicators such as ESG (environment, society, governance) and stock prices into the model and conducts a comparative study on the basis of macro policies and the geographical location of the enterprise. A comparative analysis was conducted on the efficiency of enterprises before and after the adjustment of the environmental tax burden, using the environmental tax burden as an exogenous variable. Thus, the following conclusions can be drawn: there is a certain positive correlation between the collaborative efficiency of the two links of thermal power enterprises and the economic development of their respective regions. Moreover, the green transformation efficiency of most thermal power enterprises is superior to the market performance efficiency. The environmental tax burden mainly improves the overall efficiency of thermal power enterprises by improving their operational efficiency and efficiency in the green transformation stage without affecting market performance. To further improve efficiency, thermal power enterprises should actively communicate with stakeholders to strive for more financial relief.

Self-regulated learning strategies adopted by successful Chinese nursing students in the process of learning Nursing English.

As the number of foreign patients and the frequency of international academic exchanges increase, English proficiency has become increasingly essential for Chinese nurses in the treatment and nursing processes, clinical academic exchanges, and ongoing education. However, the overall English proficiency of Chinese nurses is generally inadequate, greatly depending on the English that they acquire during their nursing education. This study aims to explore the challenges encountered by Chinese EFL (English as a Foreign Language) nursing students in the process of learning Nursing English, along with the effective self-regulated learning strategies they adopt to overcome these challenges. Data were collected from nine Chinese EFL nursing students through their reflective journals and thematic analysis was applied. Data analysis revealed the variety of challenges EFL nursing students encountered, including language-related challenges, which are linguistic difficulties that relate to Nursing English learning itself, such as Nursing English vocabulary and terminology, English-to-English translation, limited listening comprehension, and the gap between textbook knowledge and its practical application; learner-related challenges, which are difficulties that affect students' emotional, affective, and mental state, primarily caused by uncertainty about the significance of Nursing English, the unexpected difficulty of Nursing English, and failing quizzes; and context-related challenges, which are difficulties relate to social, cultural, and educational context, such as insufficient learning resources, a lack of language environment, and peer pressure. To surmount these challenges, the participants adopted diverse self-regulated learning strategies, including setting goals, previewing in advance and reviewing in time, utilizing word roots, prefixes, and suffixes to facilitate vocabulary learning, repeating, practicing with sounds and writing systems, translating, highlighting and using imagery to overcome language-related challenges; believing in the usefulness and significance of Nursing English, keeping a growth mindset, enjoying Nursing English learning and teacher support and maintaining grit in learning Nursing English to overcome learner-related challenges; and integrating resources, creating supportive language environments and seeking assistance from teachers and cooperating with peers to overcome context-related challenges. Based on these findings, implications are drawn for Nursing English teachers, material designers, curriculum developers, and program designers. We suggest incorporating explicit strategy instruction into regular Nursing English education to enhance nursing students' self-regulated learning.

Identification of Heilongjiang crossbred beef cattle pedigrees and reveals functional genes related to economic traits based on whole-genome SNP data.

Introduction: To enhance the beef cattle industry, Heilongjiang Province has developed a new Crossbred beef cattle variety through crossbreeding with exotic commercial breeds. This new variety exhibits relatively excellent meat quality, and efficient reproductive performance, catering to market demands. Method: This study employed whole genome resequencing technology to analyze the genetic pedigree and diversity of 19 Heilongjiang Crossbred beef cattle, alongside 59 published genomes from East Asian, Eurasian, and European taurine cattle as controls. In addition, genes related to production traits were also searched by identifying Runs of Homozygosity (ROH) islands and important fragments from ancestors. Results: A total of 14,427,729 biallelic SNPs were discovered, with the majority located in intergenic and intron regions and a small percentage in exon regions, impacting protein function. Population genetic analyses including Principal Component Analysis (PCA), Neighbor-Joining (NJ) tree, and ADMIXTURE identified Angus, Holstein, and Mishima as the main ancestors of Crossbred beef cattle. In genetic diversity analysis, nucleotide diversity, linkage disequilibrium, and inbreeding coefficient analysis reveal that the genetic diversity of Crossbred beef cattle is at a moderate level, and a higher inbreeding coefficient indicates the need for careful breeding management. In addition, some genes related to economic traits are identified through the identification of Runs of Homozygosity (ROH) islands and important fragments from ancestors. Conclusion: This comprehensive genomic characterization supports the targeted improvement of economically important traits in Crossbred beef cattle, facilitating advanced breeding strategies.

