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Opisthorchiosis is a parasitic liver disease found in mammals that is widespread throughout the world and causes systemic inflammation. Praziquantel remains the drug of choice for the treatment of opisthorchiosis, despite its many adverse effects. An anthelmintic effect is attributed to the main curcuminoid of Curcuma longa L. roots—curcumin (Cur)—along with many other therapeutic properties. To overcome the poor solubility of curcumin in water, a micellar complex of curcumin with the disodium salt of glycyrrhizic acid (Cur:Na2GA, molar ratio 1:1) was prepared via solid-phase mechanical processing. In vitro experiments revealed a noticeable immobilizing effect of curcumin and of Cur:Na2GA on mature and juvenile Opisthorchis felineus individuals. In vivo experiments showed that curcumin (50 mg/kg) had an anthelmintic effect after 30 days of administration to O.felineus-infected hamsters, but the effect was weaker than that of a single administration of praziquantel (400 mg/kg). Cur:Na2GA (50 mg/kg, 30 days), which contains less free curcumin, did not exert this action. The complex, just as free curcumin or better, activated the expression of bile acid synthesis genes (Cyp7A1, Fxr, and Rxra), which was suppressed by O.felineus infection and by praziquantel. Curcumin reduced the rate of inflammatory infiltration, whereas Cur:Na2GA reduced periductal fibrosis. Immunohistochemically, a decrease in liver inflammation markers was found, which is determined by calculating the numbers of tumor-necrosis-factor-positive cells during the curcumin treatment and of kynurenine-3-monooxygenase-positive cells during the Cur:Na2GA treatment. A biochemical blood test revealed a normalizing effect of Cur:Na2GA (comparable to that of curcumin) on lipid metabolism. We believe that the further development and investigation of therapeutics based on curcuminoids in relation Opisthorchis felineus and other trematode infections will be useful for clinical practice and veterinary medicine.

Vitrinite-like macerals (VLM) are ubiquitous in many pre-Devonian marine shales. The thermal maturity of these sediments, which are devoid of classical vitrinite, has been commonly evaluated using the reflectance of VLM as a substitute for vitrinite reflectance, but the molecular structure of VLM itself has seldom been examined. In this study, the immature VLM-rich Cambrian Alum shales from Scandinavia were selected and pyrolyzed at 300–550 ℃ to acquire a series of artificial pyrolysis samples with different ranks. The molecular structures and thermal evolution of VLM in natural and artificial shales were investigated by Raman spectroscopy. These Raman spectra and optical properties were compared with those of vitrinite, graptolite, and solid bitumen. The Raman spectra of VLM in natural samples of variable thermal maturities and immature samples altered by pyrolysis were generally comparable. The reduction of WD (D band position) and FWHM-G (full width at half maximum of the G band) and the increase of WG (G band position) and AD/AG (area ratio) in VLM spectra, which parallels the increasing thermal maturity of the samples, indicated an increased degree of aromatic conjugation and more structurally ordered carbon moieties. The increase in wavenumber difference between the D and G bands positions in Raman spectra (Raman band separation, RBS) demonstrated the gradual removal of oxygen-containing functional groups, the loss of aliphatic side chains, and the increased degree of aromatic ring condensation. In this way, with progressing maturity, the molecular structure of VLM gradually evolved from heterocyclic aromatic compounds and amorphous carbon structures at low maturity levels to structurally better-ordered, larger, aromatic fused-ring units characteristic of post-to-over mature samples. These molecular structures and their changes associated with thermal maturation were similar to those known from classical vitrinite. Aside from its reflectance, the thermal maturity of VLM-rich sediments could be assessed by Raman spectroscopy, notably through the RBS parameter of VLM Raman spectra, which closely correlated with VLM random reflectance throughout the reflectance interval between 0.5% and 5.5%.

