Sublobectomy and lymph node sampling are adequate for patients with invasive lung adenocarcinoma presenting as pure ground glass nodules.

PURPOSE: In this study, we aimed to investigate the prognosis of invasive lung adenocarcinoma that manifests as pure ground glass nodules (pGGNs) and confirm the effectiveness of sublobectomy and lymph node sampling in patients with pGGN-featured invasive adenocarcinoma (IAC). MATERIALS AND METHODS: We retrospectively enrolled 139 patients with pGGN-featured IAC, who underwent complete resection in two medical institutions between January 2011 and May 2022. Stratification analysis was conducted to ensure balanced baseline characteristics among the patients. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared between the groups using Kaplan-Meier survival curves and log-rank test. RESULTS: The 5-year OS and DFS rates for patients with IAC presenting as pGGNs after surgery were 96.5% and 100%, respectively. No lymph node metastasis or recurrence was observed in any of the enrolled patients. There was no statistically significant difference in the 5-year OS between patients who underwent lobectomy or sublobectomy, along with lymph node resection or sampling. CONCLUSION: IAC presented as pGGNs exhibited low-grade malignancy and had a relatively good prognosis. Therefore, these patients may be treated with sublobectomy and lymph node sampling.

Clinical relevance of somatic mutations in Chinese lung adenocarcinoma and their prognostic implications for survival.

BACKGROUND: To comprehensively elucidate the genomic and mutational features of lung cancer cases, and lung adenocarcinoma (LUAD), it is imperative to conduct ongoing investigations into the genomic landscape. In this study, we aim to analyze the somatic mutation profile and assessed the significance of these informative genes utilizing a retrospective LUAD cohort. METHODS: A total of 247 Chinese samples were analyzed to exhibit the tumor somatic genomic alterations in patients with LUAD. The Cox regression analysis was employed to identify prognosis-related genes and establish a predictive model for stratifying patients with LUAD. RESULTS: In the Dianjiang People's Hospital (DPH) cohort, the top five frequent mutated genes were (Epidermal growth factor receptor) EGFR (68%), TP53 (30%), RBM10 (13%), LRP1B (9%), and KRAS (9%). Of which, EGFR is a mostly altered driver gene, and most mutation sites are located in tyrosine kinase regions. Oncogene pathway alteration and mutation signature analysis demonstrated the RTK-RAS pathway alteration, and smoking was the main carcinogenic factor of the DPH cohort. Furthermore, we identified 34 driver genes in the DPH cohort, including EGFR (68%), TP53 (30.4%), RBM10 (12.6%), KRAS (8.5%), LRP1B (8.5%), and so on, and 45 Clinical Characteristic-Related Genes (CCRGs) were found to closely related to the clinical high-risk factors. We developed a Multiple Parameter Gene Mutation (MPGM) risk model by integrating critical genes and oncogenic pathway alterations in LUAD patients from the DPH cohort. Based on publicly available LUAD datasets, we identified five genes, including BRCA2, Anaplastic lymphoma kinase (ALK), BRAF, EGFR, and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA), according to the multivariable Cox regression analysis. The MPGM-low group showed significantly better overall survival (OS) compared to the MPGM-high group (p < 0.0001, area under the curve (AUC) = 0.754). The robust performance was validated in 55 LUAD patients from the DPH cohort and another LUAD dataset. Immune characteristics analysis revealed a higher proportion of primarily DCs and mononuclear cells in the MPGM-low risk group, while the MPGM-high risk group showed lower immune cells and higher tumor cell infiltration. CONCLUSION: This study provides a comprehensive genomic landscape of Chinese LUAD patients and develops an MPGM risk model for LUAD prognosis stratification. Further follow-up will be performed for the patients in the DPH cohort consistently to explore the resistance and prognosis genetic features.

Targeting the aryl hydrocarbon receptor with FICZ regulates IL-2 and immune infiltration to alleviate Hashimoto's thyroiditis in mice.

