Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer.

Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment.

Topoisomerases I and II facilitate condensin DC translocation to organize and repress X chromosomes in C. elegans.

Condensins are evolutionarily conserved molecular motors that translocate along DNA and form loops. To address how DNA topology affects condensin translocation, we applied auxin-inducible degradation of topoisomerases I and II and analyzed the binding and function of an interphase condensin that mediates X chromosome dosage compensation in C. elegans. TOP-2 depletion reduced long-range spreading of condensin-DC (dosage compensation) from its recruitment sites and shortened 3D DNA contacts measured by Hi-C. TOP-1 depletion did not affect long-range spreading but resulted in condensin-DC accumulation within expressed gene bodies. Both TOP-1 and TOP-2 depletion resulted in X chromosome derepression, indicating that condensin-DC translocation at both scales is required for its function. Together, the distinct effects of TOP-1 and TOP-2 suggest two distinct modes of condensin-DC association with chromatin: long-range DNA loop extrusion that requires decatenation/unknotting of DNA and short-range translocation across genes that requires resolution of transcription-induced supercoiling.

MdSVWC1, a new pattern recognition receptor triggers multiple defense mechanisms against invading bacteria in Musca domestica.

BACKGROUND: Single-domain von Willebrand factor type C (SVWC) constitute a protein family predominantly identified in arthropods, characterized by a SVWC domain and involved in diverse physiological processes such as host defense, stress resistance, and nutrient metabolism. Nevertheless, the physiological mechanisms underlying these functions remain inadequately comprehended. RESULTS: A massive expansion of the SVWC gene family in Musca domestica (MdSVWC) was discovered, with a count of 35. MdSVWC1 was selected as the representative of the SVWC family for functional analysis, which led to the identification of the immune function of MdSVWC1 as a novel pattern recognition receptor. MdSVWC1 is highly expressed in both the fat body and intestines and displays acute induction upon bacterial infection. Recombinant MdSVWC1 binds to surfaces of both bacteria and yeast through the recognition of multiple pathogen-associated molecular patterns and exhibits Ca2+-dependent agglutination activity. MdSVWC1 mutant flies exhibited elevated mortality and hindered bacterial elimination following bacterial infection as a result of reduced hemocyte phagocytic capability and weakened expression of antimicrobial peptide (AMP) genes. In contrast, administration of recombinant MdSVWC1 provided protection to flies from bacterial challenges by promoting phagocytosis and AMP genes expression, thereby preventing bacterial colonization. MdSPN16, a serine protease inhibitor, was identified as a target protein of MdSVWC1. It was postulated that the interaction of MdSVWC1 with MdSPN16 would result in the activation of an extracellular proteolytic cascade, which would then initiate the Toll signaling pathway and facilitate the expression of AMP genes. CONCLUSIONS: MdSVWC1 displays activity as a soluble pattern recognition receptor that regulates cellular and humoral immunity by recognizing microbial components and facilitating host defense.

Endoscopic closure of large gastric defects with a novel through-the-scope closing device in a porcine model (with videos).

BACKGROUND AND AIMS: After endoscopic full-thickness resection (EFTR), defects require a reliable and sustained closure. We present a novel, through-the-scope "bow-tie" (TTS-BT) closing device enabling direct defect closure without scope withdrawal. This preclinical study aimed to evaluate the feasibility and safety of this device for large defect closure after EFTR in a porcine model. METHODS: Exposed EFTR was performed for virtual lesions >2 cm in the stomach of 12 pigs. Subsequently, TTS-BT closing devices were used for defect closure. Conventional metal clips were used to close any remaining defects. Gastroscopy was performed for 8 weeks to examine the wound sites, and the pigs were subsequently killed. After killing the pigs, the wound healing was histologically verified by hematoxylin and eosin staining. The primary outcome was a successful closure rate; secondary outcomes were complete healing rate, closure time, and incidence of adverse events. RESULTS: The median long and short diameters of perforations were 4.0 cm (range, 3.0-6.0 cm) and 3.0 cm (range, 2.0-4.0 cm), respectively. Defect closure using novel TTS-BT closure devices and conventional metal clips was successfully performed in all pigs. Complete healing was achieved in the defects of 12 pigs. The median closure time was 13 minutes (range, 9-38 minutes). No serious adverse events occurred during the 8-week follow-up. CONCLUSIONS: The novel TTS-BT closure device is feasible and safe for closing large gastric perforations and could be a promising tool for clinical practice.

