Transcriptome analysis reveals that trehalose alleviates chilling injury of peach fruit by regulating ROS signaling pathway and enhancing antioxidant capacity.

Peach fruit is prone to chilling injury (CI) during low-temperature storage, resulting in quality deterioration and economic losses. Our previous studies have found that exogenous trehalose treatment can alleviate the CI symptoms of peach by increasing sucrose accumulation. The purpose of this study was to explore the potential molecular mechanism of trehalose treatment in alleviating CI in postharvest peach fruit. Transcriptome analysis showed that trehalose induced gene expression in pathways of plant MAPK signaling, calcium signaling, and reactive oxygen species (ROS) signaling. Furthermore, molecular docking analysis indicated that PpCDPK24 may activate the ROS signaling pathway by phosphorylating PpRBOHE. Besides, PpWRKY40 mediates the activation of PpMAPKKK2-induced ROS signaling pathway by interacting with the PpRBOHE promoter. Accordingly, trehalose treatment significantly enhanced the activities of antioxidant-related enzymes such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and gluathione reductase (GR), as well as the transcription levels AsA-GSH cycle related gene, which led to the reduction of H2O2 and malondialdehyde (MDA) content in peach during cold storage. In summary, our results suggest that the potential molecular mechanism of trehalose treatment is to enhance antioxidant capacity by activating CDPK-mediated Ca2 + -ROS signaling pathway and WRKY-mediated MAPK-WRKY-ROS signaling pathway, thereby reducing the CI in peach fruit.

Cascade-Targeted Nanoplatforms for Synergetic Antibiotic/ROS/NO/Immunotherapy against Intracellular Bacterial Infection.

Intracellular bacteria in dormant states can escape the immune response and tolerate high-dose antibiotic treatment, leading to severe infections. To overcome this challenge, cascade-targeted nanoplatforms that can target macrophages and intracellular bacteria, exhibiting synergetic antibiotic/reactive oxygen species (ROS)/nitric oxide (NO)/immunotherapy, were developed. These nanoplatforms were fabricated by encapsulating trehalose (Tr) and vancomycin (Van) into phosphatidylserine (PS)-coated poly[(4-allylcarbamoylphenylboric acid)-ran-(arginine-methacrylamide)-ran-(N,N'-bisacryloylcystamine)] nanoparticles (PABS), denoted as PTVP. PS on PTVP simulates a signal of "eat me" to macrophages to promote cell uptake (the first-step targeting). After the uptake, the nanoplatform in the acidic phagolysosomes could release Tr, and the exposed phenylboronic acid on the nanoplatform could target bacteria (the second-step targeting). Nanoplatforms can release Van in response to infected intracellular overexpressed glutathione (GSH) and weak acid microenvironment. l-arginine (Arg) on the nanoplatforms could be catalyzed by upregulated inducible nitric oxide synthase (iNOS) in the infected macrophages to generate nitric oxide (NO). N,N'-Bisacryloylcystamine (BAC) on nanoplatforms could deplete GSH, allow the generation of ROS in macrophages, and then upregulate proinflammatory activity, leading to the reinforced antibacterial capacity. This nanoplatform possesses macrophage and bacteria-targeting antibiotic delivery, intracellular ROS, and NO generation, and pro-inflammatory activities (immunotherapy) provides a new strategy for eradicating intracellular bacterial infections.

Feasibility of the application of deep learning-reconstructed ultra-fast respiratory-triggered T2-weighted imaging at 3 T in liver imaging.

