Non-destructive estimation of flesh oil content in avocado (Persea americana Mill.) using fluorescence images from 365-nm UV light excitation.

The flesh oil content (OC) is a crucial commercial indicator of avocado maturity and directly correlates with its nutritional quality. To meet export standards and optimize edible characteristics, avocados must be harvested at the appropriate stage of physiological maturity. The significant variability in OC during maturation, without any external morphological indicators, poses a longstanding challenge. Currently, harvesting maturity is optimized through time-consuming, destructive laboratory methods like freeze-drying and chemical extraction, which use representative samples to estimate the maturity of entire orchards. In this study, for the first time, we employed fluorescence imaging of avocado skin using 365-nm UV polarized light excitation to estimate the OC in the 'Bacon' avocado cultivar. We developed a surface fluorescence index that strongly correlates with OC, achieving correlation coefficients up to - 0.91. Our non-destructive and rapid approach achieved a cross-validation accuracy with an R2 value of 0.81, enabling the classification of avocados with low and high OC. This pioneering method shows considerable potential for further improvement and refinement. This study lays the groundwork for developing a portable, cost-effective, and real-time method for non-destructive in situ monitoring of avocado OC in the field and its integration into large-scale post-harvest grading systems.

Temperature-dependent excitonic emission characteristics of highly crystallized carbon nitride nanosheets.

Highly-crystallized carbon nitride (HCCN) nanosheets exhibit significant potential for advancements in the field of photoelectric conversion. However, to fully exploit their potential, a thorough understanding of the fundamental excitonic photophysical processes is crucial. Here, the temperature-dependent excitonic photoluminescence (PL) of HCCN nanosheets and amorphous polymeric carbon nitride (PCN) is investigated using steady-state and time-resolved PL spectroscopy. The exciton binding energy of HCCN is determined to be 109.26 meV, lower than that of PCN (207.39 meV), which is attributed to the ordered stacking structure of HCCN with a weaker Coulomb interaction between electrons and holes. As the temperature increases, a noticeable reduction in PL lifetime is observed on both the HCCN and PCN, which is ascribed to the thermal activation of carrier trapping by the enhanced electron-phonon coupling effect. The thermal activation energy of HCCN is determined to be 102.9 meV, close to the value of PCN, due to their same band structures. Through wavelength-dependent PL dynamics analysis, we have identified the PL emission of HCCN as deriving from the transitions:σ*-LP,π*-π, andπ*-LP, where theπ*-LP transition dominants the emission because of the high excited state density of the LP state. These results demonstrate the impact of high-crystallinity on the excitonic emission of HCCN materials, thereby expanding their potential applications in the field of photoelectric conversion.

Antioxidant assessment of agricultural produce using fluorescence techniques: a review.

The study of bioactive compounds like food antioxidants is getting huge attention and curiosity by researchers and other relevant stakeholders (e.g., food and pharmaceutical industries) due to their health benefits. However, the currently available protocols to estimate the antioxidant activity of foods are time-consuming, destructive, require complex procedures for sample preparation, need technical persons, and not possible for real-time application, which are very important for large-scale or industrial applications. On the other hand, fluorescence spectroscopy and imaging techniques are relatively new, fast, mostly nondestructive, and possible to apply real-time to detect the antioxidants of foods. However, there is no review article on fluorescence techniques for estimating antioxidants in agricultural produces. Therefore, the present review comprehensively summarizes the overview of fluorescence phenomena, techniques (i.e., spectroscopy and computer vision), and their potential to monitor antioxidants in fruits and vegetables. Finally, opportunities and challenges of fluorescence techniques are described toward developing next-generation protocols for antioxidants measurement. Fluorescence techniques (both spectroscopy and imaging) are simpler and faster than available traditional methods of antioxidants measurement. Moreover, the fluorescence imaging technique has the potential to apply in real-time antioxidant identification in agricultural produce such as fruits and vegetables. Therefore, this technique might be used as a next-generation protocol for qualitative and quantitative antioxidants measurement after improvements like new material technologies for sensor (detector) and light sources for higher sensitivity and reduce the cost of implementing real-world applications.