Hashimoto's thyroiditis (HT) is the most frequent autoimmune disorder. Growing work points to the involvement of aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, in the regulation of immune homeostasis. However, the roles of AhR and its ligands in HT remains unclear. In this study, we leveraged public human database analyses to postulate that the AhR expression was predominantly in thyroid follicular cells, correlating significantly with the thyroid infiltration levels of multiple immune cells in HT patients. Using a thyroglobulin-induced HT mouse model and in vitro thyroid follicular epithelial cell cultures, we found a significant downregulation of AhR expression in thyrocytes both in vivo and in vitro. Conversely, activating AhR by FICZ, a natural AhR ligand, mitigated inflammation and apoptosis in thyrocytes in vitro and conferred protection against HT in mice. RNA sequencing (RNA-seq) of thyroid tissues indicated that AhR activation moderated HT-associated immune or inflammatory signatures. Further, immunoinfiltration analysis indicated that AhR activation regulated immune cell infiltration in the thyroid of HT mice, such as suppressing cytotoxic CD8+ T cell infiltration and promoting anti-inflammatory M2 macrophage polarization. Concomitantly, the expression levels of interleukin-2 (IL-2), a lymphokine that downregulates immune responses, were typically decreased in HT but restored upon AhR activation. In silico validation substantiated the binding interaction between AhR and IL-2. In conclusion, targeting the AhR with FICZ regulates IL-2 and immune infiltration to alleviate experimental HT, shedding new light on the therapeutic intervention of this prevalent disease.

Giant cell tumor of soft tissue involving thyroid gland: a case report and review of the literature.

BACKGROUND: Giant cell tumor of soft tissue is a low malignant uncommon neoplasm, with histologic features and immunophenotype similar to its bone counterpart. Primary giant cell tumor of soft tissue in the thyroid gland is considered an exceedingly rare entity. CASE PRESENTATION: We describe a case of primary thyroid giant cell tumor of soft tissue in a 69-year-old Chinese female patient. Neck ultrasonography showed a 19 mm × 12 mm × 5 mm nodule with heterogeneous echo and clear boundary located within the left thyroid. Histopathological examination revealed that the neoplasm was composed of two morphological components, mononuclear cells admixed with multinucleated osteoclast-like giant cells. Immunohistochemically, the tumor cells were positive for CD68 and vimentin, but were negative for epithelial membrane antigen, cytokeratin, and additional muscle markers. She underwent left unilateral thyroidectomy, and total thyroidectomy was performed for local recurrence 3 months later. The patient remained well without recurrence or metastasis following up for 12 months. CONCLUSION: The significance of this case lies in its rarity, the challenge of preoperative clinical diagnosis, and the differential diagnosis with other malignancies.

Transforming electrochemical hydrogen Production: Tannic Acid-Boosted CoNi alloy integration with Multi-Walled carbon nanotubes for advanced bifunctional catalysis.

The dimensions of alloy nanoparticles or nanosheets have emerged as a critical determinant for their prowess as outstanding electrocatalysts in water decomposition. Remarkably, the reduction in nanoparticle size results in an expanded active specific surface area, elevating reaction kinetics and showcasing groundbreaking potential. In a significant leap towards innovation, we introduced tannic acid (TA) to modify multi-walled carbon nanotubes (MWCNTs) and CoNi alloys. This ingenious strategy not only finely tuned the size of CoNi alloys but also securely anchored them to the MWCNTs substrate. The resulting synergistic "carbon transportation network" accelerated electron transfer during the reaction, markedly enhancing efficiency. Furthermore, the exceptional synergy of Co and Ni elements establishes Co0.84Ni1.69/MWCNTs as highly efficient electrocatalysts. Experimental findings unequivocally demonstrate that TA-Co0.84Ni1.69/MWCNTs require minimal overpotentials of 171 and 294 mV to achieve a current density of ± 10 mA cm-2. Serving as both anode and cathode for overall water splitting, TA-Co0.84Ni1.69/MWCNTs demand a low voltage of 1.66 V at 10 mA cm-2, maintaining structural integrity throughout extensive cyclic stability testing. These results propel TA-Co0.84Ni1.69/MWCNTs as promising candidates for future electrocatalytic advancements.

