RESUMEN

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.

Asunto(s)

RESUMEN

To explore the effects of different aeration methods on the abundance of microorganisms and microorganism community structure in rice rhizosphere soil, two rice varieties, Miyang 46(MY) and Zhenshan 97B(ZS), were used with three aeration treatments:alternate wetting and drying(AWD), continuous flooding and aeration(CFA), and continuous flooding(CF). The diversity of bacterial and fungal communities in rice rhizosphere soil was analyzed using Illumina MiSeq high-throughput sequencing. Soil physical and chemical factors were also analyzed. The results showed that the dominant bacterial communities in rice rhizosphere soil were Chloroflexi, Actinobaciota, Acidobacteria, Proteobacteria, and Firmicutes, and the dominant fungal communities were Ascomycota and Basidiomycota in rice rhizosphere soil. At each growth stage, the relative abundance of Chloroflexi and Acidobacteria was higher in the AWD treatment than in the other treatments, and the relative abundance of Actinobaciota was higher in the CFA treatment than in the other treatments. The relative abundance of Firmicutes was lower in the AWD treatment than in the other treatments. Aeration methods affected the diversity and richness of rhizosphere microbial species. For example, the diversity of bacterial species was higher, and the richness of bacterial species was lower in the AWD treatment than that in the other treatments. The diversity and richness of fungal species were higher in the AWD and CFA treatments than those in the CF treatment. The physical and chemical properties of rhizosphere soil were also affected by aeration method. The soil redox potential(Eh) was the highest in AWD, followed by that in CFA and CF, and significant differences were observed among treatments. The NO3--N content was significantly higher, and the NH4+-N content was significantly lower in the AWD and CFA treatments than in the CF treatment in rhizosphere soil at all growth stages. Correlation analysis showed that the pH and Eh of rhizosphere soil were positively correlated with the diversity of bacterial species, negatively correlated with the richness of bacterial species, and positively correlated with the diversity and richness of fungal species. Redundancy analysis indicated that the relative abundance of Chloroflexi was positively correlated with the pH and NH4+-N content at each period, positively correlated with the Eh and NO3--N content at the tillering and heading stages, and negatively correlated with Eh and NO3--N content at the maturity stage. At each growth stage, the pH and Eh were positively correlated with the relative abundance of Acidobacteria, Proteobacteria, and Basidiomycota and negatively correlated with the relative abundance of Firmicutes and Ascomycota. During the entire growth period, the relative abundance of Ascomycota was negatively correlated with the NO3--N content and positively correlated with the NH4+-N content, and the opposite patterns were observed for the relative abundance of Basidiomycota. In summary, rhizosphere oxygenation enhanced the soil oxygen environment, altered soil physical and chemical properties, and affected microbial community diversity and richness to optimize microbial community structure.

Asunto(s)

RESUMEN

A [6 + 1] annulation reaction via cascade 1,6-hydride transfer/cyclization is reported to construct a polycyclic 3,4-fused azepinoindole skeleton. The newly designed 4-amino-indole-3-carbaldehyde is applied as a novel six-atom synthon, interacting with arylamines and malononitrile to achieve the [6 + 1] annulation. Notably, the reaction proceeds smoothly under redox-neutral and metal-free conditions, providing a wide range of azepinoindoles in up to 94% yields, with water as the only byproduct. Besides, the advantage of high step- and atom-economy further highlights the practicality of this methodology.

Asunto(s)

RESUMEN

An unprecedented hydride transfer-triggered cross-dehydrogenative coupling of two C(sp3)-H bonds to target nine-membered rings has been developed. Salient features of this methodology include atom and step economy and metal-free and redox-neutral conditions, with water as the byproduct and proceeding well even with decomposed aldehydes.

