Which one is the best in treating deep venous thrombosis -- percutaneous mechanical thrombectomy, catheter-directed thrombolysis or combination of them?

OBJECTIVE: To compare the treatment outcomes among percutaneous mechanical thrombectomy (PMT) with AngioJet, Catheter-directed thrombolysis (CDT), and a combination of both. METHODS: One hundred forty nine patients with acute or sub-acute iliac-femoral vein thrombosis accepting CDT and/or PMT were divided into three groups respectively: PMT group, CDT group, PMT + CDT group (PMT followed by CDT). The severity of thrombosis was evaluated by venographic scoring system. Technical success was defined as restored patent deep venous blood flow after CDT and/or PMT. Clinical follow-up were assessed by ultrasound or venography imaging. The primary endpoints were recurrence of DVT, and severity level of post-thrombotic syndrome (PTS) during the follow-up. RESULTS: Technical success and immediate clinical improvements were achieved on all patients. The proportion of sub-acute DVT and the venographic scoring in PMT + CDT group were significantly higher than that in CDT group and PMT group (proportion of sub-acute DVT: p = 0.032 and p = 0.005, respectively; venographic scoring: p < 0.001, respectively). The proportion of May-Thurner Syndrome was lower in PMT group than that in CDT and PMT + CDT group (p = 0.026 and p = 0.005, respectively). The proportion of DVT recurrence/stent thrombosis was significantly higher in CDT group than that in PMT + CDT group (p = 0.04). The severity of PTS was the highest in CDT group ( χ2 = 14.459, p = 0.006) compared to PMT group (p = 0.029) and PMT + CDT group (p = 0.006). CONCLUSION: Patients with sub-acute DVT, high SVS scoring and combined May-Thurner Syndrome were recommended to take PMT + CDT treatment and might have lower rate of DVT recurrence/stent thrombosis and severe PTS. Our study provided evidence detailing of PMT + CDT therapy.

ESM1 May Be Used as a New Indicator for the Diagnosis and Prognosis of Early and Advanced Stage Digestive Tract Cancers.

Background: The biological function and prognostic significance of endothelial cell specific molecule 1 (ESM1) in various cancers have been validated. This study aimed to explore the expression and clinical diagnosis values in patients with stomach adenocarcinoma (STAD) and esophageal carcinoma (ESCA). Methods: Online database Gene Expression Omnibus was used to screen for abnormally expressed genes in STAD and ESCA. Besides, 36 STAD and 36 ESCA patients were enrolled, and their corresponding control groups were also 36 people each. Reverse transcription-quantitative polymerase chain reaction and Western blot were performed to analyze the expression of ESM1. Overall survival (OS) curve and receiver operating characteristics curve (ROC) analysis were used to assess the prognosis, and the sensitivity and specificity of ESM1 for the diagnosis of STAD and ESCA, respectively. Additionally, the effects of ESM1 on cell viability, migration, and invasion were analyzed by cell counting kit-8, transwell migration and invasion assays. Results: The results showed that the poor OS of STAD and ESCA patients was correlated with high ESM1. Besides, ESM1 was increased in ESCA and STAD in in vivo and in vitro studies. ESM1 has a high accuracy [area under the curve (AUC) > 0.79] at stage I and IV of STAD and ESCA. Knockdown of ESM1 suppressed the cell viability, migration, and invasion and increased the apoptosis rate of AGS and TE1 cells. Conclusion: Our study suggested that ESM1 might be used as a new indicator for the diagnosis and prognosis of early and advanced stage digestive tract cancers.

Genome-wide identification of G-protein coupled receptors (GPCRs) and their expression profile in response to ß-cypermethrin stress in Zeugodacus cucurbitae.

G-protein coupled receptors (GPCRs) are the largest and most diverse transmembrane receptor family in the cell. They are involved in regulating a wide range of biological processes, including behavior, reproduction, and development. However, GPCRs have not yet been identified in Zeugodacus cucurbitae. The current study focuses on the GPCRs identification, classification, distribution, and their expression analysis under ß-cypermethrin stress to uncover novel targets for pest management and assist in the development of effective strategies for controlling the melon fly population. We identified 80 GPCRs genes including 50 GPCRs identified in family A, 17 GPCRs identified in family B, 8 identified in family C, and 5 identified in family F. Z. cucurbitae GPCRs showed significant differences in both the number of genes in families or subfamilies, as well as the sequencing of the genes. Interestingly, newly identified GPCRs genes are expressed differently at various developmental stages of Z. cucurbitae. Further, we evaluated these 80 GPCRs using Realtime quantitative PCR to confirm their expression between ß-cypermethrin-resistant (RS) strain and susceptible strain (SS) of Z. cucurbitae. We identified 50 GPCR genes were highly overexpressed in a RS. Among these genes, eight genes were strongly induced by the 30% lethal concentration (LC) while two genes were significantly increased by the 50% LC of ß-cypermethrin. This first genome-wide profiling and characterization of GPCRs could lay foundation for unraveling detoxification mechanism and target site modifications which may improve the insect resistance and could be effective insecticide targets for Z. cucurbitae management.

