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Tao Yan,1* Guo-Hua Zhang,1* Yao-Zhong Cheng,1* Lin-Xin Wu,1 Xiao-Yan Liu,1 Yu-Lin Sun,2 Hui Zheng*,1 Li Sun31Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 3Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, People’s Republic of China*These authors contributed equally to this work Background: Surgery and anesthesia-induced immunosuppression may play a critical role in tumor progression and metastasis. Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, closely linked with tumor staging, clinical therapeutic efficacy and prognosis. This study aims to investigate the effect of anesthetic technique and surgery on the expression of MDSCs and prognosis in women who received breast cancer surgery.Methods: From March 2016 to January 2017, a total of 80 patients with breast cancer were prospectively enrolled and randomized into two anesthetic groups: sevoflurane-based anesthetic group (SEV; n=38) and propofol-based total intravenous anesthetic group (TIVA; n=42). The expression of MDSCs and prognosis between different anesthetic techniques and stresses of surgical methods were compared. The primary endpoint is the postoperative expression of MDSCs and prognosis between SEV and TIVA groups. The secondary endpoint is the VAS scores at 24 hr post-operation between SEV and TIVA groups.Results: There was no significant difference in postoperative expression of MDSCs (P=0.202) and prognosis (P=0.138) between SEV and TIVA groups. Compared to breast-conserving surgery (BCS), patients who underwent breast mastectomy had significantly fewer MDSCs (P=0.040) and lower VAS score at 24 hr post-operation (P=0.044), while no significant difference in prognosis was found (P=0.953). When MDSCs were classified as subtypes of granulocytic/polymorphonuclear (PMN)-MDSCs and monocytic (Mo)-MDSCs, it showed higher ratio of Mo-MDSCs (P=0.018) or lower ratio of (PMN)-MDSCs (P=0.022) correlates to later tumor stage.Conclusion: Sevoflurane and propofol-based anesthesia do not show significant difference in MDSCs expression and prognosis after breast cancer surgery. Compared to BCS, although mastectomy with high extent of surgical stress exhibits lower levels of MDSCs, there is no significant difference in prognosis. The ratio of MDSCs subtype correlates to tumor stage.Keywords: breast cancer, anesthesia, surgery, propofol, sevoflurane, MDSCs

Ling Zhao,1 Wei Wang,1 Jiwen Zhong,1 YaYun Li,1 YanZi Cheng,1 Zhenjiao Su,1 Wei Zheng,1 Xiang-Dong Guan2 1Department of Critical Care Medicine, Zhuhai People’s Hospital, Zhuhai, Guangdong, 2Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China Purpose: To evaluate the clinical effects of magnesium sulfate in the treatment of diffuse axonal injury (DAI).Patients and methods: This study was a randomized, double-blind, placebo-controlled trial conducted in the First Affiliated Hospital of Sun Yat-sen University, Guangzhou and Zhuhai People’s Hospital, Zhuhai, two trauma center hospitals. A total of 128 patients suffered from DAI, with initial Glasgow coma scale (GCS) scores of 3–8. They were randomly divided into two groups: magnesium sulfate treatment (MST) group (n=64) and control group (n=64). The MST group received 250 µmol/kg magnesium sulfate intravenously 20 minutes after admission, followed by 750 µmol/kg magnesium sulfate intravenously daily for 5 days. The control group received standard management without MST. GCS scores and serum neuron-specific enolase values were measured and recorded at admission, and on days 3 and 7 after injury. Outcomes were determined by Glasgow outcome scale scores at discharge and at 3 months’ follow-up, respectively.Results: After the 7-day treatment, patients in the MST group, compared with those in the control group, had a lower serum neuron-specific enolase level (25.40±6.66 vs 29.58±7.32, respectively, P=0.001) and higher GCS score (8.23±2.72 vs 7.05±2.64, respectively, P=0.016). Although the length of stay and mortality did not differ between the groups in the intensive care unit, Glasgow outcome scale score was significantly lower in the MST group at discharge (3.30±1.35 vs 3.90±1.10, P=0.004) and 3 months after discharge (2.95±1.48 vs 3.66±1.44, P=0.009).Conclusion: Early treatment with magnesium sulfate resulted in a significant improvement in DAI outcome. Further studies are needed to confirm the clinical significance of treatment of DAI patients with magnesium sulfate. Keywords: diffuse axonal injury, magnesium sulfate, outcome

Tao Wu,1 Min-Cong Wang,1 Li Jing,1 Zhi-Yan Liu,2 Hui Guo,1 Ying Liu,3 Yi-Yang Bai,1 Yang-Zi Cheng,1 Ke-Jun Nan,1 Xuan Liang1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Respiratory Medicine, Xi’an Central Hospital, 3Department of Medical Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China Abstract: Resistance to cisplatin-based therapy is a major challenge in the control of lung cancer progression. However, the underlying mechanisms remain largely unclear. Autophagy is closely associated with resistance to lung cancer therapy, but the function of autophagy in cisplatin treatment is still controversial. Here, we investigated whether autophagy was involved in lung adenocarcinoma resistance to cisplatin and further elucidated the underlying molecular mechanisms. Cisplatin-refractory lung adenocarcinoma cells increased autophagic vacuole formation detected by monodansylcadaverine staining. When exposed to cisplatin, lung adenocarcinoma cells demonstrated increased levels of autophagy detected by MAP1A/1B LC3B and mammalian homologue of yeast Atg6 (Beclin-1) expression using Western blot analysis. Activation of cisplatin-induced autophagic flux was increased by using chloroquine (CQ), which can accumulate LC3B-II protein and increase punctate distribution of LC3B localization. The combination of cisplatin with CQ was more potent than cisplatin alone in inhibiting lung adenocarcinoma cell growth, which also increased cisplatin-induced apoptosis. Compared to cisplatin treatment alone, the combination of cisplatin and CQ decreased p-AMPK and increased p-mTOR protein expressions, in addition, the AMPK inhibitor Compound C plus cisplatin downregulated p-AMPK and upregulated p-mTOR as well as depressed LC3B cleavage. These findings demonstrate that activation of autophagy is a hallmark of cisplatin exposure in human lung adenocarcinoma cells, and that there is a cisplatin-induced autophagic response via activation of the AMPK/mTOR signaling pathway. We speculate that autophagy can be used as a novel therapeutic target to overcome cisplatin-resistant lung adenocarcinoma. Keywords: autophagy, lung cancer, A549 cells, A549/DDP cells, chemoresistance, AMPK, chloroquine

