Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies.

Epilepsy is a severe, relapsing, and multifactorial neurological disorder. Studies regarding the accurate diagnosis, prognosis, and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy. The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression, protein expression, ion channel activity, energy metabolites, and gut microbiota composition. Satisfactory results are lacking for conventional treatments for epilepsy. Surgical resection of lesions, drug therapy, and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy. Non-pharmacological treatments, such as a ketogenic diet, gene therapy for nerve regeneration, and neural regulation, are currently areas of research focus. This review provides a comprehensive overview of the pathogenesis, diagnostic methods, and treatments of epilepsy. It also elaborates on the theoretical basis, treatment modes, and effects of invasive nerve stimulation in neurotherapy, including percutaneous vagus nerve stimulation, deep brain electrical stimulation, repetitive nerve electrical stimulation, in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation. Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures. Additionally, many new technologies for the diagnosis and treatment of epilepsy are being explored. However, current research is mainly focused on analyzing patients' clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level, which has led to a lack of consensus regarding the mechanisms related to the disease.

Identification of male schizophrenia patients using brain morphology based on machine learning algorithms.

BACKGROUND: Schizophrenia is a severe psychiatric disease, and its prevalence is higher. However, diagnosis of early-stage schizophrenia is still considered a challenging task. AIM: To employ brain morphological features and machine learning method to differentiate male individuals with schizophrenia from healthy controls. METHODS: The least absolute shrinkage and selection operator and t tests were applied to select important features from structural magnetic resonance images as input features for classification. Four commonly used machine learning algorithms, the general linear model, random forest (RF), k-nearest neighbors, and support vector machine algorithms, were used to develop the classification models. The performance of the classification models was evaluated according to the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 8 important features with significant differences between groups were considered as input features for the establishment of classification models based on the four machine learning algorithms. Compared to other machine learning algorithms, RF yielded better performance in the discrimination of male schizophrenic individuals from healthy controls, with an AUC of 0.886. CONCLUSION: Our research suggests that brain morphological features can be used to improve the early diagnosis of schizophrenia in male patients.

LINC02257 regulates colorectal cancer liver metastases through JNK pathway.

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood. Methods: To explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM. Results: Our findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM. Conclusions: Our study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.

Clinical characteristics and risk factors of post-operative intestinal flora disorder following laparoscopic colonic surgery: A propensity-score-matching analysis.

BACKGROUND: Intestinal flora disorder (IFD) poses a significant challenge after laparoscopic colonic surgery, and no standard criteria exists for its diagnosis and treatment. AIM: To analyze the clinical features and risk factors of IFD. METHODS: Patients with colon cancer receiving laparoscopic surgery were included using propensity-score-matching (PSM) methods. Based on the occurrence of IFD, patients were categorized into IFD and non-IFD groups. The clinical characteristics and treatment approaches for patients with IFD were analyzed. Multivariate regression analysis was performed to identify the risk factors of IFD. RESULTS: The IFD incidence after laparoscopic surgery was 9.0% (97 of 1073 patients). After PSM, 97 and 194 patients were identified in the IFD and non-IFD groups, respectively. The most common symptoms of IFD were diarrhea and abdominal, typically occurring on post-operative days 3 and 4. All patients were managed conservatively, including modulation of the intestinal flora (90.7%), oral/intravenous application of vancomycin (74.2%), and insertion of a gastric/ileus tube for decompression (23.7%). Multivariate regression analysis identified that pre-operative intestinal obstruction [odds ratio (OR) = 2.79, 95%CI: 1.04-7.47, P = 0.041] and post-operative antibiotics (OR = 8.57, 95%CI: 3.31-23.49, P < 0.001) were independent risk factors for IFD, whereas pre-operative parenteral nutrition (OR = 0.12, 95%CI: 0.06-0.26, P < 0.001) emerged as a protective factor. CONCLUSION: A stepwise approach of probiotics, vancomycin, and decompression could be an alternative treatment for IFD. Special attention is warranted post-operatively for patients with pre-operative obstruction or early use of antibiotics.

Risk Factors for Postoperative Complications of Laparoscopic Right Colectomy: A Post Hoc Analysis of RELARC Trial.

