Establishment and verification of a prognostic model based on coagulation and fibrinolysis-related genes in hepatocellular carcinoma.

BACKGROUND: Studies have shown that coagulation and fibrinolysis (CFR) are correlated with Hepatocellular carcinoma (HCC) progression and prognosis. We aim to build a model based on CFR-correlated genes for risk assessment and prediction of HCC patient. METHODS: HCC samples were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. The Molecular Signatures Database (MSigDB) was used to select the CFR genes. RiskScore model were established by single sample gene set enrichment analysis (ssGSEA), weighted correlation network analysis (WGCNA), multivariate Cox regression analysis, LASSO regression analysis. RESULTS: PCDH17, PGF, PDE2A, FAM110D, FSCN1, FBLN5 were selected as the key genes and designed a RiskScore model. Those key genes were Differential expressions in HCC cell and patients. Overexpression PDE2A inhibited HCC cell migration and invasion. The higher the RiskScore, the lower the probability of survival. The model has high AUC values in the first, third and fifth year prediction curves, indicating that the model has strong prediction performance. The difference analysis of clinicopathological features found that a great proportion of high clinicopathological grade samples showed higher RiskScore. RiskScore were positively correlated with immune scores and TIDE scores. High levels of immune checkpoints and immunomodulators were observed in high RiskScore group. High RiskScore groups may benefit greatly from taking traditional chemotherapy drugs. CONCLUSIONS: We screened CFR related genes to design a RiskScore model, which could accurately evaluate the prognosis and survival status of HCC patients, providing certain value for optimizing the clinical treatment of cancer in the future.

Scalable Video Object Segmentation With Identification Mechanism.

This paper delves into the challenges of achieving scalable and effective multi-object modeling for semi-supervised Video Object Segmentation (VOS). Previous VOS methods decode features with a single positive object, limiting the learning of multi-object representation as they must match and segment each target separately under multi-object scenarios. Additionally, earlier techniques catered to specific application objectives and lacked the flexibility to fulfill different speed-accuracy requirements. To address these problems, we present two innovative approaches, Associating Objects with Transformers (AOT) and Associating Objects with Scalable Transformers (AOST). In pursuing effective multi-object modeling, AOT introduces the IDentification (ID) mechanism to allocate each object a unique identity. This approach enables the network to model the associations among all objects simultaneously, thus facilitating the tracking and segmentation of objects in a single network pass. To address the challenge of inflexible deployment, AOST further integrates scalable long short-term transformers that incorporate scalable supervision and layer-wise ID-based attention. This enables online architecture scalability in VOS for the first time and overcomes ID embeddings' representation limitations. Given the absence of a benchmark for VOS involving densely multi-object annotations, we propose a challenging Video Object Segmentation in the Wild (VOSW) benchmark to validate our approaches. We evaluated various AOT and AOST variants using extensive experiments across VOSW and five commonly used VOS benchmarks, including YouTube-VOS 2018 & 2019 Val, DAVIS-2017 Val & Test, and DAVIS-2016. Our approaches surpass the state-of-the-art competitors and display exceptional efficiency and scalability consistently across all six benchmarks. Moreover, we notably achieved the 1st position in the 3 rd Large-scale Video Object Segmentation Challenge. Project page: https://github.com/yoxu515/aot-benchmark.

The dual role of mesenchymal stem cells in apoptosis regulation.

Mesenchymal stem cells (MSCs) are widely distributed pluripotent stem cells with powerful immunomodulatory capacity. MSCs transplantation therapy (MSCT) is widely used in the fields of tissue regeneration and repair, and treatment of inflammatory diseases. Apoptosis is an important way for tissues to maintain cell renewal, but it also plays an important role in various diseases. And many studies have shown that MSCs improves the diseases by regulating cell apoptosis. The regulation of MSCs on apoptosis is double-sided. On the one hand, MSCs significantly inhibit the apoptosis of diseased cells. On the other hand, MSCs also promote the apoptosis of tumor cells and excessive immune cells. Furthermore, MSCs regulate apoptosis through multiple molecules and pathways, including three classical apoptotic signaling pathways and other pathways. In this review, we summarize the current evidence on the regulation of apoptosis by MSCs.

BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension.

