LN-439A, a novel BAP1 inhibitor, suppresses the growth of basal-like breast cancer by degrading KLF5.

Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Krüppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (BAP1) stabilizes KLF5 and promotes BLBC growth and metastasis. Therefore, pharmacological inhibition of the BAP1‒KLF5 axis is an effective therapeutic strategy for BLBC. Here, through screening, we identified a series of tetrahydro-ß-carboline derivatives that effectively reduced the protein expression of KLF5 and exhibited strong antitumour activity. Among the investigated compounds, the lead compound LN-439A presented the strongest antitumour activity and inhibitory effect on KLF5 expression. LN-439A suppressed the proliferation and migration of BLBC cells, induced G2/M arrest, and induced apoptosis. Mechanistically, LN-439A functions as a small molecule catalytic inhibitor of BAP1 by binding to the catalytic pocket of BAP1, leading to the ubiquitination and degradation of KLF5. Consistent with this finding, the overexpression of KLF5 suppressed the antitumour effects of LN-439A. In summary, LN-439A is a promising therapeutic agent for BLBC that functions by targeting the BAP1‒KLF5 axis.

GRiD: Guided Refinement for Detector-Free Multimodal Image Matching.

Multimodal image matching is essential in image stitching, image fusion, change detection, and land cover mapping. However, the severe nonlinear radiometric distortion (NRD) and geometric distortions in multimodal images severely limit the accuracy of multimodal image matching, posing significant challenges to existing methods. Additionally, detector-based methods are prone to feature point offset issues in regions with substantial modal differences, which also hinder the subsequent fine registration and fusion of images. To address these challenges, we propose a guided refinement for detector-free multimodal image matching (GRiD) method, which weakens feature point offset issues by establishing pixel-level correspondences and utilizes reference points to guide and correct matches affected by NRD and geometric distortions. Specifically, we first introduce a detector-free framework to alleviate the feature point offset problem by directly finding corresponding pixels between images. Subsequently, to tackle NRD and geometric distortion in multimodal images, we design a guided correction module that establishes robust reference points (RPs) to guide the search for corresponding pixels in regions with significant modality differences. Moreover, to enhance RPs reliability, we incorporate a phase congruency module during the RPs confirmation stage to concentrate RPs around image edge structures. Finally, we perform finer localization on highly correlated corresponding pixels to obtain the optimized matches. We conduct extensive experiments on four multimodal image datasets to validate the effectiveness of the proposed approach. Experimental results demonstrate that our method can achieve sufficient and robust matches across various modality images and effectively suppress the feature point offset problem.

Lacticaseibacillus paracasei NCU-04 relieves constipation and the depressive-like behaviors induced by loperamide in mice through the microbiome-gut-brain axis.

Constipation is a prevalent gastrointestinal condition that significantly affects patients' physical and mental well-being, yet current treatments often lack safety and efficacy. Emerging evidence highlights the critical role of the microbiota-gut-brain axis (MBGA) in managing constipation, paving the way for probiotics as an adjuvant treatment to improve constipation symptoms. In this study, we isolated a gut probiotic strain, Lacticaseibacillus paracasei NCU-04, and investigated its improvement effects on loperamide-induced constipation in mice. We demonstrated that L. paracasei NCU-04 exhibited excellent probiotic properties, including robust growth, strong antibacterial and antioxidant capacities, and a lack of hemolytic activity in vitro. The administration of L. paracasei NCU-04 effectively improved the defecation-related indicators such as the fecal water content, time to the first black stool defecation, and intestine transit rate, suggesting enhanced gut immobility in constipated mice. Additionally, L. paracasei NCU-04 significantly reduced colon inflammation induced by loperamide. Further, L. paracasei NCU-04 increased levels of colonic motilin, 5-hydroxytryptamine (5-HT), and c-kit, while decreased that of aquaporin 3, vasoactive intestinal peptide, and peptide YY. Notably, L. paracasei NCU-04 effectively upregulated the expression of 5-HT and its receptor (i.e., 5-HT4R) in the brains of constipated mice. High-throughput sequencing revealed that L. paracasei NCU-04 restored the diversity and composition of the gut microbiota disturbed by loperamide, and significantly increased the relative abundance of Prevotella and Lactobacillus genera in the stool, while decreased that of Odoribacter, Rikenella, and Parabacteroides. Importantly, L. paracasei NCU-04 also effectively improved the depression-like behaviors associated with constipation, possibly through 5-HT mediated MGBA. These results suggest that L. paracasei NCU-04 may offer a promising approach for treating constipation and its related depressive symptoms, supporting its potential as a functional food or adjuvant therapy for human health.

