Phosphate Recovery from Urban Sewage by the Biofilm Sequencing Batch Reactor Process: Key Factors in Biofilm Formation and Related Mechanisms.

The biofilm sequencing batch reactor (BSBR) technique has been deployed in the laboratory to enrich phosphorus from simulated wastewater, but it is still not clear what its performance will be when real world sewage is used. In this work, the effluent from the multi-stage anoxic-oxic (AO) activated sludge process at a sewage plant was used as the feed water for a BSBR pilot system, which had three reactors operating at different levels of dissolved oxygen (DO). The phosphorus adsorption and release, the biofilm growth, and the extracellular polymeric substances (EPS) components and contents were examined. The microbial communities and the signaling molecules N-acyl-l-homoserine lactones (AHLs) were also analyzed. Gratifyingly, the BSBR process successfully processed the treated sewage, and the biofilm developed phosphorus accumulation capability within 40 days. After entering stable operation, the system concentrated phosphate from 2.59 ± 0.77 mg/L in the influent to as much as 81.64 mg/L in the recovery liquid. Sludge discharge had profound impacts on all aspects of BSBR, and it was carried out successfully when the phosphorus absorption capacity of the biofilm alone was comparable to that of the reactor containing the activated sludge. Shortly after the sludge discharge, the phosphate concentration of the recovery liquid surged from 50 to 140 mg/L, the biofilm thickness grew from 20.56 to 67.32 µm, and the diversity of the microbial population plunged. Sludge discharge stimulated Candidatus competibacter to produce a large amount of AHLs, which was key in culturing the biofilm. Among the AHLs, both C10-HSL and 3OC12-HSL were significantly positively correlated with EPS and the abundance of Candidatus competibacter. The current results demonstrated BSBR as a viable option to enrich phosphorus from real world sewage with low phosphorus content and fluctuating chemistry. The mechanistic explorations also provided theoretical guidance for cultivating phosphorus-accumulating biofilms.

Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. METHODS: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02-1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12-1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42-2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52-3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532. CONCLUSIONS: Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

BACKGROUND: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. METHODS: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20-50) vs. 35 (30-59) mL, median difference (95%CI) - 5 (- 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) - 1.19 (- 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II-III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5-32.5) vs. 32 (27-38.5) days, median difference (95%CI) - 3 (- 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. CONCLUSION: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

Function and mechanism of exogenous AGR2 in colorectal cancer cells.

Background: Anterior gradient 2 (AGR2) is highly enriched in several malignant tumors and can boost tumor metastasis. Whereas, AGR2 role in colorectal cancer (CRC) is not clear. Methods: AGR2 expression in the GEPIA database was studied, and the results were confirmed by Western blot in CRC cell lines (SW480, SW620, and HT-29). The impact of AGR2 on the multiplication, migration, invasion and EMT of CRC cells were studied by CCK-8 assay, as well as clone formation, wound healing and transwell assays. The protein concent related to the AKT/ß-catenin signaling pathway were accessed via Western blot. Results: AGR2 concent in CRC tissues was notablely boosted versus normal colorectal tissues. Exogenous AGR2 boosted the multiplication of CRC cells. In addition, exogenous AGR2 induced EMT, which demonstrated that ZEB1, N-cadherin, Vimentin, Slug, Snail protein concent boosted and E-cadherin protein abated in CRC cells. In terms of mechanism, exogenous AGR2 upgulated p-AKT/AKT, p-GSK3ß/GSK3ß and ß-catenin concent. Exogenous AGR2 combined with AKT agonist IGF- Ⅰ can further enhance the multiplication, migration and invasion of CRC cells. Conclusion: Exogenous AGR2 enhances the multiplication of CRC cells and induces EMT process, the mechanism of which is related to AKT/ß-catenin signal pathway.

