GPNMB Expression Associates with Inferior Prognosis in Patients with Small Cell Lung Cancer.

Purpose: Small cell lung cancer (SCLC) is widely recognized for its propensity for early and frequent metastases, which contribute to its status as a refractory malignancy. While the high expression of GPNMB in SCLC is well-documented, the precise correlation between GPNMB expression and the prognosis of SCLC remains undetermined. Methods: HTG Edge-seq was used to screen the differential gene expression between primary SCLC lesions and paired metastatic lymph nodes (LN). The plasma concentration of GPNMB was measured using enzyme-linked immunosorbent assay (ELISA). The relationship between GPNMB concentration and clinical characteristics, as well as overall survival (OS) was assessed. One-to-one propensity score matching (PSM) was performed to reduce bias from confounding factors between groups. The invasive, migratory, proliferative, and apoptotic abilities of SCLC cells were evaluated using migration and matrigel invasion assays, CCK8 assay and flow cytometry respectively. Results: GPNMB exhibited a significant up-regulation in LN compared to primary SCLC lesions as determined by HTG Edge-seq. Furthermore, patients with extensive disease demonstrated a significantly elevated plasma GPNMB concentration compared to those with local disease (P = 0.043). Additionally, patients with a high baseline plasma GPNMB level exhibited a shorter OS (10.32 vs. 16.10 months, P = 0.0299). Following PSM analysis, the statistical significance of the difference between the two groups persisted (9.43 vs. 15.27 months, P = 0.0146). Notably, both univariate and multivariate analyses confirmed that higher expression of GPNMB served as an independent biomarker for OS before PSM (P = 0.033, HR = 2.304) and after PSM (P = 0.003, HR = 6.190). Additionally, our study revealed that the inhibition of GPNMB expression through the use of siRNA effectively diminished the metastatic and proliferative capabilities of SCLC. Furthermore, this inhibition resulted in an enhanced ability to induce apoptosis. Conclusions: In light of our findings, it can be inferred that the expression of GPNMB is linked to metastasis and an unfavorable prognosis, thus suggesting its potential as a novel therapeutic target in the treatment of SCLC.

Sesquilignans: Current research and potential prospective.

Lignans are widely distributed in nature, primarily found in the xylem and resins of plants, with the constituent units C6-C3, and their dimers are the most common in plants. In recent years, the trimeric sesquilignans have also received increasing attention from scholars. More than 200 derivatives have been isolated and identified from nearly 50 families, most of which are different types (monoepoxy lignans, bisepoxy lignans, benzofuran lignans) connected with simple phenylpropanoids through ether bonds, C-C bonds, and oxygen-containing rings to constitute sesquilignans. Some of them also possess pharmacological properties, including antioxidants, hepatoprotectives, antitumors, anti-inflammatory properties, and other properties. In addition, the chemical structure of sesquilignans is closely related to the pharmacological activity, and chemical modification of methoxylation enhances the pharmacological activity. In contrast, phenolic hydroxyl and hydroxyl glycosides reduce the pharmacological activity. Therefore, the present review aims to summarize the chemical diversity, bioactivities, and constitutive relationships to provide a theoretical basis for the more profound development and utilization of sesquilignans.

Schisandrol A, the Major Active Constitute in Schisandra chinensis: A Review of Its Preparation, Biological Activities, and Pharmacokinetics Analysis.

Schisandra chinensis (S. chinensis) has a long history as a traditional Chinese medicine that is astringent, beneficial to vital energy, tonifies the kidney, tranquilizes the heart, etc. Significantly, Schisandrol A (SA) is extracted from S. chinensis and shows surprising and satisfactory biological activity, including anti-inflammatory, hepatoprotective, cardiovascular protection, and antitumor properties, among others. SA has a more pronounced protective effect on central damaged nerves among its numerous pharmacological effects, improving neurodegenerative diseases such as Alzheimer's and Parkinson's through the protection of damaged nerve cells and the enhancement of anti-oxidant capacity. Pharmacokinetic studies have shown that SA has a pharmacokinetic profile with a rapid absorption, wide distribution, maximal concentration in the liver, and primarily renal excretion. However, hepatic and intestinal first-pass metabolism can affect SA's bioavailability. In addition, the content of SA, as an index component of S. chinensis Pharmacopoeia, should not be less than 0.40%, and the content of SA in S. chinensis compound formula was determined with the help of high-performance liquid chromatography (HPLC), which is a stable and reliable method, and it can lay a foundation for the subsequent quality control. Therefore, this paper systematically reviews the preparation, pharmacological effects, pharmacokinetic properties, and content determination of SA with the goal of updating and deepening the understanding of SA, as well as providing a theoretical basis for the study of SA at a later stage.