First Fully Endoscopic End-to-End Colonic Anastomoses With a Novel Endoscopic Device: A Feasibility Study in a Porcine Model.

BACKGROUND: Continuous advancements and breakthroughs in flexible gastrointestinal endoscopy have led to alternatives to colonic anastomosis. OBJECTIVE: This study aimed to evaluate the feasibility and safety of end-to-end colonic anastomosis using a single flexible endoscope with the novel through-the-scope "bow-tie" (TTS-BT) device and conventional metal clips in a porcine model. DESIGN: Animal study. SETTINGS: Animal laboratory at China Medical University. PATIENTS: Eight healthy pigs were included. INTERVENTIONS: Eight animals underwent total colonic severance and anastomoses with through-the-scope "bow-tie" devices and metal clips. MAIN OUTCOME MEASURES: The primary outcomes were the success rate of the anastomosis and survival rate during 3-month follow-up. Furthermore, the secondary outcomes were anastomotic site healing, reintervention rate, and rate of anastomotic complications such as bleeding, leakage, stenosis, and obstruction. Six pigs were euthanized, and necropsies were performed 3 months postoperatively, while two pigs were fed for long-term observation. The anastomotic stoma was histologically analyzed using Hematoxylin-eosin and Masson's trichrome staining. RESULTS: End-to-end colonic anastomoses were successfully performed using through-the-scope "bow-tie" devices, and satisfactory healing was achieved in all pigs. The success rate of anastomosis was 100% (8/8). All animals survived postoperatively without anastomotic complications, including bleeding, leakage, or obstruction; however, two cases of stenosis occurred (25%), and one case (12.5%) required reintervention. LIMITATIONS: Large-scale studies should be conducted to verify the feasibility and safety of the through-the-scope "bow-tie" device in other parts of the intestine. CONCLUSIONS: Flexible endoscopy with the through-the-scope "bow-tie" device is feasible and safe for intraluminal colonic anastomosis. This study may expand the indications for full-thickness endoscopic resection in the future. See Video abstract.

Fluorescence molecular tomography based on an online maximum a posteriori estimation algorithm.

Fluorescence molecular tomography (FMT) is a non-invasive, radiation-free, and highly sensitive optical molecular imaging technique for early tumor detection. However, inadequate measurement information along with significant scattering of near-infrared light within the tissue leads to high ill-posedness in the inverse problem of FMT. To improve the quality and efficiency of FMT reconstruction, we build a reconstruction model based on log-sum regularization and introduce an online maximum a posteriori estimation (OPE) algorithm to solve the non-convex optimization problem. The OPE algorithm approximates a stationary point by evaluating the gradient of the objective function at each iteration, and its notable strength lies in the remarkable speed of convergence. The results of simulations and experiments demonstrate that the OPE algorithm ensures good reconstruction quality and exhibits outstanding performance in terms of reconstruction efficiency.

Corneal densitometry in Chinese adults with healthy corneas: associations with sex, age, ocular metrics, and optical characteristics.

BACKGROUND: Standardized corneal densitometry (CD) values in large samples of healthy Chinese individuals are scarce. Therefore, we aimed to determine the standard CD values using a Scheimpflug camera in healthy corneas, investigate the correlations of sex, age, and ocular parameters with corneal density, and explore the impact of corneal density on the forward scattering and optical quality of the eye. METHODS: This retrospective observational study involved 990 healthy Chinese individuals, including 494 males and 496 females (mean age: 23.88 ± 6.90 years). The CD values at various depths and radial areas of 0-12 mm were measured using a Scheimpflug camera. Densitometric measurements were expressed in standardized grayscale units (GSU). The optical scatter index (OSI), modulation transfer function cutoff values (MTFcutoff), and Strehl's ratio (SR) were also determined using an optical quality analysis system. RESULTS: The average CD within a 12 mm diameter area was 16.26 ± 1.35 GSU. The highest and lowest optical densities at different depths were observed in the anterior (21.41 ± 2.16 GSU) and posterior (12.00 ± 1.01 GSU) layers, respectively (P < 0.001). Similarly, the maximum and minimum optical densities at different radial areas were observed in the 10-12 mm (14.09 ± 0.93 GSU) and 2-6 mm (25.93 ± 4.77 GSU) circles, respectively (P < 0.001). There was no significant difference in the average CD within a 12 mm diameter area between males and females (P > 0.05). However, upon adjusting for age, central corneal thickness (CCT), corneal curvature, white-to-white (WTW) corneal diameter, and axial length, females exhibited a greater average CD within the 12 mm diameter and in the 6-10 mm and 10-12 mm circles than males. Age-related changes in CD were evident, except in the 2-6 mm circle. CCT, corneal curvature, WTW corneal diameter, and partial depth correlated with CD in the radial area, and CD in different areas correlated with the OSI, MTFcutoff, and SR (P < 0.05). CONCLUSIONS: This study provides the normative CD measurement data of Chinese adults with healthy corneas, emphasizing the significance of sex, age, CCT, corneal curvature, and WTW corneal diameter in CD evaluation. Notably, elevated CD can lead to increased forward scattering within the eye, thereby affecting the optical quality.

