Classification of variant portal vein anatomy based on three-dimensional CT: surgical implications.

PURPOSES: The purpose of this study was to develop a new and more comprehensive classification system for portal vein (PV) variations using three-dimensional visualization and evaluation (3DVE) and to discuss the prevalence rates and clinical implications of the variants. METHODS: The anatomies of PVs were tracked and analyzed by using three-dimensional visualization of CT images acquired between 2013 and 2022. Scans from 200 adults were evaluated and a total of 178 patients (N = 178) were included in the study. The new classification system, named BLB classification, was developed based on the level of the absent PV branch in each variant anatomy. RESULTS: Using the BLB classification system, PVs were divided into thirteen subtypes. Only 82.6-84.8% of the portal veins of the 178 patients were depicted in Atri's, Cheng's or Covey's classification, compared with 100% identified by the BLB classification. The BLB classification was validated against external data sets from previous studies, with 97.0-98.9% of patients classified by the BLB system. CONCLUSION: Variant PV anatomies are more commonly seen based on 3DVE than in previous reports. The BLB classification covers almost all portal vein variants and may be used for planning liver surgery.

Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway.

Purpose: Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present. Methods: We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways. Results: PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, ß-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, ß-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, ß-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1. Conclusion: The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP.

Alterations of Myocardial Mitochondrial Morphology and Function in a Canine Model of Premature Ventricular Contractions-Induced Cardiomyopathy.

AIMS: Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM. METHODS AND RESULTS: Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson's trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all p < 0.01 vs the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all p < 0.05). CONCLUSION: We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.

Effect of hydrothermal pH values on the morphology of special microspheres of lignin-based porous carbon and the mechanism of carbon dioxide adsorption.

The study reports the economic and sustainable syntheses of a lignin-based porous carbon (LPC) for CO2 capture application. The pH values of hydrothermal solution affected the polymerization and aromatization of spheroidization, with morphological changes from blocky to microsphere. In addition, the reliable mechanisms of CO2 adsorption were proposed by combining experiments with Gaussian16 simulations based on DFT. The electrostatic attraction of oxygen-containing functional groups and the diffusivity resistance of CO2 in the pores are the key factors for the CO2 adsorption. ​The carboxyl groups have the strongest electrostatic attraction to CO2. LPC-pH 1 has the highest carboxyl group content, possessing a CO2 adsorption capacity of up to 5.10 mmol/g at 0℃, 1 bar. Furthermore, CO2 diffusion resistance became a main factor as the adsorption temperature increases. The innovative combination of quantum chemical calculations and microscopic properties provides a viable pathway for an insight into the future control of lignin-based carbon formation.

Biomass-based controllable morphology of carbon microspheres with multi-layer hollow structure for superior performance in supercapacitors.

The electrochemical properties of corn starch (CS)-based hydrothermal carbon microsphere (CMS) electrode materials for supercapacitor are closely related to their structures. Herein, cetyltrimethyl ammonium bromide (CTAB) was used as a soft template to form the corn starch (CS)-based carbon microspheres with radial hollow structure in the inner and middle layers by hydrothermal and sol-gel method. Due to the introduction of multi-layer hollow structure of carbon microsphere, more micropores were produced during CO2 activation, which increased the specific surface area and improved the capacitance performance. Compared to commercial activated carbon, the four different morphologies of corn starch CMS had better electrochemical performances. Consequently, the proposed CO2-(CTAB)-CS-CS exhibits a high discharge specific capacitance of 242.5F/g at 1 A/g in three-electrode system with 6 M KOH electrolyte, better than commercial activated carbon with 208.5F/g. Moreover, excellent stability is achieved for CO2-(CTAB)-CS-CS with approximately 97.14 % retention of the initial specific capacitance value after 10,000 cycles at a current density of 2 A/g, while the commercial activated carbon has 86.96 % retention. This implies that the corn starch-based multilayer hollow CMS could be a promising electrode material for high-performance supercapacitors.

Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease.

