Iridium-catalyzed reduction of o-hydroxyl phenyl enaminones for the synthesis of propiophenones and their application in 3-methyl chromone synthesis.

A method of reducing o-hydroxyphenyl enaminones with silane as the reductant to provide o-hydroxyl propiophenones has been achieved with iridium catalysis. The reduction reactions were found to proceed via the assistance of the hydroxyl group in the phenyl ring. In addition, the o-hydroxyl propiophenone products were used for the easy synthesis of 3-methyl chromones by directly incorporating N,N-dimethyl formamide dimethyl acetal (DMF-DMA) without using any catalyst.

Relationship between TIGIT expression on T cells and the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. METHODS: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. RESULTS: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. CONCLUSIONS: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

Correction: The Untranslated Regions of Classic Swine Fever Virus RNA Trigger Apoptosis.

[This corrects the article DOI: 10.1371/journal.pone.0088863.].

Inclisiran Treatment for Cardiovascular Disease Risk Reduction: A Systematic Review and Meta-Analysis.

This study was a meta-analysis of patient data to investigate the therapeutic effects of inclisiran on LDL-C, PCSK9, and TC in patients with atherosclerosis. Authors searched the Cochrane Library, Pubmed, EMBASE, and Web of Science databases for randomised controlled trials. Data of 4,731 subjects from five randomised clinical trials were included in this analysis. Patients treated with the PCSK9 inhibitor inclisiran had significantly lower LDL-C levels than those treated with placebo or a statin (mean difference (MD) -1.477; 95% CI -1.551 to -1.403; p <0.001; I2 = 7.2%). The average level of PCSK9 was also relatively lower ((MD) -2.579; 95% CI -2.694 to -2.464; p <0.001; I2 = 36%). They exhibited significant reductions in total cholesterol protein levels ((MD) -1.477; 95% CI -1.585 to -1.369; p <0.001; I2 = 46.7%). Inclisiran reduced LDL-C and PCSK9 levels as well as TC and Apo B levels significantly in patients with atherosclerotic cardiovascular disease (ASCVD). Key Words: Inclisiran, Low-density lipoprotein cholesterol, Atherosclerosis, Adverse events, Meta-analysis.

Therapeutic potential of Cordyceps sinensis targeting oxidative stress and inflammatory response in the treatment of COPD rats: insights from metabolomics analysis.

This study aimed to investigate the effects of wild Cordyceps sinensis on chronic obstructive pulmonary disease (COPD) rats through metabolomics approach, combined with biochemical parameters evaluations. Consequently, C. sinensis exhibited regulatory effects on the lung's metabolic profiles in COPD rats. Treatment with C. sinensis potentially modulated glycerophospholipid metabolism, glutathione metabolism, and tryptophan metabolism, thereby alleviating oxidative stress (by decreasing MDA and GSSG, while increasing SOD and GSH) and inflammatory response (by inhibiting TNF-α, IL-8, and MMP-9) in COPD rats while improving lung tissue damage.

Development of an emergency science popularization capacity index system for nurses in China-A Delphi study.

AIM: To construct a popularization of an emergency science capacity index system for nurses based on the iceberg model. DESIGN: A mixed-method research design incorporating quantitative and qualitative components was used. METHODS: In this study, the first draft of the questionnaire was developed through literature analysis and semi-structured interviews. According to the Delphi expert inclusion criteria, 20 experts with rich experience in the field of science popularization were selected, and the system of emergency science popularization ability of nurses was ultimately developed through two rounds of consultation according to the Delphi method. The weights of various indicators were determined through hierarchical analysis. RESULTS: Following two rounds of Delphi surveys, a total of 3 primary, 6 secondary, and 26 tertiary indicators were identified. The indicators were found to be highly significant, with variation coefficients ranging from 0.063 to 0.140. The Kendall's harmonization coefficients for the primary, secondary, and tertiary indicators were 0.350, 0.341, and 0.146, respectively. The popularization of the emergency science capacity system has a certain scientific and practical significance, which is of guidance to the competency of nurses in public health emergencies. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. This study did not involve patients, service users, caregivers, or members of the public.

18F-FDG PET/CT metrics-based stratification of large B-cell lymphoma receiving CAR-T cell therapy: immunosuppressive tumor microenvironment as a negative prognostic indicator in patients with high tumor burden.

Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27-176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax) < 6 cm (N = 60) at screening stage showed significantly higher 3-month complete response rate (85.0% vs. 33.3%, P < 0.001), progression-free survival (HR 0.17; 95% CI 0.08-0.35, P < 0.001) and overall survival (HR 0.18; 95% CI 0.08-0.40, P < 0.001) than those with Dmax ≥ 6 cm (N = 30). Besides, at the screening stage, Dmax combined with extranodal involvement was more efficient in distinguishing patient outcomes. The best cut-off values for total metabolic tumor volume (tMTV) and total lesion glycolysis (tTLG) at the screening stage were 50cm3 and 500 g, respectively. A prediction model combining maximum standardized uptake value (SUVmax) at 1 month after CAR-T cell therapy (M1) and tTLG clearance rate was established to predict early progression for partial response/stable disease patients evaluated at M1 after CAR-T cell therapy and validated in Lyon cohort. Relevant association of the distance separating the two farthest lesions, standardized by body surface area to the severity of neurotoxicity (AUC = 0.74; P = 0.034; 95% CI, 0.578-0.899) after CAR-T cell therapy was found in patients received axicabtagene ciloleucel. In patients with Dmax ≥ 6 cm, RNA-sequencing analysis conducted at the screening stage showed enrichment of immunosuppressive-related biological processes, as well as increased M2 macrophages, cancer-associated fibroblasts, myeloid-derived suppressor cells, and intermediate exhausted T cells. Collectively, immunosuppressive tumor microenvironment may serve as a negative prognostic indicator in patients with high tumor burden who respond poorly to CAR-T cell therapy.

Nerve growth factor promote VCAM-1-dependent monocyte adhesion and M2 polarization in osteosarcoma microenvironment: Implications for larotrectinib therapy.

Osteosarcoma is the most prevalent form of primary malignant bone tumor, primarily affecting children and adolescents. The nerve growth factors (NGF) referred to as neurotrophins have been associated with cancer-induced bone pain; however, the role of NGF in osteosarcoma has yet to be elucidated. In osteosarcoma samples from the Genomic Data Commons data portal, we detected higher levels of NGF and M2 macrophage markers, but not M1 macrophage markers. In cellular experiments, NGF-stimulated osteosarcoma conditional medium was shown to facilitate macrophage polarization from the M0 to the M2 phenotype. NGF also enhanced VCAM-1-dependent monocyte adhesion within the osteosarcoma microenvironment by down-regulating miR-513c-5p levels through the FAK and c-Src cascades. In in vivo xenograft models, the overexpression of NGF was shown to enhance tumor growth, while the oral administration of the TrK inhibitor larotrectinib markedly antagonized NGF-promoted M2 macrophage expression and tumor progression. These results suggest that larotrectinib could potentially be used as a therapeutic agent aimed at mitigating NGF-mediated osteosarcoma progression.

d-Orbital Induced Electronic Structure Reconfiguration toward Manipulating Electron Transfer Pathways of Metallo-Porphyrin for Enhanced AlCl2 + Storage.

The positive electrodes of non-aqueous aluminum ion batteries (AIBs) frequently encounter significant issues, for instance, low capacity in graphite (mechanism: anion de/intercalation and large electrode deformation induced) and poor stability in inorganic positive electrodes (mechanism: multi-electron redox reaction and dissolution of active materials induced). Here, metallo-porphyrin compounds (employed Fe2+, Co2+, Ni2+, Cu2+, and Zn2+ as the ion centers) are introduced to effectively enhance both the cycling stability and reversible capacity due to the formation of stable conjugated metal-organic coordination and presence of axially coordinated active sites, respectively. With the regulation of electronic energy levels, the d-orbitals in the redox reactions and electron transfer pathways can be rearranged. The 5,10,15,20-tetraphenyl-21H,23H-porphine nickle(II) (NiTPP) presents the highest specific capacity (177.1 mAh g-1), with an increment of 32.1% and 77.1% in comparison with the capacities of H2TPP and graphite, respectively, which offers a new route for developing high-capacity positive electrodes for stable AIBs.

The Vectorcardiogram Characteristic and Its Predictive Value for Reduced Left Ventricular Ejection Fraction of Children with Duchenne Muscular Dystrophy.