Associations between type 2 diabetes mellitus and risk of falls among community-dwelling elderly people in Guangzhou, China: a prospective cohort study.

BACKGROUND: Several studies have demonstrated that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of falls compared to those without T2DM, which may lead to disability and a lower quality of life. While, limited prospective studies have quantified the associations in southern China. We conducted a longitudinal cohort study to quantify the associations between T2DM and falls and investigate the risk factors of falls among community-dwelling elderly people in Guangzhou, China. METHODS: The population-based study included 8800 residents aged 65 and over in 11 counties of Guangzhou at baseline in 2020 and then prospectively followed up through 2022. Of 6169 participants had complete follow-up and were included in the present study. A fall event was identified by self-reported. The Cox regression was applied to quantify the associations between T2DM and falls, and hazard ratios (HRs) were calculated to the factors associated with falls among participants. RESULTS: The median follow-up time for participants was 2.42 years. During the follow-up period, the incidence of falls among all participants was 21.96%. After adjusting for covariates in Cox regression models, T2DM remained a significant risk factor for falls, with HR of 1.781 (95% CI: 1.600-1.983) in the unadjusted covariates model and 1.757 (1.577-1.957) in the adjusted covariates model. Female (1.286, 1.136-1.457), older age (≥ 80: 1.448, 1.214-1.729), single marital status (1.239, 1.039-1.477), lower education level (primary school and below: 1.619, 1.004-1.361), hypertension (1.149, 1.026-1.286) and stroke (1.619, 1.176-2.228) were associated with a higher risk of falls, whereas everyday physical exercise (0.793, 0.686-0.918) was associated with a lower risk of falls. CONCLUSION: Falls are common, with risks between T2DM and falls quantified and several factors investigated in the longitudinal cohort study among community-dwelling elderly people in Guangzhou, China. Targeted action on the risk factors may reduce the burden of falls in elderly people with T2DM in the future.

Association between abdominal obesity indices and falls among older community-dwellers in Guangzhou, China: a prospective cohort study.

BACKGROUND: Central obesity was considered as a risk factor for falls among the older population. Waist circumference (WC), lipid accumulation product (LAP), visceral adiposity index (VAI), and the Chinese visceral adiposity index (CVAI) are considered as surrogate markers for abdominal fat deposition in increasing studies. Nevertheless, the longitudinal relationship between these indices and falls among the older population remains indistinct. This study aimed to explore the association between abdominal obesity indices and falls among older community-dwellers. METHODS: Our study included 3501 individuals aged ≥ 65 years from the Guangzhou Falls and Health Status Tracking Cohort at baseline in 2021 and then prospectively followed up in 2022. The outcome of interest was the occurrence of falls. The Kaplan-Meier curves and multivariable Cox regression analysis were used to explore the associations between abdominal obesity indices and falls. Moreover, the restricted cubic spline analysis (RCS) was conducted to test the non-linear relationships between abdominal obesity indices and hazards of falls incident. RESULTS: After a median follow-up period of 551 days, a total of 1022 participants experienced falls. The cumulative incidence rate of falls was observed to be higher among individuals with central obesity and those falling within the fourth quartile (Q4) of LAP, VAI, and CVAI. Participants with central obesity and those in Q4 of LAP, VAI, and CVAI were associated with higher risk of falls, with hazard ratios (HRs) of 1.422 (HR 95%CI: 1.255-1.611), 1.346 (1.176-1.541), 1.270 (1.108-1.457), 1.322 (1.154-1.514), respectively. Each 1-SD increment in WC, LAP, VAI, and CVAI was a significant increased risk of falls among participants. Subgroup analysis further revealed these results were basically stable and appeared to be significantly stronger among those females, aged 65-69 years, and with body mass index (BMI) ≥ 28 kg/m2. Additionally, RCS curves showed an overall upward trend in the risk of falls as the abdominal indices increased. CONCLUSIONS: Abdominal obesity indices, as WC, LAP, VAI, and CVAI were significantly associated with falls among older community-dwellers. Reduction of abdominal obesity indices might be suggested as the strategy of falls prevention.