BACKGROUND: There is concern regarding the possibility of postoperative complications for laparoscopic right colectomy. OBJECTIVE: To evaluate the risk factors of postoperative complications for patients undergoing laparoscopic right colectomy. DESIGN: This was an observational study. SETTINGS: This was a post-hoc analysis of a prospective, multicenter, randomized controlled trial (RELARC trial, NCT02619942). PATIENTS: Patients included in the modified intention-to-treat analysis in RELARC trial were all enrolled in this study. MAIN OUTCOME MEASURES: Risk factors for postoperative complications were identified using univariate and multivariable logistic regression analysis. RESULTS: Of 995 patients, 206 (20.7%) had postoperative complications. Comorbidity (p = 0.02, OR: 1.544, 95% CI: 1.077-2.212) and operative time >180 min (p = 0.03, OR: 1.453, 95% CI: 1.032-2.044) were independent risk factors for postoperative complications. While female (p = 0.04, OR: 0.704, 95% CI: 0.506-0.980) and extracorporeal anastomosis (p < 0.001, OR: 0.251, 95% CI: 0.166-0.378) were protective factors. Eighty (8.0%) had overall surgical site infection, 53 (5.3%) had incisional SSI, and 33 (3.3%) had organ/space SSI. Side-to-side anastomosis was a risk factor for overall surgical site infection (p < 0.001, OR: 1.912, 95% CI: 1.118-3.268) and organ/space surgical site infection (p = 0.005, OR: 3.579, 95% CI: 1.455-8.805). Extracorporeal anastomosis was associated with a reduced risk of overall surgical site infection (p < 0.001, OR: 0.239, 95% CI: 0.138-0.413), organ/space surgical site infection (p = 0.002 OR: 0.296, 95% CI: 0.136-0.646), and incisional surgical site infection (p < 0.001, OR: 0.179, 95% CI: 0.099-0.322). Diabetes (p = 0.039 OR: 2.090, 95% CI: 1.039-4.205) and conversion to open surgery (p = 0.013 OR: 5.403, 95% CI: 1.437-20.319) were risk factors for incisional surgical site infection. LIMITATIONS: Due to the retrospective nature, the key limitation is the lack of prospective documentation and standardization about perioperative management of these patients such as preoperative optimization, bowel prep regimes and antibiotic regimes, which may be confounder factors of complications. All surgeries were done by experienced surgeons and the patients enrolled were relatively young, generally healthy, and non-obese. It is unclear whether the results will be generalizable to obese and other populations worldwide. CONCLUSIONS: Male, comorbidity, prolonged operative time, and intracorporeal anastomosis were independent risk factors of postoperative complications of laparoscopic right colectomy. Side-to-side anastomosis was associated with an increased risk of organ/space surgical site infection. Extracorporeal anastomosis could reduce the incidence of overall surgical site infection. Diabetes and conversion to open surgery were associated with an increased risk of incisional surgical site infection. See Video Abstract.

Robot-assisted radical resection of colorectal cancer using the KangDuo surgical robot versus the da Vinci Xi robotic system: short-term outcomes of a multicentre randomised controlled noninferiority trial.

BACKGROUND: The KangDuo surgical robot (KD-SR-01) was recently developed in China. This study aims to evaluate the short-term outcomes of KD-SR-01 for colorectal cancer surgery. METHODS: This is a multicentre randomised controlled noninferiority trial conducted in three centers in China. Enrolled patients were randomly assigned at a 1:1 ratio to receive surgery using the KD-SR-01 system (KD group) or the da Vinci Xi (DV) robotic system (DV group). The primary endpoint was the success rate of operation. The second endpoints were surgical outcomes, pathological outcomes, and postoperative outcomes. RESULTS: Between July 2022 and May 2023. A total of 100 patients were included in the trial and randomly assigned to the KD group (50 patients) and the DV group (50 patients). All cases were completed successfully without conversion to laparoscopic surgery. The time to flatus and the incidence of postoperative complications of Clavien-Dindo grade II or higher grade were comparable between the two groups. Surgeons reported a high level of comfort with the KD-SR-01 system. In the subgroup analysis of different operative procedures, there were no significant differences in docking time, console time, blood loss, and the length of the incision for extraction between the two groups. There were no differences in pathological outcomes including maximum tumor diameter, circumferential resection margin, distal resection margin, and number of harvested lymph nodes. CONCLUSIONS: The KD-SR-01 system was a viable option for colorectal cancer robotic surgery, with acceptable short-term outcomes comparable to the da Vinci Xi robotic system.

Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance.

Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal cancer-derived organoid biobank and induced acquired drug resistance by repeated low-level exposures of chemo-agents. Chemosensitivity profiling and transcriptomic analysis studies revealed that chemoresistant cancer-derived organoids exhibited elevated expression of LGR4 and activation of the Wnt signaling pathway. Further, we generated a monoclonal antibody (LGR4-mAb) that potently inhibited LGR4-Wnt signaling and found that treatment with LGR4-mAb notably sensitized drug-induced ferroptosis. Mechanistically, LGR4-dependent Wnt signaling transcriptionally upregulated SLC7A11, a key inhibitor of ferroptosis, to confer acquired drug resistance. Our findings reveal that targeting of Wnt signaling by LGR4-mAb augments ferroptosis when co-administrated with chemotherapeutic agents, demonstrating a potential opportunity to fight refractory and recurrent cancers.

Design of Boron and Transition Metal Embedded Two-Dimensional Porous Carbon Nitride for Electrocatalytic Synthesis of Urea.

Electrocatalytic coupling of CO and N2 to synthesize urea under ambient conditions is considered a promising strategy to replace traditional industrial technology. It is crucial to find efficient electrocatalysts that can adsorb and activate N2 and promote the C-N coupling reaction. Herein, a new two-dimensional porous carbon nitride material with multiactive sites is designed, in which boron and transition metal are embedded. Through a series of screening, B2Cr2, B2Mn2, and B2Os2 are predicted to be potential electrocatalysts for urea synthesis. Mechanistic studies are performed on bidentate metal-metal and metal-boron sites, and both NCON and CO mechanisms are explored. The electronic structure analysis shows that there is a strong N2 chemical adsorption within the bidentate site and that the N≡N bond is significantly activated. A new mechanism where free CO is inserted for C-N coupling within the two-dimensional porous structure is proposed.

Correlation analysis of mental health conditions and personality of patients with alcohol addiction.

BACKGROUND: Alcohol addiction, or alcohol dependence, refers to a psychological state of strong craving for alcohol caused by drinking when both the drinking times and alcohol consumption reach a certain level. Alcohol addiction can cause irreversible damage, leading to mental illness or mental disorders, negative changes in their original personality, and a tendency to safety incidents such as committing suicide or violent attacks on others. Significant attention needs to be given to the mental health of alcohol addicts, which could reflect their abnormal personality traits. However, only a few papers on this issue have been reported in China. AIM: To investigate the correlation between mental health and personality in patients with alcohol addiction. METHODS: In this single-center observational study, we selected 80 patients with alcohol addiction as the research subjects, according to the criteria of the K10 scale to evaluate the mental health of patients with alcohol addiction, and divided these patients into four groups based on the evaluation results: Good, average, relatively poor and bad. And then analyzed the correlation between mental health conditions and personality characteristics from these four groups of patients. RESULTS: The average score of the K10 scale (Kessler 10 Simple Psychological Status Assessment Scale) in 80 patients with alcohol addiction was 25.45 points, the median score was 25 points, the highest score was 50 points, and the lowest score was 11 points. Pearson's analysis showed that the K10 score was positively correlated with the scores of these two subscales, such as the P-subscale and the N-subscale (P < 0.05). In contrast, the K10 score had no significant correlation with the scores from the E-subscale and the L-subscale (P > 0.05). CONCLUSION: The mental health conditions of patients with alcohol addiction are positively correlated with their personality characteristics.

Interaction analysis of high-risk pathological features on adjuvant chemotherapy survival benefit in stage II colon cancer patients: a multi-center, retrospective study.