Rationality and implication of catheter-based adrenal ablation for bilateral primary aldosteronism.

Mineralocorticoid receptor antagonists (MRAs) for bilateral primary aldosteronism (PA) are the mainstay option recommended by guidelines, but poor compliance occurs due to numerous side effects. We aimed to examine whether catheter-based adrenal ablation could be an alternative treatment for bilateral PA.644 PA patients were included from a total of 6054 hypertensive patients. Adrenal CT scan and adrenal venous sampling (AVS) were both performed for PA subtype classification. Clinical and biochemical outcomes were assessed at 6 months after treatment according to the Primary Aldosteronism Surgical Outcome (PASO) criteria.93 patients with PA were recruited to be treated by adrenal ablation, including 25 bilateral PA and 68 unilateral PA according to AVS results. Office SBP and DBP significantly decreased from baseline levels, serum potassium levels increased and ARR significantly decreased (p < 0.01) in both the bilateral and unilateral groups. In the bilateral group, complete, partial and absent clinical success was achieved in 6 (24.0%), 11 (44.0%) and 8(32.0%) patients, respectively. In the unilateral group, complete, partial and absent clinical success was achieved in 12 (17.6%), 37 (54.4%), and 19 (27.9%) patients, respectively. The numbers of patients achieving complete, partial, and absent biochemical success were 15 (60.0%), 6 (24.0%), and 4 (16.0%), respectively, in the bilateral group versus 37 (54.4%), 9 (13.2%), and 22 (32.3%), respectively, in the unilateral group. In conclusion, we provide evidence for the beneficial outcomes of unilateral adrenal ablation for patients with bilateral PA. Our findings provide insight into an alternative option for patients with bilateral excess aldosterone.

Real-time detection and resection of sentinel lymph node metastasis in breast cancer through a rare earth nanoprobe based NIR-IIb fluorescence imaging.

Sentinel lymph node (SLN) biopsy is a commonly employed procedure for the routine assessment of axillary involvement in patients with breast cancer. Nevertheless, conventional SLN mapping cannot reliably distinguish the presence and absence of metastatic disease. Additionally, the complex anatomical structures and lymphatic drainage patterns surrounding tumor sites pose challenges to the sensitivity of the near-infrared fluorescence imaging with subcutaneously injected probes. To identifying the SLN metastases, we developed a novel nanoprobe for in vivo fluorescence imaging within the second near-infrared (NIR-II) range. This nanoprobe utilizes rare-earth nanoparticles (RENPs) to emit bright fluorescence at 1525 nm and is conjugated with tumor-targeted hyaluronic acid (HA) to facilitate the detection of metastatic SLN. Upon intravenous administration, RENPs@HA effectively migrated to SLNs and selectively entered metastatic breast tumor cells through CD44-mediated endocytosis. The RENPs@HA nanoprobes exhibited rapid accumulation in metastatic inguinal lymph nodes in mouse model, displaying a 5.8-fold-stronger fluorescence intensity to that observed in normal SLNs. Consequently, these nanoprobes effectively differentiate metastatic SLNs from normal SLNs. Importantly, the probes accurately detected micrometastases. These findings underscore the potential of RENPs@HA for real-time visualization and screening of SLNs metastasis.

Construction of gradient ionogels by self-floatable hyperbranched organosilicon crosslinkers for multi-sensing and wirelessly monitoring physiological signals.

Monitoring complex human movements requires the simultaneous detection of strain and pressure, which poses a challenge due to the difficulty in integrating high stretchability and compressive ability into a single material. Herein, a series of hyperbranched polysiloxane crosslinkers (HPSis) with self-floating abilities are designed and synthesized. Taking advantage of the self-floating capabilities of HPSis, ionogels with gradient composition distribution and conductivities are constructed by in situ one-step photopolymerization, and possess satisfactory stretchability, high compressibility and excellent resilience. The gradient-ionogel-based strain sensor exhibits extraordinary pressure sensitivity (19.33 kPa-1), high strain sensitivity (GF reaches 2.5) and temperature sensing ability, enabling the monitoring of the angles and direction of joint movements, transmitting Morse code and wirelessly detecting bioelectrical signals. This study may inspire the design of development of multi-function flexible electronics.

