Exploring the anti-inflammatory ingredients and potential of golden buckwheat (Fagopyrum dibotrys) on the TLR4/NLRP3 pathway in acute lung injury.

Golden buckwheat, also called Fagopyrum dibotrys (D. Don) H. Hara, is a plant of the genus Buckwheat in the buckwheat family. The aim of this study was to screen the bioactive ingredients of golden buckwheat extract and investigate the protective effect on acute lung injury (ALI). The ethyl acetate extract (EAE) was identified as the active fraction in LPS-induced RAW264.7 cells, with gallic acid, proanthocyanidin B2, and epicatechin at 0.0563%, 0.3707%, and 0.3868%, respectively. At the same time, 20 compounds (mainly flavonoids and organic acids) were identified by UPLC-Q-Exactive Orbitrap-HRMS in EAE. Furthermore, the EAE reduced lung histopathology scores in mice with ALI, decreased the dry-to-wet weight ratio of lung tissue, and significantly inhibited the concentrations of IL-1ß, TNFα, and IL-6 in bronchoalveolar lavage fluid (BALF). It also reduced the number of leukocytes, decreased the activity of MPO in lung tissue, and inhibited the levels of TLR4/NLRP3 pathway mRNA and protein in lung tissue. Our study indicated that golden buckwheat as a source of functional food prevents or treats associated lung diseases by modulating the activation of the TLR4/NLRP3 signaling pathway.

Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by early metastasis, rapid tumor growth and poor prognosis. In recent decades, the epidemiology, initiation and mutation characteristics of SCLC, as well as abnormal signaling pathways contributing to its progression, have been widely studied. Despite extensive investigation, fewer drugs have been approved for SCLC. Recent advancements in multi-omics studies have revealed diverse classifications of SCLC that are featured by distinct characteristics and therapeutic vulnerabilities. With the accumulation of SCLC samples, different subtypes of SCLC and specific treatments for these subtypes were further explored. The identification of different molecular subtypes has opened up novel avenues for the treatment of SCLC; however, the inconsistent and uncertain classification of SCLC has hindered the translation from basic research to clinical applications. Therefore, a comprehensives review is essential to conclude these emerging subtypes and related drugs targeting specific therapeutic vulnerabilities within abnormal signaling pathways. In this current review, we summarized the epidemiology, risk factors, mutation characteristics of and classification, related molecular pathways and treatments for SCLC. We hope that this review will facilitate the translation of molecular subtyping of SCLC from theory to clinical application.

FXR contributes to obstructive jaundice-induced vascular hyporeactivity in mesenteric arteries by reconstituting BKCa channels.

OBJECTIVE: Vascular hyporeactivity increases with the incidence of obstructive jaundice (OJ). Evidence suggests that OJ activates the farnesoid X receptor (FXR) as well as the large-conductance Ca2+-activated K+ (BKCa or MaxiK) channel. This study was designed to explore the role of the FXR in vascular hyporesponsiveness induced by cholestasis. METHODS: The OJ model rats were constructed by bile duct ligation (BDL) and treated with an FXR agonist or antagonist. Vasoconstriction of the mesenteric arteries (MAs) was assessed in vitro. Whole-cell patch clamp recordings were used to investigate BKCa channel function. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect mRNA and protein levels. RESULTS: A significant increase in vascular tone and responsiveness to norepinephrine (NE) was observed after the MaxiK channel blocker (IbTX) was administered. This effect was pronounced in BDL animals and can be mimicked by the FXR agonist GW4064 and inhibited by the FXR antagonist Z-guggulsterone (Z-Gu). GW4064 has a similar effect as cholestasis in promoting MaxiK currents in isolated arterial smooth muscle cells (ASMCs), while Z-Gu blunted this effect. The mRNA and protein expression of FXR and MaxiK-ß1, but not MaxiK-α, were significantly increased in the BDL group in comparison to the sham. Furthermore, activation or inhibition of FXR promoted or inhibited the mRNA and protein expression of the MaxiK-ß1 subunit, respectively. CONCLUSION: Activation of FXR enhances the capability of the MaxiK channel to regulate vascular tone and leads to vascular hyporesponsiveness in the MAs of BDL rats, which may be mediated by the nonparallel upregulation of MaxiK-α and MaxiK-ß1 subunit expression.

Efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients with rare KRAS mutations: a real-world retrospective study.

