Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines.

Chiral amines are commonly used in the pharmaceutical and agrochemical industries1. The strong demand for unnatural chiral amines has driven the development of catalytic asymmetric methods1,2. Although the N-alkylation of aliphatic amines with alkyl halides has been widely adopted for over 100 years, catalyst poisoning and unfettered reactivity have been preventing the development of a catalyst-controlled enantioselective version3-5. Here we report the use of chiral tridentate anionic ligands to enable the copper-catalysed chemoselective and enantioconvergent N-alkylation of aliphatic amines with α-carbonyl alkyl chlorides. This method can directly convert feedstock chemicals, including ammonia and pharmaceutically relevant amines, into unnatural chiral α-amino amides under mild and robust conditions. Excellent enantioselectivity and functional-group tolerance were observed. The power of the method is demonstrated in a number of complex settings, including late-stage functionalization and in the expedited synthesis of diverse amine drug molecules. The current method indicates that multidentate anionic ligands are a general solution for overcoming transition-metal-catalyst poisoning.

Zirconaaziridine-Mediated Ni-Catalyzed Diastereoselective C(sp2)-Glycosylation.

In the realm of organic synthesis, the catalytic and stereoselective formation of C-glycosidic bonds is a pivotal process, bridging carbohydrates with aglycones. However, the inherent chirality of the saccharide scaffold often has a substantial impact on the stereoinduction imposed by a chiral ligand. In this study, we have established an unprecedented zirconaaziridine-mediated asymmetric nickel catalysis, enabling the diastereoselective coupling of bench-stable glycosyl phosphates with a range of (hetero)aromatic and glycal iodides as feasible coupling electrophiles. Our developed method showcases a broad scope and a high tolerance for various functional groups. More importantly, precise stereocontrol toward both anomeric configurations of forming C(sp2)-glycosides can be realized by simply utilizing the popular chiral bioxazoline (biOx) ligands in this reductive Ni catalysis. Regarding the operating mechanism, both experimental and computational studies support the occurrence of a redox transmetalation process, leading to the formation of a transient, bimetallic Ni-Zr species that acts as a potent and efficient single-electron reductant in the catalytic process.

ABI3BP promotes renal aging through Klotho-mediated ferroptosis.

The aging process of the kidneys is accompanied with several structural diseases. Abnormal fiber formation disrupts the balance of kidney structure and function, causing to end-stage renal disease and subsequent renal failure. Despite this, the precise mechanism underlying renal damage in aging remains elusive. In this study, ABI3BP gene knockout mice were used to investigate the role of ABI3BP in renal aging induced by irradiation. The results revealed a significant increase in ABI3BP expression in HK2 cells and kidney tissue of aging mice, with ABI3BP gene knockout demonstrating a mitigating effect on radiation-induced cell aging. Furthermore, the study observed a marked decrease in Klotho levels and an increase in ferroptosis in renal tissue and HK2 cells following irradiation. Notably, ABI3BP gene knockout not only elevated Klotho expression but also reduced ferroptosis levels. A significant negative correlation between ABI3BP and Klotho was established. Further experiments demonstrated that Klotho knockdown alleviated the aging inhibition caused by ABI3BP downregulation. This study identifies the upregulation of ABI3BP in aged renal tubular epithelial cells, indicating a role in promoting ferroptosis and inducing renal aging by inhibiting Klotho expression.

Cytotoxic iridoid glycosides from the leaves of Paederia scandens.

A phytochemical investigation on the 80% EtOH extract of the leaves of Paederia scandens (Lour.) Merr. resulted into the isolation of three undescribed iridoid glycosides, 10-O-trans-p-coumaroyl-(4R,6R)-3,4-dihydro-3α-methylthiopaederoside (1), 10-O-trans-feruloyl-(4S,6R)-3,4-dihydro-2'-O-3α-paederoside (2), and 10-O-trans-caffeoyl-paederosidic acid ethyl ester (3). The structures of the new compounds were elucidated by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, as well as high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic activity against five endocrine tumor cell lines. As a result, compound 1 exhibited some cytotoxicities against all the tested tumor cell lines with IC50 value less than 20.0 µM.

