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A wide range of N -CF 3 imidoyl chlorides were synthesized for the first time via the N -trifluoromethylation of nitriles in DCM by using AlCl 3 -activated PhICF 3 Cl as the CF 3 source. The reactions of them with N - /O-/S-nucleophiles, as well as with 1,3-dipoles, were carried out to efficiently deliver N -CF 3 amidines/imidates/thioimidates and N -CF 3 azoles, demonstrating that they are a class of scalable NCF 3 -containing synthons in the synthesis of N -CF 3 compounds.

Objectives: To compare the clinical effect between two acupoint regimens of moxibustion on knee osteoarthritis (KOA), and observe the influences on the serum content of interleukin 1α (IL-1α), interleukin-17A (IL-17A), tumor necrosis factor α (TNF-α), bone gla protein (BGP) and osteoprotegerin (OPG)., Methods: KOA patients were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 3 cases dropped off). In the observation group, moxibustion was applied to Xiyan (EX-LE5), Dubi (ST35), Zusanli (ST36), Dazhu (BL11), Xuanzhong (GB39) and Yongquan (KI1) on the affected side. In the control group, EX-LE5, ST35 and ST36 were selected on the affected side. One session of treatment took 30 min in each group, delivered 3 times a week and the duration of treatment was 4 weeks. The scores of Western Ontario and McMaster University (WOMAC) and visual analogue scale (VAS) were observed and the serum content of IL-1α, IL-17A, TNF-α, BGP and OPG of the two groups were measured before and after treatment., Results: Compared with those before treatment, the WOMAC score, VAS score and the serum content of IL-1α, IL-17A and TNF-α were decreased ( P <0.05), and the content of BGP and OPG were increased ( P <0.05) after treatment. Compared with the control group, the WOMAC score, VAS score and the serum content of IL-1α and TNF-α in the observation group were lower ( P <0.05), and the content of BGP and OPG were higher ( P <0.05). The total effective rate of the observation group was 89.5% (34/38), and that of the control group was 83.8% (31/37), with no statistically significant difference., Conclusions: Moxibustion therapy of "nourishing the kidney and benefiting the marrow" can relieve joint pain, improve joint function, reduce the level of inflammatory factors and ameliorate bone metabolic indicators. The effect of the acupoint regimen in this moxibustion therapy is better than that of the local acupoint selection.

Objective: Isolated spinal aneurysms (ISAs) are rare causes of subarachnoid hemorrhage (SAH), which encompass a highly heterogeneous group of clinical entities with multifarious pathogeneses, clinical characteristics, and treatment strategies. Therefore, knowledge about the ISAs remains inadequate. In this study, the authors present a comprehensive analysis of clinical data associated with ISAs at their institutions to enhance the understanding of this disease., Methods: Patients with ISAs confirmed by spinal angiography or surgery at the authors' institutions between 2015 and 2022 were included. Data regarding clinical presentation, lesion location, aneurysm morphology, comorbidities, treatment results, and clinical outcomes were reviewed., Results: Seven patients with ISAs were included in the study. Among them, 4 patients (57.1%) experienced severe headache, and 3 patients (42.9%) reported sudden-onset back pain. Additionally, lower-extremity weakness and urinary retention were observed in 2 of these patients (28.6%). Four of the aneurysms exhibited fusiform morphology, whereas the remaining were saccular. All saccular aneurysms in this series were attributed to hemodynamic factors. Conservative treatment was administered to 3 patients, 2 of whom underwent follow-up digital subtraction angiography, which showed spontaneous occlusion of both aneurysms. Four patients ultimately underwent invasive treatments, including 2 who underwent microsurgery and 2 who received endovascular embolization. One patient died of recurrent SAH, while the remaining 6 patients had a favorable prognosis at the latest follow-up assessment., Conclusions: The morphology of aneurysms may be associated with their etiology. Saccular ISAs are usually caused by pressure due to abnormally increased blood flow, whereas fusiform lesions may be more likely to be secondary to vessel wall damage. The authors found that a saccular spinal aneurysm in young patients with a significant dilated parent artery may be a vestige of spinal cord arteriovenous shunts. ISAs can be managed by surgical, endovascular, or conservative procedures, and the clinical outcome is generally favorable. However, the heterogeneous nature of the disease necessitates personalized treatment decision-making based on specific clinical features of each patient.

Cancer patients are at high risk of malnutrition, which can lead to adverse health outcomes such as prolonged hospitalization, increased complications, and increased mortality. Accurate and timely nutritional assessment plays a critical role in effectively managing malnutrition in these patients. However, while many tools exist to assess malnutrition, there is no universally accepted standard. Although different tools have their own strengths and limitations, there is a lack of narrative reviews on nutritional assessment tools for cancer patients. To address this knowledge gap, we conducted a non-systematic literature search using PubMed, Embase, Web of Science, and the Cochrane Library from their inception until May 2023. A total of 90 studies met our selection criteria and were included in our narrative review. We evaluated the applications, strengths, and limitations of 4 commonly used nutritional assessment tools for cancer patients: the Subjective Global Assessment (SGA), Patient-Generated Subjective Global Assessment (PG-SGA), Mini Nutritional Assessment (MNA), and Global Leadership Initiative on Malnutrition (GLIM). Our findings revealed that malnutrition was associated with adverse health outcomes. Each of these 4 tools has its applications, strengths, and limitations. Our findings provide medical staff with a foundation for choosing the optimal tool to rapidly and accurately assess malnutrition in cancer patients. It is essential for medical staff to be familiar with these common tools to ensure effective nutritional management of cancer patients., (© 2024. Huazhong University of Science and Technology.)

The anomalous Hall effect (AHE) is an important transport signature revealing topological properties of magnetic materials and their spin textures. Recently, MnBi 2 Te 4 has been demonstrated to be an intrinsic magnetic topological insulator. However, the origin of its intriguing AHE behaviors remains elusive. Here, we demonstrate the Berry curvature-dominated intrinsic AHE in wafer-scale MnBi 2 Te 4 films. By applying back-gate voltages, we observe an ambipolar conduction and n-p transition in ∼7-layer MnBi 2 Te 4 , where a quadratic relation between the AHE resistance and longitudinal resistance suggests its intrinsic AHE nature. In particular, for ∼3-layer MnBi 2 Te 4 , the AHE sign can be tuned from pristine negative to positive. First-principles calculations unveil that such an AHE reversal originated from the competing Berry curvature between oppositely polarized spin-minority-dominated surface states and spin-majority-dominated inner bands. Our results shed light on the underlying physical mechanism of the intrinsic AHE and provide new perspectives for the unconventional sign-tunable AHE.

Alzheimer's disease (AD) is an age-related degenerative disease, which is characteristic by the deposition of senile plaques (SP) outside the cells, the neurofibrillary tangles (NFTs) inside the neurons, and the loss of synapse and neurons. Neuroinflammation may play an important role in the pathogenesis of AD. Microglia are the immune cells in the central nervous system. However, microglia might become disease-related microglia (DAMs) when stimulated by the external environment. DAMs have been shown to be involved in a series of events of AD development including Aβ accumulation and tau phosphorylation. The triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor that is mainly expressed by microglia in the central nervous system (CNS). TREM2 plays an important role in the physiological function of microglia, and the dyshomeostasis of TREM2 is related to the development of late-onset AD. This article summarized the latest advances in TREM2 biology and its impact on the roles of microglia in AD development, with a particular emphasis on the structure, ligands, signal transduction, and the agonistic antibodies of TREM2 for AD treatment. We further discussed the survival, migration, phagocytosis, inflammation, and cellular metabolism of microglia, as well as the role of sTREM2 in neuroprotection and as a biomarker for AD. It provides a reference for further research on the molecular mechanism of microglial TREM2 in the occurrence and development of AD and on the therapeutic strategies targeted on the microglial TREM2., Competing Interests: The authors have no conflict of interest to report.

