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.

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

BACKGROUND AND AIM: 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 twelve 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 sacrificed. After sacrificing the pigs, the wound healing was histologically verified by hematoxylin-eosin (HE) staining. The primary outcome was a successful closure rate, while the 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 (3.0-6.0) cm and 3.0 (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 (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.

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.

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.

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.

The value of preoperative neutrophil/lymphocyte ratio in predicting the severity of cholecystolithiasis with cholecystitis in elderly patients.

BACKGROUND: This study aims to assess the effectiveness of neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) in diagnosing cholecystolithiasis with cholecystitis in elderly patients. Additionally, the study seeks to determine the predictive value of preoperative NLR in determining the severity of the condition in this population. METHODS: This study is a retrospective cohort study, including 160 elderly patients with cholecystolithiasis with cholecystitis (45 cases of simple cholecystitis, 58 cases of suppurative cholecystitis, 57 cases of gangrenous cholecystitis) and 60 cases of normal gallbladder histology. The study collected clinical data of the patients detected the preoperative CRP content, neutrophil, and lymphocyte levels through blood routine tests, and calculated the NLR value. The diagnostic value of NLR and CRP was determined by using the Receiver Operating Characteristic Curve (ROC), and the optimal value of preoperative NLR related to the severity of elderly patients with cholecystolithiasis with cholecystitis was identified. RESULTS: This study found that for elderly patients with cholecystolithiasis with cholecystitis, preoperative NLR and CRP levels can be used to distinguish the condition. The critical value for NLR was found to be 2.995 (95% CI, 0.9465-0.9853; P < 0.001) with an area under the ROC curve of 0.9659, while the critical value for CRP was 13.05 (95% CI, 0.9284-0.9830; P < 0.001) with an area under the ROC curve of 0.9557. Both NLR and CRP were found to have equivalent diagnostic abilities. Additionally, the study found that there were significant differences in neutrophil and lymphocyte levels in elderly patients with different severity levels, with NLR increasing as severity increased (P < 0.001). The study identified cut-off values for preoperative NLR that could distinguish Simple cholecystitis and Purulent cholecystitis, as well as Purulent cholecystitis and Gangrenous cholecystitis in elderly patients with cholecystolithiasis, with respective AUCs of 0.8441 (95% CI: 0.7642-0.9239; P < 0.001) and 0.7886(95% CI: 0.7050-0.8721, P < 0.001), sensitivities of 91.38% and 87.72%, and specificities of 73.33% and 63.79%. CONCLUSIONS: Preoperative NLR and CRP values can serve as indicators to detect cholecystolithiasis with cholecystitis in elderly patients. Additionally, NLR has been recognized as a potential tool to differentiate the severity of cholecystolithiasis with cholecystitis in the elderly population.

Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review.

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder with only a few affected families reported to date. Here, we report a case of familial GISTs harboring a novel germline mutation within exon 18 of KIT. A 58-year-old male patient presented with gastric subepithelial lesions accompanied by cutaneous hyperpigmentation, which were subsequently diagnosed as multinodular GISTs. Endoscopic surgery was initially conducted to remove the larger lesions, and pathological examinations were then conducted for the diagnosis of GISTs. Family history revealed that some other family members had similar cutaneous pigmentations. Whole-exome sequencing was used to search for potential driver mutations, and Sanger sequencing was used for mutation validation. A novel primary driver mutation of KIT (c.G2485C, p.A829P) was detected in these hereditary GISTs, which has been reported in some targeted chemotherapy-resistant GISTs. Cell models were subsequently established for the rapid screening of candidate drugs and exploring potential mechanisms. This mutation could lead to cell proliferation and imatinib resistance by ligand-independent activation of KIT; however, ripretinib administration was identified as an applicable targeted therapy for this mutation. The mutation activated the JAK/STAT3 and MAPK/ERK pathways, which could be inhibited by ripretinib administration. To the best of our knowledge, this is the first report of the KIT-A829P mutation in familial GISTs, complementing the pathogenesis of familial GISTs and providing valuable information for the precision treatment of this disease.

Characteristics and health risks of population exposure to phthalates via the use of face towels.