OBJECTIVE: The evaluate the feasibility of a novel deep learning-reconstructed ultra-fast respiratory-triggered T2WI sequence (DL-RT-T2WI) In liver imaging, compared with respiratory-triggered Arms-T2WI (Arms-RT-T2WI) and respiratory-triggered FSE-T2WI (FSE-RT-T2WI) sequences. METHODS: 71 patients with liver lesions underwent 3-T MRI and were prospectively enrolled. Two readers independently analyzed images acquired with DL-RT-T2WI, Arms-RT-T2WI, and FSE-RT-T2WI. The qualitative evaluation indicators, including overall image quality (OIQ), sharpness, noise, artifacts, lesion detectability (LC), lesion characterization (LD), cardiacmotion-related signal loss (CSL), and diagnostic confidence (DC), were evaluated in two readers, and further statistically compared using paired Wilcoxon rank-sum test among three sequences. RESULTS: 176 lesions were detected in DL-RT-T2W and Arms-RT-T2WI, and 175 were detected in FSE-RT-T2WI. The acquisition time of DL-RT-T2WI was improved by 4.8-7.9 folds compared to the other two sequences. The OIQ was scored highest for DL-RT-T2WI (R1, 4.61 ± 0.52 and R2, 4.62 ± 0.49), was significantly superior to Arms-RT-T2WI (R1, 4.30 ± 0.66 and R2, 4.34 ± 0.69) and FSE-RT-T2WI (R1, 3.65 ± 1.08 and R2, 3.75 ± 1.01). Artifacts and sharpness scored highest for DL-RT-T2WI, followed by Arms-RT-T2WI, and were lowest for FSE-RT-T2WI in both two readers. Noise and CSL for DL-RT-T2WI scored similar to Arms-RT-T2WI (P > 0.05) and were significantly superior to FSE-RT-T2WI (P < 0.001). Both LD and LC for DL-RT-T2WI were significantly superior to Arms-RT-T2WI and FSE-RT-T2WI in two readers (P < 0.001). DC for DL-RT-T2WI scored best, significantly superior to Arms-RT-T2WI (P < 0.010) and FSE-RT-T2WI (P < 0.001). CONCLUSIONS: The novel ultra-fast DL-RT-T2WI is feasible for liver imaging and lesion characterization and diagnosis, not only offers a significant improvement in acquisition time but also outperforms Arms-RT-T2WI and FSE-RT-T2WI concerning image quality and DC.

Development and validation of a predictive scoring system for post-transarterial chemoembolization pain management in liver cancer patients.

Background: Patients experiencing severe postoperative pain often show lower adherence to prescribed treatments, highlighting the clinical need for effective pain prediction and management strategies. This study aims to address this gap by identifying key risk factors associated with post-transarterial chemoembolization (TACE) pain and developing a predictive scoring system. Methods: We retrospectively analyzed data from liver cancer patients who underwent their first TACE procedure at our institution between January 2019 and December 2020. Pain levels were assessed using an 11-point numerical rating scale (NRS-11). Patients were randomly assigned to training and validation cohorts. In the training cohort, logistic regression was used to evaluate the correlation between various parameters and post-TACE pain, leading to the development of a risk prediction model. This model's performance was subsequently assessed in the validation cohort. Results: The study included 255 patients. Univariate analysis in the training cohort identified tumor number, size, microsphere volume, and operation time as factors associated with postoperative pain. These factors were included in a multivariate model, which demonstrated areas under the receiver operating characteristic (ROC) curve (AUCs) of 0.71 in the training cohort and 0.74 in the validation cohort for predicting moderate to severe pain. A nomogram was also developed for clinical application, categorizing patients with scores above 72.90 as high risk for moderate to severe pain. Conclusions: Our research successfully developed and validated a novel scoring system capable of predicting moderate to severe pain following initial TACE treatment. However, the study's predictive accuracy, as reflected by AUC values, suggests that further refinement and validation in larger, diverse cohorts are necessary to enhance its clinical utility. This work underscores the importance of predictive tools in improving postoperative pain management and patient outcomes.

Chromosome level genome assembly and transcriptome analysis of E11 cells infected by tilapia lake virus.

The E11 cell line, derived from striped snakehead fish (Channa striata), possesses a distinctive feature: it is persistently infected with a C-type retrovirus. Notably, it exhibits high permissiveness to piscine nodavirus and the emerging tilapia lake virus (TiLV). Despite its popularity in TiLV research, the absence of genome assembly for the E11 cell line and Channa striata has constrained research on host-virus interactions. This study aimed to fill this gap by sequencing, assembling, and annotating the E11 cell line genome. Our efforts yielded a 600.5 Mb genome including 24 chromosomes with a BUSCO score of 98.8%. In addition, the complete proviral DNA sequence of snakehead retrovirus (SnRV) was identified in the E11 cell genome. Comparative genomic analysis between the E11 cell line and another snakehead species Channa argus revealed the loss of many immune-related gene families in the E11 cell genome, indicating a compromised immune response. We also conducted transcriptome analysis of mock- and TiLV-infected E11 cells, unveiling new perspectives on virus-virus and host-virus interactions. The TiLV infection suppressed the high expression of SnRV in E11 cells, and activated some other endogenous retroviruses. The protein-coding gene comparison revealed a pronounced up-regulation of genes involved in immune response, alongside a down-regulation of genes associated with specific metabolic processes. In summary, the genome assembly and annotation of the E11 cell line provide valuable resources to understand the SnRV and facilitate further studies on nodavirus and TiLV. The RNA-seq profiles shed light on the cellular mechanisms employed by fish cells in response to viral challenges, potentially guiding the development of therapeutic strategies against TiLV in aquaculture. This study also provides the first insights into the viral transcriptome profiles of endogenous SnRV and evading TiLV, enhancing our understanding of host-virus interactions in fish.

