α7-nAChR/P300/NLRP3-regulated pyroptosis mediated poor articular cartilage quality induced by prenatal nicotine exposure in female offspring rats.

Nicotine is developmentally toxic. Prenatal nicotine exposure (PNE) affects the development of multiple fetal organs and causes susceptibility to a variety of diseases in offspring. In this study, we aimed to investigate the effect of PNE on cartilage development and osteoarthritis susceptibility in female offspring rats. Wistar rats were orally gavaged with nicotine on days 9-20 of pregnancy. The articular cartilage was obtained at gestational day (GD) 20 and postnatal week (PW) 24, respectively. Further, the effect of nicotine on chondrogenic differentiation was explored by the chondrogenic differentiation model in human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). The PNE group showed significantly shallower Safranin O staining and lower Collagen 2a1 content of articular cartilage in female offspring rats. Further, we found that PNE activated pyroptosis in the articular cartilage at GD20 and PW24. In vitro experiments revealed that nicotine inhibited chondrogenic differentiation and activated pyroptosis. After interfering with nod-like receptors3 (NLRP3) expression by SiRNA, it was found that pyroptosis mediated the chondrogenic differentiation inhibition of WJ-MSCs induced by nicotine. In addition, we found that α7-nAChR antagonist α-BTX reversed nicotine-induced NLRP3 and P300 high expression. And, P300 SiRNA reversed the increase of NLRP3 mRNA expression and histone acetylation level in its promoter region induced by nicotine. In conclusion, PNE caused chondrodysplasia and poor articular cartilage quality in female offspring rats. PNE increased the histone acetylation level of NLRP3 promoter region by α7-nAChR/P300, which resulting in the high expression of NLRP3. Further, NLRP3 mediated the inhibition of chondrogenic differentiation by activating pyroptosis.

Sulfur occupancy-induced construction of ant-nest-like NiMo/CF(N) electrode for highly efficient hydrogen evolution.

The microstructure of the electrocatalyst plays a critical role in the reaction efficiency and stability during electrochemical water splitting. Designing an efficient and stable electrocatalyst, further clarifying the synthesis mechanism, is still an important problem to be solved urgently. Inspired by the copper pyrometallurgy theory, an exceptionally active NiMo/CF(N) electrode, consisting of an ant-nest-like copper foam substrate (defined as CF(N)) and deposited NiMo layer, was fabricated for the alkaline hydrogen evolution reaction (HER). Our findings expounded the structure construction mechanism and highlighted the pivotal role of the spatial occupancy of sulfur atoms in the construction of the ant-nest-like structure. The NiMo/CF(N) composite, characterized by channels with a 2 µm diameter, showcases strong electronic interactions, increased catalytic active sites, enhanced electron/ion transport, and facilitated gas release during HER. Remarkably, NiMo/CF(N) demonstrates ultralow overpotentials of 21 mV to deliver a current density of 10 mA cm-2 in 1 M KOH. This electrode also exhibits outstanding durability, maintaining a current density of 200 mA cm-2 for 110 h, attributed to the chemical and structural integrity of its catalytic surface and the excellent mechanical properties of the electrode. This work advances the fundamental understanding of constructing micro/nano-structured electrocatalysts for highly efficient water splitting.

Key genomes, transcriptomes, proteins, and metabolic factors involved in the detoxification/tolerance of TNT and its intermediates by bacteria in anaerobic/aerobic environments.

Novel microbial strains capable of efficient degradation of TNT and typical intermediates (2-ADNT and 4-ADNT) in aerobic/anaerobic environment were screened and isolated from ammunition-contaminated sites. The key genomes, transcriptomes, proteins, and metabolic factors for microbial detoxification/tolerance to pollutants in anaerobic and aerobic environments were analyzed for the first time. The bacterial genome, which is rich in metabolism and environmental information-processing functional genes, provides transcriptional and translational-related proteins for detoxifying/tolerating pollutants. At the transcriptional level, bacteria significantly expressed genes related to inositol phosphate metabolism for regulating membrane transport, maintaining the cytoskeleton, and signal transduction. At the protein level, genes involved in antioxidation, fat metabolism, sugar synthesis/degradation, and pyruvate metabolism were significantly expressed. At the metabolic level, riboflavin metabolism, which regulates membrane integrity, protects against oxidative stress, and maintains the sugar-protein-fat balance, showed significant responses. Bacteria simultaneously regulate amino acid metabolism, carbohydrate metabolism, and N/P/S cycles to maintain homeostatic cellular energy supplies. The key pathway for pollutant degradation in bacteria is nitrotoluene degradation. The molecular mechanism of bacterial tolerance to pollutants involves the regulation of oxidative phosphorylation and basic cycle pathways to maintain gene transcription, protein translation, and metabolic cycles.