BACKGROUND: We aimed to analyze the benefit of adjuvant chemotherapy in high-risk stage II colon cancer patients and the impact of high-risk factors on the prognostic effect of adjuvant chemotherapy. METHODS: This study is a multi-center, retrospective study, A total of 931 patients with stage II colon cancer who underwent curative surgery in 8 tertiary hospitals in China between 2016 and 2017 were enrolled in the study. Cox proportional hazard model was used to assess the risk factors of disease-free survival (DFS) and overall survival (OS) and to test the multiplicative interaction of pathological factors and adjuvant chemotherapy (ACT). The additive interaction was presented using the relative excess risk due to interaction (RERI). The Subpopulation Treatment Effect Pattern Plot (STEPP) was utilized to assess the interaction of continuous variables on the ACT effect. RESULTS: A total of 931 stage II colon cancer patients were enrolled in this study, the median age was 63 years old (interquartile range: 54-72 years) and 565 (60.7%) patients were male. Younger patients (median age, 58 years vs 65 years; P < 0.001) and patients with the following high-risk features, such as T4 tumors (30.8% vs 7.8%; P < 0.001), grade 3 lesions (36.0% vs 22.7%; P < 0.001), lymphovascular invasion (22.1% vs 6.8%; P < 0.001) and perineural invasion (19.4% vs 13.6%; P = 0.031) were more likely to receive ACT. Patients with perineural invasion showed a worse OS and marginally worse DFS (hazardous ratio [HR] 2.166, 95% confidence interval [CI] 1.282-3.660, P = 0.004; HR 1.583, 95% CI 0.985-2.545, P = 0.058, respectively). Computing the interaction on a multiplicative and additive scale revealed that there was a significant interaction between PNI and ACT in terms of DFS (HR for multiplicative interaction 0.196, p = 0.038; RERI, -1.996; 95%CI, -3.600 to -0.392) and OS (HR for multiplicative interaction 0.112, p = 0.042; RERI, -2.842; 95%CI, -4.959 to -0.725). CONCLUSIONS: Perineural invasion had prognostic value, and it could also influence the effect of ACT after curative surgery. However, other high-risk features showed no implication of efficacy for ACT in our study. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03794193 (04/01/2019).

Development and usability of a Mobile Interactive Application (VCPW) for Vascular Crisis Prewarning after Skin Flap Transplantation.

Background: In microsurgical tissue transfer, skin flap transplantation is frequently used to heal the surface of a wound. Effective microcirculation surveillance of the skin flap is crucial. However, with traditional monitoring methods-that is, clinical observation-vascular crisis can still occur, thereby impairing postoperative recovery. A smartphone application is required to assist health care professionals in the standardized collection of flap perfusion parameters for flap management. Methods: The Vascular Crisis Prewarning Application was created using a design science research methodology that prioritizes users and problems. The system usability scale was used to assess the application's usability among medical practitioners. The application was used at the clinic from December 2020 to September 2022. The unplanned return to the operating room, time to diagnose vascular crisis, and flap survival rate were compared with and without the application. Results: The application consisted of 5 modules: patient addition and basic information entry, flap labeling, flap observation, crisis warning, and case archiving. The average rating for the application's usability among medical practitioners was 97.95 score (SD 2.36). With the application, the time to detect vascular crisis reduced from 26.71 to 16.26 h (P < 0.001), the unplanned return to the operation room increased from 8.18% to 10.24% (P = 0.587), and the flap survival rate went from 94.55% to 99.21% (P = 0.083). Conclusions: An easy-to-use flap perfusion monitoring and prewarning application for medical practitioners was produced using a user-centered development method. The application provided a more standardized and accurate platform for data collection in flap management and reduced the time to detect vascular crisis. Larger cohort studies are required in the future to better assess the full potential of the application.

Proteomic profiling and functional characterization of serum-derived extracellular vesicles in the mucinous and non-mucinous colon adenocarcinoma.