Optimizing hybrid energy systems for remote communities in Asia's least developed countries.

In least-developed countries (LDCs), electricity shortages are the primary barrier to economic and social growth. Some remote areas in LDC rely on diesel-based systems. However, renewable energy must be taken into account for generating electricity because of the uncertainty of diesel fuel prices and the emissions of carbon dioxide. Hybrid energy systems (HES) are becoming increasingly popular, which is unsurprising given the rapid advancement of renewable energy technologies, which have made them the preferred method to respond to the current unreliable electricity supply, reduce the impact of global warming that occurs from electricity production, and contribute to cost reduction. This study explores the feasibility of utilizing a combination of solar PV, wind energy, and battery systems with the existing diesel generator in four different locations in Cambodia, Laos, Myanmar, and Bangladesh. Hybrid optimization multiples for electric renewables (HOMER) is used as a tool for techno-economic analysis and finding the possible combination of solar PV, wind, diesel, and battery. The multi-criteria decision-making (MCDM) technique was used to verify all configurations obtained from HOMER's results. This approach considers environmental, economic, and technological factors by utilizing the AHP, TOPSIS, EDAS, and PROMETHEEE II techniques. The results show that PV/diesel with batteries is the optimum solution. This hybrid system comprises 89% PV penetration, a cost of electricity (COE) of 0.257 $/kWh, an initial capital cost (IC) of $244,277, and a net present cost (NPC) of $476,216 for a case study in Cambodia. Furthermore, this system can reduce almost 51,005 kg/year of carbon dioxide compared to a diesel-only system, while the cost of electricity is reduced.

In-situ Ultrafast Construction of Zinc Tungstate Interface Layer for Highly Reversible Zinc Anodes.

Constructing artificial solid electrolyte interface on the Zn anode surface is recognized as an appealing method to inhibit zinc dendrites and side reactions, whereas the current techniques are complex and time-consuming. Here, a robust and zincophilic zinc tungstate (ZnWO4) layer has been in situ constructed on the Zn anode surface (denoted as ZWO@Zn) by an ultrafast chemical solution reaction. Comprehensive characterizations and theoretical calculations demonstrate that the ZWO layer can effectively modulate the interfacial electric field distribution and promote the Zn2+ uniform diffusion, thus facilitating the uniform Zn2+ nucleation and suppressing zinc dendrites. Besides, ZWO layer can prevent direct contact between the Zn/water and increase the hydrogen evolution reaction overpotential to eliminate side reactions. Consequently, the in-situ constructed ZWO layer facilitates remarkable reversibility in the ZWO@Zn||Ti battery, achieving an impressive Coulombic efficiency of 99.36% under 1.0 mA cm-2, unprecedented cycling lifespan exceeding 1800 h under 1.0 mA cm-2 in ZWO@Zn||ZWO@Zn battery, and a steady and reliable operation of the overall ZWO@Zn||VS2 battery. The work provides a simple, low cost, and ultrafast pathway to crafting protective layers for driving advancements in aqueous zinc-metal batteries.

Colonization characteristics and dynamic transition of archaea communities on polyethylene and polypropylene microplastics in the sediments of mangrove ecosystems.