Development and characterization of pectin-based composite film incorporated with cannabidiol/2,6-di-O-methyl-ß-cyclodextrin inclusion complex for food packaging.

To reduce environmental pollution and improve human health, developing green active food packaging materials is very necessary. In this study, a novel antioxidant and antibacterial composite film was produced by incorporating inclusion complex (CDIC) of cannabidiol (CBD) with 2,6-di-O-methyl-ß-cyclodextrin (DM-ß-CD) into pectin. The pectin films loaded with CBD and hemp leaf water extract (HLE) were prepared for comparison. Comprehensive characterizations showed CBD was encapsulated by DM-ß-CD and CDIC was evenly dispersed into pectin matrix, forming the compact and intact film. The composite films showed good mechanical properties and biodegradability. CDIC film showed the highest transparency and smoothness (Rrms/Rmax: 2.6/16.8 nm). The addition of bioactives reduced the water-binding capacity and CDIC film had the strongest hydrophobicity. Besides, DM-ß-CD encapsulation improved the thermal stability of CBD in CDIC film. Benefiting from encapsulation and excellent bioactivities of CBD, CDIC film showed excellent antioxidant capacity and antibacterial activity, effectively inhibiting colony growth and maintaining the strawberry color in strawberry preservation. This work could provide a novel eco-friendly candidate for food packaging material and expand the use of CBD in food industry.

Standardized Protocols for Clinical and Histopathological Characterization of Hidradenitis Suppurativa Tissue Specimens.

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects.

Deficiency of histone deacetylases 3 in macrophage alleviates monosodium urate crystals-induced gouty inflammation in mice.

BACKGROUND: Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation. METHODS: Macrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein. RESULTS: Deficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1ß release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge. CONCLUSIONS: Deficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.

ß-Catenin in Dendritic Cells Negatively Regulates CD8 T Cell Immune Responses through the Immune Checkpoint Molecule Tim-3.

Recent studies have demonstrated that ß-catenin in dendritic cells (DCs) serves as a key mediator in promoting both CD4 and CD8 T cell tolerance, although the mechanisms underlying how ß-catenin exerts its functions remain incompletely understood. Here, we report that activation of ß-catenin leads to the up-regulation of inhibitory molecule T-cell immunoglobulin and mucin domain 3 (Tim-3) in type 1 conventional DCs (cDC1s). Using a cDC1-targeted vaccine model with anti-DEC-205 engineered to express the melanoma antigen human gp100 (anti-DEC-205-hgp100), we demonstrated that CD11c-ß-cateninactive mice exhibited impaired cross-priming and memory responses of gp100-specific CD8 T (Pmel-1) cells upon immunization with anti-DEC-205-hgp100. Single-cell RNA sequencing (scRNA-seq) analysis revealed that ß-catenin in DCs negatively regulated transcription programs for effector function and proliferation of primed Pmel-1 cells, correlating with suppressed CD8 T cell immunity in CD11c-ß-cateninactive mice. Further experiments showed that treating CD11c-ß-cateninactive mice with an anti-Tim-3 antibody upon anti-DEC-205-hgp100 vaccination led to restored cross-priming and memory responses of gp100-specific CD8 T cells, suggesting that anti-Tim-3 treatment likely synergizes with DC vaccines to improve their efficacy. Indeed, treating B16F10-bearing mice with DC vaccines using anti-DEC-205-hgp100 in combination with anti-Tim-3 treatment resulted in significantly reduced tumor growth compared with treatment with the DC vaccine alone. Taken together, we identified the ß-catenin/Tim-3 axis as a potentially novel mechanism to inhibit anti-tumor CD8 T cell immunity and that combination immunotherapy of a DC-targeted vaccine with anti-Tim-3 treatment leads to improved anti-tumor efficacy.

Synergism of jet milling and deep eutectic solvent pretreatment on grapevine lignin fractionation and enhancing enzymatic hydrolysis.