Chinese giant salamander skin collagen (CGSSC) was successfully conjugated with glucose (Glu)/xylose (Xy) by ultrasound Maillard reaction (MR) in nature deep eutectic solvents (NADES). The effects of ultrasound and reducing sugar types on the degree graft (DG) of MR products (MRPs), as well as the influence of DG on the structure and functional properties of MRPs were investigated. The results indicated that the ultrasound assisted could markedly enhance the MR of CGSSC, and low molecular weight reducing sugars were more reactive in MR. The ultrasound MR significantly changed the microstructure, secondary and tertiary structures of CGSSC. Moreover, the free sulfhydryl content of MRPs were increased, thus enhancing the surface hydrophobicity, emulsifying properties and antioxidant activity, which were positively correlated with DG. These findings provided theoretical insights into the effects of ultrasound assisted and different sugar types on the functional properties of collagen induced by MR., 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 Elsevier B.V. All rights reserved.)

This study aimed to investigate the prognostic significance of tumor mutation burden (TMB) among patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Tumor tissue specimens after surgical resection were collected for DNA extraction. Somatic mutation detection and TMB analysis were conducted using next-generation sequencing (NGS). Recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and long-term survival data of patients were obtained by telephone follow-up. Univariate analysis between TMB status and prognosis was carried out by survival analysis. A retrospective review of 78 patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy showed a median disease-free survival of 3.6 years and median overall survival (OS) of 5.3 years. NGS analysis exhibited that the most common mutated somatic genes among the 78 patients were tumor suppressor protein p53 (TP53), epidermal growth factor receptor, low-density lipoprotein receptor related protein 1B, DNA methyltransferase 3 alpha and FAT atypical cadherin 3, and their prevalence was 56.4%, 48.7%, 37.2%, 30.7%, and 25.6%, respectively. TMB status was divided into TMB-L (≤ 4.5/Mb) and TMB-H (> 4.5/Mb) based on the median TMB threshold. Relevance of TMB to prognosis suggested that the median OS of patients with TMB-L was significantly longer than that of patients with TMB-H (NR vs. 4.6, P = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed., (Copyright © 2023 Korean Society of Cancer Prevention.)

Introduction: Herd immunity against norovirus (NoV) is poorly understood in terms of its serological properties and vaccine designs. The precise neutralizing serological features of genotype I (GI) NoV have not been studied., Methods: To expand insights on vaccine design and herd immunity of NoVs, seroprevalence and seroincidence of NoV genotypes GI.2, GI.3, and GI.9 were determined using blockade antibodies based on a 5-year longitudinal serosurveillance among 449 residents in Jidong community., Results: Correlation between human histo-blood group antigens (HBGAs) and GI NoV, and dynamic and persistency of antibodies were also analyzed. Seroprevalence of GI.2, GI.3, and GI.9 NoV were 15.1%-18.0%, 35.0%-38.8%, and 17.6%-22.0%; seroincidences were 10.0, 21.0, and 11.0 per 100.0 person-year from 2014 to 2018, respectively. Blockade antibodies positive to GI.2 and GI.3 NoV were significantly associated with HBGA phenotypes, including blood types A, B (excluding GI.3), and O + ; Lewis phenotypes Le b+ /Le y+ and Le a+b+ /Le x+y+ ; and secretors. The overall decay rate of anti-GI.2 antibody was -5.9%/year (95% CI: -7.1% to -4.8%/year), which was significantly faster than that of GI.3 [-3.6%/year (95% CI: -4.6% to -2.6%/year)] and GI.9 strains [-4.0%/year (95% CI: -4.7% to -3.3%/year)]. The duration of anti-GI.2, GI.3, and GI.9 NoV antibodies estimated by generalized linear model (GLM) was approximately 2.3, 4.2, and 4.8 years, respectively., Discussion: In conclusion, enhanced community surveillance of GI NoV is needed, and even one-shot vaccine may provide coast-efficient health benefits against GI NoV infection., 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 © 2023 Yu, Xie, Li, Koroma, Wang, Wang, Jing, Xu, Yu, Du, Zhou, Liang, Zhang and Dai.)

Mammalian target of rapamycin complex 1 (mTORC1) monitors cellular amino acid changes for function, but the molecular mediators of this process remain to be fully defined. Here, we report that depletion of cellular amino acids, either alone or in combination, leads to the ubiquitination of mTOR, which inhibits mTORC1 kinase activity by preventing substrate recruitment. Mechanistically, amino acid depletion causes accumulation of uncharged tRNAs, thereby stimulating GCN2 to phosphorylate FBXO22, which in turn accrues in the cytoplasm and ubiquitinates mTOR at Lys2066 in a K27-linked manner. Accordingly, mutation of mTOR Lys2066 abolished mTOR ubiquitination in response to amino acid depletion, rendering mTOR insensitive to amino acid starvation both in vitro and in vivo. Collectively, these data reveal a novel mechanism of amino acid sensing by mTORC1 via a previously unknown GCN2-FBXO22-mTOR pathway that is uniquely controlled by uncharged tRNAs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Using a systematic literature search of original articles published during 2022 in Gastrointestinal Endoscopy and other high-impact medical and gastroenterology journals, the 10-member Editorial Board of the American Society for Gastrointestinal Endoscopy composed a list of the 10 most significant topic areas in GI endoscopy during the study year. Each Editorial Board member was directed to consider 3 criteria in generating candidate lists-significance, novelty, and global impact on clinical practice-and subject matter consensus was facilitated by the Chair through electronic voting. The 10 identified areas collectively represent advances in the following endoscopic spheres: artificial intelligence, endoscopic submucosal dissection, Barrett's esophagus, interventional EUS, endoscopic resection techniques, pancreaticobiliary endoscopy, management of acute pancreatitis, endoscopic environmental sustainability, the NordICC trial, and spiral enteroscopy. Each board member was assigned a consensus topic area around which to summarize relevant important articles, thereby generating this précis of the "top 10" endoscopic advances of 2022., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2023. Published by Elsevier Inc.)