Extended lymphadenectomy based on the TRIANGLE for pancreatic head cancer: a single-center experience.

BACKGROUND: This study was to compare the safety and efficacy of different lymphadenectomy methods in patients with pancreatic head cancer undergoing pancreaticoduodenectomy (PD). MATERIAL AND METHODS: A total of 150 patients were included in this study. Patients were divided into Group A (n = 79), Group B (n = 44), and Group C (n = 27) according to the different lymphadenectomy methods. The clinical endpoint was time to progression (TTP) and overall survival (OS). Postoperative complications of different lymphadenectomy methods were compared respectively. TTP and OS of the three groups were compared by Kaplan-Meier curves. RESULTS: There were no significant differences between the three groups in operative time (P = 0.300), death in the hospital (P = 0.253), postoperative hemorrhage (P = 0.863), postoperative pancreatic fistula (POPF) B/C (P = 0.306), bile leakage (P = 0.215), intestinal fistula (P = 0.177), lymphatic leakage (P = 0.267), delayed gastric emptying [(DGE) (P = 0.283)], ICU stay (P = 0.506), and postoperative hospital stay [(PHS) (P = 0.810)]. Median TTP in Groups B and C was significantly longer than in Group A (log-rank test, A vs B: P = 0.0005, A vs C: P = 0.0001). Median OS between the three groups has no statistical difference (P = 0.1546). CONCLUSIONS: Extended lymphadenectomy methods based on the TRIANGLE do not increase perioperative complications significantly and can effectively delay tumor progression in patients with pancreatic head cancer.

Expression of ADAM17 and its clinical value for patients with pernicious placenta previa: A retrospective study of 148 PPP patients underwent cesarean section.

To explore the expression and the diagnostic value of ADAM17 in pernicious placenta previa (PPP) combined placental accreta. A total of 148 PPP patients were enrolled and divided into 2 groups: 62 patients with placenta accrete (PPP with PA group) and 86 patients without placenta accrete (PPP without PA group). In the same period, 74 pregnant women without PPP who had undergone cesarean section were selected as controls. The levels of ADAM17 were detected by qt-PCR. Diagnostic efficiency of ADAM17 were evaluated by receiver operating characteristics curve. ADAM17 was higher expression in PPP patients. Multivariate analysis showed that ADAM17 was related to gravida times (HR = 2.43 95% CI, 1.25-3.31), history of cesarean delivery (HR = 3.44, 95% CI = 2.24-4.28), history of abortions (HR = 2.22, 95% CI = 1.57-3.06) for PPP with PA patients and gravida times (HR = 2.01, 95% CI = 1.45-2.86), history of cesarean delivery (HR = 1.89, 95% CI = 1.33-2.48) for PPP patients without PA. Diagnostic efficiency of ADAM17 indicated that the sensitivity and specificity of ADAM17 detection for PPP with PA were 74.41% and 67.21% and for PPP without PA were 89.29% and 85.52%. Area under curve were 0.7876 (0.7090-0.8661) for PPP with PA and 0.9443 (0.9136-0.9750) for PPP without PA. Insummary, ADAM17 was higher expression in patients with PPP. ADAM17 was associated with gravida times, history of cesarean delivery, history of abortions. It also indicated a better diagnostic efficiency for patients with PPP. Further larger sample, multicenter studies should be conducted to confirm the conclusion from our study.

Human lens epithelial-secreted exosomes attenuate ocular angiogenesis via inhibiting microglial activation.

