Upregulation of ESPL1 is associated with poor prognostic outcomes in endometrial cancer.

BACKGROUND: Extra spindle pole bodies-like 1 (ESPL1) is known to play a crucial role in the segregation of sister chromatids during mitosis. Overexpression of ESPL1 is considered to have oncogenic effects in various human cancers. However, the specific biological function of ESPL1 in endometrial cancer (EC) remains unclear. METHODS: The TCGA and GEO databases were utilized to assess the expression of ESPL1 in EC. Immunohistochemistry was utilized to detect separase expression in EC samples. Kaplan-Meier survival analysis and Cox regression analysis were performed to evaluate the diagnostic and prognostic significance of ESPL1 in EC. Gene Set Enrichment Analysis (GSEA) was employed to explore the potential signaling pathway of ESPL1 in EC. Cell proliferation and colony formation ability were analyzed using CCK-8 and colony formation assay. RESULTS: Our analysis revealed that ESPL1 is significantly upregulated in EC, and its overexpression is associated with advanced clinical characteristics and unfavourable prognostic outcomes. Suppression of ESPL1 attenuated proliferation of EC cell line. CONCLUSION: The upregulation of ESPL1 is associated with advanced disease and poor prognosis in EC patients. These findings suggest that ESPL1 has the potential to serve as a diagnostic and prognostic biomarker in EC, highlighting its significance in the management of EC patients.

The expression of ESPL1 was higher in EC tissue than normal endometrial tissue.ESPL1 could be a potential prognostic marker for EC.

HOXA5 inhibits the proliferation and metastasis of cervical squamous cell carcinoma by suppressing the ß-catenin/Snail signaling.

HOXA5, as a transcription factor, plays an important role in a variety of malignant tumors. Nevertheless, its biological role in cervical squamous cell carcinoma (CSCC) is largely unknown. In our study, we aimed to explore the function of HOXA5 in CSCC and its molecular mechanism. Immunohistochemistry showed that HOXA5 expression was downregulated in human CSCC tissues and HOXA5 staining was negatively correlated with tumor size and histological grade of CSCC. Ectopic expression of HOXA5 inhibited proliferative and metastatic abilities of CSCC cells in vitro and in vivo. Furthermore, overexpression of HOXA5 inhibited the cell cycle by arresting the S/G2 phase by flow cytometry and that was related to the downregulation of Cyclin A. Further study showed that HOXA5 suppressed EMT by inhibiting the ß-catenin/Snail signaling resulting in reduced metastasis of CSCC cells. Altogether, our results suggested that HOXA5 inhibited the proliferation and metastasis via repression of the ß-catenin/Snail pathway, proposing the potential role of HOXA5 in the prevention and treatment of CSCC.

Total Flavonoids of Bidens pilosa Ameliorates Bone Destruction in Collagen-Induced Arthritis.

Rheumatoid arthritis is a chronic autoimmune disease characterized by the infiltration of synovial inflammatory cells and progressive joint destruction. Total flavonoids of Bidens pilosa have been used against inflammation in rheumatoid arthritis, but its role in bone destruction remains to be explored. The aim of this paper was to study whether total flavonoids of B. pilosa relieve the severity of collagen-induced arthritis in rats, particularly whether it regulates the production of proinflammatory cytokines and the receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin signaling pathway. In this research, a collagen-induced disease model was induced in adult rats by subcutaneous injection of collagen II. Total flavonoids of B. pilosa at different doses (40, 80, and 160 mg/kg/d) were administered intragastrically, while methotrexate (1 mg/kg/w) was injected intraperitoneally as a positive control. Paw swelling, arthritis score, and body weight were assessed and evaluated. The severity of joint damage was determined using X-ray and confirmed by histopathology. The expression levels of receptor activator of nuclear factor-κB ligand, osteoprotegerin, IL-1ß, IL-17, and TNF in the serum and tissue were assayed using ELISA and immunohistochemistry. We found that total flavonoids of B. pilosa attenuated collagen-induced arthritis at the macroscopic level, and total flavonoids of B. pilosa-treated rats showed reduced paw swelling, arthritis scores, and X-ray appearance of collagen-induced arthritis in addition to improved histopathological results. These findings were consistent with reduced serum and tissue receptor activator of nuclear factor-κB ligand, TNF, IL-1ß, and IL-17 levels but increased osteoprotegerin levels. Our data suggest that total flavonoids of B. pilosa attenuate collagen-induced arthritis by suppressing the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin pathway and the subsequent production of proinflammatory cytokines. In addition, total flavonoids of B. pilosa may be a promising therapeutic candidate for the management of rheumatoid arthritis.

