TIC236 gain-of-function mutations unveil the link between plastid division and plastid protein import.

SignificanceAlthough plastid division is critical for plant development, how components of the plastid division machinery (PDM) are imported into plastids remains unexplored. A forward genetic screen to identify suppressors of a crumpled leaf (crl) mutant deficient in plastid division led us to find dominant gain-of-function (GF) mutations in TIC236, which significantly increases the import of PDM components and completely rescues crl phenotypes. The defective plastid division phenotypes in crl and tic236-knockdown mutants and CRL-TIC236 association in a functional complex indicate that the CRL-TIC236 module is vital for plastid division. Hence, we report the first GF translocon mutants and unveil CRL as a novel functional partner of TIC236 for PDM import.

Increased Attenuation of Intestinal Contents at CT Indicates Bowel Necrosis in Closed-Loop Small Bowel Obstruction.

Background Preoperative recognition of irreversible bowel necrosis is important, as it provides valuable guidance for surgical strategy selection but also may inform perioperative risk assessment and communication. Few studies have focused on the association between CT signs and bowel necrosis. Purpose To assess the diagnostic accuracy of CT signs to predict bowel necrosis in patients with closed-loop small bowel obstruction (CL-SBO). Materials and Methods This retrospective single-center study included patients who were surgically confirmed to have CL-SBO caused by adhesion or internal hernia between January 2016 and May 2022. Necrosis was determined based on surgical exploration and postoperative pathologic examination. Two radiologists independently reviewed CT signs by both subjective visual assessment and objective measurement. Disagreements were resolved in consensus with a third gastrointestinal radiologist. Univariable and multivariable analyses were used to assess the association between CT signs and bowel necrosis, and Cohen κ was used to assess interobserver agreement. Sensitivity and specificity were calculated for each CT sign. Results This study included 145 patients: 61 (42.1%) in the necrotic group (median age, 62 years [IQR, 51-71.5 years]; 37 [60.7%] women) and 84 (57.9%) in the nonnecrotic group (median age, 61.5 years [IQR, 51-68.8 years]; 51 [60.7%] women). Univariable analysis and multivariable analysis showed that increased attenuation of intestinal contents and increased attenuation of intestinal wall were independent predictors for bowel necrosis (odds ratio = 45.3 and 15.1; P = .001 and P < .001, respectively). Increased attenuation of intestinal contents and increased attenuation of intestinal wall had similar sensitivity (64% and 67%, respectively) and specificity (99% and 92%, respectively) for predicting bowel necrosis. However, interobserver agreement was better for assessing the contents than the wall (κ = 0.84 and 0.59, respectively). Conclusion Increased attenuation of intestinal contents was a highly specific CT sign with good reproducibility to predict bowel necrosis in CL-SBO. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Taourel and Zins in this issue.

ETS2 alleviates acute-on-chronic liver failure by suppressing excessive inflammation.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a syndrome with high short-term mortality. The mechanism of the transcription factor ETS2 in ACLF remains unclear. This study aimed to clarify the molecular basis of ETS2 in ACLF pathogenesis. Peripheral blood mononuclear cells from patients with HBV-ACLF (n = 50) were subjected to RNA sequencing. Transcriptome analysis showed that ETS2 expression was significantly higher in ACLF patients than in patients with chronic liver diseases and healthy subjects (all p < 0.001). Area-under-ROC analysis of ETS2 demonstrated high values for the prediction of 28-/90-day mortality in ACLF patients (0.908/0.773). Significantly upregulated signatures of the innate immune response (monocytes/neutrophils/inflammation-related pathways) were observed in ACLF patients with high ETS2 expression. Myeloid-specific ETS2 deficiency in liver failure mice resulted in deterioration of biofunctions and increased expression of pro-inflammatory cytokines (IL-6/IL-1ß/TNF-α). Knockout of ETS2 in macrophages confirmed the downregulation of IL-6 and IL-1ß caused by both HMGB1 and lipopolysaccharide, and an NF-κB inhibitor reversed the suppressive effect of ETS2. ETS2 is a potential prognostic biomarker of ACLF patients that alleviates liver failure by downregulating the HMGB1-/lipopolysaccharide-triggered inflammatory response and may serve as a therapeutic target for ACLF.

FATTY ACID DESATURASE5 Is Required to Induce Autoimmune Responses in Gigantic Chloroplast Mutants of Arabidopsis.