Two new diterpenoid alkaloids from the roots of Aconitum nagarum and their cytotoxic activity.

A chemical investigation on the roots of Aconitum nagarum afforded two undescribed C19-diterpenoid alkaloids nagarumines D and E (1 and 2). The structures of the new compounds were elucidated by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, as well as HR-ESI-MS. The two isolated alkaloids were tested in vitro for cytotoxic activity against five gastric tumor cell lines. Consequently, compound 2 exhibited some cytotoxicities against several human cancer cell lines with IC50 value less than 20.0 µM.

Copper-Catalyzed Enantioselective C(sp3 )-SCF3 Coupling of Carbon-Centered Benzyl Radicals with (Me4 N)SCF3.

In contrast with the well-established C(sp2 )-SCF3 cross-coupling to forge the Ar-SCF3 bond, the corresponding enantioselective coupling of readily available alkyl electrophiles to forge chiral C(sp3 )-SCF3 bond has remained largely unexplored. We herein disclose a copper-catalyzed enantioselective radical C(sp3 )-SCF3 coupling of a range of secondary/tertiary benzyl radicals with the easily available (Me4 N)SCF3 reagent. The key to the success lies in the utilization of chiral phosphino-oxazoline-derived anionic N,N,P-ligands through tuning electronic and steric effects for the simultaneous control of the reaction initiation and enantioselectivity. This strategy can successfully realize two types of asymmetric radical reactions, including enantioconvergent C(sp3 )-SCF3 cross-coupling of racemic benzyl halides and three-component 1,2-carbotrifluoromethylthiolation of arylated alkenes under mild reaction conditions. It therefore provides a highly flexible platform for the rapid assembly of an array of enantioenriched SCF3 -containing molecules of interest in organic synthesis and medicinal chemistry.

Cu(I)-Catalyzed Chemo- and Enantioselective Desymmetrizing C-O Bond Coupling of Acyl Radicals.

Transition-metal-catalyzed enantioselective functionalization of acyl radicals has so far not been realized, probably due to their relatively high reactivity, which renders the chemo- and stereocontrol challenging. Herein, we describe Cu(I)-catalyzed enantioselective desymmetrizing C-O bond coupling of acyl radicals. This reaction is compatible with (hetero)aryl and alkyl aldehydes and, more importantly, displays a very broad scope of challenging alcohol substrates, such as 2,2-disubstituted 1,3-diols, 2-substituted-2-chloro-1,3-diols, 2-substituted 1,2,3-triols, 2-substituted serinols, and meso primary 1,4-diols, providing enantioenriched esters characterized by challenging acyclic tetrasubstituted carbon stereocenters. Partnered by one- or two-step follow-up transformations, this reaction provides a convenient and practical strategy for the rapid preparation of chiral C3 building blocks from readily available alcohols, particularly the industrially relevant glycerol. Mechanistic studies supported the proposed C-O bond coupling of acyl radicals.

An Exception to the Carothers Equation Caused by the Accelerated Chain Extension in a Pd/Ag Cocatalyzed Cross Dehydrogenative Coupling Polymerization.

The Carothers equation is often used to predict the utility of a small molecule reaction in a polymerization. In this study, we present the mechanistic study of Pd/Ag cocatalyzed cross dehydrogenative coupling (CDC) polymerization to synthesize a donor-acceptor (D-A) polymer of 3,3'-dihexyl-2,2'-bithiophene and 2,2',3,3',5,5',6,6'-octafluorobiphenyl, which go counter to the Carothers equation. It is uncovered that the second chain extension cross-coupling proceeds much more efficiently than the first cross-coupling and the homocoupling side reaction (at least 1 order of magnitude faster) leading to unexpectedly low homocoupling defects and high molecular weight polymers. Kinetic analyses show that C-H bond activation is rate-determining in the first cross-coupling but not in the second cross-coupling. Based on DFT calculations, the high cross-coupling rate in the second cross-coupling was ascribed to the strong Pd-thiophene interaction in the Pd-mediated C-H bond activation transition state, which decreases the energy barrier of the Pd-mediated C-H bond activation. These results have implications beyond polymerizations and can be used to ease the synthesis of a wide range of molecules where C-H bond activation may be the limiting factor.

Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters.

The enantioconvergent radical C(sp3)-C(sp2) cross-coupling of alkyl halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good functional group tolerance. The key to the success is the rational design of hemilabile N,N,N-ligands by mounting steric hindrance at the ortho position of one coordinating quinoline ring. Thus, the newly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliver enantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utility in the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.

Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis.

Studies have shown that diabetes is associated with the occurrence of neurodegenerative diseases and cognitive decline. However, there is currently no effective treatment for diabetes-induced cognitive dysfunction. The superior efficacy of liraglutide (LIRA) for cognitive impairment and numerous neurodegenerative diseases has been widely demonstrated. This study determined the effects of LIRA on diabetic cognitive impairment and on the levels of oxidative stress, lipid peroxidation, iron metabolism and ferroptosis in the hippocampus. Mice were injected daily with liraglutide (200 µg/kg/d) for 5 weeks. LIRA could repair damaged neurons and synapses, and it increased the protein expression levels of PSD 95, SYN, and BDNF. Furthermore, LIRA significantly decreased oxidative stress and lipid peroxidation levels by downregulating the production of ROS and MDA and upregulating SOD and GSH-Px in the serum and hippocampus, and the upregulation of SOD2 expression was also proven. The decreased levels of TfR1 and the upregulation of FPN1 and FTH proteins observed in the LIRA-treated db/db group were shown to reduce iron overload in the hippocampus, whereas the increased expression of Mtft and decreased expression of Mfrn in the mitochondria indicated that mitochondrial iron overload was ameliorated. Finally, LIRA was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4; simultaneously, the damage to the mitochondria observed by TEM was also repaired. For the first time, we proved in the T2DM model that ferroptosis occurs in the hippocampus, which may play a role in diabetic cognitive impairment. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetic cognitive disorders and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.

Banxia-Houpu decoction diminishes iron toxicity damage in heart induced by chronic intermittent hypoxia.

CONTEXT: Obstructive sleep apnoea (OSA) causes chronic intermittent hypoxia (CIH), which results in mitochondrial dysfunction and generates reactive oxygen species (ROS) in the heart. Excessive free iron could accelerate oxidative damage, which may be involved in this process. Banxia-Houpu decoction (BHD) was reported to improve the apnoea hypopnoea index in OSA patients, but the specific mechanism was still unclear. OBJECTIVE: To investigate whether BHD could reduce CIH-induced heart damage by regulating iron metabolism and mitochondrial function. MATERIALS AND METHODS: C57BL/6N mice were randomly divided into control, CIH and BHD groups. Mice were exposed to CIH (21 - 5% O2, 20 times/h, 8 h/d) and administered BHD (3.51, 7.01 and 14.02 g/kg, intragastrically) for 21 d. Cardiac and mitochondrial function, iron levels, apoptosis and mitophagy were determined. RESULTS: BHD (7.01 g/kg) significantly improved cardiac dysfunction, pathological change and mitochondrial structure induced by CIH. BHD increased the Bcl-2/Bax ratio (1.4-fold) and inhibited caspase 3 cleavage in CIH mice (0.45-fold). BHD activated mitophagy by upregulating Parkin (1.94-fold) and PINK1 (1.26-fold), inhibiting the PI3K-AKT-mTOR pathway. BHD suppressed ROS generation by decreasing NOX2 (0.59-fold) and 4-HNE (0.83-fold). BHD reduced the total iron in myocardial cells (0.72-fold) and mitochondrial iron by downregulating Mfrn2 (0.81-fold) and MtFt (0.78-fold) proteins, and upregulating ABCB8 protein (1.33-fold). Rosmarinic acid, the main component of Perilla Leaf in BHD, was able to react with Fe2+ and Fe3+ in vitro. DISCUSSION AND CONCLUSIONS: These findings encourage the use of BHD to resist cardiovascular injury and provide the theoretical basis for clinical treatment in OSA patients.