Cytochrome P450 Epoxygenase 2J2 Protects Against Lung Ischemia/Reperfusion Injury by Activating the P13K/Akt/GSK-3-ß/NF-kB Signaling Pathway During Deep Hypothermic Low Flow in Mice.

BACKGROUND: Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids, which exert anti-inflammatory effects and alleviate oxidative stress in the cardiovascular system. Our previous work revealed that CYP2J2 is expressed in pulmonary artery endothelial cells. It was therefore hypothesized that CYP2J2 overexpression may prevent lung ischemia/reperfusion injury (LIRI) in 3-week-old C57BL/6 mice during deep hypothermic low flow (DHLF). This study aimed to establish whether CYP2J2 protects against LIRI and the mechanisms of CYP2J2 overexpression during DHLF in mice. The aim of this study was to explore the effects of DHLF on lung tissue in mice and to find out the regularity of this process, so as to provide theoretical data for lung tissue protection in children undergoing this process in clinic. METHODS: A 3-week-old C57BL/6 mouse model was used to mimic LIRI conditions during DHLF by clamping the left pulmonary artery and left main bronchus for 120 min, followed by reperfusion for 2 h. The body temperature of the mice was maintained between 18°C and 19°C to induce DHLF. RESULTS: During DHLF, lung ischemia/reperfusion increased the left lung wet/dry weight, the left lung weight/body weight ratio, the protein concentration in bronchoalveolar lavage fluid, and the concentration of proinflammatory mediators in the lungs, including interleukin (IL)-1, IL-8, and necrosis factor (NF)-α, and decreased the concentration of the anti-inflammatory mediator IL-10. Furthermore, activation of NF-κB p65 and degradation of IKBα were remarkably increased in lung tissues after ischemia/reperfusion. The CYP2J2 overexpression group showed the opposite results (P < 0.05), and p-Akt1 and p-GSK-3ß expression were significantly higher in the CYP2J2 overexpression group (P < 0.05). Moreover, the changes in IL-1, IL-8, tumor necrosis factor-α, IL-10, p-Akt1, p-GSK-3ß, NF-κB p65, and IKBα were reversed in the Akt1 gene heterozygous knockout group, and lung damage was significantly higher in the Akt1 gene heterozygous knockout group than in the CYP2J2 overexpression group. CYP2J2 overexpression can protect against LIRI, whereas Akt1 gene heterozygous knockout in mice can abolish this protective effect. CONCLUSIONS: CYP2J2 overexpression can protect against LIRI by activating the P13K/Akt/GSK-3ß/NF-kB signaling pathway during DHLF. Thus, changing CYP2J2 expression can be a novel strategy for the prevention and treatment of LIRI during DHLF.

A radical cyclization cascade of 2-alkynylbenzonitriles with sodium arylsulfinates.

A convenient radical cyclization cascade procedure for the construction of sulfonated indenones from 2-alkynylbenzonitriles and sodium arylsulfinates has been explored under mild reaction conditions. The present methodology offers a low-cost and operationally straightforward approach to synthesizing various sulfonated indenones in moderate to good yields by simple use of cheap sodium persulfate as an oxidant and environmentally benign water as a co-solvent.

