Prenatal High-Sucrose Diet Induced Vascular Dysfunction of Renal Interlobar Arteries in the Offspring via PPARγ-RXRg-ROS/Akt Signaling.

SCOPE: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS. CONCLUSION: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.

Mesoporous Mn-substituted MnxZn1-xCo2O4 ternary spinel microspheres with enhanced electrochemical performance for supercapacitor applications.

Extensive investigations have been carried out on spinel mixed transition metal oxide-based materials for high-performance electrochemical energy storage applications. In this study, mesoporous Mn-substituted MnxZn1-xCo2O4 (ZMC) ternary oxide microspheres (x = 0, 0.3, 0.5, 0.7, and 1) were fabricated as electrode materials for supercapacitors through a facile coprecipitation method. Electron microscopy analysis revealed the formation of microspheres comprising interconnected aggregates of nanoparticles. Furthermore, the substitution of Mn into ZnCo2O4 significantly improved the surface area of the synthesized samples. The electrochemical test results demonstrate that the ZMC3 oxide microspheres with an optimal Mn substitution exhibited enhanced performance, displaying the largest specific capacitance of 589.9 F g-1 at 1 A g-1. Additionally, the ZMC3 electrode maintained a capacitance retention of 92.1% after 1000 cycles and exhibited a significant rate capability at a current density of 10 A g-1. This improved performance can be ascribed to the synergistic effects of multiple metals resulting from Mn substitution, along with an increase in the surface area, which tailors the redox behavior of ZnCo2O4 (ZC) and facilitates charge transfer. These findings indicate that the incorporation of Mn into mixed transition metal oxides holds promise as an effective strategy for designing high-performance electrodes for energy storage applications.

Enhancement of electron transfer via magnetite in nitrite-dependent anaerobic methane oxidation system.

Nitrite-dependent anaerobic methane oxidation (n-DAMO) is a novel denitrification process that simultaneously further removes and utilizes methane from anaerobic effluent from wastewater treatment plants. However, the metabolic activity of n-DAMO bacteria is relative low for practical application. In this study, conductive magnetite was added into lab-scale sequencing batch reactor inoculated with n-DAMO bacteria to study the influence on n-DAMO process. With magnetite amendment, the nitrogen removal rate could reach 34.9 mg N·L-1d-1, nearly 2.5 times more than that of control group. Magnetite significantly facilitated the interspecies electron transfer and built electrically connected community with high capacitance. Enzymatic activities of electron transport chain were significantly elevated. Functional gene expression and enzyme activities associated with nitrogen and methane metabolism had been highly up-regulated. These results not only propose a useful strategy in n-DAMO application but also provide insights into the stimulating mechanism of magnetite in n-DAMO process.

Syngas Production from CO2 and H2O via Solid-Oxide Electrolyzer Cells: Fundamentals, Materials, Degradation, Operating Conditions, and Applications.

Highly efficient coelectrolysis of CO2/H2O into syngas (a mixture of CO/H2), and subsequent syngas conversion to fuels and value-added chemicals, is one of the most promising alternatives to reach the corner of zero carbon strategy and renewable electricity storage. This research reviews the current state-of-the-art advancements in the coelectrolysis of CO2/H2O in solid oxide electrolyzer cells (SOECs) to produce the important syngas intermediate. The overviews of the latest research on the operating principles and thermodynamic and kinetic models are included for both oxygen-ion- and proton-conducting SOECs. The advanced materials that have recently been developed for both types of SOECs are summarized. It later elucidates the necessity and possibility of regulating the syngas ratios (H2:CO) via changing the operating conditions, including temperature, inlet gas composition, flow rate, applied voltage or current, and pressure. In addition, the sustainability and widespread application of SOEC technology for the conversion of syngas is highlighted. Finally, the challenges and the future research directions in this field are addressed. This review will appeal to scientists working on renewable-energy-conversion technologies, CO2 utilization, and SOEC applications. The implementation of the technologies introduced in this review offers solutions to climate change and renewable-power-storage problems.

Hybrid adipocyte-derived exosome nano platform for potent chemo-phototherapy in targeted hepatocellular carcinoma.

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.

