Gene panel predicts neoadjuvant chemoimmunotherapy response and benefit from immunotherapy in HER2-negative breast cancer.

BACKGROUND: It is encountering the dilemma of lacking precise biomarkers to predict the response to neoadjuvant chemoimmunotherapy (NACI) and determine whether patients should use immune checkpoint inhibitors (ICIs) in early breast cancer (BC). We aimed to develop a gene signature to predict NACI response for BC patients and identify individuals suitable for adding ICIs. PATIENTS AND METHODS: Two I-SPY2 cohorts and one West China Hospital cohort of patients treated with NACI were included. Machine learning algorithms were used to identify key genes. Principal component analysis was used to calculate the ImPredict (IP) score. The interaction effects between biomarkers and treatment regimens were examined based on the logistic regression analysis. The relationship between the IP score and immune microenvironment was investigated through immunohistochemistry (IHC) and multiplex IHC. RESULTS: The area under the curves of the IP score were 0.935, 0.865, and 0.841 in the discovery cohort, validation cohort 1, and in-house cohort. Marker-treatment interaction tests indicated that the benefits from immunotherapy significantly varied between patients with high and low IP scores (p for interaction <0.001), and patients with high IP scores were more suitable for immunotherapy addition. CONCLUSIONS: Our IP model shows favorable performance in predicting NACI response and is an effective tool for identifying BC patients who will benefit from ICIs. It may help clinicians optimize treatment strategies and guide clinical decision-making.

Hemodynamic influence of mild stenosis morphology in different coronary arteries: a computational fluid dynamic modelling study.

Introduction: Mild stenosis [degree of stenosis (DS) < 50%] is commonly labeled as nonobstructive lesion. Some lesions remain stable for several years, while others precipitate acute coronary syndromes (ACS) rapidly. The causes of ACS and the factors leading to diverse clinical outcomes remain unclear. Method: This study aimed to investigate the hemodynamic influence of mild stenosis morphologies in different coronary arteries. The stenoses were modeled with different morphologies based on a healthy individual data. Computational fluid dynamics analysis was used to obtain hemodynamic characteristics, including flow waveforms, fractional flow reserve (FFR), flow streamlines, time-average wall shear stress (TAWSS), and oscillatory shear index (OSI). Results: Numerical simulation indicated significant hemodynamic differences among different DS and locations. In the 20%-30% range, significant large, low-velocity vortexes resulted in low TAWSS (<4 dyne/cm2) around stenoses. In the 30%-50% range, high flow velocity due to lumen area reduction resulted in high TAWSS (>40 dyne/cm2), rapidly expanding the high TAWSS area (averagely increased by 0.46 cm2) in left main artery and left anterior descending artery (LAD), where high OSI areas remained extensive (>0.19 cm2). Discussion: While mild stenosis does not pose any immediate ischemic risk due to a FFR > 0.95, 20%-50% stenosis requires attention and further subdivision based on location is essential. Rapid progression is a danger for lesions with 20%-30% DS near the stenoses and in the proximal LAD, while lesions with 30%-50% DS can cause plaque injury and rupture. These findings support clinical practice in early assessment, monitoring, and preventive treatment.

In Situ Formed Gel Polymer Electrolytes Enable Stable Solid Electrolyte Interface for High-Performance Lithium Metal Batteries.

Carbonate-based electrolytes show distinct advantages in high-voltage cathodes but generate nonuniform and mechanically fragile solid-electrolyte interphase (SEI) in lithium (Li) metal batteries. Herein, we propose a LiF-rich SEI incorporating an in situ polymerized poly(hexamethylene diisocyanate)-based gel polymer electrolyte (GPE) to improve the homogeneity and mechanical stability of SEI. Fluoroethylene carbonate (FEC) as a fluorine-based additive for building LiF-rich SEI on Li metal electrodes. With this strategy, the assembled Li symmetric batteries cycled stably for 700 h, and the formation of byproducts on the Li electrode surface was significantly inhibited. The Li/LiFePO4 battery delivered significant capacity retention (91% retention after 800 cycles) at 1 C. With high-voltage LiNi0.8Co0.1Mn0.1O2 (NCM811) as cathode, the Li/GPE-FEC/NCM811 cell delivered a discharge capacity of 168.9 mAh g-1 with a capacity retention of 82% after 300 cycles at 0.5 C. From the above, the work could assist the rapid development of high-energy-density rechargeable Li metal batteries toward remarkable performance.

