Complete chloroplast genomes of the hemiparasitic genus Cymbaria: Insights into comparative analysis, development of molecular markers, and phylogenetic relationships.

The hemiparasitic tribe Cymbarieae (Orobanchaceae) plays a crucial role in elucidating the initial stage of the transition from autotrophism to heterotrophism. However, the complete chloroplast genome of the type genus Cymbaria has yet to be reported. In addition, the traditional Mongolian medicine Cymbaria daurica is frequently subjected to adulteration or substitution because of the minor morphological differences with Cymbaria mongolica. In this study, the complete chloroplast genomes of the two Cymbaria species were assembled and annotated, and those of other published 52 Orobanchaceae species were retrieved for comparative analyses. We found that the Cymbaria chloroplast genomes are characterized by pseudogenization or loss of stress-relevant genes (ndh) and a unique rbcL-matK inversion. Unlike the high variability observed in holoparasites, Cymbaria and other hemiparasites exhibit high similarity to autotrophs in genome size, guanine-cytosine (GC) content, and intact genes. Notably, four pairs of specific DNA barcodes were developed and validated to distinguish the medicinal herb from its adulterants. Phylogenetic analyses revealed that the genus Cymbaria and the Schwalbea-Siphonostegia clade are grouped into the tribe Cymbarieae, which forms a sister clade to the remaining Orobanchaceae parasitic lineages. Moreover, the diversification of monophyletic Cymbaria occurred during the late Miocene (6.72 Mya) in the Mongol-Chinese steppe region. Our findings provide valuable genetic resources for studying the phylogeny of Orobanchaceae and plant parasitism, and genetic tools to validate the authenticity of the traditional Mongolian medicine "Xinba.".

A coronary CT angiography-derived myocardial radiomics model for predicting adverse outcomes in chronic myocardial infarction.

BACKGROUND: The prognostic efficacy of a coronary computed tomography angiography (CCTA)-derived myocardial radiomics model in patients with chronic myocardial infarction (MI) is unclear. METHODS: In this retrospective study, a cohort of 236 patients with chronic MI who underwent both CCTA and cardiac magnetic resonance (CMR) examinations within 30 days were enrolled and randomly divided into training and testing datasets at a ratio of 7:3. The clinical endpoints were major adverse cardiovascular events (MACE), defined as all-cause death, myocardial reinfarction and heart failure hospitalization. The entire three-dimensional left ventricular myocardium on CCTA images was segmented as the volume of interest for the extraction of radiomics features. Five models, namely the clinical model, CMR model, clinical+CMR model, CCTA-radiomics model, and clinical+CCTA-radiomics model, were constructed using multivariate Cox regression. The prognostic performances of these models were evaluated through receiver operating characteristic curve analysis and the index of concordance (C-index). RESULTS: Fifty-one (20.16%) patients experienced MACE during a median follow-up of 1439.5 days. The predictive performance of the CCTA-radiomics model surpassed that of the clinical model, CMR model, and clinical+CMR model in both the training (area under the curve (AUC) of 0.904 vs. 0.691, 0.764, 0.785; C-index of 0.88 vs. 0.71, 0.75, 0.76, all p values <0.001) and testing (AUC of 0.893 vs. 0.704, 0.851, 0.888; C-index of 0.86 vs. 0.73, 0.85, 0.85, all p values <0.05) datasets. CONCLUSIONS: The CCTA-based myocardial radiomics model is a valuable tool for predicting adverse outcomes in chronic MI, providing incremental value to conventional clinical and CMR parameters.

0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period.

BACKGROUND: 3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women. METHODS: We conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level. RESULTS: There was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed. CONCLUSIONS: Our study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period. CLINICAL TRIAL NUMBER AND REGISTRY URL: The registration number: ChiCTR2200065201; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 31/10/2022.

Enhancing the Stability of Metallic Li Anodes for Aprotic Li-O2 Batteries with Dual-Anion Electrolytes.