BACKGROUND: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD). OBJECTIVES: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD. METHODS: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information. RESULTS: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT. CONCLUSIONS: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT.

Serinc2 deficiency exacerbates sepsis-induced cardiomyopathy by enhancing necroptosis and apoptosis.

In critical care medicine, sepsis is a potentially fatal syndrome characterized by multi-organ dysfunction and eventual failure. Sepsis-induced cardiomyopathy (SIC) is characterized by decreased venstricular contractility. Serine incorporator 2 (Serinc2) is a protein involved in phosphatidylserine biosynthesis and membrane incorporation. It may also be a protective factor in septic lung injury. However, it is unknown whether Serinc2 influences SIC onset or progression. In the present study, we found that Serinc2 was downregulated in the cardiomyocytes of cecal ligation and puncture (CLP)-induced SIC and in neonatal rat cardiomyocytes (NRCMs) exposed to lipopolysaccharides (LPS). Serinc2 knockout (KO) exacerbated sepsis-induced myocardial inflammation, necroptosis, apoptosis, myocardial damage, and contractility impairment. Furthermore, the lack of Serinc2 in cardiomyocytes aggravated LPS-induced cardiomyopathic inflammation, necroptosis, and apoptosis. An adenovirus overexpressing Serinc2 inhibited the inflammatory response and favored cardiomyocyte survival. A mechanistic analysis revealed that Serinc2 deficiency exacerbated LPS-induced cardiac dysfunction by inhibiting the protein kinase B (Akt)/glycogen synthase kinase 3 beta (GSK-3ß) signaling pathway that regulates necrotic complex formation and apoptotic pathways in cardiomyopathy. The findings of the present work demonstrated that Serinc2 plays an essential role in SIC and is, therefore, promising as a prophylactic and therapeutic target for this condition.

Gastrointestinal Fistulas in Necrotizing Pancreatitis Receiving a Step-Up Approach Incidence, Risk Factors, Outcomes and Treatment.

Purpose: Necrotizing pancreatitis (NP) complicated by gastrointestinal fistula is challenging and understudied. As the treatment of necrotizing pancreatitis changed to a step-up strategy, we attempted to evaluate the incidence, risk factors, clinical outcomes and treatment of gastrointestinal fistulas in patients receiving a step-up approach. Methods: Clinical data from 1274 patients with NP from 2014-2022 were retrospectively analyzed. Multivariable logistic regression analysis was conducted to identify risk factors and propensity score matching (PSM) to explore clinical outcomes in patients with gastrointestinal fistulas. Results: Gastrointestinal fistulas occurred in 8.01% (102/1274) of patients. Of these, 10 were gastric fistulas, 52 were duodenal fistulas, 14 were jejunal or ileal fistulas and 41 were colonic fistulas. Low albumin on admission (OR, 0.936), higher CTSI (OR, 1.143) and invasive intervention prior to diagnosis of gastrointestinal fistula (OR, 5.84) were independent risk factors for the occurrence of gastrointestinal fistula, and early enteral nutrition (OR, 0.191) was a protective factor. Patients who developed a gastrointestinal fistula were in a worse condition on admission and had a poorer clinical outcome (p<0.05). After PSM, both groups of patients had similar baseline information and clinical characteristics at admission. The development of gastrointestinal fistulas resulted in new-onset persistent organ failure, increased open surgery, prolonged parenteral nutrition and hospitalization, but not increased mortality. The majority of patients received only conservative treatment and minimally invasive interventions, with 7 patients (11.3%) receiving surgery for upper gastrointestinal fistulas and 11 patients (26.9%) for colonic fistulas. Conclusion: Gastrointestinal fistulas occurred in 8.01% of NP patients. Independent risk factors were low albumin, high CTSI and early intervention, while early enteral nutrition was a protective factor. After PSM, gastrointestinal fistulas resulted in an increased proportion of NP patients receiving open surgery and prolonged hospitalization. The majority of patients with gastrointestinal fistulas treated with step-up therapy could avoid surgery.

lncRNA Hnscr Regulates Lipid Metabolism by Mediating Adipocyte Lipolysis.