Dysregulation of microRNAs (miRNAs) exerts key roles in the development of pancreatic cancer (PCa). miR-26a is reportedly a tumor suppressor in cancers. However, whether miR-26a modulates PCa progression is poorly understood. Here, we found that miR-26a was down-regulated in PCa. Overexpressed miR-26a suppressed PCa cell proliferation, colony formation, and tumor stem cell properties. Mechanically, the transcription factor E2F7 is a downstream target of miR-26a. miR-26a decreased E2F7 expression through binding to the 3’-untranslated region (UTR) of E2F7. Decreased miR-26a in PCa tissues was inversely correlated with E2F7. The inhibitory effects of miR-26a in PCa were reversed by E2F7 overexpression. Consistently, the knockout of E2F7 further significantly inhibited the growth of PCa cells combined with miR-26a overexpression. Further study revealed that E2F7 bound the promoter of vascular endothelial growth factor A (VEGFA), a key factor in angiogenesis, and transcriptionally activated the expression of VEGFA. miR-26a overexpression attenuated the effects of E2F7 on VEGFA promotion. Our results uncovered the novel function of miR-26a/E2F7/VEGFA in PCa, making miR-26a a possible target for PCa treatment.

The causes of the global mass extinction that occurred around the Permian–Triassic boundary have been widely studied through the geological record and in various locations. The results show that volcanic activity was a key factor in initiating the crisis during the Late Permian. Compared to other thermal events triggered by volcanic activity, pyrolysis of petroleum in Pre-Permian reservoirs has rarely been suggested as a significant source of the greenhouse gases that caused the mass extinction. In this study, geochemical analysis is carried out of a huge paleo-oil reservoir in the Yangtze Block (YB), South China. The detection of mineral inclusions and pyrobitumens is evidence of rapid pyrolysis of accumulated oil in the Ediacaran reservoir. New evidence from hydrothermal minerals and the presence of domain mesophase in the pyrobitumen suggest that the pyrolysis process occurred abruptly and that greenhouse gases were rapidly released through venting pipes. The dating of such a complex geological event in this old and deeply buried reservoir is inevitably difficult and potentially unreliable. However, cross-validation of the multiple evidence sources, including hydrothermal minerals and domain mesophase, indicates that the rapid oil pyrolysis must have been driven by a major thermal event. Reconstruction of burial and thermal histories suggests that the thermal event was most likely to have been triggered by the Emeishan Large Igneous Province (ELIP), which was in a period of significant volcanic activity during the Late Permian. Massive volumes of gases, including methane, carbon dioxide, and possibly hydrogen sulfide, were released, causing a significant increase in greenhouse gases that may have contributed to global warming and the resulting mass extinction during the Late Permian Crisis (LPC).

Background: A recent study disclosed that ferroptosis was an important myocyte death style in myocardial infarction (MI). However, the diagnostic value of ferroptosis regulators and correlated underlying mechanisms in acute myocardial infarction (AMI) remain unknown.Methods: Bioinformatical analyses were conducted to identify the candidate biomarkers for AMI, and the collected local samples were used to validate the findings via real-time quantitative PCR. Bioinformatical analysis and luciferase reporter assay were implemented to identify the transcriptional factor. Transient transfection and ferroptosis characteristic measurement, including glutathione peroxidase 4, malondialdehyde, iron, and glutathione, was performed to verify the ability of the candidate gene to regulate the ferroptosis of cardiomyocytes. A meta-analysis was conducted in multiple independent cohorts to clarify the diagnostic value.Results: A total of 121 ferroptosis regulators were extracted from previous studies, and aldo-keto reductase family 1 member C3 (AKR1C3) was significantly downregulated in the peripheral blood samples of AMI cases from the analysis of GSE48060 and GSE97320. HOXB4 served as a transcriptional activator for AKR1C3 and could suppress the ferroptosis of the H9C2 cells treated with erastin. Besides this, peripheral blood samples from 16 AMI patients and 16 patients without coronary atherosclerotic disease were collected, where AKR1C3 and HOXB4 both showed a high diagnostic ability. Furthermore, a nomogram including HOXB4 and AKR1C3 was established and successfully validated in six independent datasets. A clinical correlation analysis displayed that AKR1C3 and HOXB4 were correlated with smoking, CK, CK-MB, and N-terminal-pro-B-type natriuretic peptide.Conclusion: Taken together, this study demonstrates that AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of AMI.