Medical training occurs during peak childbearing years for most medical students. Many factors influence specialty selection. The aims of this study were (i) to determine whether being a parent is a major deciding factor when picking a specialty and (ii) whether parents are more drawn to family-friendly specialties than non-parents. The authors performed a multicenter web-based survey study of medical students enrolled in Oregon Health and Science University, Dartmouth's Geisel School of Medicine, and University of Michigan Medical School. The 27-item instrument assessed parenthood status, specialty preference, specialty perceptions, and factors influencing specialty choice. A total of 537 out of 2236 (24.0%) students responded. Among respondents, 59 (10.9%) were current or expecting parents. The majority (359, 66.8%) were female and 24-35 years old (430, 80.1%). Of the students who were parents or expecting, 30 (50.9%) were female, and the majority (55, 93.2%) were partnered. Top specialties preferred by both parents and non-parents were family medicine, emergency medicine, obstetrics and gynecology (OB/GYN), internal medicine, psychiatry, and pediatrics. Specialties rated most family-friendly included family medicine, dermatology, pediatrics, psychiatry, radiology, emergency medicine, and pathology. The specialties rated least family-friendly were surgery, neurosurgery, orthopedic surgery, plastic surgery, and OB/GYN. These rankings were the same between groups. Passion for the field, culture of the specialty, and quality of life were the top three factors students considered when choosing a specialty. Being a parent or future parent ranked more highly for parents than non-parents, but was not in the top three factors for either group. US Medical School parents report that being a parent influenced their medical specialty choice "strongly" or "very strongly." However, being a parent was not weighed as heavily as passion for the field, culture of the specialty, and quality of life. These student-parents are entering perceived "non-family friendly" specialties at similar rates as their peers. US Medical school training and simultaneous parenting is daunting, yet student parents are putting their passion first when making a career choice. They must be supported., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cyclic polymers have very unique structure and properties, and thus have drawn intense research attention. However, controlled synthesis of cyclic polymers with predictable molar mass and narrow distribution is still a challenging task. In this study, we developed a novel cyclic catalyst that initiates the ring-expansion polymerisation of isocyanides, producing a series of cyclic helical polymers with predictable molecular weight and low dispersity. Interestingly, the ring-expansion polymerization of the isocyanide macromonomers gives well-defined cyclic bottlebrush polymers. The cyclic topology was demonstrated using transmission electron microscopy.

Severe injuries to the peripheral nervous system (PNS) require Schwann cells to aid in neuronal regeneration. Low-frequency electrical stimulation is known to induce the cogrowth of neurons and Schwann cells in an injured PNS. However, the correlations between electrical stimulation and Schwann cell viability are complex and not well understood. In this work, we develop a machine learning (ML)-integrated workflow that uses conductive hydrogel biointerfaces to evaluate the impacts of fabrication parameters and electrical stimulation on the Schwann cell viability. First, a hydrogel array with varying MXene and peptide loadings is fabricated, which serves as conductive biointerfaces to incubate Schwann cells and introduce various electrical stimulation (at different voltages and frequencies). Upon specific fabrication parameters and stimulation, the cell viability is evaluated and input into an artificial neural network model to train the model. Additionally, a data augmentation method is applied to synthesize 1000-fold virtual data points, enabling the construction of a high-accuracy prediction model (with a testing mean absolute error ≤11%). By harnessing the model's predictive power, we can accurately predict Schwann cell viability based on a given set of fabrication/stimulation parameters. Finally, the SHapley Additive exPlanations model interpretation provides several data-scientific insights that are validated by microscopic cellular observations. Our hybrid approach, involving conductive biointerface fabrication, ML algorithms, and data analysis, offers an unconventional platform to construct a preclinical prediction model at the cellular level.

Electrochemical reduction of CO 2 (CO 2 RR) into value-added products is a promising strategy to reduce energy consumption and solve environmental issues. Formic acid/formate is one of the high-value, easy-to-collect, and economically viable products. Herein, the reconstructed Bi 2 O 2 CO 3 nanosheets (BOC R NSs) are synthesized by an in situ electrochemical anion exchange strategy from Bi 2 O 2 SO 4 as a pre-catalyst. The BOC R NSs achieve a high formate Faradaic efficiency (FE formate ) of 95.7% at -1.1 V versus reversible hydrogen electrode (vs. RHE), and maintain FE formate above 90% in a wide potential range from -0.8 to -1.5 V in H-cell. The in situ spectroscopic studies reveal that the obtained BOC R NSs undergo the anion exchange from Bi 2 O 2 SO 4 to Bi 2 O 2 CO 3 and further promote the self-reduction to metallic Bi to construct Bi/BiO active site to facilitate the formation of OCHO * intermediate. This result demonstrates anion exchange strategy can be used to rational design high performance of the catalysts toward CO 2 RR., (© 2023 Wiley-VCH GmbH.)

A simple and efficient method for the synthesis of unsymmetrical disulfides is reported. Using sodium sulfites and 2-mercaptobenzo heterocyclic compounds as starting materials, the unsymmetrical sulfur-sulfur bonds could be quickly constructed in the PPh 3 /I 2 reaction system under transition-metal-free conditions. This protocol has the advantages of mild reaction conditions, easily available starting materials, and wide substrate scope, showing potential synthetic value for the synthesis of a diversity of biologically or pharmaceutically active compounds.

Ethnopharmacological Relevance: Banxia Xiexin decoction (BXD) is a classic Chinese herbal formulation consisting of 7 herbs including Pinelliae Rhizoma, Scutellariae Radix, Zingiberis Rhizoma, Ginseng Radix, Glycyrrhizae Radix, Coptidis Rhizoma, and Jujubae Fructus, which can exert effects on lowering lipids and alleviating depressive mood disorders via affecting gastrointestinal tract., Aim of the Study: The pathogenesis of atherosclerosis (AS) co-depression disease has not been well studied, and the current clinical treatment strategies are not satisfactory. As a result, it is critical to find novel methods of treatment. Based on the hypothesis that the gut microbiome may promote the development of AS co-depression disease by regulating host lipid metabolism, this study sought to evaluate the effectiveness and action mechanism of BXD in regulation of the gut microbiome via an intervention in AS co-depression mice., Materials and Methods: To determine the primary constituents of BXD, UPLC-Q/TOF-MS analysis was carried out. Sixteen C56BL/6 mice were fed normal chow as a control group; 64 ApoE -/- mice were randomized into four groups (model group and three treatment groups) and fed high-fat chow combined with daily bind stimulation for sixteen weeks to develop the AS co-depression mouse model and were administered saline or low, medium or high concentrations of BXD during the experimental modeling period. The antidepressant efficacy of BXD was examined by weighing, a sucrose preference test, an open field test, and a tail suspension experiment. The effectiveness of BXD as an anti-AS treatment was evaluated by means of biochemical indices, the HE staining method, and the Oil red O staining method. The impacts of BXD on the gut microbiome structure and brain (hippocampus and prefrontal cortex tissue) lipids in mice with the AS co-depression model were examined by 16S rDNA sequencing combined with lipidomics analysis., Results: The main components of BXD include baicalin, berberine, ginsenoside Rb1, and 18 other substances. BXD could improve depression-like behavioral characteristics and AS-related indices in AS co-depression mice; BXD could regulate the abundance of some flora (phylum level: reduced abundance of Proteobacteria and Deferribacteres; genus level: reduced abundance of Clostridium&#95;IV, Helicobacter, and Pseudoflavonifractor, Acetatifactor, Oscillibacter, which were significantly different). The lipidomics analysis showed that the differential lipids between the model and gavaged high-dose BXD (BXH) groups were enriched in glycerophospholipid metabolism, and lysophosphatidylcholine (LPC(20:3)(rep)(rep)) in the hippocampus and LPC(20:4)(rep) in the prefrontal cortex both showed downregulation in BXH. The correlation analysis illustrated that the screened differential lipids were mainly linked to Deferribacteres and Actinobacteria., Conclusion: BXD may exert an anti-AS co-depression therapeutic effect by modulating the abundance of some flora and thus intervening in peripheral lipid and brain lipid metabolism (via downregulation of LPC levels)., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Gastric sleeve stenosis (GSS) is an adverse event following sleeve gastrectomy for which objective tools are needed for diagnosis and treatment. Endoscopic treatment with serial pneumatic balloon dilation may relieve symptoms and prevent the need for conversion to Roux-en-Y gastric bypass. Endoluminal functional impedance planimetry (EndoFLIP) is an endoscopic tool that measures luminal diameter and distensibility indices (DI) and could be used to characterize severity of GSS., Methods: This was a retrospective analysis of a prospective database of patients referred for symptoms suggestive of GSS. Severity was determined at each endoscopy by a bariatric endoscopist blinded to EndoFLIP measurements. Successive pneumatic balloon dilations were performed until symptoms resolved; failure was defined as referral for conversion. EndoFLIP measurements of stenosis diameter and DI were obtained pre- and post-dilation. Primary outcomes were pre- and post-dilation luminal diameter and DI of GSS. Secondary outcomes were endoscopic severity of GSS, patient characteristics, and need for surgical revision., Results: 26 patients were included; 23 (85%) were female. Mean age was 45.3 (± 9.9) years. Mean number of dilations was 2.4 (± 1.3) and 10 (38%) patients were referred for conversion. Mild, moderate, and severe GSS was found in 10 (38%), 6 (23%), and 10 (38%) patients, respectively. Moderate and severe GSS underwent more dilations (2.5 ± 1.0 and 3.2 ± 1.6) than mild GSS (1.8 ± 0.8) and were more likely to be referred for conversion. Both pre- and post-dilation diameters were significantly larger in mild versus moderate or severe GSS. Additionally, pre- and post-dilation DI at 30 ml were significantly higher for mild compared to moderate and severe GSS., Discussion: EndoFLIP measurements correlate well with endoscopic assessment of GSS. While more data are needed to determine ideal balloon size and threshold measurements, our results suggest EndoFLIP may help expedite diagnosis and treatment of GSS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Okra (Abelmoschus esculentus L.) is a tropical crop species, and its growth and development are severely affected by cold stress. Recent studies have identified a potential association between WRKY transcription factors and the cold response mechanism of crops. In this study, the AeWRKY32 transcription factor that encodes 482 amino acids was amplified from A. esculentus, and its expression level was found to be the highest in the okra flower. AeWRKY32 localized to the nucleus and displayed transcriptional activation capability. Under normal conditions, overexpression of AeWRKY32 induced anthocyanin accumulation, with higher expression levels of AtCHS1, AtCHI4, AtF3H1, and AtDFR2 in transgenic Arabidopsis. Under cold stress, anthocyanin levels were further elevated in transgenic Arabidopsis plants. At the same time, AeWRKY32 overexpression promoted ABA biosynthesis, inhibited H 2 O 2 and O 2 - generation, induced stomatal closure, reduced electrolyte leakage, and thus improved the cold resistance of transgenic Arabidopsis. Furthermore, under cold stress, the expression profiles of AtCOR413, AtCOR15B, AtCBF1, and AtCBF2 were upregulated in transgenic Arabidopsis. Overall, our study provides evidence that AeWRKY32 serves as a crucial regulator in both anthocyanin accumulation and cold tolerance of transgenic Arabidopsis. Our findings could provide insights into the molecular mechanism linking AeWRKYs to plant cold tolerance., 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 Elsevier GmbH. All rights reserved.)