Risk factors and genetic characteristics of the carriage of hypervirulent and carbapenem-resistant Acinetobacter baumannii among pregnant women.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) and its emerging evolutionary branch toward hypervirulence have been neglected in pregnancy. Methods: From September 2020 to August 2021, an active surveillance culture program encompassed 138 randomly selected pregnant women, with five subjected to sample collection at two different time points. The clinical characterization was explored through statistical analysis. Whole-genome sequencing, a Galleria mellonella infection model, and a global database were used to investigate the genetic characterization, pathogenicity, evolutionary history, and phylogenetic relationships of the isolates. Results: Of the 41 CRAB isolates obtained, they were divided into four ClustersRS and an orphan pattern. ClusterRS 1 (n = 31), with eight complex types in pregnancy, was also the dominant ClusterRS globally, followed by ClusterRS 13 (n = 5), identified as hypervirulent KL49 CRAB, exhibiting phylogeographical specificity to Guangdong. A maternal carriage CRAB rate of 26.09% (36/138) was revealed, with half of the isolates representing novel complex types, prominently including CT3071, as the first KL7 isolates identified in Shenzhen. Both KL49 and KL7 isolates were most commonly found in the same participant, suggesting potential intraspecific competition as a possible reason for CRAB infection without carriers during pregnancy. The independent risk factors for carriers were revealed for the first time, including advanced maternal age, gestational diabetes mellitus, and Group B Streptococcus infection. Conclusion: The significant carriage rate and enhanced virulence of CRAB during pregnancy emphasize the imperative for routine surveillance to forestall dissemination within this high-risk group, especially in Guangdong for ClusterRS 13 isolates.

Deep learning-based radiomics of computed tomography angiography to predict adverse events after initial endovascular repair for acute uncomplicated Stanford type B aortic dissection.

PURPOSE: This study aimed to construct a predictive model integrating deep learning-derived radiomic features from computed tomography angiography (CTA) and clinical biomarkers to forecast postoperative adverse events (AEs) in patients with acute uncomplicated Stanford type B aortic dissection (uTBAD) undergoing initial thoracic endovascular aortic repair (TEVAR). METHODS: We retrospectively evaluated 369 patients treated with TEVAR for acute uTBAD from January 2015 to December 2022. A three-dimensional (3D) deep convolutional neural network (CNN) automated radiomic feature extraction from CTA images. Feature selection, using Analysis of Variance (ANOVA) and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithms, refined a radiomic score (Rad-Score). This score, alongside clinical parameters, was modelled via Extreme Gradient Boosting (XGBoost) analysis. Model calibration was assessed by calibration curves. RESULTS: The integration of the Rad-Score with clinical factors including albumin and C-reactive protein levels moderately enhanced predictive efficiency, exhibiting an area under the curve (AUC) of 1.000 (95%CI, 1.000-1.000) in the training cohort and 0.990 (95%CI, 0.966-1.000) in the internal validation cohort. In an independent validation cohort from another hospital, the combined model yielded an AUC of 0.985 (95%CI, 0.965-1.000), with an accuracy, precision, sensitivity, and specificity of 0.92, 0.92, 0.94, and 0.91, respectively. CONCLUSIONS: The synergistic application of deep learning-based radiomics from CTA and clinical indicators holds promise for anticipating AEs post-initial thoracic endovascular aortic repair in patients with acute uTBAD. The clinical utility of the constructed combined model, offering prognostic foresight during follow-up, has been substantiated.

The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicenter Real-world clinical study.

BACKGROUND: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. METHODS: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analysed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. RESULTS: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% versus [vs.] 59.0%; P<0.001), pathological complete response rate (14.36% vs. 6.41%; P=0.002) and major pathological response rate (39.49% vs. 26.15%; P=0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P=0.694) and proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P=0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P=0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence (odds ratio 0.62 [95% CI 0.41-0.92]; P=0.018). No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P=0.143). CONCLUSIONS: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates, and reduced the risk for early recurrence among patients with LAGC. TRIAL REGISTRATION: Clinical Trials.gov.

Combined therapy of dabrafenib and an anti-HER2 antibody-drug conjugate for advanced BRAF-mutant melanoma.