Efficacy and Safety of Corticosteroid in Combination with 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Addressing hypertrophic scars and keloids poses a significant challenge in the realm of preventive and curative medicine. Combination corticosteroid with 5-fluorouracil (5-FU) is presumed to enhance the treatment of hypertrophic scars and keloids, although supportive evidence is lacking. This study is aimed at comparing the efficacy and safety profile of a combined corticosteroid and 5-FU regimen in treating hypertrophic scars and keloids. METHODS: A comprehensive search was conducted for pertinent studies across various databases, including Web of Science, PubMed, Google Scholar, Cochrane Library, and Medline. The calculation of weighted mean difference (WMD), risk ratios (RR), odds ratios (OR), and 95% confidence intervals (CIs) was executed. Additionally, the Cochrane Collaboration's Risk of Bias Tool was utilized to evaluate potential bias risks. RESULTS: A total of 15 studies were involved. The effectiveness based on patient self-assessment and the effectiveness based on observer assessment were significantly higher in the corticosteroid+5-FU group compared to those treated with control. A meta-analysis of scar height showed that the corticosteroid+5-FU group performed better than the control group (WMD = -0.38, 95% CI -0.58 to -0.18). There was no significant difference between the corticosteroid+5-FU group and the control group in improving scar vascularity, pliability and pigmentation. The result revealed that the corticosteroid+5-FU group of patients had less adverse effect of hypopigmentation, skin atrophy and telangiectasia than the control group. CONCLUSION: The combined use of corticosteroids and 5-FU appears to be a more effective strategy for the treatment and prevention of hypertrophic scars and keloids, as evidenced by greater improvements in scar height and overall effectiveness, coupled with a reduced incidence of side effects. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Exploration the interaction of cadmium and copper toxic effects in pakchoi (Brassica chinensis L) roots through combinatorial transcriptomic and weighted gene co-expression network analysis.

The interaction between cadmium(Cd) and copper(Cu) during combined pollution can lead to more complex toxic effects on humans and plants.However, there is still a lack of sufficient understanding regarding the types of interactions at the plant molecular level and the response strategies of plants to combined pollution. To assess this, we investigated the phenotypic and transcriptomic patterns of pakchoi (Brassica chinensis L) roots in response to individual and combined pollution of Cd and Cu. The results showed that compared to single addition, the translocation factor of heavy metals in roots significantly decreased (p < 0.05) under the combined addition, resulting in higher accumulation of Cd and Cu in the roots. Transcriptomic analysis of pakchoi roots revealed that compared to single pollution, there were 312 and 1926 differentially expressed genes (DEGs) specifically regulated in the Cd2Cu20 and Cd2Cu100 combined treatments, respectively. By comparing the expression of these DEGs among different treatments, we found that the combined pollution of Cd and Cu mainly affected the transcriptome of the roots in an antagonistic manner. Enrichment analysis indicated that pakchoi roots upregulated the expression of genes involved in glucosetransferase activity, phospholipid homeostasis, proton transport, and the biosynthesis of phenylpropanoids and flavonoids to resist Cd and Cu combined pollution. Using weighted gene co-expression network analysis (WGCNA), we identified hub genes related to the accumulation of Cd and Cu in the roots, which mainly belonged to the LBD, thaumatin-like protein, ERF, MYB, WRKY, and TCP transcription factor families. This may reflect a transcription factor-driven trade-off strategy between heavy metal accumulation and growth in pakchoi roots. Additionally, compared to single metal pollution, the expression of genes related to Nramp, cation/H+ antiporters, and some belonging to the ABC transporter family in the pakchoi roots was significantly upregulated under combined pollution. This could lead to increased accumulation of Cd and Cu in the roots. These findings provide new insights into the interactions and toxic mechanisms of multiple metal combined pollution at the molecular level in plants.