Copper-catalyzed synthesis of 2-acylbenzo[b]thiophenes from 3-(2-iodophenyl)-1-arylpropan-1-ones and potassium sulfide under aerobic conditions.

A method was developed for the synthesis of 2-acylbenzo[b]thiophenes via a copper-catalyzed sulfuration of 3-(2-iodophenyl)-1-arylpropan-1-ones with K2S under aerobic conditions. Mechanistically, this procedure was proved to involve the formation of a dihydrobenzo[b]thiophene intermediate.

Emerging roles of circular RNAs in nasopharyngeal carcinoma: functions and implications.

Nasopharyngeal carcinoma (NPC) is a distinct malignancy primarily prevalent in Southern China and Southeast Asia. Circular RNAs (circRNAs), a class of non-coding RNAs, are evolutionarily conserved and exhibit remarkable stability. Their dysregulation has been observed in various cancers, including NPC. In this review, we investigate the pivotal role of circRNAs in NPC, focusing specifically on their involvement in tumor proliferation, apoptosis, metastasis, angiogenesis, stemness, metabolism, and the tumor microenvironment. We highlight the diagnostic and prognostic potential of circRNAs in NPC, emphasizing their utility as biomarkers for early detection, disease monitoring, and prediction of treatment outcomes. Additionally, we explore the therapeutic implications of circRNAs in NPC, highlighting their potential for targeted therapies.

Nurturing gut health: role of m6A RNA methylation in upholding the intestinal barrier.

The intestinal lumen acts as a critical interface connecting the external environment with the body's internal state. It's essential to prevent the passage of harmful antigens and bacteria while facilitating nutrient and water absorption. The intestinal barriers encompass microbial, mechanical, immunological, and chemical elements, working together to maintain intestinal balance. Numerous studies have associated m6A modification with intestinal homeostasis. This review comprehensively outlines potential mechanisms through which m6A modification could initiate, exacerbate, or sustain barrier damage from an intestinal perspective. The pivotal role of m6A modification in preserving intestinal equilibrium provides new insights, guiding the exploration of m6A modification as a target for optimizing preventive and therapeutic strategies for intestinal homeostasis.

Divergent [2 + n] Heteroannulation of ß-CF3-1,3-enynes with Alkyl Azides via Hydrogen Atom Transfer and Radical Substitution.

A copper-promoted divergent intermolecular [2 + n] heteroannulation of ß-CF3-1,3-enynes with alkyl azides via alkyl radical-driven HAT and radical substitution (C-C bond formation) to form four- to ten-membered saturated N-heterocycles is developed. This method enables the aryl-induced or kinetically controlled site selective functionalization of the remote C(sp3)-H bonds at positions 2, 3, 4, 5, 6, 7, or 8 toward the nitrogen atom through triplet nitrene formation, radical addition across the C═C bond, HAT and radical substitution cascades, and features a broad substrate scope, excellent site selectivity, and facile late-stage derivatization of bioactive molecules. Initial deuterium-labeling and control experiments shed light on the reaction mechanism via nitrene formation and HAT.

Formation processes of shallow ground ice in permafrost in the Northeastern Qinghai-Tibet Plateau: A stable isotope perspective.