Despite the impressive specific capacity of Li-O2 batteries, challenges persist, particularly with lithium metal anode (LMA). These include dendritic growth and unstable solid electrolyte interface (SEI) layers, which become more pronounced in an oxygen-rich environment, a typical operation scenario for Li-O2 batteries. Herein, utilizing a hybrid dual anion electrolyte (DAE) strategy, which incorporates both inorganic LiNO3 and organic Li[(FSO2)(C2F5SO2)N] (LiFPFSI) salts, the dendritic growth is evidently inhibited by creating a "concrete-like" SEI structure. Simultaneously, it fosters the development of a fluorine-rich SEI layer. Consequently, a robust, compact, and stable barrier is formed, adeptly suppressing side reactions between LMA and the electrolyte, particularly those relevant to dissolved O2. The practicality and efficiency of this DAE strategy are validated across a variety of battery types including Li/Li, Li/Cu, and notably Li-O2 batteries, which showcased significantly improved reversibility and durability. These results underscore the important role of multifunctional salts in interphase engineering for LMA, which could lead to advancements in Li-O2 batteries.

ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma.

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

High-Entropy Catalysis Accelerating Stepwise Sulfur Redox Reactions for Lithium-Sulfur Batteries.

Catalysis is crucial to improve redox kinetics in lithium-sulfur (Li-S) batteries. However, conventional catalysts that consist of a single metal element are incapable of accelerating stepwise sulfur redox reactions which involve 16-electron transfer and multiple Li2Sn (n = 2-8) intermediate species. To enable fast kinetics of Li-S batteries, it is proposed to use high-entropy alloy (HEA) nanocatalysts, which are demonstrated effective to adsorb lithium polysulfides and accelerate their redox kinetics. The incorporation of multiple elements (Co, Ni, Fe, Pd, and V) within HEAs greatly enhances the catalytically active sites, which not only improves the rate capability, but also elevates the cycling stability of the assembled batteries. Consequently, HEA-catalyzed Li-S batteries achieve a high capacity up to 1364 mAh g-1 at 0.1 C and experience only a slight capacity fading rate of 0.054% per cycle over 1000 cycles at 2 C, while the assembled pouch cell achieves a high specific capacity of 1192 mAh g-1. The superior performance of Li-S batteries demonstrates the effectiveness of the HEA catalysts with maximized synergistic effect for accelerating S conversion reactions, which opens a way to catalytically improving stepwise electrochemical conversion reactions.

Comparison Between Sotorasib with Docetaxel for the Treatment of Chinese Patients with Previously Treated NSCLC with KRASG12C Mutation: A Cost-Effectiveness Analysis to Inform Drug Pricing.

INTRODUCTION: This study sought to investigate the affordable price of sotorasib among patients with previously treated advanced KRASG12C-mutant non-small cell lung cancer (NSCLC) through a cost-effectiveness analysis from the perspectives of both the Chinese healthcare system and the patients. METHODS: We developed a Markov model spanning a 20-year time horizon with a cycle length of 21 days. Our data were derived from the CodeBreaK 200 clinical trial, supplemented with published literature, publicly available national databases, and local hospitals. The primary outcomes were the affordable prices of sotorasib which would result in the incremental cost-effectiveness ratios (ICERs) of sotorasib relative to docetaxel below the preset willing-to-pay (WTP) threshold. Sensitivity analyses were performed to evaluate the model's robustness. RESULTS: At the national level, from the perspective of the Chinese healthcare system and patients, the price of sotorasib should be lower than US$0.04673 and $0.03231, respectively, to make it affordable, which is equivalent to $1346 and $931 per box (120 mg × 240 pieces). At the provincial level, the price ceiling of sotorasib/mg fluctuated between $0.04084 to $0.08061 from the Chinese healthcare system's perspective and between $0.02642 to $0.06620 from the patients' perspective. Probabilistic sensitivity analyses revealed that, as the price of sotorasib decreased, its likelihood of being cost-effective increased. CONCLUSION: Sotorasib might be a cost-effective therapy in China. The pharmaco-economic evidence generated from this study has significant implications not only for guiding the drug pricing of the upcoming sotorasib but also for determining the reimbursement ratio for its potential inclusion in the National Reimbursement Drugs List in the future.