ALPPS Versus Portal Vein Embolization for Hepatitis-related Hepatocellular Carcinoma: A Changing Paradigm in Modulation of Future Liver Remnant Before Major Hepatectomy.

OBJECTIVE: The aim of this study was to evaluate the short- and long-term outcome of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for hepatitis-related hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: ALPPS has been advocated for future liver remnant (FLR) augmentation in liver metastasis or noncirrhotic liver tumors in recent years. Data on the effect of ALPPS in chronic hepatitis or cirrhosis-related HCC remained scarce. METHODS: Data for clinicopathological details, portal hemodynamics, and oncological outcome were reviewed for ALPPS and compared with portal vein embolization (PVE). Tumor immunohistochemistry for PD-1, VEGF, and AFP was evaluated in ALPPS and compared with PVE and upfront hepatectomy (UH). RESULTS: From 2002 to 2018, 148 patients with HCC (hepatitis B: n = 136, 92.0%) underwent FLR modulation (ALPPS, n = 46; PVE: n = 102). One patient with ALPPS and 33 patients with PVE failed to proceed to resection (resection rate: 97.8% vs 67.7%, P < 0.001). Among those who had resections, 65 patients (56.5%) had cirrhosis. ALPPS induced absolute FLR volume increment by 48.8%, or FLR estimated total liver volume ratio by 12.8% over 6 days. No difference in morbidity (20.7% vs 30.4%, P = 0.159) and mortality (6.5% vs 5.8%, P = 1.000) with PVE was observed. Chronic hepatitis and intraoperative indocyanine green clearance rate ≤39.5% favored adequate FLR hypertrophy in ALPPS. Five-year overall survival for ALPPS and PVE was 46.8% and 64.1% (P = 0.234). Tumor immunohistochemical staining showed no difference in expression of PD-1, V-EGF, and AFP between ALPPS, PVE, and UH. CONCLUSIONS: ALPPS conferred a higher resection rate in hepatitis-related HCC with comparable short- and long-term oncological outcome with PVE.

Cryptochrome 2 from Lilium × formolongi Regulates Photoperiodic Flowering in Transgenic Arabidopsis thaliana.

The photoperiodic flowering pathway is essential for plant reproduction. As blue and ultraviolet-A light receptors, cryptochromes play an important role in the photoperiodic regulation of flowering. Lilium × formolongi is an important cut flower that flowers within a year after seed propagation. Floral induction is highly sensitive to photoperiod. In this study, we isolated the CRYPTOCHROME2 gene (LfCRY2) from L. × formolongi. The predicted LfCRY2 protein was highly homologous to other CRY2 proteins. The transcription of LfCRY2 was induced by blue light. LfCRY2 exhibits its highest diurnal expression during the floral induction stage under both long-day and short-day photoperiods. Overexpression of LfCRY2 in Arabidopsis thaliana promoted flowering under long days but not short days, and inhibited hypocotyl elongation under blue light. Furthermore, LfCRY2 was located in the nucleus and could interact with L. × formolongi CONSTANS-like 9 (LfCOL9) and A. thaliana CRY-interacting basic-helix-loop-helix 1 (AtCIB1) in both yeast and onion cells, which supports the hypothesis that LfCRY2 hastens the floral transition via the CIB1-CO pathway in a manner similar to AtCRY2. These results provide evidence that LfCRY2 plays a vital role in promoting flowering under long days in L. × formolongi.