Wuhu decoction combined with azithromycin for treatment of Mycoplasma pneumoniae pneumonia in Asian children: a systematic review and meta analysis of randomized controlled trials.

Objective: This study constitutes a pioneering systematic review and meta analysis delving into the clinical efficacy and safety of the combined therapy involving Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. Methods: This study conducted a comprehensive computerized search, covering 6 Chinese databases and 6 English databases, to collect randomized controlled trials related to the combined use of Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. The search was extended until August 2023. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. Meta-analysis was performed using Stata 14.0 and RevMan 5.4 software. Additionally, meta-regression analysis and subgroup analysis were carried out on primary outcomes to identify potential sources of heterogeneity and confounding factors. Results: A total of 22 randomized controlled trials involving 2,026 patients were included in this study. The combined therapy of Wuhu Decoction and azithromycin demonstrated superior efficacy compared to azithromycin alone (RR = 1.17, 95% CI [1.13, 1.21], p < 0.00001; low certainty of evidence). Additionally, patients receiving the combination therapy experienced significantly reduced the disappearance time of fever (MD = -1.42, 95% CI [-1.84, -1.00], p < 0.00001; very low certainty of evidence), disappearance time of cough (MD = -2.08, 95% CI [-2.44, -1.71], p < 0.00001; very low certainty of evidence), disappearance of pulmonary rales (MD = -1.97, 95% CI [-2.31, -1.63], p < 0.00001; very low certainty of evidence), and disappearance time of wheezing (MD = -1.47, 95% CI [-1.72, -1.22], p < 0.00001; very low certainty of evidence). Meta-regression analysis suggested that course of disease, sample size, and age might be sources of heterogeneity. Subgroup and sensitivity analyses reaffirmed the stability of these results. Furthermore, analyses of secondary outcomes such as T lymphocytes, serum inflammatory factors, and the incidence rate of adverse reactions consistently favored the combination therapy of WHD and azithromycin over azithromycin alone, with statistically significant differences. Conclusion: Based on our meta-analysis findings, the combined therapy of Wuhu Decoction and azithromycin for treating pediatric Mycoplasma pneumoniae pneumonia exhibited superior overall efficacy in comparison to azithromycin monotherapy. However, in the included 22 studies, the majority of evaluated factors showed unclear bias risks, and a persistent bias risk was consistently present within one category. Moreover, due to the low quality of evidence, interpreting these results should be approached with caution. Hence, we emphasize the necessity for future high-quality, multicenter, and large-sample clinical randomized controlled trials. These trials are essential to provide more robust data for evidence-based research and to establish higher-quality evidence support. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023465606.

Efficacy of cementless porous tantalum tibial components versus cemented tibial components in primary total knee arthroplasty: A meta-analysis.

BACKGROUND: Total knee arthroplasty involves the use of cemented tibial components for fixation. In recent years, cementless porous tantalum tibial components have been increasingly utilized. The aim of this meta-analysis was to compare the efficacy of cementless porous tantalum tibial components with traditional cemented tibial components in terms of postoperative outcomes following total knee arthroplasty. METHODS: Relevant literature was retrieved from Cochrane Library, PubMed, Embase, and Web of Science using the search terms "(trabecular metal OR Porous tantalum)" AND "knee" up to July 2023. The weighted mean difference with a 95% confidence interval was used as the effect size measure to evaluate the functional recovery of the knee joint, radiological analysis, complications, and implant revisions between cementless porous tantalum tibial components and traditional cemented tibial components after total knee arthroplasty. Review Manager 5.3 was utilized to conduct a comparative analysis of all included studies. RESULTS: Nine studies with a total of 1117 patients were included in this meta-analysis, consisting of 447 patients in the porous tantalum group and 670 patients in the cemented group. Radiological analysis demonstrated that the porous tantalum group had better outcomes than the cemented group (P < .05). The combined results for the 5-year and 10-year follow-ups, range of motion, Western Ontario and McMaster University Osteoarthritis Index, complications, and implant revisions showed no significant differences between the porous tantalum and cemented groups. CONCLUSION: The results of the 5-year and 10-year follow-ups indicate that the use of cementless porous tantalum tibial components is comparable to traditional cemented tibial components, with no significant advantages observed. However, at the 5-year follow-up, the porous tantalum group demonstrated a good bone density in the proximal tibia. Future studies with a larger sample size, long-term clinical follow-up, and radiological results are needed to verify the differences between the 2 implants.

