Exploring keratin composition variability for sustainable thermal insulator design.

In pursuing sustainable thermal insulation solutions, this study explores the integration of human hair and feather keratin with alginate. The aim is to assess its potential in thermal insulation materials, focusing on the resultant composites' thermal and mechanical characteristics. The investigation uncovers that the type and proportion of keratin significantly influence the composites' porosity and thermal conductivity. Specifically, higher feather keratin content is associated with lesser sulfur and reduced crosslinking due to shorter amino acids, leading to increased porosity and pore sizes. This, in turn, results in a decrease in ß-structured hydrogen bond networks, raising non-ordered protein structures and diminishing thermal conductivity from 0.044 W/(m·K) for pure alginate matrices to between 0.033 and 0.038 W/(m·K) for keratin-alginate composites, contingent upon the specific ratio of feather to hair keratin used. Mechanical evaluations further indicate that composites with a higher ratio of hair keratin exhibit an enhanced compressive modulus, ranging from 60 to 77 kPa, demonstrating the potential for tailored mechanical properties to suit various applications. The research underscores the critical role of sulfur content and the crosslinking index within keratin's structures, significantly impacting the thermal and mechanical properties of the matrices. The findings position keratin-based composites as environmentally friendly alternatives to traditional insulation materials.

Single-Cell Transcriptomics Revealed White Matter Repair Following Subarachnoid Hemorrhage.

Existing research indicates the potential for white matter injury repair during the subacute phase following subarachnoid hemorrhage (SAH). However, elucidating the role of brain cell subpopulations in the acute and subacute phases of SAH pathogenesis remains challenging due to the cellular heterogeneity of the central nervous system. In this study, single-cell RNA sequencing was conducted on SAH model mice to delineate distinct cell populations. Gene Set Enrichment Analysis was performed to identify involved pathways, and cellular interactions were explored using the CellChat package in R software. Validation of the findings involved a comprehensive approach, including magnetic resonance imaging, immunofluorescence double staining, and Western blot analyses. This study identified ten major brain clusters with cell type-specific gene expression patterns. Notably, we observed infiltration and clonal expansion of reparative microglia in white matter-enriched regions during the subacute stage after SAH. Additionally, microglia-associated pleiotrophin (PTN) was identified as having a role in mediating the regulation of oligodendrocyte precursor cells (OPCs) in SAH model mice, implicating the activation of the mTOR signaling pathway. These findings emphasize the vital role of microglia-OPC interactions might occur via the PTN pathway, potentially contributing to white matter repair during the subacute phase after SAH. Our analysis revealed precise transcriptional changes in the acute and subacute phases after SAH, offering insights into the mechanism of SAH and for the development of drugs that target-specific cell subtypes.

Novel therapeutic activities of dragon blood from palm tree Daemonorops draco for the treatment of chronic diabetic wounds.

BACKGROUND: The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past decades. Both in vitro and in vivo angiogenic activities have been reported for its herbal ingredients, including dragon blood from the palm tree Daemonorops draco and catechu from Uncaria gambir Roxb. Additionally, crude extracts of dragon blood have exhibited hypoglycemic effects not only in animal studies but also in cell-based in vitro assays. RESULTS: Our findings indicate that crude dragon blood extract promotes the differentiation of myoblasts into myotubes. Partially purified fractions of dragon blood crude extract significantly enhance the expression of muscle cell differentiation-related genes such as myoG, myoD, and myoHC. Our results also demonstrate that crude extracts of dragon blood can inhibit platelet-derived growth factor-induced PAI-1 expression in primary rat vascular smooth muscle cells, thereby favoring changes in hemostasis towards fibrinolysis. Consistent with previous reports, reduced expression of plasminogen activator inhibitor 1 (PAI-1) accelerates wound healing. However, further separation resulted in a significant loss of both activities, indicating the involvement of more than one compound in these processes. Stem cells play a crucial role in muscle injury repair. Neither dragon blood nor catechu alone stimulated the proliferation of human telomerase reverse transcriptase (hTERT)-immortalized and umbilical cord mesenchymal stem cells. Interestingly, the proliferation of both types of stem cells was observed when crude extracts of dragon blood and catechu were present together in the stem cell growth medium. CONCLUSIONS: Dragon blood from D. draco offers multifaceted therapeutic benefits for treating chronic nonhealing diabetic wounds from various perspectives. Most drugs in Western medicine consist of small molecules with defined ingredients. However, this is not the case in TCM, as the activities of dragon blood reported in this study. Surprisingly, the activities documented here align with descriptions in ancient Chinese medical texts dating back to A.D. 1625.