Background: Kirsten rat sarcoma homolog (KRAS) mutations are one of the key drivers in non-small cell lung cancer (NSCLC) and FDA-approved specific inhibitors of KRAS-G12C mutation are available clinically. However, inhibitors of certain KRAS mutation subtypes remain unavailable, especially rare KRAS mutations including G13C, G13D, and Q61H. In this study, we retrospectively investigated the outcomes of NSCLC patients with rare KRAS-mutation to determine if they may benefit from immune checkpoint inhibitors (ICIs). Methods: Our retrospective study involved 240 advanced NSCLC patients with KRAS mutations, who visited Shanghai Chest Hospital from July 2018 to July 2021. Complete clinical and pathological data were recorded and progression-free survival (PFS) and overall survival (OS) were adopted as primary endpoints. Results: The median follow-up time was 36.5 months (range, 30.8-42.1 months) and the median OS was 9.7 months (range, 7.6-11.8 months). Of the 240 patients evaluated, 130 (54.2%) received chemotherapy and 110 (45.8%) received ICI-based treatment. Among the patients who received chemotherapy, patients with rare KRAS-mutations presented worse survival outcomes (median PFS, 3.4 vs. 4.1 months, P=0.047; median OS, 5.2 vs. 7.1 months, P=0.02) than conventional KRAS-mutant patients. PFS and OS of rare KRAS-mutation patients were prolonged after immunotherapy (median PFS 7.3 vs. 3.4 months, P<0.001; median OS, 13.3 vs. 5.2 months, P<0.001) and had no significant difference compared with conventional KRAS-mutant patients, in part of them whose programmed death-ligand 1 (PD-L1) expression data before immunotherapy were available (n=72), patients with a higher rate of PD-L1 positive tumor cells (≥50%) presented elevated PFS and OS. Conclusions: Despite having potential survival disadvantage compared with other NSCLC patients, rare KRAS-mutant patients (other than G12A, C, D, V) could benefit specifically from ICI-based therapy and survival outcomes are correlated with PD-L1 expression.

Rules of acupoint selection in treatment of cancer-related insomnia with acupuncture and moxibustion based on data mining technology. / åŸºäºŽæ•°æ®æŒ–æŽ˜æŠ€æœ¯æŽ¢æžé’ˆç¸æ²»ç–—è‚¿ç˜¤ç›¸å ³æ€§å¤±çœ çš„é€‰ç©´è§„å¾‹.

OBJECTIVES: To analyze the rules of acupoint selection in treatment of cancer-related insomnia with acupuncture and moxibustion by data mining technology. METHODS: The articles of cancer-related insomnia treated with acupuncture and moxibustion were searched from CNKI, Wanfang, VIP, SinoMed, PubMed, WOS, Cochrane, and Embase databases, from the inception of each database to January 5, 2024. The prescription database of acupuncture and moxibustion for cancer-related insomnia was established. The descriptive analysis was conducted on the use frequency, meridian tropism and distribution of acupoints. Using SPSS Modeler 18.0 Apriori algorithm, the association rules of acupoint prescriptions were analyzed. With Cytoscape3.9.1 software used, the complex network diagram was plotted, and the cluster analysis of high-frequency acupoints was performed by SPSS26.0 software. RESULTS: Forty-one articles were included, and 67 prescriptions were extracted with 89 acupoints involved, and the total use frequency was 447 times. The top 4 acupoints of the high use frequency were Baihui (GV20), Sanyinjiao (SP6), Shenmen (HT7) and Shenting (GV24). The included meridians were the governor vessel, the spleen meridian, the bladder meridian, the conception vessel, the heart meridian and the stomach meridian. The selected acupoints were mostly distributed on the head, the neck and and the upper and lower limbs. The special acupoints of the high use frequency included the five-Shu points, the crossing points and yuan-primordial points. Regarding acupoint combination, GV24, SP6, HT7, and GV20 were highly correlated. The three effective clusters were categorized among the top 12 acupoints of the high use frequency. CONCLUSIONS: In treatment of cancer-related insomnia with acupuncture and moxibustion, the principle focuses on supporting the healthy qi, eliminating pathogens, regulating yin and yang, promoting the circulation of the governor vessel for regulating the spirit, and tranquilizing the mind. The core acupoint prescription may includes GV24, SP6, HT7 and GV20；combined with Zusanli (ST36) and Yintang (GV4+) to enhance the therapeutic effect.

Research Progress on the Anti-Cancer Effects of Astragalus membranaceus Saponins and Their Mechanisms of Action.

