Aromatization-driven deconstructive functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis.

Aromatization-driven deconstruction and functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis is developed. The aromatization effect was introduced to synergistically drive unstrained cyclic C-C bond cleavage, with the aim of overcoming the ring-size limitation of nitrogen-centered radical induced deconstruction of carbocycles. Herein, we demonstrate the synergistic photoredox/nickel catalyzed deconstructive cross-coupling of spiro dihydroquinazolinones with organic halides. Remarkably, structurally diverse organic halides including aryl, alkenyl, alkynyl, and alkyl bromides were compatible for the coupling. In addition, this protocol is also characterized by its mild and redox-neutral conditions, excellent functional group compatibility, high atom economy, and easy scalability. A telescoped procedure involving condensation and ring-opening/coupling was found to be accessible. This work provides a complementary strategy to the existing radical-mediated C-C bond cleavage of unstrained carbocycles.

The safety and short-term effect of mixed approach in laparoscopic right hemicolectomy for right colon cancer compared with middle approach: a retrospective study.

PURPOSE: To investigate whether the mixed approach is a safe and advantageous way to operate laparoscopic right hemicolectomy. METHODS: A retrospective study was performed on 316 patients who underwent laparoscopic right hemicolectomy in our center. They were assigned to the middle approach group (n = 158) and the mixed approach group (n = 158) according to the surgical approaches. The baseline data like gender、age and body mass index as well as the intraoperative and postoperative conditions including operation time, blood loss, postoperative hospital stay and complications were analyzed. RESULTS: There were no significant differences in age, sex, BMI, ASA grade and tumor characteristics between the two groups. Compared with the middle approach group, the mixed approach group was significantly lower in terms of operation time (217.61 min vs 154.31 min, p < 0.001), intraoperative blood loss (73.8 ml vs 37.97 ml, p < 0.001) and postoperative drainage volume. There was no significant difference in the postoperative complications like postoperative anastomotic leakage, postoperative infection and postoperative intestinal obstruction. CONCLUSIONS: Compared with the middle approach, the mixed approach is a safe and advantageous way that can significantly shorten the operation time, reduce intraoperative bleeding and postoperative drainage volume, and does not prolong the length of hospital stay or increase the morbidity postoperative complications.

Risk factors and clinical significance of lower perigastric lymph node metastases in Siewert type II and III esophagogastric junction adenocarcinoma: a retrospective cohort study.

BACKGROUND: No consensus has been concluded with regarding to the scope of lymph node (LN) dissection for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). This study aimed to explore risk factors for lower perigastric LN (LPLN) metastases (including no. 4d, 5, 6, and 12a LN stations) and analyze the indications for LPLN dissection. METHODS: In total, 302 consecutive patients with Siewert type II and III AEG who underwent total gastrectomy (TG) were enrolled. The logistic regression model was used to perform uni- and multivariate analyses of risk factors for LPLN metastases. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used for group comparisons. Basing on the guidelines of Japanese Gastric Cancer Association, the LN metastases (LNM) as well as the efficiency index (EI) of each LN station was further evaluated. RESULTS: The independent risk factors for LPLN metastases in patients with Siewert type II and III AEG were distance from the esophagogastric junction (EGJ) to the distal end of the tumor (> 4.0 cm), preoperative carcinoembryonic antigen (CEA) ( +), pT4 stage, and HER-2 ( +). LPLN metastases was an independent risk factor for overall survival following TG. The LNM and EI of LPLN were 8.6% and 2.31%, respectively. The LNM of LPLN > 10% under the stratification of the distance from the EGJ to the distal end of the tumor (> 4.0 cm), pT4, preoperative CEA ( +), and HER-2 ( +) exhibited EI values of 3.55%, 2.09%, 2.51%, and 3.64%, respectively. CONCLUSIONS: LPLN metastases was a malignant factor for the prognosis of patients with Siewert type II and III AEG. For patients with preoperative CEA ( +), pT4 stage, HER-2 ( +), and the distance from the EGJ to the distal end of the tumor (> 4.0 cm), TG with LPLN dissection is prioritized for clinical recommendation.

Iron-Catalyzed Cyanide-Free Synthesis of Alkyl Nitriles: Oxidative Deconstruction of Cycloalkanones with Ammonium Salts and Aerobic Oxidation.

A sustainable, cyanide-free synthesis of alkyl nitriles via the aerobic oxidative deconstruction of unstrained cycloalkanones with ammonium salts has been developed. Using inexpensive and stable ammonium salts as the nitrogen source, a variety of alkyl nitriles containing a distal carbonyl group were obtained in good yields under visible-light-promoted iron catalysis. This protocol is characterized by mild conditions, abundant and environmentally benign materials, and high atom and step economy with minimal waste generation. The primary mechanism study revealed that 1O2 is likely to be involved in this reaction.