Herein, we investigated the synergistic effects of jet milling (JM) and deep eutectic solvent (DES) pretreatment on the fractionation of grapevine lignin and the consequent enhancement of enzymatic hydrolysis. Grapevine, a substantial byproduct of the wine industry, was subjected to JM pretreatment to produce finely powdered particles (median diameter D50 = 98.90), which were then further treated with acidic ChCl-LA and alkaline K2CO3-EG DESs. The results revealed that the combined JM + ChCl-LA pretreatment significantly increased the cellulose preservation under optimal conditions (110 °C, 4 h, and 20 % water content), achieving removal rates of 74.18 % xylan and 66.05 % lignin, respectively. The pretreatment temperature and inhibitor production were reduced, resulting in a remarkable threefold increase in glucose yield compared to untreated samples. Moreover, the structural analysis of the pretreated lignin indicated an enrichment of phenolic units, leading to enhanced antioxidant and antibacterial activities, particularly in the JM pretreated samples. These findings underscore the promising potential of the synergistic JM and DES pretreatment in facilitating the efficient utilization of grapevine lignocellulosic biomass for sustainable biorefinery technologies.

Langerhans cell histiocytosis: NACHO update on progress, chaos, and opportunity on the path to rational cures.

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy. However, fewer than 50% of patients who have disseminated disease are cured with the current standard-of-care vinblastine/prednisone/(mercaptopurine), and treatment failure is associated with long-term morbidity, including the risk of LCH-associated neurodegeneration. Historically, the nature of LCH-whether a reactive condition versus a neoplastic/malignant condition-was uncertain. Over the past 15 years, seminal discoveries have broadly defined LCH pathogenesis; specifically, activating mitogen-activated protein kinase pathway mutations (most frequently, BRAFV600E) in myeloid precursors drive lesion formation. LCH therefore is a clonal neoplastic disorder, although secondary inflammatory features contribute to the disease. These paradigm-changing insights offer a promise of rational cures for patients based on individual mutations, clonal reservoirs, and extent of disease. However, the pace of clinical trial development behind lags the kinetics of translational discovery. In this review, the authors discuss the current understanding of LCH biology, clinical characteristics, therapeutic strategies, and opportunities to improve outcomes for every patient through coordinated agent prioritization and clinical trial efforts.

An optimized short-term steroid therapy for chronic drug-induced liver injury: A prospective randomized clinical trial.

BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).

Will partial splenic embolization followed by splenectomy increase intraoperative bleeding?

BACKGROUND: Partial splenic embolization (PSE) has been suggested as an alternative to splenectomy in the treatment of hypersplenism. However, some patients may experience recurrence of hypersplenism after PSE and require splenectomy. Currently, there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications. AIM: To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism. METHODS: Between January 2010 and December 2021, 321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department. Based on whether PSE was performed prior to splenectomy, the patients were divided into two groups: PSE group (n = 40) and non-PSE group (n = 281). Patient characteristics, postoperative complications, and follow-up data were compared between groups. Propensity score matching (PSM) was conducted, and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding (IB). The receiver operating characteristic curve, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) were employed to evaluate the differentiation, calibration, and clinical performance of the model. RESULTS: After PSM, the non-PSE group showed significant reductions in hospital stay, intraoperative blood loss, and operation time (all P = 0.00). Multivariate analysis revealed that spleen length, portal vein diameter, splenic vein diameter, and history of PSE were independent predictive factors for IB. A nomogram predictive model of IB was constructed, and DCA demonstrated the clinical utility of this model. Both groups exhibited similar results in terms of overall survival during the follow-up period. CONCLUSION: Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB.

Development of a Machine Learning Model to Predict the Color of Extruded Thermoplastic Resins.

The conventional method for the color-matching process involves the compounding of polymers with pigments and then preparing plaques by using injection molding before measuring the color by an offline spectrophotometer. If the color fails to meet the L*, a*, and b* standards, the color-matching process must be repeated. In this study, the aim is to develop a machine learning model that is capable of predicting offline color using data from inline color measurements, thereby significantly reducing the time that is required for the color-matching process. The inline color data were measured using an inline process spectrophotometer, while the offline color data were measured using a bench-top spectrophotometer. The results showed that the Bagging with Decision Tree Regression and Random Forest Regression can predict the offline color data with aggregated color differences (dE) of 10.87 and 10.75. Compared to other machine learning methods, Bagging with Decision Tree Regression and Random Forest Regression excel due to their robustness, ability to handle nonlinear relationships, and provision of insights into feature importance. This study offers valuable guidance for achieving Bagging with Decision Tree Regression and Random Forest Regression to correlate inline and offline color data, potentially reducing time and material waste in color matching. Furthermore, it facilitates timely corrections in the event of color discrepancies being observed via inline measurements.