BACKGROUND: An imbalance of antiproliferative BMP (bone morphogenetic protein) signaling and proliferative TGF-ß (transforming growth factor-ß) signaling is implicated in the development of pulmonary arterial hypertension (PAH). The posttranslational modification (eg, phosphorylation and ubiquitination) of TGF-ß family receptors, including BMPR2 (bone morphogenetic protein type 2 receptor)/ALK2 (activin receptor-like kinase-2) and TGF-ßR2/R1, and receptor-regulated (R) Smads significantly affects their activity and thus regulates the target cell fate. BRCC3 modifies the activity and stability of its substrate proteins through K63-dependent deubiquitination. By modulating the posttranslational modifications of the BMP/TGF-ß-PPARγ pathway, BRCC3 may play a role in pulmonary vascular remodeling, hence the pathogenesis of PAH. METHODS: Bioinformatic analyses were used to explore the mechanism of BRCC3 deubiquitinates ALK2. Cultured pulmonary artery smooth muscle cells (PASMCs), mouse models, and specimens from patients with idiopathic PAH were used to investigate the rebalance between BMP and TGF-ß signaling in regulating ALK2 phosphorylation and ubiquitination in the context of pulmonary hypertension. RESULTS: BRCC3 was significantly downregulated in PASMCs from patients with PAH and animals with experimental pulmonary hypertension. BRCC3, by de-ubiquitinating ALK2 at Lys-472 and Lys-475, activated receptor-regulated Smad1/5/9 (Smad1/5/9), which resulted in transcriptional activation of BMP-regulated PPARγ, p53, and Id1. Overexpression of BRCC3 also attenuated TGF-ß signaling by downregulating TGF-ß expression and inhibiting phosphorylation of Smad3. Experiments in vitro indicated that overexpression of BRCC3 or the de-ubiquitin-mimetic ALK2-K472/475R attenuated PASMC proliferation and migration and enhanced PASMC apoptosis. In SM22α-BRCC3-Tg mice, pulmonary hypertension was ameliorated because of activation of the ALK2-Smad1/5-PPARγ axis in PASMCs. In contrast, Brcc3-/- mice showed increased susceptibility of experimental pulmonary hypertension because of inhibition of the ALK2-Smad1/5 signaling. CONCLUSIONS: These results suggest a pivotal role of BRCC3 in sustaining pulmonary vascular homeostasis by maintaining the integrity of the BMP signaling (ie, the ALK2-Smad1/5-PPARγ axis) while suppressing TGF-ß signaling in PASMCs. Such rebalance of BMP/TGF-ß pathways is translationally important for PAH alleviation.

More potential uses of specific perforator flaps in the calf - A cadaveric study on the subdermal vascular structure of the lower leg.

BACKGROUND: The perforator flap has garnered significant interest since its inception due to its advantage of not needing a vascular network at the deep fascial level. Perforator flaps are commonly utilized in different flap transplant surgeries, and the thigh flap is presently the most widely used perforator flap. Is it possible for the calf to replace the thigh as a more suitable site for harvesting materials? Currently, there is a lack of relevant anatomical research. This study aims to address this question from an anatomical and imaging perspective. METHODS: This study used cadavers to observe the branches and courses of perforators on the calf and the distribution of skin branches using microdissection techniques, digital X-ray photography, and micro-computed tomography techniques. RESULTS: The perforators had three main branches: the vertical cutaneous branch, the oblique cutaneous branch, and the superficial fascial branch. The superficial fascial branch traveled in the superficial fascia and connected with the nearby perforators. The vertical and oblique cutaneous branches entered the subdermal layer and connected with each other to create the subdermal vascular network. CONCLUSIONS: We observed an intact calf cutaneous branch chain between the cutaneous nerve and the perforator of the infrapopliteal main artery at the superficial vein site. Utilizing this anatomical structure, the calfskin branch has the potential to serve as a substitute for thigh skin flap transplantation and may be applied to perforator flap transplantation in more locations.

Meta Invariance Defense Towards Generalizable Robustness to Unknown Adversarial Attacks.

Despite providing high-performance solutions for computer vision tasks, the deep neural network (DNN) model has been proved to be extremely vulnerable to adversarial attacks. Current defense mainly focuses on the known attacks, but the adversarial robustness to the unknown attacks is seriously overlooked. Besides, commonly used adaptive learning and fine-tuning technique is unsuitable for adversarial defense since it is essentially a zero-shot problem when deployed. Thus, to tackle this challenge, we propose an attack-agnostic defense method named Meta Invariance Defense (MID). Specifically, various combinations of adversarial attacks are randomly sampled from a manually constructed Attacker Pool to constitute different defense tasks against unknown attacks, in which a student encoder is supervised by multi-consistency distillation to learn the attack-invariant features via a meta principle. The proposed MID has two merits: 1) Full distillation from pixel-, feature- and prediction-level between benign and adversarial samples facilitates the discovery of attack-invariance. 2) The model simultaneously achieves robustness to the imperceptible adversarial perturbations in high-level image classification and attack-suppression in low-level robust image regeneration. Theoretical and empirical studies on numerous benchmarks such as ImageNet verify the generalizable robustness and superiority of MID under various attacks.