An overview of microplastic pollution in the environment over the megacity of Shanghai during 2013-2022.

Microplastics (MPs) are emerging pollutants that have been globally found in the environment, and have become a focus of intensive management for the Shanghai government in China. Although there are several studies reporting the abundance of microplastics (MPs) in different matrices in Shanghai city, the general data are still limited. This work comprehensively reviews microplastic (MP) pollution in the water, sediment, atmosphere, and soil of Shanghai during 2013-2022. A summary of characteristics such as the abundance, shape, and polymer composition of MPs is presented. Additionally, the pollution trends, traceability, and ecological risks of MPs are analyzed and evaluated. Based on the analytical results, we find that the inland water in Shanghai city is the most contaminated with the highest abundance of MPs at 14.76 × 103 particles/m3 on average, while the abundances of MPs in the external water, inland sediment, external sediment, indoor atmosphere, outdoor atmosphere, inland soil, and external soil are 2.78 × 103 particles/m3, 0.80 × 103 particles/kg, 1.37 × 103 particles/kg, 0.03 × 103 particles/m3, 0.08 × 103 particles/m3, 0.27 × 103 particles/kg, and 0.18 × 103 particles/kg, respectively. Polyethylene and polypropylene are the top two detected polymer compositions of MPs. Results of ecological risk assessment using risk index and pollution load index models indicate that the risks of MPs in the water and sediment of the Yangtze Estuary are high. It is noteworthy that the abundances of MPs at the junction site of Suzhou Creek and the Huangpu River as well as in the Yangtze Estuary exhibited an increasing trend between 2017 and 2019. This work contributes to a comprehensive overview of MPs in the environment of Shanghai city during 2013-2022 and provides important data for local governments to develop urgent strategies for the management of MP pollution. However, more investigations are increasingly needed for better understand the production, migration, ecological risk, and management of MPs in the environment of Shanghai city.

WFDC3 inhibits tumor metastasis by promoting the ERß-mediated transcriptional repression of TGFBR1 in colorectal cancer.

Estrogen plays a protective role in colorectal cancer (CRC) and primarily functions through estrogen receptor ß (ERß). However, clinical strategies for CRC therapy associated with ERß are still under investigation. Our discoveries identified WFDC3 as a tumor suppressor that facilitates estrogen-induced inhibition of metastasis through the ERß/TGFBR1 signaling axis. WFDC3 interacts with ERß and increases its protein stability by inhibiting its proteasome-dependent degradation. WFDC3 represses TGFBR1 expression through ERß-mediated transcription. Blocking TGFß signaling with galunisertib, a drug used in clinical trials that targets TGFBR1, impaired the migration of CRC cells induced by WFDC3 depletion. Moreover, there was clinical significance to WFDC3 in CRC, as CRC patients with high WFDC3 expression in tumor cells had favorable prognoses. Therefore, this work suggests that WFDC3 could be an indicator for therapies targeting the estrogen/ERß pathway in CRC patients.

Performance and degradation pathway of florfenicol antibiotic by nitrogen-doped biochar supported zero-valent iron and zero-valent copper: A combined experimental and DFT study.

Fluorinated compounds are a class of organic substances resistant to degradation. Although zero-valent iron (Fe0) has a promising reducing capability, it still fails to degrade fluorine-containing antibiotics (i.e., florfenicol) efficiently. In this study, we applied a simple one-pot pyrolytic approach to synthesize nitrogen-doped biochar supported Fe0 and zero-valent copper (Cu0) composite (Fe/Cu@NBC) and investigated its performance on florfenicol removal. The results clearly showed that approximately 91.4% of florfenicol in the deionized water was removed by Fe/Cu@NBC within 8 h. As the reaction time was extended to 15 d, the total degradation rate of florfenicol reached 96.6%, in which the defluorination and dechlorination rates were 73.2% and 82.1%, respectively. Both experimental results and density functional theory calculation suggested that ∙OH and ·O2- triggered ß-fluorine elimination, resulting in defluorination prior to dechlorination. This new finding was distinct from previous viewpoints that defluorination was more difficult to occur than dechlorination. Fe/Cu@NBC also had a favorable performance for removal of florfenicol in surface water. This study provides a new insight into the degradation mechanism and pathway of florfenicol removal in the Fe/Cu@NBC system, which can be a promising alternative for remediation of fluorinated organic compounds in the environment.