The Source Area of the Yellow River (SAYR) on the Northeastern Qinghai-Tibet Plateau (QTP) stores substantial amounts of ground ice, which plays a significant role in understanding the hydrological processes and past permafrost evolution on the QTP. However, little is known about the initial sources and controlling factors of the ground ice in the SAYR. In this study, for the first time, ground ice stable isotope data (δ18O, δD, and d-excess) are presented, along with cryostratigraphic information for nine sites is integrated into three cryostratigraphic units (palsa, thermo-gully, and lake-affected sites) in the central SAYR. The ground ice in the nine sites exhibited diverse structures, ice contents, and stable isotopes due to differences in the initial water sources, ice formation mechanisms, soil types, and climate conditions. All of the freezing lines of ground ice are below those of the precipitation, streams, and lakes in most cases, suggesting the freezing of liquid water. The near-surface ground ice (NSGI) originated from precipitation, active layer water, and precipitation-fed springs. The NSGI was formed by quick freezing at the thermo-gully site (TG-1). In contrast, the formation of the NSGI at the palsa site (Palsa-1) experienced a slow segregation process during the permafrost aggradation. The NSGI was formed by quick freezing at the lake-affected sites under colder climate conditions. Conversely, the deep-layer ground ice (DLGI) at the lake-affected sites was fed by isotopically negative water and lake water occurred during a colder climate period. The DLGI at the TG-1 and Palsa-1 formed via similarly slow segregation of supra-permafrost water (mixed with precipitation), but had opposite water migration directions. The stable isotope compositions of the DLGI at the lake-affected sites became gradually more positive with decreasing distance from WL Lake, emphasizing the large influence of the lake changes on the growth of ice. The two end-member mixing model estimated that the contributions of paleo-lake water to the DLGI ranged from 9.8 % to 63.4 % towards the lake at the lake-affected sites, while the meltwater from past permafrost/ground ice contributed 36.6-90.2 % of the total input. A conceptual diagram of the δ18O trajectories of ground ice was constructed, the water migration patterns and ground ice formation processes between the palsa, thermo-gully, and lake-affected sites were clarified. The results of this study emphasize the influence of lake changes and past permafrost evolution on ground ice growth and improve our understanding of permafrost changes on the QTP.

Experimental Study on the Dynamic Tensile Characteristics of Coal Samples.

As coal mines continue deep mining, the frequency of coal and rock dynamic disasters has also gradually increased. In this paper, dynamic tensile strength deformation, energy evolution, and crack development under an impact test were studied on Brazilian coal samples, using a split Hopkinson pressure bar (SHPB) test device. A high-speed camera was adopted to capture the failure process of the coal specimens. The research results demonstrate that when the impact velocity is greater than 4.75 m/s, the dynamic tensile strength of the vertical bedding direction is higher than that of the parallel bedding direction of the coal samples. With the increase in the impact velocity, the dynamic strain and ultimate strain rate of two types of coal samples are increased, and the average value of the first and second dynamic deformation moduli of coal samples shows decreasing characteristics. As the incident energy increases, the sum of reflected and transmitted energy increases, and the absorbed energy also increases in the two types of coal samples. The two types of Brazilian disc coal samples mainly showed tensile and shear failure characteristics. The dynamic tensile deformation characteristics of the two types of coal specimens are less affected by the impact angles. However, the crack propagation of coal samples was mainly influenced by the impact angles. The test results can be used for the prediction of coal and rock outburst in deep underground coal excavation.

m6A modification on the fate of colorectal cancer: functions and mechanisms of cell proliferation and tumorigenesis.

N6-methyladenosine (m6A) is the most pervasive RNA modification in eukaryotic cells. The dynamic and reversible m6A modification of RNA plays a critical role in the occurrence and progression of tumors by regulating RNA metabolism, including translocation, mRNA stability or decay, pre-mRNA splicing, and lncRNA processing. Numerous studies have shown that m6A modification is involved in the development of various cancers. This review aims to summarize the significant role of m6A modification in the proliferation and tumorigenesis of CRC, as well as the potential of modulating m6A modification for tumor treatment. These findings may offer new therapeutic strategies for clinical implementation of m6A modification in CRC in the near future.

The function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.

Lactate is an end product of glycolysis. Owing to the lactate shuttle concept introduced in the early 1980s, increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a precursor of gluconeogenesis. Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells, resulting in diverse biological consequences including decreased lipolysis, immune regulation, and anti-inflammation wound healing, and enhanced exercise performance in association with the gut microbiome. Furthermore, increasing evidence reveals that lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones, which accounts for its key role in immune modulation and maintenance of homeostasis. Here, we summarize the function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.

