Anti-aging effects of medicinal plants and their rapid screening using the nematode Caenorhabditis elegans.

BACKGROUND: Aging is the primary risk factor of most chronic diseases in humans, including cardiovascular diseases, osteoporosis and neurodegenerative diseases, which extensively damage the quality of life for elderly individuals. Aging is a multifaceted process with numerous factors affecting it. Efficient model organisms are essential for the research and development of anti-aging agents, particularly when investigating pharmacological mechanisms are needed. PURPOSE: This review discusses the application of Caenorhabditis elegans for studying aging and its related signaling pathways, and presents an overview of studies exploring the mechanism and screening of anti-aging agents in C. elegans. Additionally, the review summarizes related clinical trials of anti-aging agents to inspire the development of new medications. METHOD: Literature was searched, analyzed, and collected using PubMed, Web of Science, and Science Direct. The search terms used were "anti-aging", "medicinal plants", "synthetic compounds", "C. elegans", "signal pathway", etc. Several combinations of these keywords were used. Studies conducted in C. elegans or humans were included. Articles were excluded, if they were on studies conducted in silico or in vitro or could not offer effective data. RESULTS: Four compounds mainly derived through synthesis (metformin, rapamycin, nicotinamide mononucleotide, alpha-ketoglutarate) and four active ingredients chiefly obtained from plants (resveratrol, quercetin, Astragalus polysaccharide, ginsenosides) are introduced emphatically. These compounds and active ingredients exhibit potential anti-aging effects in preclinical and clinical studies. The screening of these anti-aging agents and the investigation of their pharmacological mechanisms can benefit from the use of C. elegans. CONCLUSION: Medicinal plants provide valuable resource for the treatment of diseases. A wide source of raw materials for the particular plant medicinal compounds having anti-aging effects meet diverse pharmaceutical requirements, such as immunomodulatory, anti-inflammation and alleviating oxidative stress. C. elegans possesses advantages in scientific research including short life cycle, small size, easy maintenance, genetic tractability and conserved biological processes related to aging. C. elegans can be used for the efficient and rapid evaluation of compounds with the potential to slow down aging.

Clinical and genetic analysis of methylmalonic aciduria in 60 patients from Southern China: a single center retrospective study.

BACKGROUND: Methylmalonic aciduria (MMA) is a group of rare genetic metabolic disorders resulting from defects in methylmalonyl coenzyme A mutase (MCM) or intracellular cobalamin (cbl) metabolism. MMA patients show diverse clinical and genetic features across different subtypes and populations. METHODS: We retrospectively recruited 60 MMA patients from a single center and diagnosed them based on their clinical manifestations and biochemical assays. We then performed genetic analysis to confirm the diagnosis and identify the causal variants. RESULTS: We confirmed the common clinical manifestations of MMA reported previously. We also described four rare MMA cases with unusual symptoms or genetic variants, such as pulmonary hypertension or limb weakness in late-onset patients. We identified 15 MMACHC and 26 MMUT variants in 57 patients, including 6 novel MMUT variants. Two patients had only one MMAA variant each, and one patient had mild MMA due to mitochondrial DNA depletion syndrome caused by a SUCLA2 variant. Among 12 critically ill patients, isolated MMA was associated with higher C3, blood ammonia, and acidosis, while combined MMA was linked to hydrocephalus on skull MRI. MMACHC c.658-660delAAG and MMUT c.1280G > A variants were correlated with more severe phenotypes. CONCLUSIONS: Our study demonstrates the clinical and genotypic heterogeneity of MMA patients and indicates that metabolic screening and genetic analysis are useful tools to identify rare cases.

Colon cancer inhibitory properties of Caulerpa lentillifera polysaccharide and its molecular mechanisms based on three-dimensional cell culture model.