Temozolomide (TMZ) is an oral DNA-alkylating drug used in colorectal cancer (CRC) chemotherapy. In this work, we proposed a safe and biomimetic platform for macrophages-targeted delivery of TMZ and O 6 -benzylguanine (O 6 -BG). TMZ was loaded in poly (D, l-lactide-coglycolide) (PLGA) nanoparticles, followed by sequential coating with O 6 -BG-grafted chitosan (BG-CS) layers and yeast shell walls (YSW) via layer-by-layer assembly (LBL) process, forming TMZ@P-BG/YSW biohybrids. Due to the yeast cell membrane-camouflage, TMZ@P-BG/YSW particles exhibited significantly enhanced colloidal stability as well as low premature drug leakage in simulated gastrointestinal conditions. In vitro drug release profiles of TMZ@P-BG/YSW particles revealed noticeable higher TMZ release in simulated tumor acidic environment within 72 h. Meanwhile, O 6 -BG could down-regulate MGMT expression in CT26 colon carcinoma cells, ultimately facilitating TMZ-induced tumor cell death. After oral delivery of yeast cell membrane-camouflaged particles containing fluorescent tracer (Cy5), TMZ@P-BG/YSW and bare YSW displayed high retention time of 12 h in the colon and small intestine (ileum). Correspondingly, oral gavage administration of TMZ@P-BG/YSW particles afforded favorable tumor-specific retention and superior tumor growth inhibition. Overall, TMZ@P-BG/YSW is validated to be a safe, targetable and effective formulation, paving a new avenue towards highly effective and precise treatment of malignancies., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Neuroinflammation plays a crucial role in the occurrence and development of cognitive impairment in type 2 diabetes mellitus (T2DM), but the specific injury mechanism is not fully understood. Astrocyte polarization has attracted new attention and has been shown to be directly and indirectly involved in neuroinflammation. Liraglutide has been shown to have beneficial effects on neurons and astrocytes. However, the specific protection mechanism still needs to be clarified. In this study, we assessed the levels of neuroinflammation and A1/A2-responsive astrocytes in the hippocampus of db/db mice and examined their relationships with iron overload and oxidative stress. First, in db/db mice, liraglutide alleviated the disturbance of glucose and lipid metabolism, increased the postsynaptic density, regulated the expression of NeuN and BDNF, and partially restored impaired cognitive function. Second, liraglutide upregulated the expression of S100A10 and downregulated the expression of GFAP and C3, and decreased the secretion of IL-1β, IL-18, and TNF-α, which may confirm that it regulates the proliferation of reactive astrocytes and A1/A2 phenotypes polarize and attenuate neuroinflammation. In addition, liraglutide reduced iron deposition in the hippocampus by reducing the expression of TfR1 and DMT1 and increasing the expression of FPN1; at the same time, liraglutide by up-regulating the levels of SOD, GSH, and SOD2 expression, as well as downregulation of MDA levels and NOX2 and NOX4 expression to reduce oxidative stress and lipid peroxidation. The above may attenuate A1 astrocyte activation. This study preliminarily explored the effect of liraglutide on the activation of different astrocyte phenotypes and neuroinflammation in the hippocampus of a T2DM model and further revealed its intervention effect on cognitive impairment in diabetes. Focusing on the pathological consequences of astrocytes may have important implications for the treatment of diabetic 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 © 2023 An, Liu, Gao, Wang, Sun, Su, Zhang, Yu, Yang and Shi.)

Studies on insects have contributed significantly to a better understanding of learning and memory, which is a necessary cognitive capability for all animals. Although the formation of memory has been studied in some model insects, more evidence is required to clarify the characteristics of memory formation, especially long-term memory (LTM), which is important for reliably storing information. Here, we explored this question by examining Bactrocera dorsalis, an agricultural pest with excellent learning abilities. Using the classical conditioning paradigm of the olfactory proboscis extension reflex (PER), we found that paired conditioning with multiple trials (>3) spaced with an intertrial interval (≥10 min) resulted in stable memory that lasted for at least 3 d. Furthermore, even a single conditioning trial was sufficient for the formation of a 2-d memory. With the injection of protein inhibitors, protein-synthesis-dependent memory was confirmed to start 4 h after training, and its dependence on translation and transcription differed. Moreover, the results revealed that the dependence of memory on protein translation exhibited a time-window effect (4-6 h). Our findings provide an integrated view of LTM in insects, suggesting common mechanisms in LTM formation that play a key role in the biological basis of memory., (© 2022 Institute of Zoology, Chinese Academy of Sciences.)

