Insights into the role of mitophagy in lung cancer: current evidence and perspectives.

Lung cancer, recognized globally as a leading cause of malignancy-associated morbidity and mortality, is marked by its high prevalence and lethality, garnering extensive attention within the medical community. Mitophagy is a critical cellular process that plays a crucial role in regulating metabolism and ensuring quality control within cells. Its relevance to lung cancer has garnered significant attention among researchers and scientists. Mitophagy's involvement in lung cancer encompasses its initiation, progression, metastatic dissemination and treatment. The regulatory landscape of mitophagy is complex, involving numerous signaling proteins and pathways that may exhibit aberrant alterations or mutations within the tumor environment. In the field of treatment, the regulation of mitophagy is considered key to determining cancer chemotherapy, radiation therapy, other treatment options, and drug resistance. Contemporary investigations are directed towards harnessing mitophagy modulators, both inhibitors and activators, in therapeutic strategies, with an emphasis on achieving specificity to minimize collateral damage to healthy cellular populations. Furthermore, molecular constituents and pathways affiliated with mitophagy, serving as potential biomarkers, offer promising avenues for enhancing diagnostic accuracy, prognostic assessment, and prediction of therapeutic responses in lung cancer. Future endeavors will also involve investigating the impact of mitophagy on the composition and function of immune cells within the tumor microenvironment, aiming to enhance our understanding of how mitophagy modulates the immune response to lung cancer. This review aims to comprehensively overview recent advancements about the role of mitophagy in the tumor genesis, progenesis and metastasis, and the impact of mitophagy on the treatment of lung cancer. We also discussed the future research direction of mitophagy in the field of lung cancer.

The relationship between nocturia and suicidal ideation: A study on The National Health and Nutrition Survey data.

OBJECTIVES: The focus of this research was to explore any potential link between nocturia and the risk of suicidal ideation. METHODS: Drawing from the National Health and Nutrition Survey, data relating to 25 241 participants was scrutinized. This included 13 421 individuals identifying as male and 11 820 individuals identifying as female. Participants provided information on nocturia and suicidal ideation via self-completed questionnaires. To determine if nocturia was independently related to suicidal ideation, a multivariable logistic regression analysis was employed. Analyses were also undertaken separately for adult males and females. RESULTS: It was found that around 3.5% of participants had experienced suicidal ideation. The results indicated that nocturia increased the risk for suicidal ideation in all adult groups (odds ratio [OR] = 1.67, 95% confidence interval[CI]: 1.37-2.03, p < 0.0001), including both males (OR = 1.91, 95% CI: 1.38-2.65, p < 0.001) and females (OR = 1.48, 95% CI: 1.158-1.90, p = 0.002). The risk for suicidal ideation increased with the severity of nocturia, with significant trends observed in adult males (p for trend = 0.04) and adult females (p for trend = 0.01). Additionally, subgroup examination showed a significant interaction between nocturia and educational level in adult males (p for interaction = 0.03). Among adult females, a noteworthy interaction was observed between nocturia and body mass index (p for interaction = 0.02). CONCLUSION: The research uncovered a connection between nocturia and an elevated risk of suicidal ideation.

Joint association of weight-adjusted-waist index and physical activity with insulin resistance in adolescents: a cross-sectional study.