Molecular and Heterojunction Device Engineering of Solution-Processed Conjugated Reticular Oligomers: Enhanced Photoelectrochemical Hydrogen Evolution through High-Effective Exciton Separation.

Covalent organic frameworks (COFs) face limited processability challenges as photoelectrodes in photoelectrochemical water reduction. Herein, sub-10 nm benzothiazole-based colloidal conjugated reticular oligomers (CROs) are synthesized using an aqueous nanoreactor approach, and the end-capping molecular strategy to engineer electron-deficient units onto the periphery of a CRO nanocrystalline lattices (named CROs-Cg). This results in stable and processable "electronic inks" for flexible photoelectrodes. CRO-BtzTp-Cg and CRO-TtzTp-Cg expand the absorption spectrum into the infrared region and improve fluorescence lifetimes. Heterojunction device engineering is used to develop interlayer heterojunction and bulk heterojunction (BHJ) photoelectrodes with a hole transport layer, electron transport layer, and the main active layers, using a CROs/CROs-Cg or one-dimensional (1D) electron-donating polymer HP18 mixed solution via spinning coating. The ITO/CuI/CRO-TtzTp-Cg-HP18/SnO2/Pt photoelectrode shows a photocurrent of 94.9 µA cm‒2 at 0.4 V versus reversible hydrogen electrode (RHE), which is 47.5 times higher than that of ITO/Bulk-TtzTp. Density functional theory calculations show reduced energy barriers for generating adsorbed H* intermediates and increased electron affinity in CROs-Cg. Mott-Schottky and charge density difference analyses indicate enhanced charge carrier densities and accelerated charge transfer kinetics in BHJ devices. This study lays the groundwork for large-scale production of COF nanomembranes and heterojunction structures, offering the potential for cost-effective, printable energy systems.

Anti-skin aging effect of sea buckthorn proanthocyanidins in D-galactose-induced aging mice.

Oxidative stress in skin cells caused by changes in the external environment is one of the principal causes of skin aging. Sea buckthorn proanthocyanidins (SBPs) have good free radical scavenging ability. We established a senescence model by injecting 500 mg/kg D-galactose into the dorsal necks of mice, and then different doses of SBP (25, 50, and 100 mg/kg) were gavaged to explore the effects of SBP on the skin tissues of senescent mice and elucidate the related mechanism of action. The results reveal that SBP can alleviate the skin aging phenomenon caused by D-galactose-induced aging. It can also enhance the total antioxidant capacity in the body, thereby strengthening the body's antioxidant defense capability. In addition, SBP can effectively improve skin aging by regulating the TGF-ß1/Smads pathway and MMPs/TIMP system, increasing the relative content of Col I and tropoelastin, further maintaining the stability of collagen fiber and elastic fiber structure. These results will provide the development and production of the antioxidant function of cosmetics and health products, providing a new train of thought.

Related cellular signaling and consequent pathophysiological outcomes of ubiquitin specific protease 24.

Ubiquitin-specific protease 24 (USP24) is an essential member of the deubiquitinating protease family found in eukaryotes. It engages in interactions with multiple proteins, including p53, MCL-1, E2F4, and FTH1, among others. Through these interactions, USP24 plays a critical role in regulating vital cellular processes such as cell cycle control, DNA damage response, cellular iron autophagy, and apoptosis. Increased levels of USP24 have been observed in various cancer types, including bladder cancer, lung cancer, myeloma, hepatocellular carcinoma, and gastric cancer. However, in certain tumors like kidney cancer, USP24 is significantly downregulated, and the specific mechanism behind this remains unclear. Currently, there are no officially approved USP24 inhibitors available for clinical use. Some existing inhibitors targeting USP24 have shown promising effects in treating malignancies; however, their precise mode of action and information regarding binding sites are not well understood. Moreover, further optimization is required to enhance the selectivity and efficacy of these inhibitors. This review aims to provide a comprehensive overview of recent advancements in understanding the cellular functions of USP24, its association with various diseases, and the development of small-molecule inhibitors that target this protein. In conclusion, USP24 represents a promising therapeutic target for various diseases, and ongoing research will contribute to validating its role and facilitating the development of effective treatments.