Minor Spliceosomal 65K/RNPC3 Interacts with ANKRD11 and Mediates HDAC3-Regulated Histone Deacetylation and Transcription.

RNA splicing is crucial in the multilayer regulatory networks for gene expression, making functional interactions with DNA- and other RNA-processing machineries in the nucleus. However, these established couplings are all major spliceosome-related; whether the minor spliceosome is involved remains unclear. Here, through affinity purification using Drosophila lysates, an interaction is identified between the minor spliceosomal 65K/RNPC3 and ANKRD11, a cofactor of histone deacetylase 3 (HDAC3). Using a CRISPR/Cas9 system, Deletion strains are constructed and found that both Dm65KΔ/Δ and Dmankrd11Δ/Δ mutants have reduced histone deacetylation at Lys9 of histone H3 (H3K9) and Lys5 of histone H4 (H4K5) in their heads, exhibiting various neural-related defects. The 65K-ANKRD11 interaction is also conserved in human cells, and the HsANKRD11 middle-uncharacterized domain mediates Hs65K association with HDAC3. Cleavage under targets and tagmentation (CUT&Tag) assays revealed that HsANKRD11 is a bridging factor, which facilitates the synergistic common chromatin-binding of HDAC3 and Hs65K. Knockdown (KD) of HsANKRD11 simultaneously decreased their common binding, resulting in reduced deacetylation of nearby H3K9. Ultimately, this study demonstrates that expression changes of many genes caused by HsANKRD11-KD are due to the decreased common chromatin-binding of HDAC3 and Hs65K and subsequently reduced deacetylation of H3K9, illustrating a novel and conserved coupling mechanism that links the histone deacetylation with minor spliceosome for the regulation of gene expression.

Surgical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with ankylosing spondylitis.

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.

Histone methyltransferase MLL4 protects against pressure overload-induced heart failure via a THBS4-mediated protection in ER stress.

Pressure overload-induced pathological cardiac hypertrophy eventually leads to heart failure (HF). Unfortunately, lack of effective targeted therapies for HF remains a challenge in clinical management. Mixed-lineage leukemia 4 (MLL4) is a member of the SET family of histone methyltransferase enzymes, which possesses histone H3 lysine 4 (H3K4)-specific methyltransferase activity. However, whether and how MLL4 regulates cardiac function is not reported in adult HF. Here we report that MLL4 is required for endoplasmic reticulum (ER) stress homeostasis of cardiomyocytes and protective against pressure overload-induced cardiac hypertrophy and HF. We observed that MLL4 is increased in the heart tissue of HF mouse model and HF patients. The cardiomyocyte-specific deletion of Mll4 (Mll4-cKO) in mice leads to aggravated ER stress and cardiac dysfunction following pressure overloading. MLL4 knockdown neonatal rat cardiomyocytes (NRCMs) also display accelerated decompensated ER stress and hypertrophy induced by phenylephrine (PE). The combined analysis of Cleavage Under Targets and Tagmentation sequencing (CUT&Tag-seq) and RNA sequencing (RNA-seq) data reveals that, silencing of Mll4 alters the chromatin landscape for H3K4me1 modification and gene expression patterns in NRCMs. Interestingly, the deficiency of MLL4 results in a marked reduction of H3K4me1 and H3K27ac occupations on Thrombospondin-4 (Thbs4) gene loci, as well as Thbs4 gene expression. Mechanistically, MLL4 acts as a transcriptional activator of Thbs4 through mono-methylation of H3K4 and further regulates THBS4-dependent ER stress response, ultimately plays a role in HF. Our study indicates that pharmacologically targeting MLL4 and ER stress might be a valid therapeutic approach to protect against cardiac hypertrophy and HF.

Bioinspired Dopamine and N-Oxide-Based Zwitterionic Polymer Brushes for Fouling Resistance Surfaces.