Chloroplasts mediate genetically controlled cell death via chloroplast-to-nucleus retrograde signaling. To decipher the mechanism, we examined chloroplast-linked lesion-mimic mutants of Arabidopsis (Arabidopsis thaliana) deficient in plastid division, thereby developing gigantic chloroplasts (GCs). These GC mutants, including crumpled leaf (crl), constitutively express immune-related genes and show light-dependent localized cell death (LCD), mirroring typical autoimmune responses. Our reverse genetic approach excludes any potential role of immune/stress hormones in triggering LCD. Instead, transcriptome and in silico analyses suggest that reactive electrophile species (RES) generated via oxidation of polyunsaturated fatty acids (PUFAs) or lipid peroxidation-driven signaling may induce LCD. Consistent with these results, the one of the suppressors of crl, dubbed spcrl4, contains a causative mutation in the nuclear gene encoding chloroplast-localized FATTY ACID DESATURASE5 (FAD5) that catalyzes the conversion of palmitic acid (16:0) to palmitoleic acid (16:1). The loss of FAD5 in the crl mutant might attenuate the levels of RES and/or lipid peroxidation due to the reduced levels of palmitic acid-driven PUFAs, which are prime targets of reactive oxygen species. The fact that fad5 also compromises the expression of immune-related genes and the development of LCD in other GC mutants substantiates the presence of an intrinsic retrograde signaling pathway, priming the autoimmune responses in a FAD5-dependent manner.

The Arabidopsis CRUMPLED LEAF protein, a homolog of the cyanobacterial bilin lyase, retains the bilin-binding pocket for a yet unknown function.

The photosynthetic bacterial phycobiliprotein lyases, also called CpcT lyases, catalyze the biogenesis of phycobilisome, a light-harvesting antenna complex, through the covalent attachment of chromophores to the antenna proteins. The Arabidopsis CRUMPLED LEAF (CRL) protein is a homolog of the cyanobacterial CpcT lyase. Loss of CRL leads to multiple lesions, including localized foliar cell death, constitutive expression of stress-related nuclear genes, abnormal cell cycle, and impaired plastid division. Notwithstanding the apparent phenotypes, the function of CRL still remains elusive. To gain insight into the function of CRL, we examined whether CRL still retains the capacity to bind with the bacterial chromophore phycocyanobilin (PCB) and its plant analog phytochromobilin (PΦB). The revealed structure of the CpcT domain of CRL is comparable to that of the CpcT lyase, despite the low sequence identity. The subsequent in vitro biochemical assays found, as shown for the CpcT lyase, that PCB/PΦB binds to the CRL dimer. However, some mutant forms of CRL, substantially compromised in their bilin-binding ability, still restore the crl-induced multiple lesions. These results suggest that although CRL retains the bilin-binding pocket, it seems not functionally associated with the crl-induced multiple lesions.

Microfluidic Synthesis of Lignin/Chitosan Nanoparticles for the pH-Responsive Delivery of Anticancer Drugs.

In this work, lignin/chitosan nanoparticles (Lig/Chi NPs) with controlled structures were synthesized in a simple and scalable microfluidic system. When the positively charged chitosan and the negatively charged lignin solution were blended in a microreactor, Lig/Chi NPs were rapidly formed via the electrostatic coassembly between the amino groups of chitosan and the carboxyl groups of lignin. The ζ potential changes from negative (-13 mV) to positive (+54.5 mV) for Lig NPs and Lig/Chi NPs, respectively. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results demonstrated that Lig/Chi NPs have an average particle size of about 180 nm, which can be used as nanocarriers for drug delivery. The anticancer drug nanoparticles with docetaxel (DTX) and curcumin (CCM) were prepared by coassembly with Lig/Chi NPs in a microreactor, which had good drug loading efficiency, biocompatibility, and can release drugs in response to pH in the weakly acidic environment of the tumor. The drug release amounts in acidic solutions that simulated the tumor microenvironment were 51% (DTX@Lig/Chi NPs) and 50% (CCM@Lig/Chi NPs), respectively, which were better than the release amounts at pH 7.4, and have an obvious killing effect on HeLa cells.

Study on Active Components of Cuscuta chinensis Promoting Neural Stem Cells Proliferation: Bioassay-Guided Fractionation.