Astragalus membranaceus saponins are the main components of A. membranaceus, a plant widely used in traditional Chinese medicine. Recently, research on the anti-cancer effects of A. membranaceus saponins has received increasing attention. Numerous in vitro and in vivo experimental data indicate that A. membranaceus saponins exhibit significant anti-cancer effects through multiple mechanisms, especially in inhibiting tumor cell proliferation, migration, invasion, and induction of apoptosis, etc. This review compiles relevant studies on the anti-cancer properties of A. membranaceus saponins from various databases over the past two decades. It introduces the mechanism of action of astragalosides, highlighting their therapeutic benefits in the management of cancer. Finally, the urgent problems in the research process are highlighted to promote A. membranaceus saponins as an effective drug against cancer.

Unraveling the future: Innovative design strategies and emerging challenges in HER2-targeted tyrosine kinase inhibitors for cancer therapy.

Human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor-like protein with tyrosine kinase activity that plays a vital role in processes such as cell proliferation, differentiation, and angiogenesis. The degree of malignancy of different cancers, notably breast cancer, is strongly associated with HER2 amplification, overexpression, and mutation. Currently, widely used clinical HER2 tyrosine kinase inhibitors (TKIs), such as lapatinib and neratinib, have several drawbacks, including susceptibility to drug resistance caused by HER2 mutations and adverse effects from insufficient HER2 selectivity. To address these issues, it is essential to create innovative HER2 TKIs with enhanced safety, effectiveness against mutations, and high selectivity. Typically, SPH5030 has advanced to phase I clinical trials for its strong suppression of four HER2 mutations. This review discusses the latest research progress in HER2 TKIs, with a focus on the structural optimization process and structure-activity relationship analysis. In particular, this study highlights promising design strategies to address these challenges, providing insightful information and inspiration for future development in this field.

Discovery and mechanistic insights into thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines inhibitors targeting tubulin for cancer therapy.

Guided by the X-ray cocrystal structure of the lead compound 4a, we developed a series of thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines demonstrating potent antiproliferative activity against four tumor cell lines. Two analogs, 13 and 25d, exhibited IC50 values around 1 nM and overcame P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). At low concentrations, 13 and 25d inhibited both the colony formation of SKOV3 cells in vitro and tubulin polymerization. Furthermore, mechanistic studies showed that 13 and 25d induced G2/M phase arrest and apoptosis in SKOV3 cells, as well as dose-dependent inhibition of tumor cell migration and invasion at low concentrations. Most notably, the X-ray cocrystal structures of compounds 4a, 25a, and the optimal molecule 13 in complex with tubulin were elucidated. This study identifies thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines as representatives of colchicine-binding site inhibitors (CBSIs) with potent antiproliferative activity.

Primary and Orthotopic Murine Models of Nasopharyngeal Carcinoma Reveal Molecular Mechanisms Underlying its Malignant Progression.

Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein-Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV- (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC-associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene-edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV-coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV- and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study.

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC.

Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

Cross-species metabolomic profiling reveals phosphocholine-mediated liver protection from cold and ischemia/reperfusion.

Cold and ischemia/reperfusion (IR)-associated injuries are seemingly inevitable during liver transplantation and hepatectomy. Because Syrian hamsters demonstrate intrinsic tolerance to transplantation-like stimuli, cross-species comparative metabolomic analyses were conducted with hamster, rat, and donor liver samples to seek hepatic cold and IR-adaptive mechanisms. Lower hepatic phosphocholine contents were found in recipients with early graft-dysfunction and with virus-caused cirrhosis or high model for end-stage liver disease scores (≥30). Choline/phosphocholine deficiency in cultured human THLE-2 hepatocytes and animal models weakened hepatocellular cold tolerance and recovery of glutathione and ATP production, which was rescued by phosphocholine supplements. Among the biological processes impacted by choline/phosphocholine deficiency, 3 lipid-related metabolic processes were downregulated, whereas phosphocholine elevated the expression of genes in methylation processes. Consistently, in THLE-2, phosphocholine enhanced the overall RNA m6A methylation, among which the transcript stability of fatty acid desaturase 6 (FADS6) was improved. FADS6 functioned as a key phosphocholine effector in the production of polyunsaturated fatty acids, which may facilitate the hepatocellular recovery of energy and redox homeostasis. Thus, our study reveals the choline-phosphocholine metabolism and its downstream FADS6 functions in hepatic adaptation to cold and IR, which may inspire new strategies to monitor donor liver quality and improve recipient recovery from the liver transplantation process.

Long-term monitoring chlorophyll-a concentration using HJ-1 A/B imagery and machine learning algorithms in typical lakes, a cold semi-arid region.