Comparison of the 2022 world health organization classification and international consensus classification in myelodysplastic syndromes/neoplasms.

In 2022, two novel classification systems for myelodysplastic syndromes/neoplasms (MDS) have been proposed: the International Consensus Classification (ICC) and the 2022 World Health Organization (WHO-2022) classification. These two contemporary systems exhibit numerous shared features but also diverge significantly in terminology and the definition of new entities. Thus, we retrospectively validated the ICC and WHO-2022 classification and found that both systems promoted efficient segregation of this heterogeneous disease. After examining the distinction between the two systems, we showed that a peripheral blood blast percentage ≥ 5% indicates adverse survival. Identifying MDS/acute myeloid leukemia with MDS-related gene mutations or cytogenetic abnormalities helps differentiate survival outcomes. In MDS, not otherwise specified patients, those diagnosed with hypoplastic MDS and single lineage dysplasia displayed a trend of superior survival compared to other low-risk MDS patients. Furthermore, the impact of bone marrow fibrosis on survival was less pronounced within the ICC framework. Allogeneic transplantation appears to improve outcomes for patients diagnosed with MDS with excess blasts in the ICC. Therefore, we proposed an integrated system that may lead to the accurate diagnosis and advancement of future research for MDS. Prospective studies are warranted to validate this refined classification.

Indole-3 acetic acid negatively regulates rose black spot disease resistance through antagonizing the salicylic acid signaling pathway via jasmonic acid.

MAIN CONCLUSION: IAA cooperates with JA to inhibit SA and negatively regulates rose black spot disease resistance. Black spot disease caused by the fungus Marssonina rosae is the most prevalent and severe ailment in rose cultivation, leading to the appearance of black spots on leaves and eventual leaf fall, significantly impacting the utilization of roses in gardens. Salicylic acid (SA) and jasmonic acid (JA) are pivotal hormones that collaborate with indole-3 acetic acid (IAA) in regulating plant defense responses; however, the detailed mechanisms underlying the induction of black spot disease resistance by IAA, JA, and SA remain unclear. In this study, transcript analysis was conducted on resistant (R13-54) and susceptible (R12-26) lines following M. rosae infection. In addition, the impact of exogenous interference with IAA on SA- and JA-mediated disease resistance was examined. The continuous accumulation of JA, in synergy with IAA, inhibited activation of the SA signaling pathway in the early infection stage, thereby negatively regulating the induction of effective resistance to black spot disease. IAA administration alleviated the inhibition of SA on JA to negatively regulate the resistance of susceptible strains by further enhancing the synthesis and accumulation of JA. However, IAA did not contribute to the negative regulation of black spot resistance when high levels of JA were inhibited. Virus-induced gene silencing of RcTIFY10A, an inhibitor of the JA signaling pathway, further suggested that IAA upregulation led to a decrease in disease resistance, a phenomenon not observed when the JA signal was inhibited. Collectively, these findings indicate that the IAA-mediated negative regulation of black spot disease resistance relies on activation of the JA signaling pathway.

Cytosolic ABA Receptor Kinases phosphorylate the D6 PROTEIN KINASE leading to its stabilization which promotes Arabidopsis growth.

The polar auxin transport is required for proper plant growth and development. D6 PROTEIN KINASE (D6PK) is required for the phosphorylation of PIN-FORMED (PIN) auxin efflux carriers to regulate auxin transport, while the regulation of D6PK stabilization is still poorly understood. Here, we found that Cytosolic ABA Receptor Kinases (CARKs) redundantly interact with D6PK, and the interactions are dependent on CARKs' kinase activities. Similarly, CARK3 also could interact with paralogs of D6PK, including D6PKL1, D6PKL2, and D6PKL3. The genetic analysis shows that D6PK acts the downstream of CARKs to regulate Arabidopsis growth, including hypocotyl, leaf area, vein formation, and the length of silique. Loss-of-function of CARK3 in overexpressing GFP-D6PK plants leads to reduce the level of D6PK protein, thereby rescues plant growth. In addition, the cell-free degradation assays indicate that D6PK is degraded through 26 S proteasome pathway, while the phosphorylation by CARK3 represses this process in cells. In summary, D6PK stabilization by the CARK family is required for auxin-mediated plant growth and development.

A Multifunctional CaII-EuIII Heterometallic Organic Framework with Sensing and Selective Adsorption in Water.