The overmature Precambrian to Lower Paleozoic marine shales from China contain relatively simple organic matter (OM) composition, which is dominated by in-source solid bitumen (i.e., solid bitumen in the hydrocarbon source rocks). The thermal evolution behavior of the original OM and the determination of thermal maturity in the Precambrian to Cambrian marine shales have been challenging for decades. The vitrinite-like maceral (VLM) is widely present in these marine shales, and its origin is still unknown. To address these issues, the immature Proterozoic Xiamaling shales from China and the immature Cambrian Alum shales from Sweden, and a Chinese immature Carboniferous coal were heat-treated at temperature range of 300 ◦C to 550 ◦C. The carbonized residue of the artificially matured samples was examined for their morphological and reflectance variation, and the results were compared with data on the other overmature natural shales from China and Sweden. OM components are similar in the Xiamaling and Alum immature oil shales, consisting of filamentous algae, matrix bituminite, bituminite, VLM and liptodetrinite, and rare thucholites are present in the Xiamaling shales. The algal-derived OM decomposed gradually due to hydrocarbon generation at 300–350 ◦C. OM is mainly composed of the in-source solid bitumen in the artificially heated shales after 350 ◦C, similar to the overmature Precambrian to Cambrian natural shales, and the in-source solid bitumen gradually loses its mass with increasing thermal maturity. The in-source solid bitumen is derived from the thermal cracking of the retained oil or the direct conversion of algal-derived liptinite macerals (e.g., the bituminite) or their mixture. VLM in the Xiamaling oil shales can not be observed after 350 ◦C, but VLM is still present in the Alum oil shales. It can be inferred that there is a different source of VLM in these shales, and VLM in the Xiamaling oil shales contains more volatile material. The VLM in the Xiamaling shales may be biodegradation products of liptinites under anoxic environments. The origin of VLM in the Cambrian Alum shales requires further study to be verified, although it is certain that graptolites are not its sources. The reflectance of in-source solid bitumen (SBRo) increases with heat-treated temperature in both the Xiamaling shales and the Alum shales, but at different rates, which may be due to the difference of the original kerogen composition in these shales. VLM reflectance (VLMRo) and SBRo in sections perpendicular to bedding can be used to determine the maturation level of the Precambrian-Cambrian sediments. Their relation to equivalent vitrinite reflectance (EqVRo) can be expressed by the following equations: EqVRo = 1.07 × VLMRo – 0.18, EqVRo = 0.87 × SBRo + 0.25 (in the Precambrian sediments) and EqVRo = 1.15 × SBRo + 0.01 (in the Cambrian sediments). This work was supported by the National Natural Science Foundation of China (No. 41773031), the National Key Research and Development Program of China (No. 2017YFC0603102) and the Science Foundation of China University of Petroleum, Beijing (No. 2462020YXZZ021 and 2462021QNXZ001). One of the co-authors (V.S.) wishes to acknowledge the support of OP RDE, MEYS Czech Republic (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000728), which enabled him to contribute to this study