Caulerpa lentillifera is rich in polysaccharides, and its polysaccharides show a significant effect in different biological activities including anti-cancer activity. As an edible algae-derived polysaccharide, exploring the role of colon cancer can better develop the application from a dietary therapy perspective. However, more in-depth studies of C. lentillifera polysaccharide on anti-colon cancer activity and mechanism are needed. In this study, we found that Caulerpa lentillifera polysaccharides (CLP) showed potential anti-colon cancer effect on human colon cancer cell HT29 in monolayer (IC50 = 1.954 mg/mL) and spheroid (IC50 = 0.402 mg/mL). Transcriptomics and metabolomics analyses revealed that CLP had an inhibitory effect on HT29 3D spheroid cells by activating aminoacyl-tRNA biosynthesis as well as arginine and proline metabolism pathways. Furthermore, the anti-colon cancer effects of CLP were confirmed through other human colon cancer cell HCT116 and LoVo in monolayer cells (IC50 = 1.890 mg/mL and 1.437 mg/mL, respectively) and 3D spheroid cells (IC50 = 0.344 mg/mL and 0.975 mg/mL, respectively), and three patient-derived organoids with IC50 values of 6.333-8.780 mg/mL. This study provided basic data for the potential application of CLP in adjuvant therapeutic food for colon cancer on multiple levels, while further investigation of detailed mechanism in vivo was still required.

Biotransformation of Bioactive Metabolites in Cassiae Semen by Endogenous Enzymes and Probiotics.

The present study evaluated the potential of endogenous enzymes and probiotics in transforming bioactive metabolites to reduce the purgative effect and improve the functional activity of Cassiae Semen and verified and revealed the biotransformation effect of endogenous enzymes. Although probiotics, especially Lactobacillus rhamnosus, exerted the transformation effect, the endogenous enzymes proved to be more effective in transforming the components of Cassiae Semen. After biotransformation by endogenous enzymes for 12 h, the levels of six anthraquinones in Cassiae Semen increased by at least 2.98-fold, and free anthraquinones, total phenolics, and antioxidant activity also showed significant improvement, accompanied by an 82.2% reduction in combined anthraquinones responsible for the purgative effect of Cassiae Semen. Further metabolomic analysis revealed that the biotransformation effect of endogenous enzymes on the bioactive metabolites of Cassiae Semen was complex and diverse, and the biotransformation of quinones and flavonoids was particularly prominent and occurred by three primary mechanisms, hydrolyzation, methylation, and dimerization, might under the action of glycosyl hydrolases, SAM-dependent methyltransferases, and CYP450s. Accordingly, biotransformation by endogenous enzymes emerges as a mild, economical, food safety risk-free, and effective strategy to modify Cassiae Semen into an excellent functional food.

High-Quality Spherical Silver Alloy Powder for Laser Powder Bed Fusion Using Plasma Rotating Electrode Process.

The plasma rotating electrode process (PREP) is an ideal method for the preparation of metal powders such as nickel-based, titanium-based, and iron-based alloys due to its low material loss and good degree of sphericity. However, the preparation of silver alloy powder by PREP remains challenging. The low hardness of the mould casting silver alloy leads to the bending of the electrode rod when subjected to high-speed rotation during PREP. The mould casting silver electrode rod can only be used in low-speed rotation, which has a negative effect on particle refinement. This study employed continuous casting (CC) to improve the surface hardness of S800 Ag (30.30% higher than mould casting), which enables a high rotation speed of up to 37,000 revolutions per minute, and silver alloy powder with an average sphericity of 0.98 (5.56% higher than gas atomisation) and a sphericity ratio of 97.67% (36.28% higher than gas atomisation) has been successfully prepared. The dense S800 Ag was successfully fabricated by laser powder bed fusion (LPBF), which proved the feasibility of preparing high-quality powder by the "CC + PREP" method. The samples fabricated by LPBF have a Vickers hardness of up to 271.20 HV (3.66 times that of mould casting), leading to a notable enhancement in the strength of S800 Ag. In comparison to GA, the S800 Ag powder prepared by "CC + PREP" exhibits greater sphericity, a higher sphericity ratio and less satellite powder, which lays the foundation for dense LPBF S800 Ag fabrication.

Clinical and multiparametric MRI features for differentiating uterine carcinosarcoma from endometrioid adenocarcinoma.