Multifunctional N, Fe-doped carbon dots with peroxidase-like activity for the determination of H2O2 and ascorbic acid and cell protection against oxidation.

Multifunctional N, Fe-doped carbon dots (N, Fe-CDs) were synthesized by the one-step hydrothermal method using ferric ammonium citrate and dicyandiamide as raw materials. The N, Fe-CDs exhibited peroxidase-like (POD) activity by catalyzing the oxidization of 3,3',5,5'-tetramethylbenzidine (TMB) to the green oxidation state ox-TMB in the presence of hydrogen peroxide (H2O2). Subsequently, based on the POD activity of N, Fe-CDs, an efficient and sensitive colorimetric method for the detection of H2O2 and ascorbic acid (AA) was established with a limit of detection of 0.40 µM and 2.05 µM. The proposed detection method has been successfully applied to detect AA in fruit juice, vitamin C tablets, and human serum samples and has exhibited excellent application prospects in biotechnology and food fields. Furthermore, N, Fe-CDs also showed a protective effect on the cell damage caused by H2O2 and could be used as an antioxidant agent.

[Study on Down-regulation of Interleukin-1ß Secretion by Inhibiting ABCC1/MRP1 Transporter].

OBJECTIVE: To screen interleukin (IL)-1ß secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice. METHODS: THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1ß was detected by ELISA, Western blot, and immunofluorescence. RESULTS: After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1ß decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1ß secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group (P < 0.05). CONCLUSION: ABCC1/MRP1 transporter is a newly discovered IL-1ß secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Hinokione: an abietene diterpene with pancreatic ß cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara.

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.

Nucleic Acid Plate Culture: Label-Free and Naked-Eye-Based Digital Loop-Mediated Isothermal Amplification in Hydrogel with Machine Learning.

Digital nucleic acid amplification enables the absolute quantification of single molecules. However, due to the ultrasmall reaction volume in the digital system (i.e., short light path), most digital systems are limited to fluorescence signals, while label-free and naked-eye readout remain challenging. In this work, we report a digital nucleic acid plate culture method for label-free, ultrasimple, and naked-eye nucleic acid analysis. As simple as the bacteria culture, the nanoconfined digital loop-mediated isothermal amplification was performed by using polyacrylamide (PAM) hydrogel as the amplification matrix. The nanoconfinement of PAM hydrogel with an ionic polymer chain can remarkably accelerate the amplification of target nucleic acids and the growth of inorganic byproducts, namely, magnesium pyrophosphate particles (MPPs). Compared to that in aqueous solutions, MPPs trapped in the hydrogel with enhanced light scattering characteristics are clearly visible to the naked eye, forming white "colony" spots that can be simply counted in a label-free and instrument-free manner. The MPPs can also be photographed by a smartphone and automatically counted by a machine-learning algorithm to realize the absolute quantification of antibiotic-resistant pathogens in diverse real samples.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Global trends in colorectal cancer and metabolic syndrome research: a bibliometric and visualization analysis.

Numerous studies have demonstrated a robust correlation between metabolic syndrome (MetS) and colorectal cancer (CRC). Nonetheless, no systematic analysis or visualization of relevant publications has been conducted via bibliometrics. This research, centred on 616 publications obtainable through the Web of Science Core Collection (WoSCC), employed CiteSpace software and VOSviewer software for correlation analyses of authors, journals, institutions, countries, keywords, and citations. The findings indicate that the Public Library of Science had the highest number of publications, while the United States, China, and South Korea were the most contributory nations. Recent years have seen the mechanisms linking Metabolic Syndrome with Colorectal Cancer, including diet, obesity, insulin resistance, and intestinal flora, remain a burgeoning research area. Furthermore, bariatric surgery appears to be a promising new area of study. This paper presents the initial bibliometric and visualization analysis of research literature concerning CRC and MetS which examines research trends and hotspots.