Background. At present, COVID-19 is sweeping the world, and all countries are actively responding. During the COVID-19 epidemic, the treatment of patients with acute myocardial infarction (AMI) may be affected. Methods. We reviewed data of patients with AMI from January 23 to April 23, 2020 (2020), and January 23 to April 23, 2019 (2019), who were admitted to two hospitals from Southern China. We collected clinical characteristics, comorbidities, treatment, prognosis, and key time segments to analyze. Results. The total number of patients that had been diagnosed with AMI in the two hospitals was 218 in 2020 and 260 in 2019. The number of AMI patients that were admitted to hospitals per day decreased in 2020. The percentage of patients with AMI who refused hospitalization in 2020 was significantly higher than that in 2019 (5.0% vs 1.5%, p = 0.028 ). There is no statistical difference in symptoms of the first medical contact (S2FMC) time between 2020 and 2019 ( p = 0.552 ). Door-to-balloon (D2B) time of ST-elevation myocardial infarction (STEMI) patients who were treated with a primary percutaneous coronary intervention (pPCI) in 2020 was 79 (63.75–105.25) mins, while D2B time in 2019 was 57.5 (41.5–76.5) mins, which was statistically different from the two groups. Conclusions. COVID-19 had an impact on the number of AMI patients who were admitted to hospitals and the time of treatment. During the COVID-19 epidemic, the number of AMI patients that were admitted to hospitals per day was decreased, while the percentage of AMI patients that refused therapy in these two hospitals increased, and the D2B time of STEMI patients was also delayed.

The Paleogene lacustrine mudstone is one of the most important sets of source rocks in Termit Basin, Niger. However, studies on the Paleogene source kitchen are scarce. In this study, the source rock types, spatial distribution and their hydrocarbon generative potential within the Paleogene Sokor-1 and LV formations are systematically evaluated. A total of two third-order sequences (SSQ1 and SSQ2, from the bottom to top) and six systems tracts were identified in the Sokor-1 Formation, while the LV Formation mainly comprises pure shale and is regarded as a compositive stratigraphic sequence with no need of subdivision. Six types of source rocks could be distinguished within the three depositional environments of the sequence stratigraphic framework: (1) deep lake mudstones and shale deposited in the lacustrine deep-water facies, (2) shallow lake mudstones and carbonaceous mudstones occurring in the shallow lake environment, and (3) deltaic-front mudstones and prodeltaic mudstones developed in the deltaic facies. Deep lake mudstones/shale, which mainly occurred in the SSQ1-TST (transgressive systems tract), SSQ2-TST and LV Formation, are considered organic-rich source rocks with oil-prone generative potential. The shallow lake mudstones and deltaic mudstones were predominantly distributed in the tectonic slope and marginal areas of the Agadem Block within the lowstand systems tract and high stand systems tract of the SSQ1 and SSQ2. Nevertheless, geochemical results indicated that the deltaic mudstones are good gas-prone source rocks but the shallow lake mudstones were classified as poor potential source rocks. The variance in organic matter accumulation and preservation conditions within different depositional facies and the fluctuation of relative lake level are the controlling factors for the occurrence and distribution of high-quality source rocks. The effective Paleogene source kitchen is limitedly distributed around the depocenter of the Dinga Depression within a small scale, and therefore exploration for oil and gas resources from the Paleogene source kitchen should focus on the eastern Dinga fault-step zone adjacent to the depocenter of the Dinga Depression.

Introduction: Ketamine, which is widely used in anesthesia, can induce cortical neurotoxicity in patients. This study aims to investigate the effects of long non-coding RNA (lncRNA) LINC00641 on the ketamine-induced neural injury. Materials and Methods: In this study, rat brain embryonic stem cell (ESC)-derived neurons were used as a cell model and Sprague–Dawley postnatal day 7 rat were used for experiments in vivo. Ketamine-induced aberrant expression levels of LINC00641, miR-497-5p and brain-derived neurotrophic factor (BDNF) were examined by qRT-PCR. The effects of LINC00641 and miR-497-5p on ketamine-induced neural injury were then examined by MTT assays and TUNEL analysis. In addition, the activity of ROS and csapase-3 was measured. The regulatory relationships between LINC00641 and miR-497-5p, miR-497-5p and BDNF were detected by dual-luciferase reporter assay, respectively. Results: Ketamine induced the apoptosis of ESC-derived neurons, accompanied with down-regulation of LINC00641 and BDNF, and up-regulation of miR-497-5p. LINC00641 overexpression enhanced the resistance to the apoptosis of ESC-derived neurons, while transfection of miR-497 -5p had opposite effects. Furthermore, LINC00641 could bind to miR-497-5p and reduce its expression, but indirectly increase the BDNF expression, which was considered as a protective factor in neural injury and activated TrkB/PI3K/Akt pathway. Conclusion: Collectively, LINC00641/miR-497-5p/BDNF axis was validated to be an important signaling pathway in modulating ketamine-induced neural injury.