Cold-adapted influenza vaccine carrying three repeats of a respiratory syncytial virus (RSV) fusion glycoprotein epitope site protects BALB/c mice and cotton rats against RSV infection.

Respiratory syncytial virus is the major cause of respiratory viral infections, particularly in infants, immunocompromised populations, and the elderly (over 65 years old), the prevention of RSV infection has become a priority. In this study, we generated a chimeric influenza virus, termed LAIV/RSV/HA-3F, using reverse genetics technology which contained three repeats of the RSV fusion protein neutralizing epitope site II to the N terminal in the background of the hemagglutinin (HA) gene of cold adapted influenza vaccine A/California/7/2009 ca. LAIV/RSV/HA-3F exhibited cold-adapted (ca) and attenuated (att) phenotype. BALB/c mice immunized intranasally with LAIV/RSV/HA-3F showed robust immunogenicity, inducing viral-specific antibody responses against both influenza and RSV, eliciting RSV-specific humoral, cellular and mucosal immune responses. LAIV/RSV/HA-3F also conferred protection as indicated by reduced viral titers and improved lung histopathological alterations against live RSV virus challenge. Mechanismly, single-cell RNA sequencing (scRNA-seq) and single-cell T cell antigen receptor (TCR) sequencing were employed to characterize the immune responses triggered by chimeric RSV vaccine, displaying that LAIV/RSV/HA-3F provided protection mainly via interferon-γ (IFN-γ). Moreover, we found that LAIV/RSV/HA-3F significantly inhibited viral replication in the challenged lung and protected against subsequent RSV challenge in cotton rats without causing lung disease. Taken together, our findings demonstrated that LAIV/RSV/HA-3F has potential as a promising bivalent vaccine with dual purpose candidate for the prevention of influenza and RSV, and preclinical and clinical studies warrant further investigations.

The expected changes with different periods of home-based resistance exercise in patients with chronic kidney disease.

BACKGROUND: The comprehensive impact of prolonged home-based resistance training on individuals grappling with chronic kidney disease (CKD) have yet to be fully elucidated. This study aimed to explore the outcomes of varying exercise durations on physical performance, nutritional status, and kidney function within this specific population, encompassing patients undergoing dialysis and those affected by severe sarcopenia. METHODS: This was a 1-year observational double cohort study following a 52-week longitudinal design, we enrolled 101 adult CKD outpatients. These participants were divided into two groups: the continuous group, comprising individuals who consistently exercised for over 6 months, and the interrupted group, which included those who did not sustain regular exercise for the same duration. The exercise regimen involved resistance exercises conducted at least 3 to 5 days per week, involving activities like lifting dumbbells and executing weighted wall squats. Physical activity assessments and biochemical blood tests were conducted at weeks 0, 4, 16, 28, 40, and 52 for all participants. RESULTS: The continuous exercise group exhibited better handgrip strength and sit-to-stand movement compared to the interrupted group. Their estimated glomerular filtration rate stayed steady while the interrupted group was declined. Additionally, those who exercised consistently had better metabolism: higher carbon dioxide levels, increased albumin, better nutritional scores, and lower levels of blood urea nitrogen, creatinine, fasting blood glucose, and body weight. Subsequent adjustments for potential confounding factors continued to show improved physical performance and kidney function over time. CONCLUSION: Our findings indicate the advantageous impact of extended resistance exercise training on overall health of CKD patients, even those on dialysis or with severe sarcopenia. Dedication to this exercise routine could improve kidney function, metabolism, and physical abilities in these patients.

Endoscopic variceal ligation combined with sclerotherapy for management of gastroesophageal variceal bleeding in pediatric patients: a single-center retrospective study.