The nodal positivity rate in breast pCR patients with initially, clinically node-negative breast cancer after neoadjuvant systemic therapy: A systematic review and meta-analysis.

Background: The axillary lymph node positive (ypN+) rate in patients with clinically node-negative (cN0) breast cancer who have achieved breast pathologic complete response (bpCR) after neoadjuvant systemic therapy (NST) is extremely low, and this population has the potential to be exempt from sentinel lymph node biopsy (SLNB). However, an overview of the ypN+ rate in this population for different breast cancer subtypes is lacking. Objective: To provide the pooled ypN+ rate in cN0 patients who achieved bpCR after NST in different breast cancer subtypes defined by hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status. Methods: A systematic literature search was conducted in Embase and PubMed on July 20, 2022. Two authors independently selected studies that met the inclusion criteria and extracted all data. The pooled ypN+ rates for each subtype were calculated by a random-effects model using the Stata 16.0 metaprop command. Results: The pooled analysis of 9609 cN0 patients who achieved bpCR showed that the ypN+ rate was lowest for the HR+/HER2+ (0%) subtype, followed by HR+/HER2- (5.1%), HR-/HER2+ (0.6%), and HR-/HER2- (0.3%). Additionally, 6571 cT1-T2N0 patients who achieved bpCR had a pooled ypN+ rate of 0.6%, and the ypN+ rates for different subtypes were as follows: HR+/HER2+ (1.7%), HR+/HER2- (2.7%), HR-/HER2+ (0.1%), and HR-/HER2- (0.8%). Conclusion: Our results suggested that cN0 patients who achieve bpCR may be exempt from axillary surgery in the HR+/HER2-, HR+/HER2+, and HR-/HER2- subtypes because of the extremely low probability of residual axillary lymph node disease. However, the safety of omitting axillary surgery needs to be further confirmed by prospective studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022351739.

Serum and peritoneal biomarkers for the early prediction of symptomatic anastomotic leakage in patients following laparoscopic low anterior resection: A single-center prospective cohort study.

BACKGROUND: Anastomotic leakage (AL) is one of the common complications after rectal cancer surgery. This study aimed to evaluate the combination of biomarkers for the early prediction of symptomatic AL after surgery. METHODS: A prospective cohort study evaluated the serum and peritoneal biomarkers of patients who underwent laparoscopic low anterior resection (Lap LAR) from November 1, 2021, to May 1, 2022. Multivariate-penalized logistic regression was performed to explore the independent biomarker with a P-value <.1, and receiver operating characteristic (ROC) curve was used to analyze the area under the curve (AUC), sensitivity, and specificity of the independent biomarkers. A predictive model for symptomatic AL was built based on the independent biomarkers and was visualized with a nomogram. The calibration curve with the concordance index (c-index) was further applied to evaluate the efficacy of the predictive model. RESULTS: A total of 157 patients were included in this study, and 7 (4.5%) were diagnosed with symptomatic AL. C-reactive protein/album ratio (CAR) on postoperative day 1 and systemic immune-inflammation index (SII) and peritoneal interleukin-6 (IL-6) on postoperative day 3 were proven to be independent predictors for the early prediction of symptomatic AL. The optimal cutoff values of CAR, SII, and peritoneal IL-6 were 1.04, 916.99, and 26430.09 pg/ml, respectively. Finally, the nomogram, including these predictors, was established, and the c-index of this nomogram was 0.812, indicating that the nomogram could be used for potential clinical reference. CONCLUSION: The combination of CAR, SII, and peritoneal IL-6 might contribute to the early prediction of symptomatic AL in patients following Lap LAR. Given the limitations of this study and the emergence of other novel biomarkers, multicenter prospective studies are worthy of further exploration.

Rectal gastrointestinal stromal tumor with metachronous liver metastasis demonstrated no relapse after multidisciplinary team discussion and comprehensive treatment: a case report.