Yanzi Cheng,1 Jiwen Zhong,1 Yang Xiang,1 Fan Zeng,1 Dehong Cai,2,† Ling Zhao11Department of Intensive Care Unit, Zhuhai People’s Hospital, Zhuhai, Guangdong, People’s Republic of China; 2Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China†Dehong Cai passed away on April 19, 2014Purpose: To investigate the possible associations between serum levels of soluble receptor for advanced glycation end products (sRAGE) and specific clinical markers and prognosis in critically ill patients diagnosed with stress hyperglycemia.Patients and methods: A total of 70 critically ill patients and 25 normal controls were recruited for this study. Serum levels of sRAGE and advanced glycation end products (AGEs) were determined using enzyme-linked immunosorbent assay. Additional data on other clinical markers were obtained from patient records in the intensive care unit. Comparisons of sRAGE and AGEs levels between groups were assessed by t-test. The relationships between sRAGE and other clinical markers were assessed by Pearson’s correlation analyses and multiple linear regression analyses. Risk factors for prognosis, such as 28-day mortality were analyzed using logistic regression analysis.Results: Serum sRAGE and AGEs levels were significantly higher in critically ill patients, compared to normal controls (P,0.05). The increase in serum sRAGE levels was significantly correlated with AGEs levels, interleukin-6 levels, and the sequential organ failure assessment score (P,0.01). Using multiple linear regression analysis, the association between AGEs and sRAGE remained significant after adjustment of other clinical factors. However, there were no significant correlations between sRAGE levels and patient outcome in these critically ill patients.Conclusion: Serum sRAGE levels were significantly elevated in critically ill patients and positively correlated with higher AGEs levels, but sRAGE levels were not associated with increased mortality, suggesting sRAGE levels are not a predictor of prognosis in critically ill patients.Keywords: soluble receptor for advanced glycation end products, advanced glycation end products, critically ill patients, predictor, relationship

Background: Pterosin B (PB) exhibits strong neuroprotective effects in vitro, but its therapeutic effect and underlying mechanism on Alzheimer's disease (AD) remain elusive., Purpose: This study aimed to investigate the anti-AD effect and mechanism of PB., Study Design: The therapeutic effect and mechanism of PB were investigated in APP/PS1 mice and lipopolysaccharide (LPS)-induced BV-2 cells., Methods: After 8 weeks of oral administration of PB or donepezil, the cognitive function was assessed using behavioral tests. Pathological damage was evaluated using histological analysis and immunohistochemical staining. Flow cytometry was applied to detect M1/M2 polarization. The expression levels of glycolysis- and oxidative phosphorylation-related proteins as well as enzyme activities were determined using Western blot and biochemical kits, respectively. The levels of inflammatory cytokines and Kruppel-like factor 5 (Klf5) were measured using enzyme-linked immunosorbent assay. AD biomarkers in serum were analyzed using single-molecular array. RNA sequencing identified the downstream molecules of Klf5, and interaction was evaluated using dual-luciferase reporter assay., Results: Our findings demonstrated that PB effectively ameliorated cognitive impairment and reduced pathological damage in APP/PS1 mice. Furthermore, PB facilitated the transition of the phenotype of LPS-induced BV-2 cells from M1 to M2 by modulating metabolic reprogramming. Additionally, Klf5 had high expression levels in the serum of patients with AD, which strongly correlated with cognitive performance and AD biomarkers. PB downregulated Klf5 expression both in vitro and in vivo. Subsequently, poly-ADP ribosyl polymerase 14 (Parp14) was identified as a downstream molecule of Klf5 involved in regulating metabolic reprogramming, and PB regulated microglia M1/M2 polarization by inhibiting the Klf5/Parp14 pathway., Conclusion: The findings suggested that PB ameliorated cognitive dysfunction in AD by modulating microglia M1/M2 polarization via inhibiting Klf5/Parp14 pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Precious metals are valuable materials for the chemical industry, but they are scarce and pose a risk of supply disruption. Recycling precious metals from waste is a promising strategy, here we tactfully utilize light irradiation as an environmental-friendly and energy-saving adjunctive strategy to promote the reduction of precious metal ions, thereby improving the adsorption capacity and kinetics. A newly light-sensitive covalent organic framework (PP-COF) was synthesized to illustrate the effectiveness and feasibility of this light auxiliary strategy. The equilibrium adsorption capacities of PP-COF with light irradiation towards gold, platinum, and silver ions are 4729, 573, and 519 mg g-1, which are 3.3, 1.9, and 1.2 times the adsorption capacities under dark condition. Significantly, a filtration column with PP-COF can recover more than 99.8% of the gold ions in the simulated e-waste leachates with light irradiation, and 1 gram of PP-COF can recover gold from up to 0.15 tonne of e-waste leachates. Interestingly, the captured precious metals by PP-COF with light irradiation mainly exist in the micron-sized particles, which can be easily separated by extraction. We believe this work can contribute to precious metal recovery and circular economy for recycling resources., (© 2024 Wiley‐VCH GmbH.)

Competing Interests: Conflicts of Interest: Cheng YZ, None; Sun LM, None; Yuan ME, None; Zhang LY, None; Ke SY, None; Ding XY, None.

The vinylene-linked covalent organic frameworks (viCOFs) have been generally synthesized in the presence of homogeneous catalysts such as KOH or trifluoroacetic acid. However, highly ordered viCOFs cannot always be obtained due to the uncommitted growth of viCOF layers in the homogeneous system with ubiquitous catalysts. Here, we propose a scalable protocol to restrict the growth of viCOFs along the two-dimensional (2D) plane by introducing a heterogeneous catalyst, polyoxometalates (POMs). With the unique Brønsted alkalinity and catalytic surface, POMs induce the growth of 2D viCOF layers along the surface of the catalytic substrate and restrain the generation of out-of-plane branches. Based on this protocol, six typical 2D viCOFs with high crystallinity and porosity were synthesized within a shorter reaction time as compared with the reported works using the common homogeneous catalysts for viCOF synthesis. On the basis of the density functional theory calculations and experimental results, a bottom intercalation growth pattern of viCOFs was revealed during the heterogeneous reaction. The unique growth pattern greatly promotes the orderly assembly of monomers, thus shortening the reaction time and improving the crystallinity of viCOFs. Furthermore, this heterogeneous catalysis strategy is suitable for the gram-scale preparation of 2D viCOFs. These results provide a novel avenue for the synthesis of high-quality viCOFs and may bring new insights into the synthetic methodology of COFs.

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)] 2 ( 1 ), [Ag(3-apy)(mef)] ( 2 ), [Ag 2 (tmpyz)(mef) 2 ] ( 3 ), and {[Ag(4,4'-bipy)(mef)] 2 (CH 3 CN) 1.5 (H 2 O) 2 } n ( 4 ), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C-C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C-H-activation, and facilitating cycloaddition and C-S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C-C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry., (© 2024 Wiley‐VCH GmbH.)