Human Amniotic Epithelial Stem Cells Promote Functional Recovery After Spinal Cord Injury In Rats By Regulating The Polarization Of Macrophages.

Spinal cord injury (SCI) is a catastrophic nerve injury caused by extremely severe damage to the spinal cord, for which effective treatments are currently unavailable. Human amniotic epithelial stem cells (hAESCs) are considered promising candidates for transplantation in various clinical and preclinical applications, due to their lack of limitations such as ethical barriers, immune rejection, tumorigenicity, or cell origin. Nevertheless, the effectiveness and mechanism by which hAESCs treat SCI remain elusive. To assess the motor function recovery process following SCI in rats, the Basso Beattie Bresnahan (BBB) behavior test, inclined plate scale and motor evoked potential (MEP) analysis were used in this study after transplantation of hAESCs at different doses. And the underlying mechanism was investigated by histological and molecular methods. The transplantation of hAESCs can significantly promote the recovery of motor function in SCI group, and the higher the dose, the better the effect. Compared with SCI group, hAESCs group had reduced tissue damage, significantly increased the number of neurons, neurofilaments and myelin sheath, and significantly reduced syringomyelia and glial scars. In addition, hAESCs inhibited the Levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) and increased the expression of the interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13), and promoted the shift of M1-polarized macrophages to M2-polarized macrophages. Our results demonstrate that hAESCs promoted the recovery of motor function after SCI by promoting M2 polarization of macrophages and reducing neuroinflammation. These findings may provide novel therapeutic strategies for SCI.

Plant lncRNA-miRNA Interaction Prediction Based on Counterfactual Heterogeneous Graph Attention Network.

Identifying interactions between long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) provides a new perspective for understanding regulatory relationships in plant life processes. Recently, computational methods based on graph neural networks (GNNs) have been widely employed to predict lncRNA-miRNA interactions (LMIs), which compensate for the inadequacy of biological experiments. However, the low-semantic and noise of graph limit the performance of existing GNN-based methods. In this paper, we develop a novel Counterfactual Heterogeneous Graph Attention Network (CFHAN) to improve the robustness to against the noise and the prediction of plant LMIs. Firstly, we construct a real-world based lncRNA-miRNA (L-M) heterogeneous network. Secondly, CFHAN utilizes the node-level attention, the semantic-level attention, and the counterfactual links to enhance the node embeddings learning. Finally, these embeddings are used as inputs for Multilayer Perceptron (MLP) to predict the interactions between lncRNAs and miRNAs. Evaluating our method on a benchmark dataset of plant LMIs, CFHAN outperforms five state-of-the-art methods, and achieves an average AUC and average ACC of 0.9953 and 0.9733, respectively. This demonstrates CFHAN's ability to predict plant LMIs and exhibits promising cross-species prediction ability, offering valuable insights for experimental LMI researches.

Simultaneous determination of pesticides, mycotoxins and ferulic acid in Angelica sinensis by GC/LC-Q-TOF/MS.

In this study, a strong applicable method that could determine a total of 33 pesticides (54 compounds), 11 mycotoxins and functional components (ferulic acid) simultaneously in Angelica sinensis was developed. The compatibility of the sample pretreatment method for pesticides, mycotoxins, and functional components was improved by optimizing the acidity of extraction solvents, the sequence of ice bath and oscillation, the volumetric solution, and so on. The PRiME HLB SPE pretreatment method was chosen as the optimal one when comparing four pretreatment methods. Among the 65 contaminants, 38 of those determined by liquid chromatography and 41 of those by gas chromatography, which showed good linearity (R2 > 0.9801), 97 % of them had a limit of quantitation (LOQ) of lower than 0.02 mg kg-1. The recovery of all compounds were suited between 70 % to 120 % and the RSD were all lower than 20 % at the spiked levels of LOQ, 2 × LOQ, and 10 × LOQ. For ferulic acid, the LOQ was 50 ng/mL, and it showed good linearity (R2=0.9988) within the range of 0.5 to 10 µg/mL. The recovery and RSD were 98.1 %, and 3.2 % (n = 6), respectively. The simultaneous determination of cross-category compounds in a single sample preparation was obtained by the combination of SPE and GC/LC-Q-TOF/MS. Therefore, this study could not only shorten the time for data acquisition and data analysis, but also improve the experimental efficiency.