The lens is an avascular tissue, where epithelial cells (LECs) are the primary living cells. The role of LECs-derived exosomes (LEC-exos) is largely unknown. In our study, we determined the anti-angiogenic role of LEC-exos, manifested as regressed retinal neovascularization (NV) using the oxygen-induced retinopathy (OIR), and reduced choroidal NV size and pathological vascular leakage using the laser-induced choroidal neovascularization (laser-induced CNV). Furthermore, the activation and accumulation of microglia were also restricted by LEC-exos. Based on Luminex multiplex assays, the expressions of chemokines such as SCYB16/CXCL16, MCP-1/CCL2, I-TAC/CXCL11, and MIP 3beta/CCL19 were decreased after treatment with LEC-exos. Transwell assays showed that LEC-exos restricted the migration of the mouse microglia cell line (BV2 cells). After incubation with LEC-exos-treated BV2 cells, human umbilical vein endothelial cells (hUVECs) were collected for further evaluation using tube formation, Transwell assays, and 5-ethynyl-2'-deoxyuridine (EDU) assays. Using in vitro experiments, the pro-angiogenic effect of microglia was restricted by LEC-exos. Hence, it was investigated that LEC-exos attenuated ocular NV, which might attribute to the inhibition of microglial activation and accumulation.

Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy.

Ocular angiogenic diseases, such as proliferative diabetic retinopathy (PDR), are often characterized by pathological new vessels and fibrosis formation. Anti-vascular endothelial growth factor (VEGF) therapy, despite of its efficiency to inhibit new vessels, has limitations, including drug resistance and retinal fibrosis. Here, we identified that Gremlin1, a novel angiogenesis and fibrosis inducer, was secreted from Müller glial cells, and its expression increased in the vitreous fluid from patients with PDR. Mechanistically, Gremlin1 triggered angiogenesis by promoting endothelial-mesenchymal transition via the EGFR/RhoA/ROCK pathway. In addition, Gremlin1 activated microglia to present profibrotic and fibrogenic properties. Further, anti-Gremlin1 antibody inhibited ocular angiogenesis and microglia fibrosis in mouse models. Collectively, Gremlin1 could be a potential therapeutic target in the treatment of ocular angiogenic diseases.

Smart Lipid Nanoparticle that Remodels Tumor Microenvironment for Activatable H2S Gas and Photodynamic Immunotherapy.

Hydrogen sulfide (H2S) has shown promise for gas therapy. However, it is still controversial whether H2S can remodel the tumor microenvironment (TME) and induce robust antitumor immunity. Here, a tumor-targeting and TME-responsive "smart" lipid nanoparticle (1-JK-PS-FA) is presented, which is capable of delivering and releasing H2S specifically in tumor tissues for on-demand H2S gas and photodynamic immunotherapy. 1-JK-PS-FA enables a burst release of H2S in the acidic TME, which promptly reduces the embedded organic electrochromic materials and consequently switches on near-infrared fluorescence and photodynamic activity. Furthermore, we found that high levels of H2S can reprogram the TME by reducing tumor interstitial fluid pressure, promoting angiogenesis, increasing vascular permeability, ameliorating hypoxia, and reducing immunosuppressive conditions. This leads to increased tumor uptake of 1-JK-PS-FA, thereby enhancing PDT efficacy and eliciting strong immunogenic cell death during 808 nm laser irradiation. Therefore, 1-JK-PS-FA permits synergistic H2S gas and photodynamic immunotherapy, effectively eradicating orthotopic breast tumors and preventing tumor metastasis and recurrence. This work showcases the capacity of H2S to reprogram the TME to enhance H2S gas and immunotherapy.

Origin, evolution, and diversification of the wall-associated kinase gene family in plants.

KEY MESSAGE: The study of the origin, evolution, and diversification of the wall-associated kinase gene family in plants facilitates their functional investigations in the future. Wall-associated kinases (WAKs) make up one subfamily of receptor-like kinases (RLKs), and function directly in plant cell elongation and responses to biotic and abiotic stresses. The biological functions of WAKs have been extensively characterized in angiosperms; however, the origin and evolutionary history of the WAK family in green plants remain unclear. Here, we performed a comprehensive analysis of the WAK family to reveal its origin, evolution, and diversification in green plants. In total, 1061 WAK genes were identified in 37 species from unicellular algae to multicellular plants, and the results showed that WAK genes probably originated before bryophyte differentiation and were widely distributed in land plants, especially angiosperms. The phylogeny indicated that the land plant WAKs gave rise to five clades and underwent lineage-specific expansion after species differentiation. Cis-acting elements and expression patterns analyses of WAK genes in Arabidopsis and rice demonstrated the functional diversity of WAK genes in these two species. Many gene gains and losses have occurred in angiosperms, leading to an increase in the number of gene copies. The evolutionary trajectory of the WAK family during polyploidization was uncovered using Gossypium species. Our results provide insights into the evolution of WAK genes in green plants, facilitating their functional investigations in the future.