Paint sludge derived activated carbon encapsulating with cobalt nanoparticles for non-radical activation of peroxymonosulfate.

Industrial solid waste management and recycling are important to environmental sustainability. In this study, cobalt (Co) nanoparticles encapsulated in paint sludge-derived activated carbon (AC) were fabricated. The Co-AC possessed high conductivity, magnetic properties and abundant metal oxide impurities (TiAlSiOx), which was applied as multifunctional catalyst for peroxymonosulfate (PMS) activation. Compared to pure AC, the Co-AC exhibited significant enhanced performance for degradation of tetracycline hydrochloride (TCH) via PMS activation. Mechanism studies by in situ Raman spectroscopy, Fourier infrared spectroscopy, electrochemical analysis and electron paramagnetic resonance suggested that surface-bonded PMS (PMS*) and singlet oxygen (1O2) are the dominant reactive species for TCH oxidation. The non-radical species can efficiently oxidize electron-rich pollutants with high efficiency, which minimized the consumption of PMS and the catalyst. The removal percentages of TCH reached 97 % within 5 min and âˆ¼ 99 % within 15 min in the Co-AC/PMS system. The Co active sites facilitated PMS adsorption to form the PMS* and the TiAlSiOx impurities provided abundant oxygen vacancy for generation of the 1O2. In addition, the Co-AC/PMS system achieved high efficiency and stability for oxidation of the target pollutants over a long-term continuous operation. This work not only offers a cost-effective approach for recycling industrial waste but also provides new insights into the application of waste-derived catalyst for environmental remediation.

A novel bi-functional cold-adaptive chitinase from Chitinilyticum aquatile CSC-1 for efficient synthesis of N-acetyl-D-glucosaminidase.

In order to better utilize chitinolytic enzymes to produce high-value N-acetyl-D-glucosamine (GlcNAc) from chitinous waste, there is an urgent need to explore bi-functional chitinases with exceptional properties of temperature, pH and metal tolerance. In this study, we cloned and characterized a novel bi-functional cold-adaptive chitinase called CaChi18A from a newly isolated strain, Chitinilyticum aquatile CSC-1, in Bama longevity village of Guangxi Province, China. The activity of CaChi18A at 50 °C was 4.07 U/mg. However, it exhibited significant catalytic activity even at 5 °C. Its truncated variant CaChi18A_ΔChBDs, containing only catalytic domain, demonstrated significant activity levels, exceeding 40 %, over a temperature range of 5-60 °C and a pH range of 3 to 10. It was noteworthy that it displayed tolerance towards most metal ions at a final concentration of 0.1 mM, including Fe3+ and Cu2+ ions, retaining 122.52 ± 0.17 % and 116.42 ± 1.52 % activity, respectively. Additionally, it exhibited favorable tolerance towards organic solvents with the exception of formic acid. Interestedly, CaChi18A and CaChi18A_ΔChBDs had a low Km value towards colloidal chitin (CC), 0.94 mg mL-1 and 2.13 mg mL-1, respectively. Both enzymes exhibited chitobiosidase and N-acetyl-D-glucosaminidase activities, producing GlcNAc as the primary product when hydrolyzing CC. The high activities across a broader temperature and pH range, strong environmental adaptability, and hydrolytic properties of CaChi18A_ΔChBDs suggested that it could be a promising candidate for GlcNAc production.

Role of the tripartite motif-containing (TRIM) family of proteins in insulin resistance and related disorders.