A novel method was developed for synthesizing γ-alkyl ketones via nickel-catalyzed cross-electrophile coupling of cyclopropyl ketones and non-activated primary alkyl chlorides. High reactivity and selectivity can be achieved with sodium iodide as a crucial cocatalyst that generates a low concentration of alkyl iodide via halide exchange, thus avoiding the formation of alkyl dimers. This reaction possessed excellent regioselectivity and high step economy circumventing in situ or pregenerated organometallics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To explore the relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration. Methods: A total of 48 specific pathogen-free (SPF) male C57BL/6J mice, aged 16-17 months, were divided into two groups by random number table method: control group ( n =24) and operation group ( n =24). Mice in the operation group were induced with 1.4% isoflurane for 15 minutes, followed by a 10 minutes exploratory laparotomy anesthetized with 1.4% isoflurane and 100% oxygen, and anesthesia continued for 2 hours after surgery. Mice in control group were put in 100% oxygen for 2 hours. Feces and venous blood samples of both groups were collected 48 hours after surgery. Changes in the abundance and diversity of intestinal bacteria in the feces were detected by 16S rDNA gene sequencing. Functional changes of fecal metabolic profiles were detected by liquid chromatography tandem mass spectrometry (LC/MS) metabolomics and differential metabolite functions were analyzed. The serum level of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The cognitive function of the mice was detected by Morris water maze test 3 days after operation. Results: The postoperative escape latency of mice in control group and operation group was (22.0±4.9) and (35.0±5.1) s, and the target quadrant residence time was (26.0±3.7) and (16.0±2.9) s, respectively. Compared with the control group, the postoperative escape latency of mice in the operation group was prolonged ( P =0.035), and the residence time in the target quadrant was reduced ( P =0.006). The difference of intestinal flora between the two groups was comparable. The expression levels of Escherichia coli, shigella and clostridium in the operation group were up-regulated, while the expression levels of rumen bacteria and butyricobacteria were down-regulated. Fecal metabolic profiles of mice in control group and operation group were obtained by LC/MS, and 14 and 21 different metabolites were screened in positive and negative ion modes, respectively. The different metabolites in positive ion mode were glutamic acid, 2-indoleic acid, kynuuric acid and glyceraldehyde. The negative ion pattern differential metabolites are methionine, aspartic acid, L-threonine, tyrosyl-threonine and 5-hydroxyindole-3-acetic acid. The identified differential metabolite pathways are mainly involved in amino acid, fatty acid and tryptophan metabolism and nucleotide synthesis. There were no significant differences in serum levels of IL-1β, IL-6 and TNF-α between the two groups (all P >0.05). Conclusion: The dysregulated changes of gut microbiota and its metabolites are correlated with the occurrence of postoperative cognitive dysfunction in elderly male C57BL/6J mice. Anesthesia and surgery alter the structure of mice intestinal bacteria on the level of abundance, and change the metabolic balance and feces metabolomic phenotype.

Multiple evanescent white dot syndrome (MEWDS) is a rare fundus disease, characterized by acute vision loss and visual field defects. Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS. However, as the number of reported cases increases, secondary MEWDS occurs in other related retinal diseases and injuries, exhibiting some special characteristics. The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy (MFC/PIC), acute zonal occult outer retinopathy, best vitelliform macular dystrophy, pseudoxanthoma elasticum, and ocular toxoplasmosis. The related retinal injury is laser photocoagulation, surgery, and trauma. Although primary MEWDS often have a self-limiting course, secondary MEWDS may require treatment in some cases, according to the severity of concomitant diseases and complications. Notably, MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation, needs positive treatment with corticosteroids. The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch's membrane. The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances. Its prognosis and treatment depend on the severity of complications. Current studies propose that the etiology is associated with immune factors, including viral infection, inflammation in choroid and Bruch's membrane, and antigen exposure caused by retinal and/or choroidal insults. More pathogenic studies should be conducted in the future. Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis., Competing Interests: Conflicts of Interest: Chen CL, None; Cheng YZ, None; Zhang ZH, None; Wang G, None; Peng XY, None., (International Journal of Ophthalmology Press.)

Background: Analyses of author collaborations and keyword co-occurrences are frequently used in bibliographic research. However, no studies have introduced a straightforward yet effective approach, such as utilizing ChatGPT with Code Interpreter (ChatGPT_CI) or the R language, for creating cluster-oriented networks. This research aims to compare cluster analysis methods in ChatGPT_CI and R, visualize country-specific author collaborations, and then demonstrate the most effective approach., Methods: The research focused on articles and review pieces from Medicine (Baltimore) published in 2023. By August 20, 2023, we had gathered metadata for 1976 articles using the Web of Science core collections. The efficiency and effectiveness of cluster displays between ChatGPT_CI and R were compared by evaluating their time consumption. The best method was then employed to present a series of visualizations of country-specific author collaborations, rooted in social network and cluster analyses. Visualization techniques incorporating network charts, chord diagrams, circle bar plots, circle packing plots, heat dendrograms, dendrograms, and word clouds were demonstrated. We further highlighted the research profiles of 2 prolific authors using timeline visuals., Results: The research findings include that (1) the most active contributors were China, Nanjing Medical University (China), the Medical School Department, and Dr Chou from Taiwan when considering countries, institutions, departments, and individual authors, respectively; (2) the highest cited articles originated from Medicine (Baltimore) accounting for 4.53%: New England Journal of Medicine, PLOS ONE, LANCET, and The Journal of the American Medical Association, with respective contributions of 3.25%, 2.7%, 2.52%, and 1.54%; (3) visual cluster analysis in R proved to be more efficient and effective than ChatGPT_CI, reducing the time taken from 1 hour to just 3 minutes; (4) 7 cluster-focused networks were crafted using R on a custom platform; and (5) the research trajectories of 2 prominent authors (Dr Brin from the United States and Dr Chow from Taiwan) and articles themes in Medicine 2023 were depicted using timeline visuals., Conclusions: This research highlighted the efficient and effective methods for conducting cluster analyses of author collaborations using R. For future related studies, such as keyword co-occurrence analysis, R is recommended as a viable alternative for bibliographic research., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Studies evaluating the characteristics of dual primary gastric and colorectal cancer (CRC) (DPGCC) are limited., Aim: To analyze the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with DPGCC., Methods: From October 2010 to August 2021, patients with DPGCC were retrospectively reviewed. The patients with DPGCC were divided into two groups (synchronous and metachronous). We compared the overall survival (OS) between the groups using Kaplan-Meier survival methods. Univariate and multivariate analyses were performed using Cox's proportional hazards model to identify the independent prognostic factors for OS., Results: Of the 76 patients with DPGCC, 46 and 30 had synchronous and metachronous cancers, respectively. The proportion of unresectable CRC in patients with synchronous cancers was higher than that in patients with metachronous cancers (28.3% vs 3.3%, P = 0.015). The majority of the second primary cancers had occurred within 5 years. Kaplan-Meier survival analysis showed that the patients with metachronous cancers had a better prognosis than patients with synchronous cancers ( P = 0.010). The patients who had undergone gastrectomy ( P < 0.001) or CRC resection ( P < 0.001) had a better prognosis than those who had not. In the multivariate analysis, synchronous cancer [hazard ratio (HR) = 6.8, 95% confidence interval (95%CI): 2.0-22.7, P = 0.002)] and stage III-IV gastric cancer (GC) [HR = 10.0, 95%CI: 3.4-29.5, P < 0.001)] were risk prognostic factor for OS, while patients who underwent gastrectomy was a protective prognostic factor for OS [HR = 0.2, 95%CI: 0.1-0.6, P = 0.002]., Conclusion: Regular surveillance for metachronous cancer is necessary during postoperative follow-up. Surgical resection is the mainstay of therapy to improve the prognosis of DPGCC. The prognosis appears to be influenced by the stage of GC rather than the stage of CRC. Patients with synchronous cancer have a worse prognosis, and its treatment strategy is worth further exploration., Competing Interests: Conflict-of-interest statement: All authors have no conflicts to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Two Ag(I) complexes containing triphenylphosphine and non-steroidal anti-inflammatory drug ligands were synthesized and investigated using various spectroscopic studies and single crystal X-ray crystallography. The binding properties of tolfenamic acid, ibuprofen and the two complexes with DNA and BSA were investigated using UV or fluorescence spectroscopy. The results showed that two Ag(I) complexes bound to DNA by the intercalation mode and interacted with BSA using a static quenching procedure. Furthermore, the results of fluorescence titration suggested that the complexes had good affinity for BSA and one binding site close to BSA. The in vitro cytotoxicity of tolfenamic acid, ibuprofen, and the two complexes against four human carcinoma cell lines (MCF-7, HepG-2, A549, and HeLa cells) was tested using an MTT assay. Complex 1 had higher cytotoxicity against HeLa cells. The intracellular reactive oxygen species (ROS) assay showed complex 1 induced the ROS generation in HeLa cells in a concentration dependent manner. Flow cytometry analysis showed complex 1 could suppress the HeLa cells growth during the G0/G1 phase and induce apoptosis in dose-depended manner., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Covalent organic frameworks (COFs) with structural designability and tunability of photophysical properties enable them to be a promising class of organic luminescent materials by incorporating well-designed fluorescent units directly into the periodic skeletons. The photophysical properties of COFs are mainly affected by the structural features, which determine the conjugation degree, charge delocalization ability, and exciton dynamics of COFs. To understand the relationship between COF structures and their photophysical properties, two COFs with the same pyrene chromophore units but different linkages (imine or vinylene) were designed and synthesized. Interestingly, different linkages endow COFs with huge differences in solid-state photoluminescence quantum yield (PLQY) for imine- and vinylene-linked pyrene-based COFs, which possess PLQY values of 0.34 % and 15.43 %, respectively. The femtosecond-transient absorption spectra and time-dependent density functional theory reveal the different charge-transfer pathways in imine- and vinylene-linked COFs, which influence the exciton relaxation way and fluorescence intensity. In addition, an effective white-light device was obtained by coating the vinylene-linked COF on a light-emitting diode strip., (© 2023 Wiley-VCH GmbH.)

Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, and its derivatives have been extensively used as key synthons in organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched cyclobutane derivatives. The reaction proceeds in a cascade fashion involving Ir-catalyzed asymmetric allylic etherification and visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates and cinnamyl alcohols are directly used as the substrates under mild reaction conditions, providing a broad range of chiral cyclobutanes in good yields with excellent diastereo- and enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all substrates and catalysts were simultaneously added without any separated step in this approach. The gram-scale reaction and diverse transformations of product further enhance the potential utility of this method.

Background: Ferroptosis playsa crucial role in the development of dementia and dendrobine (Den)possesseshypoglycemic and neuroprotective effects. However, the character of ferroptosis in diabetic encephalopathy (DE) and Den's therapeutic effect remains unclear., Purpose: This study aimed to verify the effects of Den on ferroptosis in treating DE and underlying mechanisms., Study Design: Den's therapeutic effect was assessed in db/db mice and advanced glycation end products (AGEs)-induced HT22 cells., Methods: After oral administration with Den orMetformin for 8-week, behavioral tests were used to assess cognitive capacity. Then, biochemical analysis was preformed to detect glucose and lipid metabolism levels; histological analysis and transmission electron microscope were applied to evaluate pathological injuries. Meanwhile, EdU staining and flow cytometry were applied to test cell apoptosis. Furthermore, mitochondrial dynamics, iron transport, and Nrf2/GPX4 axis related proteins were detected by western blot or immunofluorescence., Results: Our results demonstrated that Den remarkably alleviated glucose and lipid metabolism disorders, as well as ameliorated mnemonic deficits of db/db mice. Meanwhile, Den could protect AGEs-induced HT22 cells from death and apoptosis. In addition, we noted that Den inhibited lipid peroxidation by restoring mitochondrial function and reducing reactive oxygen species production. Furthermore, ferroptosis was proven to exist in db/db mice brain and Den could inhibit it via activating Nrf2/GPX4 axis., Conclusion: These findings indicated that Den could rescue cognitive dysfunction in DE by inhibiting ferroptosis via activating Nrf2/GPX4 axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

The topology type and the functionalization of pores play an important role in regulating the performance of covalent organic frameworks. Herein, we designed and synthesized the covalent organic framework with hetero-environmental pores using predesigned asymmetrical dialdehyde monomer. According to the results of structural characterization, crystallinity investigation, and theoretical calculation, the hetero-environmental pores of the obtained framework are regarded as the alternant arrangement. The distinctive hetero pore structure leads the designed material to show more advantages as compared with control materials in loading both hydrophobic and hydrophilic antibiotics for wound healing. This dual-antibiotic strategy can expand the antibacterial range as compared with the single antibiotic one, and reduce the generation of drug resistance. In summary, this strategy for designing covalent organic frameworks with hetero-environmental pores can extend the structural variety and provide a pathway for improving the practical application performance of these materials., (© 2023. The Author(s).)

There are inconsistencies in treatment outcomes, measurement instruments, and criteria for assessing clinical effectiveness in studies related to distal radius fractures (DRF), resulting in potential biases and failing to provide high-quality clinical evidence. To address these challenges, international researchers have reached a consensus on developing the core outcome indicator set for distal radius fractures(COS-DRF). However, it's important to note that the existing COS-DRF framework could not reflect the unique characteristics of Traditional Chinese Medicine (TCM) treatment. Currently, there are no established standards for treatment outcomes and measurement instruments specific to TCM clinical research, nor has a COS-DRF been established for TCM clinical studies in China. In light of these gaps, our research team aims to construct a core set of treatment outcomes for TCM clinical research on distal radius fractures. This involves compiling a comprehensive list of treatment outcomes and measurement instruments, initially derived from a thorough literature review and expert consensus, which will then undergo further refinement and updates based on real-world clinical experiences, incorporating feedback from 2 to 3 rounds of expert consensus or Delphi questionnaire surveys. Our goal is to establish a COS-DRF or CMS-DRF that aligns with the principles and practices of TCM, and provide high-quality evidence for clinical practice.

Objective: To evaluate the needle puncture safety and clinical efficacy of manual reduction combined with external fixation of ankle frame in the treatment of trimalleolar fracture under the guidance of Chinese Osteosynthesis (CO) theory., Methods: The clinical data of 118 patients with trimalleolar fractures admitted from December 2010 to December 2021 were retrospectively analyzed. Fifty-three patients were treated with manual reduction combined with external fixation of ankle frame(observation group). Sixty-five patients were treated with open reduction and internal fixation with plate and screws(control group). The operation time, hospitalization days, non-weight-bearing time of the affected limb, clinical healing time of fracture, incidence of complications, visual analogue scale (VAS) before and 1 month after operation, and American Orthopedic Foot and Ankle Society(AOFAS) score of ankle joint before and 1 year after operation were compared between the two groups., Results: Patients in both groups were followed up for more than 1 year. All patients were followed up, and the duration ranged from 14 to 70 months, with an average of(35.28±14.66) months. There were statistically significant in operation time, hospitalization days, non-load-bearing time of affected limbs, clinical healing time of fractures and VAS score one month after operation between the two groups. One month after operation, the VAS score of the observation group was lower than that of the control group( t =3.343, P =0.001). The operation time of the observation group was significantly shorter than that of the control group( t =9.091, P =0.000). The hospitalization days in the observation group were significantly less than those in the control group( t =5.034, P =0.000). The non-load-bearing time of the affected limb in the observation group was significantly shorter than that in the control group( t =11.960, P =0.000). The clinical healing time of fracture in the observation group was significantly shorter than that in the control group( t =4.007, P =0.000). There was no significant difference in AOFAS score between the two groups one year after operation( t =0.417, P =0.678). In the observation group, there were 2 cases of pinhole infection and 3 cases of loss of reduction less than 2 mm. There were 3 cases of surgical incision infection in the control group. There was no significant difference in the incidence of complications between the two groups( χ 2 =0.446, P =0.504)., Conclusion: Manual reduction combined with external fixation is safe and effective in the treatment of trimalleolar fracture under the guidance of CO theory, and the function of ankle joint recovers well after operation. This therapy has good clinical value.