Initial attitudes toward a drug predict medication adherence in first-episode patients with schizophrenia: a 1-year prospective study in China.

BACKGROUND: Patients' attitudes toward medication have been shown to be a predictor of nonadherence to antipsychotic treatment. However, most previous studies that explored this relationship used a cross-sectional design. It is important to explore the association of attitudes toward drugs with discontinuation at different time points during antipsychotic treatment. In this study, we investigated the association of attitudes toward drugs (measured by the Drug Attitude Inventory (DAI-10)) with adherence at seven time points (baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks, and 52 weeks) during 1 year of treatment. Factors that were potentially associated with attitudes toward drugs at the time point of interest were also studied. METHODS: Demographic characteristics, psychopathology, social functioning, and attitudes toward drugs (measured by the DAI-10) were collected at baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks and 52 weeks. The association of attitudes toward drugs (measured by DAI-10) with adherence at the seven time points was calculated using the Mann‒Whitney U test. The optimal cutoff point for the DAI-10 was then determined using receiver operating characteristic (ROC) analysis. Cox regression analysis was conducted to further investigate the association of DAI-10 scores with discontinuation, controlling for potential confounding variables. We used multiple regression analysis to identify the factors associated with DAI-10 scores. RESULTS: Among the six time points, only baseline DAI-10 total scores were significantly different between the completed and discontinued groups (p = 0.004). Female sex and a baseline DAI-10 total score greater than - 1 were found to be independent protective factors against discontinuation of antipsychotic drug treatments during the 1-year follow-up. At baseline, the severity of the disease (CGI-s) and insight regarding the disease were shown to be associated with DAI-10 total scores. CONCLUSION: Attitudes toward antipsychotic drugs at baseline were shown to play a crucial role in predicting treatment discontinuation. TRIAL REGISTRATION: The data were collected from a clinical trial and the clinical trials.gov ID of the study is NCT01057849.

Virtual Screening of Novel 24-Dehydroxysterol Reductase (DHCR24) Inhibitors and the Biological Evaluation of Irbesartan in Cholesterol-Lowering Effect.

Hyperlipidemia is a risk factor for the development of fatty liver and cardiovascular diseases such as atherosclerosis and coronary heart disease, and hence, cholesterol-lowering drugs are considered important and effective in preventing cardiovascular diseases. Thus, researchers in the field of new drug development are endeavoring to identify new types of cholesterol-lowering drugs. 3ß-hydroxysterol-Δ(24)-reductase (DHCR24) catalyzes the conversion of desmosterol to cholesterol, which is the last step in the cholesterol biosynthesis pathway. We speculated that blocking the catalytic activity of DHCR24 could be a novel therapeutic strategy for treating hyperlipidemia. In the present study, by virtually screening the DrugBank database and performing molecular dynamics simulation analysis, we selected four potential DHCR24 inhibitor candidates: irbesartan, risperidone, tolvaptan, and conivaptan. All four candidates showed significant cholesterol-lowering activity in HepG2 cells. The experimental mouse model of hyperlipidemia demonstrated that all four candidates improved high blood lipid levels and fat vacuolation in the livers of mice fed with a high-fat diet. In addition, Western blot analysis results suggested that irbesartan reduced cholesterol levels by downregulating the expression of the low-density lipoprotein receptor. Finally, the immune complex activity assay confirmed the inhibitory effect of irbesartan on the enzymatic activity of DHCR24 with its half-maximal inhibitory concentration (IC50) value of 602 nM. Thus, to the best of our knowledge, this is the first study to report that blocking the enzymatic activity of DHCR24 via competitive inhibition is a potential strategy for developing new cholesterol-lowering drugs against hyperlipidemia or multiple cancers. Furthermore, considering that irbesartan is currently used to treat hypertension combined with type 2 diabetes, we believe that irbesartan should be a suitable choice for patients with both hypertension and hyperlipidemia.

Structural characterization and analysis of different epimers of neutral glycosphingolipid LcGg4 by ion mobility spectrometry-mass spectrometry.