PURPOSE: Mucinous adenocarcinoma (MC) is a distinct pathological subtype of colon adenocarcinoma, which is associated with a worse prognosis compared with non-mucinous adenocarcinoma (AC). However, clear distinctions between MC and AC remain unknown. Extracellular vesicles (EVs) are a class of enclosed vesicles containing proteins, lipids, and nucleic acids that are secreted by cells into surrounding tissues or into serum. The EVs could facilitate tumorigenesis by regulating tumor cell proliferation, invasiveness, metastasis, angiogenesis, and evasion of immune surveillance. METHODS: Quantitative proteomics analysis was performed to determine the characterization and biological differences of serum-derived EVs in two subtypes of colon adenocarcinoma (MC and AC). Serum-derived EVs from patients with MC, AC, and healthy volunteers were included in this study. The role of PLA2G2A in cell migration and invasion were evaluate with transwell assay, and its prognostic predictive value was further assessed based on TCGA database. RESULTS: Quantitative proteomics analysis revealed 846 differentially expressed proteins (DEPs) in EVs from MC patients compared with those from AC patients. Bioinformatics analysis revealed that the most prominent protein cluster included those involved in cell migration and the tumor microenvironment. Overexpression of PLA2G2A, one of the key EV proteins upregulated in patients with MC, in colon cancer cell line SW480 promoted the cell invasion and migration ability. In addition, the high level of PLA2G2A is associated with poor prognosis of colon cancer patients harboring BRAF mutations. Further, after EV stimulation, proteomic analysis of recipient SW480 cells showed that MC-derived EVs activated multiple cancer-related pathways, including the Wnt/ß-Catenin signaling pathway, and might promote the malignancy of mucinous adenocarcinoma through these pathways. CONCLUSIONS: The identification of differential protein profiles between MC and AC helps to elucidate the underlying molecular mechanisms of MC pathogenesis. The PLA2G2A in EVs is a potential prognostic predictive marker for those patients harboring with BRAF mutations.

Surgical site infection after intracorporeal and extracorporeal anastomosis in laparoscopic left colectomy for colon cancer: a multicenter propensity score-matched cohort study.

BACKGROUND: Intracorporeal anastomosis (IA) is associated with reduced surgical site infection (SSI) and other postoperative complications in laparoscopic right colectomy (LRC). However, evidence is inadequate for IA in laparoscopic left colectomy (LLC). This study aimed to determine the effect of IA and extracorporeal anastomosis (EA) on SSI and other short-term postoperative complications in LLC. METHODS: In this retrospective multicenter propensity score-matched (PSM) cohort study, we enrolled consecutive patients who underwent LLC with IA (TLLC/IA) and laparoscopic-assisted left colectomy with EA (LALC/EA) at two medical centers between January 2015 and September 2021. Propensity score matching with a 1:2 ratio was employed. The primary outcome was SSI occurrence. Secondary outcomes were operating time, intraoperative hemorrhage, other postoperative complications, and pathological outcomes. RESULTS: Overall, 574 and 99 patients received LALC/EA and TLLC/IA, respectively. After PSM, 84 patients with TLLC/IA were matched with 141 patients with LALC/EA. Thirty patients (13.3%) patients experienced SSI (17.0% in LALC/EA vs 7.1% in TLLC/IA). IA was associated with a reduced risk of overall SSI and superficial/deep SSI compared with EA after PSM, with OR of 0.375 (95% CI, 0.147-0.959, P = 0.041). and 0.148 (95% CI, 0.034-0.648, P = 0.011), respectively. Multivariate analysis of unmatched patients indicated similar results. In the analysis of secondary outcomes, LALC/EA may have a shorter operating time (absolute mean difference - 13.41 [95% CI, - 23.76 to - 3.06], P = 0.002) and a higher risk of intraoperative hemorrhage (absolute risk difference 4.96 [95% CI, - 0.09 to 9.89], P = 0.048). CONCLUSIONS: IA in LLC is associated with a reduced risk of overall SSI and superficial/deep SSI. However, it may require a longer operating time.

Association of serum folate with prevalence of non-alcoholic fatty liver disease among adults (NHANES 2011-2018).