Background: This study sought to explore the role and significance of multidisciplinary team (MDT) discussion and comprehensive treatment in the diagnosis and treatment of a gastrointestinal stromal tumor (GIST) with liver metastasis. For GIST patients with liver metastasis, MDT can evaluate whether the liver metastasis is resectable, so as to formulate accurate treatment goals and the best diagnosis and treatment plan. Case Description: A 53-year-old male patient with localized rectal GIST with metachronous liver metastasis (MLM) was admitted to Yunnan Cancer Hospital in October 2014. At the 1st visit, he was diagnosed with locally advanced rectal GIST, and a MDT discussion was held by departments of colorectal surgery, imaging, pathology and oncology. The tumor shrank after neoadjuvant targeted treatment with imatinib. A local resection of the rectal GIST was successfully performed via the anal approach. R0 resection was achieved and the function of the anal sphincter was preserved. Following the operation, oral imatinib treatment was discontinued after 2 years. The patient developed isolated liver metastasis 6 months later. After the MDT discussion by departments of colorectal surgery, hepatobiliary surgery, imaging, pathology, and oncology, R0 resection of the liver metastasis was achieved. After the operation, sunitinib was administered for 4.5 years. The patient's overall survival (OS) has reached 7.5 years. No tumor recurrence or metastasis was found in the re-examinations. The follow-up is ongoing. Conclusions: Targeted therapy combined with surgery is the most suitable way to cure GIST patients with liver metastasis. More importantly, the multi-disciplinary management and the standardized diagnosis and treatment of GIST patients with liver metastasis through MDT discussion can improve the quality of life and prolong the survival of patients.

Trichloroethylene remediation using zero-valent iron with kaolin clay, activated carbon and bacteria.

Nanoscale particles of zero-valent iron were used to form a permeable reactive barrier whose performance in dechlorinating a solution of trichloroethylene was compared with that of a barrier formed from limestone. The iron was combined with kaolin by calcination. The test liquid contained sewage sludge, and also added NH4Cl and KH2PO4. The average removal rates of trichloroethylene and phosphorus over 365 days both exceeded 94%. Chemical oxygen demand was reduced by 92% and ammonium nitrogen by 43.6%. All were significantly greater than the removals with the limestone barrier. The ceramsite barrier retained 85% of its effectiveness even after 365 days of use. Dechloromonas sp. was the main dechlorinating bacterium, but its removal ability is limited. The removal of trichloroethylene in such a barrier mainly depends on reduction by the zero-valent iron and biodegradation. The results show that the prepared ceramsite is stable and effective in removing trichloroethylene from water. It is a promising in-situ remediation material for groundwater.

Immobile Iron-Rich Particles Promote Arsenic Retention and Regulate Arsenic Biotransformation in Treatment Wetlands.

Remediation of arsenic (As)-contaminated wastewater by treatment wetlands (TWs) remains a technological challenge due to the low As adsorption capacity of wetland substrates and the release of adsorbed As to pore water. This study investigated the feasibility of using immobile iron-rich particles (IIRP) to promote As retention and to regulate As biotransformation in TWs. Iron-rich particles prepared were immobilized in the interspace of a gravel substrate. TWs with IIRP amendment (IIRP-TWs) achieved a stable As removal efficiency of 63 ± 4% over 300 days, while no As removal or release was observed in TWs without IIRP after 180 days of continuous operation. IIRP amendment provided additional adsorption sites and increased the stability of adsorbed As due to the strong binding affinity between As and Fe oxides. Microbially mediated As(III) oxidation was intensified by iron-rich particles in the anaerobic bottom layer of IIRP-TWs. Myxococcus and Fimbriimonadaceae were identified as As(III) oxidizers. Further, metagenomic binning suggested that these two bacterial taxa may have the capability for anaerobic As(III) oxidation. Overall, this study demonstrated that abiotic and biotic effects of IIRP contribute to As retention in TWs and provided insights into the role of IIRP for the remediation of As contamination.

Switchable In Situ SO2 Capture and CF3 Migration of Enol Triflates with Peroxyl Compounds under Iron Catalysis.

Switchable in situ SO2 capture and CF3 migration of enol triflates with peroxyl compounds under iron catalysis are presented. By regulating the structure of peroxides, a variety of keto-functionalized dialkyl sulfones and α-trifluoromethyl ketones were selectively synthesized in good yields under mild conditions.

Modified π-shaped esophagojejunostomy in totally laparoscopic total gastrectomy: a report of 40 consecutive cases from a single center.

OBJECTIVE: Intracorporeal esophagojejunostomy remains a challenging technique in totally laparoscopic total gastrectomy (TLTG) because of the lack of an established standard anastomosis method. However, π-shaped esophagojejunostomy in TLTG is reportedly safe and feasible. Therefore, we evaluated the short-term surgical outcomes of our modified π-shaped esophagojejunostomy in TLTG. METHODS: This study involved patients without neoadjuvant therapy diagnosed with gastric cancer who underwent TLTG by the same surgeon with modified π-shaped esophagojejunostomy from April 2018 to October 2019. Clinicopathologic data were collected and retrospectively analyzed. RESULTS: Forty patients diagnosed with gastric cancer were included. The mean operative time and estimated blood loss were 264.6 ± 56.9 minutes and 68.5 ± 53.3 mL, respectively. Postoperative flatus occurred at 4.6 ± 1.7 days. The mean time to resumption of diet was 7.4 ± 1.7 days postoperatively. One patient was diagnosed with anastomotic leakage and managed with conservative therapy. Pleural effusion was the most common complication, occurring in four (10%) patients. One patient developed intra-abdominal bleeding that required reoperation. Other complications were atrial fibrillation and wound infection. No mortality occurred during the 6-month follow-up. CONCLUSIONS: Modified π-shaped esophagojejunostomy is safe and feasible for intracorporeal anastomosis in TLTG and showed favorable surgical outcomes in this study.

