[Value of SOX1 and PAX1 Gene Methylation Detection in Secondary Triage of High-Grade Cervical Lesions].

Objective To evaluate the value of SOX1 and PAX1 gene methylation detection in the secondary triage of high-grade cervical lesions.Methods Exfoliated cervical cells were collected from 122 patients tested positive for human papilloma virus (HPV) and subjected to thin-prep cytologic test (TCT) and SOX1/PAX1 gene methylation tests.Results The HPV test combined with TCT showed the sensitivity of 95.24% and the specificity of 23.75% for detecting cervical intraepithelial neoplasia (CIN) grade 2 and above (CIN2+).After the addition of the SOX1/PAX1 gene methylation detection in secondary triage,the sensitivity for detecting CIN2+ was 83.33%,which had no statistically significant difference from the sensitivity of TCT combined with HPV test (P=0.078).However,the specificity reached 77.50%,which was significantly higher than that of HPV test combined with TCT (P<0.001).The SOX1/PAX1 gene methylation level in the CIN2+ group was higher than those in the normal cervical tissue and the CIN1 group(P<0.001).The cut-off values of SOX1 and PAX1 gene methylation for CIN2+ detection were -11.81 and -11.98,respectively.Conclusion Adding the detection of SOX1/PAX1 gene methylation in secondary triage significantly improves the efficiency and accuracy of CIN2+ detection.

Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma.

BACKGROUND: Conventional five-port laparoscopic surgery, the current standard treatment for colorectal carcinoma (CRC), has many disadvantages. AIM: To assess the influence of reduced-port laparoscopic surgery (RPLS) on perioperative indicators, postoperative recovery, and serum inflammation indexes in patients with CRC. METHODS: The study included 115 patients with CRC admitted between December 2019 and May 2023, 52 of whom underwent conventional five-port laparoscopic surgery (control group) and 63 of whom underwent RPLS (research group). Comparative analyses were performed on the following dimensions: Perioperative indicators [operation time (OT), incision length, intraoperative blood loss (IBL), and rate of conversion to laparotomy], postoperative recovery (first postoperative exhaust, bowel movement and oral food intake, and bowel sound recovery time), serum inflammation indexes [high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], postoperative complications (anastomotic leakage, incisional infection, bleeding, ileus), and therapeutic efficacy. RESULTS: The two groups had comparable OTs and IBL volumes. However, the research group had a smaller incision length; lower rates of conversion to laparotomy and postoperative total complication; and shorter time of first postoperative exhaust, bowel movement, oral food intake, and bowel sound recovery; all of which were significant. Furthermore, hs-CRP, IL-6, and TNF-α levels in the research group were significantly lower than the baseline and those of the control group, and the total effective rate was higher. CONCLUSION: RPLS exhibited significant therapeutic efficacy in CRC, resulting in a shorter incision length and a lower conversion rate to laparotomy, while also promoting postoperative recovery, effectively inhibiting the inflammatory response, and reducing the risk of postoperative complications.

Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.

BACKGROUND: Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear. METHODS: We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection. RESULTS: Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts. CONCLUSIONS: Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.

Aptamer-Functionalized Magnetic Ti3C2 Based Nanoplatform for Simultaneous Enrichment and Detection of Exosomes.