Microplastics are a growing concern in mangrove ecosystems; however, their effects on archaeal communities and related ecological processes remain unclear. We conducted in situ biofilm-enrichment experiments to investigate the ecological influence of polyethylene (PE) and polypropylene microplastics on archaeal communities in the sediments of mangrove ecosystems. The archaeal community present on microplastics was distinct from that of the surrounding sediments at an early stage but became increasingly similar over time. Bathyarchaeota, Thaumarchaeota, Euryarchaeota, and Asgardaeota were the most abundant phyla. Methanolobus, an archaeal biomarker, was enriched in PE biofilms, and significantly controlled by homogeneous selection in the plastisphere, indicating an increased potential risk of methane emission. The dominant archaeal assembly process in the sediments was deterministic (58.85%-70.47%), while that of the PE biofilm changed from stochastic to deterministic during the experiment. The network of PE plastispheres showed less complexity and competitive links, and higher modularity and stability than that of sediments. Functional prediction showed an increase in aerobic ammonia oxidation during the experiment, whereas methanogenesis and chemoheterotrophy were significantly higher in the plastisphere. This study provides novel insights into the impact of microplastic pollution on archaeal communities and their mediating ecological functions in mangrove ecosystems.

Olive oil intake and cardiovascular disease, cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

Background: Currently, the reported links between olive oil intake and cardiovascular disease (CVD), cancer morbidity and mortality, and all-cause mortality are inconsistent. The aim of this meta-analysis is to study the reported correlations of olive oil intake with CVD, coronary heart disease (CHD), stroke and cancer incidence and mortality, and all-cause mortality. Methods: PubMed, Embase, and Web of Science were searched until March 7, 2024. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the random-effects model. Nonlinear dose-response relationships were modeled with restricted cubic splines. This study has been registered at PROSPERO (CRD42023419001). Results: Overall, 30 articles covering 2 710 351 participants were identified. Higher olive oil intake was linked with a reduced risk of CVD incidence (RR: 0.85; 95% CI: 0.77, 0.93), CHD incidence (RR: 0.85; 95% CI: 0.72, 0.99), CVD mortality (RR: 0.77; 95% CI: 0.67, 0.88), and all-cause mortality (RR: 0.85; 95% CI: 0.81, 0.89). For a 10 g d-1 increment of olive oil intake, the risk of CVD incidence, stroke incidence, CVD mortality, and all-cause mortality decreased by 7%, 5%, 8%, and 8%, respectively. No association was found between olive oil intake and cancer incidence and mortality. Nonlinear relationships between olive oil intake and CVD and all-cause mortality were observed, with a reduced risk from intakes ranging from 0 to 18 g d-1 and 0 to 22 g d-1, respectively. Conclusion: Our study found that high olive oil intake was related to a lower risk of CVD and CHD incidence and CVD mortality and all-cause mortality.

Strain-Specific Benefits of Bacillus Probiotics in Hybrid Grouper: Growth Enhancement, Metabolic Health, Immune Modulation, and Vibrio harveyi Resistance.

In the realm of modern aquaculture, the utilization of probiotics has gained prominence, primarily due to their ability to enhance growth, boost immunity, and prevent diseases in aquatic species. This study primarily investigates the efficacy of Bacillus subtilis strains, both host-derived and from other sources, in influencing fish growth, immunity, lipid metabolism, and disease resistance. Employing a 42-day feeding trial, we divided hybrid grouper into four distinct groups: a control group on a basal diet and three experimental groups supplemented with 1 × 108 CFU/g of different Bacillus subtilis strains-BS, 6-3-1, and HAINUP40. Remarkably, the study demonstrated that the 6-3-1 and HAINUP40 groups exhibited significant enhancements across key growth parameters: final body weight (FBW), weight gain rate (WGR), feed intake (FI), feed efficiency ratio (FER), and feed conversion ratio (FCR). The investigation into lipid metabolism revealed that the 6-3-1 strain upregulated seven metabolism-related genes, HAINUP40 affected four metabolism-related genes, and the BS strain influenced two metabolism-related genes, indicating diverse metabolic impacts by different strains. Further, a notable reduction in liver enzymes AST and ALT was observed across all supplemented groups, implying improved liver health. Noteworthy was the BS strain's superior antioxidative capabilities, positively affecting all four measured parameters (CAT, GSH-Px, MDA). In the sphere of immune-related gene expression, the BS strain significantly decreased the expression of both inflammation and apoptosis-related genes, whereas the HAINUP40 strain demonstrated an upregulation in these genes. The challenge test results were particularly telling, showcasing improved survival rates against Vibrio harveyi infection in the BS and 6-3-1 groups, unlike the HAINUP40 group. These outcomes highlight the strain-specific nature of probiotics and their varying mechanisms of action within the host. In conclusion, this study reveals that probiotic strains, varying by source, demonstrate unique, strain-specific effects in promoting growth and modulating immunity in hybrid grouper. This research highlights the promise of tailored probiotic applications in improving aquaculture practices. Such advancements contribute to more sustainable and efficient fish farming methods.