INTRODUCTION: The purpose of our study was to differentiate uterine carcinosarcoma (UCS) from endometrioid adenocarcinoma (EAC) by the multiparametric magnetic resonance imaging (MRI) features. METHODS: We retrospectively evaluated clinical and MRI findings in 17 patients with UCS and 34 patients with EAC proven by histologically. The following clinical and pathological features were evaluated: post- or pre-menopausal, clinical presentation, invasion depth, FIGO stage, lymphaticmetastasis. The following MRI features were evaluated: tumor dimension, cystic degeneration or necrosis, hemorrhage, signal intensity (SI) on T2-weighted images (T2WI), relative SI of lesion to myometrium on T2WI, T1WI, DWI, ADCmax, ADCmin, ADCmean (RSI-T2, RSI-T1, RSI-DWI, RSI-ADCmax, RSI-ADCmin, RSI-ADCmean), ADCmax, ADCmin, ADCmean, the maximum, minimum and mean relative enhancement (RE) of lesion to myometrium on the arterial and venous phases (REAmax, REAmin, REAmean, REVmax, REVmin, REVmean). Receiver operating characteristic (ROC) analysis and the area under the curve (AUC) were used to evaluate prediction ability. RESULTS: The mean age of UCS was higher than EAC. UCS occurred more often in the postmenopausal patients. UCS and EAC did not significantly differ in depth of myometrial invasion, FIGO stage and lymphatic metastasis. The anterior-posterior and transverse dimensions were significantly larger in UCS than EAC. Cystic degeneration or necrosis and hemorrhage were more likely occurred in UCS. The SI of tumor on T2WI was more heterogeneous in UCS. The RSI-T2, ADCmax, ADCmean, RSI-ADCmax and RSI-ADCmean of UCS were significantly higher than EAC. The REAmax, REAmin, REAmean, REVmax, REVmin and REVmean of UCS were all higher than EAC. The AUCs were 0.72, 0.71, 0.86, 0.96, 0.89, 0.84, 0.73, 0.97, 0.88, 0.94, 0.91, 0.69 and 0.80 for the anterior-posterior dimension, transverse dimension, RSI-T2, ADCmax, ADCmean, RSI-ADCmax, RSI-ADCmean, REAmax, REAmin, REAmean, REVmax, REVmin and REVmean, respectively. The AUC was 0.997 of the combined of ADCmax, REAmax and REVmax. Our study showed that ADCmax threshold value of 789.05 (10-3mm2/s) can differentiate UCS from EAC with 100% sensitivity, 76.5% specificity, and 0.76 AUC, REAmax threshold value of 0.45 can differentiate UCS from EAC with 88.2% sensitivity, 100% specificity, and 0.88 AUC. CONCLUSION: Multiparametric MRI features may be utilized as a biomarker to distinguish UCS from EAC.

Clinical-Radiologic Morphology-Radiomics Model on Gadobenate Dimeglumine-Enhanced MRI for Identification of Highly Aggressive Hepatocellular Carcinoma: Temporal Validation and Multiscanner Validation.

BACKGROUND: Highly aggressive hepatocellular carcinoma (HCC) is characterized by high tumor recurrence and poor outcomes, but its definition and imaging characteristics have not been clearly described. PURPOSE: To develop and validate a fusion model on gadobenate dimeglumine-enhanced MRI for identifying highly aggressive HCC. STUDY TYPE: Retrospective. POPULATION: 341 patients (M/F = 294/47) with surgically resected HCC, divided into a training cohort (n = 177), temporal validation cohort (n = 77), and multiscanner validation cohort (n = 87). FIELD STRENGTH/SEQUENCE: 3T, dynamic contrast-enhanced MRI with T1-weighted volumetric interpolated breath-hold examination gradient-echo sequences, especially arterial phase (AP) and hepatobiliary phase (HBP, 80-100 min). ASSESSMENT: Clinical factors and diagnosis assessment based on radiologic morphology characteristics associated with highly aggressive HCCs were evaluated. The radiomics signatures were extracted from AP and HBP. Multivariable logistic regression was performed to construct clinical-radiologic morphology (CR) model and clinical-radiologic morphology-radiomics (CRR) model. A nomogram based on the optimal model was established. Early recurrence-free survival (RFS) was evaluated in actual groups and risk groups calculated by the nomogram. STATISTICAL TESTS: The performance was evaluated by receiver operating characteristic curve (ROC) analysis, calibration curves analysis, and decision curves. Early RFS was evaluated by using Kaplan-Meier analysis. A P value <0.05 was considered statistically significant. RESULTS: The CRR model incorporating corona enhancement, cloud-like hyperintensity on HBP, and radiomics signatures showed the highest diagnostic performance. The area under the curves (AUCs) of CRR were significantly higher than those of the CR model (AUC = 0.883 vs. 0.815, respectively, for the training cohort), 0.874 vs. 0.769 for temporal validation, and 0.892 vs. 0.792 for multiscanner validation. In both actual and risk groups, highly and low aggressive HCCs showed statistically significant differences in early recurrence. DATA CONCLUSION: The clinical-radiologic morphology-radiomics model on gadobenate dimeglumine-enhanced MRI has potential to identify highly aggressive HCCs and non-invasively obtain prognostic information. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Tumor-targeting polymer nanohybrids with amplified ROS generation for combined photodynamic and chemodynamic therapy.