The effect of neoadjuvant chemotherapy on surgical site wound infection after immediate breast reconstruction in patients with breast cancer: A meta-analysis.

Using a meta-analysis approach, we conducted a comprehensive evaluation of the effect of neoadjuvant chemotherapy (NACT) on the incidence of surgical site wound infection during immediate breast reconstruction (IBR) following breast cancer. The aim was to provide evidence-based support for the prevention of wound surgical site infection during IBR after breast cancer surgery. Relevant literature on the effects of NACT on IBR in patients with breast cancer published up until May 2023, was retrieved from various databases, including PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang databases, and China Biology Medicine Database. Two researchers performed the literature screening, data collection, and quality assessment of the included studies independently. The meta-analysis was conducted using Stata version 17.0. Fourteen studies involving 3401 patients (599 in the intervention group and 2802 in the control group) were included in the analysis. The incidence of surgical site infection in the NACT group was higher than that in the control group, but the difference between the two groups was not statistically significant (7.17% vs. 4.85%, odds ratio: 1.02, 95% confidence interval: 0.70-1.50, p = 0.902). These findings suggest that NACT does not increase the risk of surgical site infection during IBR. However, owing to the variation in sample size and literature quality among the included studies, randomised controlled trials are needed to confirm the safety of IBR in patients receiving neoadjuvant chemotherapy.

Hydroxychloroquine inhibits the growth of lung cancer cells by inducing G1 cell cycle arrest and apoptosis.

Hydroxychloroquine, used initially as an anti-malarial drug, is now recognized for its anti-tumor effects in a range of human cancers. Nevertheless, there has been limited attention given to the molecular mechanisms of anti-tumor action of hydroxychloroquine. Here, we investigated the anti-tumor effect of hydroxychloroquine in human A549 cells and further analyzed the potential molecular mechanisms involved. Hydroxychloroquine was found to effectively inhibit the growth of A549 cells. This inhibition was observed to be both dose-dependent and time-dependent. Moreover, in a tumor xenograft mouse model, hydroxychloroquine remarkably suppressed tumor growth. Mechanistically, treatment with hydroxychloroquine led to the inhibition of phosphorylation in JNK, STAT3 and AKT. This biochemical interference subsequently induced G1 cell cycle arrest and promoted mitochondrial-mediated apoptosis in A549 cells. The findings from this study offered robust evidence supporting the use of hydroxychloroquine as a treatment for non-small cell lung cancer (NSCLC). Consequently, hydroxychloroquine emerges as a potential therapeutic agent for the treatment of this cancer.

Autoimmune pancreatitis type 2 (idiopathic duct-centric pancreatitis): A comprehensive review.

Autoimmune pancreatitis (AIP) is an uncommon fibro-inflammatory disorder precipitated by autoimmune/inflammatory reactions. Currently, there are two clinical subtypes of AIP (type 1 [AIP-1] and type 2 [AIP-2]) that correspond to two histologic descriptors (lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis, respectively). While our understanding of AIP-1 has evolved considerably over the years, little is known about AIP-2 due to its rarity, often leading to misdiagnosis, delayed treatment, and even unnecessary surgical resection. Compared to AIP-1, AIP-2 exhibits distinct clinical and histologic features. Because AIP-2 is a pancreas-restricted disease without a specific serum marker, the evaluation of histologic features (e.g., granulocytic epithelial lesions) is essential for an accurate diagnosis. Patients with AIP-2 respond well to glucocorticoids, with anti-tumor necrosis factor-alpha antibodies as a promising alternative therapy. The prognosis of AIP-2 is generally favorable and relapse is uncommon. Here, we provide an overview of our current knowledge on the clinical features, diagnosis, therapeutic regimens, prognosis, and putative mechanisms underlying AIP-2. Notably, the diagnostic differentiation between AIP-2, especially the mass-forming/focal type, and pancreatic cancer is important, but challenging. In this regard, endoscopic ultrasound-guided core biopsy has a key role, but novel diagnostic markers and modalities are clearly needed.

Comparative analysis of changes in diarrhea and gut microbiota in Beigang pigs.