Severe Vincristine-Induced Peripheral Neuropathic Weakness in Both Lower Limbs in an Asian Adolescent with CYP3A4 rs2740574 TT Genotype.

Background: Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common adverse reaction during cancer treatment, typically characterized by numbness and paresthesias. This study aimed to report a rare case of VIPN with an atypical genotype, manifesting as grade 3 weakness of the lower limbs. Case Presentation: A 19-year-old man, diagnosed with alveolar rhabdomyosarcoma for 8 months, was transferred to our hospital for further treatment after the failure of first-line treatment. He developed severe long-standing weakness in both lower limbs and could not walk after four sessions of second-line chemotherapy. The diagnosis of VIPN was confirmed based on the patient's physical examination, imaging studies, electromyogram results, and treatment history. Furthermore, the pharmacogenetic analysis indicated that the patient harbored CYP3A4 rs2740574 TT genotypes. Conclusion: We have reported for the first time a VIPN patient whose main clinical manifestation is severe weakness in both lower limbs, accompanied by the CYP3A4 rs2740574 TT phenotype. This case may provide new information on the phenotypic features of VIPN, and may help to better understand the disease pathogenesis and contributing factors.

Hypoxic microenvironment-induced exosomes confer temozolomide resistance in glioma through transfer of pyruvate kinase M2.

OBJECTIVE: Glioma, a malignant primary brain tumor, is notorious for its high incidence rate. However, the clinical application of temozolomide (TMZ) as a treatment option for glioma is often limited due to resistance, which has been linked to hypoxic glioma cell-released exosomes. In light of this, the present study aimed to investigate the role of exosomal pyruvate kinase M2 (PKM2) in glioma cells that exhibit resistance to TMZ. METHODS: Sensitive and TMZ-resistant glioma cells were subjected to either a normoxic or hypoxic environment, and the growth patterns and enzymatic activity of glycolysis enzymes were subsequently measured. From these cells, exosomal PKM2 was isolated and the subsequent effect on TMZ resistance was examined and characterized, with a particular focus on understanding the relevant mechanisms. Furthermore, the intercellular communication between hypoxic resistant cells and tumor-associated macrophages (TAMs) via exosomal PKM2 was also assessed. RESULTS: The adverse impact of hypoxic microenvironments on TMZ resistance in glioma cells was identified and characterized. Among the three glycolysis enzymes that were examined, PKM2 was found to be a critical mediator in hypoxia-triggered TMZ resistance. Upregulation of PKM2 was found to exacerbate the hypoxia-mediated TMZ resistance. Exosomal PKM2 were identified and isolated from hypoxic TMZ-resistant glioma cells, and were found to be responsible for transmitting TMZ resistance to sensitive glioma cells. The exosomal PKM2 also contributed towards mitigating TMZ-induced apoptosis in sensitive glioma cells, while also causing intracellular ROS accumulation. Additionally, hypoxic resistant cells also released exosomal PKM2, which facilitated TMZ resistance in tumor-associated macrophages. CONCLUSION: In the hypoxic microenvironment, glioma cells become resistant to TMZ due to the delivery of PKM2 by exosomes. Targeted modulation of exosomal PKM2 may be a promising strategy for overcoming TMZ resistance in glioma.

Strengthening the Synergy between Oxygen Vacancies in Electrocatalysts for Efficient Glycerol Electrooxidation.