Objective: To compare the clinical efficacy between closed reduction combined with semi-circular external fixator and minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of middle anddistal tibia fractures., Methods: The clinical data of sixty patients with middle and distal tibia fractures admitted between January 2019 and November 2022, were retrospectively analyzed. These patients were categorized into external fixation group ( n =30) and internal fixation group ( n =30). There were 18 males and 12 females in the external fixation group, with an average age of (49.29±2.35) years old. Among them, 14 patients presented with fractures on the left side, and 16 patients presented with fractures on the right side. Closed reduction, arched wire, and semi-circular external fixator were used for treatment. There were 20 males and 10 females in the internal fixation group, with an average age of (48.96±1.87) years old. Among them, 15 patients presented with fractures on the left side, and 15 patients presented with fractures on the right side. MIPPO technique was used for the treatment. Perioperative parameters, including time injury to surgery, surgical duration, incision length, intraoperative bleeding, time to active activity, and incision healing level, were compared between the two groups. Clinical outcomes were also assessed, including Johner-Wruhs scores, time to minimum pain-adapted full weight-bearing, visual analog scale (VAS), SF-36 scale, and complications., Results: The external fixation group exhibited a significantly shorter incision length (1.36±0.86) cm and lower intraoperative bleeding (10.83±5.73) ml compared to the internal fixation group (12.74±3.12) cm and (86.47±8.90) ml, respectively( P <0.05). The postoperative active activity time (1.50±0.54) days and minimum pain-adapted full weight-bearing activity time(108.87±3.43) days in the external fixation group were slightly delayed than the internal fixation group(1.15±0.98) days and (105.27±3.68) days, respectively( P <0.05). Over a mean postoperative follow-up duration of (6.23±1.89) months, both groups showed improved VAS and SF-36 scale scores. There were no statistically significant differences in VAS and SF-36 scale scores 1, 3, 6 months post-operatively between the two groups( P >0.05). The intraoperative surgical time in the external fixation group (35.42±9.31) minutes was shorter than that in the internal fixation group(74.22±7.81) minutes ( P <0.05). There was no intraoperative vascular or nerve injury, nor postoperative skin necrosis in the external fixation group. However, skin necrosis was observed in 6 patientsin the internal fixation group, representing a statistically significant difference ( P <0.05)., Conclusion: Both external fixation and plate internal fixation are effective methods for the treatment of middle and distal tibia fractures. External fixation exhibits the advantage of less surgical trauma and a lower incidence of complications.

Constructing a powerful photocatalytic system that can achieve the carbon dioxide (CO 2 ) reduction half-reaction and the water (H 2 O) oxidation half-reaction simultaneously is a very challenging but meaningful task. Herein, a porous material with a crystalline topological network, named viCOF-bpy-Re, was rationally synthesized by incorporating rhenium complexes as reductive sites and triazine ring structures as oxidative sites via robust -C=C- bond linkages. The charge-separation ability of viCOF-bpy-Re is promoted by low polarized π-bridges between rhenium complexes and triazine ring units, and the efficient charge-separation enables the photogenerated electron-hole pairs, followed by an intramolecular charge-transfer process, to form photogenerated electrons involved in CO 2 reduction and photogenerated holes that participate in H 2 O oxidation simultaneously. The viCOF-bpy-Re shows the highest catalytic photocatalytic carbon monoxide (CO) production rate (190.6 μmol g -1  h -1 with about 100 % selectivity) and oxygen (O 2 ) evolution (90.2 μmol g -1 h -1 ) among all the porous catalysts in CO 2 reduction with H 2 O as sacrificial agents. Therefore, a powerful photocatalytic system was successfully achieved, and this catalytic system exhibited excellent stability in the catalysis process for 50 hours. The structure-function relationship was confirmed by femtosecond transient absorption spectroscopy and density functional theory calculations., (© 2023 Wiley-VCH GmbH.)

Aim: 6S-5-methyltetrahydrofolate is the predominant form of dietary folate in circulation and is used as a crystalline form of calcium salt (MTHF-Ca). Reports revealed that MTHF-Ca was more safe than folic acid, a synthetic and highly stable version of folate. Folic acid has been reported to have anti-inflammatory effects. The study's objective was to assess the anti-inflammatory effect of MTHF-Ca in vitro and in vivo., Main Methods: In vitro, the ROS production was assessed by H2DCFDA, and nuclear translocation of NF-κB were evaluated by the NF-κB nuclear translocation assay kit. Interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) were assessed using ELISA. In vivo, ROS production was assessed by H2DCFDA, neutrophils and macrophages recruitment were evaluated in tail transection-induced and CuSO 4 -induced zebrafish inflammation models. Expression of inflammation related genes were also investigated based on CuSO 4 -induced zebrafish inflammation model., Key Findings: MTHF-Ca treatment decreased LPS-induced ROS production, inhibited nuclear translocation of NF-κB and decreased the levels of IL-6, IL-1β and TNF-α in RAW264.7 cells. In addition, MTHF-Ca treatment inhibited ROS production, suppressed the recruitment of neutrophils and macrophages, and reduced the expression of inflammation related genes, including jnk, erk, nf-κb, myd88, p65, tnf-α, and il-1b in zebrafish larvae., Significance: MTHF-Ca may play an anti-inflammatory role by reducing the recruitment of neutrophils and macrophages and keeping the low levels of proinflammatory mediators and cytokines. MTHF-Ca may have a potential role in the treatment of inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer. However, their relevant pathogenesis is not clear. In the present study, we investigated the potential role of exosome-delivered α-synuclein (α-syn) in the regulation between PD and liver cancer. We cultured hepatocellular carcinoma (HCC) cells with exosomes derived from conditioned medium of the PD cellular model, and injected exosomes enriched with α-syn into the striatum of a liver cancer rat model. We found that α-syn-contained exosomes from the rotenone-induced cellular model of PD suppressed the growth, migration, and invasion of HCC cells. Integrin αVβ5 in exosomes from the rotenone-induced PD model was higher than that in the control, resulting in more α-syn-contained exosomes being taken up by HCC cells. Consistently, in vivo experiments with rat models also confirmed exosome-delivered α-syn inhibited liver cancer. These findings illustrate the important role of PD-associated protein α-syn inhibiting hepatoma by exosome delivery, suggesting a new mechanism underlying the link between these two diseases and therapeutics of liver cancer., (© 2023 Wiley Periodicals LLC.)