GLObal Building heights for Urban Studies (UT-GLOBUS) for city- and street- scale urban simulations: Development and first applications.

We introduce University of Texas - GLObal Building heights for Urban Studies (UT-GLOBUS), a dataset providing building heights and urban canopy parameters (UCPs) for more than 1200 city or locales worldwide. UT-GLOBUS combines open-source spaceborne altimetry (ICESat-2 and GEDI) and coarse-resolution urban canopy elevation data with a machine-learning model to estimate building-level information. Validation using LiDAR data from six U.S. cities showed UT-GLOBUS-derived building heights had a root mean squared error (RMSE) of 9.1 meters. Validation of mean building heights within 1-km2 grid cells, including data from Hamburg and Sydney, resulted in an RMSE of 7.8 meters. Testing the UCPs in the urban Weather Research and Forecasting (WRF-Urban) model resulted in a significant improvement (55% in RMSE) in intra-urban air temperature representation compared to the existing table-based local climate zone approach in Houston, TX. Additionally, we demonstrated the dataset's utility for simulating heat mitigation strategies and building energy consumption using WRF-Urban, with test cases in Chicago, IL, and Austin, TX. Street-scale mean radiant temperature simulations using the SOlar and LongWave Environmental Irradiance Geometry (SOLWEIG) model, incorporating UT-GLOBUS and LiDAR-derived building heights, confirmed the dataset's effectiveness in modeling human thermal comfort in Baltimore, MD (daytime RMSE = 2.85°C). Thus, UT-GLOBUS can be used for modeling urban hazards with significant socioeconomic and biometeorological risks, enabling finer scale urban climate simulations and overcoming previous limitations due to the lack of building information.

Characterization of the flavor profile and dynamic changes in Chinese traditional fish sauce (Yu-lu) based on electronic nose, SPME-GC-MS and HS-GC-IMS.

In this study, flavor characteristics and dynamic change of Chinese traditional fermented fish sauce (Yu-lu) with different fermentation time (2, 4, 6, 8, and 12 months) were analyzed. The electronic nose analyses confirmed a notable flavor change in fish sauce samples from different stages. During the 12-months fermentation, the total volatile compounds in fish sauce increased from 3.9 mg/L to 13.53 mg/L. Acids, aldehydes, esters and phenols were the main aroma substances and their contents gradually increased during the fermentation process. The PCA of GC-MS and GC-IMS showed that fish sauce samples from different fermentation periods can be well distinguished. A total of 110 volatile compounds identified by GC-MS, and 102 volatile compounds were detected by GC-IMS. Among them, 13 compounds were identified by both GC-MS and GC-IMS. The most varieties (49) of volatiles appeared after 8 months of fermentation. The odor activity value (OAV) analysis showed that 10 volatile compounds were considered as characteristic flavor in traditional fish sauce. The variable influence on projections (VIPs) in PLS-DA models constructed by GC-MS and GC-IMS identified 5 and 10 volatile compounds as biomarkers, respectively. Our results revealed the dynamic changes of characteristic flavor in fish sauce in combination of GC-MS and GC-IMS, which provides theoretical basis for the production and flavor regulation of fish sauce.

Direct antiglobulin test type, red blood cell distribution width, and estimated glomerular filtration rate for early prediction of in-hospital mortality of patients with COVID-19.