Emerging evidence suggests that the ubiquitin-mediated degradation of insulin-signalling-related proteins may be involved in the development of insulin resistance and its related disorders. Tripartite motif-containing (TRIM) proteins, a superfamily belonging to the E3 ubiquitin ligases, are capable of controlling protein levels and function by ubiquitination, which is essential for the modulation of insulin sensitivity. Recent research has indicated that some of these TRIMs act as key regulatory factors of metabolic disorders such as type 2 diabetes mellitus, obesity, nonalcoholic fatty liver disease, and atherosclerosis. This review provides a comprehensive overview of the latest evidence linking TRIMs to the regulation of insulin resistance and its related disorders, their roles in regulating multiple signalling pathways or cellular processes, such as insulin signalling pathways, peroxisome proliferator-activated receptor signalling pathways, glucose and lipid metabolism, the inflammatory response, and cell cycle control, as well as recent advances in the development of TRIM-targeted drugs.

Multi-omics analysis reveals the molecular basis of flavonoid accumulation in fructus of Gardenia (Gardenia jasminoides Ellis).

BACKGROUND: The fruits of Gardenia are rich in flavonoids and geniposides, which have various pharmacological effects such as antioxidant, anti-inflammatory and anticancer. In this study, we analyzed the transcriptome and metabolome of gardenia peel and kernel at different growth stages, revealed the regulatory network related to flavonoid synthesis, and identified the key regulatory genes. RESULTS: The results showed that in terms of flavonoid metabolic pathways, gardenia fruits mainly synthesized cinnamic acid through the phenylpropanoid pathway, and then synthesized flavonoids through the action of catalytic enzymes such as 4-coumaroyl-CoA ligase, chalcone synthase, chalcone isomerase and flavanol synthase, respectively. In addition, we found that the metabolomics data showed a certain spatial and temporal pattern in the expression of genes related to the flavonoid metabolism pathway and the relative content of metabolites, which was related to the development and ripening process of the fruit. CONCLUSIONS: In summary, this study successfully screened out the key genes related to the biosynthesis metabolism of flavonoids in gardenia through the joint analysis of transcriptome and metabolome. This is of certain significance to the in-depth study of the formation mechanism of gardenia efficacy components and the improvement of quality.

Structural and Physical Properties of Alginate Pretreated by High-Pressure Homogenization.

To develop a high-efficient extraction method, we investigated the use of high-pressure homogenization (HPH) as a novel pretreatment technology for the extraction of sodium alginate (SA) from Laminaria japonica. After the single-factor experiment, the results demonstrated that under the conditions of 100 MPa HPH pressure, 4 cycles, pH 6.0, and 0.5% EDTA for 3.0 h, the optimized extraction yield of HPH reached 34%. To further clarify the effect on the structural properties of HPH-extracted SA, we conducted comprehensive analysis using SEM, FTIR, MRS, NMR, XRD, TGA, and a T-AOC assay. Our findings revealed that HPH pretreatment significantly disrupted the structure of L. japonica cells and reduced their crystallinity to 76.27%. Furthermore, the antioxidant activity of HPH-extracted SA reached 0.02942 mgVceq∙mg-1. Therefore, the HPH pretreatment method is a potential strategy for the extraction of alginate.

Enhanced methane yield in anaerobic digestion of waste activated sludge by combined pretreatment with fungal mash and free nitrous acid.

This study explores a novel approach for enhancing anaerobic digestion of waste activated sludge (WAS) through the combined pretreatment of fungal mash and free nitrous acid (FNA). Aspergillus PAD-2, a fungal strain with superior hydrolase secretion, was isolated from WAS and cultivated in-situ on food waste to produce fungal mash. The solubilization of WAS by fungal mash achieved a high soluble chemical oxygen demand release rate of 548 mg L-1 h-1 within first 3 h. The combined pretreatment of fungal mash and FNA further improved the sludge solubilization by 2-fold and resulted in a doubled methane production rate of 416±11 mL CH4 g-1 volatile solids. The Gompertz model analysis revealed a higher maximum specific methane production rate and shortened lag time by the combined pretreatment. These results demonstrate that the combined fungal mash and FNA pretreatment offers a promising alternative for fast anaerobic digestion of WAS.

Controlling the electronic structure of Fe-MOF electrocatalyst for enhanced water splitting and urea oxidation: A plasma-assisted approach.