The NLRP3 inhibitor, OLT1177 attenuates brain injury in experimental intracerebral hemorrhage.

BACKGROUND AND PURPOSE: It has been reported activation of NLRP3 inflammasome after intracerebral hemorrhage (ICH) ictus exacerbates neuroinflammation and brain injury. We hypothesized that inhibition of NLRP3 by OLT1177 (dapansutrile), a novel NLRP3 inflammasome inhibitor, could reduce brain edema and attenuate brain injury in experimental ICH. METHODS: ICH was induced by injection of autologous blood into basal ganglia in mice models. Sixty-three C57Bl/6 male mice were randomly grouped into the sham, vehicle, OLT1177 (Dapansutrile, 200 mg/kg intraperitoneally) and treated for consecutive three days, starting from 1 h after ICH surgery. Behavioral test, brain edema, brain water content, blood-brain barrier integrity and vascular permeability, cell apoptosis, and NLRP3 and its downstream protein levels were measured. RESULTS: OLT1177 significantly reduced cerebral edema after ICH and contributed to the attenuation of neurological deficits. OLT1177 could preserve blood-brain barrier integrity and lessen vascular leakage. In addition, OLT1177 preserved microglia morphological shift and significantly inhibited the activation of caspase-1 and release of IL-1ß. We also found that OLT1177 can protect against neuronal loss in the affected hemisphere. CONCLUSIONS: OLT1177 (dapansutrile) could significantly attenuate the brain edema after ICH and effectively alleviate the neurological deficit. This result suggests that the novel NLRP3 inhibitor, OLT1177, might serve as a promising candidate for the treatment of ICH.

Compounds from Agathis dammara exert hypoglycaemic activity by enhancing glucose uptake: lignans, terpenes and others.

In this study, two new kaurane diterpenes (16, 17), together with 12 lignans (1-12), a triterpene (15), and two other compounds (13, 14) were isolated from the woods of Agathis dammara. The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy, and its absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. Compounds 5, 11, 14 exhibit significant hypoglycaemic activity in zebrafish, and their mechanism of action is to enhance glucose uptake in zebrafish.

Development of a Novel Contrast-Enhanced Ultrasound-Based Nomogram for Superficial Lymphadenopathy Differentiation: Postvascular Phase Value.

OBJECTIVE: The aim of this study was to develop and prospectively validate a prediction model for superficial lymphadenopathy differentiation using Sonazoid contrast-enhanced ultrasound (CEUS) combined with ultrasound (US) and clinical data. METHODS: The training cohort comprised 260 retrospectively enrolled patients with 260 pathological lymph nodes imaged between January and December 2020. Two clinical US-CEUS models were created using multivariable logistic regression analysis and compared using receiver operating characteristic curve analysis: Model 1 included clinical and US characteristics; Model 2 included all confirmed predictors, including CEUS characteristics. Feature contributions were evaluated using the SHapley Additive exPlanations (SHAP) algorithm. Data from 172 patients were prospectively collected between January and May 2021 for model validation. RESULTS: Age, tumor history, long-axis diameter of lymph node, blood flow distribution, echogenic hilus, and the mean postvascular phase intensity (MPI) were identified as independent predictors for malignant lymphadenopathy. The area under the curve (AUC), sensitivity, specificity, and accuracy of MPI alone was 0.858 (95% confidence interval [CI], 0.817-0.891), 86.47%, 74.55%, and 81.2%, respectively. Model 2 had an AUC of 0.919 (95% CI, 0.879-0.949) and good calibration in training and validation cohorts. The incorporation of MPI significantly enhanced diagnostic capability (p < 0.0001 and p = 0.002 for training and validation cohorts, respectively). Decision curve analysis indicated Model 2 as the superior diagnostic tool. SHAP analysis highlighted MPI as the most pivotal feature in the diagnostic process. CONCLUSION: The employment of our straightforward prediction model has the potential to enhance clinical decision-making and mitigate the need for unwarranted biopsies.

Hypoglycemic effects of dracorhodin and dragon blood crude extract from Daemonorops draco.