LcGg4, a neutral glycosphingolipid (GSL) and cancer antigen, its epimers GalNAc-LcGg4 and GlcNAc-LcGg4, and three lipid forms of GalNAc-LcGg4 were studied by mass spectrometry (MS). It was found that different forms of GalNAc-LcGg4 carrying homologous (d16:1/18:0) and (d18:1/18:0) lipids were easily separated and identified using liquid chromatography (LC)-MS. In addition, like gangliosides, homologous lipid forms of GalNAc-LcGg4 showed the same fragmentation pattern, except for a uniform shift of their glycolipid product ions by a certain m/z number determined by the varied lipid structure. It was also disclosed that LcGg4 and its epimers GalNAc-LcGg4 and GlcNAc-LcGg4, which are different only in the C4-configuration of their non-reducing end sugar residues, gave the same MS/MS product ions in similar relative intensities, as well as the same LC retention time, suggesting the challenge to differentiate epimeric GSLs by LC-MS. However, ion mobility spectrometry (IMS)-MS was able to efficiently separate and distinguish these epimers. This study has demonstrated the promise of IMS-MS for isomeric GSL characterization and the IMS-MS and LC-MS/MS combination for natural GSL analysis.

Effect of combined epidural-general anesthesia on long-term survival of patients with colorectal cancer: a meta-analysis of cohort studies.

PURPOSE: This study aimed to analyze the long-term survival of patients with colorectal cancer after receiving combined epidural-general anesthesia (EGA) or general anesthesia (GA) alone. METHODS: The PubMed, MEDLINE, Web of Science, Cochrane Library, and Embase databases were used to search for cohort studies that explored the differences between the effects of EGA and GA on overall survival (OS) and recurrence-free survival (RFS) of patients with colorectal cancer. The hazard ratios (HRs) and their 95% confidence intervals (95%CIs) were used as indicators to evaluate the strength of the effects and were pooled. RESULTS: Nine studies were included in the meta-analysis. EGA improved the OS of patients with colorectal cancer compared with GA (HR = 0.904, 95%CI 0.871-0.938, P < 0.05). In the subgroup analysis, EGA was more protective for OS of patients with colon cancer than GA (HR = 0.840, 95%CI 0.732-0.963, P < 0.05), but not for OS of patients with rectal cancer (HR = 0.764, 95%CI 0.398-1.469, P > 0.05). Additionally, EGA could not further prolong RFS in patients with colorectal cancer (HR = 1.015, 95%CI 0.942-1.093, P > 0.05), which was the same in the subgroup analysis of patients with colon cancer (HR = 0.908, 95%CI 0.760-1.085, P > 0.05). CONCLUSION: EGA could improve the OS of patients with colorectal cancer, especially those with colon cancer, but it could not improve the OS in the subgroup of patients with rectal cancer. This difference may be due to the immune protective function of the parasympathetic nerve innervating the intestinal tubes above the splenic flexure retained by EGA. Additionally, although EGA has a protective effect on RFS in patients with colorectal cancer, the difference was not significant.  The design of this analysis is registered and displayed in the PROSPERO database (CRD42021274864).

Characterization of Glycosphingolipids and Their Diverse Lipid Forms through Two-Stage Matching of LC-MS/MS Spectra.

Glycosphingolipids (GSLs) play a key role in various biological and pathological events. Thus, determination of the complete GSL compositions in human tissues is essential for comparative and functional studies of GSLs. In this work, a new strategy was developed for GSL characterization and glycolipidomics analysis based on two-stage matching of experimental and reference MS/MS spectra. In the first stage, carbohydrate fragments, which contain only glycans and thus are conserved within a GSL species, are directly matched to yield a species identification. In the second stage, glycolipid fragments from the matched GSL species, which contain both the lipid and glycans and thus shift due to lipid structural changes, are treated according to lipid rule-based matching to characterize the lipid compositions. This new strategy uses the whole spectrum for GSL characterization. Furthermore, simple databases containing only a single lipid form per GSL species can be utilized to identify multiple GSL lipid forms. It is expected that this method will help accelerate glycolipidomics analysis and disclose new and diverse lipid forms of GSLs.