RPI-SE: a stacking ensemble learning framework for ncRNA-protein interactions prediction using sequence information.

BACKGROUND: The interactions between non-coding RNAs (ncRNA) and proteins play an essential role in many biological processes. Several high-throughput experimental methods have been applied to detect ncRNA-protein interactions. However, these methods are time-consuming and expensive. Accurate and efficient computational methods can assist and accelerate the study of ncRNA-protein interactions. RESULTS: In this work, we develop a stacking ensemble computational framework, RPI-SE, for effectively predicting ncRNA-protein interactions. More specifically, to fully exploit protein and RNA sequence feature, Position Weight Matrix combined with Legendre Moments is applied to obtain protein evolutionary information. Meanwhile, k-mer sparse matrix is employed to extract efficient feature of ncRNA sequences. Finally, an ensemble learning framework integrated different types of base classifier is developed to predict ncRNA-protein interactions using these discriminative features. The accuracy and robustness of RPI-SE was evaluated on three benchmark data sets under five-fold cross-validation and compared with other state-of-the-art methods. CONCLUSIONS: The results demonstrate that RPI-SE is competent for ncRNA-protein interactions prediction task with high accuracy and robustness. It's anticipated that this work can provide a computational prediction tool to advance ncRNA-protein interactions related biomedical research.

Rise in Low-Density Lipoprotein Cholesterol during Hospitalization is Related with Poor Outcome at Discharge in Patients with Acute Ischemic Stroke.

BACKGROUND: The statistical association between a short-term rise in low-density lipoprotein cholesterol (LDL-C) levels and the short-term outcome of acute ischemic stroke remains unknown. We aimed to evaluate the association in acute ischemic stroke patients during hospitalization. METHODS: Patients with acute ischemic stroke who received statin at discharge were enrolled in this multicenter registry study. LDL-C values were measured on the first day after admission and on the day before discharge to determine the rise in LDL-C levels. Poor outcome was defined as a modified Ranking Scale score ≥2 at discharge. The National Institutes of Health Stroke Scale increase from admission to discharge by 2 points was defined as clinical deterioration. Logistic regression analyses were used to analyze the relationship between LDL-C rise during hospitalization and poor outcome at discharge. Variables that were significantly different between the LDL-C rise and LDL-C fall groups were considered in adjustment for confounding variables in model 1. Age, sex, and those variables in model 1 were considered in adjustment for confounding variables in model 2. RESULTS: Among the 676 patients, 110 (16.3%) showed a rise in LDL-C levels during hospitalization. Multivariate analyses showed that LDL-C at admission <1.6 mmol/L was significantly correlated with LDL-C rise during hospitalization (p < 0.001). There were significantly more patients with a poor outcome in the "LDL-C rise" group than in the "LDL-fall" group (p = 0.002). Multiple models consistently showed that LDL-C rise increased the risk of a poor outcome at discharge in model 1 (OR [95% CI] 1.351 [1.059-1.723], p = 0.016) and model 2 (OR [95% CI] 1.370 [1.071-1.751], p = 0.012). LDL-C rise also increased the risk of clinical deterioration, although its p value only was 0.043 in model 1 and 0.048 in model 2. CONCLUSIONS: Rise in LDL-C during hospitalization from acute ischemic stroke is an independent predictor of poor outcome at discharge. In particular, patients with lower LDL-C values at admission are a higher at risk, and LDL-C in these patients should thus be monitored while in hospital.

Preventable Deaths in Multiple Trauma Patients: The Importance of Auditing and Continuous Quality Improvement.