RESUMEN

BACKGROUND: Many genetic and metabolic diseases affect the liver, but diagnosis can be difficult because these diseases may have complex clinical manifestations and diverse clinical patterns. There is also incomplete clinical knowledge of these many different diseases and limitations of current testing methods. CASE SUMMARY: We report a 53-year-old female from a rural area in China who was hospitalized for lower limb edema, abdominal distension, cirrhosis, and hypothyroidism. We excluded the common causes of liver disease (drinking alcohol, using traditional Chinese medicines, hepatitis virus infection, autoimmunity, and hepatolenticular degeneration). When she was 23-years-old, she developed night-blindness that worsened to complete blindness, with no obvious cause. Her parents were first cousins, and both were alive. Analysis of the patient's family history indicated that all 5 siblings had night blindness and impaired vision; one sister was completely blind; and another sister had night-blindness complicated with cirrhosis and subclinical hypothyroidism. Entire exome sequencing showed that the patient, parents, and siblings all had mutations in the cytochrome P450 4V2 gene (CYP4V2). The CYP4V2 mutations of the parents and two sisters were heterozygous, and the others were homozygous. Two siblings also had heterozygous dual oxidase activator 2 (DUOXA2) mutations. CONCLUSION: Mutations in the CYP4V2 gene may affect lipid metabolism and lead to chronic liver injury, fibrosis, and cirrhosis.

RESUMEN

Background: Pancreatic acinar cells are susceptible to nuclear factor kappa B (NF-κB)-mediated inflammation and resulting cell necrosis during early acute pancreatitis. As adenosine monophosphate-activated protein kinase alpha (Ampkα)/sirtuin 1 (Sirt1) pathway activity attenuates NF-κB activity, we examined whether the Ampkα/Sirt1 axis affects the progression of acute pancreatitis and associated lung injury in vivo. Furthermore, we explored the role of the ciliary protein sperm flagellar 2 (Spef2, Kpl2) in regulating Ampkα/Sirt1 activity in vitro and in vivo. Methods: Pancreatic injury, oxidative stress, acinar cell necrosis and apoptosis, acinar levels of Ampkα/Sirt1/NF-κB signaling activity, NF-kB-mediated inflammatory markers, and markers of associated lung injury were measured in rat models of acute pancreatitis following pharmacological Ampkα activation with A769662 or self-complementary recombinant adeno-associated virus serotype 6 (scAAV6)-mediated Spef2 overexpression. Additional in vivo rescue studies involving Ampkα silencing and/or constitutively active (CA)-Sirt1 overexpression were performed in acute pancreatitis rats. In vitro immunoblotting and Ampkα activity assays were conducted in the pancreatic acinar cell line AR42J. Results: Pharmacological Ampkα activation or Spef2 overexpression reduced acute pancreatitis severity, oxidative stress, necrosis, apoptosis, NF-kB-mediated inflammatory markers, and the degree of associated lung injury. Spef2 overexpression in AR42J cells in vitro promoted AmpkαThr172 phosphorylation and Ampkα activity. In vivo rescue studies revealed that Spef2's suppressive effect on acute pancreatitis and associated lung injury is mediated via the Ampkα/Sirt1 axis. Conclusions: This study established the existence of a Spef2/Ampkα/Sirt1 axis in pancreatic acinar cells that is involved in the regulation of NF-κB-mediated acinar cell inflammation and resulting cell necrosis during acute pancreatitis.

RESUMEN

A cascade aldimine condensation/1,6-hydride transfer/Mannich-type cyclization of indole-derived phenylenediamine with aldehydes was developed for one-step construction of a polycyclic indole-3,4-fused skeleton. Aldehyde serves as a key to start the whole process, including 1,6-hydride transfer enabled δ-C(sp3)-H activation of the secondary amine. The challenges of construction of medium-sized rings are addressed via hydride transfer chemistry.

RESUMEN

Drug resistance in small cell lung cancer (SCLC) significantly affects the efficacy of chemotherapy treatment. However, due to the lack of tumor tissue samples, especially serial tumor samples during chemotherapy, the mechanism of chemotherapy resistance has not been fully studied. Circulating tumor DNA, which can be obtained in a noninvasive manner, can complement tumor sampling approaches for research in this field. We identified an SCLC patient with acquired drug resistance from 52 SCLC patients for whom follow-up data were available. By comparing somatic mutations in circulating tumor DNA before and after chemotherapy, for the first time, we found that the somatic mutation eIF3A R803K may be related to acquired chemotherapy resistance. Then, the association between the eIF3A R803K mutation and chemotherapy resistance was confirmed by samples from 254 lung cancer patients receiving chemotherapy. We found that the eIF3a R803K mutation weakened the proliferation ability of tumor cells but increased their resistance to chemotherapy. Further studies revealed that the eIF3A R803K mutation promotes cellular senescence. In addition, fisetin showed a synergistic effect with chemotherapy in eIF3A R803K mutant cells. These results suggest that the eIF3A R803K somatic mutation has the potential to predict chemotherapy resistance in SCLC. Moreover, the eIF3A R803K mutation promotes chemotherapy resistance by inducing senescence. Furthermore, a senolytic drug, fisetin, can reverse chemotherapy resistance mediated by the eIF3A R803K mutation.