Neural stem cells (NSCs) exist in the central nervous system of adult animals and capable of self-replication. NSCs have two basic functions, namely the proliferation ability and the potential for multi-directional differentiation. In this study, based on the bioassay-guided fractionation, we aim to screen active components in Cuscuta chinensis to promote the proliferation of NSCs. CCK-8 assays were used as an active detection method to track the active components. On the basis of isolating active fraction and monomer compounds, the structures of these were identified by LC-MS and (1H, 13C) NMR. Moreover, active components were verified by pharmacodynamics and network pharmacology. The system solvent extraction method combined with the traditional isolation method were used to ensure that the fraction TSZE-EA-G6 of Cuscuta chinensis exhibited the highest activity. Seven chemical components were identified from the TSZE-EA-G6 fraction by UPLC-QE-Orbitrap-MS technology, which were 4-O-p-coumarinic acid, chlorogenic acid, 5-O-p-coumarinic acid, hyperoside, astragalin, isochlorogenic acid C, and quercetin-3-O-galactose-7-O-glucoside. Using different chromatographic techniques, five compounds were isolated in TSZE-EA-G6 and identified as kaempferol, kaempferol-3-O-glucoside (astragalin), quercetin-3-O-galactoside (hyperoside), chlorogenic acid, and sucrose. The activity study of these five compounds showed that the proliferation rate of kaempferol had the highest effects; at a certain concentration (25 µg/mL, 3.12 µg/mL), the proliferation rate could reach 87.44% and 59.59%, respectively. Furthermore, research results using network pharmacology techniques verified that kaempferol had an activity of promoting NSCs proliferation and the activity of flavonoid aglycones might be greater than that of flavonoid glycosides. In conclusion, this research shows that kaempferol is the active component in Cuscuta chinensis to promote the proliferation of NSCs.

[Study on therapeutic mechanism of Rehmanniae Radix Praeparata- Corni Fructus in sequelae of ischemic stroke based on network pharmacology technology].

In ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair has the effect in protecting damaged neurons, but its mechanism has not been clear. In this study, network pharmacology was used to predict the mechanism of Rehmanniae Radix Praeparata-Corni Fructus in the treatment of ischemic stroke sequela. Through database search and literature retrie-val, 40 active ingredients of Rehmanniae Radix Praeparata and Corni Fructus were obtained, and their targets were obtained through STITCH and TCMSP databases. The targets of ischemic stroke sequela were obtained through OMIM,GAD,TTD and DrugBank databases. By screening the intersections of active ingredients targets and stroke treatment targets, 21 potential targets were obtained. The DAVID database was used for GO enrichment analysis and KEGG pathway analysis of potential targets. GO enrichment analysis showed that Rehmanniae Radix Praeparata-Corni Fructus were mainly involved in regulation of blood pressure, negative regulation of extrinsic apoptotic signaling and positive regulation of angiogenesis. KEGG pathway analysis showed that Rehmanniae Radix Praeparata-Corni Fructus could inhibit inflammatory response and apoptosis signaling pathway by regulating HIF-VEGFA signaling pathway in neural stem cell proliferation, TNF signaling pathway and NF-kappaB signaling pathway. Molecular docking technique was used to verify that Rehmanniae Radix Praeparata-Corni Fructus component has a good binding activity with potential targets. The results showed that in ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair could play an important role in recovering neural function, promoting the proliferation of neural stem cells, angiogenesis, preventing neural cells apoptosis and regulating inflammatory factors.

Epidermoid cyst in intrapancreatic accessory spleen: A systematic review.

BACKGROUND/OBJECTIVES: Due to its rarity, epidermoid cyst in intrapancreatic accessory spleen (ECIPAS) is still a diagnostic dilemma during clinical practice. The aim of this review was to summarize the epidemiologic features and management of ECIPAS. METHODS: MEDLINE and EMBASE were searched for English articles reporting on ECIPAS up to April 30th, 2018 following the methodology suggested by the PRISMA guidelines. Categorical variables were reported as frequency and percentage. Continuous variables were reported as median (range). RESULTS: A total of 56 patients from 47 full articles were included for the final data synthesis. More than half of the ECIPASs (59%) were found incidentally. The female/male ratio was 1.33. ECIPAS is typically a single mono-/multi-lobular cystic lesions in the pancreatic tail with thickened cystic wall or various amount of solid component which had identical density/signal to the spleen on imaging examinations. The cyst is filled with serous or non-serous fluid. Recognition of the surrounding ectopic splenic tissue is the key point to diagnose ECIPAS. However, no preoperative examination was able to make a definite diagnosis. Almost all the patients (96%) received surgical treatment, due to the suspicion of pancreatic malignant or potentially malignant cystic tumor, especially mucinous cystic neoplasm (MCN). CONCLUSIONS: Although seldom encountered, ECIPAS should be considered as a differential diagnosis for pancreatic cystic lesions, especially when solid component was detected. As a benign disease, unnecessary surgery should be avoided. Because it is difficult to make a definite diagnosis preoperatively by one single examination, multiple modalities may be required.