Lens epithelial cell-derived exosome inhibits angiogenesis in ocular pathological neovascularization through its delivery of miR-146a-5p.

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)-derived exosomes (Lec-exo) is largely unknown. Thus, we aimed to investigate whether Lec-exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen-induced retinopathy and laser-induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec-exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high-throughput miRNAs sequencing analysis detected that miR-146a-5p was enriched in Lec-exo. Mechanistically, exosomal miR-146a-5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec-exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.

A novel nomogram based on the hematological prognosis risk scoring system can predict the overall survival of patients with hepatocellular carcinoma.

BACKGROUND: This study aimed to establish and validate a nomogram based on a hematological prognostic risk scoring system to predict the overall survival in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients diagnosed with unresectable HCC undergoing transcatheter arterial chemoembolization (TACE) in 2012-2016 and 2017-2018 were included in the development set and validation set, respectively. The clinical outcome was overall survival (OS). The LASSO regression analysis was used to construct a hematological prognostic risk scoring system (HPR) by using the 18 hematological markers of patients in the development set. Combining the features of oncology on the basis of HPR to construct a nomogram for OS. In the development set and validation sets, the C-index, calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction performance of the nomogram. RESULTS: Multiple markers of immunity, coagulation, liver function, and nutrition, including red blood cell distribution width-coefficient of variation (RDW-CV), platelet (PLT), aspartate transferase (AST), alkaline phosphatase (ALP), prognostic nutritional index (PNI), and fibrinogen (Fib), construct the HPR. HPR was an independent risk factor for OS in patients with HCC. The C-index of the nomogram was 0.731 (95% confidence interval (CI) 0.712-0.749) and 0.696 (95% CI 0.668-0.725) in the development set and the validation set, respectively. CONCLUSIONS: HPR was a complement to the clinical features of patients with unresectable HCC. The nomogram based on HPR proved to be a practical and effective method for prognosticating HCC patients who undergo TACE.

Epidemiology of hand, foot and mouth disease and genomic surveillance of coxsackievirus A10 circulating in Zhejiang Province, China during 2017 to 2022.

BACKGROUND: Coxsackievirus A10 (CA10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD). OBJECTIVES: We aimed to perform a retrospective analysis of the molecular epidemiological characteristics and genetic features of HFMD associated with CA10 infections in Zhejiang Province from 2017 to 2022. STUDY DESIGN: Epidemiologic features were summarized. Throat swab specimens were collected and tested. The VP1 regions were sequenced for genotyping. CA10 positive samples were isolated. Whole genomes of CA10 isolations were sequenced. Nucleotide and amino acid changes were characterized. Phylogenetic trees were constructed. RESULTS: The number of HFMD cases fluctuated from 2017 to 2022. Children aged below 3 years accounted for the majority (66.29%) and boys were more frequently affected than girls. Cases peaked in June. The positivity rate of HEV was 62.69%. A total of 90 strains of CA10 were isolated and 53 genomes were obtained. All CA10 in this study could be assigned to two genogroups, C (C2) and F (F1 and F3). CONCLUSION: The clinical manifestations of HFMD associated with HEV are complex and diverse. CA10 infection may be emerging as a new and major cause of HFMD because an upward trend was observed in the proportion of CA10 cases after the use of EV71 vaccines. Different genogroups of CA10 had different geographic distribution patterns. Surveillance should be strengthened and further comprehensive studies should be continued to provide a scientific basis for HFMD prevention and control.

AaWRKY6 contributes to artemisinin accumulation during growth in Artemisia annua.

Artemisinin, which is extracted from the plant Artemisia annua L., is a crucial drug for curing malaria and has potential applications for treating cancer, diabetes, pulmonary tuberculosis, and other conditions. Demand for artemisinin is therefore high, and enhancing its yield is important. Artemisinin dynamics change during the growth cycle of A. annua; however, the regulatory networks underlying these changes are poorly understood. Here, we collected A. annua leaves at different growth stages and identified target genes from transcriptome data. We determined that WRKY6 binds to the promoters of the artemisinin biosynthesis gene artemisinic aldehyde Δ11(13) reductase (DBR2). In agreement, overexpression of WRKY6 in A. annua resulted in higher expression levels of genes in the artemisinin biosynthesis pathway and greater artemisinin contents than in the wild type. When expression of WRKY6 was down-regulated, artemisinin biosynthesis pathway genes were also down-regulated and the content of artemisinin was lower. WRKY6 mediates the transcriptional activation of artemisinin biosynthesis by binding to the promoter of DBR2, making it a key regulator for modulating the dynamics of artemisinin changes during the A. annua growth cycle.