Asunto(s)

RESUMEN

Numerous studies have investigated the relationship between income inequality and objective environmental pollution, but few focus on the nexus between income inequality and subjective environmental pollution (SEP). Using micro data from the Chinese General Society Survey (CGSS) in 2013 and official statistical data at the provincial level, this paper tests the impact of individual-level income inequality on subjective environmental pollution in China. The results show that individual-level income inequality has an inverted U-shape relationship with subjective environmental pollution, which indicates that increasing the income inequality at the individual level will first rise and then reduce their perceived subjective environmental pollution after reaching the peak. For about 84% of respondents, their subjective environmental pollution decreases with the increase of individual-level income inequality. Furthermore, the heterogeneity analyses show that the income inequality of urban residents and of the locals have an inverted U-shape effect on SEP, and the SEP of females and of individuals with positive environmental attitude are more sensitive to the effect of income inequality. Additionally, we find that subjective well-being plays a mediating role in the relation between income inequality and SEP. Individual income inequality decreases their self-reported well-being, and an increase in well-being has a negative effect on their subjectively perceived environmental quality. We also find non-television media exposures, such as newspaper, magazine, broadcasting, Internet, and mobile custom messages, will amplify the effect of individual-level income inequality on subjective environmental pollution.

Asunto(s)

RESUMEN

This paper examines a causal relationship between the opening of a city's subway system and its air quality by exploiting daily data on prefecture-level cities in China from 2000 to 2012. Using multi-period difference in differences (DID) method, we find that air quality can be significantly improved following a subway system opening. Robustness tests support the fundamental empirical results. Heterogeneity analysis shows that cities in the eastern and western regions and cities with higher GDP or cities with larger population experience greater and more significant reduction in pollution. We further find that the air pollution continues to decrease with the extension and prolonged operating period of a subway system. Mechanism analysis shows that the resulted air pollution index (API) reduction is due to the substitution effect of taxi.

Asunto(s)

RESUMEN

We combined a microporous polymer backbone with an organic redox-active dopant to construct a reversible electrode system based on the conversion-(de)incorporation behaviour of the dopant. The correspondence between the reversible conversion-(de)incorporation mechanism of the dopant and the electrochemical performance of the designed electrode system was established by electrochemical quartz crystal microbalance and in situ Fourier transform infrared spectroscopy.

RESUMEN

In this paper, the effects and mechanism of ciprofloxacin (CIP) degradation with peroxymonosulfate (PMS) catalyzed by solid waste red mud (RM) was firstly studied. The results indicated that RM has large specific surface area (10.96 m2·g-1) and complex pore structure, containing ferric, alumina and calcium oxide, which enhanced ciprofloxacin degradation by PMS effectively. Radical quenching experiments revealed that SO4-·and HO·were contributed to ciprofloxacin oxidation, and the reaction was mainly occurred on RM's surface. An increase in temperature could accelerate CIP degradation, and the corresponding reaction activation energy Ea was about 5.74 kJ·mol-1. Meanwhile, CIP degradation rate increased with PMS concentration and the optimal dosage of RM was 1.0 g·L-1. Eight degradation intermediates were identified using HPLC/MS/MS, and consequently, CIP was degraded mainly through two pathways; the piperazine groups were preferentially attacked by active free radicals. This study further indicated that RM is a cheap catalyst and can be potentially used in the treatment of antibiotic contaminated wastewater.