BACKGROUND: The weight-adjusted waist index (WWI) is a recently developed obesity metric, and the aim of this study was to investigate the relationship between physical activity (PA) and WWI and the homeostasis model assessment of insulin resistance (HOMA-IR) in adolescents, as well as the joint association of HOMA-IR. METHODS: This study was based on the National Health and Nutrition Survey conducted between 2013 and 2016 and included 1024 adolescents whose median age was 15.4. Multivariate linear regression was used to examine the associations between HOMA-IR and PA and WWI. Using generalized additive models, a potential nonlinear link between WWI and HOMA-IR was evaluated. Subgroup analysis was also carried out. RESULTS: The fully adjusted model revealed a positive association (ß: 0.48, 95% CI: 0.43, 0.53) between the WWI and HOMA-IR. The HOMA-IR was lower in physically active (ß: -0.16, 95% CI: -0.26, -0.05) participants versus inactive participants. Participants who had higher WWI and were not physically active (ß: 0.69; 95% CI: 0.56, 0.82) had the highest levels of HOMA-IR compared to participants who had lower WWI and were physically active. Subgroup analysis revealed that these correlations were similar in males and females. CONCLUSION: Our results demonstrated that higher WWI and PA were associated with a lower HOMA-IR and that WWI and PA had a combined association with HOMA-IR. The findings of this study are informative for the preventing insulin resistance in adolescents.

Histone demethylase PHF8 promotes prostate cancer metastasis via the E2F1-SNAI1 axis.

Metastasis is the primary culprit behind cancer-related fatalities in multiple cancer types, including prostate cancer. Despite great advances, the precise mechanisms underlying prostate cancer metastasis are far from complete. By using a transgenic mouse prostate cancer model (TRAMP) with and without Phf8 knockout, we have identified a crucial role of PHF8 in prostate cancer metastasis. By complexing with E2F1, PHF8 transcriptionally upregulates SNAI1 in a demethylation-dependent manner. The upregulated SNAI1 subsequently enhances epithelial-to-mesenchymal transition (EMT) and metastasis. Given the role of the abnormally activated PHF8/E2F1-SNAI1 axis in prostate cancer metastasis and poor prognosis, the levels of PHF8 or the activity of this axis could serve as biomarkers for prostate cancer metastasis. Moreover, targeting this axis could become a potential therapeutic strategy for prostate cancer treatment. © 2024 The Pathological Society of Great Britain and Ireland.

Combined effect of thermal hydrolysis process and low-temperature pyrolysis on the classification and bioavailability of phosphorus in sewage sludge.

Existing phosphorus (P) resources are becoming increasingly scarce, so it is necessary to recover P from potential sources. This paper is based on thermal hydrolysis process (THP) at 140-180 °C, coupled with low-temperature pyrolysis at 300 °C, to study its effect on the recovery and conversion of P from sewage sludge. Most significant change was observed in apatite P, which increased from 3.43 ±â€¯0.48 mg/g in raw sludge to 30.17 ±â€¯1.17 mg/g in biochar (BTHP-180-4-300) during optimal process (THP condition: 180 °C, 4 h; pyrolysis condition: 300 °C). Reactions between phosphates and metal ions became more complete during this combined process. Unstable forms of P were converted into more stable forms, with transformations from Al-P and Fe-P toward Ca-P compounds like Ca3(PO4)2, Ca3Mg3(PO4)4, Ca2P2O7, and Ca(H2PO4)2, making P less degradable and more suitable as slow-release fertilizers. Additionally, P characteristics of actual THP in a sewage treatment plant were similar to those of laboratory THP.

Role of cell division cycle-associated proteins in regulating cell cycle and promoting tumor progression.

The cell division cycle-associated protein (CDCA) family is important in regulating cell division. High CDCA expression is significantly linked to tumor development. This review summarizes clinical and basic studies on CDCAs conducted in recent decades. Furthermore, it systematically introduces the molecular expression and function, key mechanisms, cell cycle regulation, and roles of CDCAs in tumor development, cell proliferation, drug resistance, invasion, and metastasis. Additionally, it presents the latest research on tumor diagnosis, prognosis, and treatment targeting CDCAs. These findings are pivotal for further in-depth studies on the role of CDCAs in promoting tumor development and provide theoretical support for their application as new anti-tumor targets.

Cryogenic Photoelectron Spectroscopic and Theoretical Study of the Electronic and Geometric Structures of Undercoordinated Osmium Chloride Anions OsCln- (n = 3-5).