Background: Folate was involved in oxidative stress, hepatic lipid metabolism and chronic hepatic inflammation. However, evidence about the association between serum folate level and non-alcoholic fatty liver disease (NAFLD) in general population is scarce. This study aimed to explore the relationship between serum folate level and NAFLD among adults. Methods: 7,146 adult participants aged 20 years and over who have complete data of serum folate level and liver function biomarkers in NHANES 2011-2018 were included. Serum folate level was measured by isotope-dilution high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). And suspected NAFLD was defined according to the United States fatty liver index (USFLI). Logistic regression and the restricted cubic spline models were performed. Results: Serum folate level was inversely associated with the presence of NAFLD. When comparing the second, third and fourth quartiles of serum folate level to the lowest quartile, the adjusted ORs of the presence of NAFLD were 0.62 (0.49-0.78), 0.65 (0.51-0.84), and 0.43 (0.32-0.56) respectively (p for trend<0.001). The non-linear and L-shaped relationship was found between serum folate level and the presence of NAFLD in the restricted cubic spline regression (p for non-linearity <0.01). Consistent with serum total folate, serum 5-Methyltetrahydrofolate level was also inversely associated with the presence of NAFLD. Conclusion: Higher serum folate level may be negatively associated with NAFLD.

UTP18-mediated p21 mRNA instability drives adenoma-carcinoma progression in colorectal cancer.

Colorectal cancer (CRC) often develops slowly from adenoma, but the underlying mechanism remains unclear, hampering the prevention or treatment of colorectal adenoma-carcinoma progression. In this study, we use in-depth quantitative proteomics combined with survival analysis, revealing that the ribosome protein U3 small nucleolar RNA-associated protein 18 homolog (UTP18) is consistently upregulated in the progression of colorectal adenoma to carcinoma and is associated with adenoma recurrence, effective serodiagnosis, and poor prognosis of CRC. Furthermore, deSUMOylation induces the nucleocytoplasmic transport of UTP18, driving cell-cycle progression and tumorigenesis via mediation of the instability of p21 mRNA. In addition, the growth and ribosome biogenesis of adenoma organoids is found to be promoted by overexpression of UTP18. Thus, UTP18 contributes to multiple roles in adenogenesis and malignancy of CRC, suggesting that it could be a potential biomarker and drug target for colorectal adenoma and cancer.

Design of a Four-Atom Cluster Embedded in Carbon Nitride for Electrocatalytic Generation of Multi-Carbon Products.

The development of efficient and stable catalysts for the electrocatalytic CO2 and CO reduction reactions (CORR) is under active investigation, but the problems of poor selectivity and low efficiency for C2 products still exist. We design a two-dimensional carbon nitride material (C5N2H2) that contains an eight N-atom structure capable of coordinating four-metal atom clusters and supporting simultaneously two carbon oxide molecules needed for the C2 coupling. The designed material has excellent electrical conductivity and stability. After high-throughput screening of catalytic performance of multiple four-metal clusters embedded into the framework, we systematically investigate the CORR process of 11 candidates. We find that Cu4-C5N2H2 has superior selectivity and low limiting potential for generating ethylene, while Cu2Zn2-C5N2H2 is selective and efficient to synthesize ethanol. Further, we discover a novel type of descriptor related to 2D material flexibility to evaluate the potential-determining step for generating ethylene. Our report both broadens the possibilities for few-atom CO reduction and demonstrates a novel substrate flexibility-related descriptor to predict the catalytic performance of materials.

Prediction of Three-Metal Cluster Catalysts on Two-Dimensional W2N3 Support with Integrated Descriptors for Electrocatalytic Nitrogen Reduction.

In the electrocatalytic nitrogen reduction reaction (NRR), nitrogen (N2) is chemically inert, it is difficult to break the triple bond, and the subsequent protonation step is very challenging. Suitable catalysts with high selectivity and high activity are needed to promote the electrocatalytic NRR. We screen a large number of clusters composed of three metal atoms embedded into a two-dimensional metal nitride, W2N3, with a N vacancy, and calculate the reaction energetics. The VNiCu cluster has the best catalytic activity among all the catalysts proposed so far. The Fe3 and Fe2Co clusters are excellent catalysts as well. In all cases, spin polarization is needed to observe the catalytic effect. We establish the optimal NRR path and confirm that it remains unchanged in the presence of a solvent. We find three groups of descriptors that can well predict the materials' properties and exhibit linear relationships with the NRR limiting potential.

Intracorporeal Anastomosis Versus Extracorporeal Anastomosis in Laparoscopic Right Colectomy: An Observational Cohort Study.