Increasing evidence indicated that the gut microbiota is a large and complex organic combination, which is closely related to the host health. Diarrhea is a disease with devastating effects on livestock that has been demonstrated to be associated with gut microbiota. Currently, studies on gut microbiota and diarrhea have involved multiple species, but changes in gut microbiota of Beigang pigs during diarrhea have not been characterized. Here, we described gut microbial changes of Beigang pigs during diarrhea. Results indicated that a total of 4423 OTUs were recognized in diarrheic and healthy Beigang pigs, and Firmicutes and Bacteroidota were the most dominant phyla regardless of health status. However, the major components of the gut microbiota changed between diarrheic and healthy Beigang pigs. Bacterial taxonomic analysis revealed that the relative abundances of 3 phyla (Synergistota, Actinobacteriota and Spirochaetota) and 30 genera increased significantly during diarrhea, whereas the relative abundances of 3 phyla (Patescibacteria, Bacteroidota and Fibrobacterota) and 41 genera decreased significantly. In conclusion, this study found significant changes in the gut microbiota of Beigang pigs during diarrhea. Meanwhile, this also lays the foundation for the prevention and treatment of diarrhea in Beigang pigs and the further discovery of more anti-diarrhea probiotics.

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages.

ABSTRACT: Salidroside has anti-inflammatory and antiatherosclerotic effects, and mitochondrial homeostasis imbalance is closely related to cardiovascular disease. The aim of this study was to investigate the effect of salidroside on mitochondrial homeostasis after macrophage polarization and elucidate its possible mechanism against atherosclerosis. RAW264.7 cells were stimulated with 1 µg·mL -1 Lipopolysaccharide and 50 ng·mL -1 IFN-γ establish M1 polarization and were also pretreated with 400 µM salidroside. The relative expression of proinflammatory genes was detected by RT-PCR whereas that of mitochondrial homeostasis-related proteins and nuclear factor kappa-B (NF-κB) was detected by WB. Levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential, and mass were measured by chemifluorescence whereas that of NF-κB nuclear translocation was detected by immunofluorescence. Compared with the Mφ group, the M1 group demonstrated increased mRNA expression of interleukin-1ß , inductible nitric oxide synthase (iNOS), and tumor necrosis factor-α ; increased protein expression of iNOS, NOD-like receptor protein 3, putative kinase 1 , and NF-κB p65 but decreased protein expression of MFN2, Tom20, and PGC-1α; decreased mitochondrial membrane potential and mass; and increased ROS levels and NF-κB p65 nuclear translocation. Salidroside intervention decreased mRNA expression of interleukin-1ß and tumor necrosis factor-α compared with the M1 group but did not affect that of iNOS. Furthermore, salidroside intervention prevented the changes in protein expression, mitochondrial membrane potential and mass, ROS levels, and NF-κB p65 nuclear translocation observed in the M1 group. In summary, salidroside ultimately inhibits M1 macrophage polarization and maintains mitochondrial homeostasis after macrophage polarization by increasing mitochondrial membrane potential, decreasing ROS levels, inhibiting NF-κB activation, and in turn regulating the expression of proinflammatory factors and mitochondrial homeostasis-associated proteins.

A highly efficient method to access unprotected C-3 bifunctional quaternary 3-allyl-3-(amino)oxindoles.

A highly efficient Rh(II) catalyzed non-radical protocol to access NH-free C-3 bifunctional oxindoles, which possess 3-allyl and 3-amino simultaneously, was first achieved by employing an intermolecular [2,3]-sigmatropic rearrangement reaction between diazooxindoles and tertiary allylic amines. Utilizing readily available allylamines as the nitrogen and allyl source concurrently, a wide range of bio-active 3-allyl-3-(amino)oxindoles were obtained in excellent yields under very mild reaction conditions; meanwhile, the TON can be up to 90 000. Our study addresses a gap in the literature by investigating intermolecular rearrangements of ammonium ylides with diazoamides, which have been relatively understudied.