BACKGROUND: Dragon blood is a red fruit resin from the palm tree Daemonorops draco and is a herbal ingredient used in the traditional Chinese medicine, "Jinchuang Ointment," which is used to treat non-healing diabetic wounds. According to the Taiwan Herbal Pharmacopeia, the dracorhodin content in dragon blood should exceed 1.0%. RESULTS: Our findings indicate that dracorhodin and dragon blood crude extracts can stimulate glucose uptake in mouse muscle cells (C2C12) and primary rat aortic smooth muscle cells (RSMC). Dracorhodin is not the only active compound in dragon blood crude extracts from D. draco. Next, we orally administered crude dragon blood extracts to male B6 mice. The experimental group displayed a decreasing trend in fasting blood glucose levels from the second to tenth week. In summary, crude extracts of dragon blood from D. draco demonstrated in vivo hypoglycemic effects in B6 male mice. CONCLUSIONS: We provide a scientific basis "Jinchuang ointment" in treating non-healing wounds in patients with diabetes.

Molecular features and clinical outcomes of EGFR-mutated, MET-amplified non-small-cell lung cancer after resistance to dual-targeted therapy.

Background: Some studies of dual-targeted therapy (DTT) targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Consequently, patient management following DTT resistance has gained significance. However, the underlying resistance mechanisms and clinical outcomes in these patients remain unclear. Objectives: This study aimed to delineate the molecular characteristics and survival outcomes of patients with NSCLC harboring EGFR mutations and acquired MET amplification after developing resistance to DTT. Design: We conducted a retrospective analysis of patients with NSCLC with EGFR mutations and acquired MET amplification who exhibited resistance to EGFR/MET DTT. Methods: Next-generation sequencing (NGS) was performed on patients with available tissue samples before and/or after the development of resistance to DTT. Stratified analyses were carried out based on data sources and subsequent salvage treatments. Univariate/multivariate Cox regression models and survival analyses were employed to explore potential independent prognostic factors. Results: The study included 77 NSCLC patients, with NGS conducted on 19 patients. We observed many resistance mechanisms, including EGFR-dependent pathways (4/19, 21.1%), MET-dependent pathways (2/19, 10.5%), EGFR/MET co-dependent pathways (2/19, 10.5%), and EGFR/MET-independent resistance mechanisms (11/19, 57.9%). Post-progression progression-free survival (pPFS) and post-progression overall survival (pOS) significantly varied among patients who received the best supportive care (BSC), targeted therapy, or chemotherapy (CT), with median pPFS of 1.5, 3.9, and 4.9 months, respectively (p = 0.003). Median pOS were 2.3, 7.7, and 9.2 months, respectively (p < 0.001). The number of treatment lines following DTT resistance and the Eastern Cooperative Oncology Group performance status emerged as the independent prognostic factors. Conclusion: This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT.

Implementing advance care planning in palliative and end of life care: a scoping review of community nursing perspectives.

BACKGROUND: Advance care planninganning (ACP) is a priority within palliative care service provision. Nurses working in the community occupy an opportune role to engage with families and patients in ACP. Carers and family members of palliative patients often find ACP discussions difficult to initiate. However, community nurses caring for palliative patients can encourage these discussions, utilising the rapport and relationships they have already built with patients and families. Despite this potential, implementation barriers and facilitators continue to exist. To date, no research synthesis has captured the challenges community nurses face when implementing ACP, nor the facilitators of community nurse-led ACP. Considering this, the review question of: 'What factors contribute to or hinder ACP discussion for nurses when providing care to palliative patients?' was explored. METHOD: To capture challenges and facilitators, a global qualitative scoping review was undertaken in June 2023. The Arksey and O'Malley framework for scoping reviews guided the review methodology. Six databases were searched identifying 333 records: CINAHL (16), MEDLINE (45), PUBMED (195), EMBASE (30), BJOCN (15), IJOPN (32). After de-duplication and title and abstract screening, 108 records remained. These were downloaded, hand searched (adding 5 articles) and subject to a full read. 98 were rejected, leaving a selected dataset of 15 articles. Data extracted into a data extraction chart were thematically analysed. RESULTS: Three key themes were generated: 'Barriers to ACP', 'Facilitators of ACP' and 'Understanding of professional role and duty'. Key barriers were - lack of confidence, competence, role ambiguity and prognostic uncertainty. Key facilitators concerned the pertinence of the patient-practitioner relationship enabling ACP amongst nurses who had both competence and experience in ACP and/or palliative care (e.g., palliative care training). Lastly, nurses understood ACP to be part of their role, however, met challenges understanding the law surrounding this and its application processes. CONCLUSIONS: This review suggests that community nurses' experience and competence are associated with the effective implementation of ACP with palliative patients. Future research is needed to develop interventions to promote ACP uptake in community settings, enable confidence building for community nurses and support higher standards of palliative care via the implementation of ACP.