Antimicrobial mechanisms and antifungal activity of compounds generated by banana rhizosphere Pseudomonas aeruginosa Gxun-2 against fusarium oxysporum f. sp. cubense.

Introduction: Fusarium wilt of banana, also recognized as Panama disease, is caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense tropical race 4 (FOC TR4). In recent years, strategies utilizing biocontrol agents, comprising antifungal microorganisms and their associated bioactive compounds from various environments, have been implemented to control this destructive disease. Our previous study showed that Pseudomonas aeruginosa Gxun-2 had significant antifungal effects against FOC TR4. However, there has been little scientific investigation of the antibacterial or antifungal activity. The aim of this study was to isolate, identify and evaluate the inhibition strength of active compounds in P. aeruginosa Gxun-2, so as to explain the mechanism of the strain inhibition on FOC TR4 from the perspective of compounds. Methods: The main antibacterial compounds of strain Gxun-2 were isolated, purified and identified using by fermentation extraction, silica gel column chromatography, thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) techniques. The effect of the compounds on the mycelial growth, morphology and spore germination of strain FOC TR4 was observed by 96-well plate method and AGAR diffusion method. Results: Among the metabolites produced by the strain, four antifungal compounds which were identified phenazine (C12H8N2), phenazine-1-carboxylic acid (PCA) (C13H8N2O2), 2-acetamidophenol (C8H9NO2) and aeruginaldehyde (C10H7NO2S) were identified through HPLC and NMR. Of these compounds, phenazine and PCA exhibited the most pronounced inhibitory effects on the spore germination and mycelial growth of FOC TR4. Phenazine demonstrated potent antifungal activity against FOC TR4 with a minimum inhibitory concentration (MIC) of 6.25 mg/L. The half-maximal effective concentration (EC50) was calculated to be 26.24 mg/L using the toxicity regression equation. PCA exhibited antifungal activity against FOC TR4 with an MIC of 25 mg/L and an EC50 of 89.63 mg/L. Furthermore, phenazine and PCA triggered substantial morphological transformations in the mycelia of FOC TR4, encompassing folding, bending, fracturing, and diminished spore formation. Discussion: These findings indicate that strain Gxun-2 plays a crucial role in controlling FOC TR4 pathogenesis, predominantly through producing the antifungal compounds phenazine and PCA, and possesses potential as a cost-efficient and sustainable biocontrol agent against Fusarium wilt of banana in forthcoming times.

The relationship between arterial partial pressure of oxygen and pressure injuries in intensive care unit patients: A multi-center cross-sectional study.

BACKGROUND: Pressure injuries significantly impact patients in intensive care units and the healthcare system. Hypoxia, a major contributor to pressure injury development, can be promptly identified by monitoring arterial partial pressure of oxygen. However, the dose-response relationship between arterial partial pressure of oxygen and pressure injuries remains unclear. OBJECTIVES: To determine how mean arterial partial pressure of oxygen within 24 h before the appearance of a pressure injury influences pressure injury outcomes in ICU patients, elucidating the dose-response relationship, and underscoring the importance of including arterial oxygen pressure in routine pressure injury risk assessments. METHODS: We conducted this multi-center cross-sectional study in Gansu province of China from April 2021 to July 2023. The incidence and influencing factors of pressure injuries were collected. Logistic and restricted cubic spline regression analyses were used to assess the association between pressure injuries and arterial partial pressure of oxygen. Subgroup analyses stratified by age and sex were conducted to explore potential correlations. RESULTS: Among 6078 participants, the incidence of pressure injury was 2.34 %. After adjusting for all confounding factors, patients with low arterial partial pressure of oxygen were more likely to develop pressure injury than those with normal levels (OR 1.753, 95 %CI 1.142 âˆ¼ 2.693). The dose-response relationship shows a significant non-linear dose-response correlation between arterial partial pressure of oxygen and pressure injury risk (P = 0.011). Layered analysis shows that the impact is more pronounced in older individuals and males. CONCLUSIONS: As arterial partial pressure of oxygen decreases, the occurrence of pressure injuries gradually increases. Incorporating arterial partial pressure of oxygen into daily pressure injury risk assessments is crucial. IMPLICATIONS FOR CLINICAL PRACTICE: Our study results will offer targeted insights for the prevention and management of pressure injuries.

Multidisciplinary team quality improves the survival outcomes of locally advanced rectal cancer patients: A post hoc analysis of the STELLAR trial.