Exosomes are nanovesicles secreted by cells, which play a crucial role in various pathological processes. Exosomes have shown great promise as tumor biomarkers because of the abundant secretion during tumor formation. The development of a convenient, efficient, and cost-effective method for simultaneously enriching and detecting exosomes is of utmost importance for both basic research and clinical applications. In this study, an aptamer-functionalized magnetic Ti3C2 composite material (Fe3O4@Ti3C2@PEI@DSP@aptamer@FAM-ssDNA) is prepared for the simultaneous enrichment and detection of exosomes. CD63 aptamers are utilized to recognize and capture the exosomes, followed by magnetic separation. The exosomes are then released by cleaving the disulfide bonds of DSP. Compared to traditional methods, Fe3O4@Ti3C2@PEI@DSP@aptamer@FAM-ssDNA exhibited superior efficiency in enriching exosomes while preserving their structural and functional integrity. Detection of exosome concentration is achieved through the fluorescence quenching of Ti3C2 and the competitive binding between the exosomes and a fluorescently labeled probe. This method exhibited a low detection limit of 4.21 × 104 particles mL-1, a number that is comparable to the state-of-the-art method in the detection of exosomes. The present study demonstrates a method of simultaneous enrichment and detection of exosomes with a high sensitivity, accuracy, specificity, and cost-effectiveness providing significant potential for clinical research and diagnosis.

Advances in Natural Polymers: Extraction Methods and Applications.

Biomass-based alternatives for the manufacturing of bioplastic materials are important aspects of a more sustainable future; their physicochemical properties need to be able to compete with the existing market to establish them as a viable alternative [...].

ZO-1 and IL-1RAP Phosphorylation: Potential Role in Mediated Brain-Gut Axis Dysregulation in Irritable Bowel Syndrome-like Stressed Mice.

Background and Objectives: Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder often exacerbated by stress, influencing the brain-gut axis (BGA). BGA dysregulation, disrupted intestinal barrier function, altered visceral sensitivity and immune imbalance defects underlying IBS pathogenesis have been emphasized in recent investigations. Phosphoproteomics reveals unique phosphorylation details resulting from environmental stress. Here, we employ phosphoproteomics to explore the molecular mechanisms underlying IBS-like symptoms, mainly focusing on the role of ZO-1 and IL-1RAP phosphorylation. Materials and Methods: Morris water maze (MWM) was used to evaluate memory function for single prolonged stress (SPS). To assess visceral hypersensitivity of IBS-like symptoms, use the Abdominal withdrawal reflex (AWR). Colonic bead expulsion and defecation were used to determine fecal characteristics of the IBS-like symptoms. Then, we applied a phosphoproteomic approach to BGA research to discover the molecular mechanisms underlying the process of visceral hypersensitivity in IBS-like mice following SPS. ZO-1, p-S179-ZO1, IL-1RAP, p-S566-IL-1RAP and GFAP levels in BGA were measured by western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay to validate phosphorylation quantification. Fluorescein isothiocyanate-dextran 4000 and electron-microscopy were performed to observe the structure and function of the intestinal epithelial barrier. Results: The SPS group showed changes in learning and memory ability. SPS exposure affects visceral hypersensitivity, increased fecal water content, and significant diarrheal symptoms. Phosphoproteomic analysis displayed that p-S179-ZO1 and p-S566-IL-1RAP were significantly differentially expressed following SPS. In addition, p-S179-ZO1 was reduced in mice's DRG, colon, small intestine, spinal and hippocampus and intestinal epithelial permeability was increased. GFAP, IL-1ß and p-S566-IL-1RAP were also increased at the same levels in the BGA. And IL-1ß showed no significant difference was observed in serum. Our findings reveal substantial alterations in ZO-1 and IL-1RAP phosphorylation, correlating with increased epithelial permeability and immune imbalance. Conclusions: Overall, decreased p-S179-ZO1 and increased p-S566-IL-1RAP on the BGA result in changes to tight junction structure, compromising the structure and function of the intestinal epithelial barrier and exacerbating immune imbalance in IBS-like stressed mice.

Therapeutic effect of San Bi Tang combined with glucosamine sulfate capsules in cold-dampness-type knee osteoarthritis.