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer, indicating that PD-associated proteins may mediate the development of cancer. Here, we investigated a potential role of PD-associated protein α-synuclein in regulating liver cancer progression in vivo and in vitro. We found the negative correlation of α-synuclein with metabotropic glutamate receptor 5 (mGluR5) and γ-synuclein by analyzing the data from The Cancer Genome Atlas database, liver cancer patients and hepatoma cells with overexpressed α-synuclein. Moreover, upregulated α-synuclein suppressed the growth, migration, and invasion. α-synuclein was found to associate with mGluR5 and γ-synuclein, and the truncated N-terminal of α-synuclein was essential for the interaction. Furthermore, overexpressed α-synuclein exerted the inhibitory effect on hepatoma cells through the degradation of mGluR5 and γ-synuclein via α-synuclein-dependent autophagy-lysosomal pathway (ALP). Consistently, in vivo experiments with rotenone-induced rat model of PD also confirmed that, upregulated α-synuclein in liver cancer tissues through targeting on mGluR5/α-synuclein/γ-synuclein complex inhibited tumorigenesis involving in ALP-dependent degradation of mGluR5 and γ-synuclein. These findings give an insight into an important role of PD-associated protein α-synuclein accompanied by the complex of mGluR5/α-synuclein/γ-synuclein in distant communications between PD and liver cancer, and provide a new strategy in therapeutics for the treatment of liver cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: A new approach to showcasing author publications on a website involves using a visual representation instead of the conventional paper list. The creation of an impact beam plot (IBP) as a research profile for individuals is crucial, especially when incorporating collection edges that include self-cited articles through a rare cluster analysis technique not commonly found in the literature. This study presents the application of a unique method called the following-leading clustering algorithm (FLCA) to generate IBPs for 3 highly productive authors., Methods: For the 3 highly productive authors, Sung-Ho Jang from South Korea, Chia-Hung Kao from Taiwan, and Chin-Hsiao Tseng from Taiwan, all their published articles indexed in the Web of Science Core Collection were downloaded. Sung-Ho Jang published 593 articles, Chia-Hung Kao published 732 articles, and Chin-Hsiao Tseng published 160 articles. To analyze and showcase their publications, the FLCA was utilized. This algorithm helped cluster their articles and identify representative publications for each author. To assess the effectiveness and validity of the FLCA algorithm, both network charts and heatmaps with dendrograms were employed. IBPs were then created and compared for each of the 3 authors, taking into consideration their h-index, x-index, and self-citation rate. This allowed for a comprehensive visual representation of their research impact and citation patterns., Results: The results show that these authors' h-index, x-index, and self-citation rates were (37, 44.01, 1.66%), (42, 61.47, 0.23%), and (37, 40.3, 6.62%), respectively. A higher value in these metrics indicates a more remarkable research achievement. A higher self-citation rate with a lower cluster number indicates that manuscripts are more likely to have been self-drafted. Using the FLCA algorithm, IBPs were successfully generated for each author., Conclusion: The FLCA algorithm allows for the easy generation of visual IBPs based on authors' publication profiles. These IBPs incorporate 3 important bibliometric metrics: h-index, x-index, and self-citations. These metrics are highly recommended for use by researchers globally, particularly with the self-citation rate, as they offer valuable insights into the scholarly impact and citation patterns of individual researchers., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Covalent organic frameworks (COFs) are a type of crystalline porous polymers that possess ordered structures and eternal pores. Because of their unique structural characteristics and diverse functional groups, COFs have been used in various application fields, such as adsorption, catalysis, separation, ion conduction, and energy storage. Among COFs, the fluorine-containing COFs (fCOFs) have been developed for special applications by virtue of special physical and chemical properties resulting from fluorine element, which is a nonmetallic halogen element and possesses strong electronegativity. In the organic chemistry field, introducing fluorine into chemicals enables those chemicals to exhibit many interesting properties, and fluorine chemistry increasingly plays an important role in the history of chemical development. The introduction of fluorine in COFs can enhance the crystallinity, porosity, and stability of COFs, making COFs having superior performances and some new applications. In this review, the synthesis and application of fCOFs are systematically summarized. The application involves photocatalytic production of hydrogen peroxide, photocatalytic water splitting, electrocatalytic CO 2 reduction, adsorption for different substances (H 2 , pesticides, per-/polyfluoroalkyl substances, polybrominated diphenyl ethers, bisphenols, and positively charged organic dye molecules), oil-water separation, energy storage (e.g., zinc-ion batteries, lithium-sulfur batteries), and proton conduction. Perspectives of remaining challenges and possible directions for fCOFs are also discussed., (© 2022 Wiley-VCH GmbH.)

Objective: In view of the important role of risk prediction models in the clinical diagnosis and treatment of sepsis, and the limitations of existing models in terms of timeliness and interpretability, we intend to develop a real-time prediction model of sepsis with high timeliness and clinical interpretability., Patients and Methods: We used eight real-time basic physiological monitoring indicators of patients, including heart rate, respiratory rate, oxygen saturation, mean arterial pressure, systolic blood pressure, diastolic blood pressure, temperature and blood glucose, extracted three-hour dynamic feature sequences, and calculated 3 linear parameters (mean, standard deviation, and endpoint value), a 24-dimensional feature vector was constructed, and finally a real-time sepsis prediction model was constructed based on the Local Interpretable Model-Agnostic Explanation (LIME) interpretability method., Results: The area under the receiver operating characteristic curve (AUROC), Accuracy and F1 scores of Extremely Randomized Trees we built were higher than those of other models, with AUROC above 0.76, showing the best performance. The Imbalance XGBoost has a high specificity (0.86) in predicting sepsis. The LIME local interpretable model we built can display a large amount of valid model prediction details for clinical workers' reference, including the prediction probability and the influence of each feature on the prediction result, thus effectively assisting the work of clinical workers and improving diagnostic efficiency., Conclusions: This model can provide real-time dynamic early warning of sepsis for critically ill patients under supervision and provide a reference for clinical decision support. At the same time, interpretive analysis of sepsis prediction models can improve the credibility of the models.

Pearl of Csaba (PC) is a valuable backbone parent for early-ripening grapevine (Vitis vinifera) breeding, from which many excellent early ripening varieties have been bred. However, the genetic basis of the stable inheritance of its early ripening trait remains largely unknown. Here, the pedigree, consisting of 40 varieties derived from PC, was re-sequenced for an average depth of ∼30×. Combined with the resequencing data of 24 other late-ripening varieties, 5,795,881 high-quality single nucleotide polymorphisms (SNPs) were identified following a strict filtering pipeline. The population genetic analysis showed that these varieties could be distinguished clearly, and the pedigree was characterized by lower nucleotide diversity and stronger linkage disequilibrium than the non-pedigree varieties. The conserved haplotypes (CHs) transmitted in the pedigree were obtained via identity-by-descent analysis. Subsequently, the key genomic segments were identified based on the combination analysis of haplotypes, selective signatures, known ripening-related quantitative trait loci (QTLs), and transcriptomic data. The results demonstrated that varieties with a superior haplotype, H1, significantly (one-way ANOVA, P < 0.001) exhibited early grapevine berry development. Further analyses indicated that H1 encompassed VIT&#95;16s0039g00720 encoding a folate/biopterin transporter protein (VvFBT) with a missense mutation. VvFBT was specifically and highly expressed during grapevine berry development, particularly at veraison. Exogenous folate treatment advanced the veraison of "Kyoho". This work uncovered core haplotypes and genomic segments related to the early ripening trait of PC and provided an important reference for the molecular breeding of early-ripening grapevine varieties., Competing Interests: Conflict of interest statement. The authors declare no conflicts of interest., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

An iridium-catalyzed asymmetric allylic benzylation of aryl vinyl carbinols under light irradiation is described. 2-Methylbenzophenone derivatives are employed and activated to hydroxy-o-quinodimethanes by an ultraviolet (UV) light. This approach enables asymmetric allylic benzylation with high enantioselectivity (up to 99 % ee) from readily available 2-methylbenzophenones without the utilization of strong bases, and pre-activation or pre-functionalization of the substrates. Moreover, deuterium experiments reveal the generation of nucleophilic benzyl species from 2-methylbenzophenone under UV irradiation., (© 2022 Wiley-VCH GmbH.)