BACKGROUND: Melanoma is the most lethal skin cancer characterized by its high metastatic potential. In the past decade, targeted and immunotherapy have brought revolutionary survival benefits to patients with advanced and metastatic melanoma, but these treatment responses are also heterogeneous and/or do not achieve durable responses. Therefore, novel therapeutic strategies for improving outcomes remain an unmet clinical need. The aim of this study was to evaluate the therapeutic potential and underlying molecular mechanisms of RC48, a novel HER2-target antibody drug conjugate, either alone or in combination with dabrafenib, a V600-mutant BRAF inhibitor, for the treatment of advanced BRAF-mutant cutaneous melanoma. METHODS: We evaluated the therapeutic efficacy of RC48, alone or in combination with dabrafenib, in BRAF-mutant cutaneous melanoma cell lines and cell-derived xenograft (CDX) models. We also conducted signaling pathways analysis and global mRNA sequencing to explore mechanisms underlying the synergistic effect of the combination therapy. RESULTS: Our results revealed the expression of membrane-localized HER2 in melanoma cells. RC48 effectively targeted and inhibited the growth of HER2-positive human melanoma cell lines and corresponding CDX models. When used RC48 and dabrafenib synergically induced tumor regression together in human BRAF-mutant melanoma cell lines and CDX models. Mechanically, our results demonstrated that the combination therapy induced apoptosis and cell cycle arrest while suppressing cell motility in vitro. Furthermore, global RNA sequencing analysis demonstrated that the combination treatment led to the downregulation of several key signaling pathways, including the PI3K-AKT pathway, MAPK pathway, AMPK pathway, and FOXO pathway. CONCLUSION: These findings establish a preclinical foundation for the combined use of an anti-HER2 drug conjugate and a BRAF inhibitor in the treatment of BRAF-mutant cutaneous melanoma.

Rapid Correction of the Hypoglycemia State in Nonhuman Primates Using a Glucagon Long-Dissolving Microneedle Patch.

The timely administration of glucagon is a standard clinical practice for the treatment of severe hypoglycemia. However, the process involves cumbersome steps, including the reconstitution of labile glucagon and filling of the syringe, which cause considerable delays in emergency situations. Moreover, multiple dosages are often required to prevent the recurrence of the hypoglycemic episode because of the short half-life of glucagon in plasma. Herein, we develop a glucagon-loaded long-dissolving microneedle (GLMN) patch that exhibits the properties of fast onset and sustained activity for the effective treatment of severe hypoglycemia. Three types of MN patches were fabricated with different dimensions (long, medium, and short). The longer MN patch packaged a higher dosage of glucagon and exhibited supreme mechanical strength compared to the shorter one. Additionally, the longer MN patch could insert more deeply into the skin, resulting in higher permeability of glucagon across the skin tissue and more rapid systemic absorption as compared with the shorter MN patch. The GLMN patch was observed to reverse the effects of hypoglycemia within 15 min of application in animal models (specifically, rat and rhesus monkey models) and maintained long-term glycemic control, owing to highly efficient drug permeation and the drug reservoir effect of the MN base. The current study presents a promising strategy for the rapid reversal of severe hypoglycemia that exhibits the desirable properties of easy use, high efficiency, and sustained action.

The safety, feasibility and oncological outcomes of laparoscopic completion total gastrectomy for remnant gastric cancer: a prospective study with 3-year follow-up (FUGES-004 study).

BACKGROUND: The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. METHODS: The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. RESULTS: Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0% vs. 35.0%, P=0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9% vs. 32.8%, P=0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P=0.173; OS: log-rank P=0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P>0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. CONCLUSIONS: This prospective study suggested that LCTG was non-inferior to OCTG in both short- and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.

Deep learning-based arterial subtraction images improve the detection of LR-TR algorithm for viable HCC on extracellular agents-enhanced MRI.