Background:  In the literature, filum terminale arteriovenous shunts (FTAVSs) always feature a single shunt point. Nidus-type FTAVSs have rarely been reported, and the best treatment strategy is unclear. This is a report of one exceptional case of a nidus-type FTAVS and surgical treatment of the lesion., Case Description: The patient suffered from cauda equina syndrome for 9 months. Magnetic resonance imaging and spinal angiography revealed a nidus-type FTAVF at the L2 level. Surgical resection was performed in the hybrid operating room, and the nidus was completely resected with the assistance of intraoperative methylene blue angiography and neurophysiological monitoring. The postoperative neurological function was stable., Conclusions: A nidus-type arteriovenous shunt could originate from the FT, and in such cases, complete surgical resection with intraoperative neurophysiological monitoring in a hybrid operating room should be suggested.

Background: Water shortage caused by global warming seriously affects the yield and quality of vegetable crops. β-carotene, the lipid-soluble natural product with important pharmacological value, is abundant in celery. Transcription factor MYB family extensively disperses in plants and plays regulatory roles in carotenoid metabolism and water scarcity response., Results: Here, the AgMYB5 gene encoding 196 amino acids was amplified from celery cv. 'Jinnanshiqin'. In celery, the expression of AgMYB5 exhibited transactivation activity, tissue specificity, and drought-condition responsiveness. Further analysis proved that ectopic expression of AgMYB5 increased β-carotene content and promoted drought tolerance in transgenic Arabidopsis thaliana. Moreover, AgMYB5 expression promoted β-carotene biosynthesis by triggering the expression of AtCRTISO and AtLCYB, which in turn increased antioxidant enzyme activities, and led to the decreased contents of H 2 O 2 and MDA, and the inhibition of O 2 - generation. Meanwhile, β-carotene accumulation promoted endogenous ABA biosynthesis of transgenic Arabidopsis, which resulted in ABA-induced stomatal closing and delayed water loss. In addition, ectopic expression of AgMYB5 increased expression levels of AtERD1, AtP5CS1, AtRD22, and AtRD29., Conclusions: The findings indicated that AgMYB5 up-regulated β-carotene biosynthesis and drought tolerance of Arabidopsis., (© 2023. The Author(s).)

Advanced object detection methods always face high algorithmic complexity or low accuracy when used in pedestrian target detection for the autonomous driving system. This paper proposes a lightweight pedestrian detection approach called the YOLOv5s-G2 network to address these issues. We apply Ghost and GhostC3 modules in the YOLOv5s-G2 network to minimize computational cost during feature extraction while keeping the network's capability of extracting features intact. The YOLOv5s-G2 network improves feature extraction accuracy by incorporating the Global Attention Mechanism (GAM) module. This application can extract relevant information for pedestrian target identification tasks and suppress irrelevant information, improving the unidentified problem of occluded and small targets by replacing the GIoU loss function used in the bounding box regression with the α-CIoU loss function. The YOLOv5s-G2 network is evaluated on the WiderPerson dataset to ensure its efficacy. Our proposed YOLOv5s-G2 network offers a 1.0% increase in detection accuracy and a 13.2% decrease in Floating Point Operations (FLOPs) compared to the existing YOLOv5s network. As a result, the YOLOv5s-G2 network is preferable for pedestrian identification as it is both more lightweight and more accurate.

Plant-derived monoterpene indole alkaloids (MIAs) from Uncaria rhynchophylla (UR) have huge medicinal properties in treating Alzheimer's disease, Parkinson's disease, and depression. Although many bioactive UR-MIA products have been isolated as drugs, their biosynthetic pathway remains largely unexplored. In this study, untargeted metabolome identified 79 MIA features in UR tissues (leaf, branch stem, hook stem, and stem), of which 30 MIAs were differentially accumulated among different tissues. Short time series expression analysis captured 58 pathway genes and 12 hub regulators responsible for UR-MIA biosynthesis and regulation, which were strong links with main UR-MIA features. Coexpression networks further pointed to two strictosidine synthases (UrSTR1/5) that were coregulated with multiple MIA-related genes and highly correlated with UR-MIA features (r > 0.7, P < 0.005). Both UrSTR1/5 catalyzed the formation of strictosidine with tryptamine and secologanin as substrates, highlighting the importance of key residues (UrSTR1: Glu309, Tyr155; UrSTR5: Glu295, Tyr141). Further, overexpression of UrSTR1/5 in UR hairy roots constitutively increased the biosynthesis of bioactive UR-MIAs (rhynchophylline, isorhynchophylline, corynoxeine, etc), whereas RNAi of UrSTR1/5 significantly decreased UR-MIA biosynthesis. Collectively, our work not only provides candidates for reconstituting the biosynthesis of bioactive UR-MIAs in heterologous hosts but also highlights a powerful strategy for mining natural product biosynthesis in medicinal plants., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Human-sensitive mechanosensation depends on ionic currents controlled by skin mechanoreceptors. Inspired by the sensory behavior of skin, we investigate zwitterionic hydrogels that generate ions under an applied force in a mobile-ion-free system. Within this system, water dissociates as the distance between zwitterions reduces under an applied pressure. Meanwhile, zwitterionic segments can provide migration channels for the generated ions, significantly facilitating ion transport. These combined effects endow a mobile-ion-free zwitterionic skin sensor with sensitive transduction of pressure into ionic currents, achieving a sensitivity up to five times that of nonionic hydrogels. The signal response time, which relies on the crosslinking degree of the zwitterionic hydrogel, was ~38 ms, comparable to that of natural skin. The skin sensor was incorporated into a universal throat-worn silent-speech recognition system that transforms the tiny signals of laryngeal mechanical vibrations into silent speech., (© 2023. The Author(s).)

HLA-B*55:130 differs from HLA-B*55:35 by two nucleotides in exon 2., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study aimed at elucidating some characteristics of the shock wave overpressure generated by a non-traditional layered charge comprising an inner high-energy explosive and an outer polymer matrix composite. Two models for predicting the peak overpressure (Δ p m ) of the charge were established, namely, a model based on the initial parameters of the blast wave, and a model considering the weakening of the explosion energy through the introduction of polymer matrix cladding. The overpressure of a typical layered charge was experimentally measured for model validation. It was found that the difference between the Δ p m predicted by the two models and the experimental data is less than 15.12% and 14.17%, respectively. The model that was established based on the conservation of energy law, is in best agreement with the experimental data under different cladding/charge mass ratios ( α m ). The model that was based on the initial parameters of the blast wave obtained a low predicted value when α m was 0.4-0.8, which is attributed to the non-uniformity of the gas-solid mixture during the explosive dispersion stage.

A direct strategy for the difunctionalization of alkenes, with acylation occurring at the more substituted alkene position, would be attractive for complex ketone synthesis. We report herein a reaction driven by a single photocatalyst that enables α-acylation in this way with the introduction of a fluoromethyl, alkyl, sulfonyl or thioether group at the β-position of the alkene with high chemo- and regioselectivity under extremely mild conditions. Crucial to the success of this method are rate differences in the kinetics of radical generation through single-electron transfer (SET) between different radical precursors and the excited photocatalyst (PC*). Thus, the β-position of the alkene is first occupied by the group derived from the radical precursor that can be generated most readily, and α-keto acids could be used as an electrophilic reagent for the α-acylation of alkenes., (© 2022 Wiley-VCH GmbH.)