Embrittlement Mechanisms of HR3C Pipe Steel at Room Temperature in Ultra-Supercritical Unit.

HR3C steel is an austenitic high-temperature-resistant steel. Because of its good strength and high-temperature performance, it has been widely used in ultra-supercritical power plant boilers. With the increasingly frequent start-up and shutdown of thermal power units, leakages of HR3C steel pipes have occasionally occurred due to the embrittlement of HR3C pipe steel after a long service duration. In this study, the embrittlement mechanisms of HR3C pipe steel are investigated systematically. The mechanical properties of the pipe steel after running for 70,000 h in an ultra-supercritical unit were determined. As a comparison, the pipe steel supplied in the same batch was aged at 700 degrees Celsius for 500 h. The mechanical properties and the micro-precipitation of the aged counterparts were also determined for comparison. The results show that the embrittlement of HR3C pipe steel in service for 70,000 h is obvious. The average impact absorption is only 5.5 J, which is a decrease of 96.7%. It is found that embrittlement of HR3C steel also occurs after 500 h of aging at 700 °C, and the average value of impact absorption energy decreases by 70.4%. The comparison experiment between the in-service pipe steel and the aged pipe steel shows that in the rapid decline stage of the impact toughness of HR3C steel, the M23C6 carbide in the microstructure has a continuous chain distribution in the grain boundary. There were no other precipitated phases observed. The rapid precipitation and aggregation of M23C6 carbides leads to the initial embrittlement of HR3C steel at room temperature. The CRFe-type σ phase was found in the transmission electron microscope (TEM) image of the steel pipe after 70 thousand hours of use. The precipitation of the σ phase further induces the embrittlement of HR3C pipe steel after a long service duration.

Comparison of different criteria for estimating major pathological response in resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy.

BACKGROUND: Major pathological response (MPR) is proposed as a surrogate endpoint for survival in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. However, the criteria for estimating MPR differ between the recommendations of the International Association for the Study of Lung Cancer (IASLC) and the immune-related pathologic response criterion (irPRC). IASLC's criteria focus solely on evaluating the primary tumor, while irPRC's criteria encompass both the primary tumor and lymph node metastasis. Our objective is to compare the prognostic value of different criteria for estimating MPR. METHODS: We conducted a retrospective study on a cohort of 235 patients with NSCLC after neoadjuvant chemoimmunotherapy. The survival endpoint was event-free survival (EFS). The MPR status of each patient was evaluated using both IASLC's criteria and irPRC's criteria. The prognostic value was compared using the Area Under Curve (AUC). RESULTS: The MPR rates were 63.4 % (149/235) and 57.4 % (135/235) according to IASLC's and irPRC's criteria, respectively. Inconsistent cases, characterized by MPR status according to IASLC's criteria but non-MPR status according to irPRC's criteria, constituted 6.0 % (14/235) of the overall cohort and 15.2 % (14/92) of patients with pretreatment N positive disease. Interestingly, all inconsistent patients showed no recurrence during the study period. Although both MPR statuses according to IASLC (p = 0.00039) and irPRC (p = 0.0094) were associated with improved EFS, IASLC's criteria (AUC = 0.65) were superior to irPRC's criteria (AUC = 0.62) with a higher AUC value. CONCLUSION: IASLC's criteria for estimating MPR were superior to irPRC's criteria in predicting EFS for NSCLC after neoadjuvant chemoimmunotherapy.

Effect of different hydrogen evolution rates at cathode on bioelectrochemical reduction of CO2 to acetate.