A series of anionic transition metal halides, OsCln- (n = 3-5), have been investigated using a newly developed, home-constructed, cryogenic anion cluster photoelectron spectroscopy. The target anionic species are generated through collision-induced dissociation in a two-stage ion funnel. The measured vertical detachment energies (VDEs) are 3.48, 4.54, and 4.81 eV for n = 3, 4, and 5, respectively. Density functional theory calculations at the B3LYP-D3(BJ)//aug-cc-pVTZ(-pp) level predict the lowest energy structures of the atomic form of OsCln- (n = 3-5) to be a quintet triangle, quartet square, and quintet square-based pyramid, respectively. The CCSD(T)-calculated VDEs and corresponding adiabatic detachment energies agree well with our experimental measurements. Analysis of the corresponding frontier molecular orbitals and charge density differences suggests that the d-orbitals of the transition metal Os play a primary role in the single-photon detachment processes, and the detached electrons originating from different molecular orbitals are distinguishable.

Perioperative intravenous lidocaine infusion improves postoperative analgesia after hysterectomy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The effectiveness of intravenous lidocaine in reducing acute pain after hysterectomy remains uncertain. We conducted a meta-analysis of randomized controlled trials (RCTs) to investigate the impact of intravenous lidocaine on post-hysterectomy recovery. METHODS: This study was completed based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. A systematic search was conducted in PubMed/MEDLINE, the Cochrane Controlled Trials Register (CENTRAL), and Embase up to July 27, 2023. We identified randomized controlled trials (RCTs) involving hysterectomy patients comparing lidocaine to a placebo. Outcome measures included postoperative pain scores at rest and during movement, opioid consumption, postoperative nausea and vomiting (PONV), improvements in functional gastrointestinal recovery, and Quality of Recovery (QoR) scores. RESULTS: Nine RCTs were included in the meta-analysis, comprising 352 patients who received intravenous lidocaine and 354 controls. The analysis revealed that intravenous lidocaine significantly reduced postoperative pain scores at rest at 2, 6, 8, and 24 hours following hysterectomy, as well as postoperative opioid consumption within 24 hours and PONV rates. Furthermore, no observed benefit was noted in shortening the time to first flatus with intravenous lidocaine administration post-hysterectomy. CONCLUSION: Intravenous lidocaine administration effectively reduces acute postoperative pain, opioid consumption, and PONV rates following hysterectomy. Lidocaine serves as an opioid-sparing agent, reducing the morphine equivalent dose while maintaining a similar degree of postoperative pain.

Correction to: Unveiling the next generation of MRI contrast agents: current insights and perspectives on ferumoxytol-enhanced MRI.

[This corrects the article DOI: 10.1093/nsr/nwae057.].

Effective and mechanistic insights into shale gas wastewater reverse osmosis concentrate treatment using ozonation-biological activated carbon process.

Reverse osmosis (RO) plays a pivotal role in shale gas wastewater resource utilization. However, managing the reverse osmosis concentrate (ROC) characterized by high salinity and increased concentrations of organic matter is challenging. In this study, we aimed to elucidate the enhancement effects and mechanisms of pre-ozonation on organic matter removal efficacy in ROC using a biological activated carbon (BAC) system. Our findings revealed that during the stable operation phase, the ozonation (O3 and O3/granular activated carbon)-BAC system removes 43.6-72.2 % of dissolved organic carbon, achieving a 4-7 fold increase in efficiency compared with that in the BAC system alone. Through dynamic analysis of influent and effluent water quality, biofilm performance, and microbial community structure, succession, and function prediction, we elucidated the following primary enhancement mechanisms: 1) pre-ozonation significantly enhances the biodegradability of ROC by 4.5-6 times and diminishes the organic load on the BAC system; 2) pre-ozonation facilitates the selective enrichment of microbes capable of degrading organic compounds in the BAC system, thereby enhancing the biodegradation capacity and stability of the microbial community; and 3) pre-ozonation accelerates the regeneration rate of the granular activated carbon adsorption sites. Collectively, our findings provide valuable insights into treating ROC through pre-oxidation combined with biotreatment.