Lignin nanoparticles formation by multiscale structure control to regulate morphology and their adsorption, nucleation, and growth on chitin nanofibers.

The lignin nanoparticles (LNPs) synthesis relies on lignin polymers with heterogeneous molecules and properties, which impose significant limitations on the preparation and property regulation. The multiscale structure of lignin from monomers to oligomers, provides a potential pathway for precise regulation of its physical and chemical properties. The study addresses this challenge by employing coniferyl alcohol and sinapyl alcohol as monomers and separately utilizing the Zulaufverfaren (ZL) and Zutropfverfaren (ZT) methods to synthesize different types of lignin dehydrogenation polymers (DHPs) including guaiacyl (G)-ZL-DHP, G-ZT-DHP, syringyl (S)-ZL-DHP, and S-ZT-DHP. The investigation highlights the chemical bonds as essential components of lignin primary structure. Additionally, the secondary structure is influenced by branched and linear molecular structures. G unit provides some branching points, which are utilized and amplified in the ZL process of DHPs synthesis. The branched DHPs aggregate at the edge and form rod-like LNPs. While linear DHPs aggregate around the center, presenting polygonal LNPs. The study identifies that the branched LNPs, characterized by more surface charges and lower steric hindrance, can form a stable complex with chitin nanofibers. Emulsions with varying oil-to-water ratios were subsequently prepared, opening a new window for the application of LNPs in fields such as food and cosmetics.

Structure of POU2AF1 recombinant protein and it affects the progression and treatment of liver cancer based on WGCNA and molecular docking analysis.

Hepatocellular carcinoma, also referred to as HCC, is the most frequent form of primary liver cancer. It is anticipated that the discovery of the molecular pathways related with HCC would open up new possibilities for the treatment of HCC.WGCNA (Weighted gene co-expression network analysis) and molecular docking analysis were used to study the structural characteristics of POU2AF1 recombinant protein and its interaction with related proteins. Normal samples were placed in one group, and tumor samples were placed in another group inside the GEO database. We continued our investigation of the DEGs by performing an enrichment analysis using GO and KEGG. The GSCA platform is utilized in the process of doing an analysis of the connection between gene expression and medication sensitivity. In the end, the core target and the active molecule were both given the green light for a molecular docking investigation. POU2AF1 is being considered as a possible therapeutic target for HCC, and the results of our work have presented novel concepts for the treatment of HCC.

Prediction of laser printers and cartridges based on three-dimensional profiles via discrimination analysis.

Printer source prediction is an important task when examining questioned documents. While some research has provided methods to predict the source printer of documents, with the advent of compatible consumables, printer prediction could become more complex and difficult. Predicting the source printer after replacing cartridges and identifying the source of printer cartridges are unresolved issues that are rarely addressed in current research. Herein, we introduce a novel technique to predict the manufacturer, model, and cartridges of laser printers (i.e., compatible, and original cartridges) used to produce a given document. Document samples produced using eight laser printers and 247 cartridges were collected to establish a dataset. Common manufacturers included HP, Canon, Lenovo, and Epson. After obtaining white-light images and three-dimensional profile images of printed characters, a morphological analysis was conducted by questioned document examiners (QDEs) using microscopy. Microscopic image features across a series of images were also extracted and analyzed using algorithms. Then, six high-dimensional reduction algorithms were used to obtain between- and within-printer variations as well as between- and within-cartridge variations. Finally, we conducted principal component analysis (PCA) and discriminant analysis. For 40 % of the samples, mixed discrimination analysis (MDA) and fixed discrimination analysis (FDA) were employed to predict the manufacturer, model and cartridge of laser printers used to produce the questioned printed document; the remaining 60 % samples comprised the training dataset. In the prediction of manufacturer, model and cartridge, our method achieved mean accuracies of 95.5 %, 97.5 %, and 90.2 %, respectively. Hence, this technique could reasonably aid in predicting the manufacturer, model, and cartridge of a laser printer, even if different cartridges are loaded into printers.

Higher immune cell radiation dose is correlated with poor tumor control and survival in patients with non-small cell lung cancer receiving postoperative radiotherapy.

INTRODUCTION: The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. METHODS: Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan-Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. RESULTS: In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P = .007), DFS (HR 1.129, P = .015), LRFS (HR 1.211, P = .002), and DMFS (HR 1.131, P = .057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. CONCLUSIONS: EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning.