Histone demethylases containing the JmjC domain play an extremely important role in maintaining the homeostasis of histone methylation and are closely related to plant growth and development. Currently, the JmjC domain-containing proteins have been reported in many species; however, they have not been systematically studied in grapes. In this paper, 21 VviJMJ gene family members were identified from the whole grape genome, and the VviJMJ genes were classified into five subfamilies: KDM3, KDM4, KDM5, JMJD6, and JMJ-only based on the phylogenetic relationship and structural features of Arabidopsis and grape. After that, the conserved sites of VviJMJ genes were revealed by protein sequence analysis. In addition, chromosomal localization and gene structure analysis revealed the heterogeneous distribution of VviJMJ genes on grape chromosomes and the structural features of VviJMJ genes, respectively. Analysis of promoter cis-acting elements demonstrated numerous hormone, light, and stress response elements in the promoter region of the VviJMJ genes. Subsequently, the grape fruit was treated with MTA (an H3K4 methylation inhibitor), which significantly resulted in the early ripening of grape fruits. The qRT-PCR analysis showed that VviJMJ genes (except VviJMJ13c) had different expression patterns during grape fruit development. The expression of VviJMJ genes in the treatment group was significantly higher than that in the control group. The results indicate that VviJMJ genes are closely related to grape fruit ripening., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To examine the prevalence and trend of tobacco and e-cigarettes uses and identify the influencing factors for smoking behavior in junior middle school students in Shanghai, and provide data support and scientific basis for the development of tobacco control intervention strategy in adolescents. Methods: Multi-stage stratified random sampling method was used to select junior middle school students in 8 districts and 10 districts in Shanghai in 2013 and in 2019 respectively. Information about tobacco and e-cigarettes uses in the students were collected by using self-administrated questionnaire. The prevalence of tobacco and e-cigarettes uses were calculated, the difference between two years was compared with χ 2 test. The influencing factors were identified by multivariate logistic regression analysis. Results: In 2019, the current smoking rate was 0.6% in junior middle school students in Shanghai, and the smoking attempt rate was 2.9%, both were lower than the levels in 2013 (0.7% and 6.9%). The current use rate of e-cigarettes was 0.6% in 2019,with no significant change compared with 2013 (0.6%). The proportion of the students who had heard of e-cigarettes in 2019 (78.4%) was higher than that in 2013 (47.2%). In 2019, the second-hand smoke (SHS) exposure rate at home, in both indoor and outdoor public places and on public transportations was 72.5%, which was slightly lower than the level in 2013 (73.0%), the differences were all significant ( P <0.05). In 2019, the students seeing close friend smoking ( OR =27.381, 95% CI : 12.037-62.287), seeing someone smoking in school ( OR =2.477, 95% CI : 1.155-5.312), believing that SHS may not be harmful ( OR =8.471, 95% CI : 1.464-49.005) had higher possibility of smoking. Being aged ≥15 years (compared with being aged ≤12 years, OR =8.688, 95% CI : 1.922-39.266), exposure to SHS in outdoor public place ( OR =8.608, 95% CI : 1.048-70.692), close friend smoking ( OR =8.115, 95% CI : 1.754-37.545) were positively associated with e-cigarettes use, and believing that smoking results in uncomfortable social contact [compared with believing that smoking results in comfortable social contact ( OR =0.105,95% CI : 0.018-0.615)] were negatively associated with e-cigarettes use, the difference was significant ( P <0.05). Conclusion: The prevalence of tobacco and e-cigarette uses in junior middle school students in Shanghai remained at a low level in recent years. The SHS exposure rate in junior middle school students is high. Smoking behavior of junior middle school students is closely related to personal attitude and awareness of tobacco, exposure to SHS, peer smoking and the situation of tobacco control in schools. Prevention and intervention should be carried out from multi-dimensions to effectively protect teenagers from tobacco hazards.

Preclinical studies have clearly indicated that offspring of mothers who suffered sleep deprivation during pregnancy exhibit anxiety, depression-like behaviors, and cognitive deficits. The cognitive impairment induced by maternal sleep deprivation (MSD) is currently poorly treated. Growing evidence indicates that an enriched environment (EE) improves cognition function in models of Alzheimer's disease, schizophrenia, and lipopolysaccharide. However, the effects of EE on hippocampal-dependent learning and memory, as well as synaptic plasticity markers changes induced by MSD, are unclear. In the present study, pregnant CD-1 mice were randomly divided into a control group, MSD group, and MSD+EE group. Two different living environments, including standard environment and EE, were prepared. When male and female offspring were 2 months, the open field test and elevated plus maze were used to assess anxiety-like behavior, and the Morris water maze was used to evaluate hippocampal learning and memory. Western blotting and real-time fluorescence quantitative polymerase chain reaction were used to detect the expression of brain-derived neurotrophic factor and Synaptotagmin-1 in the hippocampus of offspring. The results revealed that MSD-induced offspring showed anxiety-like behaviors and cognitive impairment, while EE alleviated anxiety-like behavior and cognitive impairment in offspring of the MSD+EE group. The cognitive impairment induced by MSD was associated with a decreased brain-derived neurotrophic factor and an increased Synaptotagmin-1, while EE increased and decreased brain-derived neurotrophic factor and Synaptotagmin-1 in the hippocampus of mice from the MSD+EE group, respectively. Taken together, we can conclude that EE has beneficial effects on MSD-induced synaptic plasticity markers changes and can alleviate anxiety-like behaviors and cognitive impairment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Cheng, Wang, Wei, Ge, Kong and Li.)

Herein, chiral Brønsted acid-catalyzed intramolecular asymmetric allylic alkylation of indoles with allylic primary alcohols is described. The allyl alcohols were directly employed as the allylic precursors in this metal-free protocol, without preactivation or any additional activating reagents. This method provides the convenient synthesis of a broad range of functionalized tetrahydrocarbazoles in excellent yields (≤97%) with good enantioselectivity (≤93% ee). The optimal conditions are compatible for gram-scale reaction.

Dearomatization reactions provide rapid access to structurally complex three-dimensional molecules from simple aromatic compounds. Plenty of reports have demonstrated their utilities in the synthesis of natural products, medicinal chemistry, and materials science in the last decades. Recently, visible-light mediated photocatalysis has emerged as a powerful tool to promote many kinds of transformations. The dearomatization reactions induced by visible-light have also made significant progress during the past several years. This review provides an overview of visible-light induced dearomatization reactions classified based on the manner in which aromaticity is disrupted.

Phytochemical investigation on the 80% EtOH extract of the whole plants of Zephyranthes grandiflora afforded three new 4a- epi -plicamine-type alkaloids, zephyranthines A-C ( 1-3 ). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D ( 1 H - 1 H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the alkaloids were in vitro evaluated for their cytotoxic activities against six glioma cell lines (CHG - 5, SH-SY5Y, SHG - 44, U251, U343, and GL15). Alkaloids 2 and 3 exhibited significant cytotoxic activities against all tested cell lines with IC 50 values of less than 20 μM.