Objective: This study aimed to investigate the correlation between COVID-19 and the direct antiglobulin test (DAT) and establish an in-hospital mortality risk predictive model based on the DAT type, which can be used for the early prediction of inpatients with COVID-19. Methods: In this study, 502 patients admitted to our hospital who underwent DAT testing from January 29 to February 8, 2023, were included (252 DAT-positive and 250 DAT-negative). Among them, 241 cases of COVID-19 were screened(171 DAT-positive and 70 DAT-negative), clinical and laboratory indicators were compared between DAT-positive and DAT-negative groups. Univariate and multivariate logistic regression analysis, the Kaplan-Meier survival curve and receiver operating curves were used to explore the relation between the DAT type and in-hospital mortality of patients with COVID-19. Results: The proportion of confirmed COVID-19 cases was higher in the DAT-positive group than in the DAT-negative group (67.9 % vs. 28.0 %, P < 0.05). Patients with COVID-19 in the DAT-positive group had higher age-adjusted Charlson comorbidity index scores, red blood cell distribution width (RDW), lactate dehydrogenase, prothrombin time, D-dimer, creatinine, and high-sensitive cardiac troponin T levels than the negative group (P < 0.05), In contrast, hemoglobin and estimated glomerular filtration rate (eGFR) levels were lower in the DAT-positive group. The DAT-positive group also had a higher red blood cell usage volume and in-hospital mortality rate than the DAT-negative group. The mortality rate of patients with COVID-19 with both IgG and C3d positive was higher than that of the other groups. Multivariate logistic regression analysis showed that RDW and eGFR were associated with mortality in patients with COVID-19. The combined predictive model of DAT type, RDW, and eGFR showed an area under the curve of 0.782, sensitivity of 0.769, and specificity of 0.712 in predicting in-hospital mortality risk in patients with COVID-19. Conclusion: The established predictive model for in-hospital mortality risk of patients with COVID-19 based on DAT type, RDW, and eGFR can provide a basis for timely intervention to reduce the mortality rates of patients with COVID-19. This model is accessible at https://jijijiduola.shinyapps.io/0531// for research purposes.

The application of gradually expanding pedicle technology in the placement of screws in thinner pedicle of patients with idiopathic scoliosis.

Objective: To propose a technique of gradual expansion of pedicle diameter to place screws on the thinner pedicle that is difficult to place screws in scoliosis orthopedic surgery, in order to place thicker pedicle screws in the premise of good safety to achieve good stability and orthopaedic effect. Methods: The authors reviewed that 36 patients with Adolescent idiopathic scoliosis (AIS) (20 females, 16 males) in our department from June 2020 to March 2024 underwent posterior spinal correction and internal fixation were enrolled in the present study. 194 pedicles had narrower diameter ranging from 0 mm to 4.5 mm. After analysis, 155 pedicles (internal diameter: 2.5 mm-4.5 mm) were treated with gradually expanding pedicles technology. The angle between the inserted screws and the upper endplate of the vertebral body was measured 1 week after operation and 3 months after operation to evaluate the placement of the screws after pedicle expansion. Results: All operations were completed without dura mater rupture, nerve root injury, infection and poor incision healing. There was no screw breaking or screw pull-out in DR film at 3 months after operation compared with 1 week after operation. There was no significant difference in the angle between screw and upper endplate measured by the three observers at 3 months and 1 week after operation (Wilcoxon's signed rank test, p > 0.05). In the measurement at 1 week or 3 months after operation, there was no statistically significant difference among the three observers. There is a good consistency between the observers (Cronbach's alpha > 0.80). Conclusion: In AIS patients, the thinner pedicle with a diameter range of 2.5 mm to 4.5 mm can be safely inserted with relatively thicker pedicle screws after gradually expanding pedicle technology.

A sequential dual-locked luminescent copper nanocluster probe for tumor cell imaging and killing.

A sequential dual-locked luminescent copper nanoclusters (CuNCs) probe was designed and synthesized for the specific imaging and selective killing of tumor cells. This nanoprobe was prepared by first forming a Fe3+-coupled tannic acid (TA)-stabilized CuNCs (CuNCs-FeIII), which is in quenching state due to the electron transfer between CuNCs and Fe3+, and then coating a protectable layer of hyaluronic acid (HA) on the surface of CuNCs-FeIII to form the final dual-locked nanoprobe (CuNCs-FeIII@HA). When the nanoprobe of CuNCs-FeIII@HA target enter the tumor cells through CD44-HA receptor, HAase will first digest the HA layer of the nanoprobes, and then, GSH over-expressed in tumor cells will reduce Fe3+ to Fe2+, thus restoring the fluorescence emission of CuNCs and at the same time killing the tumor cells with the hydroxyl free radicals (∙OH) produced by the Fenton reaction between Fe2+ and H2O2. This sequential dual-locked luminescent nanoprobe of CuNCs-FeIII@HA has been successfully used for the specific imaging and selective killing of tumor cells.

Mitochondrial fragmentation in early differentiation of human MB135 myoblasts: Role of mitochondrial ROS production in the absence of depolarization.