Promoting OH* adsorption by defect engineering of CuO catalysts for selective electro-oxidation of amines to nitriles coupled with hydrogen production.

Developing a high-efficiency benzylamine oxidation reaction (BOR) to replace the sluggish oxygen evolution reaction (OER) is an attractive pathway to promote H2 production and concurrently realize organic conversion. However, the electrochemical BOR performance is still far from satisfactory. Herein, we present a self-supported CuO nanorod array with abundant oxygen vacancies on copper foam (Vo-rich CuO/CF) as a promising anode for selective electro-oxidation of benzylamine (BA) to benzonitrile (BN) coupled with cathodic H2 generation. In situ infrared spectroscopy demonstrates the selective conversion of BA into BN on Vo-rich CuO. Furthermore, in situ Raman spectroscopy discloses a direct electro-oxidation mechanism of BA driven by electroactive hydroxyl species (OH*) over the Vo-rich CuO catalyst. Theoretical and experimental studies verify that the presence of oxygen vacancies is more favorable for the adsorption of OH* and BA molecules, enabling accelerated kinetics for the BOR. As expected, the Vo-rich CuO/CF electrode delivers outstanding BOR activity and stability, giving a high faradaic efficiency (FE) of over 93% for BN production at a potential of 0.40 V vs. Ag/AgCl. Impressively, almost 100% FE for H2 production can be further achieved at the NiSe cathode by integrating BA oxidation in a two-electrode electrolyzer.

Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome.

BACKGROUND: Chronic heart failure is a complex clinical syndrome. The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure; however, the underlying molecular mechanism is still not clear. AIM: To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure. METHODS: The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target genes of chronic heart failure were searched in the Genecards database. The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drug-disease targets, which were then used to construct a key chemical component-target network using Cytoscape 3.7.2 software. The protein-protein interaction network was constructed using the String database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database. Finally, our previously published relevant articles were searched to verify the results obtained via network pharmacology. RESULTS: A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified, of which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, HSP90AA1, p65, MAPK8, MAPK14, IL6, EGFR, EDN1, FOS, and other proteins. The pathways identified by KEGG enrichment analysis include pathways in cancer, IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, cAMP signaling pathway, NF-kappaB signaling pathway, AMPK signaling pathway, etc. Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α, IL-6, MAPK, cAMP, and AMPK pathways to affect the mitochondrial structure of myocardial cells, oxidative stress, and energy metabolism, thus achieving the therapeutic effects on chronic heart failure. CONCLUSION: The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes, oxidative stress, energy metabolism, and other processes. Future studies are warranted to investigate the role of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Patient-reported outcomes in lung cancer surgery: A narrative review.

Lung cancer is a leading cause of cancer-related mortality worldwide, profoundly affecting patients' quality of life. Patient-reported outcomes (PROs) provide essential insights from the patients' perspective, a crucial aspect often overlooked by traditional clinical outcomes. This review synthesizes research on the role of PROs in lung cancer surgery to enhance patient care and outcomes. We conducted a comprehensive literature search across PubMed, Scopus, and Web of Science up to March 2024, using terms such as "lung cancer," "Patient Reported Outcome," "lobectomy," "segmentectomy," and "lung surgery." The criteria included original studies on lung cancer patients who underwent surgical treatment and reported on PROs. After screening and removing duplicates, reviews, non-English articles, and irrelevant studies, 36 research articles were selected, supported by an additional 53 publications, totaling 89 references. The findings highlight the utility of PROs in assessing post-surgical outcomes, informing clinical decisions, and facilitating patient-centered care. However, challenges in standardization, patient burden, and integration into clinical workflows remain, underscoring the need for further research and methodological refinement. PROs are indispensable for understanding the quality-of-life post-surgery and enhancing communication and decision-making in clinical practice. Their integration into routine care is vital for a holistic approach to lung cancer treatment, promising significant improvements in patient outcomes and quality of care.

SLC12A8 promotes the migration and invasion of non-small cell lung cancer (NSCLC) cells.