BACKGROUND: Cold-dampness-type knee osteoarthritis is a common middle-aged and elderly disease, but its pathogenesis is not fully understood, and its clinical treatment has limitations. Glucosamine sulfate capsules are commonly used for treating arthritis, and San Bi Tang is a classic formula of traditional Chinese medicine (TCM) that has the effects of warming yang, dispelling dampness, relaxing muscles, and activating collaterals. This research hypothesized that the combination of modified San Bi Tang and glucosamine sulfate capsules could enhance the clinical efficacy of treating cold-dampness-type knee osteoarthritis through complementary effects. AIM: To analyze the clinical efficacy of San Bi Tang combined with glucosamine sulfate capsules when treating cold-dampness-type knee osteoarthritis. METHODS: A total of 110 patients with cold-dampness-type knee osteoarthritis were selected as research subjects and randomly divided into a control group and an experimental group of 55 cases each. The control group received only treatment with glucosamine sulfate capsules, while the experimental group received additional treatment with modified San Bi Tang for a duration of 5 wk. The patients' knee joint functions, liver and kidney function indicators, adverse reactions, and vital signs were evaluated and analyzed using SPSS 26.0 software. RESULTS: Before treatment, the two groups' genders, ages, and scores were not significantly different, indicating comparability. Both groups' scores improved after treatment, which could indicate pain and knee joint function improvement, but the test group had better scores. The TCM-specific symptoms and the clinical efficacy of the treatment in the test group were higher. Before and after treatment, there were no abnormalities in the patients' liver and kidney function indicators. CONCLUSION: The combination of modified San Bi Tang and glucosamine sulfate capsules is superior to treatment with sulfated glucosamine alone and has high safety.

Enhancing the performance of electrorheological fluids by structure design.

By incorporating polar fibers into the design of electrorheological (ER) fluids, a 130% performance improvement can be achieved with the addition of only 0.8 vol% of polar long fibers. We quantitatively analyzed the impact of relatively long fibers on improving ER performance by measuring the yield stress, shear stress, and current density after adding fibers. Both optical microscopy and transmission electron microscopy were used to observe and analyze the interaction between ER particles and polar fibers. The results indicate that, under the influence of an electric field, the fibers transform the one-dimensional chain-like structure into a two-dimensional mesh structure, greatly improving the ER performance. The transformation of structure induced by the polar fibers in the ER fluids amplifies the ER effect. However, the inclusion of non-polar fibers does not contribute to this enhancement, as a point of comparison. Moreover, to ensure the universality of this method, we used two different types of ER fluids in experiments. The utilization of this method offers a straightforward, environmentally friendly, and highly effective approach. Furthermore, this study provides a novel technical solution aimed at enhancing the performance of ER fluids.

[Characteristics and Source Analysis of Volatile Organic Compounds in Typical Ozone Pollution Processes During Summer in Jinan, China].