In this study, polyaminophosphoric acid (PA)-functionalized ion-imprinted chitosan (CS) aerogel was fabricated for the first time, exhibiting good antibacterial property for selective La(III) recovery and oil/water separation. The as-prepared PA-CS-IIA-2 shows a remarkable adsorption capacity of 114.6 mg/g toward La(III) and high selectivity in the competitive adsorption systems, which is attributed to its abundant imprinting sites and surface functional groups. Benefiting from the amphiphilic property, the PA-CS-IIA-2 also exhibits an excellent adsorption performance for the extractant, oils, and organic solvents. Besides, the PA-CS-IIA-2 presents excellent regeneration and reusability characteristics. Moreover, compared with CS, the PA-CS-IIA-2 exhibits a significantly improved antibacterial activity originating from the PA component. Most importantly, the PA-CS-IIA-2 aerogel is capable of removing multiple pollutants all together and effectively inhibiting bacteria in the complex wastewater environments. Therefore, this study paves the way for developing high-performance rare-earth capture materials with multiple functions to meet diverse applications.

The biogenic amine octopamine (OA, invertebrate counterpart of noradrenaline) plays critical roles in the regulation of olfactory behavior. Historically, OA has been thought to mediate appetitive but not aversive learning in honeybees, fruit flies (Drosophila), and crickets. However, this viewpoint has recently been challenged because OA activity through a β-adrenergic-like receptor drives both appetitive and aversive learning. Here, we explored the roles of OA neurons in olfactory learning and memory retrieval in Bactrocera dorsalis. We trained flies to associate an orange odor with a sucrose reward or to associate methyl eugenol, a male lure, with N,N-diethyl-3-methyl benzoyl amide (DEET) punishment. We then treated flies with OA receptor antagonists before appetitive or aversive conditioning and a memory retention test. Injection of OA receptor antagonist mianserin or epinastine into the abdomen of flies led to impaired of appetitive learning and memory retention with a sucrose reward, while aversive learning and memory retention with DEET punishment remained intact. Our results suggest that the OA signaling participates in appetitive but not aversive learning and memory retrieval in B. dorsalis through OA receptors., (© 2022 Institute of Zoology, Chinese Academy of Sciences.)

The 9-member Editorial Board of the American Society for Gastrointestinal Endoscopy performed a systematic literature search of original articles published during 2021 in Gastrointestinal Endoscopy and 10 other high-impact medical and gastroenterology journals on endoscopy-related topics. Votes from each editorial board member were tallied to identify a consensus list of the 10 most significant topic areas in GI endoscopy over the calendar year of study, with a focus on 3 criteria: significance, novelty, and global impact on clinical practice. The 10 areas identified collectively represent advances in the following endoscopic topics: colonoscopy optimization, bariatric endoscopy, endoscopic needle sampling and drainage, peroral endoscopic myotomy, endoscopic defect closure, meeting systemic challenges in endoscopic training and practice, endohepatology, FNA versus fine-needle biopsy sampling, endoscopic mucosal and submucosal procedures, and cold snare polypectomy. Each board member contributed a summary of important articles relevant to 1 to 2 of the consensus topic areas, leading to a collective summary that is presented in this document of the "top 10" endoscopic advances of 2021., (Published by Elsevier Inc.)

The hexagonal rare earth ferrites h -RFeO 3 (R = rare earth element) have been recognized as promising candidates for a room-temperature multiferroic system, and the primary issue for these materials is how to get a stable hexagonal structure since the centrosymmetric orthorhombic structure is generally stable for most RFeO 3 at room-temperature, while the hexagonal phase is only stable under some strict conditions. In the present work, h -Lu 1- x In x FeO 3 ( x = 0-1) thin films were prepared on a Nb-SrTiO 3 (111) single-crystal substrate by a pulsed laser deposition (PLD) process, and the multiferroic characterization was performed at room temperature. With the combined effects of chemical pressure and epitaxial strain, the stable hexagonal structure was achieved in a wide composition range ( x = 0.5-0.7), and the results of XRD (X-ray diffraction) and SAED (selected area electron diffraction) indicate the super-cell match relations between the h -Lu 0.3 In 0.7 FeO 3 thin film and substrate. The saturated P - E hysteresis loop was obtained at room temperature with a remanent polarization of about 4.3 μC/cm 2 , and polarization switching was also confirmed by PFM measurement. Furthermore, a strong magnetoelectric coupling with a linear magnetoelectric coefficient of 1.9 V/cm Oe was determined, which was about three orders of magnitude larger than that of h -RFeO 3 ceramics. The present results indicate that the h -Lu 1- x In x FeO 3 thin films are expected to have great application potential for magnetoelectric memory and detection devices.

The development of immunotherapy agents has revolutionized the field of oncology. The only FDA-approved immunotherapeutic approach in breast cancer consists of immune checkpoint inhibitors, yet several novel immune-modulatory strategies are being actively studied and appear promising. Innovative immunotherapeutic strategies are urgently needed in triple negative breast cancer (TNBC), a subtype of breast cancer known for its poor prognosis and its resistance to conventional treatments. TNBC is more primed to respond to immunotherapy given the presence of more tumor infiltrating lymphocytes, higher PD-L1 expression, and higher tumor mutation burden relative to the other breast cancer subtypes, and therefore, immuno-oncology represents a key area of promise for TNBC research. The aim of this review is to highlight current data and ongoing efforts to establish the safety and efficacy of immunotherapeutic approaches beyond checkpoint inhibitors in TNBC., (© 2022. The Author(s).)

In order to improve the mechanical strength and imprinting efficiency, a novel bovine serum albumin (BSA) molecularly imprinted poly(ionic liquid)/calcium alginate composite cryogel membrane (MICM) was prepared. The results of the tensile test indicated that the MICM had excellent mechanical strength which could reach up to 90.00 KPa, 30.30 times higher than the poly (ionic liquid) membrane without calcium alginate; the elongation of it could reach up to 93.70%, 8.28 times higher than the poly (ionic liquid) membrane without calcium alginate. The MICM had a very high welling ratio of 1026.56% and macropore porosity of 62.29%, which can provide effective mass transport of proteins. More remarkably, it had a very high adsorption capacity of 485.87 mg g -1 at 20 °C and 0.66 mg mL -1 of the initial concentration of BSA. Moreover, MICM also had good selective and competitive recognition toward BSA, exhibiting potential utility in protein separation. This work can provide a potential method to prepare the protein-imprinted cryogel membrane with both high mechanical strength and imprinting efficiency.

The aim of this study was to reveal the influence of heavy metal emissions from the flue gas of coal-fired power plants on the surrounding soil environment. Seven heavy metals, including As, Cd, Cr, Cu, Pb, Hg, and Ni, were detected in the flue gas of six coal-fired power plants in Shijiazhuang, and the heavy metals in the soil surrounding the power plants were analyzed. The source analysis and health risk assessment of the heavy metals were carried out. The results showed that after a series of flue gas pollutant control measures, the emission concentrations of different heavy metals in the flue gas of the coal-fired power plants ranged from 0.11 to 6.32 mg·(MW·h) -1 , and Cu, Cr, and Ni were the main pollutants. The total amount of the seven heavy metal elements discharged into the atmosphere by each power plant was 33.56-275.71 kg·a -1 . The average contents of Cr, Cu, Pb, Hg, and Ni in the surface soil surrounding the coal-fired power plant were higher than the background values of Hebei soil, and the contents were 1.16-2.32 times higher than the background values. The heavy metal content in the soil around the power plants was proportional to the heavy metal emissions in the flue gas. The heavy metal content in the soil under different wind directions first increased and then decreased gradually with the increase in distance from the power plants. Source analysis showed that coal combustion emissions contributed the most to heavy metals in soil around the power plants (41.4%), followed by industrial emissions (23.6%) and transportation emissions (19.6%). Altogether, human activities played a leading role in soil heavy metal enrichment, accounting for 84.6%. The health risk assessment showed that the overall health risk of metal elements in the soil surrounding the power plant was within acceptable limits.