Objectives: Portal hypertension (PH) frequently gives rise to severe and life-threatening complications, including hemorrhage accompanied by the rupture of esophageal and gastric varices. In contrast to the guidelines for the management of PH in adults, the optimal endoscopic management of variceal bleeding for secondary prophylaxis in children remains unclear. The present study evaluated the efficacy and safety of endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST) to control gastroesophageal variceal bleeding in children. Methods: This retrospective study included children with gastroesophageal variceal bleeding who underwent EST or EVL at Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between February 2013 and March 2020. Short-term hemostasis rate and long-term rebleeding rate were evaluated. Adverse events related to the procedures, such as esophageal ulcer, esophageal stricture, abnormal embolization, pneumonia and perforation, were also recorded. Results: EVL (n = 8) and EST (n = 13) were performed successfully in all pediatric patients diagnosed with moderate to severe esophageal varices concurrent with gastric varices. Hemostasis was achieved during episodes of upper gastrointestinal bleeding. The mean volume of each single aliquot of cyanoacrylate injected was 0.3 ± 0.1 ml (range: 0.1-0.5 ml). Varices were eradicated in six (75%) of the eight patients who underwent EVL after a median 2 (range: 1-4) procedures and a median time of 3.40 months (range: 1.10-13.33 months). Eleven (52.4%) of the 21 patients developed rebleeding events, with the mean duration of hemostasis being 11.1 ± 11.6 months (range 1.0-39.2 months). No treatment-related complications, for example, distal embolism, occurred except for abdominal pain in one patient (4.8%). Conclusions: EST, alone or in combination with EVL, is an effective and safe method of managing gastroesophageal variceal hemorrhage in children undergoing secondary prophylaxis.

The Predictive Value of Atherogenic Index of Plasma, Non- High Density Lipoprotein Cholesterol (Non-HDL-C), Non-HDL-C/HDL-C, and Lipoprotein Combine Index for Stroke Incidence and Prognosis in Maintenance Hemodialysis Patients.

Purpose: The serum lipid level is strongly associated with atherosclerosis. However, research on the relationship between lipid-derived indices and acute ischemic stroke (AIS) occurrence in hemodialysis populations is limited. This study aimed to explore the predictive value of lipid-derived indices, including atherogenic index of plasma (AIP), Non- high density lipoprotein cholesterol (Non-HDL-C), Non-HDL-C/HDL-C, and lipoprotein combine index (LCI) in clinical practice for the occurrence and prognosis of AIS in hemodialysis patients. Methods: A total of 451 patients undergoing maintenance hemodialysis were screened and 350 were enrolled in this study. The lipid parameters exhibit a progressive increase across the tertiles, with values rising from Q1 through Q3. Enrolled patients were divided into three groups (Q1, Q2, and Q3) based on tertiles of AIP, Non-HDL-C, Non-HDL-C/HDL-C, and LCI values. Kaplan-Meier curves were performed to investigate the association between the AIP, Non-HDL-C, Non-HDL-C/HDL-C, LCI and AIS-free survival in hemodialysis patients. Chi-square analysis was used to explore the association between the AIP, Non-HDL-C, Non-HDL-C/HDL-C, LCI and AIS outcomes in hemodialysis patients. AIS outcomes were assessed using the modified Rankin Scale (mRS). Results: Kaplan-Meier analysis revealed that the AIS-free survival rates were significantly higher in the Q1 group compared to Q2 and Q3 groups for AIP, Non-HDL-C, Non-HDL-C/HDL-C, and LCI. Log rank tests showed statistically significant differences between the Q1 group and the Q2 and Q3 groups (p < 0.05 for all). The proportion of patients with a good outcome mRS was higher in the Q1 group compared to the Q2-Q3 groups (AIP: 0.818 vs 0.792; Non- HDL-C: 0.866 vs 0.767; Non- HDL-C/HDL-C: 0.867 vs 0.767; LCI: 0.938 vs 0.750). Conclusion: The four lipid-derived parameters are effective predictors of AIS in patients undergoing hemodialysis, and AIP has a strongest correlation with the risk of AIS. Hemodialysis patients with elevated levels of the four lipid-derived indices had a higher incidence of AIS and poorer functional outcomes compared to those with lower levels. Our conclusions may require confirmation by further research in the future.