Based on a typical ozone （O3） pollution process in Jinan City from June 16 to 26, 2021, the variation characteristics of O3 and its precursor volatile organic compounds （VOCs） during different pollution periods （clean period （CP）, pollution rise period （PRP）, heavy pollution period （HPP）, and pollution decline period （PDP）） in the urban area were analyzed. Both positive matrix factorization （PMF） and an observation-based model （OBM） were used to identify the main sources of VOCs, O3 production mechanisms, and sensitive species. The results showed that the average value of ρ（O3-8h） during the HPP period in the urban area was （246.67±11.24） µg·m-3, and ρ（O3-1h） had a peak value of 300 µg·m-3. The volume fractions of VOCs and NO2 concentration were affected by the decrease in planetary boundary layer and wind speed, which were 76.99%-145.36% and 127.78%-141.18% higher than those in the other three periods, respectively, and were the main reasons for the aggravation of O3 pollution. Alkanes, oxygenated volatile organic compounds （OVOCs）, and halogenated hydrocarbons accounted for 43.81%, 20.98%, and 17.43% of VOCs in urban areas, respectively. All of them showed significant growth during the HPP period, with acetone, propane, and ethane being the top three species by volume in each stage and isopentane showing the highest growth during the HPP period. Alkene, alkanes, and aromatic hydrocarbons accounted for 40.19%, 28.06%, and 21.92% of the ozone generation potential （OFP）. 1-butene, toluene, isopentane, and isoprene were the species with higher OFP. Isoprene had the highest OFP during the PRP phase, and 1-butene had the highest OFP during the HPP phase. The volume fraction of isopentane significantly increased OFP. The correlation coefficient between VOCs and CO preliminarily indicated that motor vehicle exhaust and oil and gas volatilization were the main sources of VOCs during the HPP period. Further use of PMF revealed that solvent use sources, combustion sources, motor vehicle exhaust+oil and gas volatilization sources, industrial emission sources, and plant sources were important sources of VOCs in urban areas. The contribution of motor vehicle exhaust+oil and gas volatilization sources in the HPP period to VOCs was 3.09-14.72 times higher than that in other periods. The contribution of solvent use sources to VOCs was approximately 2.50 times higher than that in the CP and PRP periods. The main sources of VOCs volume fraction increase were motor vehicle exhaust, oil and gas volatilization sources, and solvent use sources. Potential sources and concentration weight analysis found that VOCs were also affected by the transmission of VOCs to Binzhou and Dongying in the northeast direction. The OBM results indicated that the main pathway of O3 formation in urban areas was the reaction of peroxide hydroxyl radicals （HO2·ï¼‰ and methyl peroxide radicals （CH3O2·ï¼‰ with NO, and the net ozone generation rate during the HPP phase [P（O3）net] was 24×10-9 h-1. Based on the sensitivity experiment results, the alkene components of 1-butene, propylene, cis-2-butene, and ethylene were the dominant species for O3 production.

Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Thianthrenium Salts with Arylalkynes.

Alkynones are valuable compounds with applications in various areas. In this work, we developed an efficient carbonylation procedure for the carbonylative cross-coupling of aryl thianthrenium salts with aromatic alkynes. Various useful alkynones were produced in moderate to excellent yields under mild conditions. Notably, among the various tolerated functional groups, the bromide group can be maintained, which is ready for further coupling reactions.

Inactivated cGAS-STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2- Breast Cancer.

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

A TrmBL2-like transcription factor mediates the growth phase-dependent expression of halolysin SptA in a concentration-dependent manner in Natrinema gari J7-2.

To cope with a high-salinity environment, haloarchaea generally employ the twin-arginine translocation (Tat) pathway to transport secretory proteins across the cytoplasm membrane in a folded state, including Tat-dependent extracellular subtilases (halolysins) capable of autocatalytic activation. Some halolysins, such as SptA of Natrinema gari J7-2, are produced at late-log phase to prevent premature enzyme activation and proteolytic damage of cellular proteins in haloarchaea; however, the regulation mechanism for growth phase-dependent expression of halolysins remains largely unknown. In this study, a DNA-protein pull-down assay was performed to identify the proteins binding to the 5'-flanking sequence of sptA encoding halolysin SptA in strain J7-2, revealing a TrmBL2-like transcription factor (NgTrmBL2). The ΔtrmBL2 mutant of strain J7-2 showed a sharp decrease in the production of SptA, suggesting that NgTrmBL2 positively regulates sptA expression. The purified recombinant NgTrmBL2 mainly existed as a dimer although monomeric and higher-order oligomeric forms were detected by native-PAGE analysis. The results of electrophoretic mobility shift assays (EMSAs) showed that NgTrmBL2 binds to the 5'-flanking sequence of sptA in a non-specific and concentration-dependent manner and exhibits an increased DNA-binding affinity with the increase in KCl concentration. Moreover, we found that a distal cis-regulatory element embedded in the neighboring upstream gene negatively regulates trmBL2 expression and thus participates in the growth phase-dependent biosynthesis of halolysin SptA. IMPORTANCE: Extracellular proteases play important roles in nutrient metabolism, processing of functional proteins, and antagonism of haloarchaea, but no transcription factor involved in regulating the expression of haloaechaeal extracellular protease has been reported yet. Here we report that a TrmBL2-like transcription factor (NgTrmBL2) mediates the growth phase-dependent expression of an extracellular protease, halolysin SptA, of haloarchaeon Natrinema gari J7-2. In contrast to its hyperthermophilic archaeal homologs, which are generally considered to be global transcription repressors, NgTrmBL2 functions as a positive regulator for sptA expression. This study provides new clues about the transcriptional regulation mechanism of extracellular protease in haloarchaea and the functional diversity of archaeal TrmBL2.