Reactive oxygen species (ROS) generating strategies have been widely adopted for cancer therapy, but therapeutic efficacies are often low due to the complicated tumor microenvironment. In this study, we present the development of tumor-targeting polymer nanohybrids that amplify ROS generation by combining photodynamic therapy (PDT) and chemodynamic therapy (CDT) for cancer treatment. Such polymer nanohybrids contained three main components: a semiconducting polymer (SP) that acted as the photosensitizer for PDT, manganese dioxide (MnO2) that acted as the catalyst for CDT, and transferrin that mediated tumor targeting via binding to transferrin receptors overexpressed on the surface of tumor cells. The formed nanohybrids (TSM) showed obviously enhanced accumulation efficacy in tumor sites because of their targeting ability. In tumor sites, TSM produced singlet oxygen (1O2) under near-infrared (NIR) laser irradiation and a hydroxyl radical (˙OH) via reacting with hydrogen peroxide (H2O2), which resulted in amplified generation of ROS to achieve PDT/CDT combinational therapy. The growth of subcutaneous 4T1 tumors was remarkably inhibited via TSM-mediated treatment. In addition, this therapeutic efficacy could suppress tumor metastasis in the liver and lungs. This study presents a targeting hybrid nanoplatform to combine different ROS generating strategies for effective cancer therapy.

The third case of Marbach-Rustad progeroid syndrome caused by a de novo LEMD2 variant.

Marbach-Rustad progeroid syndrome is an extremely rare disease caused by a heterozygous variant in the LEMD2 gene. To date, only two patients and one LEMD2 pathogenic variant have been reported in Marbach-Rustad progeroid syndrome. Here we describe the third case of Marbach-Rustad progeroid syndrome worldwide, which is also the first case in China. The proband was affected with premature birth, failed to thrive, facial abnormalities, feeding difficulties, skull defects and delayed motor milestones, but had a normal intelligence and speech. Whole exome sequencing (WES) initially did not find a phenotype-causing variant when the proband was 1 year of age. The reanalysis of WES data 4 years later revealed the proband harbored a de novo heterozygous c.1436C>T(p.Ser479Phe) variant in the LEMD2 gene, which is known responsible for Marbach-Rustad progeroid syndrome. Sanger sequencing confirmed the presence of this variant in the proband and absence in his parents and two elder sisters. Our study provides accurate clinical diagnosis for the proband and adds a new patient with Marbach-Rustad progeroid syndrome. Our study suggests the LEMD2 c.1436C>T(p.Ser479Phe) variant as a hotspot. Our work also indicates reanalysis of WES data of negative cases might identify pathogenic variant and improve diagnostic efficiency.

Severe Zellweger spectrum disorder due to a novel missense variant in the PEX13 gene: A case report and the literature review.