PURPOSE: To determine the role of deep learning-based arterial subtraction images in viability assessment on extracellular agents-enhanced MRI using LR-TR algorithm. METHODS: Patients diagnosed with HCC who underwent locoregional therapy were retrospectively collected. We constructed a deep learning-based subtraction model and automatically generated arterial subtraction images. Two radiologists evaluated LR-TR category on ordinary images and then evaluated again on ordinary images plus arterial subtraction images after a 2-month washout period. The reference standard for viability was tumor stain on the digital subtraction hepatic angiography within 1 month after MRI. RESULTS: 286 observations of 105 patients were ultimately enrolled. 157 observations were viable and 129 observations were nonviable according to the reference standard. The sensitivity and accuracy of LR-TR algorithm for detecting viable HCC significantly increased with the application of arterial subtraction images (87.9% vs. 67.5%, p < 0.001; 86.4% vs. 75.9%, p < 0.001). And the specificity slightly decreased without significant difference when the arterial subtraction images were added (84.5% vs. 86.0%, p = 0.687). The AUC of LR-TR algorithm significantly increased with the addition of arterial subtraction images (0.862 vs. 0.768, p < 0.001). The arterial subtraction images also improved inter-reader agreement (0.857 vs. 0.727). CONCLUSION: Extended application of deep learning-based arterial subtraction images on extracellular agents-enhanced MRI can increase the sensitivity of LR-TR algorithm for detecting viable HCC without significant change in specificity.

Xiaozhi formula attenuates non-alcoholic fatty liver disease by regulating lipid metabolism via activation of AMPK and PPAR pathways.

BACKGROUND: Xiaozhi formula (XZF) is a practical Chinese herbal formula for the treatment of non-alcoholic fatty liver disease (NAFLD), which possesses an authorized patent certificate issued by the State Intellectual Property Office of China (ZL202211392355.0). However, the underlying mechanism by which XZF treats NAFLD remains unclear. PURPOSE: This study aimed to explore the main component of XZF and its mechanism of action in NAFLD treatment. METHODS: UHPLC-Q-Orbitrap HRMS was used to identify the components of the XZF. A high-fat diet (HFD)-induced NAFLD mouse model was used to demonstrate the effectiveness of XZF. Body weight, liver weight, and white fat weight were recorded to evaluate the therapeutic efficacy of XZF. H&E and Oil Red O staining were applied to observe the extent of hepatic steatosis. Liver damage, lipid metabolism, and glucose metabolism were detected by relevant assay kits. Moreover, the intraperitoneal insulin tolerance test and the intraperitoneal glucose tolerance test were employed to evaluate the efficacy of XZF in insulin homeostasis. Hepatocyte oxidative damage markers were detected to assess the efficacy of XZF in preventing oxidative stress. Label-free proteomics was used to investigate the underlying mechanism of XZF in NAFLD. RT-qPCR was used to calculate the expression levels of lipid metabolism genes. Western blot analysis was applied to detect the hepatic protein expression of AMPK, p-AMPK, PPARɑ, CPT1, and PPARγ. RESULTS: 120 compounds were preliminarily identified from XZF by UHPLC-Q-Orbitrap HRMS. XZF could alleviate HFD-induced obesity, white adipocyte size, lipid accumulation, and hepatic steatosis in mice. Additionally, XZF could normalize glucose levels, improve glucolipid metabolism disorders, and prevent oxidative stress damage induced by HFD. Furthermore, the proteomic analysis showed that the major pathways in fatty acid metabolism and the PPAR signaling pathway were significantly impacted by XZF treatment. The expression levels of several lipolytic and ß-oxidation genes were up-regulated, while the expression of fatty acid synthesis genes declined in the HFD + XZF group. Mechanically, XZF treatment enhanced the expression of p-AMPK, PPARɑ, and CPT-1 and suppressed the expression of PPARγ in the livers of NAFLD mice, indicating that XZF could activate the AMPK and PPAR pathways to attenuate NALFD progression. CONCLUSION: XZF could attenuate NAFLD by moderating lipid metabolism by activating AMPK and PPAR signaling pathways.

Aggregation-Induced Emission Luminogens: A New Possibility for Efficient Visualization of RNA in Plants.