BACKGROUND: Management errors during pre-hospital care, triage process and resuscitation have been widely reported as the major source of preventable and potentially preventable deaths in multiple trauma patients. Common tools for defining whether it is a preventable, potentially preventable or non-preventable death include the Advanced Trauma Life Support (ATLS®) clinical guideline, the Injury Severity Score (ISS) and the Trauma and Injury Severity Score (TRISS). Therefore, these surrogated scores were utilized in reviewing the study's trauma services. METHODS: Trauma data were prospectively collected and retrospectively reviewed from January 1, 2018, to December 31, 2018. All cases of trauma death were discussed and audited by the Hospital Trauma Committee on a regular basis. Standardized form was used to document the patient's management flow and details in every case during the meeting, and the final verdict (whether death was preventable or not) was agreed and signed by every member of the team. The reasons for the death of the patients were further classified into severe injuries, inappropriate/delayed examination, inappropriate/delayed treatment, wrong decision, insufficient supervision/guidance or lack of appropriate guidance. RESULTS: A total of 1913 trauma patients were admitted during the study period, 82 of whom were identified as major trauma (either ISS > 15 or trauma team was activated). Among the 82 patients with major trauma, eight were trauma-related deaths, one of which was considered a preventable death and the other 7 were considered unpreventable. The decision from the hospital's performance improvement and patient safety program indicates that for every trauma patient, basic life support principles must be followed in the course of primary investigations for bedside trauma series X-ray (chest and pelvis) and FAST scan in the resuscitation room by a person who meets the criteria for trauma team activation recommended by ATLS®. CONCLUSION: Mechanisms to rectify errors in the management of multiple trauma patients are essential for improving the quality of trauma care. Regular auditing in the trauma service is one of the most important parts of performance improvement and patient safety program, and it should be well established by every major trauma center in Mainland China. It can enhance the trauma management processes, decision-making skills and practical skills, thereby continuously improving quality and reducing mortality of this group of patients.

Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation.

Molecular hydrogen is reported to be used medically to ameliorate various systemic pathological conditions. This study aimed to investigate the effect of hydrogen (H2 ) gas on hypertension induced by intermittent hypoxia in rats. The adult rats were exposed to chronic intermittent hypoxia (CIH) 8 hours/day for 5 weeks and/or H 2 gas 2 hours/day. We found that the systolic and diastolic blood pressure (BP) increased significantly in rats exposed to intermittent hypoxia, both of which were markedly attenuated after H treatment. Furthermore, intermittent hypoxia exposure elevated renal sympathetic nerve activity, consistent with plasma norepinephrine. Additionally, H 2 gas significantly improved CIH-induced abnormal vascular relaxation. Nevertheless, inhalation of H 2 gas alone did not cause such changes. Moreover, H 2 gas-treated rats exposed to CIH showed a significant reduction in 8-hydroxy-2 deoxyguanosine content and increases in superoxide dismutase activity, indicating improved oxidative stress. Taken together, these results indicate that H 2 gas has significant effects on the reduction of BP without any side effects. Mechanistically, inhibition of sympathetic activity and reduction of systemic vascular resistance may participate in this process via the antioxidant activity of H 2 .

Cu/Chiral Phosphoric Acid-Catalyzed Asymmetric Three-Component Radical-Initiated 1,2-Dicarbofunctionalization of Alkenes.

An asymmetric intermolecular, three-component radical-initiated dicarbofunctionalization of 1,1-diarylalkenes with diverse carbon-centered radical precursors and electron-rich heteroaromatics by a copper(I) and chiral phosphoric acid cooperative catalysis strategy has been developed, providing straightforward access to chiral triarylmethanes bearing quaternary all-carbon stereocenters with high efficiency as well as excellent chemo- and enantioselectivity. The key to success is not only the introduction of a sterically demanding chiral phosphoric acid to favor radical difunctionalization over the otherwise remarkable side reactions but also the in situ generation of carbocation intermediates from benzylic radical to realize asymmetric induction with the aid of a removable hydroxy directing group via cooperative interactions with chiral phosphate. Density functional theory calculations elucidated the critical chiral environment created by the hydrogen-bonding and ion-pair interactions between the chiral phosphoric acid catalyst and substrates, which leads to the enantioselective C-C bond formation.