PURPOSE: We sought to determine the association between multidisciplinary team (MDT) quality and survival of patients with locally advanced rectal cancer. METHODS: In a post hoc analysis of the randomized phase III STELLAR trial, 464 patients with distal or middle-third, clinical tumor category cT3-4 and/or regional lymph node-positive rectal cancer who completed surgery were evaluated. Disease-free survival (DFS) and Overall survival (OS) were stratified by Multidisciplinary team (MDT) quality, which was also included in the univariable and multivariable analyses of DFS and OS. RESULTS: According to the univariable analyses, a significantly worse DFS was associated with a fewer specialized medical disciplines participating in MDT (<5 vs ≥ 5; P=0.049),a lower frequency of MDT meetings ( 200; P=0.039). In addition, a lower number of specialized medical disciplines participating in MDT (<5 vs ≥ 5; P<0.001), a lower frequency of MDT meetings ( 200; P=0.001) were the variables associated with OS. These 3 factors were considered when assessing MDT quality, which was classified into 2 categories: high quality or general quality. Patients treated in hospitals with high MDT quality had longer 3-year OS (90.5 % vs 78.1 %; P=0.001) and similar 3-year DFS (70.3 % vs 61.3 %; P=0.109) compared to those treated in hospitals of the general MDT quality group. Furthermore, multivariable analyses revealed a significance for DFS (HR, 1.648; 95 % CI, 1.143-2.375; P=0.007) and OS (HR, 2.771; 95 % CI, 1.575-4.877; P<0.001) in MDT quality. CONCLUSIONS: The use of hospitals with optimized multidisciplinary infrastructure had a significant influence on survival of patients with locally advanced rectal cancer.

Broadband blue light emissions of one-dimensional hybrid Cu(I) halides with ultrahigh anti -water stability.

Low-dimensional organic-inorganic hybrid lead halide perovskites have attracted much interest in solid-state lighting and displays, but the toxicity and instability of lead halide are obstacles to their industrial applications, which must be overcome. As an alternative, Cu(I)-based hybrid metal halides have emerged as a new type of luminescent material owing to their diversified structure, adjustable luminescence, low toxicity and low cost. Herein, we report three one-dimensional (1D) hybrid Cu(I)-based halides with the general formula ACu2Br4 (A = [(Me)4-Pipz]2+ and [BuDA]2+ and [TMEDA]2+). These 1D hybrid Cu(I) halides display stable broadband blue emission with maximum emission peaks in the range of 445-474 nm and the highest photoluminescence quantum yield of 37.8%. Furthermore, in-depth experimental and theoretical investigations revealed that the broadband blue emissions originate from the radiative recombination of self-trapped excitons. Most importantly, there is no structural degradation and attenuation of emission intensity even after continuously soaking these halides in water for at least two months, demonstrating their ultra-high anti-water stability. Hirshfeld surface analysis shows that a large number of weak hydrogen bonds can protect the inorganic skeleton from degradation due to water. This work provides a new strategy for the design of water-stable Cu(I)-based halides with efficient blue emission and wide potential applications in humid environments.

Linear positive association of metabolic score for insulin resistance with stroke risk among American adults: a cross-sectional analysis of National Health and Nutrition Examination Survey datasets.

BACKGROUND: Insulin Resistance (IR) is associated with stroke. This study aimed to investigate the correlation between metabolic score for insulin resistance (METS-IR) level, a new biomarker for assessing IR, and stroke. METHODS: This is a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020 and included participants aged ≥ 20 years. All participants provided complete stroke and METS-IR related data. The study employed statistical techniques, including multivariate logistic regression analysis, restricted cubic splines (RCS), and stratified analyses to evaluate the relationship between the amounts of METS-IR and the risk of stroke. RESULTS: The study included 14,029 participants aged 20 years or older. The fully adjusted model revealed a statistically significant correlation between METS-IR and stroke (OR=1.21, 95% CI: 1.00, 1.46; P<0.05). Specifically, for every 10-unit increase in METS-IR, there was a 21% increase in the prevalence of stroke. The prevalence of stroke was 60% higher in the Q4 group compared to the Q1 group, as indicated by a significant association with METS-IR (OR=1.60, 95% CI: 1.01, 2.54; P<0.05). The RCS analysis revealed a strong linear correlation between METS-IR and the incidence of stroke (P<0.05). Subgroup analyses showed that gender, age, race, alcohol consumption, smoking, diabetes, and hypertension exhibited correlation with this positive association, and a significant interaction was observed in age (P for interaction < 0.05). CONCLUSIONS: The findings of this study indicate that elevated METS-IR levels are strongly linked to a greater risk of stroke in adults.