Background: The prognosis of Duchenne muscular dystrophy (DMD) is poor once it develops to the stage of cardiac impairment. Recent studies have demonstrated that electrocardiogram (ECG), which consists of general ECG and vectorcardiogram (VCG), retains an extremely powerful role in the assessment of patients with reduced left ventricular (LV) systolic dysfunction. However, data regarding VCG recordings in DMD and its prognostic value for reduced left ventricular ejection fraction (LVEF) of DMD have never been reported. This study aims to describe the characteristics of VCG in children with DMD and to explore the predictive value of VCG for reduced LVEF in children with DMD. Methods: A total of 306 patients with a known diagnosis of DMD confirmed by the genetic test were retrospectively enrolled at our hospital between August 2018 and August 2022. This resulted in a total study group of 486 VCG recordings. Among them, 75 DMD patients who underwent cardiac magnetic resonance (CMR) later after one year follow-up were prospectively enrolled. The trend of VCG parameters of DMD patients across the different age span were compared with age-matched normal children. Concordance statistic analysis was further performed to assess the validity of VCG parameters in predicting the occurrence of reduced LVEF in patients with DMD. Results: DMD patients have a significantly higher heart rate, R waves in V1, QRS loop percentage in the right anterior quadrant in the horizontal plane (horizontal quadrant II) and QRS loop percentage in the anterior superior quadrant in the sagittal plane (sagittal quadrant IV) than normal children. Concordance statistic (C-statistic) showed an area under the curve of quadrant IV in the sagittal plane of baseline was 0.704. The receiver operating characteristic (ROC) curve shows that quadrant IV in the sagittal plane of 7.57% was the optimal cutoff with a sensitivity of 53.3% and a specificity of 88.3% for predicting reduced LVEF in DMD patients. Conclusions: Our study firstly showed that QRS loop percentage in the right anterior quadrant in the horizontal plane (horizontal quadrant II) and QRS loop percentage in the anterior superior quadrant in the sagittal plane (sagittal quadrant IV) could be abnormal in DMD boys as early as before 5 years old. Evaluation of the myocardium by VCG in the early age to predict possible cardiac systolic dysfunction may have important implications for the ongoing management of DMD boys.

Diagnosis of periprosthesis joint infection and selection of replantation timing: A novel nomogram diagnosis model.

Preoperative diagnosis of periprosthetic joint infection (PJI) is critical to guide treatment options and improve patient outcomes. In this letter, we discuss results from our experiences with a novel nomogram diagnosis model based on serum and synovial fluid indicators for the preoperative diagnosis of PJI. The results showed that the novel nomogram diagnosis model can distinguish PJI from aseptic loosening before the operation. And it is also a useful candidate for the selection of the timing of current secondary revision.

Machine Learning to Enhance Electronic Detection of Diagnostic Errors.

This cohort study examines whether machine learning (ML) can enhance the ability of electronic triggers to identify possible missed opportunities in diagnosis.

The Risk of Deep Vein Thrombosis and Optimal Timing of Breast Cancer Surgery After COVID-19 Infection.

PURPOSE: The aim of this study was to assess the risk of postoperative deep vein thrombosis (DVT) in breast cancer patients with coronavirus disease 2019 (COVID-19) to determine the optimal timing for surgery in the era of "post COVID-19 pandemic." METHODS: This prospective study included breast cancer patients who contracted COVID-19 and underwent surgery from December 20th, 2022, to March 20th, 2023 (n = 577). A control group comprised patients who underwent surgery from May 1st, 2019, to October 1st, 2019 (n = 327) and had not contracted COVID-19 prior to surgery. Patients were categorized based on the timing of their surgery relative to their COVID-19 infection. Data were analyzed using logistic regression. RESULTS: Patients with COVID-19 had a higher incidence of postoperative DVT compared to those without COVID-19 (3.64% vs. 1.21%). Multivariable logistic regression analysis indicated that the timing of surgery was significantly associated with the risk of DVT (odds ratio [OR], 2.795; 95% confidence interval [CI], 0.692-11.278; p = 0.024). Patients who underwent surgery within two weeks of COVID-19 infection experienced the highest DVT rates (OR, 10.556; 95% CI, 1.095-303.313; p = 0.003). However, the incidence decreased to 2.85% when surgery was delayed until two weeks or more after infection. The median follow-up period was 10 months, all patients with DVT after surgery were recovered without serious complications or death. There were no adverse effects on subsequent anti-tumor therapy. CONCLUSION: Caution is advised when performing breast cancer surgery within two weeks after a COVID-19 infection. Although the risk of DVT remains somewhat elevated even after two weeks, surgery can be considered safe given the urgency of treatment, favorable complication outcomes, and lack of impact on subsequent adjuvant therapy.

TACE Combined with Portal Vein Tumor Thrombus 125I Seed Implantation in the Treatment of HCC with Hepatic Arterioportal Shunts.

Background and Objectives: Transarterial chemoembolization (TACE) and 125I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125I seed implantation in the treatment of HCC patients with APS. Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed. Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients' 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (P=0.02). Conclusion: For HCC patients with PVTT and APS, TACE combine with 125I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.

Effect of Repetitive Pitching on the Control of Lower Extremity Joints and Center of Mass in Collegiate Baseball Pitchers.