Effect of DES lignin incorporation on physicochemical, antioxidant and antimicrobial properties of carboxymethyl cellulose-based films.

Herein, three pretreated grapevine lignins were incorporated into carboxymethyl cellulose films. The effects of traditional NaOH pretreated lignin and DES (ChCl-LA, ChCl-LA & K2CO3-EG) pretreated lignin on film properties were compared. Modern analytical techniques were employed to systematically characterize the pretreated lignin and the different CMC-lignin films. The results showed that DES lignin was of high purity, low molecular weight, and homogeneous structure. It outperformed traditional NaOH lignin in terms of compatibility with CMC, enabling it to perform its bioactivity and physicochemical functions in films. This feature effectively enhanced the hydrophobicity, UV shielding ability, water vapor barrier, thermal stability, mechanical properties, and biological activity of CMC-DES lignin film. NMR (2D HSQC) showed that the excellent antioxidant and antibacterial capabilities of CMC-DES lignin film are due to the retention of butyl (S) and p-hydroxyphenyl (H) units in DES lignin, resulting in its rich phenolic hydroxyl content. The detailed structural elucidation of DES lignin's chemical interactions with CMC provided valuable insights into the advantageous properties observed in the films, presenting innovative solutions for applications in the food packaging and preservation industries.

Allulose mitigates chronic enteritis by reducing mitochondria dysfunction via regulating cathepsin B production.

Metabolic changes have been linked to the development of inflammatory bowel disease (IBD), which includes colitis. Allulose, an endogenous bioactive monosaccharide, is vital to the synthesis of numerous compounds and metabolic processes within living organisms. Nevertheless, the precise biochemical mechanism by which allulose inhibits colitis remains unknown. Allulose is an essential and intrinsic protector of the intestinal mucosal barrier, as it maintains the integrity of tight junctions in the intestines, according to the current research. It is also important to know that there is a link between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), chemically-induced colitis in rodents, and lower levels of allulose in the blood. Mice with colitis, either caused by dextran sodium sulphate (DSS) or naturally occurring colitis in IL-10-/- mice, had less damage to their intestinal mucosa after being given allulose. Giving allulose to a colitis model starts a chain of reactions because it stops cathepsin B from ejecting and helps lysosomes stick together. This system effectively stops the activity of myosin light chain kinase (MLCK) when intestinal epithelial damage happens. This stops the breakdown of tight junction integrity and the start of mitochondrial dysfunction. To summarise, the study's findings have presented data that supports the advantageous impact of allulose in reducing the advancement of colitis. Its ability to stop the disruption of the intestinal barrier enables this. Therefore, allulose has potential as a medicinal supplement for treating colitis.

Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer.

Gastric cancer (GC) is a prevalent malignant tumor within the digestive system, with over 40% of new cases and deaths related to GC globally occurring in China. Despite advancements in treatment modalities, such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents, the prognosis for GC remains poor. New targeted therapies and immunotherapies are currently under investigation, but no significant breakthroughs have been achieved. Studies have indicated that GC is a heterogeneous disease, encompassing multiple subtypes with distinct biological characteristics and roles. Consequently, personalized treatment based on clinical features, pathologic typing, and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer (PLGC). Current research has categorized GC into four subtypes: Epstein-Barr virus-positive, microsatellite instability, genome stability, and chromosome instability (CIN). Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas. Among these, ultrasensitive chromosomal aneuploidy detection (UCAD) can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology, in conjunction with bioinformatics analysis, to achieve qualitative and quantitative detection of chromosomal stability. This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

High-resolution mapping of age- and gender-specific risk of Clonorchis sinensis infection risk in Guangdong, China: a geostatistical modeling study.