Untargeted urine metabolomics and machine learning provide potential metabolic signatures in children with autism spectrum disorder.

Background: Complementary to traditional biostatistics, the integration of untargeted urine metabolomic profiling with Machine Learning (ML) has the potential to unveil metabolic profiles crucial for understanding diseases. However, the application of this approach in autism remains underexplored. Our objective was to delve into the metabolic profiles of autism utilizing a comprehensive untargeted metabolomics platform coupled with ML. Methods: Untargeted metabolomics quantification (UHPLC/Q-TOF-MS) was performed for urine analysis. Feature selection was conducted using Lasso regression, and logistic regression, support vector machine, random forest, and extreme gradient boosting were utilized for significance stratification. Pathway enrichment analysis was performed to identify metabolic pathways associated with autism. Results: A total of 52 autistic children and 40 typically developing children were enrolled. Lasso regression identified ninety-two urinary metabolites that significantly differed between the two groups. Distinct metabolites, such as prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, were revealed to be associated with autism through the application of four different ML methods (p<0.05). The alterations observed in the phosphatidylinositol and inositol phosphate metabolism pathways were linked to the pathophysiology of autism (p<0.05). Conclusion: Significant urinary metabolites, including prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, exhibit associations with autism. Additionally, the involvement of the phosphatidylinositol and inositol phosphate pathways suggests their potential role in the pathophysiology of autism.

Electric manipulation on deformation of ionic ferrofluid sessile droplets.

Active electric-driven droplet manipulation in digital microfluidics constitutes a promising domain owing to the unique and programmable wettability inherent in sessile ionic droplets. The coupling between the electric field and flow field enables precise control over wetting characteristics and droplet morphology. This study delves into the deformation phenomena of ionic sessile ferrofluid droplets in ambient air induced by uniform electric fields. Under the assumption of a pinned mode throughout the process, the deformation is characterized by variations in droplet height and contact angle in response to the applied electric field intensity. A numerical model is formulated to simulate the deformation dynamics of ferrofluid droplets, employing the phase field method for tracking droplet deformation. The fidelity of the numerical outcomes is assessed through the validation process, involving a comparison of droplet geometric deformations with corresponding experimental results. The impact of the electric field on the deformation of dielectric droplets is modulated by parameters such as electric field strength and droplet size. Through meticulously designed experiments, the substantial influence of both field strength and droplet size is empirically verified, elucidating the behavior of ionic sessile droplets. Considering the interplay of electric force, viscous force, and interfacial tension, the heightened field intensity is observed to effectively reduce the contact angle, augment droplet height, and intensify internal droplet flow. Under varying electric field conditions, droplets assume diverse shapes, presenting a versatile approach for microfluidic operations. The outcomes of this research hold significant guiding implications for microfluidic manipulation, droplet handling, and sensing applications.

Plasma ddPCR for the detection of MET amplification in advanced NSCLC patients: a comparative real-world study.