High-sensitivity C-reactive protein predicts microalbuminuria progression in essential hypertensive patients: a 3-year follow-up study.

OBJECTIVES: To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period. METHODS AND RESULTS: Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ±â€…9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group (n = 99, 50%), the group with baseline hs-CRP above the median (n = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) (P = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes (ß = 0.342; P < 0.001), baseline SBP (ß = 0.148; P = 0.02), and baseline log-transformed hs-CRP (ß = 0.169; P = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) (ß = -0.163; P = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes (ß = 0.359; P < 0.001) and baseline log-transformed hs-CRP (ß = 0.190; P = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups. CONCLUSION: Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria.

Beneficial effects of Dendrobium officinale National Herbal Drink on metabolic immune crosstalk via regulate SCFAs-Th17/Treg.

BACKGROUND: The development of gut-liver axis metabolic immune crosstalk is intimately associated with intestinal barrier disorder, intestinal SCFAs-Th17/Treg immunological imbalance, and disorders of the gut microbiota. Prior research has discovered that Dendrobium officinale National Herbal Drink (NHD), a traditional Chinese medicine drink with enhanced immunity, may enhance the immunological response in animals with impaired immune systems brought on by cyclophosphamide by repairing intestinal barrier function and controlling turbulence in the gut microbiota. However, whether NHD can further improve the gut-liver axis metabolic immune crosstalk and its related mechanisms need to be systematically studied. OBJECTIVES: The purpose of this study is to clarify the function and mechanism of NHD in enhancing the gut-liver axis metabolic immunological crosstalk brought on by excessive alcohol intake. METHODS: In this work, we set up a mouse model to analyze the metabolic and immunological crosstalk involving the gut-liver axis across 7 weeks of continuous, excessive drinking. At the same time, high and low doses (20,10 ml/kg) of NHD were given by gavage. The effect of NHD on improving the metabolism of gut-liver axis was evaluated by blood lipid, liver lipid deposition, liver function and intestinal pathophysiology. By measuring serum immunological indices, intestinal barrier, and intestinal immune barrier, the impact of NHD on enhancing immune and intestinal barrier function was assessed. Furthermore, immunohistochemistry, immunofluorescence, 16S rRNA, Western blot, q-PCR and other methods were used to detect gut microbiota, SCFAs-GPR41/43 pathway, intestinal Th17/Treg immune cells and PPAR-α-NPC1L1/SREBP1 pathway to elucidate the mechanism by which NHD enhances the gut-liver axis' metabolic immune crosstalk. RESULTS: Our study demonstrated that NHD has the potential to improve the pathophysiological damage caused by gut-liver axis in model mice. NHD also ameliorated the disorder of lipid metabolism. In addition, it regulated the levels of peripheral blood T cell immunity and serum immune factors. And NHD can restore intestinal mechanical and immune barrier damage. NHD has a favorable impact on the quantity of beneficial bacteria, including uncultured_bacterium_g__norank_f__muribaculacea and uncultured_bacterium_g__Turicibacter. Additionally, it raised the model mice's levels of SCFAs (n-butyric acid, isovaleric acid, etc.). This resulted in the promotion of intestinal GPR41/43-ERK1/2 expression and the reshaping of intestinal CD4+T cell Th17/Treg homeostasis. As a consequence, colon IL-22 and IL-10 levels increased, while colon IL-17A levels decreased. Lastly, NHD raised the amount of intestinal IAP/LPS, regulated the development of PPAR-α-NPC1L1/SREBP1 pathway in gut-liver axis, and improve lipid metabolism disorder. CONCLUSIONS: Our study found that NHD can improve the gut-liver axis metabolic immune crosstalk in model mice caused by excessive drinking. The mechanism might be connected to how NHD controls gut microbiota disorders in model mice, the activation of intestinal SCFAs-GPR41/43 pathway, the remodeling of Th17/Treg immune homeostasis of intestinal CD4+T cells, the improvement of IAP/LPS abnormality, and further mediating the PPAR-α-NPC1L1/SREBP1 pathway of lipid metabolism in gut-liver axis.