Biofouling is a great challenge for engineering material in medical-, marine-, and pharmaceutical-related applications. In this study, a novel trimethylamine N-oxide (TMAO)-analog monomer, 3-(2-methylacrylamido)-N,N-dimethylpropylamine N-oxide (MADMPAO), was synthesized and applied for the grafting of poly(MADMPAO) (pMPAO) brushes on quartz crystal microbalance (QCM) chips by the combination of bio-inspired poly-dopamine (pDA) and surface-initiated atom transfer radical polymerization technology. The result of ion adsorption exhibited that a sequential pDA and pMPAO arrangement from the chip surface had different characteristics from a simple pDA layer. Ion adsorption on pMPAO-grafted chips was greatly inhibited at low salt concentrations of 1 and 10 mmol/L due to strong surface hydration in the presence of charged N+ and O- of zwitterionic pMPAO brushes on the outer layer on the chip surface, well known as the "anti-polyelectrolyte" effect. During BSA adsorption, pMPAO grafting also led to a marked decrease in frequency shift, indicating great inhibition of protein adsorption. It was attributed to weaker BSA-pMPAO interaction. In this study, the Au@pDA-4-pMPAO chip with the highest coating concentration of DA kept stable dissipation in BSA adsorption, signifying that the chip had a good antifouling property. The research provided a novel monomer for zwitterionic polymer and demonstrated the potential of pMPAO brushes in the development and modification of antifouling materials.

Metabolomics reveals the reasons for the occurrence of Pendulous-comb related to egg production performance.

The chicken comb is an essential secondary sexual characteristic to measure sexual maturity and is closely related to reproductive performance. Pendulous comb (PC) and upright comb (UC) are 2 common comb phenotypes in hens, which have been highly associated with egg production performance. However, the reasons for the formation of PC remain undetermined. In this study, we first characterized the PC and UC chicken at start (at 175 d age), peak (at 217 d age), and postlaying (at 300 d age) and found that PC and UC could transform for each other. Furthermore, we suggested that PC chicken demonstrated better egg production performance than UC chicken, especially characterizing comb type in the start-laying period. Moreover, we performed histological evaluation of PC and UC tissue, which suggested that the low density of collagen fibers and acid mucopolysaccharides might lead to the formation of PC. To further explore the possible reasons for PC formation, we performed an untargeted metabolomic analysis of serum between PC and UC chicken in the start, peak, and postlaying periods. The enrichment analysis of period-unique differentially expressed metabolites (DEMs) between PC and UC showed that the different metabolic pathways and nutritional levels might contribute to the formation of PC in the different laying periods. Our research provided critical insights into the phenotypic diversity of chicken comb, establishing a foundation for early selection of chicken egg production performance.

Quantification of trace heavy metals in environmental water, soil and atmospheric particulates with their bioaccessibility analysis.

In this work, sulfhydryl (SH) functionalized magnetic covalent organic framework (COF) was synthesized by using 4-aldehyde phenyl butadiyne (DEBD) and 1,3,5-tris(4-aminophenyl) benzene (TAPB) as the monomers and ethanedithiol as the modifier, with the aid of thiol-alkyne "click" reaction. The prepared Fe3O4@COFTAPB-DEBD@SH exhibited relatively strong magnetism (32.8 emu g-1), good stability and selectivity to target analytes with a high sulfhydryl content (0.24 mmol g-1). Based on Fe3O4@COFTAPB-DEBD@SH, a method combining magnetic solid phase extraction with inductively coupled plasma mass spectrometry (ICP-MS) was developed for the quantitative analysis of trace metals. Under the optimal conditions, the method merited fast desorption kinetics (<2 min), adsorption kinetics (<20 min), fast phase separation (<1 min), high enrichment factor (100), and the detection limits for Cd, Hg, Pb and Bi were determined to be 1.18, 0.51, 4.91 and 0.39 ng L-1, respectively. A good resistance to complex matrices was demonstrated for the method in the analysis of soil, atmospheric particles and simulated pulmonary fluids samples. Certified reference materials (coal fly ash GBW08401 and soil GBW07427) were employed to validate the accuracy of the method. Four target metals in the range of 12.9-215 ng L-1, 0.06-24.6 µg g-1 and 0.52-33.1 ng m-3 were found in local water, soil and atmospheric particulates (PM), respectively. Additionally, artificial lysosome solution and gamble's solution were used to simulate human pulmonary fluid and the bioaccessibility of Cd, Hg, Pb and Bi in PM2.5 was evaluated to be 58.6-73.1 % and 1.3-7.1 %, respectively.