High nuclear Survivin expression as a poor prognostic marker in pancreatic ductal adenocarcinoma.

BACKGROUND: Survivin, one of the key regulators of mitosis and apoptosis, has long been well recognized to play important biological roles in many neoplasms, including pancreatic ductal adenocarcinoma (PDAC). However, its prognostic value in PDAC remains controversial. PATIENTS AND METHODS: Nuclear expression of Survivin was detected, using tissue microarray-based immunohistochemistry, in paired-tumor and nontumor samples from 306 patients with radically resected PDAC. The staining H scores were further correlated with clinicopathologic features and disease-specific survival (DSS). RESULTS: Nuclear Survivin expression was much higher in tumor than in nontumor tissues (P < 0.001). No significant association between tumoral Survivin expression and clinicopathologic variables was found. For prognosis, high Survivin expression was associated with shortened DSS in all eligible patients and four subgroups, that is, male and nondiabetic patients as well as those with head-located and G1-2 tumors, shown by univariate analyses. In addition, a statistically marginal significance was revealed in eight subgroups. For the entire cohort and two subgroups, nuclear Survivin expression was also multivariate identified as an independent predictor for DSS. For patients with G1-2 tumors, it was the single prognostic marker. CONCLUSION: Our data suggest an association between high nuclear Survivin expression and poor prognosis in PDAC. However, further confirmation might be necessary.

Intrapancreatic accessory spleen: a diagnostic dilemma.

BACKGROUND: As intrapancreatic accessory spleen (IPAS) is rarely encountered during clinical practice, the aim of this review was to summarize the epidemiologic features, the diagnosis and treatment of IPAS. METHODS: MEDLINE and EMBASE were searched for articles reporting on IPAS. Categorical variables were reported as frequency and percentage. Continuous variables were reported as median (range). RESULTS: A total of 105 patients were included, of which 73% were detected incidentally. The male/female ratio was 1.23. The size of IPAS in patients who had previously undergone splenectomy was larger than that of patients without prior splenectomy (2.5 cm vs 1.5 cm; p = 0.020). No preoperative examination was able to make a definite diagnosis for all IPASs. More than half of the patients (55%) received surgical treatment, most of which (87%) were suspected as pancreatic neuroendocrine tumors (p-net) preoperatively. CONCLUSIONS: Although rare, IPAS should be considered in the differential of patients with suspected incidental p-net, especially if there has been a past history of splenectomy. Preoperative diagnosis is important as unnecessary surgery can be avoided. As it is difficult to make a definite diagnosis of IPAS by one single examination, multiple techniques may be required.

Surgeons' knowledge regarding the diagnosis and management of pancreatic cancer in China: a cross-sectional study.

BACKGROUND: Pancreatic cancer is rare but highly malignant. Studies have shown that surgeons' knowledge closely links to the correct diagnosis and treatment outcomes of pancreatic cancer. The purpose of this study was to survey current surgeons' knowledge regarding pancreatic cancer. METHODS: A cross-sectional study was conducted among 705 surgeons who attended the 2011 China Surgical Week's meeting in Beijing. A questionnaire regarding the risk factors, clinical manifestations, diagnosis, and treatment of pancreatic cancer was used. Surgeons' answers were analyzed and compared among different regions, levels of hospital, and professional ranks. RESULTS: Most surgeons had a correct knowledge toward the risk factors, diagnosis, and management of pancreatic cancer. However, several knowledge gaps were identified. They include "The association between type 2 diabetes and pancreatic cancer", "The most common histologic type of pancreatic neoplasm", "the typical clinical symptoms of pancreatic cancer", "The accuracy of ultrasound in screening pancreatic cancer", "Enhanced CT in the diagnosis of pancreatic cancer", and "Which is more superior between MRI and CT in the diagnosis of pancreatic cancer". We also found that overall surgeons' responses did not depend on their geographic locations, but on hospital levels and professional ranks. Surgeons working at level three hospitals had better knowledge than others in certain areas and resident surgeons had fewer correct answers in some areas. CONCLUSIONS: Although most surgeons have a good knowledge in most areas related to the diagnosis and treatment of pancreatic cancer in China, certain knowledge gaps exist, particularly among trainees and those from low level hospitals. Continuing medical education programs to improve these knowledge gaps should be implemented.