Obesity is a process of fat accumulation due to the imbalance between energy intake and consumption. Long noncoding RNA (lncRNA) Hnscr is crucial for metabolic regulation, but its roles in lipid metabolism during obesity are still unknown. In this article, we found that the expression of Hnscr gradually decreased in adipose tissues of diet-induced obese mice. Furthermore, the deletion of Hnscr promoted an increase in body weight and adipose tissue weight by upregulating the expression of lipogenesis genes and downregulating lipolysis genes in inguinal white adipose tissue (iWAT) and brown adipose tissue. In vitro knockdown of Hnscr in adipocytes resulted in reduced lipolysis of adipocytes. Overexpression of Hnscr by adenovirus or drug mimics showed the opposite. Mechanistically, Hnscr regulated adipose lipid metabolism by mediating the cyclic adenosine monophosphate/protein kinase A signaling pathway. This study identifies the initial characterization of Hnscr as a critical modifier that regulates lipid metabolism, suggesting that lncRNA Hnscr is a potential target for treating obesity.

Investigation of Polymer-Assisted CO2 Flooding to Enhance Oil Recovery in Low-Permeability Reservoirs.

CO2 flooding is a favorable technical means for the efficient development of low-permeability reservoirs, and it can also contribute to the realization of net-zero CO2 emissions. However, due to the unfavorable viscosity ratio and gravity overriding effect, CO2 channeling will inevitably occur, seriously affecting its storage and displacement effects. This paper conducts a systematic study on the application of polymer-assisted CO2 flooding in low-permeability reservoirs. Firstly, the polymer agent suitable for low-permeability reservoirs is optimized through the viscosity-increasing, rheological, and temperature- and salt-resistant properties of the solution. Then, the injectivity performance, resistance-increasing ability, and profile-improving effect of the polymer solution were evaluated through core experiments, and the optimum concentration was optimized. Finally, the enhanced oil recovery (EOR) effects of polymer-assisted and water-assisted CO2 flooding were compared. The results show that the temperature-resistant polymer surfactant (TRPS) has a certain viscosity-increasing performance, good temperature resistance performance, and can react with CO2 to increase the solution viscosity significantly. Meanwhile, TRPS has good injection performance and resistance-increasing effect. The resistance increasing factor (η and η') of TRPS-assisted CO2 flooding increases with increased permeability, the concentration of TRPS solution, and injection rounds. Considering η' and the profile improvement effect comprehensively, the application concentration of TRPS should be 1000 mg/L. The EOR effect of TRPS-assisted CO2 flooding is 8.21% higher than that of water-assisted CO2 flooding. The main effective period is in the first and second rounds, and the best injection round is three. The research content of this paper can provide data support for the field application of polymer-assisted CO2 flooding in low-permeability reservoirs.

Augmented temperature fluctuation aggravates muscular atrophy through the gut microbiota.

Large temperature difference is reported to be a risk factor for human health. However, little evidence has reported the effects of temperature fluctuation on sarcopenia, a senile disease characterized by loss of muscle mass and function. Here, we demonstrate that higher diurnal temperature range in humans has a positive correlation with the prevalence of sarcopenia. Fluctuated temperature exposure (10-25 °C) accelerates muscle atrophy and dampens exercise performance in mid-aged male mice. Interestingly, fluctuated temperature alters the microbiota composition with increased levels of Parabacteroides_distasonis, Duncaniella_dubosii and decreased levels of Candidatus_Amulumruptor, Roseburia, Eubacterium. Transplantation of fluctuated temperature-shaped microbiota replays the adverse effects on muscle function. Mechanically, we find that altered microbiota increases circulating aminoadipic acid, a lysine degradation product. Aminoadipic acid damages mitochondrial function through inhibiting mitophagy in vitro. And Eubacterium supplementation alleviates muscle atrophy and dysfunction induced by fluctuated temperature. Our results uncover the detrimental impact of fluctuated temperature on muscle function and provide a new clue for gut-muscle axis.