Correlation of Stress Hyperglycemia after Ischemic Stroke with Early Vascular Cognitive Impairment.

Objective To investigate the influence and forecast value of stress hyperglycemia on the early vascular cognitive impairment (VCI) in stroke patients.Methods Totally 422 patients with acute non-diabetic stroke were divided into three groups according to the fasting plasma glucose level:the euglycemia group (<6.1 mmol/L),the mild stress hyperglycemia group (6.1-7.0 mmol/L),and the severe stress hyperglycemia group (≥7.0 mmol/L).Mini-mental state examination,Alzheimer's disease rating scale cognitive subscale,and clinical dementia rating scale were used to evaluate early cognition in post-stroke patients,and patients were divided into three groups accordingly:normal cognitive function group,mild VCI group,and vascular dementia group.Correlation analysis was carried out on the level of stress hyperglycemia and the degree of VCI.Results Of these 422 patients,stress hyperglycemia was identified in 62 cases (14.7%).The risk of stress hyperglycemia was higher in patients with a high degree of education [(8.39±3.85)years vs.(6.62±4.39)years,P=0.037)] or a history of cardiovascular disease (45.2% vs.18.3%,P=0.001).VCI was detected in 270 patients (64.0%).Age,sex,smoking,National Institute of Health Stroke Scale score,Hamilton Depression Rating Scale score,stress hyperglycemia,and history of cardiovascular disease were related with early VCI after non-diabetic ischemic stroke (P<0.05).Multivariate Logistic regression analysis showed that stress hyperglycemia was an independent risk factor for VCI in patients with non-diabetic ischemic stroke (OR=3.086,95% CI=1.065-8.929).The risks of cognitive impairment in the mild stress hyperglycemia group and the severe stress hyperglycemia group were higher than that of the euglycemia group,while it was also higher in the severe stress hyperglycemia group than in the mild stress hyperglycemia group (61.11% vs.75.00% vs.90.91%).Stress hyperglycemia was positively correlated with the high risk of early cognitive impairment in stroke patients (rs=0.185,P=0.007).Conclusion There is a significant correlation between stress hyperglycemia and early VCI after ischemic stroke.

Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression.

EPB41L3 may play a role as a metastasis suppressor by supporting regular arrangements of actin stress fibres and alleviating the increase in cell motility associated with enhanced metastatic potential. Downregulation of epb41l3 has been observed in many cancers, but the role of this gene in esophageal squamous cell carcinoma (ESCC) remains unclear. Our study aimed to determine the effect of epb41l3 on ESCC cell migration and invasion. We investigated epb41l3 protein expression in tumour and non-tumour tissues by immunohistochemical staining. Expression in the non-neoplastic human esophageal cell line Het-1a and four ESCC cell lines - Kyse150, Kyse510, Kyse450 and Caes17 - was assessed by quantitative Polymerase Chain Reaction (qPCR) and Western blotting. Furthermore, an EPB41L3 overexpression plasmid and EPB41L3-specific small interfering RNA were used to upregulate EPB41L3 expression in Kyse150 cells and to downregulate EPB41L3 expression in Kyse450 cells, respectively. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The expression levels of p-AKT, matrix metalloproteinase (MMP)2 and MMP9 were evaluated. Expression of epb41l3 was significantly lower in tumour tissues than in non-tumour tissues and in ESCC cell lines compared with the Het-1a cell line. Kyse450 and Caes17 cells exhibited higher expression of epb41l3 than Kyse150 and Kyse510 cells. Overexpressing epb41l3 decreased Kyse150 cell migration and invasion, whereas EPB41L3-specific small interfering RNA silencing increased these functions in Kyse450 cells. Furthermore, overexpressing epb41l3 led to downregulation of MMP2 and MMP9 in Kyse150 and Kyse510 cells. Our findings reveal that EPB41L3 suppresses tumour cell invasion and inhibits MMP2 and MMP9 expression in ESCC cells.