Misdiagnosis of a Drain-site Hernia Containing Fallopian Tube Fimbria on 18F-FDG PET/CT.

In a 55-year-old woman with sigmoid colon cancer, a subcutaneous mass in the left lower abdomen was incidentally found and gradually enlarged. For further diagnosis and staging, an 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scan was performed, which revealed a subcutaneous mass in the left lower abdomen with mild uptake of 18F-FDG, suggesting the possibility of metastasis. However, post-surgery and pathological confirmation, this mass was diagnosed as a drain-site hernia containing fallopian tube fimbria, which is extremely rare but should be considered in the differential diagnosis of subcutaneous mass in the lower abdomen.

Plasma thrombomodulin as a candidate biomarker for the diagnosis and prognosis of HBV-related acute-on-chronic liver failure.

Background and Aim: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with high short-term mortality. Effective biomarkers are required for its early diagnosis and prognosis. This study aimed to determine the diagnostic and prognostic value of thrombomodulin (TM) in patients with HBV-ACLF. Methods: The expression of TM during disease progression was evaluated through transcriptomics analysis. The plasma TM concentrations of 393 subjects with HBV-ACLF (n=213), acute-on-chronic hepatic dysfunction (ACHD, n=50), liver cirrhosis (LC, n=50) or chronic hepatitis B (CHB, n=50), and normal controls (NC, n=30) from a prospective multicenter cohort, were measured to verify the diagnostic and prognostic significance of plasma TM for HBV-ACLF patients by enzyme-linked immunosorbent assay (ELISA). Results: TM mRNA was highly expressed in the HBV-ACLF group compared with the ACHD group (AUROC=0.710). High expression of TM predicted poor prognosis for HBV-ACLF patients at 28/90 days (AUROCs=0.823/0.788). Functional analysis showed that TM was significantly associated with complement activation and the inflammatory signaling pathway. External validation confirmed its high diagnostic accuracy for HBV-ACLF patients (AUROC=0.796). Plasma TM concentrations were correlated with organ failure, including coagulation and kidney failure. Plasma TM concentrations showed a potential prognostic value for 28-day mortality rates (AUROC=0.702). Risk stratification specifically identified HBV-ACLF patients with a high risk of death as having a plasma TM concentration of ≥8.4 ng/mL. Conclusion: This study reveals that the plasma TM can be a candidate biomarker for early diagnosis and prognosis of HBV-ACLF, and might play a vital role in coagulation and inflammation.

Prediction of bowel necrosis by reduced bowel wall enhancement in closed-loop small bowel obstruction: Quantitative methods.

PURPOSE: To assess diagnostic performance and reproducibility of reduced bowel wall enhancement evaluated by quantitative methods using CT to identify bowel necrosis among closed-loop small bowel obstruction (CL-SBO) patients. METHODS: This retrospective single-center study included patients who diagnosed with CL-SBO caused by adhesion or internal hernia during January 2016 and May 2022. Patients were divided into necrotic group (n = 41) and non-necrotic group (n = 67) according to surgical exploration and postoperative pathology. Two doctors independently measured the attenuation of bowel wall and consensus was reached through panel discussion with a third gastrointestinal radiologist. Reduced bowel wall enhancement was assessed by four quantitative methods. Univariate analyses were used to evaluate the association between each method and bowel necrosis, and kappa/intraclass correlation coefficient values were used to assess interobserver agreement. Diagnostic performance parameters were calculated for each method. RESULTS: Reduced bowel wall enhancement in arterial phase (OR 8.98, P < 0.0001), reduced bowel wall enhancement in portal phase (OR 16.84, P < 0.001), adjusted reduced bowel wall enhancement in arterial phase (OR 29.48, P < 0.001), adjusted reduced bowel wall enhancement in portal phase (OR 145.69, P < 0.001) were significantly associated with bowel necrosis. Adjusted reduced bowel wall enhancement in portal phase had the best diagnostic performance (AUC: 0.92; Youden index: 0.84; specificity: 94.03 %) and interobserver agreement (kappa value of 0.59-0.73) to predict bowel necrosis. CONCLUSION: When assessing reduced bowel enhancement to predict bowel necrosis among CL-SBO patients, using unenhanced CT images and proximal dilated loop as standard references in portal phase is the most accurate quantitative method among those tested.