AN INTER-COMPARISON OF PASSIVE DOSEMETERS FOR TERRESTRIAL GAMMA RADIATION MEASUREMENTS.

To evaluate the measurement method of passive dosemeters for terrestrial gamma radiation measurements. An inter-comparison of passive dosemeters for terrestrial gamma radiation measurements was organized alternately by the Japan Chemical Analysis Center, National Institute for Radiological Protection of Chinese Center for Disease Control and Prevention and Radiation Monitoring Technical Center of Ministry of Environmental Protection every 2 years. The procedures and exposure conditions of the field-exposure and reference irradiation test were provided by the organizer. During 2019-2020, the En values of Field-1 and Field-2 in three laboratories were lower than 1.0 and assigned 'acceptable' according to inter-comparison criteria. After the correction of the fading effect of dosemeter material, the En values of reference irradiation test (0.301 mGy, 1.000 mGy) in three laboratories were lower than 1.0 and assigned 'acceptable'.

A stop-gain mutation in GXYLT1 promotes metastasis of colorectal cancer via the MAPK pathway.

Genomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC.

Health-Related Quality of Life in Patients With Locally Advanced Gastric Cancer Undergoing Perioperative or Postoperative Adjuvant S-1 Plus Oxaliplatin With D2 Gastrectomy: A Propensity Score-Matched Cohort Study.

Background: Some high-quality clinical trials have proven the efficacy and safety of perioperative and postoperative S-1 with oxaliplatin (peri-SOX and post-SOX) for patients with locally advanced gastric cancer (LAGC) undergoing D2 gastrectomy. However, little is known about how health-related quality of life (HRQOL) changes over time in patients receiving peri-SOX or post-SOX chemotherapy. Methods: A prospective observational cohort (NCT04408859) identified 151 eligible patients with LAGC who underwent D2 gastrectomy with at least six cycles of peri-SOX or post-SOX chemotherapy from 2018 to 2020. HRQOL was assessed using the EROTC QLQ-C30 and its gastric module, QLQ-STO22, at indicated measurements, including the baseline, 1st, 3rd, 6th and 12th month after initiation of therapy. Baseline characteristics, therapeutic effects, and longitudinal HRQOL were compared between the peri-SOX and post-SOX groups after propensity score matching. HRQOL changes over time and the risk factors for scales with severe deterioration were further analyzed. Results: No statistically significant differences in longitudinal HRQOL were observed between patients in the peri-SOX and post-SOX groups, with comparable surgical outcomes and adverse chemotherapy events. Scales of social functioning, abnormal taste, and anxiety improved earlier in the peri-SOX group than in the post-SOX group. Score changes in both groups indicated that general deterioration and slower recovery usually occurred in the scales of physical, social, and role functioning, as well as symptoms of fatigue, reflux, diarrhea, and anxiety. Conclusion: Peri-SOX showed a longitudinal HRQOL comparable to post-SOX in patients with LAGC who underwent D2 gastrectomy. The peri-SOX group had better performance in social functioning, abnormal taste, and anxiety at some measurements.

Downregulation of STK25 promotes autophagy via the Janus kinase 2/signal transducer and activator of transcription 3 pathway in colorectal cancer.

Autophagy plays a crucial role in colorectal cancer (CRC) development. Our previous study suggested that serine/threonine protein kinase 25 (STK25) regulates aerobic glycolysis in CRC cells. Glycolysis modulates cellular autophagy during tumor growth; however, the role of STK25 in autophagy remains unclear. In this study, we found that STK25 expression was decreased in CRC tissues and CRC patients with high STK25 expression had a favorable prognosis. Functional assays suggested that STK25 inhibition promoted autophagy in CRC cells. Overexpression of STK25 exhibited the opposite effects. Moreover, the results of western blot demonstrated that silencing STK25 induced autophagy by activating the JAK2/STAT3 pathway. Therefore, STK25 could be a potential indicator for therapies targeting the JAK2/STAT3 pathway in CRC.