Chlorophyll a (Chl-a) in lakes serves as an effective marker for assessing algal biomass and the nutritional level of lakes, and its observation is feasible through remote sensing methods. HJ-1 (Huanjing-1) satellite, deployed in 2008, incorporates a CCD capable of a 30 m resolution and has a revisit interval of 2 days, rendering it a superb choice or supplemental sensor for monitoring trophic state of lakes. For effective long-term and regional-scale mapping, both the imagery and the evaluation of machine learning algorithms are essential. The several typical machine learning algorithms, i.e., Support Vector Regression (SVR), Gradient Boosting Decision Trees (GBDT), XGBoost (XGB), Random Forest (RF), K-Nearest Neighbor (KNN), Kernel Ridge Regression (KRR), and Multi-Layer Perception Network (MLP), were developed using our in-situ measured Chl-a. A cross-validation grid to identify the most effective hyperparameter combinations for each algorithm was used, as well as the selected optimal superparameter combinations. In Chl-a mapping of three typical lakes, the R2 of GBDT, XGB, RF, and KRR all reached 0.90, while XGB algorithm also exhibited stable performance with the smallest error (RMSE = 3.11 µg/L). Adjustments were made to align the Chl-a spatial-temporal patterns with past data, utilizing HJ1-A/B CCD images mapping through XGB algorithm, which demonstrates its stability. Our results highlight the considerable effectiveness and utility of HJ-1 A/B CCD imagery for evaluation and monitoring trophic state of lakes in a cold arid region, providing the application cases contribute to the ongoing efforts to monitor water qualities.

Immunogenic cell death inducers for cancer therapy: An emerging focus on natural products.

BACKGROUND: Immunogenic cell death (ICD) is a specific form of regulated cell death induced by a variety of stressors. During ICD, the dying cancer cells release damage-associated molecular patterns (DAMPs), which promote dendritic cell maturation and tumor antigen presentation, subsequently triggering a T-cell-mediated anti-tumor immune response. In recent years, a growing number of studies have demonstrated the potential of natural products to induce ICD and enhance tumor cell immunogenicity. Moreover, there is an increasing interest in identifying new ICD inducers from natural products. PURPOSE: This study aimed to emphasize the potential of natural products and their derivatives as ICD inducers to promote research on using natural products in cancer therapy and provide ideas for future novel immunotherapies based on ICD induction. METHOD: This review included a thorough search of the PubMed, Web of Science, Scopus, and Google Scholar databases to identify natural products with ICD-inducing capabilities. A comprehensive search for clinical trials on natural ICD inducers was also conducted using ClinicalTrials.gov, as well as the approved patents using the Espacenet and CNKI Patent Database. RESULTS: Natural compounds that induce ICD can be categorized into several groups, such as polyphenols, flavonoids, terpenoids, and alkaloids. Natural products can induce the release of DAMPs by triggering endoplasmic reticulum stress, activation of autophagy-related pathways, and reactive oxygen species generation, etc. Ultimately, they activate anti-tumor immune response and improve the efficacy of cancer treatments. CONCLUSION: A growing number of ICD inducers from natural products with promising anti-cancer potential have been identified. The detailed information presented in this review will contribute to the further development of natural ICD inducers and cancer treatment strategies based on ICD-induced responses.

A review of phytoremediation of environmental lead (pb) contamination.

An estimated one billion people globally are exposed to hazardous levels of lead (Pb), resulting in intellectual disabilities for over 600,000 children each year. This critical issue aligns with the expanding worldwide population and the demand for food security, emphasizing the urgency of effectively addressing heavy metal pollution especially from Pb for sustainable development. Phytoremediation, a highly favoured approach in conjunction with conventional physical, chemical, and microbial methods, is a promising approach to mitigating soil and environmental contamination. In this review, we delve into a range of soil pollution mitigation strategies, with focus on the mechanisms that underpin the phytoremediation of environmental Pb. This detailed exploration sheds light on the efficacy and complexities of utilizing plants for the detoxification and removal of lead from contaminated environments. It also examines strategies to enhance phytoremediation by incorporating microbiology, composting, nanotechnology, and foliar spraying. The potential remediation strategies largely depend on the investigation and incorporation of environmentally friendly catalysts, as well as the utilization of innovative methods such as genetic engineering to improve phytoremediation processes. Studies have also shown that biochar has the capability to lower heavy metal concentrations in plant branches by over 50%, without affecting the pH of the soil. Specifically, magnetic biochar (MBC) has been shown to decrease lead levels in plants by up to 42%. Employing these methods showcases an effective strategy to enhance the efficacy of remediation techniques and fosters sustainable solutions to the pervasive issue of Pb pollution, thereby contributing to sustainable development efforts globally.