DL-Serine Hydrazide Hydrochloride Multiple-site Synergy Induced Effective and Stable Formamidine-Rich Perovskite Solar Cells.

The efficiency and stability of solar cells are two key indicators that determine for the commercial feasibility of photovoltaic devices. Formamidine-cesium perovskite has been extensively investigated since its excellent thermal stability and has great potential in achieving high power conversion efficiency. However, during the aging process, especially under light conditions, formamidine-rich perovskites are prone to produce iodine, and the escape of iodine is one of the important factors leading to device degradation. Here, DL-Serine Hydrazide Hydrochloride containing the reducing group is introduced into the precursor solution of formamidine-cesium perovskite, which achieves multiple-site passivation. Hydrazine reacts with iodine to reduce it to iodine ions, inhibiting the escape of iodine. In addition, carbonyl groups and uncoordinated lead ions form coordination bonds to reduce defects. In the end, the perovskite solar cell with DL-Serine Hydrazide Hydrochloride added achieves a champion efficiency of 22.22%, and maintains 85.88% of the initial efficiency after continuous exposure under 1 sun for 7000 s at a relative humidity of ≈40%. Additionally, DL-Serine Hydrazide Hydrochloride added device shows good stability in air environments with relative humidity of 50%-60%. DL-Serine Hydrazide Hydrochloride improves the stability of formamidine-rich perovskite solar cells and provides a low-cost strategy for commercial development.

Polyglycerol-Shelled Reduction-Sensitive Polymersome for DM1 Delivery to HER-2-Positive Breast Cancer.

Supramolecular delivery systems with the prolonged circulation, the potential for diverse functionalization, and few toxin-related limitations have been extensively studied. For the present study, we constructed a linear polyglycerol-shelled polymersome attached with the anti-HER-2-antibody trastuzumab. We then covalently loaded the anticancer drug DM1 in the polymersome via dynamic disulfide bonding. The resulted trastuzumab-polymersome-DM1 (Tra-PS-DM1) exhibits a mean size of 95.3 nm and remarkable drug loading efficiency % of 99.3%. In addition to its superior stability, we observed the rapid release of DM1 in a controlled manner under reductive conditions. Compared to the native polymersomes, Tra-PS-DM1 has shown greatly improved cellular uptake and significantly reduced IC50 up to 17-fold among HER-2-positive cancer cells. Moreover, Tra-PS-DM1 demonstrated superb growth inhibition of HER-2-positive tumoroids; specifically, BT474 tumoroids shrunk up to 62% after 12 h treatment. With exceptional stability and targetability, the PG-shelled Tra-PS-DM1 appears as an attractive approach for HER-2-positive tumor treatment.

Relationship of urinary glyphosate concentrations with glycosylated hemoglobin and diabetes in US adults: a cross-sectional study.

BACKGROUND: Glyphosate is a commonly used herbicide worldwide and is purportedly associated with multiple health effects. Research assessing the association of glyphosate concentrations with glycosylated hemoglobin (HbA1c) levels and the prevalence of diabetes is scarce. We sought to evaluate the association between urinary glyphosate levels and HbA1c levels and the prevalence of diabetes. METHODS: A total of 2,745 adults in the National Health and Nutrition Examination Survey from 2013 to 2016 were included in this study. Generalized linear models (GLM) were applied to evaluate the associations of glyphosate concentrations with HbA1c levels and the prevalence of diabetes. The dose-response relationship was examined using restricted cubic splines (RCS). RESULTS: Significantly positive correlations of urinary glyphosate concentrations with HbA1c levels (percentage change: 1.45; 95% CI: 0.95, 1.96; P < 0.001) and the prevalence of diabetes (OR: 1.45; 95% CI: 1.24, 1.68; P < 0.001) were found after adjustment. Compared with the lowest quartile of glyphosate levels, the highest quartile was positively associated with HbA1c levels (percentage change: 4.19; 95% CI: 2.54, 5.85; P < 0.001) and the prevalence of diabetes (OR: 1.89; 95% CI: 1.37, 2.63; P < 0.001). The RCS curves demonstrated a monotonically increasing dose-response relationship between urinary glyphosate levels and the prevalence of diabetes and HbA1c levels. CONCLUSIONS: Urinary glyphosate concentrations are positively associated with HBA1c levels and the prevalence of diabetes. To verify our findings, additional large-scale prospective investigations are required.