RNAs play important roles in regulating biological growth and development. Advancements in RNA-imaging techniques are expanding our understanding of their function. Several common RNA-labeling methods in plants have pros and cons. Simultaneously, plants' spontaneously fluorescent substances interfere with the effectiveness of RNA bioimaging. New technologies need to be introduced into plant RNA luminescence. Aggregation-induced emission luminogens (AIEgens), due to their luminescent properties, tunable molecular size, high fluorescence intensity, good photostability, and low cell toxicity, have been widely applied in the animal and medical fields. The application of this technology in plants is still at an early stage. The development of AIEgens provides more options for RNA labeling. Click chemistry provides ideas for modifying AIEgens into RNA molecules. The CRISPR/Cas13a-mediated targeting system provides a guarantee of precise RNA modification. The liquid-liquid phase separation in plant cells creates conditions for the enrichment and luminescence of AIEgens. The only thing that needs to be looked for is a specific enzyme that uses AIEgens as a substrate and modifies AIEgens onto target RNA via a click chemical reaction. With the development and progress of artificial intelligence and synthetic biology, it may soon be possible to artificially synthesize or discover such an enzyme.

Effect of Sarcopenic Obesity on Weight Loss Outcomes and Quality of Life after Laparoscopic Sleeve Gastrectomy: A Retrospective Cohort Study.

BACKGROUND: Sarcopenic obesity may affect the health outcome of people with obesity after laparoscopic sleeve gastrectomy (LSG). To assess the impact of sarcopenic obesity (SO) on weight loss outcomes and improvement of quality of life after LSG. MATERIALS AND METHODS: This observational study included patients who underwent LSG with SO (99 patients) or without SO (146 patients) from a single center. The primary endpoint was weight loss and disease-specific quality of life in patients with or without SO after the operation. Fat-free mass (FFM) and fat mass (FM) were calculated based on the L3-level images of preoperative CT scans. SO was diagnosed if FM/FFM ≥ 0.80. RESULTS: Operative time and postoperative hospital stay days were longer in the SO group (p < 0.001). After LSG, weight, BMI, and EBMI were significantly lower in the NSO group than in the SO group (all P < 0.05), while %EWL and the number of patients with %EWL ≥ 100% were significantly lower in the SO group (both p < 0.05). The total BAROS scores of patients in the NSO group were higher than those in the SO group (p < 0.05). Additionally, the MA II questionnaire assessment showed a lower percentage of "very good" and "good" outcomes in the SO group (p < 0.05). CONCLUSIONS: Patients with SO take a slower rate, longer time to reach the ideal weight, and lower quality of life self-ratings than NSO patients after LSG. Thus, preoperative evaluation and tailoring rehabilitation guidance for people with SO should be accounted.

Long-term survival outcomes of robotic total gastrectomy for locally advanced proximal gastric cancer: a prospective study.

BACKGROUND: Robotic gastrectomy is a safe and feasible approach for gastric cancer (GC); however, its long-term oncological efficacy remains unclear. We evaluated the long-term survival outcomes and recurrence patterns of patients with locally advanced proximal GC who underwent robotic total gastrectomy (RTG). METHODS: This prospective study (FUGES-014 study) enrolled 48 patients with locally advanced proximal GC who underwent RTG between March 2018 and February 2020 at a tertiary referral teaching hospital. Patients who underwent laparoscopic total gastrectomy (LTG) in the FUGES-002 study were enrolled in a 2:1 ratio to compare the survival outcomes between RTG and LTG. The primary endpoint of the FUGES-014 study was postoperative 30-day morbidity and has been previously reported. Here we reported the results of 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence patterns. RESULTS: After propensity score matching, 48 patients in the RTG and 96 patients in the LTG groups were included. The 3-year DFS rates were 77.1% (95% confidence interval [CI] 66.1-89.9%) for the RTG and 68.8% (95% CI 60.1-78.7%) for the LTG groups ( P =0.261). The 3-year OS rates were not significantly different between the groups (85.4% vs. 74.0%, P =0.122). Recurrence occurred in nine patients (18.8%) in the RTG and 27 (28.1%) patients in the LTG groups ( P =0.234). Recurrence patterns and causes of death were similar between the groups ( P >0.05). CONCLUSIONS: The oncological outcome of RTG was non-inferior to that of LTG. Thus, RTG might be an alternative surgical treatment for locally advanced proximal GC.

Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology.