Asunto(s)

RESUMEN

OBJECTIVE To compare Mesh-plug, Lichtenstein, transabdominal preperitoneal (TAPP), and totally extraperitoneal (TEP) repairs in regards to operation time, seroma, infection, and recurrence of inguinal hernia repair. METHODS Relevant literature was searched in the Cochrane Library, Pubmed, and Embase. Furthermore, the analysis of randomized controlled studies (RCTs) was performed using methods recommended by the Cochrane Collaboration. The main outcomes including operation time, seroma, infection, and recurrence were evaluated. RESULTS A total of 38 RCTs with 3255 patients were included in the meta-analysis. In addition, the comparison between Mesh-plug, Lichtenstein, TAPP, and TEP showed the differences were not significant regarding operation time, seroma, infection, and recurrence. CONCLUSIONS Meta-analysis suggests that Mesh-plug, Lichtenstein, TAPP, and TEP are comparable in the outcomes of hernia repair, such as operation time, seroma, infection, and recurrence.

Asunto(s)

RESUMEN

The merger of photoredox-initiated enamine-imine tautomerization and nucleophilic addition processes to access ß-substituted pyrroles from pyrrolidines has been achieved. The significant advantage of this method is suppressing the Friedel-Crafts reaction, which usually occurs between N-aryl pyrrolidines and the highly electrophilic ketoesters. The good functional group tolerance, high atom economy, and high regioselectivity as well as easy handling conditions make it an appealing alternative to synthesize ß-substituted pyrroles.

RESUMEN

OBJECTIVE: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B 1 (AFB 1) in rats. METHODS: Forty Sprague Dawley rats were randomly divided into control, AFB 1, AFB 1 + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB 1 groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB 1 and AFB 1 + PCB2 groups were intraperitoneally injected with AFB 1 (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. RESULTS: AFB 1 significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB 1. CONCLUSION: Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB 1.

Asunto(s)

RESUMEN

PURPOSE: In order to clarify which variants of the MMR gene could provide current "healthy" members in affected families a more accurate risk assessment or predictive testing. PATIENTS AND METHODS: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing. RESULTS: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro. CONCLUSION: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study.

RESUMEN

Reported herein is the hydride transfer initiated redox-neutral cascade cyclizations of aurones, providing a variety of [6,5] spiro-heterocycles in satisfactory yields and good diastereoselectivities.

RESUMEN

An unprecedented cascade ß-functionalization/aromatization reaction of N-arylpyrrolidines was established. A series of ß-substituted arylpyrroles embedded with trifluoromethyl groups are provided directly from N-arylpyrrolidines. The deuterium-labeling experiments indicate that sequential double hydride transfer processes serve as the key steps in this transformation.

RESUMEN

Fluorinated alcohols have been widely used in the synthetic organic chemistry over the past decades. The unique properties such as the strong hydrogen-bonding donor ability and low nucleophilicity allow them to promote organic reactions in the absence of any catalyst. These approaches have distinct advantages in terms of operational simplicity, practicability and environmental friendliness. Reactions promoted by fluorinated alcohols, including nucleophilic substitution reactions, annulation reactions, electrophilic reactions, dearomatization reactions, functionalization of multiple bond, epoxidation reactions and miscellaneous reactions have been summarized in this account.

RESUMEN

BACKGROUND: MicroRNAs (miRNAs) were aberrantly regulated in cancers, showing their roles as novel classes of oncogenes and tumor suppressors. Hence, an integrated method was introduced in this study to explore miRNA targets for hepatocellular carcinoma (HCC). METHODS: The Borda count election algorithm was applied to combine a correlation method (Pearson's correlation coefficient, PCC), a causal inference method (IDA), and a regression method (Lasso) to generate an integrated method. Subsequently, to confirm the performance of the integrated method, the predicted miRNA targets results were compared with the confirmed database. Finally, pathway enrichment analysis was applied to evaluate the target genes in the top 1,000 miRNA-messenger RNA (mRNA) interactions. RESULTS: The method was confirmed to be an approach to predict miRNA targets. Moreover, 50 highly confident miRNA-mRNA interactions were obtained, including 6 miRNA targets with predicted times ≥10 (for instance, MEG3). The 860 target genes of the top 1,000 miRNA-mRNA interactions were enriched in 26 pathways, of which complement and coagulation cascades were most significant. CONCLUSIONS: The results might supply great insights for revealing the pathological mechanism underlying HCC and explore potential biomarkers for the diagnosis and treatment of this tumor. However, these biomarkers have not been confirmed, and the related validations should be performed in future studies.