Objective: To investigate the populations of freshwater crabs, the intermediate host of Paragonimus and Paragonimus infections in freshwater crabs in the Minjiang River basin along the middle section of Wuyi Mountain, so as to provide baseline data for parasitic disease control and research and expansion of the parasite resource bank., Methods: From November 2020 to April 2021, freshwater crabs were sampled from streams and ditches neighboring residential areas in Jianning County and its neighboring Ninghua, Shaowu, Jiangle and Shunchang counties. The crab species was identified based on the morphological features of the terminal segment of the first abdominal appendage of male crabs, and Paragonimus infections were detected in freshwater crabs. The Paragonimus metacercariae were isolated, and the types of metacercariae were identified based on the metacercaria size, cystic wall thickness, and the excretory bladder and intestinal tract morphology. In addition, the prevalence, intensity and index of metacercaria infections were calculated in freshwater crabs., Results: There were seven crab species found in Jianning County and six neighboring water systems along the Minjiang River basin, including Sinopotamon jianglense , S. fukinense , Huananpotamon lichuanense , H. lini , H. shenni , H. planopodum , Bottapotamon engelhardti , and there were metacercariae of three Paragonimus species detected in these crabs, including P. westermani , P. skrjabini and P. sanpingensis , with a prevalence rate of 43.6% (125/287). The infection rates of P. westermani , P. sanpingensis and P. skrjabini were 57.1% (48/84), 26.2% (22/84) and 61.8% (21/34) in S. jianglense , and the infection rates of P. westermani and P. sanpingensis were 52.6% (51/97) and 30.9% (30/97) in S. fukinense , while the rate of P. westermani infection was 6.9% (5/72) in H. lichuanense , which is the first record of P. westermani infections in H. lichuanense . Mixed P. westermani and P. sanpingensis infections were predominantly found in freshwater crabs sampled from Jianning County, where the rate of Paragonimus infections was 70.4% (76/108), with 15.3 metacercariae identified in each crab with Paragonimus infections and 1.9 metacercariae found in each gram of crabs with Paragonimus infections, and the index of metacercariae infections was 20.5. In addition, P. westermani , P. skrjabini and P. sanpingensi metacercariae were found in freshwater crabs sampled from Jianning-neighboring counties, where the rate of Paragonimus infections was 52.3% (56/107), with 9.8 metacercariae identified in each crab with Paragonimus infections and 0.9 metacercariae found in each gram of crabs with Paragonimus infections, and the index of metacercariae infections was 4.6., Conclusions: There are multiple freshwater crab species and Paragonimus infection is high in freshwater crabs in Jianning County and its neighboring Minjiang River basin, which is a high-risk natural focus for Paragonimus infections.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

An N d : Y A G / C r 4+ : Y A G passively Q -switched (PQS) laser in a near-hemispherical cavity is exploited to generate high-order structured pulsed fields. Under tightly focused on-axis pumping, radial-order Laguerre-Gaussian (LG) modes with controllable mode orders by the input pump power are realized to exhibit quite stable temporal behavior. The pulse repetition rates of radial-LG modes can reach up to 78 kHz with an average output power of 0.57 W and peak power beyond 300 W under a 5-W pump level. Furthermore, by introducing 1D off-axis pumping into the PQS laser, various structured pulsed fields with transverse morphologies as high-order Ince-Gaussian (IG) modes are further created. With clean and well-defined beam structures, the IG pulsed fields can be nicely reconstructed by the resonant modes of the inhomogeneous Helmholtz equation for spherical cavities. More importantly, these high-order PQS IG modes reveal highly regular pulse trains with the maximum pulse repetition rate beyond 20 kHz and overall peak power higher than 1.5 kW.

High-power structured beams with the transverse morphologies as the Lissajous figures are generated by an Nd:YVO 4 laser under two-dimensional off-axis pumping. By fine-tuning the cavity length in the neighborhood around the condition of longitudinal-transverse coupling, different cases of accidental degeneracies from the intracavity astigmatism are achieved to lead the output emission to be various Lissajous modes with different transverse frequency ratios. The generated Lissajous modes reveals good power performance with slope efficiency up to 47% and optical-to-optical conversion efficiency to be higher than 37.5% at a pump power of 16 W. Moreover, by applying beam transformation via a single-lens astigmatic mode converter, the generated Lissajous modes are further converted into structured vortex beams with transverse patterns localized on the trochoidal curves. The transformed trochoidal vortex beams are confirmed to preserve well-defined mode structures even when the average output power has been scaled up to be higher than 4 W.

Background: Microvascular tissue transfer is a common reconstructive procedure. We designed a bioelectrical impedance assessment (BIA) system for quantitative analysis of tissue status. This study attempts to verify it through the animal model., Methods: The flaps of the rat model were monitored by the BIA system., Results: The BIA variation of the free flap in the rat after the vascular compromise was recorded. The non-vascular ligation limbs of the same rat served as a control group. The bio-impedance in the experimental group was larger than the control group. The bio-impedances of both the thigh / feet flaps in the experimental group were increased over time. In the thigh , the difference in bio-impedance from the control group was first detected at 10 kHz at the 3rd and last at 1 kHz at the 6th h, after vascular compromise. The same finding was observed in the feet . Compared with the control group, the bio-impedance ratio (1 kHz/20 kHz) of the experimental group decreased with time, while their variation tendencies in the thigh and feet were similar., Conclusions: The flap may be monitored by the BIA for vascular status.

Background: An unmet need for more effective and affordable kinase inhibitors remains in patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) in China, where only sorafenib is approved for this indication. This study evaluated the 24-week objective response rate (ORR) to donafenib-a new, domestic multikinase inhibitor-in the treatment of locally advanced or metastatic RAIR-DTC in patients with measurable lesions. Two dose regimens (300 mg twice daily vs. 200 mg twice daily) were used to determine its optimal dosage and safety for further phase III studies. Methods: This study was a randomized, open-label, multicenter phase II trial. Thirty-five adult RAIR-DTC patients with at least one measurable targeted lesion according to RECIST 1.1 were enrolled from 12 centers in China and randomized to receive either 200 mg (17 patients) or 300 mg (18 patients) of donafenib orally twice daily for 24 weeks. The primary endpoint was ORR, and the secondary endpoints included progression-free survival (PFS) among others. Additionally, biochemical (serum thyroglobulin) and structural (total tumor diameter [TTD]) responses were assessed, change (ΔTTD) rates were calculated, and safety was evaluated. Results: The ORRs for the 200- and 300-mg arms were 12.5% and 13.33% ( p  = 1.000), respectively. The 300-mg arm had a nonsignificant, longer median PFS than the 200-mg arm (14.98 months vs. 9.44 months) ( p  = 0.351). There was a trend toward more tumor shrinkage in the 300-mg arm compared with the 200-mg arm (average ΔTTD rate -0.52 ± 0.71 vs. -0.04 ± 1.55 mm/month, p  = 0.103). Most treatment-related adverse events (AEs) in both arms were grades 1-2. The most common grade 3 treatment-related AEs in both arms were palmar-plantar erythrodysesthesia and hypertension; the sum occurrence rates of these two AEs in the 200-mg and 300-mg arms were 11.43% and 22.86%, respectively. Conclusions: Donafenib was generally well tolerated. Both donafenib regimens demonstrated similar efficacy in terms of the ORR in locally advanced or metastatic RAIR-DTC. The results warrant further studies on donafenib as a new, feasible treatment option for RAIR-DTC patients. Clinical Trials.gov IDs: NCT02870569; CTR20160220.