Associations between the waist-to-height ratio index and migraine: A cross-section study of the NHANES 1999-2004.

BACKGROUND: The importance of obesity as a factor that increases the probability of migraine episodes is increasingly acknowledged. Thus, this study aimed to explore the potential correlation between central obesity and migraine, emphasizing the waist-to-height ratio (WHtR) as a key measure in assessing this relationship. METHODS: This cross-sectional analysis included 13,344 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. To investigate the association associations between WHtR and migraine, we utilized refined multivariate logistic regression models, smoothing curve fitting methods, subpopulation analysis, and interactive testing. RESULTS: Of the 13,344 participants, 2,764 (20.72%) had migraines. A significant positive correlation was observed between the WHtR and migraine incidence in both the partially adjusted model (3.08 [95% CI: 1.92-4.94]) and the crude model (1.95 [95% CI: 1.23-3.08]). The participants in the highest quartile of the WHtR had a 13% greater incidence of migraine than those in the lowest quartile [1.13(0.99,1.28)]. The interaction analysis revealed a statistically significant difference (p<0.01) in this relationship among the subgroups. Notably, the correlation between WHtR and migraine risk was not significant and negative in patients ≥60 years, indicating that obesity has a mitigating role in preventing migraine in this elderly population. CONCLUSIONS: The incidence of migraine increased concomitantly with increased WHtR. However, central obesity has a protective effect against migraine occurrence in individuals ≥60 years. Thus, our findings underscore the importance of WHtR in migraine prevention and management strategies and highlight its potential as a critical biomarker for mitigating migraine incidence.

An acid-tolerant metal-organic framework for industrial CO2 electrolysis using a proton exchange membrane.

Industrial CO2 electrolysis via electrochemical CO2 reduction has achieved progress in alkaline solutions, while the same reaction in acidic solution remains challenging because of severe hydrogen evolution side reactions, acid corrosion, and low target product selectivity. Herein, an industrial acidic CO2 electrolysis to pure HCOOH system is realized in a proton-exchange-membrane electrolyzer using an acid-tolerant Bi-based metal-organic framework guided by a Pourbaix diagram. Significantly, the Faradaic efficiency of HCOOH synthesis reaches 95.10% at a large current density of 400 mA/cm2 with a high CO2 single-pass conversion efficiency of 64.91%. Moreover, the proton-exchange-membrane device also achieves an industrial-level current density of 250 mA/cm2 under a relatively low voltage of 3.5 V for up to 100 h with a Faradaic efficiency of 93.5% for HCOOH production, which corresponds to an energy consumption of 200.65 kWh/kmol, production rate of 12.1 mmol/m2/s, and an energy conversion efficiency of 38.2%. These results will greatly aid the contemporary research moving toward commercial implementation and success of CO2 electrolysis technology.

Anthropometric indicators may explain the high incidence of follicular lymphoma in Europeans: Results from a bidirectional two-sample two-step Mendelian randomisation.

BACKGROUND: Non-Hodgkin's lymphoma incidence rates vary between European and Asian populations. The reasons remain unclear. This two-sample two-step Mendelian randomisation (MR) study aimed to investigate the causal relationship between anthropometric indicators (AIs) and diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and the possible mediating role of basal metabolic rate (BMR) in Europe. METHODS: We used the following AIs as exposures: body mass index (BMI), whole-body fat mass (WBFM), whole-body fat-free mass (WBFFM), waist circumference(WC), hip circumference(HC), standing height (SH), and weight(Wt). DLBCL and FL represented the outcomes, and BMR was a mediator. A two-sample MR analysis was performed to examine the association between AIs and DLBCL and FL onset. We performed reverse-MR analysis to determine whether DLBCL and FL interfered with the AIs. A two-step MR analysis was performed to determine whether BMR mediated the causality. FINDINGS: WBFFM and SH had causal relationships with FL. A causal association between AIs and DLBCL was not observed. Reverse-MR analysis indicated the causal relationships were not bidirectional. Two-step MR suggested BMR may mediate the causal effect of WBFFM and SH on FL. CONCLUSIONS: We observed a causal relationship between WBFFM and SH and the onset of FL in Europeans, Which may explain the high incidence of follicular lymphoma in Europeans.