BACKGROUND: Repetitive motion can alter joint angles and subsequently affect the control of the center of mass (CoM). While the CoM has been studied as a fatigue indicator in various sports, the control of the whole-body CoM during repetitive pitching in baseball pitchers has not been examined. This study aimed to investigate changes in lower-extremity joint angles and CoM control in collegiate baseball pitchers after repetitive pitching. HYPOTHESIS: Baseball pitchers would exhibit significant increase in lower-extremity flexion angles, CoM position, and CoM variability after repetitive pitching. STUDY DESIGN: Descriptive laboratory study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 23 pitchers from the Collegiate Baseball League were recruited. A motion analysis system was employed to assess lower-extremity joint angles and CoM position during the simulated game, while pitching accuracy and velocity were also recorded. RESULTS: The results revealed a significant forward and downward shift in CoM position (P < 0.05), along with increased CoM variability in all directions (P < 0.05) after the simulated game. Furthermore, there was a significant increase in flexion angles of the knee and hip (P < 0.05); however, pitching velocity and accuracy did not demonstrate significant changes. CONCLUSION: Repetitive pitching leads to kinematic changes that should be monitored to prevent sports injuries. CLINICAL RELEVANCE: Baseball pitchers have the ability to modify the control of their CoM and angles of their lower-extremity joints to sustain their pitching performance. It is crucial to monitor compensatory strategies closely to avoid shoulder and elbow injuries among these pitchers.

Robust symbol detection for single-carrier underwater acoustic communication in impulsive noise environment.

This paper addresses robust underwater acoustic communication in the presence of impulsive noise. We propose a single-carrier iterative symbol detection method, which combines variational Bayesian inference (VBI) and vector approximate message passing (VAMP) for impulsive noise cancellation. Unlike existing methods, we model the measurements as a combination of two components: clean data without impulsive noise and impulse-noise-induced outliers. A set of binary indicator variables is used to identify outliers automatically. Under the proposed mixed model, we derive a VBI-based symbol detection method that can alternatively detect communication symbols and impulsive noise, and compensate for the impulsive noise when detecting communication symbols. To further improve detection performance, we integrate the VAMP into the VBI framework for communication symbols detection. Additionally, to reduce the overall complexity of the communication system, we propose a channel estimation method based on damped generalized approximate message passing. Simulation and experimental results show that the proposed detection method outperforms existing methods in terms of robustness and bit error rate.

Spin Manipulation of Heterogeneous Molecular Electrocatalysts by an Integrated Magnetic Field for Efficient Oxygen Redox Reactions.

Understanding the spin-dependent activity of nitrogen-coordinated single metal atom (M-N-C) electrocatalysts for oxygen reduction and evolution reactions (ORR and OER) remains challenging due to the lack of structure-defined catalysts and effective spin manipulation tools. Herein, both challenges using a magnetic field integrated heterogeneous molecular electrocatalyst prepared by anchoring cobalt phthalocyanine (CoPc) deposited carbon black on polymer-protected magnet nanoparticles, are addressed. The built-in magnetic field can shift the Co center from low- to high-spin (HS) state without atomic structure modification, affording one-order higher turnover frequency, a 50% increased H2O2 selectivity for ORR, and a ≈4000% magnetocurrent enhancement for OER. This catalyst can significantly minimize magnet usage, enabling safe and continuous production of a pure H2O2 solution for 100 h from a 100 cm2 electrolyzer. The new strategy demonstrated here also applies to other metal phthalocyanine-based catalysts, offering a universal platform for studying spin-related electrochemical processes.

Population genomics uncovers global distribution, antimicrobial resistance, and virulence genes of the opportunistic pathogen Klebsiella aerogenes.

Klebsiella aerogenes is an understudied and clinically important pathogen. We therefore investigate its population structure by genome analysis aligned with metadata. We sequence 130 non-duplicated K. aerogenes clinical isolates and identify two inter-patient transmission events. We then retrieve all publicly available K. aerogenes genomes (n = 1,026, accessed by January 1, 2023) and analyze them with our 130 genomes. We develop a core-genome multi-locus sequence-typing scheme. We find that K. aerogenes is a species complex comprising four phylogroups undergoing evolutionary divergence, likely forming three species. We delineate remarkable clonal diversity and identify three worldwide-distributed carbapenemase-encoding clonal clusters, representing high-risk lineages. We uncover that K. aerogenes has an open genome equipped by a large arsenal of antimicrobial resistance genes. We identify two genetic regions specific for K. aerogenes, encoding a type VI secretion system and flagella/chemotaxis for motility, respectively, both contributing to the virulence. These results provide much-needed insights into the population structure and pan-genomes of K. aerogenes.

Post-hoc analysis of clinicopathological factors affecting lateral lymph node metastasis based on STELLAR study for rectal cancer.

PURPOSE: In post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). METHODS: LPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. RESULTS: Among 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. CONCLUSIONS: LPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.