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Presents a study which examined the hepatotoxicity of alcohol-induced polar retinol metabolites (PRM) which involves apoptosis via loss of mitochondrial membrane potential. Identification and purification of polar retinol; Effect of PRM on cell viability and nuclear morphology; Impact of PRM on mitochondrial membrane.

Purpose: Few studies have focused on the management of inoperable ampullary carcinoma (AC), and patients with jaundice suffer from biliary stents replacement frequently. Iodine-125 (125I) brachytherapy has been used in the treatment of malignant tumors owing to its curative effect, minimal surgical trauma, and tolerable complications. The aim of the study was to investigate the role of 125I seed implantation in patients with unresectable ampullary carcinoma after relief of obstructive jaundice. Material and methods: A total of 44 patients with obstructive jaundice resulting from unresectable ampullary carcinoma from January 1, 2010 to October 31, 2020 were enrolled in the study. Eleven patients underwent implantation of 125I seeds under endoscopic ultrasound (EUS) after receiving biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) (treatment group), and 33 patients received a stent alone via ERCP (control group). Cox regression model was applied in this single-center retrospective comparison study. Results: The median maximum intervention interval for biliary obstruction was 381 days (interquartile range [IQR]: 204-419 days) in the treatment group and 175 days (IQR: 126-274 days) in the control group (p < 0.05). Stent occlusion rates at 90 and 180 days in the control group were 12.9% and 51.6%, respectively. No stent occlusion occurred in the treatment group. Patients in the treatment group obtained longer survival time (median, 26 vs. 13 months; p < 0.01) and prolonged duodenal obstruction (median, 20.5 vs. 11 months; p < 0.05). No brachytherapy-related grade 3 or 4 adverse events were observed. Conclusions: Longer intervention interval for biliary obstruction and survival as well as better stent patency and prolonged time to duodenal obstruction could be achieved by implanting 125I seeds combined with biliary stent in patients with unresectable ampullary cancer. [ABSTRACT FROM AUTHOR]

This paper describes the successful fabrication of 4H-SiC junction barrier Schottky (JBS) rectifiers with a linearly graded field limiting ring (LG-FLR). Linearly variable ring spacings for the FLR termination are applied to improve the blocking voltage by reducing the peak surface electric field at the edge termination region, which acts like a variable lateral doping profile resulting in a gradual field distribution. The experimental results demonstrate a breakdown voltage of 5 kV at the reverse leakage current density of 2 mA/cm2 (about 80% of the theoretical value). Detailed numerical simulations show that the proposed termination structure provides a uniform electric field profile compared to the conventional FLR termination, which is responsible for 45% improvement in the reverse blocking voltage despite a 3.7% longer total termination length. [ABSTRACT FROM AUTHOR]

Purpose: Biliary stents combined with percutaneous or endoscopic ultrasound-guided iodine-125 seed implantation into primary tumor have been confirmed to relieve malignant obstructive jaundice (MOJ), and prolong patient's stent patency. The aim of the study was to evaluate meaningful clinical application indications and better guide the application of this technology. Material and methods: Patients with MOJ, who have received bile duct stenting combined with iodine-125 (125I) seed implantation from October, 2010 to April, 2022, were retrospectively analyzed. Univariate and multivariate analyses were adopted to indicate factors of stent patency in MOJ and influencing factors of jaundice reduction at one week after surgery. Results: A total of 90 patients were enrolled into the study, including 52 males (57.8%) and 38 females (42.2%), with a mean age of 68.66 ±12.53 years. The median stent patency was 8 months. No serious adverse events occurred during follow-up. Multivariate analysis showed that Child-Pugh score (HR = 2.221, 95% CI: 1.081-4.562), biliary infection (HR = 1.901, 95% CI: 1.084-3.335), and pre-operative jaundice duration (HR = 1.977, 95% CI: 1.106-3.533) were the independent risk factors for stent patency. Child-Pugh B/C (OR = 4.647, 95% CI: 1.080-19.982) and bile duct infection (OR = 3.583, 95% CI: 1.095-11.725) were the independent risk factors for jaundice reduction at one week after surgery. Conclusions: MOJ patients treated with biliary stents combined with 125I seed implantation, and patients with better pre-operative liver function and no biliary tract infection, present not only longer biliary stent patency, but also better early jaundice reduction. [ABSTRACT FROM AUTHOR]