Background: Mesenchymal-epithelial transition (MET) amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection. However, it is inapplicable when tissue samples are unavailable. Objective: This study assessed the performance of plasma droplet digital polymerase chain reaction (ddPCR) in MET amplification detection in NSCLC patients. Design and methods: A total of 87 NSCLC patients were enrolled, and 94 paired tissue and plasma samples were analyzed for the concordance between FISH and plasma ddPCR/tissue next-generation sequencing (NGS) in detecting MET amplification. In addition, the efficacy of patients with MET amplification using different detection methods who were treated with MET-TKIs was evaluated. Results: Plasma ddPCR showed substantial concordance with FISH (74.1% sensitivity, 92.5% specificity, and 87.2% accuracy with a kappa value of 0.68) and outperformed tissue NGS (kappa value of 0.64) in MET amplification detection. Combined plasma ddPCR and tissue NGS showed substantial concordance with FISH (92.3% sensitivity, 89.2% specificity, and an accuracy of 90.1% with a kappa value of 0.77). The efficacy is comparable in these NSCLC patients with MET amplification detected by FISH and plasma ddPCR who were treated with MET-TKIs. Conclusion: Plasma ddPCR is a potentially reliable method for detecting MET amplification in advanced NSCLC patients. Combined plasma ddPCR and tissue NGS might be an alternative or complementary method to MET amplification detection.

Promotion of ROS-mediated apoptosis, G2/M arrest, and autophagy by naringenin in non-small cell lung cancer.

Background: As lung cancer is the leading cause of cancer death worldwide, the development of new medicines is a crucial endeavor. Naringenin, a flavanone derivative, possesses anti-cancer and anti-inflammatory properties and has been reported to have cytotoxic effects on various cancer cells. The current study investigated the underlying molecular mechanism by which naringenin induces cell death in lung cancer. Methods: The expression of apoptosis, cell cycle arrest, and autophagy markers in H1299 and A459 lung cancer cells was evaluated using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL), Western blot, Annexin V/PI stain, PI stain, acridine orange staining, and transmission electron microscopy (TEM). Using fluorescence microscopy, DALGreen was used to observe the degradation of p62, a GFP-LC3 plasmid was used to evaluate puncta formation, and a pcDNA3-GFP-LC3-RFP-LC3ΔG plasmid was used to evaluate autophagy flux. Furthermore, the anti-cancer effect of naringenin was evaluated in a subcutaneous H1299 cell xenograft model. Results: Naringenin treatment of lung cancer cells (H1299 and A459) reduced cell viability and induced cell cycle arrest. Pretreatment of cells with ROS scavengers (N-acetylcysteine or catalase) suppressed the naringenin-induced cleavage of apoptotic protein and restored cyclin-dependent kinase activity. Naringenin also triggered autophagy by mediating ROS generation, thereby activating AMP-activated protein kinase (AMPK) signaling. ROS inhibition not only inhibited naringenin-induced autophagic puncta formation but also decreased the ratio of microtubule-associated proteins 1A/1B light chain 3 II (LC3II)/LC3I and activity of the AMPK signaling pathway. Furthermore, naringenin suppressed tumor growth and promoted apoptosis in the xenograft mouse model. Conclusion: This study demonstrated the potent anti-cancer effects of naringenin on lung cancer cells, thereby providing valuable insights for developing small-molecule drugs that can induce cell cycle arrest, apoptosis, and autophagic cell death.

Octylammonium Iodide Induced in-situ Healing Behavior at Perovskite / Carbon Interface: the "Slow-Release Effect" Caused by Carbon Black Adsorption.

"Perovskite / Carbon" interface has remained a key bottleneck for the hole-conductor-free perovskite solar cells based on carbon-electrode (CPSCs), due to problems like loose physics contact, defects, energy mismatch, poor chemical coupling, etc. A previous study shows that octylammonium iodide (OAI) blending in carbon paste induced a kind of "in-situ healing" effect for "perovskite / carbon" interface, and improved power conversion efficiency from ≈13% to >19%. Here the beneath mechanism is further explored by careful examination of the interaction between OAI molecule and carbon black (CB) nanoparticles. It comes to show that, the famous "CB adsorption" plays a key role during the "healing" processes. Due to CB adsorption behavior, the mass ratio between OAI and CB influences much on the healing effect. By suitably adjusting the mass ratio between OAI and CB, and increasing the light harvest of perovskite, an efficiency of 19.41% is achieved for the hole-conductor-free CPSCs. Device efficiency and the charge-extraction and recombination process are tracked with the storage period, continuous improvement appears for devices assembled by relatively higher CB mass. A kind of "slow-release effect" is revealed during the OAI-induced "in-situ healing" process, which is caused by the famous "CB adsorption" behavior.