Fabricating a high-performance anode by coating a carbon layer on a yolk-shell bimetallic selenide microsphere for enhanced lithium storage.

The rational synthesis of an electrode material with a highly active and stable architecture is very critical to achieving high-performance electrochemical energy storage. Herein, N-doped carbon restricting yolk-shell CoSe2/Ni3Se4 (CoSe2/Ni3Se4@NC) flower-like microspheres were successfully synthesized from solid CoNi-glycerate microspheres using a coating technology as an anode material for lithium-ion batteries (LIBs). The unique yolk-shell CoSe2/Ni3Se4@NC microspheres with hierarchical pores can increase the contact area with the electrolyte and provide enough transfer channels for the diffusion of Li+. The carbon layer on the surface of CoSe2/Ni3Se4@NC can not only improve the conductivity of the electrode but also provide the protective effect of active nanosheets during the process of synthesis, avoiding the overall structure collapse during the charge/discharge process of LIBs. Benefiting from the high conductivity, hollow structure, and elastic NC shell bestowed by the unique architecture, the yolk-shell CoSe2/Ni3Se4@NC anode shows excellent lithium storage performances, such as an excellent reversible specific capacity of 319 mA h g-1 at a current density of 1000 mA g-1 after 500 cycles and excellent cycling stability. This synthesis strategy provides a new way to optimize the lithium storage performance of transition metal compound electrode materials, which is helpful to the design of the next generation of high-performance LIBs.

Serum trace elements and osteoarthritis: A meta-analysis and Mendelian randomization study.

OBJECTIVE: This study aims to establish the correlation between shifts in serum trace element (TE) levels and the progression of osteoarthritis (OA), while also exploring the underlying causal relationship between these variables. METHODS: An investigation was conducted, which included a systematic review, a meta-analysis of observational studies, and a two-sample Mendelian randomization (MR) study. RESULTS: This meta-analysis revealed significant differences in serum levels of copper, manganese, cadmium, and selenium between OA patients and healthy controls, after adjusting for heterogeneity. Specifically, significant disparities were observed for copper (SMD 0.118 [95 % CI: 0.061 ∼ 0.175], P < 0.001), manganese (SMD -0.180 [95 % CI: -0.326 ∼ -0.034], P = 0.016), cadmium (SMD 0.227 [95 % CI: 0.131 ∼ 0.322], P < 0.001), and selenium (SMD -0.138 [95 % CI: -0.209 ∼ -0.068], P < 0.001), while zinc levels did not show a significant difference (SMD -0.02 [95 % CI: -0.077 ∼ 0.038], P = 0.503). Further, MR analysis suggested a causal link between genetically predicted serum copper level changes and OA development, but not for other TEs. CONCLUSION: The study suggests that there is an association between the occurrence of OA and variations in serum levels of copper, manganese, cadmium, and selenium. Elevated serum copper may play a pivotal role. Further research is needed to explore the therapeutic potential of TE level modulation in OA management.

Improvement of social functioning in patients with first-episode schizophrenia using blonanserin treatment: a prospective, multi-centre, single-arm clinical trial.

Objectives: This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. Methods: In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. Results: A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Conclusion: Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.

A recombinant pseudorabies virus surface - displaying the classical swine fever E2 protein induces specific antibodies rapidly.