The design of high-performance electrocatalysts for water splitting and urea oxidation reactions requires effective regulation of their electronic structure and electrochemical surface area (ECSA). In this study, we developed an in-situ grown Fe-MOF electrocatalyst on Fe foam (FF) by using a combination of easy hydrothermal synthesis and advanced plasma technology (Fe-MOF/FF). By varying the plasma treatment time, we could tailor the surface morphology and electronic structure of the Fe-MOF/FF microrods. Meanwhile, density functional theory (DFT) calculations investigated the catalytic mechanism, revealing that plasma-treated Fe-MOF/FF has a lower energy barrier for water splitting and H* adsorption during the HER process, and higher catalytic activity for UOR. Additionally, the electronic density of optimized Fe-MOF/FF is significantly expanded near the Fermi level. Remarkably, our catalysts achieved exceptional activity in both water splitting and urea electrolysis, requiring only 1.54 V and 1.472 V, respectively, at 10 mA cm-2, with excellent stability. Our findings highlight the potential of plasma technology as a powerful tool for developing multifunctional electrocatalysts for clean energy and industrial wastewater treatment applications.

Coupling Zn2+ doping and rich oxygen vacancies in MnO2 nanowire toward advanced aqueous zinc-ion batteries.

Easy collapse of structure and sluggish reaction kinetics restrict the practical application of MnO2 in the field of aqueous Zn-ion batteries (ZIBs). To circumvent these obstacles, Zn2+ doping MnO2 nanowire electrode material with rich oxygen vacancies is prepared by one-step hydrothermal method combined with plasma technology. The experimental results indicate that Zn2+ doping MnO2 nanowire not only stabilizes the interlayer structure of MnO2, but also provide additional specific capacity as electrolyte ions. Meanwhile, plasma treatment technology induces the oxygen-deficient Zn-MnO2 electrode optimizing the electronic structure to improve the electrochemical behavior of the cathode materials. Especially, the optimized Zn/Zn-MnO2 batteries obtain outstanding specific capacity (546 mAh g-1 at 1 A g-1) and superior cycling durability (94% over 1000 continuous discharge/charge tests at 3 A g-1). Greatly, the H+ and Zn2+ reversible co-insertion/extraction energy storage system of Zn//Zn-MnO2-4 battery is further revealed by the various characterization analyses during the cycling test process. Further, from the perspective of reaction kinetics, plasma treatment also optimizes the diffusion control behavior of electrode materials. This research proposes a synergistic strategy of element doping and plasma technology, which has enhanced the electrochemical behaviors of MnO2 cathode and shed light on the design of the high-performance manganese oxide-based cathodes for ZIBs.

BRG1 alleviates microglial activation by promoting the KEAP1-NRF2/HO-1 signaling pathway and minimizing oxidative damage in cerebral ischemia-reperfusion.

BRG1 is a key factor in the process of apoptosis and oxidative damage; however, its role in the pathophysiology of ischemic stroke is unclear. Here, we discovered that during middle cerebral artery occlusion (MCAO) reperfusion in mice, microglia were significantly activated in the cerebral cortex of the infarct area, and BRG1 expression was increased in the mouse MCAO/R model, peaking at 4 days. In microglia subjected to OGD/R, BRG1 expression increased and peaked at 12 h after reoxygenation. After ischemic stroke, in vitro changing the expression of BRG1 expression levels greatly altered the activation of microglia and the production of antioxidant and pro-oxidant proteins. Knocking down BRG1 expression levels in vitro increased the inflammatory response, promoted microglial activation, and decreased the expression of the NRF2/HO-1 signaling pathway after ischemic stroke. In contrast, overexpression of BRG1 dramatically reduced the expression of NRF2/HO-1 signaling pathway and microglial activation. Our research reveals that BRG1 reduces postischemic oxidative damage via the KEAP1-NRF2/HO-1 signaling pathway, protecting against brain ischemia/reperfusion injury. Using BRG1 as a pharmaceutical target to inhibit inflammatory responses to reduce oxidative damage may be a unique way to explore techniques for the treatment of ischemic stroke and other cerebrovascular illnesses.