Roles of S-Adenosylmethionine and Its Derivatives in Salt Tolerance of Cotton.

Salinity is a major abiotic stress that restricts cotton growth and affects fiber yield and quality. Although studies on salt tolerance have achieved great progress in cotton since the completion of cotton genome sequencing, knowledge about how cotton copes with salt stress is still scant. S-adenosylmethionine (SAM) plays important roles in many organelles with the help of the SAM transporter, and it is also a synthetic precursor for substances such as ethylene (ET), polyamines (PAs), betaine, and lignin, which often accumulate in plants in response to stresses. This review focused on the biosynthesis and signal transduction pathways of ET and PAs. The current progress of ET and PAs in regulating plant growth and development under salt stress has been summarized. Moreover, we verified the function of a cotton SAM transporter and suggested that it can regulate salt stress response in cotton. At last, an improved regulatory pathway of ET and PAs under salt stress in cotton is proposed for the breeding of salt-tolerant varieties.

Rosmarinic acid, the active component of Rubi Fructus, induces apoptosis of SGC-7901 and HepG2 cells through mitochondrial pathway and exerts anti-tumor effect.

Rosmarinic acid (RA) is a well-known phenolic acid widely present in over 160 species of herbal plants and known to exhibit anti-tumor effects on breast, prostate, and colon cancers in vitro. However, its effect and mechanism in gastric cancer and liver cancer are unclear. Moreover, there is no RA report yet in the chemical constituents of Rubi Fructus (RF). In this study, RA was isolated from RF for the first time, and the effect and mechanism of RA on gastric and liver cancers were evaluated using SGC-7901 and HepG2 cells models. The cells were treated with different concentrations of RA (50, 75, and 100 µg/mL) for 48 h, and the effect of RA on cell proliferation was evaluated by the CCK-8 assay. The effect of RA on cell morphology and mobility was observed by inverted fluorescence microscopy, cell apoptosis and cell cycle were determined by flow cytometry, and the expression of apoptosis-related proteins cytochrome C, cleaved caspase-3, Bax, and Bcl-2 was detected by western blotting. The results revealed that, with an increase in the RA concentration, the cell viability, mobility, and Bcl-2 expression decreased, while the apoptosis rate, Bax, cytochrome C, and cleaved caspase-3 expression increased, and SGC-7901 and HepG2 cells could be induced to arrest their cell cycle in the G0/G1 and S phases, respectively. These results together indicate that RA can induce apoptosis of SGC-7901 and HepG2 cells through the mitochondrial pathway. Thus, this study supplements the material basis of the anti-tumor activity of RF and provides an insight into the potential mechanism of RA-inducing apoptosis of gastric cancer SGC-7901 cells and liver cancer HepG2 cells, thereby facilitating further developmental studies on and the utilization of the anti-tumor activity of RF.

Bulk and single-cell transcriptome profiling reveal the metabolic heterogeneity in gastric cancer.

Metabolic reprogramming has been defined as a key hall mark of human tumors. However, metabolic heterogeneity in gastric cancer has not been elucidated. Here we separated the TCGA-STAD dataset into two metabolic subtypes. The differences between subtypes were elaborated in terms of transcriptomics, genomics, tumor-infiltrating cells, and single-cell resolution. We found that metabolic subtype 1 is predominantly characterized by low metabolism, high immune cell infiltration. Subtype 2 is mainly characterized by high metabolism and low immune cell infiltration. From single-cell resolution, we found that the high metabolism of subtype 2 is dominated by epithelial cells. Not only epithelial cells, but also various immune cells and stromal cells showed high metabolism in subtype 2 and low metabolism in subtype 1. Our study established a classification of gastric cancer metabolic subtypes and explored the differences between subtypes from multiple dimensions, especially the single-cell resolution.

Hepatocyte CD36 modulates UBQLN1-mediated proteasomal degradation of autophagic SNARE proteins contributing to septic liver injury.