Pseudorabies virus (PRV) and classical swine fever virus (CSFV) are both economically important pathogens threatening the pig industry in many countries. The triple-gene-deleted variant of PRV, herein referred to as rPRVTJ-delgE/gI/TK, has exhibited pronounced efficacy and safety profiles. This underscores its viability as a prospective vaccine vector. However, the generation of specific anti-E2 antibodies necessitates elevated immunization doses and extended durations when the extracellular domain of the E2 protein of CSFV is secreted via the recombinant rPRVTJ-delgE/gI/TK vector. To enhance the presentation of exogenous antigens by antigen-presenting cells (APCs), we engineered the E2 protein expressed on the surface of PRV particles in this study. The recombinant virus expressing the E2 protein with a heterogonous transmembrane domain was generated in the backbone of rPRVTJ-delgE/gI/TK and designated as rPRVTJ-UL44-E2. The E2 gene was fused to the 3' terminus of the UL44 gene utilizing P2A, a self-cleaving peptide sequence. The electron microscopy showed that the E2 protein was anchored on the surface of the viral particles of rPRVTJ-delgE/gI/TK-E2. The insertion of the E2 gene did not alter the native biological characteristics of the viral vector. Rabbits immunized with 107 median tissue culture infective doses (TCID50) of rPRVTJ-UL44-E2 exhibited a rapid seroconversion to anti-E2 specific antibodies within 7 days post-immunization (dpi). All the rabbits immunized with the rPRVTJ-UL44-E2 had generated antibodies specific to E2 prior to the administration of the booster immunization. However, the immunized rabbits were not protected from the CSFV C-strain challenge. Nevertheless, this strategy has notably achieved rapid induction of E2-specific non-neutralizing antibodies. These findings provide insights that the design of rPRVTJ-UL44-E2 requires optimization, thereby indicating a promising avenue for augmenting vaccine-induced immune responses.

Dynamics of symptom network in patients with first-episode schizophrenia: Insight from the CNFEST project.

BACKGROUND: Schizophrenia is a heterogeneous psychotic disorder. Recent theories have emphasized the importance of interactions among psychiatric symptoms in understanding the pathological mechanisms of schizophrenia. In the current study, we examined the symptom network in patients with first-episode schizophrenia (FES) at four time points during a six-month follow-up period. METHODS: In total, 565 patients with FES were recruited from the Chinese First-Episode Schizophrenia Trial (CNFEST) project. Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up (514 patients at one month, 429 at three months, and 392 at six months). We used a network analysis approach to estimate symptom networks with individual symptoms as nodes and partial correlation coefficients between symptoms as edges. A cross-lagged panel network (CLPN) model was used to identify predictive pathways for clinical symptoms. RESULTS: We found stable and strongly connected edges in patients across the time points, such as links between delusions and suspiciousness/persecution (P1:P6), and emotional withdrawal and passive/apathetic social withdrawal (N2:N4). Emotional withdrawal (N2), poor rapport (N3), and passive/apathetic social withdrawal (N4) had high centrality estimates across all four time points. CLPN analysis showed that negative symptoms, including emotional withdrawal (N2), poor rapport (N3), and passive/apathetic social withdrawal (N4), and stereotyped thinking (N7) may have predictive effects for negative and general symptoms at follow-ups. CONCLUSIONS: The symptom network of schizophrenia may be dynamic as treatment progresses. Negative symptoms remain the central and stable symptoms of schizophrenia. Negative symptoms may be potential therapeutic targets that predict other symptoms.