Directional and Ultrafast Charge Transfer in Oxygen-Vacancy-Rich ZnO@Single-Atom Cobalt Core-Shell Junction for Photo-Fenton-Like Reaction.

In photosynthesis, solar energy is harvested by photosensitizers, and then, the excited electrons transfer via a Z-Scheme mode to enzymatic catalytic centers to trigger redox reactions. Herein, we constructed a core-shell Z-scheme heterojunction of semiconductor@single-atom catalysts (SACs). The oxygen-vacancy-rich ZnO core and single-atom Co-N4 sites supported on nitrogen-rich carbon shell (SA-Co-CN) act as the photosensitizer and the enzyme-mimicking active centers, respectively. Driven by built-in electric field across the heterojunction, photoexcited electrons could rapidly (2 ps) transfer from the n-type ZnO core to the p-type SA-Co-CN shell, finally boosting the catalytic performance of the surface-exposed single-atom Co-N4 sites for peroxymonosulfate (PMS) activation under light irradiation. The synergies between photocatalysis and heterogeneous Fenton-like reaction lead to phenomenally enhanced production of various reactive oxygen species for rapid degradation of various microcontaminants in water. Experimental and theoretical results validate that the interfacial coupling of SA-Co-CN with ZnO greatly facilitates PMS adsorption and activation by reducing the adsorption energy and enhancing the cascade electron transfer processes for the photo-Fenton-like reaction.

Perineal nerve block versus periprostatic block for patients undergoing transperineal prostate biopsy (APROPOS): a prospective, multicentre, randomised controlled study.

Background: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Methods: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. Findings: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means -1.17, P < 0.001). Although the perineal nerve block had a lower mean pain score at 1 h post-biopsy compared with the periprostatic block (0.23 vs 0.43, P = 0.042), they were equivalent at 6 h (0.16 vs 0.25, P = 0.389) and 24 h (0.10 vs 0.26, P = 0.184) respectively. For the change in vital signs during biopsy procedure, perineal nerve block was significantly superior to periprostatic block in terms of maximum value of systolic blood pressure, maximum value of mean arterial pressure and maximum value of heart rate. There are no statistical differences in average value of systolic blood pressure, average value of mean, average value of heart rate, diastolic blood pressure and breathing rate. Perineal nerve block was also superior to periprostatic block in external manifestations of pain (1.88 vs 3.00, P < 0.001) and anaesthesia satisfaction (8.93 vs 11.90, P < 0.001). Equivalence was shown for the detection rate of PCa (31.25% for perineal nerve block and 29.17% for periprostatic block, P = 0.753) or csPCa (23.96% for perineal nerve block and 20.83% for periprostatic block, P = 0.604). 33 (34.8%) of 96 patients in the perineal nerve block group and 40 (41.67%) of 96 patients in the periprostatic block group had at least one complication. Interpretation: Perineal nerve block was superior to periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Funding: Grant 2019YFC0119100 from the National Key Research and Development Program of China.

Constructing oxygen vacancy-rich MXene @Ce-MOF composites for enhanced energy storage and conversion.

Oxygen vacancies can regulate the coordination structure and electronic states of atoms, thus promoting the formation of surface-active sites and increasing the conductivity of the electrode material. This work presents a design for MXene@Ce-MOF composites with abundant oxygen vacancies. The hydroxyl groups on the surface of monolayer MXene attract cerium ions, which create surface defects in Ce-MOF and further promote the formation of oxygen vacancies. This results in a significant improvement in energy storage capacity, as well as performance in oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). The MXene@Ce-MOF composite exhibits a specific capacity of 496 F g-1, which is 1.8 times higher than that of pure Ce-MOF and 3.5 times higher than MXene alone. At a current density of 10 mA cm-2, the overpotential for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is as low as 270 and 220 mV, respectively, and the composite exhibits excellent cycling stability. Oxygen vacancy-based MOF composites play a crucial role in electrocatalysis and energy conversion.