Identification of BRAF, CCND1, and MYC mutations in a patient with multiple primary malignant tumors: a case report and review of the literature.

BACKGROUND: Multiple primary malignant tumors (MPMTs), usually associated with worse malignant behavior and prognosis comparing to a single primary tumor, and have recently been found to have an increasing incidence globally. However, the pathogenesis of MPMTs remains to be clarified. Here, we report a unique case of the coexistence of malignant melanoma (MM), papillary thyroid carcinoma (PTC), and clear-cell renal cell carcinoma (ccRCC) along with our perceptions on its pathogenesis. CASE PRESENTATION: The case reported is of a 59-year-old male patient with unilateral nasal obstruction as well as a renal occupying lesion. Positron emission tomography-computed tomography (PET-CT) revealed a palpable mass of 32 × 30 mm on the posterior and left walls of the nasopharynx. In addition, an isodense nodule was observed in the right superior renal pole, approximately 25 mm in diameter, as well as a slightly hypodense shadow in the right leaf of the thyroid, approximately 13 mm in diameter. Nasal endoscopy and magnetic resonance imaging (MRI) confirmed the existence of a nasopharyngeal neoplasm. Afterward, biopsies of the nasopharyngeal neoplasm, thyroid gland and kidney were performed, and the patient was diagnosed with MM, PTC, and ccRCC according to the pathological and immunohistochemical results. Moreover, mutation of BRAFV600E was detected in bilateral thyroid tissues, and amplification of both CCND1 and MYC oncogenes were detected in the nasopharyngeal melanoma. After chemotherapy, the patient is now in good overall condition. CONCLUSIONS: This is the first reported case of a patient with the co-existence of MM, PTC and ccRCC undergoing chemotherapy with a favorable prognosis. Herein, we suggest that such a combination may be non-random, as for mutation of BRAFV600E might account for the co-occurrence of PTC and MM, while mutations of CCND1 and MYC cause the coexistence of MM and ccRCC. This finding may provide valuable guidance on the diagnosis and treatment of such disease, as well as the prevention of developing a second or third tumor for patients with a single primary.

Carnosic acid protects against doxorubicin-induced cardiotoxicity through enhancing the Nrf2/HO-1 pathway.

Doxorubicin (DOX) is used extensively in anticancer therapy, but its clinical application is limited due to its cardiotoxicity. Carnosic acid (CA) is a bioactive compound found in rosemary. It has been shown to reduce inflammation and reactive oxygen species. The purpose of this study was to investigate the potential cardioprotective effects of CA in response to DOX-induced cardiotoxicity. Here, C57BL/6 mice were administered an intraperitoneal injection of DOX (5 mg kg-1, ip) once a week for three consecutive weeks and treated with CA (40 mg kg-1, ig) for a three-week experimental period. For in vitro study, neonatal rat ventricular cardiomyocytes were used to validate the protective effects of CA (20 µM) in response to DOX-induced cardiotoxicity. CA markedly suppressed oxidative stress, apoptosis, and pyroptosis responses in the mouse hearts, eventually improving cardiac function. CA showed its antioxidant effect by activating nuclear factor erythroid 2-related factor (Nrf2) and its downstream heme oxygenase-1 (HO-1); CA also reduced oxidative stress by lowering the MDA and lipid ROS levels and raising the SOD and GSH-px levels. Additionally, CA treatment significantly increased Bcl-2 and inhibited Bax and Caspase-3 cleavage in DOX-induced cardiotoxicity. Moreover, CA suppressed the NOD-like receptor protein 3 (NLRP3) pathway to mitigate pyroptosis, as evidenced by lowered caspase1, interleukin-18, and interleukin-1ß. Consistently, the transfection of Nrf2-siRNA eliminated the protective effects of CA on cardiomyocytes. Altogether, our findings demonstrated that CA inhibited NLRP3 inflammasomes via activating the Nrf2-related cytoprotective system and protected the heart from oxidative damage, apoptosis, and pyroptosis, implying that the use of CA could be a potential therapeutic strategy in the prevention of DOX-associated myocardiopathy.