Defect-engineered bimetallic oxides exhibit high potential for the electrolysis of small organic molecules. However, the ambiguity in the relationship between the defect density and electrocatalytic performance makes it challenging to control the final products of multi-step multi-electron reactions in such electrocatalytic systems. In this study, controllable kinetics reduction is used to maximize the oxygen vacancy density of a Cu─Co oxide nanosheet (CuCo2O4 NS), which is used to catalyze the glycerol electrooxidation reaction (GOR). The CuCo2O4-x NS with the highest oxygen-vacancy density (CuCo2O4-x-2) oxidizes C3 molecules to C1 molecules with selectivity of almost 100% and a Faradaic efficiency of ≈99%, showing the best oxidation performance among all the modified catalysts. Systems with multiple oxygen vacancies in close proximity to each other synergistically facilitate the cleavage of C─C bonds. Density functional theory calculations confirm the ability of closely spaced oxygen vacancies to facilitate charge transfer between the catalyst and several key glycolic-acid (GCA) intermediates of the GOR process, thereby facilitating the decomposition of C2 intermediates to C1 molecules. This study reveals qualitatively in tuning the density of oxygen vacancies for altering the reaction pathway of GOR by the synergistic effects of spatial proximity of high-density oxygen vacancies.

Electron Accumulation Induced by Electron Injection-Incomplete Discharge on NiFe LDH for Enhanced Oxygen Evolution Reaction.

Optimizing the local electronic structure of electrocatalysts can effectively lower the energy barrier of electrochemical reactions, thus enhancing the electrocatalytic activity. However, the intrinsic contribution of the electronic effect is still experimentally unclear. In this work, the electron injection-incomplete discharge approach to achieve the electron accumulation (EA) degree on the nickel-iron layered double hydroxide (NiFe LDH) is proposed, to reveal the intrinsic contribution of EA toward oxygen evolution reaction (OER). Such NiFe LDH with EA effect results in only 262 mV overpotential to reach 50 mA cm-2, which is 51 mV-lower compared with pristine NiFe LDH (313 mV), and reduced Tafel slope of 54.8 mV dec-1 than NiFe LDH (107.5 mV dec-1). Spectroscopy characterizations combined with theoretical calculations confirm that the EA near concomitant Vo can induce a narrower energy gap and lower thermodynamic barrier to enhance OER performance. This study clarifies the mechanism of the EA effect on OER activity, providing a direct electronic structure modulation guideline for effective electrocatalyst design.

Optimizing the Heat Treatment Method to Improve the Aging Response of Al-Fe-Ni-Sc-Zr Alloys.

This work has studied the co-addition of Sc and Zr elements into the Al-1.75wt%Fe-1.25wt%Ni eutectic alloy. The changes in the microstructure, electrical conductivity, and Vickers hardness of the Al-1.75wt%Fe-1.25wt%Ni-0.2wt%Sc-0.2wt%Zr alloy during heat treatment were studied. The results showed that two-step aging can effectively improve the aging response of the alloy over the single-step aging method. This was ascribed to the minimization of the diffusion difference between Sc and Zr elements. Furthermore, the homogenization treatment can also improve the aging response of the alloy by alleviating the uneven distribution of Sc and Zr. Nevertheless, the micro-alloyed elements exceeded the solid solubility limit in the Al-1.75wt%Fe-1.25wt%Ni-0.2wt%Sc-0.2wt%Zr alloy, and their strengthening effect has ever achieved the best prospect. Finally, both Sc and Zr contents were reduced simultaneously, and the aging response of the Al-1.75wt%Fe-1.25wt%Ni-0.15wt%Sc-0.1wt%Zr alloy was improved by optimized heat treatment. The underlying mechanisms for this alloy design and the corresponding microstructure-mechanical property relationship were analytically discussed.

Influence of Bacillus subtilis strain Z-14 on microbial ecology of cucumber rhizospheric vermiculite infested with fusarium oxysporum f. sp. cucumerinum.