An optimized filter design approach for enhancing imaging quality in industrial linear accelerator.

BACKGROUND: The polychromatic X-rays generated by a linear accelerator (Linac) often result in noticeable hardening artifacts in images, posing a significant challenge to accurate defect identification. To address this issue, a simple yet effective approach is to introduce filters at the radiation source outlet. However, current methods are often empirical, lacking scientifically sound metrics. OBJECTIVE: This study introduces an innovative filter design method that optimizes filter performance by balancing the impact of ray intensity and energy on image quality. MATERIALS AND METHODS: Firstly, different spectra under various materials and thicknesses of filters were obtained using GEometry ANd Tracking (Geant4) simulation. Subsequently, these spectra and their corresponding incident photon counts were used as input sources to generate different reconstructed images. By comprehensively comparing the intensity differences and noise in images of defective and non-defective regions, along with considering hardening indicators, the optimal filter was determined. RESULTS: The optimized filter was applied to a Linac-based X-ray computed tomography (CT) detection system designed for identifying defects in graphite materials within high-temperature gas-cooled reactor (HTR), with defect dimensions of 2 mm. After adding the filter, the hardening effect reduced by 22%, and the Defect Contrast Index (DCI) reached 3.226. CONCLUSION: The filter designed based on the parameters of Average Difference (AD) and Defect Contrast Index (DCI) can effectively improve the quality of defect images.

Polarization-independent edge detection based on the spin-orbit interaction of light.

In previous edge detection schemes based on the spin-orbit interaction of light, the direction and intensity of the edge-enhanced images are influenced by the incident polarization state. In this study, we develop an edge detection strategy that is insensitive to changes in both the incident polarization and the incident angle. The output intensity and transfer function remain entirely impervious to changes in incident polarization, being explicitly formulated as functions of the incident angle, specifically in terms of cot 2⁡θ i and cot⁡θ i , respectively. This behavior is attributed to the opposing nature of the polarization components E~r H-H and E~r V-V in the x-direction after undergoing mapping through the Glan polarizer, while the sum of polarization components E~r H-V and E~r V-H in the y-direction can be simplified to terms independent of incident polarization. Furthermore, we propose a metasurface design to achieve the required optical properties in order to realize the derived edge detection scheme.

Associations between maternal exposure to multiple metals and metalloids and blood pressure in preschool children: A mixture-based approach.