Piecing together the history of carbon (C) perturbation events throughout Earth’s history has provided key insights into how the Earth system responds to abrupt warming. Previous studies, however, focused on short-term warming events that were superimposed on longer-term greenhouse climate states. Here, we present an integrated proxy (C and uranium [U] isotopes and paleo CO2) and multicomponent modeling approach to investigate an abrupt C perturbation and global warming event (∼304 Ma) that occurred during a paleo-glacial state. We report pronounced negative C and U isotopic excursions coincident with a doubling of atmospheric CO2 partial pressure and a biodiversity nadir. The isotopic excursions can be linked to an injection of ∼9,000 Gt of organic matter–derived C over ∼300 kyr and to near 20% of areal extent of seafloor anoxia. Earth system modeling indicates that widespread anoxic conditions can be linked to enhanced thermocline stratification and increased nutrient fluxes during this global warming within an icehouse. [ABSTRACT FROM AUTHOR]

Cigarette smoking increases the risk for gastric cancer. Higher intakes or blood levels of lycopene are associated with a decreased risk of gastric cancer. However, the biological mechanisms by which lycopene may protect against gastric carcinogenesis are poorly understood. We evaluated the effects of lycopene supplementation on smoke-induced changes in protein levels of p53, p53 target genes (P21waf1/Cip1)1 and Bax-1), cell proliferation, and apoptosis in the gastric mucosa of ferrets. Ferrets were assigned to cigarette smoke exposure or to no exposure and to no, low-dose, or high-dose lycopene supplementation (2 × 3 factorial design) for 9 wk. Lycopene concentrations were significantly elevated in a dose-dependent manner in the gastric mucosa of ferrets supplemented with lycopene alone, but were markedly reduced in ferrets supplemented with lycopene and exposed to smoke. Although ferrets were given lycopene containing 95% all-transisomers, cis isomers were the predominant forms in the gastric mucosa. Total p53 and phosphorylated p53 levels were greater in ferrets exposed to smoke alone than in all other groups. Levels were ∼300 and 500% of the controls, respectively. However, smoke-elevated total p53 and phosphorylated p53 were markedly attenuated by both doses of lycopene. P21Waf1/Cip1, Bax-1, and cleaved caspase 3 were substantially decreased, whereas cyclin D1 and proliferating cellular nuclear antigen (PCNA) were increased in ferrets exposed to smoke alone. Lycopene prevented smoke-induced changes in p21Waf1/Cip1, Bax-1, cleaved caspase 3, cyllin D1, and PCNA in a dose-dependent fashion. These data indicate that lycopene may prevent smoke exposure-induced changes in p53, p53 phosphorylation, p53 target genes, cell proliferation, and apoptosis in the gastric mucosa of ferrets. [ABSTRACT FROM AUTHOR]

The article presents a study exploring felsic volcanism as a factor driving the end-Permian mass extinction. It mentions about the Siberian Traps large igneous province (STLIP) as commonly invoked as the primary driver of global environmental changes that triggered the end-Permian mass extinction (EPME).

Previous studies of the end-Permian mass extinction have established that it was geologically rapid, but condensed sections have made it difficult to establish the exact timing of the extinction relative to fluctuations in the ocean carbon cycle, oxygen levels, and temperature. Integrated high-precision U-Pb geochronology, biostratigraphy, and chemostratigraphy from a highly expanded section at Penglaitan, Guangxi, South China reveal a sudden end-Permian mass extinction that occurred at 251.939 ± 0.031 Ma, which is temporally coincident with the extinction recorded in Bed 25 of the Meishan section. Despite the significantly expanded nature of the section and extensive collecting of more than ten major marine fossil groups, there is no evidence of a decline of biotic diversity prior to the extinction interval and no Permiantype species survive the extinction at this location. Fossil range data suggest a nearly instantaneous extinction at the top of a narrow stratigraphic interval limited to 31 ± 31 k.y. The extinction was preceded by and/or accompanied by fluctuations in δ13Ccarb and δ13Corg of 2-3‰, and 3-5 °C in seawater temperature. A larger, more rapid seawater temperature rise of 6-8 °C immediately followed the extinction level at Penglaitan. The extinction is spatially associated with a thick unit of tuff and tuffaceous sandstones (Bed 141) indicating massive pyroclastic input. It is correlative with an ash layer (Bed 25) in the deeper water setting at Meishan, where some Permian-type organisms survived the extinction. Our study reveals that the survivability of Permian taxa after the major extinction pulse is variable and dependent upon the severity of environmental perturbation in different sedimentary settings. The sudden extinction may fit a scenario in which the onset of Siberian Traps and South China intensive volcanism ~420 k.y. before the extinction may have diminished the ecological resilience of communities and reduced ecological functions with little change in diversity. In such an environmentally stressed condition, a single environmental disturbance could trigger the sudden collapse of global ecosystems. [ABSTRACT FROM AUTHOR]