Multiple sclerosis (MS) is a neurological disease characterized by multifocal lesions and smoldering pathology. Although single-cell analyses provided insights into cytopathology, evolving cellular processes underlying MS remain poorly understood. We investigated the cellular dynamics of MS by modeling temporal and regional rates of disease progression in mouse experimental autoimmune encephalomyelitis (EAE). By performing single-cell spatial expression profiling using in situ sequencing (ISS), we annotated disease neighborhoods and found centrifugal evolution of active lesions. We demonstrated that disease-associated (DA)-glia arise independently of lesions and are dynamically induced and resolved over the disease course. Single-cell spatial mapping of human archival MS spinal cords confirmed the differential distribution of homeostatic and DA-glia, enabled deconvolution of active and inactive lesions into sub-compartments, and identified new lesion areas. By establishing a spatial resource of mouse and human MS neuropathology at a single-cell resolution, our study unveils the intricate cellular dynamics underlying MS.

Photo-induced intramolecular dearomative [5 + 4] cycloaddition of arenes for the construction of highly strained medium-sized-rings.

Medium-sized-ring compounds have been recognized as challenging synthetic targets in organic chemistry. Especially, the difficulty of synthesis will be augmented if an E-olefin moiety is embedded. Recently, photo-induced dearomative cycloaddition reactions that proceed via energy transfer mechanism have witnessed significant developments and provided powerful methods for the organic transformations that are not easily realized under thermal conditions. Herein, we report an intramolecular dearomative [5 + 4] cycloaddition of naphthalene-derived vinylcyclopropanes under visible-light irradiation and a proper triplet photosensitizer. The reaction affords dearomatized polycyclic molecules possessing a nine-membered-ring with an E-olefin moiety in good yields (up to 86%) and stereoselectivity (up to 8.8/1 E/Z). Detailed computational studies reveal the origin behind the favorable formation of the thermodynamically less stable isomers. Diverse derivations of the dearomatized products have also been demonstrated.

Textbook oncological outcomes and prognosis after curative gastrectomy in advanced gastric cancer: A multicenter study.

BACKGROUND: The impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. METHODS: Patients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. RESULTS: Among 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61-0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66-0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33-39% and 28-37%, respectively. CONCLUSIONS: TOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.

Tunable C-H functionalization and dearomatization enabled by an organic photocatalyst.

C-H functionalization and dearomatization constitute fundamental transformations of aromatic compounds, which find wide applications in various research areas. However, achieving both transformations from the same substrates with a single catalyst by operating a distinct mechanism remains challenging. Here, we report a photocatalytic strategy to modulate the reaction pathways that can be directed toward either C-H functionalization or dearomatization under redox-neutral or net-reductive conditions, respectively. Two sets of indoles and indolines bearing tertiary alcohols are divergently furnished with good yields and high selectivity. The key to success is the introduction of isoazatruxene ITN-2 as a novel photocatalyst (PC), which outperforms the commonly used PCs. The ready synthesis and high modulability of isoazatruxene type PCs indicate their great application potential.

EasyDAM_V4: Guided-GAN-based cross-species data labeling for fruit detection with significant shape difference.

Traditional agriculture is gradually being combined with artificial intelligence technology. High-performance fruit detection technology is an important basic technology in the practical application of modern smart orchards and has great application value. At this stage, fruit detection models need to rely on a large number of labeled datasets to support the training and learning of detection models, resulting in higher manual labeling costs. Our previous work uses a generative adversarial network to translate the source domain to the target fruit images. Thus, automatic labeling is performed on the actual dataset in the target domain. However, the method still does not achieve satisfactory results for translating fruits with significant shape variance. Therefore, this study proposes an improved fruit automatic labeling method, EasyDAM_V4, which introduces the Across-CycleGAN fruit translation model to achieve spanning translation between phenotypic features such as fruit shape, texture, and color to reduce domain differences effectively. We validated the proposed method using pear fruit as the source domain and three fruits with large phenotypic differences, namely pitaya, eggplant, and cucumber, as the target domain. The results show that the EasyDAM_V4 method achieves substantial cross-fruit shape translation, and the average accuracy of labeling reached 87.8, 87.0, and 80.7% for the three types of target domain datasets, respectively. Therefore, this research method can improve the applicability of the automatic labeling process even if significant shape variance exists between the source and target domain.