Microbial electrosynthesis (MES) offers a promising approach for converting CO2 into valuable chemicals such as acetate. However, the relative low conversion rate severely limits its practical application. This study investigated the impact of different hydrogen evolution rates on the conversion rate of CO2 to acetate in the MES system. Three potentials (-0.8 V, -0.9 V and -1.0 V) corresponding to various hydrogen evolution rates were set and analyzed, revealing an optimal hydrogen evolution rate, yielding a maximum acetate formation rate of 1410.9 mg/L and 73.5 % coulomb efficiency. The electrochemical findings revealed that an optimal hydrogen evolution rate facilitated the formation of an electroactive biofilm. The microbial community of the cathode biofilm highlighted key genera, including Clostridium and Acetobacterium, which played essential roles in electrosynthesis within the MES system. Notably, a low hydrogen evolution rate failed to provide sufficient energy for the electrochemical reduction of CO2 to acetate, while a high rate led to cathode alkalinization, impeding the reaction and causing significant energy wastage. Therefore, maintaining an appropriate hydrogen evolution rate is crucial for the development of mature electroactive biofilms and achieving optimal performance in the MES system.

Construction synergetic adsorption and activation surface via confined Cu/Cu2O and Ag nanoparticles on TiO2 for effective conversion of CO2 to CH4.

High-performance photocatalysts for catalytic reduction of CO2 are largely impeded by inefficient charge separation and surface activity. Reasonable design and efficient collaboration of multiple active sites are important for attaining high reactivity and product selectivity. Herein, Cu-Cu2O and Ag nanoparticles are confined as dual sites for assisting CO2 photoreduction to CH4 on TiO2. The introduction of Cu-Cu2O leads to an all-solid-state Z-scheme heterostructure on the TiO2 surface, which achieves efficient electron transfer to Cu2O and adsorption and activation of CO2. The confined nanometallic Ag further enhances the carrier's separation efficiency, promoting the conversion of activated CO2 molecules to •COOH and further conversion to CH4. Particularly, this strategy is highlighted on the TiO2 system for a photocatalytic reduction reaction of CO2 and H2O with a CH4 generation rate of 62.5 µmol∙g-1∙h-1 and an impressive selectivity of 97.49 %. This work provides new insights into developing robust catalysts through the artful design of synergistic catalytic sites for efficient photocatalytic CO2 conversion.

A Novel Method for the Measurement of Retinal Arteriolar Bifurcation.

INTRODUCTION: The purpose of this research was to develop protocols for evaluating the bifurcation parameters of retinal arteriole and establish a reference range of normal values. METHODS: In this retrospective study, we measured a total of 1314 retinal arteriolar bifurcations from 100 fundus photographs. We selected 200 from these bifurcations for testing inter-measurer and inter-method agreement. Additionally, we calculated the normal reference range for retinal arteriolar bifurcation parameters and analyzed the effects of gender, age, and anatomical features on retinal arteriolar bifurcation. RESULTS: The measurement method proposed in this study has demonstrated nearly perfect consistency among different measurers, with interclass correlation coefficient (ICC) for all bifurcation parameters of retinal arteriole exceeding 0.95. Among healthy individuals, the retinal arteriolar caliber was narrowest in young adults and increased in children, teenagers, and the elderly; retinal arteriolar caliber was greater in females than in males; and the diameter of the inferior temporal branch exceeded that of the superior temporal branch. The angle between the two branches of retinal arteriolar bifurcation was also greater in females than in males. When using the center of the optic disc as a reference point, the angle between the two branches of the retinal arteriole at the proximal or distal ends increased. In contrast, the estimated optimum theoretical values of retinal arteriolar bifurcation were not affected by these factors. CONCLUSIONS: The method for the measurement of retinal arteriolar bifurcation in this study was highly accurate and reproducible. The diameter and branching angle of the retinal arteriolar bifurcation were more susceptible to the influence of gender, age, and anatomical features. In comparison, the estimated optimum theoretical values of retinal arteriolar bifurcation were relatively stable. Video available for this article.

Riboflavin-loaded carbon cloth aids the anaerobic digestion of cow dung by promoting direct interspecies electron transfer.

Cow dung generates globally due to increased beef and milk consumption, but its treatment efficiency remains low. Previous studies have shown that riboflavin-loaded conductive materials can improve anaerobic digestion through enhance direct interspecies electron transfer (DIET). However, its effect on the practical anaerobic digestion of cow dung remained unclear. In this study, carbon cloth loaded with riboflavin (carbon cloth-riboflavin) was added into an anaerobic digester treating cow dung. The carbon cloth-riboflavin reactor showed a better performance than other two reactors. The metagenomic analysis revealed that Methanothrix on the surface of the carbon cloth predominantly utilized the CO2 reduction for methane production, further enhanced after riboflavin addition, while Methanothrix in bulk sludge were using the acetate decarboxylation pathway. Furthermore, the carbon cloth-riboflavin enriched various major methanogenic pathways and activated a large number of enzymes associated with DIET. Riboflavin's presence altered the microbial communities and the abundance of functional genes relate to DIET, ultimately leading to a better performance of anaerobic digestion for cow dung.