We report the petrology, whole-rock geochemistry, zircon LA-ICP-MS U-Pb chronology and zircon Hf isotopic data of Daxigou granitoids (western part of the Kuluketage Block, NW China) to evaluate their likely petrogenesis and tectonic setting. Zircons from syenogranite can be divided into two groups: 1) those that display oscillatory zoning and high Th/U ratios (average =1.38), implying their magmatic origin and 2) those that exhibit weak zoning and extremely high U and Pb contents but low Th/U ratios (average = 0.35), resembling zircons that experienced hydrothermal alteration. The zircon LA-ICP-MS U-Pb dating of the two groups of zircons yielded weighted mean ages of 1830 ±12 Ma (MSWD = 0.78) and 1798 ± 21 Ma (MSWD = 1.6) respectively. The Daxigou granitoids belong mostly to normal-K and sodium-rich metaluminous calc-alkaline type, systematically enriched in LREE and large ion lithophile elements (LILE, e.g., K, Ba and Rb), but significantly depleted in high field strength elements (HFSE, e.g., Ti, P, Nb, Ta and U). Their εHf(t) values and two-stage Hf model ages range from -7.16 to -5.03 and 2.69 to 2.76 Ga, respectively. Taken together, it is suggested that Daxigou granitoids are of I-type affinity and that they were derived by partial melting of a Neoarchaean TTG (e.g., Tuoge Complex) rocks in a continental-arc environment. These new data, combined with previous regional geological studies, demonstrate that a series of Palaeoproterozoic (c. 2.0-1.8 Ga) tectono-magmatic events occurred in Kuluketage Block during the assembly of Columbia. [ABSTRACT FROM AUTHOR]

Lycopene has been shown to be beneficial in protecting against high-fat diet-induced fatty liver. The recent demonstration that lycopene can be converted by carotene 9' 10'-oxygenase into a biologically active metabolite, ALA, led us to propose that the function of lycopene can be mediated by ALA. In the present study, male ob/ob mice were fed a liquid high-fat diet (60% energy from fat) with ALA supplementation (ALA group, 240 μg kg body weigh-1 . d-1) or without ALA supplementation as the control (C group) for 16 wk. Steatosis, SIRT1 expression and activity, genes involved in lipid metabolism, and ALA concentrations in the livers of mice were examined. The results showed that ALA supplementation resulted in a significant accumulation of ALA in the liver and markedly decreased the steatosis in the ALA group without altering body and liver weights compared to the C group. The mRNA and protein levels of hepatic SIRT1 were higher in the ALA group compared to the C group. SIRT1 activity also was higher in the ALA group, as indicated by the lower levels of acetylated forkhead box class O1 protein levels. In addition, the mRNA level of acetyl CoA carboxylase 1 was significantly lower in the ALA group than in the C group. Because SIRT1 plays a key role in lipid homeostasis, the present study suggests that the lycopene metabolite, ALA, protects against the development of steatosis in ob/ob mice by upregulating SIRT1 gene expression and activity. [ABSTRACT FROM AUTHOR]

The article discusses research into the chronology and possible causes of the mass extinction event at the end-Permian of the Phanerozoic era. Biodiversity data from sediments in South China was studied, including the mass spectrometric geochronological, isotopic, and biostratigraphic information from several sites. The results indicate that the mass extinction occurred in marine and terrestrial ecosystems 252.28 ± 0.08 million years ago over the course of 20,000 years or more, and point toward thermogenic carbon dioxide or methane emissions as possible causes of the extinction event.