Experimental Study on the Determinant Factors and Energy Criterion of Coal and Gas Outbursts.

A series of coal and gas outburst tests were conducted on coal seams in north China to determine the important order of gas pressure, in situ stress, and coal strength during coal and gas outbursts. And the typical phenomena of coal and gas outbursts were investigated. In addition, improved outburst energy equations were built to study the coal energy evolution process during coal and gas outbursts. The results show that the coal strength has the strongest influence on coal and gas outbursts, followed by the gas pressure and the in situ stress. The weights of pulverized coal with a particle size of less than 0.28 mm are consistent with the changing trend of the total weights of the pulverized coal particles in the corresponding outburst interval. Furthermore, the results suggest that the gas pressure monitored by the sensors close to the outburst hole begins to drop first and lasts for the longest time. The outburst coal presents obvious fracture and pulverization damage characteristics, and the pulverization damage features of the coal near the outburst hole are more obvious. In addition, the improved outburst energy equation was established, and the rationality of the improved outburst energy equation was verified by using the outburst orthogonal simulation experimental data and the on-site outburst accident cases. The results of this experiment have important guiding significance for preventing and controlling the occurrence of coal and gas outbursts and ensuring safe and efficient mining of coal mines.

Glaucoma in rural China (the Rural Epidemiology for Glaucoma in China (REG-China)): a national cross-sectional study.

OBJECTIVE: This study aimed to investigate the prevalence of glaucoma with associated factors in the rural populations of 10 provinces in China. DESIGN: A population-based cross-sectional study. METHODS: All participants aged 6 years or older from 10 provinces completed visual acuity testing, slit-lamp examination, ophthalmoscopy and non-contact tonometry. Glaucoma suspects underwent fundus photography, Goldmann applanation tonometry, visual field testing and gonioscopy. Glaucoma was determined according to the International Society of Geographical and Epidemiological Ophthalmology classification scheme. Associations of demographics and medical factors with glaucoma were assessed using multiple logistic regression models. RESULTS: From June 2017 to October 2018, 48 398 of 52 041 participants were included in the final analyses. The age-standardised prevalence of glaucoma was 1.7% (95% CI 1.55% to 1.78%) among the participants older than 6 years, which was 2.1% (95% CI 1.93% to 2.23%) in participants aged over 40 years. The constituent ratios of glaucoma were: 44.4% primary angle-closure glaucoma (PACG), 34.7% primary open-angle glaucoma, 2.6% congenital glaucoma and 18.3% other types of glaucoma. Increasing age, smoking, cerebral stroke, type 2 diabetes, higher education (college or more) and higher personal income were significant risk factors for PACG. The unilateral and bilateral blindness rates in the entire study population were 4.692% and 1.068%, respectively. A family history of glaucoma was a significant risk factor for the prevalence of glaucoma and blindness in at least one eye. CONCLUSIONS: Rural populations have a high prevalence of glaucoma, which should be included in chronic disease management programmes in China for long-term care.

Nickel-Catalyzed C-S Reductive Cross-Coupling of Alkyl Halides with Arylthiosilanes toward Alkyl Aryl Thioethers.

A nickel-catalyzed C-S reductive cross-coupling of alkyl halides with arylthiosilanes for producing alkyl aryl thioethers is developed. This reaction is initiated by umpolung transformations of arylthiosilanes followed by C-S reductive cross-coupling with alkyl halides to manage an electrophilic alkyl group onto the electrophilic sulfur atom and then construct a C(sp3)-S bond, and features exquisite chemoselectivity, excellent tolerance of diverse functional groups, and wide applications for late-stage modification of biologically relevant molecules.

Strength, Deformation, and Acoustic Emission Characteristics of Raw Coal and Briquette Coal Samples under a Triaxial Compression Experiment.