This study aims to investigate the impacts of SLC12A8 on the invasion, migration, and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) cells. GEPIA database was employed to examine SLC12A8 expression pattern in lung cancer cells. Subsequently, qRT-PCR and Western blot analyses were conducted to assess SLC12A8 expression in NSCLC tissues and cell lines. The overall prognosis of NSCLC patients was evaluated using Kaplan-Meier plot and univariate and multivariate COX regression curves. The knockdown of SLC12A8 was established using lentivirus-mediated shRNA in A549 and H1299 cells. Cell proliferation, invasion, migration, and apoptosis were evaluated using CCK-8 assay, transwell, and flow cytometry techniques, respectively. Western blot analysis was performed to measure the expression levels of EMT-related proteins (E-cadherin and vimentin). The expression level of SLC12A8 was found to be significantly higher in both NSCLC cell lines and tissues. High SLC12A8 expression was correlated with a poor prognosis in NSCLC patients. Knocking down SLC12A8 led to a significant decrease in proliferation, migration, and invasion abilities, while promoting apoptosis in NSCLC cells. Additionally, SLC12A8 knockdown resulted in decreased levels of N-cadherin and vimentin, along with increased E-cadherin expression. The results indicate that reducing SLC12A8 expression may suppress the malignant phenotype of NSCLC cells, as well as the EMT. SLC12A8 may serve as a target for the clinical management of NSCLC progression.

Design and Evaluation of 3-Phenyloxetane Derivative Agonists of the Glucagon-Like Peptide-1 Receptor.

Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.

Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. METHOD: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. RESULTS: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978-0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. CONCLUSION: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Safety of propofol-assisted deep extubation in the dental treatment of children-a retrospective, observational study.

PURPOSE: Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of children was assessed. MATERIALS AND METHODS: Children with severe caries who received dental treatment under general anesthesia and deep extubation between January 2017 and June 2023 were included in this study. Data were collected on the following variables: details and time of anesthesia, perioperative vital signs, and incidence of postoperative complications. The incidence of laryngeal spasm (LS) was considered to be the primary observation indicator. RESULTS: The perioperative data obtained from 195 children undergoing dental treatment was reviewed. The median age was 4.2 years (range: 2.3 to 9.6 years), and the average duration of anesthesia was 2.56 h (range 1 to 4.5 h). During intubation with a videoscope, purulent mucus was found in the pharyngeal cavity of seven children (3.6%); LS occurred in five of them (2.6%), and one child developed a fever (T = 37.8 °C) after discharge. Five children (2.6%) experienced emergence agitation (EA) in the recovery room. Also, 13 children (6.7%) experienced epistaxis; 10 had a mild experience and three had a moderate experience. No cases of airway obstruction (AO) and hypoxemia were recorded. The time to open eyes (TOE) was 16.3 ± 7.2 min. The incidence rate of complications was 23/195 (11.8%). Emergency tracheal reintubation was not required. Patients with mild upper respiratory tract infections showed a significantly higher incidence of complications (P < 0.001). CONCLUSIONS: Propofol-assisted deep extubation is a suitable technique that can be used for pediatric patients who exhibited non-cooperation in the outpatient setting. Epistaxis represents the most frequently encountered complication. Preoperative upper respiratory tract infection significantly increases the risk of complications. The occurrence of EA was notably lower than reported in other studies.

Dietary salt promotes cognitive impairment through repression of SIRT3/PINK1-mediated mitophagy and fission.

Dietary salt is increasingly recognized as an independent risk factor for cognitive impairment. However, the exact mechanisms are not yet fully understood. Mitochondria, which play a crucial role in energy metabolism, are implicated in cognitive function through processes such as mitochondrial dynamics and mitophagy. While mitochondrial dysfunction is acknowledged as a significant determinant of cognitive function, the specific relationship between salt-induced cognitive impairment and mitochondrial health has yet to be fully elucidated. Here, we explored the underlying mechanism of cognitive impairment of mice and N2a cells treated with high-salt focusing on the mitochondrial homeostasis with western blotting, immunofluorescence, electron microscopy, RNA sequencing, and more. We further explored the potential role of SIRT3 in salt-induced mitochondrial dysfunction and synaptic alteration through plasmid transfection and siRNA. High salt diet significantly inhibited mitochondrial fission and blocked mitophagy, leading to dysfunctional mitochondria and impaired synaptic plasticity. Our findings demonstrated that SIRT3 not only promote mitochondrial fission by modulating phosphorylated DRP1, but also rescue mitophagy through promoting PINK1/Parkin-dependent pathway. Overall, our data for the first time indicate that mitochondrial homeostasis imbalance is a driver of impaired synaptic plasticity in a cognitive impairment phenotype that is exacerbated by a long-term high-salt diet, and highlight the protective role of SIRT3 in this process.

Efficient recovery of highly pure CaF2 from fluorine-containing wastewater using an icy lime solution.