Ghrelin alleviates intestinal ischemia-reperfusion injury by activating the GHSR-1α/Sirt1/FOXO1 pathway.

Ischemia-reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia-reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 µg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.

The detoxification ability of sex-role reversed seahorses determines the sexual dimorphism in immune responses to benzo[a]pyrene exposure.

Sexual dimorphism in immune responses is an essential factor in environmental adaptation. However, the mechanisms involved remain obscure owing to the scarcity of data from sex-role-reversed species in stressed conditions. Benzo[a]pyrene (BaP) is one of the most pervasive and carcinogenic organic pollutants in coastal environments. In this study, we evaluated the potential effects on renal immunotoxicity of the sex-role-reversed lined seahorse (Hippocampus erectus) toward environmental concentrations BaP exposure. Our results discovered the presence of different energy-immunity trade-off strategies adopted by female and male seahorses during BaP exposure. BaP induced more severe renal damage in female seahorses in a concentration-dependent manner. BaP biotransformation and detoxification in seahorses resemble those in mammals. Benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide (BPDE) and 9-hydroxybenzo[a]pyrene (9-OH-BaP) formed DNA adducts and disrupted Ca2+ homeostasis may together attribute the renal immunotoxicity. Sexual dimorphisms in detoxification of both BPDE and 9-OH-BaP, and in regulation of Ca2+, autophagy and inflammation, mainly determined the extent of renal damage. Moreover, the mechanism of sex hormones regulated sexual dimorphism in immune responses needs to be further elucidated. Collectively, these findings contribute to the understanding of sexual dimorphism in the immunotoxicity induced by BaP exposure in seahorses, which may attribute to the dramatic decline in the biodiversity of the genus.

Perioperative outcomes of robotic versus video-assisted thoracoscopic surgery in non-small cell lung cancer patients after neoadjuvant chemoimmunotherapy.

Background: Limited data are available regarding perioperative outcomes in patients with non-small cell lung cancer (NSCLC) who undergo robotic-assisted thoracic surgery (RATS) after neoadjuvant chemoimmunotherapy. This study aimed to compare the perioperative outcomes of RATS and video-assisted thoracic surgery (VATS) in NSCLC patients after neoadjuvant chemoimmunotherapy. Methods: The study involved consecutive NSCLC patients treated with minimally invasive surgery (MIS) after neoadjuvant chemoimmunotherapy at a high-volume single center from September 2020 to October 2022. Short-term effects, including demographic, perioperative and pathological parameters, were compared between the RATS group and the VATS group. Results: A total of 119 patients were included in this study. Of these, 33 (27.7%) patients received RATS and 86 (72.3%) patients received VATS. Major pathological response (MPR) and pathological complete response (pCR) rates were comparable between the two groups. The RATS group had a higher number of dissected lymph nodes (21 vs. 18, P=0.03) and lymph node stations (7 vs. 6, P=0.004) compared with the VATS group but no differences were found in perioperative outcomes. Conclusions: These findings suggest that both RATS and VATS are safe and feasible options for NSCLC patients who have received neoadjuvant chemoimmunotherapy. Furthermore, RATS may offer advantages over VATS in patients who require a more extensive lymph node dissection.

Superwetting Nanofluids of NiOx-Nanocrystals/CsBr Solution for Fabricating Quality NiOx-CsPbBr3 Gradient Hybrid Film in Carbon-Based Perovskite Solar Cells.

The wettability of precursor solution on substrates is the critical factor for fabricating quality film. In this work, superwetting nanofluids (NFs) of non-stoichiometric nickel oxide (NiOx) nanocrystals (NCs)-CsBr solution are first utilized to fabricate quality NiOx-CsPbBr3 hybrid film with gradient-distributed NiOx NCs in the upper part for constructing hole transport ladder in carbon-based perovskite solar cells (C-PSCs). As anticipated, the crystalline properties (improved crystalline grain diameters and reduced impurity phase) and hole extraction/transport of the NiOx-CsPbBr3 hybrid film are improved after incorporating NiOx NCs into CsPbBr3. This originates from the superb wettability of NiOx-CsBr NFs on substrates and the excellent hole-transport properties of NiOx. Consequently, the C-PSCs with the structure of FTO/SnO2/NiOx-CsPbBr3/C displays a power conversion efficiency of 10.07%, resulting in a 23.6% improvement as compared with the pristine CsPbBr3 cell. This work opens up a promising strategy to improve the absorber layer in PSCs by incorporating NCs into perovskite layers through the use of the superwettability of NFs and by composition gradient engineering.