Automated insulin delivery in children with type 1 diabetes during physical activity: a meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity. RESULTS: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I2=96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I2=94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I2>50 %). CONCLUSIONS: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia.

Perioperative Hypothermia in Elderly Patients During Pelvic Floor Reconstruction Surgery: An Observational Study.

INTRODUCTION AND HYPOTHESIS: The potential predictors of pelvic floor reconstruction surgery hypothermia remain unclear. This prospective cohort study was aimed at identifying these predictors and evaluating the outcomes associated with perioperative hypothermia. METHODS: Elderly patients undergoing pelvic floor reconstruction surgery were consecutively enrolled from April 2023 to September 2023. Perioperative temperature was measured at preoperative (T1), every 15 min after the start of anesthesia (T2), and 15 min postoperative (T3) using a temperature probe. Perioperative hypothermia was defined as a core temperature below 36°C at any point during the procedure. Multivariate logistic regression analysis was conducted to determine factors associated with perioperative hypothermia. RESULTS: A total of 229 patients were included in the study, with 50.7% experiencing hypothermia. Multivariate analysis revealed that the surgical method involving pelvic floor combined with laparoscopy, preoperative temperature < 36.5°C, anesthesia duration ≥ 120 min, and the high levels of anxiety were significantly associated with perioperative hypothermia. The predictive value of the multivariate model was 0.767 (95% CI, 0.706 to 0.828). CONCLUSIONS: This observational prospective study identified several predictive factors for perioperative hypothermia in elderly patients during pelvic floor reconstruction surgery. Strategies aimed at preventing perioperative hypothermia should target these factors. Further studies are required to assess the effectiveness of these strategies, specifically in elderly patients undergoing pelvic floor reconstruction surgery.

Association of stress hyperglycemia ratio with left ventricular function and microvascular obstruction in patients with ST-segment elevation myocardial infarction: a 3.0 T cardiac magnetic resonance study.

BACKGROUND: Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio (SHR). Impaired left ventricular function and microvascular obstruction (MVO) diagnosed using cardiac magnetic resonance (CMR) have also been proven to be linked to poor prognosis in patients with AMI and aid in risk stratification. However, there have been no studies on the correlation between fasting SHR and left ventricular function and MVO in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Therefore, this study aimed to investigate the additive effect of fasting SHR on left ventricular function and global deformation in patients with ASTEMI and to explore the association between fasting SHR and MVO. METHODS: Consecutive patients who underwent CMR at index admission (3-7 days) after primary percutaneous coronary intervention (PPCI) were enrolled in this study. Basic clinical, biochemical, and CMR data were obtained and compared among all patients grouped by fasting SHR tertiles: SHR1: SHR < 0.85; SHR2: 0.85 ≤ SHR < 1.01; and SHR3: SHR ≥ 1.01. Spearman's rho (r) was used to assess the relationship between fasting SHR and left ventricular function, myocardial strain, and the extent of MVO. Multivariable linear regression analysis was performed to evaluate the determinants of left ventricular function and myocardial strain impairment in all patients with AMI. Univariable and multivariable regression analyses were performed to investigate the correlation between fasting SHR and the presence and extent of MVO in patients with AMI and those with AMI and diabetes mellitus (DM). RESULTS: A total of 357 patients with ASTEMI were enrolled in this study. Left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI) were significantly lower in SHR2 and SHR3 than in SHR1. Compared with SHR1 and SHR2 groups, left ventricular strain was lower in SHR3, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strains. Fasting SHR were negatively correlated with LVEF, LVGFI, and GRS (r = - 0.252; r = - 0.261; and r = - 0.245; all P<0.001) and positively correlated with GCS (r = 0.221) and GLS (r = 0.249; all P <0.001). Multivariable linear regression analysis showed that fasting SHR was an independent determinant of impaired LVEF, LVGFI, GRS, and GLS. Furthermore, multivariable regression analysis after adjusting for covariates signified that fasting SHR was associated with the presence and extent of MVO in patients with AMI and those with AMI and DM. CONCLUSION: Fasting SHR in patients with ASTEMI successfully treated using PPCI is independently associated with impaired cardiac function and MVO. In patients with AMI and DM, fasting SHR is an independent determinant of the presence and extent of MVO.