Geochemical analysis of 64 oils sampled from an Ordovician carbonate reservoir in the Tuoputai region was undertaken to study the composition of molecular markers. All the oils have similar geochemical characteristics and belong to a single oil family. They are presumed to derive from the same source kitchen and have similar oil charging history. A histogram of homogenization temperatures (T h) of aqueous inclusions in reservoir rocks shows a bimodal distribution pattern, indicating that the Ordovician reservoir has been charged twice. Coupling the measured T h (°C) with the burial and geothermal histories reconstructed using 1D basin modeling, we relate the homogenization temperature to the relevant geological ages: i.e., 425–412 and 9–4 Ma, corresponding to the Middle to Late Silurian and the Miocene to Pliocene, respectively. The oil filling orientation and pathways are traced using molecular indicators related to alkyldibenzothiophenes and benzo[b]naphthothiophenes. The oil charging orientation is from south to north generally. It can be predicted that the Ordovician reservoirs were sourced from a kitchen located to the south of the Tuoputai region, most probably between the Awati and Manjiaer Depressions. Traps located in the southern side of the Tuoputai region, along the oil charging pathways, should therefore be preferred oil exploration targets.

During the working period of decay heat removal system, the flow rate of liquid sodium in wire-wrapped fuel assembly is very low, generally Re < 1000 . In the present study, both experimental methods and numerical simulation methods are applied. First, water experiment of 37-pin wire-wrapped rod bundle was carried out. Then, the numerical simulation study was carried out, the experimental data and the numerical simulation results were compared and analyzed, and a suitable turbulence model was selected to simulate the liquid sodium medium. Finally, numerical simulations under different boundary conditions were performed. Results indicate that except for the low Reynolds number k - ε turbulence model, other turbulence models have little difference with the experimental results. The results of realizable k - ε turbulence model are the most close to the experimental results. Compared with the friction factor obtained by using water medium and liquid sodium medium, the calculation results of water medium and sodium medium under the same condition are basically consistent, with the deviation within 1%. The reason is that the velocity of water is higher than sodium medium at the same Reynolds number, and the transverse disturbance caused by helical wire is larger.

Objectives To evaluate associations between different definitions of prediabetes and the risk of cardiovascular disease and all cause mortality. Design Meta-analysis of prospective cohort studies. Data sources Electronic databases (PubMed, Embase, and Google Scholar). Selection criteria Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes. Review methods Two authors independently reviewed and selected eligible studies, based on predetermined selection criteria. Prediabetes was defined as impaired fasting glucose according to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose 5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L during an oral glucose tolerance test), or raised haemoglobin A 1c (HbA 1c ) of 39-47 mmol/mol (5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals. Results 53 prospective cohort studies with 1 611 339 individuals were included for analysis. The median follow-up duration was 9.5 years. Compared with normoglycaemia, prediabetes (impaired glucose tolerance or impaired fasting glucose according to IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO, and impaired glucose tolerance, respectively), coronary heart disease (1.10, 1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA 1c to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality. Conclusions Prediabetes, defined as impaired glucose tolerance, impaired fasting glucose, or raised HbA 1c , was associated with an increased risk of cardiovascular disease. The health risk might be increased in people with a fasting glucose concentration as low as 5.6 mmol/L or HbA 1c of 39 mmol/mol.