Timing of minimally invasive step-up intervention for symptomatic pancreatic necrotic fluid collections: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Minimally invasive step-up interventions are now the standard treatment recommended by current guidelines for symptomatic pancreatic necrotic fluid collections (PNFC); however, it is controversial whether delayed treatment after four weeks should always be used in patients who have failed conservative treatment and whose condition has not improved or worsened. The aim of this meta-analysis was to evaluate the impacts of the different timing of interventions on the clinical outcomes and prognosis of patients with symptomatic PNEC requiring intervention. METHODS: We searched Embase, Cochrane Library, PubMed and Web of Science databases to identify comparative studies assessing the safety and efficacy of early and postponed interventions in treating symptomatic PNFC. PRIMARY OUTCOME: Mortality. Secondary outcomes included some major complications, need for further minimally invasive necrosectomy and length of hospital stay. RESULTS: This meta-analysis included ten studies (2 RCTs and 8 observational studies) with a total of 1178 symptomatic PNFC patients who required intervention. Pooled results showed that there was no significant difference between early minimally invasive intervention and postponed intervention in mortality(OR 1.41, 95%CI 0.93-2.12;p = 0.10) and the incidence of early and late complications, but the early intervention group had a significantly increased need for further minimally invasive necrosectomy compared with postponed intervention (OR 2.04,95%CI 1.04-4.03; p = 0.04). There was no increase in length of stay for patients who received early intervention compared to postponed drainage (MD 3.53, 95% CI -4.20, 11.27; p = 0.37). CONCLUSION: Intervention before four weeks should be considered for patients with PNFC complicated by persistent organ failure or infections, who have been treated conservatively to the maximum extent possible.

Establishment of a genetic transformation system for Codonopsis pilosula callus.

Codonopsis pilosula, a traditional Chinese medicinal and edible plant, contains several bioactive components. However, the biosynthetic mechanism is unclear because of the difficulties associated with functional gene analysis. Therefore, it is important to establish an efficient genetic transformation system for gene function analysis. In this study, we established a highly efficient Agrobacterium-mediated callus genetic transformation system for C. pilosula using stems as explants. After being pre-cultured for 3 days, the explants were infected with Agrobacterium tumefaciens strain GV3101 harboring pCAMBIA1381-35S::GUS at an OD600 value of 0.3 for 15 min, followed by co-cultivation on MS induction medium for 1 day and delayed cultivation on medium supplemented with 250 mg l-1 cefotaxime sodium for 12 days. The transformed calli were selected on screening medium supplemented with 250 mg l-1 cefotaxime sodium and 2.0 mg l-1 hygromycin and further confirmed by PCR amplification of the GUS gene and histochemical GUS assay. Based on the optimal protocol, the induction and transformation efficiency of calli reached a maximum of 91.07%. The establishment of a genetic transformation system for C. pilosula calli lays the foundation for the functional analysis of genes related to bioactive components through genetic engineering technology.

Molecular selectivity in the water flooding heavy oil process from porous rocks.

Water flooding increases the recovery factor of crude oil and has been proven to be an economical and viable technique for enhancing the oil recovery of oil fields. The process has been systematically studied previously, in which the oil was considered a substance of constant composition. However, the molecular selectivity during the water flooding process has rarely been addressed, especially for heavy oil. Herein, the properties and compositional changes of heavy oil have been investigated in a simulated water flooding process at 60 °C and 85 °C. The crude oil and produced oils from different water flooding stages were characterized by gas chromatography, gas chromatography-mass spectrometry, and Fourier transform ion cyclotron resonance mass spectrometry. The results show that with the increase in temperature, the content of resins in the produced oils from different water flooding stages decreases, and the content of asphaltenes increases slightly. The viscosity of the produced oils increases at low temperatures and decreases at high temperatures as the water cut increases. The composition of the produced oils from different water flooding stages is different. Compared with the no water cut and high water cut stages, the changes in the produced oils of the low water cut stages are significant at different temperatures. The molecular selectivity of heteroatoms is higher than that of hydrocarbons in the water flooding process. Water flooding preferentially extracts small-molecule low-carbon hydrocarbons and small-molecule heteroatoms with low condensation degrees. The compositional differences between the produced oils were characterized by the double bond equivalent versus carbon number distribution of the S, N, and O-containing compounds. This study can not only provide some explanations on the viscosity-forming mechanism of heavy oil but also explains the watered-out phenomena in the development of oilfields.

Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy.

Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. However, low response rates and immune-related adverse events remain important limitations. Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy.

A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma.

Background: Immune checkpoint inhibitors have been successfully used in a variety of tumors, however, the efficacy of immune checkpoint blockade therapy for patients with glioma is limited. In this study, we tried to clarify gene expression signatures related to the prognosis of gliomas and construct a signature to predict the survival of patients with gliomas. Methods: Calcium-related differential expressed genes (DEGs) between gliomas and normal brain tissues were comprehensively analyzed in two independent databases. Univariate, multivariate Cox regression analysis and proportional hazards model were used to identify the prognostic of calcium-related risk score signature. The CIBERSORT algorithm and association analysis were carried out to evaluate the relationship between calcium-related signature and characteristic clinical features, tumor-infiltrating immune cell signatures as well as immune checkpoint molecules in glioma. A nomogram model was developed for predicting the overall survival for patients with gliomas. Results: We found the intersection of 415 DEGs between gliomas and normal brain tissues, and identified that an eighteen calcium-related gene panel was significantly enriched in these DEGs. A calcium-related signature derived risk score was developed to divide patients into high- and low-risk groups. Low levels of calcium-related gene expression in high-risk score cases were accompanied with worse outcomes of patients. Calcium-related risk scores were significantly associated with characteristic clinical features, immune infiltrating signatures of tumor microenvironment, and exhausted T cell markers including programmed cell death 1 (PD-1), lymphocyte activating 3 (LAG3), and T cell membrane protein 3 (TIM-3), which contribute to an adverse therapeutic effect of immunotherapy. Calcium-related signature risk score was considered as an independent prognostic parameter to predict the of overall survival of patients with gliomas in nomogram model. Conclusion: Our study demonstrated that calcium signaling pathway is highly associated with immunosuppression of gliomas and overall survival of patients. Targeting the calcium signaling pathway might be a new strategy to reverse the immunosuppressive microenvironment of gliomas and improve the efficacy of glioma immunotherapy.

Gadobutrol-Enhanced Cardiac Magnetic Resonance Imaging for Detection of Coronary Artery Disease.

BACKGROUND: Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies. OBJECTIVES: The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging. METHODS: Two international, single-vendor, phase 3 clinical trials of near identical design, "GadaCAD1" and "GadaCAD2," were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD. RESULTS: Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2. CONCLUSIONS: Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U.S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD.

The leaching mechanism of heavy metals (Ni, Cd, As) in a gasification slag during acidification.

The gasification slag by acidification can leach abundant heavy metals. In this paper, the fate of heavy metals (Ni, Cd, and As) in the raw slag and the acidified slag that treated by HAc and HCl was systematically investigated combined with Density Functional Theory (DFT) calculations. The results show that the content of Ni and Cd is reduced with an increasing acid concentration and meets the regulatory standards by 7 M HAc and 3 M HCl, respectively. Most of Ni combined with gehlenite is released as gehlenite dissolves during acid treatment, whereas Cd in combination with gehlenite and iron compounds is hard to release at lower HAc concentrations. Unexpectedly, the content of As tends to elevate at a higher concentration of HAc, which is due to the increase in the content of Ca by new Ca-compound formation and the higher binding capacity of Ca to As according to DFT results. Additionally, if the acid-base ratio reaches about 2.0 by acid treatment, there would be a maximum leaching rate. It is recommended that acid concentration should be controlled to avoid a secondary risk of heavy metals.