AIMS: Study of the role of mitochondria-generated reactive oxygen species (mtROS) and mitochondrial polarization in mitochondrial fragmentation at the initial stages of myogenesis. MAIN METHODS: Mitochondrial morphology, Drp1 protein phosphorylation, mitochondrial electron transport chain components content, mtROS and mitochondrial lipid peroxidation levels, and mitochondrial polarization were evaluated on days 1 and 2 of human MB135 myoblasts differentiation. A mitochondria-targeted antioxidant SkQ1 was used to elucidate the effect of mtROS on mitochondria. KEY FINDINGS: In immortalized human MB135 myoblasts, mitochondrial fragmentation began on day 1 of differentiation before the myoblast fusion. This fragmentation was preceded by dephosphorylation of p-Drp1 (Ser-637). On day 2, an increase in the content of some mitochondrial proteins was observed, indicating mitochondrial biogenesis stimulation. Furthermore, we found that myogenic differentiation, even on day 1, was accompanied both by an increased production of mtROS, and lipid peroxidation of the inner mitochondrial membrane. SkQ1 blocked these effects and partially reduced the level of mitochondrial fragmentation, but did not affect the dephosphorylation of p-Drp1 (Ser-637). Importantly, mitochondrial fragmentation at early stages of MB135 differentiation was not accompanied by depolarization, as an important stimulus for mitochondrial fragmentation. SIGNIFICANCE: Mitochondrial fragmentation during early myogenic differentiation depends on mtROS production rather than mitochondrial depolarization. SkQ1 only partially inhibited mitochondrial fragmentation, without significant effects on mitophagy or early myogenic differentiation.

Does vegetation greening have a positive effect on global vegetation carbon and water use efficiency?

Terrestrial ecosystems have undergone significant changes as a result of climate change, profoundly affecting global carbon and water cycling processes. Notably, the synergistic changes in vegetation carbon use efficiency (CUE) and water use efficiency (WUE) and their response to patterns of climate change over the last 40 years are unknown. Therefore, in this study, global vegetation WUE and CUE were inverted using Gross primary productivity (GPP), Net primary productivity (NPP) and total evaporation (ET) data from 1981 to 2019 to reveal their temporal and spatial patterns of change through trend analysis and stability analysis. A stepwise regression algorithm was used to reveal the potential driving law of environmental factors on vegetation WUE and CUE. The results shows that (1) From 1981 to 2019, the global vegetation WUE and CUE showed in a relatively stable state, and the trends of WUE and CUE were -0.00004/year and 0.006 g C m-2 mm-1/year, respectively; (2) the greening of vegetation was the most important cause of the changes in WUE and CUE, and the driving force of rain and heat conditions on the CUE of vegetation was smaller than that of solar radiation and soil water, the regions where CO2 is the dominant factor affecting CUE and WUE are mainly in the north temperate zone; (3) the region of synergistic growth of WUE and CUE accounts for about 31.38 % of the global terrestrial area, and this pattern of change suggests that the global vegetation carbon sink potential is huge, and the popularization of vegetation planting patterns under the synergistic growth of CUE and WUE should be strengthened. The research has shown that vegetation greening is a key factor influencing changes in the WUE and CUE of vegetation, therefore, the implementation of ecological engineering will be an important step in combating climate change.

The key role of iroBCDN-lacking pLVPK-like plasmid in the evolution of the most prevalent hypervirulent carbapenem-resistant ST11-KL64 Klebsiella pneumoniae in China.

AIMS: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP), coharboring hypervirulence and carbapenem-resistance genes mediated by plasmids, causes infections with extremely high mortality and seriously impacts public health. Exploring the transfer mechanisms of virulence/carbapenem-resistance plasmids, as well as the formation and evolution pathway of hv-CRKP is of great significance to the control of hv-CRKP infections. METHODS: In this study, we identified the predominant clone of hv-CRKP in China and elucidated its genomic characteristics and formation route based on 239 multicenter clinical K. pneumoniae isolates and 1014 GenBank genomes by using comparative genomic analysis. Further, we revealed the factors affecting the transfer of virulence plasmids, and explained the genetic foundation for the prevalence of Chinese predominant hv-CRKP clone. RESULTS: ST11-KL64 is the predominant clone of hv-CRKP in China and primarily evolved from ST11-KL64 CRKP by acquiring the pLVPK-like virulence plasmid from hvKP. Significantly, the virulence gene cluster iroBCDN was lost in the virulence plasmid of ST11-KL64 hv-CRKP but existed in that of hvKP. Moreover, the absence of iroBCDN didn't decrease the virulence of hv-CRKP, which was proved by bacterial test, cell-interaction test and mice infection model. On the contrary, loss of iroBCDN was observed to regulate virulence/carbapenem-resistance plasmid transfer and oxidative stress-related genes in strains and thus promoted the mobilization of nonconjugative virulence plasmid from hvKP into ST11-KL64 CRKP, forming hv-CRKP which finally had elevated antioxidant capacity and enhanced survival capacity in macrophages. The loss of iroBCDN increased the survival ability of hv-CRKP without decreasing its virulence, endowing it with an evolutionary advantage. CONCLUSIONS: Our work provides new insights into the key role of iroBCDN loss in convergence of CRKP and hvKP, and the genetic and biological foundation for the widespread prevalence of ST11-KL64 hv-CRKP in China.