The formation process and mechanism of gastrointestinal anastomosis after retrieval anchor-assisted endoscopic ultrasound-guided gastroenterostomy: a preclinical study.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a promising method of treating gastric outlet obstruction. However, no study has investigated gastrointestinal anastomosis formation after EUS-GE. We aimed to evaluate the formation of gastrointestinal anastomosis after EUS-GE in a porcine model. METHODS: Retrieval anchor-assisted EUS-GE was performed on 15 Bama mini pigs. Five pigs each were randomly euthanized 3, 7, and 14 days postoperatively to evaluate the formation of gastrointestinal anastomosis and measure the anastomotic distance. The expression of transforming growth factor-ß1(TGF-ß1) and Smad3 in the anastomosis site were examined by immunohistochemistry. RESULTS: EUS-GE was successfully performed in all 15 pigs. The mean procedure time was 29.2 ± 6.0 (range 18-40) minutes. The anastomotic distance was 34.0 ± 3.6 cm in 14 pigs. The site of gastroenterostomy of one pig was at the ileum. For pigs euthanized 3 days postoperatively, the structure was mechanically maintained by a stent. For pigs euthanized 7 or 14 days postoperatively, the stomach and small intestine were anastomosed to form a stable structure. The level of TGF-ß1 and Smad3 in the anastomosis site gradually increased from 3 to 14 days after EUS-GE. TGF-ß1 and Smad3 expression had a significant difference between 3 days, 7 days, and 14 days after EUS-GE (P < 0.05). CONCLUSIONS: For EUS-GE, the stomach and small intestine were initially linked together mechanically and spontaneously anastomosed to form a stable structure 7 days postoperatively. TGF-ß1 and Smad3 play an important role in the formation of a stable structure of gastrointestinal anastomosis.

Effects of cadmium and copper mixtures on antibiotic resistance genes in rhizosphere soil.

The evolvement and development of antibiotic resistance in microorganisms may be influenced by metals; however, it is still unclear how cadmium (Cd) and copper (Cu) combined affect the distribution and presence of antibiotic-resistance genes (ARGs) in rhizosphere soil. The aims of this research were to (1) compare the distribution patterns of bacterial communities and ARGs in response to the effects of Cd and Cu both separately and combined; (2) explore the possible mechanisms underlying the variation in soil bacterial communities and ARGs in addition to the combined effects of Cd, Cu, and various environmental variables (nutrients, pH, etc.); and (3) provide a reference for assessing the risks of metals (Cd and Cu) and ARGs. The findings showed that the multidrug resistance genes acrA and acrB and the transposon gene intI-1 were present in high relative abundance in bacterial communities. Cadmium and Cu had a substantial interaction effect on the abundance of acrA, whereas Cu had a notable main effect on the abundance of intI-1. According to the network analysis, the strong links between bacterial taxa and specific ARGs revealed that most ARGs were hosted by Proteobacteria, Actinobacteria, and Bacteroidetes. According to structural equation modeling, Cd had a larger effect on ARGs than Cu. Compared to previous analyses of ARGs, bacterial community diversity had little effect on ARGs in this study. Overall, the results may have important consequences for determining the possible hazard of soil metals and extend the understanding of how Cd and Cu co-select ARGs in rhizosphere soils.

Exposure estimates of parabens from personal care products compared with biomonitoring data in human hair from Northeast China.

Parabens (PBs), a class of endocrine-disrupting chemicals (EDCs), are extensively used as additives in personal care products (PCPs); however, distinguishing between endogenous and exogenous contamination from PCPs in hair remains a challenge. We conducted a comprehensive analysis of the levels, distribution patterns, impact factors, and sources of PBs in 119 human hair samples collected from Changchun, northeast China. The detection rates of methylparaben (MeP), propylparaben (PrP), and ethylparaben (EtP) in hair samples were found to be 100%. The concentration of PBs in hair followed the order of MeP (57.48 ng/g) > PrP (46.40 ng/g) > EtP (6.80 ng/g). The concentration of PrP in female hair was significantly higher (65.38 ng/g) than that observed in male hair (7.82 ng/g) (p < 0.05). The levels of excretion rates of MeP (ERMeP) and excretion rates of PrP (ERPrP) in the hair-dying samples (ERMeP: 17.89 ng/day; ERPrP: 14.15 ng/day) were found to be 2.52 and 2.40 times higher, respectively, compared to the non-hair-dying samples (ERMeP: 7.09 ng/day; ERPrP: 6.05 ng/day). However, the system exposure dosage (SED) results revealed that although hair dyes exhibited higher PBs, human exposure was found to be lower than certain PCPs. The results of the correlation analysis revealed that toner, face cream, body lotion, and hair conditioner were identified as the primary sources of PBs in male hair. Furthermore, the human exposure resulting from the utilization of female hair dye and serum exhibited a positive correlation with hair ERMeP and ERPrP levels, indicating in the screening of samples, excluding hair samples using hair dye and haircare essential oil can effectively avoid the interference caused by exogenous contamination from PCPs.