Anticancer activity of 8-hydroxyquinoline-triphenylphosphine rhodium(III) complexes targeting mitophagy pathways.

Metallodrugs exhibiting distinct mechanisms of action compared with cisplatin hold promise for overcoming cisplatin resistance and improving the efficacy of anticancer drugs. In this study, a new series of rhodium (Rh)(III) complexes containing tris(triphenylphosphine)rhodium(I) chloride [(TPP)3RhCl] (TPP = triphenylphosphine, TPP=O = triphenylphosphine oxide) and 8-hydroxyquinoline derivatives (H-XR1-H-XR4), namely [Rh(XR1)2(TPP)Cl]·(TPP=O) (Yulin Normal University-1a [YNU-1a]), [Rh(XR2)2(TPP)Cl] (YNU-1b), [Rh(XR3)2(TPP)Cl] (YNU-1c), and [Rh(XR4)2(TPP)Cl] (YNU-1d), was synthesized and characterized via X-ray diffraction, mass spectrometry and IR. The cytotoxicity of the compounds YNU-1a-YNU-1d in Hep-G2 and HCC1806 human cancer cell lines and normal HL-7702 cell line was evaluated. YNU-1c exhibited cytotoxicity and selectivity in HCC1806 cells (IC50 = 0.13 ± 0.06 µM, selectivity factor (SF) = 384.6). The compounds YNU-1b and YNU-1c, which were selected for mechanistic studies, induced the activation of apoptotic pathways and mitophagy. In addition, these compounds released cytochrome c, cleaved caspase-3/pro-caspase-3 and downregulated the levels of mitochondrial respiratory chain complexes I/IV (M1 and M4) and ATP. The compound YNU-1c, which was selected for in vivo experiments, exhibited tumor growth inhibition (58.9 %). Importantly, hematoxylin and eosin staining and TUNEL revealed that HCC1806 tumor tissues exhibited significant apoptotic characteristics. YNU-1a-YNU-1d compounds are promising drug candidates that can be used to overcome cisplatin resistance.

Clinical analysis and literature review of two paediatric cases of anti-IgLON5 antibody-related encephalitis.

Introduction: Anti-IgLON5 antibody-related encephalitis is a rare autoimmune disorder of the central nervous system, predominantly occurring in middle-aged elderly individuals, with paediatric cases being exceptionally rare. This study aims to enhance the understanding of paediatric anti-IgLON5 antibody-related encephalitis by summarising its clinical and therapeutic characteristics. Method: A retrospective analysis was conducted on two paediatric patients diagnosed with anti-IgLON5 antibody-related encephalitis at Hunan Children's Hospital from August 2022 to November 2023. This involved reviewing their medical records and follow-up data, in addition to a literature review. Results: The study involved two patients, one male and one female, aged between 2.5 and 9.6 years, both presenting with an acute/subacute course of illness. Clinically, both exhibited movement disorders (including dystonia, involuntary movements, and ataxia), cognitive impairments, sleep disturbances, and psychiatric symptoms. Patient 1 experienced epileptic seizures, while Patient 2 exhibited brainstem symptoms and abnormal eye movements. Neither patient showed autonomic dysfunction. Patient 1 had normal cerebrospinal fluid (CSF) and Brain MRI findings, whereas Patient 2 showed moderate leukocytosis and mild protein elevation in the CSF, and Brain MRI revealed symmetrical lesions in the basal ganglia and cerebellum. Oligoclonal bands in the CSF were positive in both cases. Both patients tested negative for HLA-DQB*05:01 and HLA-DRB*10:01. They received both first-line and second-line immunotherapies, with Patient 2 showing a poor response to treatment. Discussion: Paediatric cases of anti-IgLON5 antibody-related encephalitis similarly present sleep disturbances as a core symptom, alongside various forms of movement disorders. Immunotherapy is partially effective. Compared to adult patients, these paediatric cases tend to exhibit more pronounced psychiatric symptoms, a more rapid onset, and more evident inflammatory changes in the CSF. The condition appears to have a limited association with HLA-DQB*05:01 and HLA-DRB*10:01 polymorphisms.