BACKGROUND: The latest national survey on the distribution of human parasites in China demonstrated that Guangdong was among the endemic provinces with the highest Clonorchis sinensis infection rates. High-resolution, age- and gender-specific risk maps of the temporal and spatial distributions are essential for the targeted control work. METHODS: Disease data on the prevalence of C. sinensis infection from 1990 onwards, either age- and gender-specific or aggregated across age and gender, were collected through systematic review and four large-scale surveys in Guangdong Province. Environmental and socioeconomic variables were obtained from open-access databases and employed as potential predictors. A Bayesian geostatistical model was developed to estimate the C. sinensis infection risk at high spatial resolution. RESULTS: The final dataset included 606 surveys at 463 unique locations for C. sinensis infection. Our findings suggested that following an initial increase and stabilization, the overall population-adjusted prevalence had declined to 2.2% (95% Bayesian credible interval: 1.7-3.0%) in the period of 2015 onwards. From 2015 onwards, moderate and high infection risks were found in the northern regions (e.g. Heyuan and Shaoguan cities) and the southern Pearl River Delta (e.g. Foshan, Zhongshan, Zhuhai and Jiangmen cities), respectively. Age- and gender-specific risk maps revealed that males had a higher infection risk than females, and the infection risk was higher in adults compared to children. CONCLUSIONS: Our high-resolution risk maps of C. sinensis infection in Guangdong Province identified the spatial, temporal, age and gender heterogeneities, which can provide useful information assisting tailored control strategies.

Genome-wide identification and expression analysis of NIN-like protein (NLP) genes: Exploring their potential roles in nitrate response in tea plant (Camellia sinensis).

NIN-like proteins (NLPs) are evolutionarily conserved transcription factors that are unique to plants and play a pivotal role in responses to nitrate uptake and assimilation. However, a comprehensive analysis of NLP members in tea plants is lacking. The present study performed a genome-wide analysis and identified 33 NLP gene family members of Camellia sinensis that were distributed unequally across 5 chromosomes. Subcellular localisation predictions revealed that all CsNLP proteins were localised in the nucleus. Conservative domain analysis revealed that all of these proteins contained conserved RWP-RK and PB1 domains. Phylogenetic analysis grouped the CsNLP gene family into four clusters. The promoter regions of CsNLPs harboured cis-acting elements associated with plant hormones and abiotic stress responses. Expression profile analysis demonstrated that CsNLP8 was significantly upregulated in roots under nitrate stress conditions. Subcellular localisation analysis found CsNLP8 localised to the nucleus. Dual-luciferase reporter assay demonstrated that CsNLP8 positively regulated the expression of a nitrate transporter gene (CsNRT2.2). These findings provide a comprehensive characterisation of NLP genes in Camellia sinensis and offer insights into the biological function of CsNLP8 in regulating the response to nitrate-induced stress.

NCOA5 Haploinsufficiency in Myeloid-Lineage Cells Sufficiently Causes Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma.

BACKGROUND & AIMS: The nuclear receptor coactivator 5 (NCOA5) is a putative type 2 diabetes susceptibility gene. NCOA5 haploinsufficiency results in the spontaneous development of nonalcoholic fatty liver disease (NAFLD), insulin resistance, and hepatocellular carcinoma (HCC) in male mice; however, the cell-specific effect of NCOA5 haploinsufficiency in various types of cells, including macrophages, on the development of NAFLD and HCC remains unknown. METHODS: Control and myeloid-lineage-specific Ncoa5 deletion (Ncoa5ΔM/+) mice fed a normal diet were examined for the development of NAFLD, nonalcoholic steatohepatitis (NASH), and HCC. Altered genes and signaling pathways in the intrahepatic macrophages of Ncoa5ΔM/+ male mice were analyzed and compared with those of obese human individuals. The role of platelet factor 4 (PF4) in macrophages and the underlying mechanism by which PF4 affects NAFLD/NASH were explored in vitro and in vivo. PF4 expression in HCC patient specimens and prognosis was examined. RESULTS: Myeloid-lineage-specific Ncoa5 deletion sufficiently causes spontaneous NASH and HCC development in male mice fed a normal diet. PF4 overexpression in Ncoa5ΔM/+ intrahepatic macrophages is identified as a potent mediator to trigger lipid accumulation in hepatocytes by inducing lipogenesis-promoting gene expression. The transcriptome of intrahepatic macrophages from Ncoa5ΔM/+ male mice resembles that of obese human individuals. High PF4 expression correlated with poor prognosis of HCC patients and increased infiltrations of M2 macrophages, regulatory T cells, and myeloid-derived suppressor cells in HCCs. CONCLUSIONS: Our findings reveal a novel mechanism for the onset of NAFLD/NASH and HCC initiated by NCOA5-deficient macrophages, suggesting the NCOA5-PF4 axis in macrophages as a potential target for developing preventive and therapeutic interventions against NAFLD/NASH and HCC.