Developing a feasible and low-cost strategy for the recovery of calcium fluoride efficiently from fluoride-containing wastewater is very essential for the recycle of fluoride resources. Herein, a modified lime precipitation method was employed to recover CaF2 from fluorinated wastewater using a special icy lime solution. Intriguingly, the highest F- removal was greater than 95% under the optimal condition, leaving a fluoride concentration from 200 to 8.64 mg/L, while the lime dosage was much lower than that of industry. Importantly, spherical-shaped CaF2 particles with a 93.47% purity and size smaller than 600 nm were recovered, which has a high potential for the production of hydrofluoric acid. Besides, the precipitation was significantly affected by Ca/F molar ratio, stirring time, temperature, and solution pH. Furthermore, the thermodynamics and kinetics were investigated in detail to reveal the crystallization process. As a result, the defluorination reaction followed the pseudo-second order reaction kinetics model. Also, CO2 in the air adversely influenced the CaF2 purity. Based on this facile method, a high lime utilization efficiency was applied to defluorination, which contributed to protecting the environment and saving costs. This study, therefore, provides a feasible approach for the green recovery of fluorine resources and has significance for related research.

Integration of PSAd and multiparametric MRI to forecast biopsy outcomes in biopsy-naïve patients with PSA 4~20 ng/ml.

Introduction: This study aims to investigate whether the transrectal ultrasound-guided combined biopsy (CB) improves the detection rates of prostate cancer (PCa) and clinically significant PCa (csPCa) in biopsy-naïve patients. We also aimed to compare the Prostate Imaging Reporting and Data System (PI-RADS v2.1) score, ADC values, and PSA density (PSAd) in predicting csPCa by the combined prostate biopsy. Methods: This retrospective and single-center study included 389 biopsy-naïve patients with PSA level 4~20 ng/ml, of whom 197 underwent prebiopsy mpMRI of the prostate. The mpMRI-based scores (PI-RADS v2.1 scores and ADC values) and clinical parameters were collected and evaluated by logistic regression analyses. Multivariable models based on the mpMRI-based scores and clinical parameters were developed by the logistic regression analyses to forecast biopsy outcomes of CB in biopsy-naïve patients. The ROC curves measured by the AUC values, calibration plots, and DCA were performed to assess multivariable models. Results: The CB can detect more csPCa compared with TRUSB (32.0% vs. 53%). The Spearman correlation revealed that Gleason scores of the prostate biopsy significantly correlated with PI-RADS scores and ADC values. The multivariate logistic regression confirmed that PI-RADS scores 4, 5, and prostate volume were important predictors of csPCa. The PI-RADS+ADC+PSAd (PAP) model had the highest AUCs of 0.913 for predicting csPCa in biopsy-naïve patients with PSA level 4~20 ng/ml. When the biopsy risk threshold of the PAP model was greater than or equal to 0.10, 51% of patients could avoid an unnecessary biopsy, and only 5% of patients with csPCa were missed. Conclusion: The prebiopsy mpMRI and the combined prostate biopsy have a high CDR of csPCa in biopsy-naïve patients. A multivariable model based on the mpMRI-based scores and PSAd could provide a reference for clinicians in forecasting biopsy outcomes in biopsy-naïve patients with PSA 4~20 ng/ml and make a more comprehensive assessment during the decision-making of the prostate biopsy.

Mechanisms of exacerbation of Th2-mediated eosinophilic allergic asthma induced by plastic pollution derivatives (PPD): A molecular toxicological study involving lung cell ferroptosis and metabolomics.

Polystyrene microplastics (PS-MP) and dibutyl phthalate (DBP) are plastic pollution derivatives (PPDs) commonly found in the natural environment. To investigate the effects of PPD exposure on the risk of allergic asthma, we established a PPD exposure group in a mouse model. The dose administered for PS-MP was 0.1 mg/d and for DBP was 30 mg/kg/d, with a 5-week oral administration period. The pathological changes of airway tissue and the increase of oxidative stress and inflammatory response confirmed that PPD aggravated eosinophilic allergic asthma in mice. The mitochondrial morphological changes and metabolomics of mice confirmed that ferrotosis and oxidative stress played key roles in this process. Treatment with 100 mg/Kg deferoxamine (DFO) provided significant relief, and metabolomic analysis of lung tissue supported the molecular toxicological. Our findings suggest that the increased levels of reactive oxygen species (ROS) in the lungs lead to Th2-mediated eosinophilic inflammation, characterized by elevated IL-4, IL-5, and eosinophils, and reduced INF-γ levels. This inflammatory response is mediated by the NFκB pathway and exacerbates type I hypersensitivity through increased IL-4 production. In this study, the molecular mechanism by which PPD aggravates asthma in mice was elucidated, which helps to improve the understanding of the health effects of PPD and lays a theoretical foundation for addressing the health risks posed by PPD.