A Self-supervised Learning-Based Fine-Grained Classification Model for Distinguishing Malignant From Benign Subcentimeter Solid Pulmonary Nodules.

RATIONALE AND OBJECTIVES: Diagnosing subcentimeter solid pulmonary nodules (SSPNs) remains challenging in clinical practice. Deep learning may perform better than conventional methods in differentiating benign and malignant pulmonary nodules. This study aimed to develop and validate a model for differentiating malignant and benign SSPNs using CT images. MATERIALS AND METHODS: This retrospective study included consecutive patients with SSPNs detected between January 2015 and October 2021 as an internal dataset. Malignancy was confirmed pathologically; benignity was confirmed pathologically or via follow-up evaluations. The SSPNs were segmented manually. A self-supervision pre-training-based fine-grained network was developed for predicting SSPN malignancy. The pre-trained model was established using data from the National Lung Screening Trial, Lung Nodule Analysis 2016, and a database of 5478 pulmonary nodules from the previous study, with subsequent fine-tuning using the internal dataset. The model's efficacy was investigated using an external cohort from another center, and its accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. RESULTS: Overall, 1276 patients (mean age, 56 ± 10 years; 497 males) with 1389 SSPNs (mean diameter, 7.5 ± 2.0 mm; 625 benign) were enrolled. The internal dataset was specifically enriched for malignancy. The model's performance in the internal testing set (316 SSPNs) was: AUC, 0.964 (95% confidence interval (95%CI): 0.942-0.986); accuracy, 0.934; sensitivity, 0.965; and specificity, 0.908. The model's performance in the external test set (202 SSPNs) was: AUC, 0.945 (95% CI: 0.910-0.979); accuracy, 0.911; sensitivity, 0.977; and specificity, 0.860. CONCLUSION: This deep learning model was robust and exhibited good performance in predicting the malignancy of SSPNs, which could help optimize patient management.

Online sequential analysis of volatile and semivolatile organic compounds in water matrices by double robotic sample preparations and dual-channel mono and comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry system.

The monitoring of organic compounds in aquatic matrices poses challenges due to its complexity and time-intensive nature. To address these challenges, we introduce a novel approach utilizing a dual-channel mono (1D) and comprehensive two-dimensional (2D) gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS) system, integrated with a robotic pretreatment platform, for online monitoring of both volatile organic compounds (VOCs) and semivolatile organic compounds (SVOCs) in water matrices. Employing the robotic platform, we establish a suite of online liquid-liquid extraction (LLE) pretreatment processes for water samples, marking the first instance of such procedures. Leveraging the automatic headspace (HS) module, dual robotic preparations of HS and LLE are sequentially executed to extract VOCs and SVOCs from water matrices. The GC × GC-TOFMS system is distinguished by its dual-channel analytical column configuration, facilitating sequential analysis of VOCs in GC-TOFMS mode and SVOCs in GC × GC-TOFMS mode. Quantitative detection of 55 target VOCs and 104 SVOCs is achieved in a water sample using the instrument system. Our method demonstrates excellent correlation coefficients ranging from 0.990 to 1.000, method detection limits ranging from 0.08 to 4.78 µg L-1, relative standard deviations below 19.3 %, and recovery rates ranging from 50.0 % to 124.0 %. To validate the online monitoring capabilities of our system, we assess target SVOCs at three different concentration levels over a 3-day period. Most compounds exhibit recovery rates ranging from 70.0 % to 130.0 %. Furthermore, we apply our method to analyze a real water sample, successfully identifying over 100 target and nontarget VOCs/SVOCs, including alcohols, aldehydes, ketones, acids, esters, and phenols. These results highlight the efficacy of the proposed analysis system, capable of conducting two distinct analyses in automatic sequence, thereby enhancing the efficiency and accuracy of organic compound analysis in water matrices.