BACKGROUND: Peroxisome biogenesis disorders (PBDs) are caused by variants in PEX genes that impair peroxisome function. Zellweger spectrum disorders (ZSDs) are the most severe and common subtype of PBDs, affecting multiple organ systems due to peroxisomal involvement in various metabolic functions. PEX13 gene variants are rare causes of ZSDs, with only 21 cases reported worldwide and none in China. METHODS: We describe an infant with biochemically and molecularly confirmed ZSDs due to variants in the PEX13 gene, identified by whole exome sequencing and validated by Sanger sequencing. The patient's treatment and prognosis were followed up. We also reviewed the literature on previously reported cases with PEX13 variants. RESULTS: The patient had severe hypotonia, seizures, hepatic dysfunction, failure to thrive, and dysmorphic features. Serum analysis revealed elevated levels of very long-chain fatty acids (VLCFA), phytanic acid, and pipecolic acid. We detected a novel homozygous missense variant c.493G>C (p. Ala165Pro) in the PEX13 gene (NM_002618.3), which caused severe clinical manifestations and was inherited from the consanguineous parents. The patient died at the age of 14 months. CONCLUSION: We report the first case of ZSDs due to the PEX13 variant in China. Our findings broaden the mutational spectrum of the PEX13 gene and indicate that missense variants can lead to severe ZSDs phenotypes, which has implications for genotype-phenotype correlations and genetic counseling.

The value of diffusion-weighted imaging in the natural history of meningiomas: a predictor of tumor growth.

OBJECTIVE: The general trend in meningioma treatment is shifting from surgery to active surveillance. However, the natural history of meningioma still needs to be clarified, and a simple, practical method is needed to identify fast-growing tumors. The authors aimed to determine whether diffusion-weighted imaging (DWI) could be a valuable imaging modality for predicting meningioma growth. METHODS: Consecutive asymptomatic patients with a meningioma diagnosed on MRI and followed up at the authors' institution between July 2011 and July 2019 were eligible for inclusion in this retrospective study. Univariable and multivariable Cox regression analyses were used to explore whether the relative apparent diffusion coefficient (rADC) was an independent predictor of meningioma growth. Correlations between tumor growth rate (TGR), tumor volume doubling time (VDT), Ki-67, and rADC were assessed using the Pearson correlation coefficient. The predictive ability of rADC was evaluated using receiver operating characteristic (ROC) curves and validated with internal validation data. RESULTS: Sixty-four patients (47 females, 17 males) with a mean age of 62.2 ± 1.4 years were included in this study. Univariable and multivariable analyses revealed that rADC was an independent predictor of meningioma growth (p < 0.05). ROC curve analysis showed that baseline rADC had good predictive power for growing meningiomas (AUC = 0.88, 95% CI 0.78-0.96), as well as slow- or fast-growing meningiomas (AUC = 0.83, 95% CI 0.59-0.98). Moreover, rADC still had a good ability to discriminate between growing and nongrowing meningiomas in the validation set (AUC = 0.85, 95% CI 0.64-1.00). In the 20 patients with tumor growth, baseline rADC was moderately negatively correlated with TGR (r = -0.50, p = 0.02) and strongly positively correlated with VDT (r = 0.63, p = 0.003). Moreover, Ki-67 was significantly associated with rADC in 8 patients who had undergone surgery (r = -0.75, p = 0.03). CONCLUSIONS: In asymptomatic meningiomas, the lower the rADC at baseline, the faster the TGR and the shorter the VDT. DWI could be a valuable tool in predicting meningioma growth in asymptomatic patients.

Histogram analysis of mono-exponential, bi-exponential and stretched-exponential diffusion-weighted MR imaging in predicting consistency of meningiomas.

BACKGROUND: The consistency of meningiomas is critical to determine surgical planning and has a significant impact on surgical outcomes. Our aim was to compare mono-exponential, bi-exponential and stretched exponential MR diffusion-weighted imaging in predicting the consistency of meningiomas before surgery. METHODS: Forty-seven consecutive patients with pathologically confirmed meningiomas were prospectively enrolled in this study. Two senior neurosurgeons independently evaluated tumour consistency and classified them into soft and hard groups. A volume of interest was placed on the preoperative MR diffusion images to outline the whole tumour area. Histogram parameters (mean, median, 10th percentile, 90th percentile, kurtosis, skewness) were extracted from 6 different diffusion maps including ADC (DWI), D*, D, f (IVIM), alpha and DDC (SEM). Comparisons between two groups were made using Student's t-Test or Mann-Whitney U test. Parameters with significant differences between the two groups were included for Receiver operating characteristic analysis. The DeLong test was used to compare AUCs. RESULTS: DDC, D* and ADC 10th percentile were significantly lower in hard tumours than in soft tumours (P ≤ 0.05). The alpha 90th percentile was significantly higher in hard tumours than in soft tumours (P < 0.02). For all histogram parameters, the alpha 90th percentile yielded the highest AUC of 0.88, with an accuracy of 85.10%. The D* 10th percentile had a relatively higher AUC value, followed by the DDC and ADC 10th percentile. The alpha 90th percentile had a significantly greater AUC value than the ADC 10th percentile (P ≤ 0.05). The D* 10th percentile had a significantly greater AUC value than the ADC 10th percentile and DDC 10th percentile (P ≤ 0.03). CONCLUSION: Histogram parameters of Alpha and D* may serve as better imaging biomarkers to aid in predicting the consistency of meningioma.