Raw coal and briquette coal samples have similar deformation characteristics. Addition of binders added into briquette coal could change the coal property. To better capture the characteristics of briquette coal samples in comparison to raw coal samples, we performed triaxial compression tests on raw coal and briquette coal samples with 7% content of four different binders. The experiment results show that the MD group (7% rosin) briquette coal has strong similarities to raw coal samples in strength, deformation, and acoustic emission (AE) features. We find that although four different binders (water, cement, rosin, and coal tar) are added into the briquette coal samples, the failure characteristic has high consistence. Briquette coal samples always show plastic failure, but raw coal always shows brittle failure. The increase in raw and briquette coal samples' peak strength is associated with an increase in the confining pressure constant. However, as the confining pressure constant increases, the raw and briquette coal samples' residual strength gradually reaches close to the peak strength. After the peak strength is reached, briquette coal samples always show a stronger strain and the raw coal samples have a weaker strain characteristic. AE events have a peak value on compression and elastic stage of briquette coal samples. AE events do not show a positive correlation relationship with the material strength of the briquette coal samples. Our study highlights that briquette coal samples with 7% rosin have more similarity in strength, deformation, and AE characteristic with raw coal samples.

Surgical site infection after delayed sternal closure in neonates with congenital heart disease: retrospective case-control study.

OBJECTIVES: To determine the prevalence of surgical site infections (SSIs) in neonatal congenital heart disease patients undergoing delayed sternal closure (DSC) and evaluate risk factors for SSI. METHODS: Hospital records of 483 consecutive neonates who underwent surgical intervention between January 2013 and December 2017 were reviewed, and perioperative variables were recorded. RESULTS: We found that the prevalence of SSI was 87.5% when the body weight was less than 1500 g. When the operative age was between seven and 14 days, the probability of no SSI is about 93.9%. When the duration of the aortic cross-clamp was more than 60 min, the prevalence of SSI was 91.2%. The prevalence without SSI was 96.6% when the duration of DSC was less than 24 h. However, when the duration of DSC was more than 120 h, the prevalence of SSI was 88.9% (p = 0.000). CONCLUSIONS: With the prolongation of aortic clamping duration, the probability of occurrence of SSI increased in neonatal CHD with DSC. The age at operation and body weight are closely related to the occurrence of SSI in neonatal CHD patients with DSC.

Rhodium-Catalyzed Reductive trans-Alkylacylation of Internal Alkynes via a Formal Carborhodation/C-H Carbonylation Cascade.

A rhodium-catalyzed reductive annulation cascade reaction that consists of a formal anti-carborhodation of a C≡C bond and an aromatic C-H carbonylation cascade for producing cyclopenta[de]quinoline-2,5(1H,3H)-diones is described. This method uses the Mn reductant to reductively regenerate the active rhodium species, hence obviating the need for prefunctionalization, and represents a new route to the carbonylation of aromatic C-H bonds with alkynes leading to aryl vinyl ketone frameworks.

Experimental Study on Briquette Coal Sample Mechanics and Acoustic Emission Characteristics under Different Binder Ratios.

In order to find briquette coal with mechanical characteristics close to those of raw coal samples, we conducted triaxial compression experiments on raw coal and briquette coal samples with different proportions of cement contents. The mechanical characteristics and acoustic emission (AE) characteristics of the coal samples in the triaxial compression process were analyzed in detail. The test results show that the evolution of deformation and strength characteristics of the briquette coal and raw coal samples follow certain common laws. The confining pressure can improve the mechanical properties of both types of coal samples: as the confining pressure continues to increases according to the set values, the elastic modulus, peak strain, and peak strength of both samples show an increasing linear trend. When the value of the confining pressure setting was the same, the compressive strength of the raw coal samples exceeded that of briquette ones, but the deformation and shape variations of the latter exceeded those of the former. When performing triaxial compression experiments on both kinds of coal samples, the AE amplitude and counts showed a close correlation with the stress evolution curves. When the confining pressure was set to 5 MPa, 20% cement content briquette coal was seen to be the closest to raw coal samples regarding mechanical and AE characteristics.