BACKGROUND: Exposure to metals during pregnancy can potentially influence blood pressure (BP) in children, but few studies have examined the mixed effects of prenatal metal exposure on childhood BP. We aimed to assess the individual and combined effects of prenatal metal and metalloid exposure on BP in preschool children. METHODS: A total of 217 mother-child pairs were selected from the Zhuang Birth Cohort in Guangxi, China. The maternal plasma concentrations of 20 metals [e.g. lead (Pb), rubidium (Rb), cesium (Cs), and zinc (Zn)] in early pregnancy were measured by inductively coupled plasmamass spectrometry. Childhood BP was measured in August 2021. The effects of prenatal metal exposure on childhood BP were explored by generalized linear models, restricted cubic spline and Bayesian kernel machine regression (BKMR) models. RESULTS: In total children, each unit increase in the log10-transformed maternal Rb concentration was associated with a 10.82-mmHg decrease (95% CI: -19.40, -2.24) in childhood diastolic BP (DBP), and each unit increase in the log10-transformed maternal Cs and Zn concentrations was associated with a 9.67-mmHg (95% CI: -16.72, -2.61) and 4.37-mmHg (95% CI: -8.68, -0.062) decrease in childhood pulse pressure (PP), respectively. The log10-transformed Rb and Cs concentrations were linearly related to DBP (P nonlinear=0.603) and PP (P nonlinear=0.962), respectively. Furthermore, an inverse association was observed between the log10-transformed Cs concentration and PP (ß =-12.18; 95% CI: -22.82, -1.54) in girls, and between the log10-transformed Rb concentration and DBP (ß =-12.54; 95% CI: -23.87, -1.21) in boys, while there was an increasing association between the log10-transformed Pb concentration and DBP there was an increasing in boys (ß =6.06; 95% CI: 0.36, 11.77). Additionally, a U-shaped relationship was observed between the log10-transformed Pb concentration and SBP (P nonlinear=0.015) and DBP (P nonlinear=0.041) in boys. Although there was no statistically signiffcant difference, there was an inverse trend in the combined effect of maternal metal mixture exposure on childhood BP among both the total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to both individual and mixtures of metals and metalloids influences BP in preschool children, potentially leading to nonlinear and sex-specific effects.

Ring-Opening Coupling of Cyclopropanol with 1,2,3-Triazole for the Synthesis of Fused Triazoles.

A radical ring-opening arylation of cyclopropanol with 1,2,3-triazole has been achieved. This synthetic protocol provides straightforward access to a wide range of structurally diverse and chiral 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridines with high efficiency from readily available chiral cyclopropanols.

Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.

Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5' end sequences derived from cap-snatching in influenza virus mRNA. Here, we report cryo-EM structures to characterize THOV polymerase RNA synthesis initiation and elongation. The structures demonstrate that THOV RNA transcription and replication are able to start with short dinucleotide primers and that the polymerase cap-snatching machinery is likely non-functional. Triggered by RNA synthesis, asymmetric THOV polymerase dimers can form without the involvement of host factors. We confirm that, distinctive from influenza viruses, THOV-polymerase RNA synthesis is weakly dependent of the host factors ANP32A/B/E in human cells. This study demonstrates varied mechanisms in RNA synthesis and host factor utilization among orthomyxoviruses, providing insights into the mechanisms behind thogotoviruses' broad-infectivity range.

Removal of 6-methylquinoline from shale gas wastewater using electrochemical carbon nanotubes filter.

6-Methylquinoline (6-MQ) is identified as a high-concentration organic compound pervasive in shale gas wastewater (SGW) and poses a significant risk of environmental pollution. In response, this study aimed to address these challenges by introducing an innovative electrochemical membrane constructed with multi-walled carbon nanotubes (CNTs) for the removal of 6-MQ. The investigation systematically explored the impact of voltage, initial pollutant concentration, and salinity on the performance of the electrochemical CNTs filter. It was found a positive correlation between removal efficiency and increasing voltage and salinity levels. Conversely, as the initial concentration of pollutants increased, the efficiency showed a diminishing trend. The electrochemical CNTs filter exhibited remarkable efficacy in both adsorption removal and electrochemical oxidation of 6-MQ. Notably, the CNTs membrane exhibited robust adsorption capabilities, evidenced by the sustained adsorption of 6-MQ for over 33 h. Furthermore, applying an electrochemical oxidation voltage of 3 V consistently maintained a removal rate exceeding 34.0% due to both direct and indirect oxidation, underscoring the sustained efficacy of the electrochemical membranes. Besides, real wastewater experiments, while displaying a reduction in removal efficiency compared to synthetic wastewater experiments, emphasized the substantial potential of the electrochemical CNTs filter for practical applications. This study underscores the significant promise of electrochemical membranes in addressing low molecular weight contaminants in SGW, contributing valuable insights for advancing SGW treatment strategies.

Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment.

BACKGROUND: Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC). METHODS: We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC. RESULTS: The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells. CONCLUSION: ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.