DLL4-Notch signalling in acute-on-chronic liver failure: State of the art and perspectives.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with multiple-organ failures and high short-term mortality. Acute insults to patients with chronic liver disease can lead to ACLF, among which, hepatitis B virus-related ACLF is the most common type of liver failure in the Asia-Pacific region. Currently, immune-metabolism disorders and systemic inflammation are proposed to be the main mechanisms of ACLF. The resulting cholestasis and intrahepatic microcirculatory dysfunction accelerate the development of ACLF. Treatments targeting immune regulation, metabolic balance, microcirculation maintenance and bile duct repair can alleviate inflammation and restore the tissue structure. An increasing number of studies have demonstrated that delta-like ligand 4 (DLL4), one of the Notch signalling ligands, plays a vital role in immune regulation, metabolism, angiogenesis, and biliary regeneration, which participate in liver pathological and physiological processes. The detailed mechanism of the DLL4-Notch signalling pathway in ACLF has rarely been investigated. Here, we review the evidence showing that DLL4-Notch signalling is involved in ACLF and analyse the potential role of DLL4 in the treatment of ACLF.

Circ_0006944 aggravates LPS-induced HK2 cell injury via modulating miR-205-5p/UBL4A pathway.

Circular RNAs (circRNAs) has been manifested to be involved in the development of human diseases, including sepsis-associated acute kidney injury (SA-AKI). However, the function and mechanism of circ_0006944 in SA-AKI has not been validated. Lipopolysaccharide (LPS) was utilised to induce AKI cell model. Levels of genes and proteins were monitored by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell counting kit 8 assay, EdU assay and flow cytometry were exploited to estimate cell proliferation and apoptosis. The concentrations of inflammation factors were measured via using ELISA assay. The levels of MDA and SOD were tested by the corresponding kits. The relationship between miR-205-5p and circ_0006944 or UBL4A was verified by dual-luciferase reporter assay and RIP assay. Circ_0006944 was overexpressed in SA-AKI patients, and interference of circ_0006944 restrained LPS-stimulated HK2 cell proliferation repression, apoptosis, inflammation and oxidative stress. Mechanistically, circ_0006944 could sponge miR-205-5p, and miR-205-5p interference counteracted circ_0006944 inhibition-mediated impact on the biological functions in LPS-induced HK2 cell. Additionally, UBL4A was targeted by miR-205-5p, and UBL4A overexpression also partially abolished the repressive impacts of miR-205-5p on LPS-triggered HK2 cell damage. Importantly, circ_0006944 sponged miR-205-5p to mediate the expression of UBL4A. Our outcomes identified that circ_0006944 exacerbated SA-AKI development via miR-205-5p/UBL4A axis, which might be a potential treatment and diagnosis biomarker for SA-AKI.

Preparation of a Transient Thermal Expansion Rock Cracking Agent by Deposition Method and Its Nonisothermal Kinetics Study with Isoconversional Procedure and DAEM.

Cracking agents are indispensable and important products for national energy exploitation and large-scale infrastructure construction. Transient thermal expansion rock cracking agent is a new cracking agent product with excellent performance that has just appeared in recent years. However, it is still prepared by mechanical ball milling, which is considered not the best choice among traditional methods for preparing energetic materials. In this paper, a transient thermal expansion rock splitting agent was prepared by the chemical deposition method using carbon black and calcium peroxide as raw materials. The TG/DTG results show that the mass loss of the sample can be divided into four stages with the increase of temperature. It is worth noting that the mass loss of the TG curve of the sample during the entire thermal decomposition process is 93.385%, and the instantaneous weight loss is 78.07% (ß = 15 °C/min). Kinetic analysis of the thermal decomposition process of the samples was performed using an isotransformation program and a distributed activation energy model (DAEM). The activation energy E α of the thermal decomposition of the sample was iteratively calculated. The results show that the a-E a curve of the sample can be divided into two stages. The pyrolysis kinetics of the first stage was successfully analyzed by the DAEM method and its thermal conversion behavior was predicted. The thermal decomposition behavior of the second stage was analyzed by a traditional kinetic analysis method.