Previous studies have shown that β-carotene 15,15′-mono- oxygenase catalyzes the cleavage of β-carotene at the central carbon 15,15′-double bond but cleaves lycopene with much lower activity. However, expressing the mouse carotene 9′,10′- monooxygenase (CMO2) in β-carotene/lycopene-synthesizing and -accumulating Escherichia coli strains leads to both a color shift and formation of apo-10′-carotenoids, suggesting the oxidative cleavage of both carotenoids at their 9′,10′-double bond. Here we provide information on the biochemical characterization of CMO2 of the ferret, a model for human carotenoid metabolism, in terms of the kinetic analysis of β-carotene/lycopene cleavage into β-apo-10′-carotenal/apo-10′-lycopenal in vitro and the formation of apo-10′-lycopenoids in ferrets in vivo. We demonstrate that the recombinant ferret CMO2 catalyzes the excentric cleavage of both all-trans-β-carotene and the 5-cis- and 13-cis-isomers of lycopene at the 9′,10′-double bond but not all-trans-lycopene. The cleavage activity of ferret CMO2 was higher toward lycopene cis-isomers as compared with β-carotene as substrate. Iron was an essential co-factor for the reaction. Furthermore, all-trans-lycopene supplementation in ferrets resulted in significant accumulation of cis-isomers of lycopene and the formation of apo-10′-lycopenol, as well as up-regulation of the CMO2 expression in lung tissues. In addition, in vitro incubation of apo-10′-lycopenal with the post-nuclear fraction of hepatic homogenates of ferrets resulted in the production of both apo-10′-lycopenoic acid and apo-10′-lycopenol, respectively, depending upon the presence of NAD+ or NADH as cofactors. Our finding of bioconversion of cis-isomers of lycopene into apo-10′-lycopenoids by CMO2 is significant because cis-isomers of lycopene are a predominant form of lycopene in mammalian tissues and apo-lycopenoids may have specific biological activities related to human health. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the diagnostic value and safety mainly regarding incidents of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic cystic lesions (PCLs)., Methods: A total of 150 consecutive patients with suspected PCLs were prospectively enrolled from April 2015 to November 2016. We finally enrolled 140 patients undergoing EUS-FNA. We compared the diagnostic accuracy of EUS-FNA and pathological diagnosis, which is regarded as the gold standard, for PCLs. Patients undergoing EUS-FNA at least 1 wk preoperatively were monitored for incidents and adverse events to evaluate its safety., Results: There were 88 (62.9%) women and 52 (37.1%) men among 140 patients, with a mean age of 50.1 (± 15.4) years. There were 67 cysts located in the head/uncinate of the pancreas and 67 in the body/tail, and 6 patients had at least 1 cyst in the pancreas. There were 75 patients undergoing surgery and 55 undergoing EUS-FNA with interval at least 1 wk before other operations, with 3 patients undergoing the procedure twice. The accuracy of EUS-FNA in differentiating benign and malignant lesions was 97.3% (73/75), while the accuracy of characterizing PCL subtype was 84.0% (63/75). The incident rate was 37.9% (22/58), whereas only 1 AE was observed in 58 cases., Conclusion: EUS-FNA is effective and safe for diagnosis of PCLs, however procedure-related incidents are common. Caution should be taken in patients undergoing EUS-FNA., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest in relation to this manuscript.

Aim: To evaluate the advantages of endoscopic ultrasound (EUS) in the assessment of detailed structures of pancreatic cystic neoplasms (PCNs) compared to computed tomography (CT) and magnetic resonance imaging (MRI)., Methods: All patients with indeterminate PCNs underwent CT, MRI, and EUS. The detailed information, including size, number, the presence of a papilla/nodule, the presence of a septum, and the morphology of the pancreatic duct of PCNs were compared among the three imaging modalities. The size of each PCN was determined using the largest diameter measured. A cyst consisting of several small cysts was referred to as a mother-daughter cyst. Disagreement among the three imaging modalities regarding the total number of mother cysts resulted in the assumption that the correct number was the one in which the majority of imaging modalities indicated., Results: A total of 52 females and 16 males were evaluated. The median size of the cysts was 42.5 mm by EUS, 42.0 mm by CT and 38.0 mm by MRI; there was no significant difference in size as assessed among the three imaging techniques. The diagnostic sensitivity and ability of EUS to classify PCNs were 98.5% (67/68) and 92.6% (63/68), respectively. These percentages were higher than those of CT (73.1%, P < 0.001; 17.1%, P < 0.001) and MRI (81.3%, P = 0.001; 20.3%, P < 0.001). EUS was also able to better assess the number of daughter cysts in mother cysts than CT ( P = 0.003); however, there was no significant difference between EUS and MRI in assessing mother-daughter cysts ( P = 0.254). The papilla/nodule detection rate by EUS was 35.3% (24/68), much higher than those by CT (5.8%, 3/52) and MRI (6.3%, 4/64). The detection rate of the septum by EUS was 60.3% (41/68), which was higher than those by CT (34.6%, 18/52) and by MRI (46.9%, 30/64); the difference between EUS and CT was significant ( P = 0.02). The rate of visualizing the pancreatic duct using EUS was 100%, whereas using CT and MRI it was less than 10%., Conclusion: EUS helps visualize the detailed structures of PCNs and has many advantages over CT and MRI. EUS is valuable in the diagnosis and assessment of PCNs., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest in relation to this manuscript.