Room-Temperature Oxygen Dissociative Chemisorption on Carbon Surface-Experimental Evidence.

Oxygen interaction with the carbon surface is one of the most important topics of study in the field of material chemistry. In this work, experimental evidence for molecular oxygen dissociative chemisorption on a carbon surface at room temperature is shown for the first time. It was determined that the process occurs only on the bare carbon surface, and the quantitative description of the phenomena is possible using the Temkin model, which explains an almost linear decrease in the calorimetric heat of adsorption. The results provided by in situ infrared studies show that surface carbonyl oxides appear as intermediates of final functionality, i.e., carbonyl structures. Examining the thermal stability of surface structures shows that all surface species decompose at temperatures below 500 °C, leaving a pristine carbon surface.

Clonality Analysis for the Relationship between the Pulmonary Combined Neuroendocrine Carcinoma and "the So-Called Reported Histologic Transformation".

Histologic transformation (HT) is common following targeted therapy in adenocarcinoma. However, whether the transformed tumor is a new component or a combined neuroendocrine carcinoma (C-NEC) remains controversial. We aimed to explore the relationship between pulmonary C-NEC and HT. Macro-dissection was performed on different components of surgically resected C-NEC samples. Molecular alterations and clonal evolution were analyzed using whole exome sequencing (WES). The gene statuses for TP53 and RB1 were determined using immunohistochemistry (IHC) and WES to analyze the relationship between C-NEC and reported HT. Sixteen combined small-cell lung cancer patients and five combined large-cell neuroendocrine carcinoma patients were enrolled. The frequency of p53 and Rb inactivation, assessed using IHC in NEC and non-NEC components, was 76.2/76.2% and 66.7/61.9%, respectively. The expression consistency between the components was 81.0 and 85.7% for p53 and Rb, respectively. The frequencies of TP53, RB1, and EGFR mutations, assessed using WES in NEC and non-NEC components, were 81.0/81.0%, 28.6/28.6%, and 42.9/42.9%, respectively. The concordance rates for TP53, RB1, and EGFR were 90.5, 71.4, and 90.5%, respectively. The consistency rate between IHC and WES was 81.0 and 61.9% for TP53 and RB1, respectively. The different components had a common clonal origin for the 21 C-NECs in the clonal analysis, consistent with previous studies on HT. Our study shows that IHC is more sensitive for Rb detection and C-NEC, and the reported HT may be due to differences in evaluations between pathologist and clinicians. Assessing the p53/Rb and EGFR status for such cases would help in recognizing potential transformation cases or uncovering potential combined components.

Single-cell transcriptomics reveals variations in monocytes and Tregs between gout flare and remission.

Gout commonly manifests as a painful, self-limiting inflammatory arthritis. Nevertheless, the understanding of the inflammatory and immune responses underlying gout flares and remission remains ambiguous. Here, based on single-cell RNA-Seq and an independent validation cohort, we identified the potential mechanism of gout flare, which likely involves the upregulation of HLA-DQA1+ nonclassical monocytes and is related to antigen processing and presentation. Furthermore, Tregs also play an essential role in the suppressive capacity during gout remission. Cell communication analysis suggested the existence of altered crosstalk between monocytes and other T cell types, such as Tregs. Moreover, we observed the systemic upregulation of inflammatory and cytokine genes, primarily in classical monocytes, during gout flares. All monocyte subtypes showed increased arachidonic acid metabolic activity along with upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2). We also detected a decrease in blood arachidonic acid and an increase in leukotriene B4 levels during gout flares. In summary, our study illustrates the distinctive immune cell responses and systemic inflammation patterns that characterize the transition from gout flares to remission, and it suggests that blood monocyte subtypes and Tregs are potential intervention targets for preventing recurrent gout attacks and progression.