Macroautophagy/autophagy plays a protective role in sepsis-induced liver injury. As a member of class B scavenger receptors, CD36 plays important roles in various disorders, such as atherosclerosis and fatty liver disease. Here we found that the expression of CD36 in hepatocytes was increased in patients and a mouse model with sepsis, accompanied by impaired autophagy flux. Furthermore, hepatocyte cd36 knockout (cd36-HKO) markedly improved liver injury and the impairment of autophagosome-lysosome fusion in lipopolysaccharide (LPS)-induced septic mice. Ubqln1 (ubiquilin 1) overexpression (OE) in hepatocyte blocked the protective effect of cd36-HKO on LPS-induced liver injury in mice. Mechanistically, with LPS stimulation, CD36 on the plasma membrane was depalmitoylated and distributed to the lysosome, where CD36 acted as a bridge molecule linking UBQLN1 to soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and hence promoting the proteasomal degradation of SNARE proteins, resulting in fusion impairment. Overall, our data reveal that CD36 is essential for modulating the proteasomal degradation of autophagic SNARE proteins in a UBQLN1-dependent manner. Targeting CD36 in hepatocytes is effective for improving autophagic flux in sepsis and therefore represents a promising therapeutic strategy for clinical treatment of septic liver injury.Abbreviations: AAV8: adeno-associated virus 8; AOSC: acute obstructive suppurative cholangitis; ATP1A1: ATPase, Na+/K+ transporting, alpha 1 polypeptide; CASP3: caspase 3; CASP8: caspase 8; CCL2: chemokine (C-C motif) ligand 2; cd36-HKO: hepatocyte-specific cd36 knockout; Co-IP: co-immunoprecipitation; CQ: chloroquine; Cys: cysteine; GOT1: glutamic-oxaloacetic transaminase 1, soluble; GPT: glutamic-pyruvic transaminase, soluble; IL1B: interleukin 1 beta; IL6: interleukin 6; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LDH, lactate dehydrogenase; LPS: lipopolysaccharide; LYPLA1: lysophospholipase 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OE: overexpression; qPCR: quantitative polymerase chain reaction; SNAP29: synaptosome associated protein 29; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TNF: tumor necrosis factor; TRIM: tripartite motif-containing; UBA: ubiquitin-associated; UBL: ubiquitin-like; UBQLN: ubiquilin; VAMP8: vesicle associated membrane protein 8; WT: wild-type.

Predictors of peri-implant bone remodeling outcomes after the osteotome sinus floor elevation: a retrospective study.

BACKGROUND: This study aimed to evaluate the radiographic outcomes of implants after osteotome sinus floor elevation (OSFE), and further identify the separate predictors for these radiographic outcomes. METHODS: In this retrospective cohort study, a total of 187 implants were inserted into 138 patients using the OSFE technique. Seventy-four patients in the grafted group, and 64 patients in the non-grafted group completed this study. The vertical bone gain (VBG) and marginal bone loss (MBL) at 3 years following surgery were assessed as outcome variables. Based on extensive literature results, variables considered potential predictors of outcome variables included sex, age, tooth position, implant length, implant diameter, with or without grafting materials, residual bone height, sinus width, bone density, and sinus membrane thickness. Subsequently, the binary logistic regression analysis was applied with VBG and MBL as dependent variables, respectively. The receiver operating characteristic curve (ROC) with its area under the curve (AUC) was performed to further determine the predictive value of these predictors. RESULTS: One hundred and six implants in grafted group and 81 implants in the non-grafted group were analyzed. The average VBG was 2.12 ± 1.94 mm for the grafted group and 0.44 ± 1.01 mm for the non-grafted group at 3 years (P < 0.05). The mean MBL was 1.54 ± 1.42 mm for the grafted group and 1.13 ± 1.69 mm for the non-grafted group at 3 years (P > 0.05). After the adjustment for confounders, logistic regression analysis demonstrated that implant length, grafting, residual bone height, and sinus membrane thickness were predictors of VBG. The odds ratio for VBG was 3.90, 4.04, 4.13 and 2.62, respectively. Furthermore, grafting exhibited the largest AUC at 0.80. While tooth position and implant length were predictors of MBL, the odds ratio for MBL was 3.27 and 7.85, respectively. Meanwhile, implant length exhibited the largest AUC at 0.72. CONCLUSIONS: OSFE with or without simultaneous grafting materials both showed predictable clinical outcomes. Additionally, the present study is the first quantitative and significant verification that VBG has a significant association with sinus membrane thickness, as well as residual bone height, implant length and grafting. Whereas tooth position and implant length are markedly associated with MBL.