Herein, cobaloxime is used for the first time as a catalyst for the synthesis of phosphorylated heteroaromatics, which is an intriguing and versatile functional motif. With visible-light irradiation, cobaloxime not only oxidizes phosphine oxides to form phosphorus radicals (P-radicals) for a subsequent reaction with radical acceptor isocyanides or heteroaromatics, but also combines the radical intermediate with β-H elimination, thereby producing phosphorylated heteroaromatics with only H 2 or CH 4 as byproduct. Phosphine oxides with dialkyl, alkylaryl, and diaryl substituents could be directly transformed into phosphorylated phenanthridines, benzothiazoles, isoquinolines, and common heteroaromatics. This catalytic system features extremely mild conditions, broad substrate scope and good to excellent yields. Scale-up reaction and sunlight reaction show the great application potential in the green synthesis of important organophosphorus chemicals., (© 2022 Wiley-VCH GmbH.)

Objective: To investigate the relationship between high density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) and all-cause mortality in the elderly population. Methods: A total of 14 355 elderly persons aged ≥65 years, who participated in the annual physical examination in Kailuan Group in 2006 were included in this prospective cohort study. According to HDL-C level, the participants were divided into 4 groups: low-level group (HDL-C<1.30 mmol/L), intermediate-level group (1.30 mmol/L ≤HDL-C≤1.54 mmol/L), medium-high-level group (1.55 mmol/L ≤HDL-C≤1.80 mmol/L), high-level group (HDL-C≥1.81 mmol/L). Baseline data such as age, sex and blood lipid levels were collected and compared. Inpatient medical records and death information were obtained through the social security system, and CVD and all-cause mortality were analyzed. After adjusting for confounding factors, the medium-high-level group was used as the reference group. Cox proportional risk regression model was used to evaluate the impact of HDL-C on CVD and all-cause mortality events. The linear or nonlinear relationship between HDL-C level and CVD and all-cause mortality events was evaluated by restricted cubic spline regression model. Death competitive risk analysis was conducted, and sensitivity analysis was performed after excluding subjects with CVD or all-cause mortality within 1 year of follow-up and female participants. Results: The average age of this cohort was (71.5±5.5) years and follow-up time was (10.9±3.3) years. Compared with medium-high-level group, Cox proportional risk regression analysis showed that the HR (95% CI ) of CVD and all-cause mortality in low-level group were 1.21 (1.06-1.38) ( P <0.05) and 1.02 (0.95-1.11) ( P >0.05), respectively; the HR (95% CI ) of CVD events in high-level group was 1.17 (1.03-1.33) ( P <0.05), and there was a marginal significant association with all-cause mortality, the HR (95% CI ) was 1.07 (1.00-1.16) (0.05< P <0.1). The restricted cubic spline regression analysis showed that HDL-C was nonlinearly correlated with CVD (nonlinear correlation P <0.1), and presented a U-shaped curve trend, while HDL-C was linearly correlated with all-cause mortality (nonlinear correlation P >0.1). Conclusions: In the elderly population, the risk of CVD is lowest when the HDL-C level is 1.55-1.80 mmol/L, either high or low HDL-C is a risk factor for CVD. High HDL-C tends to be related to increased risk of all-cause mortality and low HDL-C is not related to increased risk of all-cause mortality.

The development of highly efficient adsorptive material for the selective capture of Pd(II), and re-utilization of spent Pd(II)-loaded adsorbent as an efficient catalyst for organic synthesis are of great significance, but challenging. Particularly, the heterogeneous palladium-catalyzed Suzuki reaction in aqueous media is much more challenging than that of homogeneous. Herein, several novel Pd(II) ion-imprinted polymers (PIIPs) based on dendritic fibrous silica particles are constructed by surface ion imprinting technology (SIIT), using Schiff base and pyridine groups functionalized organosilicon as functional monomer. The PIIP-3 prepared by 3 g of functional monomer exhibits the best adsorption performance, and shows ultrafast (10 min) and selective capture of Pd(II) with high uptake capacity (382.5 mg/g). Moreover, the waste Pd(II) loaded PIIP-3 (PIIP-3-Pd) can serve as a catalyst towards the Suzuki reaction in water, affording 94.2 % yield of the desired product. Interestingly, the PIIP-3-Pd can be reused 12 times without an appreciable decrease in catalytic activity, which is probably due to the imprinted cavity and specific recognition site of PIIP-3 can match and recapture Pd active species in a complex catalytic environment. Thus, this work demonstrates huge potentials of SIIT to enhance the selectivity of adsorption process and increase the lifetime of catalysts., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Linker histone H1 proteins contain many variants in mammalian and can stabilize the condensed state of chromatin by binding to nucleosomes and promoting a more inaccessible structure of DNA. However, it is poorly understood how the binding of histone H1s to chromatin DNA is regulated. Screened as one of a collection of epithelial cells-enriched long non-coding RNAs (lncRNAs), here we found that small nucleolar RNA host gene 8 (SNHG8) is a chromatin-localized lncRNA and presents strong interaction and phase separation with histone H1 variants. Moreover, SNHG8 presents stronger ability to bind H1s than linker DNA, and outcompetes linker DNA for H1 binding. Consequently, loss of SNHG8 increases the amount of H1s that bind to chromatin, promotes chromatin condensation, and induces an epithelial differentiation-associated gene expression pattern. Collectively, our results propose that the highly abundant SNHG8 in epithelial cells keeps histone H1 variants out of nucleosome and its loss contributes to epithelial cell differentiation., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Background: Gastric sleeve stenosis (GSS) occurs in up to 4% of patients after laparoscopic sleeve gastrectomy (LSG). Typical symptoms include reflux, abdominal pain, dysphagia, and regurgitation. Serial pneumatic balloon dilation (PBD) is a successful treatment in many cases obviating the need for revisional surgery, but the potential for weight regain is unknown. The aim of the current study was to assess weight trends following serial pneumatic dilation for GSS., Methods: Retrospective analysis of a prospectively maintained database of patients undergoing serial PBD for GSS at one institution. Primary outcome was change in BMI before and after serial PBD. Secondary outcomes included complication rates and need for revisional surgery. Sub-group analyses were performed to determine the relationship of patient and procedural factors to BMI after PBD., Results: Forty-four patients met inclusion criteria, 34 (84.1%) women. Mean age was 46.7 (SD 11.9). Mean pre-sleeve BMI was 47.8 (SD 9.2), and mean BMI prior to first dilation was 34.2 (SD 6.8). Median follow-up was 395 days (range 48-571). Mean BMI at time of last follow up was 33.7 (SD 6.7). There was no statistical difference in BMI pre- or post-PBD (p 0.980). The lowest 10th and highest 90th BMI percentile trended toward a higher and lower BMI after PBD, respectively, though not significant., Discussion: As the prevalence of sleeve gastrectomy continues to rise, an increasing number of patients will require treatment for GSS. Stenosis is effectively treated with serial PBD in most patients without any impact on weight gain, making this an effective and appealing option for many patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

PTENα and PTENβ (PTENα/β), two long translational variants of phosphatase and tensin homolog on chromosome 10 (PTEN), exert distinct roles from canonical PTEN, including promoting carcinogenesis and accelerating immune-resistant cancer progression. However, their roles in carcinogenesis remain greatly unknown. Herein, we report that, after secreting into the extracellular space, PTENα/β proteins are efficiently cleaved into a short N-terminal and a long C-terminal fragment by the proprotein convertase Furin at a polyarginine stretch in their N-terminal extensions. Although secreted PTENα/β and their cleaved fragment cannot enter cells, treatment of the purified C-terminal fragment but not cleavage-resistant mutants of PTENα exerts a tumor-suppressive role in vivo. As a result, overexpression of cleavage-resistant PTENα mutants manifest a tumor-promoting role more profound than that of wild-type PTENα. In line with these, the C-terminal fragment is significantly downregulated in liver cancer tissues compared to paired normal tissues, which is consistent with the downregulated expression of Furin. Collectively, we show that extracellular PTENα/β present opposite effects on carcinogenesis from intracellular PTENα/β, and propose that the tumor-suppressive C-terminal fragment of PTENα/β might be used as exogenous agent to treat cancer., (© 2022. The Author(s).)