Recognition of Emotional Prosody in Mandarin-Speaking Children: Effects of Age, Noise, and Working Memory.

Age, babble noise, and working memory have been found to affect the recognition of emotional prosody based on non-tonal languages, yet little is known about how exactly they influence tone-language-speaking children's recognition of emotional prosody. In virtue of the tectonic theory of Stroop effects and the Ease of Language Understanding (ELU) model, this study aimed to explore the effects of age, babble noise, and working memory on Mandarin-speaking children's understanding of emotional prosody. Sixty Mandarin-speaking children aged three to eight years and 20 Mandarin-speaking adults participated in this study. They were asked to recognize the happy or sad prosody of short sentences with different semantics (negative, neutral, or positive) produced by a male speaker. The results revealed that the prosody-semantics congruity played a bigger role in children than in adults for accurate recognition of emotional prosody in quiet, but a less important role in children compared with adults in noise. Furthermore, concerning the recognition accuracy of emotional prosody, the effect of working memory on children was trivial despite the listening conditions. But for adults, it was very prominent in babble noise. The findings partially supported the tectonic theory of Stroop effects which highlights the perceptual enhancement generated by cross-channel congruity, and the ELU model which underlines the importance of working memory in speech processing in noise. These results suggested that the development of emotional prosody recognition is a complex process influenced by the interplay among age, background noise, and working memory.

[Retracted] MicroRNA­642a­5p inhibits colon cancer cell migration and invasion by targeting collagen type I α1.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell invasion assay data shown in Fig. 6B on p. 940, and western blot data featured in Fig. 7B on p. 942, had already appeared in previously published articles written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 933­944, 2021; DOI: 10.3892/or.2020.7905].

Lifestyle, air pollution, and risk of multimorbidity in a prospective analysis of the UK Biobank cohort.

Background: Although associations between chronic obstructive pulmonary disease (COPD) or ischaemic heart disease (IHD) and lifestyle factors or air pollution factors (referred as LAFs below) are well-established, it is unclear the influences of LAFs on the trajectory of IHD and COPD multimorbidity (referred as ICM below). Therefore, this study investigated the influences of LAFs on the trajectory of ICM from healthy to IHD or COPD, to ICM, and to all-cause death. Methods: A cohort of 339,213 participants from the UK Biobank aged 37-73 who were free of IHD and COPD were included. A multi-state model was used to analyse the influences of high-risk factors including current smoking or quitting due to illness or physician's advice, current excessive alcohol drinking, physical inactivity, unhealthy body shape, and excessive air pollution with particulates matter with an aerodynamic diameter ≤2.5 µm (PM2.5) on ICM trajectory. Results: During a median follow-up of 13.74 years, 46,398 participants developed IHD or COPD (referred as IOC below), 3949 developed ICM, and 35,691 died from any cause. All five high-risk factors played crucial but different roles in these transitions. The hazard ratios (95 % confidence intervals) per one-factor increase were 1.29 (1.27-1.3), 1.38 (1.33-1.44), and 1.69 (1.56-1.84) for transitions from baseline to IOC, from IOC to ICM, and from baseline to ICM and 1.19 (1.17-1.21), 1.18 (1.15-1.21), and 1.12 (1.05-1.19) for mortality risk from baseline to all-cause death, from IOC to all-cause death, and from ICM to all-cause death, respectively. Conclusions: Our study revealed that LAFs have a stronger impact on morbidity outcomes than on morbidity outcomes. These findings provide evidence to develop strategies for managing the trajectory of ICM.