An Isolable Radical Anion Featuring a 2-Center-3-Electron π-Bond without a Clearly Defined σ-Bond.

Featuring an extra electron in the π* antibonding orbital, species with a 2-center-3-electron (2c3e) π bond without an underlying σ bond are scarcely known. Herein, we report the synthesis, isolation and characterization of a radical anion salt [K(18-C-6)]+ {[(HCNDipp)2 Si]2 P2 }⋅- (i.e. [K(18-C-6)]+ 3⋅- ) (18-C-6=18-crown-6, Dipp=2,6-diisopropylphenyl), in which 3⋅- features a perfectly planar Si2 P2 four-membered ring. This species represents the first example of a Si- and P-containing analog of a bicyclo[1.1.0]butane radical anion. The unusual bonding motif of 3⋅- was thoroughly investigated via X-ray diffraction crystallography, electron paramagnetic resonance spectroscopy (EPR), and calculations by density functional theory (DFT), which collectively unveiled the existence of a 2c3e π bond between the bridgehead P atoms and no clearly defined supporting P-P σ bond.

4D DIA-PRM proteomic study identifying modulated pathways and biomarkers associated with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a highly disabling condition that negatively affects the quality of life of millions of women worldwide. However, the underlying mechanisms associated with the development and progression of the disease remain poorly understood. Here, an untargeted four-dimensional data-independent acquisition (4D DIA)-based proteomics approach was applied to vaginal wall tissue samples from POP (n = 19) and control (n = 8) patients to identify potential diagnostic biomarker(s) for POP and examine the molecular mechanisms underlying the disease. Of the 5713 tissue proteins that were detected, 1957 proteins were significantly changed in POP patients. Further bioinformatics analysis revealed that multiple biological processes including protein digestion & absorption, retrograde endocannabinoid signaling, tyrosine metabolism, and nucleotide metabolism were significantly enriched and associated with the pathogenesis of POP. Interestingly, 16 of these differentially expressed proteins associated with four pathways were also identified by targeted parallel reaction monitoring (PRM) proteomics analysis on the same 27 tissue samples. Changes in 94 % (15/16) of these proteins were consistent with the 4D DIA data. Furthermore, most proteins displayed good diagnostic accuracy with high area under the curve (AUC) values (AUC＞0.8). Specifically, five proteins including ELN, COL6A2, ENTPD1, AOC3, and COX7A2 distinguished between POP and control patients with very high accuracy (AUC ≥ 0.95) in both 4D DIA and PRM analyses, and may therefore be potential diagnostic biomarkers for POP. In summary, the present study not only provided several potential biomarker(s) for effective POP diagnosis, but extended our knowledge of the key regulatory pathways associated with the disease.

Thermal Reduction of MoO3 Particles and Formation of MoO2 Nanosheets Monitored by In Situ Transmission Electron Microscopy.