With increasing global industrialization, it is urgent and challenging to develop multifunctional species for detection and adsorption in the environment. For this purpose, a novel anionic heterometallic organic framework, [(CH3)2NH2][CaEu(CAM)2(H2O)2]·4H2O·4DMF (CaEuCAM), is hydrothermally synthesized based on chelidamic acid (H3CAM). Single crystal analysis shows that CaEuCAM features two different oxygen-rich channels along the c-axis in which one CAM3- bridges two sextuple-coordinated Ca2+ and two octuple-coordinated Eu3+ with a µ4-η1: η1: η1: η1: η1: η1 new chelating and bridging mode. The characteristic bright red emission and superior hydrostability of CaEuCAM under harsh acidic and basic conditions benefit it by acting as a highly sensitive sensor for Fe3+ and 3-nitrophenol (3-NP) with extremely low LODs through remarkable quenching. The combination of experiments and theoretical calculations for sensing mechanisms shows that the competitive absorption and interaction are responsible for Fe3+-induced selective emission quenching, while that for 3-NP is the result of the synergism of host-guest chemistry and the inner filter effect. Meanwhile, the assimilation of negative charge plus channels renders CaEuCAM a highly selective adsorbent for methylene blue (MB) due to a synergy of electrostatic affinity, ion-dipole interaction, and size matching. Of note is the reusability of CaEuCAM toward Fe3+/3-NP sensing and MB adsorption besides its fast response. These findings could be very useful in guiding the development of multifunctional Ln-MOFs for sensing and adsorption applications in water media.

MXene-Enabled Pneumatic Multiscale Shape Morphing for Adaptive, Programmable and Multimodal Radar-infrared Compatible Camouflage.

Achieving radar-infrared compatible camouflage with dynamic adaptability has been a long-sought goal, but faces significant challenges owing to the limited dispersion relations of conventional material systems operating in different wavelength ranges. Here, this work proposes the concept of pneumatic multiscale shape morphing and design a periodically arranged pneumatic unit consisting of MXene-based morphable conductors and intake platforms. During gas actuation, the morphable conductor transforms centimeter-scale 2D flat sheets into 3D balloon shapes to enhance microwave absorption behavior, and also reconfigures micrometer-scale MXene wrinkles into smooth planes in combination with cavity-induced low heat transfer to minimize infrared (IR) signatures. Through theory-guided reverse engineering, the final pneumatic matrix shows remarkable frequency tunability (2.64-18.0 GHz), moderate IR emissivity regulation (0.14 at 7-16.5 µm), rapid responsiveness (≈30 ms), wide-angle operation (>45°), and excellent environmental tolerance. Additionally, the multiplexed pneumatic matrix enables over 14 programmable coding sequences that independently alter thermal radiation without compromising radar stealth, and allows multimodal camouflage switching between three distinct compatible states. The approach may facilitate the evolution of camouflage techniques and electromagnetic functional materials toward multispectral, adaptability and intelligence.

A probabilistic approach for assessing the mechanical performance of intertrochanteric fracture stabilized with proximal femoral nail antirotation.

Maintaining post-operative mechanical stability is crucial for successfully healing intertrochanteric fractures treated with the Proximal Femoral Nail Antirotation (PFNA) system. This stability is primarily dependent on the bone mineral density (BMD) and strain on the fracture. Current PFNA failure analyses often overlook the uncertainties related to BMD and body weight (BW). Therefore, this study aimed to develop a probabilistic model using finite element modeling and engineering reliability analysis to assess the post-operative performance of PFNA under various physiological loading conditions. The model predictions were validated through a series of experimental test. The results revealed a negative nonlinear relationship between the BMD and compressive strain. Conversely, the BW was positively and linearly correlated with the compressive strain. Importantly, the compressive strain was more sensitive to BW than to BMD when the BMD exceeded 0.6 g/cm3. Potential trabecular bone compression failure is also indicated if BMD is equal to or below 0.15 g/cm3 and BW increases to approximately 2.5 times the normal or higher. This study emphasizes that variations in the BMD significantly affect the probability of failure of a PFNA system. Thus, careful planning of post-operative physical therapy is essential. For patients aged > 50 years restrictions on high-intensity activities are advised, while limiting strenuous movements is recommended for those aged > 65 years.

Beyond the ß-amino alcohols framework: identification of novel ß-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

BACKGROUND: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases. RESULTS: A series of novel ß-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an half maximal effective concentration (EC50) value of 0.28 µg mL-1. A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analysis of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity: 71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo. CONCLUSION: Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. © 2024 Society of Chemical Industry.