BACKGROUND: Current studies did not draw definitive conclusions on comparison of intracorporeal anastomosis (ICA) with extracorporeal anastomosis (ECA) in laparoscopic right colectomy. Whether the intraperitoneal contamination induced by ICA can result in higher risk of postoperative abdominal infection remains unclear. This study was aimed to compare the short-term outcomes, especially the risk of abdominal infection after ICA versus ECA. METHODS: This was an observational cohort study as a secondary analysis of a randomized controlled trial (RCT)-RELARC trial (NCT02619942). The patients enrolled in the RELARC trial were diagnosed with primary colon adenocarcinoma without distant metastasis and underwent radical laparoscopic right colectomy between Jan 2016 and Dec 2019. In our study the patients who converted to open surgery in RELARC trial were excluded. The short-term outcomes were compared between ICA and ECA. The primary endpoint was abdominal infection. The inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) was used for adjusting the potential confounders. RESULTS: This study enrolled 975 patients with 119 patients undergoing ICA and 856 patients undergoing ECA. The incidence of abdominal infection was higher in ICA group (9.2% versus 1.5%, RR from IPTW = 5.7 (95%CI: 2.6-12.6), P < 0.001) as well as the incidence of wound infection (14.3% vs 3.3%, RR from IPTW = 5.0 (95%CI: 2.9-8.6), P < 0.001). ICA was associated with higher incidence of Clavien-Dindo (CD) grade I and II complications (CD-I: 15.1% versus 6.8%, RR from IPTW = 2.4 (95%CI: 1.5-3.9), P < 0.001; CD-II: 26.9% versus 8.2%, RR from IPTW = 3.6 (95%CI: 2.5-5.1), P < 0.001) but similar incidence of CD-III ~ IV complications compared to ECA (3.4% vs 2.1%, RR from IPTW = 1.2 (95%CI: 0.4-4.0), P = 0.73). In ICA group, choosing another incision rather than lengthening main port site decreased the incidence of wound infection although without statistical significance (17.3% (14/81) versus 7.9% (3/38), crude RR = 2.2 (95%CI: 0.7-7.2), P = 0.17). CONCLUSION: ICA is likely to be associated with higher risk of abdominal infection and CD-I ~ II complications.

Comparison of safety of loop ileostomy and loop transverse colostomy for low-lying rectal cancer patients undergoing anterior resection: A retrospective, single institution, propensity score-matched study.

INTRODUCTION: This study was to compare the prevalence of stoma-related complications and stoma reversal perioperative complications of patients with low-lying rectal cancer who received preventative loop ileostomy and those who underwent loop transverse colostomy. METHODS: This retrospective single-center study analyzed the clinicopathologic and surgical data of 288 patients with pathologically proven primary rectal cancer who underwent anterior resection with either preventative loop ileostomy (n = 82) or loop transverse colostomy. To achieve comparability of a propensity score matching method was used to match patients from each group in a 1:2 ratio. Determinants of stoma-related complications were analyzed by multivariate logistic regression analysis. RESULTS: Forty-nine (74.3%) patients in the loop ileostomy group experienced stoma-related complications versus 48.7% in the loop transverse colostomy group (P < 0.01). Irritant dermatitis was the most frequent complication in both groups. The loop ileostomy group had a significantly higher rate (24.24%) of stoma reversal perioperative complications than the loop transverse colostomy group. Multivariate logistic regression analysis showed that ileostomy versus loop transverse colostomy was a significant independent risk for stoma-related complications and stoma reversal perioperative complications. Furthermore, by Clavien-Dindo classification, patients receiving loop ileostomy had an overall higher rate of complications and stoma reversal perioperative complications versus those undergoing loop transverse colostomy (P < 0.01). The rate of grade II complications was significantly higher in the loop ileostomy group (43.9%) than that of loop transverse colostomy group (13.5%, P < 0.01), whereas the rate of grade I, and grade IIIa and IIIb complications and stoma reversal perioperative complications was comparable between the two groups. CONCLUSION: The study has demonstrated that loop transverse colostomy is associated with significantly lower rates of stoma-related complications and stoma reversal perioperative complications compared to loop transverse colostomy.

Spatiotemporal Dynamics of the Molecular Expression Pattern and Intercellular Interactions in the Glial Scar Response to Spinal Cord Injury.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.