Larimichthys crocea (large yellow croaker): A bibliometric study.

Larimichthys crocea is an important economic fish of East Asia, and numerous studies have been conducted on its breeding, aquaculture, preservation and processing; however, there is no systematic review of the literature on the research of Larimichthys crocea. Derwent Data Analyzer (DDA) was used to analyze 1192 Larimichthys crocea research papers indexed by SCI-E, CSCD and KCI from 2001 to 2023. The number of research publications on Larimichthys crocea has rapidly increased, and institutions and scholars from China, the United States, South Korea, Japan, and Norway have conducted the majority of Larimichthys crocea research. The immune response, Pseudomonas plecoglossicida, gene expression, lipid immune response, transcriptomics and other areas have attracted the most attention. To increase the immunity and disease resistance of Larimichthys crocea and improve its survival, growth, storage and transport, researchers have carried out a large amount of research, which has promoted not only the culture of Larimichthys crocea but also the restoration of wild Larimichthys crocea and the rehabilitation of the ecological environment.

Roles of leukemia inhibitory factor receptor in cancer.

Leukemia inhibitory factor receptor (LIFR), in complex with glycoprotein 130 (gp130) as the receptor for leukemia inhibitory factor (LIF), can bind to a variety of cytokines and subsequently activate a variety of signaling pathways, including Janus kinase/signal transducer and activator of transcription 3. LIF, the most multifunctional cytokines of the interleukin-6 family acts as both a growth factor and a growth inhibitor in different types of tumors. LIF/LIFR signaling regulates a broad array of tumor-related processes including proliferation, apoptosis, migration, invasion. However, due to the activation of different signaling pathways, opposite regulatory effects are observed in certain tumor cells. Therefore, the role of LIFR in human cancers varies across different tumor and tissue, despite their recognized value in tumor treatment and prognosis observation is affirmed. Given its aberrant expression in numerous tumor cells and crucial regulatory function in tumorigenesis and progression, LIFR is considered as a promising targeted therapeutic agent. This review provides an overview of LIFR's initiating signaling pathway function as a cytokine receptor and summarize the current literature on the role of LIFR in cancer and its possible use in therapy.

Asynchronous Numerical Spiking Neural Membrane Systems with Local Synchronization.

Since the spiking neural P system (SN P system) was proposed in 2006, it has become a research hotspot in the field of membrane computing. The SN P system performs computations through the encoding, processing, and transmission of spiking information and can be regarded as a third-generation neural network. As a variant of the SN P system, the global asynchronous numerical spiking neural P system (ANSN P system) is adaptable to a broader range of application scenarios. However, in biological neuroscience, some neurons work synchronously within a community to perform specific functions in the brain. Inspired by this, our work investigates a global asynchronous spiking neural P system (ANSN P system) that incorporates certain local synchronous neuron sets. Within these local synchronous sets, neurons must execute their production functions simultaneously, thereby reducing dependence on thresholds and enhancing control uncertainty in ANSN P systems. By analyzing the ADD, SUB, and FIN modules in the generating mode, as well as the INPUT and ADD modules in the accepting mode, this paper demonstrates the novel system's computational capacity as both a generator and an acceptor. Additionally, this paper compares each module to those in other SN P systems, considering the maximum number of neurons and rules per neuron. The results show that this new ANSN P system is at least as effective as the existing SN P systems.

Naringin alleviates gefitinib-induced hepatotoxicity through anti-oxidation, inhibition of apoptosis, and autophagy.

Objectives: Gefitinib (GEF) is a targeted medicine used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). However, GEF's hepatotoxicity limits its clinical use. This study aims to investigate the protective effect of naringin (NG) against GEF-induced hepatotoxicity. Materials and Methods: Fifty female ICR mice were randomly divided into 5 groups: Control, GEF (200 mg/kg), NG (50 mg/kg) + GEF (200 mg/kg), NG (100 mg/kg) +GEF (200 mg/kg), NG (200 mg/kg) +GEF (200 mg/kg). After 4 weeks of continuous administration, the mice were euthanized. The blood and liver tissue samples were collected. Results: The results indicated that the GEF group showed increased liver index, liver enzyme activities, and decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Some hepatocytes showed hydropic degeneration and focal necrosis. Cell apoptosis, Cleaved-caspase3, and Poly (ADP-ribose) polymerase 1 (PARP1) increased. Transmission electron microscopy revealed the presence of numerous autophagic lysosomes or autophagosomes around the cell nucleus. Compared to the GEF group, NG can reverse these changes. Conclusion: In summary, NG alleviates GEF-induced hepatotoxicity by anti-oxidation, inhibiting cell apoptosis, and autophagy. Therefore, this study suggests the use of NG to mitigate GEF's toxicity to the liver.