Transcriptomics unveils immune metabolic disruption and a novel biomarker of mortality in patients with HBV-related acute-on-chronic liver failure.

Background & Aims: HBV-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome associated with high short-term mortality. This study aims to reveal the molecular basis and identify novel HBV-ACLF biomarkers. Methods: Seventy patients with HBV-ACLF and different short-term (28 days) outcomes underwent transcriptome sequencing using peripheral blood mononuclear cells. Candidate biomarkers were confirmed in two external cohorts using ELISA. Results: Cellular composition analysis with peripheral blood mononuclear cell transcriptomics showed that the proportions of monocytes, T cells and natural killer cells were significantly correlated with 28-day mortality. Significant metabolic dysregulation of carbohydrate, energy and amino acid metabolism was observed in ACLF non-survivors. V-set and immunoglobulin domain-containing 4 (VSIG4) was the most robust predictor of patient survival (adjusted p = 1.74 × 10-16; variable importance in the projection = 1.21; AUROC = 0.89) and was significantly correlated with pathways involved in the progression of ACLF, including inflammation, oxidative phosphorylation, tricarboxylic acid cycle and T-cell activation/differentiation. Plasma VSIG4 analysis externally validated its diagnostic value in ACLF (compared with chronic liver disease and healthy groups, AUROC = 0.983). The prognostic performance for 28-/90-day mortality (AUROCs = 0.769/0.767) was comparable to that of three commonly used scores (COSSH-ACLFs, 0.867/0.884; CLIF-C ACLFs, 0.840/0.835; MELD-Na, 0.710/0.737). Plasma VSIG4 level, as an independent predictor, could be used to improve the prognostic performance of clinical scores. Risk stratification based on VSIG4 expression levels (>122 µg/ml) identified patients with ACLF at a high risk of death. The generality of VSIG4 in other etiologies was validated. Conclusions: This study reveals that immune-metabolism disorder underlies poor ACLF outcomes. VSIG4 may be helpful as a diagnostic and prognostic biomarker in clinical practice. Impact and implications: Acute-on-chronic liver failure (ACLF) is a lethal clinical syndrome associated with high mortality. We found significant immune cell alterations and metabolic dysregulation that were linked to high mortality in patients with HBV-ACLF based on transcriptomics using peripheral blood mononuclear cells. We identified VSIG4 (V-set and immunoglobulin domain-containing 4) as a diagnostic and prognostic biomarker in ACLF, which could specifically identify patients with ACLF at a high risk of death.

Orthotopic Transplantation of Functional Bioengineered Livers in Rats.

Functional bioengineered livers (FBLs) are promising alternatives to orthotopic liver transplantation. However, orthotopic transplantation of FBLs has not yet been reported. This study aimed to perform the orthotopic transplantation of FBLs in rats subjected to complete hepatectomy. FBLs were developed using rat whole decellularized liver scaffolds (DLSs) with human umbilical vein endothelial cells implanted via the portal vein, and human bone marrow mesenchymal stem cells (hBMSCs) and mouse hepatocyte cell line implanted via the bile duct. FBLs were evaluated in terms of endothelial barrier function, biosynthesis, and metabolism and orthotopically transplanted into rats to determine the survival benefit. The FBLs with well-organized vascular structures exhibited endothelial barrier function, with reduced blood cell leakage. The implanted hBMSCs and hepatocyte cell line were well aligned in the parenchyma of the FBLs. The high levels of urea, albumin, and glycogen in the FBLs indicated biosynthesis and metabolism. Orthotopic transplantation of FBLs achieved a survival time of 81.38 ± 4.263 min in rats (n = 8) subjected to complete hepatectomy, whereas control animals (n = 4) died within 30 min (p < 0.001). After transplantation, CD90-positive hBMSCs and the albumin-positive hepatocyte cell line were scattered throughout the parenchyma, and blood cells were limited within the vascular lumen of the FBLs. In contrast, the parenchyma and vessels were filled with blood cells in the control grafts. Thus, orthotopic transplantation of whole DLS-based FBLs can effectively prolong the survival of rats subjected to complete hepatectomy. In summary, this work was the first to perform the orthotopic transplantation of FBLs, with limited survival benefits, which still has important value for the advancement of bioengineered livers.