Unusual cadinane-involved sesquiterpenoid dimers from Artemisia annua and their antihepatoma effect.

Artemisia annua L. ("Qinghao" in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 µg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins A‒N (1-14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1-9 represented the first examples of sesquiterpenoid dimers formed via the C-3‒C-3' single bond of two 5(4 â†’ 3)-abeo-cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1, 4, 6, and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values ranging from 30.5 to 57.2 µM.

Rab11b promotes M1-like macrophage polarization by restraining autophagic degradation of NLRP3 in alcohol-associated liver disease.

Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases. Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease (ALD) pathology. Rab GTPases play critical roles in regulating vesicular transport. In this study we investigated the role of Rab11b in ALD, aiming to identify effective therapeutic targets. Here, we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice. Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation, injury and steatosis. We found that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages (BMDM) cells. Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization. Rab11b overexpression in BMDMs inhibited autophagic flux, leading to the suppression of LC3B-mediated NLRP3 degradation. We conclude that impaired Rab11b could alleviate alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.

Highly Efficient Electrosynthesis of Urea from CO2 and Nitrate by a Metal-Organic Framework with Dual Active Sites.

Electrosynthesis of urea from CO2 and NO3- is a sustainable alternative to energy-intensive industrial processes. The challenge hindering the progress is the development of advanced electrocatalysts that yield urea with both high Faradaic efficiency (FE) and current density. In this work, we designed a new two-dimensional MOF, namely PcNi-Fe-O, constructed by nickel-phthalocyanine (NiPc) ligands and square-planar FeO4 nodes. PcNi-Fe-O exhibits remarkable performance to yield urea at a high current density of 10.1 mA cm-2 with a high FE(urea) of 54.1% in a neutral aqueous solution, surpassing those of most reported electrocatalysts. No obvious performance degradation was observed over 20 hours of continuous operation at the current density of 10.1 mA cm-2. By expanding the electrode area to 25 cm2 and operating for 8 hours, we obtained 0.164 g of high-purity urea, underscoring its potential for industrial applications. Mechanism study unveiled the enhanced performance might be ascribed to the synergistic interaction between NiPc and FeO4 sites. Specifically, NH3 produced at the FeO4 site can efficiently migrate and couple with the *NHCOOH intermediate adsorbed on the urea-producing site (NiPc). This synergistic effect results in a lower energy barrier for C-N bond formation than those of the reported catalysts with single active sites.

[Exploring the mechanism of IgA vasculitis pathogenesis through the interaction of thrombin and inflammatory factors using urinary proteomics]. / è¿ç”¨å°¿è›‹ç™½ç»„å­¦æŠ€æœ¯æŽ¢ç´¢å‡è¡€é ¶ä¸Žç‚Žç—‡å› å­ç›¸äº’ä½œç”¨å‚ä¸ŽIgAè¡€ç®¡ç‚Žå‘ç— çš„æœºåˆ¶.