[Banxia Xiexin Decoction inhibiting colitis-associated colorectal cancer infected with Fusobacterium nucleatum by regulating Wnt/ß-catenin pathway].

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.

Pathogen-specific alterations in intestinal microbiota precede urinary tract infections in preterm infants: a longitudinal case-control study.

Urinary tract infections (UTIs) are among the most common late-onset infections in preterm infants, characterized by nonspecific symptoms and a pathogenic spectrum that diverges from that of term infants and older children, which present unique diagnostic and therapeutic challenges. Existing data on the role of gut microbiota in UTI pathogenesis in this demographic are limited. This study aims to investigate alterations in gut microbiota and fecal calprotectin levels and their association with the development of UTIs in hospitalized preterm infants. A longitudinal case-control study was conducted involving preterm infants admitted between January 2018 and October 2020. Fecal samples were collected weekly and analyzed for microbial profiles and calprotectin levels. Propensity score matching, accounting for key perinatal factors including age and antibiotic use, was utilized to match samples from UTI-diagnosed infants to those from non-UTI counterparts. Among the 151 preterm infants studied, 53 were diagnosed with a UTI, predominantly caused by Enterobacteriaceae (79.3%) and Enterococcaceae (19.0%). Infants with UTIs showed a significantly higher abundance of these families compared to non-UTI infants, for both Gram-negative and positive pathogens, respectively. Notably, there was a significant pre-UTI increase in the abundance of pathogen-specific taxa in infants later diagnosed with UTIs, offering high predictive value for early detection. Shotgun metagenomic sequencing further confirmed the dominance of specific pathogenic species pre-UTI and revealed altered virulence factor profiles associated with Klebsiella aerogenes and Escherichia coli infections. Additionally, a decline in fecal calprotectin levels was observed preceding UTI onset, particularly in cases involving Enterobacteriaceae. The observed pathogen-specific alterations in the gut microbiota preceding UTI onset offer novel insight into the UTI pathogenesis and promising early biomarkers for UTIs in preterm infants, potentially enhancing the timely management of this common infection. However, further validation in larger cohorts is essential to confirm these findings.

Exploring the autophagy-related pathogenesis of active ulcerative colitis.

BACKGROUND: The pathogenesis of ulcerative colitis (UC) is complex, and recent therapeutic advances remain unable to fully alleviate the condition. AIM: To inform the development of novel UC treatments, bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC. METHODS: The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria. Differential analysis was conducted to obtain differentially expressed genes (DEGs). Autophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes (DEARGs) associated with active UC. DEARGs were then subjected to KEGG, GO, and DisGeNET disease enrichment analyses using R software. Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm. The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs, and the top five targets in the Dgree ranking were designated as core targets. RESULTS: A total of 4822 DEGs were obtained, of which 58 were classified as DEARGs. SERPINA1, BAG3, HSPA5, CASP1, and CX3CL1 were identified as core targets. GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy. KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways. Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion. Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls. CONCLUSION: Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Comparison of prognosis and postoperative morbidities between standard pancreaticoduodenectomy and the TRIANGLE technique for resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocarcinoma (PDAC), although tumor recurrence, especially locally, still inhibits the treatment efficacy. The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC. However, there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC. AIM: To compare the prognosis and postoperative morbidities between standard pancreaticoduodenectomy (PD) and the TRIANGLE technique for resectable PDAC. METHODS: Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study. All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure. Baseline characteristics, surgical data, and postoperative morbidities were recorded. All of the patients were followed up, and the date and location of tumor recurrence, and death were recorded. The Kaplan-Meier method and log-rank test were used for the survival analysis. RESULTS: There were 93 patients included in the study and 37 underwent the TRIANGLE technique. Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group [440 (410-480) min vs 320 (265-427) min] (P = 0.001). Intraoperative blood loss [700 (500-1200) mL vs 500 (300-800) mL] (P = 0.009) and blood transfusion [975 (0-1250) mL vs 400 (0-800) mL] (P = 0.009) were higher in the PDTRIANGLE group. There was a higher incidence of surgical site infection (43.2% vs 12.5%) (P = 0.001) and postoperative diarrhea (54.1% vs 12.5%) (P = 0.001) in the PDTRIANGLE group. The rates of R0 resection and local recurrence, overall survival, and disease-free survival did not differ significantly between the two groups. CONCLUSION: The TRIANGLE technique is safe, with acceptable postoperative morbidities compared with standardized PD, but it does not improve prognosis for patients with resectable PDAC.

Crosstalk between metabolism and cell death in tumorigenesis.

It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.