Aim: To evaluate the change in spectrum of gastric polyps in the Chinese population in the past ten years., Methods: A total of 157902 consecutive patients undergoing esophagogastroduodenoscopy (EGD) from 2004 to 2013 in a tertiary hospital were retrospectively reviewed using an EGD database. Endoscopic records of 4043 patients diagnosed with gastric polyps were recalled for analysis. Data including demographics, information on polyps such as location, pathological diagnosis, reflux esophagitis and Helicobacter pylori infection were obtained. We focused on epithelial polyps, especially hyperplastic polyps, fundic gland polyps and adenomas, and histological classification of specimens from biopsy and endoscopic polypectomy was performed by professional pathologists, based on the updated guidelines. To explore the age distribution of gastric polyps over time, we divided patients with polyps into four groups: A (aged < 30 years), B (aged 30-44 years), C (aged 45-59 years) and D (aged > 60 years). Differences in localization, age, and sex distribution of gastric polyps were analyzed by statistical software., Results: A total of 157902 EGD procedures were performed in ten years at our digestive endoscopy center, of which 4043 cases were diagnosed with gastric polyps confirmed by pathology. There were 2574 (63%) female and 1469 (37%) male patients with an average age of 54.7 years. The overall prevalence of gastric polyps was 2.6% (4043/157902). Our database demonstrated a rising prevalence of gastric polyps over the decade, increasing from 1.0% (80/8025) to 4.70% (828/17787) between 2004 and 2013. There has been a change in the spectrum of gastric polyps with the frequencies of FGPs increasing from 19% (15/80) to 77% (638/828) and hyperplastic polyps decreasing from 65% (52/80) to 15% (123/828). Moreover, data on 1921 polyps in 828 patients diagnosed with gastric polyps in 2013 showed that FGP was the most common type in the current polyp spectrum, making up 81.3% (1562/1921). Location and age distribution of gastric polyps have also altered. The prevalence of polyps located in the antrum decreased from 37.5% (30/80) to 9.30% (77/828), with an increasing prevalence of polyps in the corpus, from 45% (36/80) to 64.25% (532/828). The constituent ratio of older patients (aged > 60 years) in the polyp population decreased from 62.5% (50/80) to 32.13% (266/828), while that of patients aged 45-60 years showed an increased trend., Conclusion: There was a shift change in the spectrum of gastric polyps in the Chinese population with altered location and age distribution in the past ten years.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a broadly-expressed immunoglobulin-like cell adhesion molecule with a wide range of biological functions to regulate cell signaling. The present article mainly focuses on the role of CEACAM1 as a therapeutic target in lung diseases and discusses the potential of therapeutic strategies targeting CEACAM1. The article overviews the structure and its sub-types, biological function, and potential roles of CEACAM1 in lung diseases. Alterations of CEACAM1 expression and CEACAM1-S/CEACAM1-L ratio promote the growth and metastasis of non-small cell lung carcinoma (NSCLC). Moreover, CEACAM1 mediates bacterial adherence and transcellular transcytosis, resulting in the suppression of immune cell activities and inflammatory responses, which may trigger acute exacerbation of chronic obstructive pulmonary disease (AECOPD). CEACAM1 plays a critical role in the development of NSCLC and AECOPD and can be a diagnostic biomarker and therapeutic target in lung diseases.