Nanoscale forms of molybdenum trioxide have found widespread use in optoelectronic, sensing, and battery applications. Here, we investigate the thermal evolution of micrometer-sized molybdenum trioxide particles during in situ heating in vacuum using transmission electron microscopy and observed drastic structural and chemical changes that are strongly dependent on the heating rate. Rapid heating (flash heating) of MoO3 particles to a temperature of 600 °C resulted in large-scale formation of MoO2(001) nanosheets that were formed in a wide area around the reducing MoO3 particles, within a few minutes of time frame. In contrast, when heated more gently, the initially single-crystal MoO3 particles were reduced into hollow nanostructures with polycrystalline MoO2 shells. Using density functional theory calculations employing the DFT-D3 functional, the surface energy of MoO3(010) was calculated to be 0.187 J m-2, and the activation energy for exfoliation of the van der Waals bonded MoO3 (010) layers was calculated to be 0.478 J m-2. Ab initio molecular dynamics simulations show strong fluctuations in the distance between the (010) layers, where thermal vibrations lead to additional separations of up to 1.8 Å at 600 °C. This study shows efficient pathways for the generation of either MoO2 nanosheets or hollow MoO2 nanostructures with very high effective surface areas beneficial for applications.

Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients.

Objective: To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). Materials and Methods: From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. Results: A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P < 0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P=0.00), vasoactive inotropic score (P=0.03), GAP (P=0.00), HCY (P=0.00), creatinine (P=0.00), C-reactive protein (P=0.00), HbAlc (P=0.00), CI (P=0.01), quartiles of CD34+/CD133+ cells (P=0.00), and quartiles of CD34+/CD133+/KDR+ cells (P=0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10-10 and P=0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. Conclusions: The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.

Machine learning-based integration develops a neutrophil-derived signature for improving outcomes in hepatocellular carcinoma.

Introduction: The heterogeneity of tumor immune microenvironments is a major factor in poor prognosis among hepatocellular carcinoma (HCC) patients. Neutrophils have been identified as playing a critical role in the immune microenvironment of HCC based on recent single-cell studies. However, there is still a need to stratify HCC patients based on neutrophil heterogeneity. Therefore, developing an approach that efficiently describes "neutrophil characteristics" in HCC patients is crucial to guide clinical decision-making. Methods: We stratified two cohorts of HCC patients into molecular subtypes associated with neutrophils using bulk-sequencing and single-cell sequencing data. Additionally, we constructed a new risk model by integrating machine learning analysis from 101 prediction models. We compared the biological and molecular features among patient subgroups to assess the model's effectiveness. Furthermore, an essential gene identified in this study was validated through molecular biology experiments. Results: We stratified patients with HCC into subtypes that exhibited significant differences in prognosis, clinical pathological characteristics, inflammation-related pathways, levels of immune infiltration, and expression levels of immune genes. Furthermore, A risk model called the "neutrophil-derived signature" (NDS) was constructed using machine learning, consisting of 10 essential genes. The NDS's RiskScore demonstrated superior accuracy to clinical variables and correlated with higher malignancy degrees. RiskScore was an independent prognostic factor for overall survival and showed predictive value for HCC patient prognosis. Additionally, we observed associations between RiskScore and the efficacy of immune therapy and chemotherapy drugs. Discussion: Our study highlights the critical role of neutrophils in the tumor microenvironment of HCC. The developed NDS is a powerful tool for assessing the risk and clinical treatment of HCC. Furthermore, we identified and analyzed the feasibility of the critical gene RTN3 in NDS as a molecular marker for HCC.

Pleomorphic undifferentiated sarcoma of the mediastinal thymus: A case report and literature review.

Pleomorphic undifferentiated sarcoma (PUS) of the mediastinal thymus is a rare type of cancer. In the present case report, a 67-year-old female patient presenting a mediastinal mass for >1 year was assessed for clinical characteristics, histopathological, immunohistochemical expression and gene mutation using fluorescence in situ hybridization (FISH), and relevant literature was reviewed. Histological analysis revealed nodular changes of different sizes in the thymus, which consisted of a mixture of pleomorphic and spindle cells. The pleomorphic cells with distinct atypia were giant cells and multinucleated cells with large cell sizes and frequent nuclear divisions. The spindle cells were mild to moderate atypical and arranged in a woven pattern, and nuclear division was rare. Immunohistochemical analysis indicated that vimentin was diffusively expressed in tumor cells. No amplification was found in CDX2 and MDM4 genes using the FISH analysis. In conclusion, mediastinal thymus neoplasm should be considered in the presence of PUS and it is an exclusionary diagnosis based on clinical and pathological examination of the patient.