The production of face towels is growing at an annual rate of about 4% in China, reaching 1.13 million tons by 2021. Phthalates (PAEs) are widely used in textiles, and face towels, as an important household textile, may expose people to PAEs via the skin, further leading to health risks. We collected new face towels and analyzed the distribution characterization of PAEs in them. The changes of PAEs were explored in a face towel use experiment and a simulated laundry experiment. Based on the use of face towels by 24 volunteers, we calculated the estimated daily intake (EDI) and comprehensively assessed the hazard quotient (HQ), hazard index (HI), and dermal cancer risk (DCR) of PAEs exposure in the population. PAEs were present in new face towels at total concentrations of

Rh(II)-catalyzed Doyle-Kirmse reaction: access to unprotected 3-allyl/3-allenyl-3-(thio)oxindoles.

The construction of the 3-allyl/3-allenyl-3-(thio)oxindole core remains a challenge in organic synthesis. Herein, we report a novel Rh2(esp)2 catalytic Doyle-Kirmse reaction to furnish the oxindole core, bearing unbiased NH as well as a quaternary stereogenic center at the 3-position, in good to excellent yields under mild conditions. These reactions are concise, practical, atom-economic, and highly efficient, and feature a TON of up to 3700. Moreover, a non-radical pathway was observed in this approach.

The necessarity of treatment for small gastric subepithelial tumors (1-2 cm) originating from muscularis propria: an analysis of 972 tumors.

BACKGROUND AND OBJECTIVES: Up till now, there are still controversies about the specific indication of endoscopic resection for small gastric subepithelial tumors (gSETs) originating from muscularis propria. We aimed to investigate the safety of endoscopic resection and postoperative pathology analysis. METHOD: The patients with primary small gSETs originating from muscularis propria, treated by endoscopic resection in the endoscopic center of Shengjing Hospital between January, 2011 and September, 2019 were enrolled. The complete resection rate, adverse events and clinicopathological features were recorded. RESULT: A total of 936 patients with 972 gastric SETs ≤ 2 cm originating from muscularis propria were included in our study. All the lesions were successfully treated by endoscopic resection. Nearly half of lesions were proved to be gastrointestinal stromal tumor (GIST) [n = 411 (42.3%)] according to postoperative pathology. All the objects were further subdivided into 2 groups, ≤ 1 cm, > 1 and ≤ 2 cm gSETs. The risk of gastric GIST of intermediate/high risk in the group (> 1 and ≤ 2 cm gSETs) is 8.41 times as that of gastric GIST in the group (the size of gastric ≤ 1 cm gSETs) (P < 0.05). CONCLUSION: Endoscopic resection is a safe and effective treatment for small gSETs. gSETs (1-2 cm) is more risky than gSETs (≤ 1 cm) and should be resected. This should be evaluated by further studies.

Diversity distribution and characteristics of comammox in different ecosystems.

The discovery of complete ammonia oxidizers (comammox), which can oxidize ammonia into nitrate, has recently changed the concept of traditional nitrification. However, comparative studies on the analysis of comammox microbial community in different ecosystems are still scarce. In this study, the distribution and diversity of the comammox microbial community in farmlands, riparian zones, and river sediments in summer and winter were investigated by high-throughput sequencing. And the relative abundance of ammonia-oxidizing microorganisms was measured via their amoA genes of real-time quantitative polymerase chain reaction (qPCR). The relationships between ammonia oxidation microorganisms and the environmental factors were further analyzed. The abundance of comammox clade A was one order of magnitude lower than that of ammonia-oxidizing archaea (AOA) but higher than that of ammonia-oxidizing bacteria (AOB). The abundance of comammox was higher in summer than in winter and higher in farmland soils (1.81 ± 0.95 × 107 copies g-1) than in riparian zones and river sediments. Meanwhile, Candidatus Nitrospira nitrosa were the most widespread comammox in most samples (up to 86.31%), followed by Candidatus Nitrospira nitrificans, with a low abundance of Candidatus Nitrospira inopinata (lower than 0.61%). Furthermore, the abundance of comammox clade A had a significantly negative correlation with pH and NH4+ concentration (P < 0.05). The study revealed the potential advantages of comammox in farmlands and may be conducive to further research on comammox in microbial nitrogen cycling.