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34) but was not met for sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials., (© 2022. The Author(s).)

Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (M pro ), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV M pro and can thermodynamically stabilize its folding. The structure of CCoV M pro in complex with GC376 was subsequently determined at 2.75 Å. GC376 reacts with the catalytic residue C144 of CCoV M pro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV M pro and other animal CoV M pro s with SARS-CoV-2 M pro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral M pro s, SARS-CoV-2 M pro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46-49 in animal coronaviral M pro s has been replaced by a stable α-helix in SARS-CoV-2 M pro . In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV M pro s. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV M pro s among different species.

Gaseous arsenic emitted from coal combustion flue gas (CCFG) causes not only severe contamination of the environment but also the failure of selective catalytic reduction (SCR) catalysts in power plants. Development of inexpensive and effective adsorbents or techniques for the removal of arsenic from high-temperature CCFG is crucial. In this study, halloysite nanotubes (HNTs) at low price were modified with CuCl 2 (CuCl 2 -HNTs) through ultrasound assistance and applied for capturing As 2 O 3 (g) in simulated flue gas (SFG). Experiments on arsenic adsorption performance, adsorption mechanism, and adsorption energy based on density functional theory were performed. Modification with CuCl 2 clearly enhanced the arsenic uptake capacity (approximately 12.3 mg/g) at 600 °C for SFG. The adsorbent exhibited favorable tolerance to high concentrations of NO x and SO x . The As 2 O 3 (III) was oxidized and transformed into As 2 O 5 (V) on the CuCl 2 -HNTs. The Al-O bridge had the highest adsorption energy for the O end of the As-O group (-2.986 eV), and the combination formed between arsenic-containing groups and aluminum was stable. In addition, the captured arsenic could be stabilized in the sorbent at high temperature, making it possible to use the sorbent before the SCR system. This demonstrates that CuCl 2 -HNTs is a promising sorbent for arsenic oxidation and removal from CCFG.

Although polyacrylonitrile fiber (PANF) and metal-organic frameworks (MOFs) have been extensively investigated to remove U(VI) from water, their practical applications are seriously hindered by the relatively low stability of PANF in acidic solution and great difficulty of separating MOFs nanoparticles from solution, beside that, little attention is paid to the fabrication of MOFs and PANF composite materials (MPCMs) with excellent adsorption capacity for U(VI). Herein, we report the synthesis of novel MPCMs by decorating different concentrations of UiO-66-NH2 crystals onto polyamine and amidoxime groups functionalized PANF (PA-AO-PANF) through cross-linking method for U(VI) extraction. The characterization results reveal that the combination of PA-AO-PANF and UiO-66-NH2 crystals endows MPCMs with excellent separation ability, large surface area, good stability and plentiful surface functional groups, which contributes to good selectivity and enhanced adsorption performance. Consequently, the obtained UN-PA-AO-PANF-2 shows the maximum uptake capacity of 441.8 mg/g and equilibrium uptake time of 30 min towards U(VI). Besides, the U(VI) uptake ability and structure of UN-PA-AO-PANF-2 are well preserved after ten adsorption-desorption cycles. With these outstanding properties, the adsorbent has great potential for the capture of U(VI) from aqueous solutions. Importantly, this work provides a cost-effective and efficient way to construct extremely stable MPCMs hybrid fibers., (Copyright © 2021 Elsevier B.V. All rights reserved.)

With the deepening of the concept of recycling economy and green chemistry, selective capture of Cu(II) from wastewater by biosorbent and reuse of the spent Cu(II)-loaded adsorbent are of great significance. Herein, we synthesized composite of rice husk (RH) with mesoporous silica MCM-41 (RH@MCM-41) modified by organosilane containing amino and schiff groups as functional monomer and cross-linking agent. The silica modified RH@MCM-41 was employed as supporter to fabricate copper ion-imprinted polymers as absorbents (named as RM-CIIPs) via surface ion imprinting technique. Adsorption isotherms, kinetics, selectivity and mechanism of RM-CIIPs to remove Cu(II) were investigated with respect to different adsorption condition. Furthermore, we explored the catalytic activity of spent Cu(II)-loaded adsorbent in Glaser coupling reaction. Batch adsorption studies revealed that RM-CIIP-3 prepared with functional monomer shows the best adsorption capacity (91.4 mg/g) for Cu(II), and adsorption equilibrium could be reached within 30 min. RM-CIIP-3 exhibited an excellent selectivity for capturing Cu(II) and reusability in six adsorption/desorption cycles. More importantly, the spent Cu(II)-loaded adsorbent could be used as bio-heterogeneous catalyst and afford the desired product (1,4-diphenylbutadiyne) in 99.1% yield. Our research indicates an eco-friendly systematic strategy to utilize the waste material as an adsorbent for removing heavy metals and catalyst for industry., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To analyze the time distribution of the first positive nucleic acid detection in imported cases infected with SARS-CoV-2 reported nationwide in China and provide references for further improvement of the prevention and control of COVID-19 in international travelers. Methods: The data of imported cases infected with SARS-CoV-2 reported by provinces from 24 July 2020 and 23 July 2021 were collected for the analysis on the time distribution of the first positive nucleic acid detection after entering China. Results: A total of 7 199 imported cases infected with SARS-CoV-2 were reported in 28 provinces during 24 July 2020 to 23 July 2021. The median interval ( Q 1 , Q 3 ) from the entry to the first positive nucleic acid detection of SARS-CoV-2 was 1 (0, 5) day. The imported cases who had the first positive nucleic acid detections within 14 days and 14 days later after the entry accounted for 95.15% (6 850/7 199) and 4.85% (349/7 199) respectively. Among these cases, 3.65% (263/7 199), 0.88% (63/7 199) and 0.32% (23/7 199) had the first positive nucleic acid detections within 15-21 days, 22-28 days and 28 days later after the entry respectively. The proportion of asymptomatic infections were 47.24% (3 236/6 850) and 63.61% (222/349) among the cases who had the first positive nucleic acid detections within 14 days and 14 days later after the entry respectively. A total of 39.54% (138/349) of cases infected with SARS-CoV-2 with the first positive nucleic acid detections 14 days later after the entry had inter-provincial travel after the discharge of entry point isolation. Conclusions: About 5% of the imported cases infected with SARS-CoV-2 were first positive 14 days later after the entry. In order to effectively reduce the risk of domestic COVID-19 secondary outbreaks caused by imported cases, it is suggested to add a nucleic acid test on 8 th -13 th day after the entry.