Identification of Drought Stress-Responsive Genes in Rice by Random Walk with Multi-Restart Probability on MultiPlex Biological Networks.

Exploring drought stress-responsive genes in rice is essential for breeding drought-resistant varieties. Rice drought resistance is controlled by multiple genes, and mining drought stress-responsive genes solely based on single omics data lacks stability and accuracy. Multi-omics correlation analysis and biological molecular network analysis provide robust solutions. This study proposed a random walk with a multi-restart probability (RWMRP) algorithm, based on the Restarted Random Walk (RWR) algorithm, to operate on rice MultiPlex biological networks. It explores the interactions between biological molecules across various levels and ranks potential genes. RWMRP uses eigenvector centrality to evaluate node importance in the network and adjusts the restart probabilities accordingly, diverging from the uniform restart probability employed in RWR. In the random walk process, it can be better to consider the global relationships in the network. Firstly, we constructed a MultiPlex biological network by integrating the rice protein-protein interaction, gene pathway, and gene co-expression network. Then, we employed RWMRP to predict the potential genes associated with rice tolerance to drought stress. Enrichment and correlation analyses resulted in the identification of 12 drought-related genes. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) analysis on these 12 genes, ultimately identifying 10 genes responsive to drought stress.

Successful treatment of trichilemmal carcinoma with distant metastasis using pembrolizumab: a case report and review.

Trichilemmal carcinoma (TC) is a rare, malignant cutaneous adnexal tumor. TC often has nonspecific clinical manifestations and its aggressive nature is frequently overlooked. Metastasis of TC is rarely reported and there is no standard treatment for recurrent or metastatic TC. We report a complicated case of TC arising from the parotid gland with metastasis to cervical lymph nodes. The tumor progressed after multiple surgeries, radiation and chemotherapy. Finally, the patient achieved good response and disease control with pembrolizumab, an immune checkpoint inhibitor targeting programmed cell death protein-1. Currently, the patient has received 19 cycles of pembrolizumab and the disease remains well controlled. This represents the first reported use of immune checkpoint blockade to treat TC.

This paper discusses a rare form of skin cancer called trichilemmal carcinoma (TC) and presents a distant metastasis TC case. The patient was treated with an immunotherapy called pembrolizumab and after 19 courses of treatment, the tumor was significantly reduced and the symptoms were relieved. This case report is the first recorded case study of pembrolizumab for the treatment of TC and provides a new approach to the treatment of challenging malignancies.

Melatonin attenuates hepatic oxidative stress by regulating the P62/LC3 autophagy pathway in PCOS.

The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial to reduce the risk of PCOS-related liver diseases. Melatonin (MT), recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanism by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in the PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)，while concurrently ameliorating mitochondrial structural damage in PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PCOS rats and an inhibition of the Keap1-Nrf2 pathway. Through MT pretreatment, the expression of LC3 was significantly decreased, while the Keap1-Nrf2 pathway was activated. Our study showed that MT could affect the Nrf2 pathway dependent on the P62/LC3 autophagy pathway, thereby attenuating hepatic OS in PCOS. These findings offer novel insights and research avenues for the study of PCOS-related liver diseases.

NCAPD2 serves as a potential prognostic biomarker for lung adenocarcinoma and promotes cell proliferation, migration, invasion and cell cycle in vitro.

Objectives: The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types; however, its precise role within the context of lung adenocarcinoma (LUAD) remains elusive. This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways. Methods: Utilizing bioinformatics methodologies, we explored the differential expression of NCAPD2 between normal and tumor samples, along with its correlations with clinical-pathological characteristics, survival prognosis, and immune infiltration. Results: In the TCGA-LUAD dataset, tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples (p < 0.001). Clinically, higher NCAPD2 expression was notably associated with advanced T, N, and M stages, pathologic stage, gender, smoking status, and diminished overall survival (OS). Moreover, differentially expressed genes (DEGs) associated with NCAPD2 were predominantly enriched in pathways related to cell division. Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells, naïve CD4+ T cells, activated memory CD4+ T cells, and M1 macrophages. In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cell cycle progression. Conclusions: In summary, NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.