Fusarium oxysporum (FO) is a typical soil-borne pathogenic fungus, and the cucumber wilt disease caused by F. oxysporum f. sp. cucumerinum (FOC) seriously affects crop yield and quality. Vermiculite is increasingly being used as a culture substrate; nevertheless, studies exploring the effectiveness and mechanisms of biocontrol bacteria in this substrate are limited. In this study, vermiculite was used as a culture substrate to investigate the control effect of Bacillus subtilis strain Z-14 on cucumber wilt and the rhizospheric microecology, focusing on colonization ability, soil microbial diversity, and rhizosphere metabolome. Pot experiments showed that Z-14 effectively colonized the cucumber roots, achieving a controlled efficacy of 61.32% for wilt disease. It significantly increased the abundance of Bacillus and the expression of NRPS and PKS genes, while reducing the abundance of FO in the rhizosphere. Microbial diversity sequencing showed that Z-14 reduced the richness and diversity of the rhizosphere bacterial community, increased the richness and diversity of the fungal community, and alleviated the effect of FO on the community structure of the cucumber rhizosphere. The metabolomics analysis revealed that Z-14 affected ABC transporters, amino acid synthesis, and the biosynthesis of plant secondary metabolites. Additionally, Z-14 increased the contents of phenylacetic acid, capsidol, and quinolinic acid, all of which were related to the antagonistic activity in the rhizosphere. Z-14 exhibited a significant control effect on cucumber wilt and influenced the microflora and metabolites in rhizospheric vermiculite, providing a theoretical basis for further understanding the control effect and mechanism of cucumber wilt in different culture substrates.

Large-scale uterine myoma MRI dataset covering all FIGO types with pixel-level annotations.

Uterine myomas are the most common pelvic tumors in women, which can lead to abnormal uterine bleeding, abdominal pain, pelvic compression symptoms, infertility, or adverse pregnancy. In this article, we provide a dataset named uterine myoma MRI dataset (UMD), which can be used for clinical research on uterine myoma imaging. The UMD is the largest publicly available uterine MRI dataset to date including 300 cases of uterine myoma T2-weighted imaging (T2WI) sagittal patient images and their corresponding annotation files. The UMD covers 9 types of uterine myomas classified by the International Federation of Obstetrics and Gynecology (FIGO), which were annotated and reviewed by 11 experienced doctors to ensure the authority of the annotated data. The UMD is helpful for uterine myomas classification and uterine 3D reconstruction tasks, which has important implications for clinical research on uterine myomas.

Succinic Acid Ameliorates Concanavalin A-Induced Hepatitis by Altering the Inflammatory Microenvironment and Expression of BCL-2 Family Proteins.

Autoimmune hepatitis (AIH) is a severe immune-mediated inflammatory liver disease that currently lacks feasible drug treatment methods. Our study aimed to evaluate the protective effect of succinic acid against AIH and provide a reliable method for the clinical treatment of AIH. We performed an in vivo study of the effects of succinic acid on concanavalin A (ConA)-induced liver injury in mice. We examined liver transaminase levels, performed hematoxylin and eosin (HE) staining, and observed apoptotic phenotypes in mice. We performed flow cytometry to detect changes in the number of neutrophils and monocytes, and used liposomes to eliminate the liver Kupffer cells and evaluate their role. We performed bioinformatics analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting to detect mitochondrial apoptosis-induced changes in proteins from the B-cell lymphoma 2(Bcl-2) family. Succinic acid ameliorated ConA-induced AIH in a concentration-dependent manner, as reflected in the survival curve. HE and TUNEL staining and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed decreased alanine transaminase and aspartate aminotransferase levels, and reduced liver inflammation and apoptosis. RT-qPCR and enzyme-linked immunosorbent assay revealed that succinic acid significantly reduced liver pro-inflammatory cytokine levels. Flow cytometry revealed significantly decreased levels of liver neutrophils. Moreover, the protective effect of succinic acid disappeared after the Kupffer cells were eliminated, confirming their important role in the effect. Bioinformatics analysis, RT-qPCR, and western blotting showed that succinic acid-induced changes in proteins from the Bcl-2 family involved mitochondrial apoptosis, indicating the molecular mechanism underlying the protective effect of succinic acid. Succinic acid ameliorated ConA-induced liver injury by regulating immune balance, inhibiting pro-inflammatory factors, and promoting anti-apoptotic proteins in the liver. This study provides novel insights into the biological functions and therapeutic potential of succinic acid in the treatment of autoimmune liver injury.