Mechanistic insights into Yifei Sanjie pill's regulation of EMT to enhance gefitinib treatment effect in NSCLC by in silico analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yi-Fei San-Jie pill (YFSJ) is a well-known Chinese medicine that has been used to treat non-small cell lung cancer in China for decades. AIM OF THE STUDY: Previous studies have shown that YFSJ combined with gefitinib can effectively inhibit the proliferation of gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines by promoting apoptosis and autophagy, but the molecular biological mechanisms involved and whether YFSJ combined with gefitinib can have synergistic effects still need to be further explored. Thus, the present study aimed to establish an in silico and experimental framework to decipher the underlying mechanism by which YFSJ augments the efficacy of gefitinib in treating NSCLC. MATERIALS AND METHODS: Integrated approaches, including microarray analysis, network pharmacology, RNA sequencing, bioinformatics algorithm analysis and in vivo and in vitro experiments, were applied to elucidate the underlying mechanism. RESULTS: Analysis of microarray datasets indicated that gefitinib may play a role in the regulation of the epithelial-mesenchymal transition (EMT) of PC9 cells. EMT-related Gene Ontology (GO) terms and the MAPK pathway were found to be enriched in the differentially expressed genes (DEGs), and a decreasing trend was observed in the EMT score. Network pharmacology analysis revealed that the potential NSCLC-related targets of YFSJ also showed enrichment in EMT-related GO terms and the MAPK pathway. Experimental findings demonstrated that combined YFSJ-treated serum and gefitinib treatment significantly inhibited PC9 cell migration and invasion. In addition, the combined treatment dramatically reduced the tumour volume in an animal model. The effectiveness of the combination treatment surpassed that of gefitinib alone in both cell and animal experiments. RNA sequencing analysis revealed significant enrichment of DEGs in EMT-related GO terms for the gefitinib treatment group, YFSJ treatment group, and combination treatment group compared to the control group. Notably, the negative regulation of EMT showed significant enrichment in the DEGs of the combination treatment group. The MAPK pathway was significantly enriched among the different groups. Moreover, combined treatment with YFSJ and gefitinib may exert synergistic anti-NSCLC effects by inhibiting the p-p38 MAPK/GSK3ß signalling axis, subsequently suppressing downstream EMT processes. CONCLUSION: Combined treatment with YFSJ and gefitinib could enhance the sensitivity of NSCLC cells to gefitinib by suppressing EMT through the EGFR/p-p38 MAPK/GSK3ß signalling axis. YFSJ may serve as an important adjunctive medication for NSCLC patients receiving gefitinib treatment in clinical practice.

Sequencing of cerebrospinal fluid in non-small-cell lung cancer patients with leptomeningeal metastasis: A systematic review.

Leptomeningeal metastasis (LM) refers to the dissemination of malignant cells in the subarachnoid space, pia, and arachnoid mater and is a severe condition associated with metastatic solid tumors. The most common solid tumor that develops into LM is lung cancer and the incidence increased in patients with advanced non-small-cell lung cancer (NSCLC) with targetable mutations. However, tissue biopsy of LM is inaccessible, leading to the paucity of genomic profiles of LM to guide targeted treatments and explore biological mechanisms. In recent years, liquid biopsy is considered a minimally invasive and dynamic method to trace the genomic alterations of cancer cells and some studies started to perform sequencing of cerebrospinal fluid (CSF) in patients with LM to reveal the targeted mutations and genomic profiles. In this review, we focused on studies performed sequencing of CSF in NSCLC patients with LM and summarized the sequencing results and their commonality. As the only way to reveal the genomic landscapes of LM, our review provided evidence that sequencing of CSF is a promising management method in LM patients to dynamically guide target therapy and monitor intracranial tumor response. Furthermore, it reveals a unique genomic profile of LM including driver genes, drug-resistant mutations, and a number of copy number variations. Sequencing of CSF in LM patients seems to provide more comprehensive genomic information than we expected and the biological significance behind the genomic alternations needs further study.

Semisupervised Change Detection Based on Bihierarchical Feature Aggregation and Extraction Network.

With the rapid development of remote sensing (RS) technology, high-resolution RS image change detection (CD) has been widely used in many applications. Pixel-based CD techniques are maneuverable and widely used, but vulnerable to noise interference. Object-based CD techniques can effectively utilize the abundant spectrum, texture, shape, and spatial information but easy-to-ignore details of RS images. How to combine the advantages of pixel-based methods and object-based methods remains a challenging problem. Besides, although supervised methods have the capability to learn from data, the true labels representing changed information of RS images are often hard to obtain. To address these issues, this article proposes a novel semisupervised CD framework for high-resolution RS images, which employs small amounts of true labeled data and a lot of unlabeled data to train the CD network. A bihierarchical feature aggregation and extraction network (BFAEN) is designed to achieve the pixelwise together with objectwise feature concatenation feature representation for the comprehensive utilization of the two-level features. In order to alleviate the coarseness and insufficiency of labeled samples, a confident learning algorithm is used to eliminate noisy labels and a novel loss function is designed for training the model using true-and pseudo-labels in a semisupervised fashion. Experimental results on real datasets demonstrate the effectiveness and superiority of the proposed method.