OBJECTIVES: To explore the evidence, urinary biomarkers, and partial mechanisms of hypercoagulability in the pathogenesis of IgA vasculitis (IgAV). METHODS: Differential expression of proteins in the urine of 10 healthy children and 10 children with IgAV was screened using high-performance liquid chromatography-tandem mass spectrometry, followed by Reactome pathway analysis. Protein-protein interaction (PPI) network analysis was conducted using STRING and Cytoscape software. In the validation cohort, 15 healthy children and 25 children with IgAV were included, and the expression levels of differential urinary proteins were verified using enzyme-linked immunosorbent assay. RESULTS: A total of 772 differential proteins were identified between the IgAV group and the control group, with 768 upregulated and 4 downregulated. Reactome pathway enrichment results showed that neutrophil degranulation, platelet activation, and hemostasis pathways were involved in the pathogenesis of IgAV. Among the differential proteins, macrophage migration inhibitory factor (MIF) played a significant role in neutrophil degranulation and hemostasis, while thrombin was a key protein in platelet activation and hemostasis pathways. PPI analysis indicated that thrombin directly interacted with several proteins involved in inflammatory responses, and these interactions involved MIF. Validation results showed that compared to healthy children, children with IgAV had significantly higher urine thrombin/creatinine and urine MIF/creatinine levels (P<0.05). CONCLUSIONS: Thrombin contributes to the pathogenesis of IgAV through interactions with inflammatory factors. Urinary thrombin and MIF can serve as biomarkers reflecting the hypercoagulable and inflammatory states in children with IgAV.

The association between serum folate and elderly diastolic hypertension: results from the NHANES (2007-2018).

AIM: To explore the association between serum folate concentration and the prevalence of elderly diastolic hypertension. This study aims to identify potential relationships that could inform further research into the mechanisms underlying hypertension management. METHODS: Data from six NHANES cycles (2007-2008, 2009-2010, 2011-2012, 2013-2014, 2015-2016, and 2017-2018) were analysed for individuals aged over 60. Weighted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and restricted cubic spline (RCS) regression explored the serum folate concentration and elderly diastolic hypertension relationship. RESULTS: This study included 9,419 participants (4,734 females and 4,685 males) with a mean age of 70.0 ± 7.0 years. Among them, 360 were diagnosed with diastolic hypertension. In the fully adjusted model, there was a negative correlation between serum folate concentration and the prevalence of diastolic hypertension (OR 0.65; 95% CI: 0.52-0.82). When serum folate concentration levels were divided into quartiles (in µg/dL), the ORs for diastolic hypertension corresponding to Q2 (1.29-1.98), Q3 (1.99-3.08), and Q4 (3.09-5.56) levels compared to Q1 (0.18-1.28) were 1.41 (95% CI: 0.60-3.33), 0.48(95% CI: 0.20-1.16), and 0.35 (95% CI: 0.16-0.74), respectively, with a P for trend <.05. Restricted cubic spline plots showed a negative correlation between serum folate concentration and the prevalence of diastolic hypertension (non-linearity: p = .495). Subgroup analysis indicated that the negative correlation between serum folate concentration and the prevalence of diastolic hypertension was more significant in female participants (interaction p = .009). CONCLUSION: Higher serum folate concentration is associated with a lower prevalence of diastolic hypertension in the elderly.

What is the context?Diastolic hypertension, characterised by high blood pressure during the relaxation phase of the heartbeat.It significantly elevates the risk of cardiovascular diseases such as heart attacks and strokes.This study examines how serum folate levels relate to diastolic hypertension in the elderly, aiming to uncover correlations that inform future management strategies.What is new?This study investigated the relationship between serum folate concentration and the prevalence of diastolic hypertension in individuals aged over 60.Analysing data from multiple cycles of the National Health and Nutrition Examination Survey (NHANES), researchers found a noteworthy correlation between higher serum folate levels and a lower prevalence of diastolic hypertension.This association remained significant even after adjusting for various factors such as age, sex, and other health variables.What is the impact?The findings underscore the potential significance of folate intake in lowering the prevalence of diastolic hypertension among the elderly.It suggests avenues for further research into nutritional interventions targeting hypertension in this vulnerable population, potentially leading to more effective preventive measures and improved health outcomes.