Corrigendum: Single-cell RNA sequencing of peripheral blood mononuclear cells from acute myocardial infarction.

[This corrects the article DOI: 10.3389/fimmu.2022.908815.].

Changes in technological innovation efficiency and influencing factors of listed textile and apparel companies research--Based on three-stage DEA with Tobit modeling.

The key to high-quality development in the textile and apparel industry lies in enhancing technological innovation and optimizing the efficiency of technological innovation. Based on data from 60 A-share listed companies in the textile and apparel sector in China from 2013 to 2022, this study employs a three-stage DEA model and the Malmquist index model to measure changes in technological innovation efficiency from static and dynamic perspectives. Additionally, it uses a Tobit model to analyze the impact and mechanisms of management and financial factors on technological innovation efficiency. The results indicate that: (1) Compared to the manufacturing industry and its sub-sectors, the overall technological innovation efficiency of listed textile and apparel companies was relatively low and showed a declining trend between 2013 and 2022; (2) Over the decade, the average total factor productivity of these listed companies increased by 1.7%, exhibiting a "W" shaped fluctuation, with technological progress, pure technical efficiency, and scale efficiency all showing weak improvement; (3) Management and financial factors significantly influence technological innovation efficiency. Specifically, employee quality, profitability, and operational capability are positively correlated with technological innovation efficiency and have long-term effectiveness, while firm age, management costs, equity concentration, development ability, and debt repayment capacity are negatively correlated with technological innovation efficiency; (4) Different types of enterprises show differences in the significance of management factors, while whether the same person holds both managerial positions significantly affects financial factors.

Ensembled-SAMs for Enhanced Small Coronary Artery Segmentation in CCTA Images.

Accurate coronary artery segmentation is crucial for quantitative analysis of coronary arteries in noninvasive coronary computed tomography angiography (CCTA) images. However, current segmentation algorithms often have unsatisfactory recall due to the small size and complex morphology of coronary arteries, particularly in the distal segments. To address this issue, we introduce a new fully automated method named Ensembled-SAMs, which harnesses the strengths of the Segment Anything Model (SAM) and the no-new-U-Net (nnU-Net). First, noisy bounding box prompts are automatically generated by a vesselness algorithm that highlights the tubular structures in the CCTA images. These noisy prompts are then used to fine-tune the SAM and its two variants separately. The SAM variants introduce a classification head in their mask decoder to alleviate the false positives. In addition, an nnU-Net segmentation network is trained from scratch. Finally, the outputs of the SAMs and the nnU-Net are strategically aggregated to obtain the final segmentation result. Experiments on both a self-built dataset and the public Automated Segmentation of Coronary Arteries (ASOCA) challenge dataset demonstrate that the proposed Ensembled-SAMs outperforms the state-of-the-arts, achieving precise segmentation of coronary arteries, with particular enhancement in delineating small coronary artery segments.

Prognostic effect of the TyG index on patients with severe aortic stenosis following transcatheter aortic valve replacement: a retrospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index, as a reliable marker of insulin resistance, is associated with the incidence and poor prognosis of various cardiovascular diseases. However, the relationship between the TyG index and clinical outcomes in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) remains unclear. METHODS: This study consecutively enrolled 1569 patients with AS underwent TAVR at West China Hospital of Sichuan University between April 2014 and August 2023. The outcomes of interest included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Multivariate adjusted Cox regression and restricted cubic splines (RCS) regression analyses were used to assess the associations between the TyG index and the clinical outcomes. The incremental prognostic value of the TyG index was further assessed by the time-dependent Harrell's C-index, integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: During a median follow-up of 1.09 years, there were 146, 70, and 196 patients experienced all-cause death, cardiovascular death, and MACE, respectively. After fully adjusting for confounders, a per-unit increase of TyG index was associated with a 441% (adjusted HR: 5.41, 95% CI: 4.01-7.32), 385% (adjusted HR: 4.85, 95% CI: 3.16-7.43), and 347% (adjusted HR: 4.47, 95% CI: 3.42-5.85) higher risk of all-cause mortality, cardiovascular mortality and MACE, respectively. The RCS regression analyses revealed a linear association between TyG index and endpoints (all P for non-linearity > 0.05) with 8.40 as the optimal binary cutoff point. Furthermore, adding TyG index to the basic risk model provided a significant incremental value in predicting poor prognosis (Time-dependent Harrell's C-index increased for all the endpoints; All-cause mortality, IDI: 0.11, P < 0.001; NRI: 0.32, P < 0.001; Cardiovascular mortality, IDI: 0.043, P < 0.001; NRI: 0.37, P < 0.001; MACE, IDI: 0.092, P < 0.001; NRI: 0.32, P < 0.001). CONCLUSIONS: In patients with severe AS receiving TAVR, there was a positive linear relationship between TyG index and poor prognosis, with 8.4 as the optimal bivariate cutoff value. Our findings suggest TyG index holds potential value for risk stratification and guiding therapeutic decisions in patients after TAVR.

SPL50 Regulates Cell Death and Resistance to Magnaporthe Oryzae in Rice.

BACKGROUND: The identification of spotted leaf 50 (spl50), a novel lesion mimic mutant (LMM) in rice, provides critical insights into the mechanisms underlying programmed cell death (PCD) and innate immunity in plants. RESULTS: Based on ethyl methane sulfonate (EMS)-induced mutagenesis, the spl50 mutant mimics hypersensitive responses in the absence of pathogen by displaying spontaneous necrotic lesions after the tillering phase. SPL50, an ARM repeat protein essential for controlling reactive oxygen species (ROS) metabolism and boosting resistance to blast disease, was identified by map-based cloning techniques. This work also demonstrates the detrimental effects of spl50 on photosynthetic efficiency and chloroplast development. The crucial significance of SPL50 in cellular signaling and stress response is shown by its localization to the cytoplasm and constitutive expression in various plant tissues. In light of growing concerns regarding global food security, this study highlights the pivotal role of SPL50 in regulating programmed cell death (PCD) and enhancing the immune response in plants, contributing to strategies for improving crop disease resistance. CONCLUSIONS: The novel identification of the SPL50 gene in rice, encoding an ARM repeat protein, reveals its pivotal role in regulating PCD and innate immune responses independently of pathogen attack.

Acupuncture for senile insomnia: A systematic review of acupuncture point.

OBJECTIVE: Insomnia is one of the most common diseases among the elderly. The elderly with long-term insomnia are more likely to have symptoms such as vertigo, fatigue, and immunity decline. Acupuncture is increasingly being used to treat insomnia. The purpose of this review is to summarize the critical acupoints in the treatment of senile insomnia and evaluate the effectiveness of the treatment. To provide a research basis for acupuncture treatment of senile insomnia in the future. METHODS: We will search the clinical studies on acupuncture in the treatment of senile insomnia published by CNKI (China National Knowledge Infrastructure), Wanfang (Wan Fang Data Knowledge Service Platform), CSTJ (China Science and Technology Journal Database), Pubmed, and ScienceDirect before December 31, 2023. Acupoint will be analyzed using TCMISS (TCM Inheritance Assistance Platform). RESULTS: 265 literatures were retrieved, and 94 were selected as the criteria. The results showed that there were 90 acupoints related to treatment. The acupoints with the highest frequency were shenmen (HT7), sanyinjiao (SP6), baihui (GV20), zusanli (ST36), neiguan (PC6), xinshu (BL15), taixi (KI3), and sishencong (EX-HN1) anmian (JLSXX-QX), shenshu (BL23). The most frequently used meridians were bladder meridian (BL), governor vessel (GV), and stomach meridian (ST). They were mainly distributed in the lower limbs and head. The most frequent specific points are the five transport points and source points. The most frequently used combinations are "shenmen (HT7) - sanyinjiao (SP6)", "shenmen (HT7) - baihui (GV20)", and "shenmen (HT7) - neiguan (PC6)". Association rule analysis showed that the acupoints with the highest confidence were shenmen (HT7), neiguan (PC6), and sanyinjiao (SP6). Network topology analysis showed that sanyinjiao (SP6), zusanli (ST36), and shenmen (HT7) were the core acupuncture points for the treatment of senile insomnia. CONCLUSION: The primary Acupuncture acupoints for senile insomnia are shenmen (HT7), sanyinjiao (SP6), baihui (GV20), zusanli (ST36), and neiguan (PC6), indicating that these acupoints have a strong correlation with senile insomnia. Sanyinjiao (SP6), zusanli (ST36), and shenmen (HT7) may be the core acupuncture acupoints for the treatment of senile insomnia.