Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic ß-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3ß proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3ß signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.
Purpose: Minimally invasive therapies (MIT) have gained popularity due to their capacity to reduce trauma, enhance aesthetic outcomes, and shorten recovery periods. This article explores patients' perceptions and preferences regarding MIT for varicose veins (VVs) while analyzing associated influencing factors to provide a better understanding. Patients and methods: A cross-sectional survey at Zhejiang Rongjun Hospital was performed from January 2022 to June 2023, involving 305 participants with VVs. The questionnaire assessed patient demographics, VVs severity, prior treatment experiences, and treatment preferences. Statistical analyses, including chi-square and Kruskal-Wallis tests, were conducted to explore the correlations between patient characteristics, treatment preferences, and factors influencing these choices. Results: Nearly half of the participants (44.3%) lacked information on any surgical options, whereas a slight majority (55.7%) possessed familiarity with at least one treatment modality, and only 9.8% knew of all six treatment methods presented. Patient surveys discerned that the majority (68.5%) declared an inadequate grasp of treatment methodologies to articulate a treatment preference. Among the 96 patients who made a treatment choice, 24.0% opted for traditional surgery, while 76.0% chose MIT and a higher preference for MIT among male patients compared to female patients (p = 0.006). The patients preferred treatment options for VVs significantly affected by vascular surgeon recommendations and the number of follow-up visits (r = 0.129, p = 0.024; r = 0.122, p = 0.033). Conclusion: The study highlights limited awareness of MIT among Chinese patients with VVs. The insights emphasize the influential role of vascular surgeons' recommendations and suggest a growing predilection for less invasive treatments due to their advantages in recovery and aesthetics. Provider-patient communication, including education about available treatments and shared decision-making, is essential to align treatment plans with patient expectations and improve outcomes.
Thyroid-associated ophthalmopathy (TAO) is the most prevalent orbital disease in adults caused by an autoimmune disorder, which can lead to disfigurement and vision impairment. Developing effective treatments for this condition presents challenges due to our limited understanding of its underlying immune aberrations. In this study, we profiled the immune components in the peripheral blood of patients with TAO as well as healthy individuals, utilizing single-cell RNA sequencing and B-cell receptor repertoires (BCR) analysis. We observed a significant reduction in the proportions of regulatory B cells (Bregs) and type 2 conventional dendritic cells (DCs) in patients with TAO during the active phase. Conversely, there was a significant increase in the proportion of type 1 DCs. Further analysis of cell differentiation trajectory revealed potential impairment in the transition of B cells towards Breg phenotype during the active phase of TAO. Besides, the activation process of TAO appeared to involve inflammation and immune dysfunction, as indicated by the dynamic changes in the activities of key regulators. The abnormalities in the peripheral immune system, such as the reduced capacity of Bregs to suppress inflammation, were primarily driven by the enhanced interaction among Breg, DCs, and monocytes (i.e., CD22-PTPRC and BTLA-TNFRSF14). Collectively, our findings offer a comprehensive insight into the molecular regulation and cellular reconfiguration during the active phase of TAO at the single-cell level, in order to explore the pathogenesis of TAO and provide new ideas for the future treatment of TAO.
BACKGROUND: Perioperative myocardial injury (PMI) is associated with increased mobility and mortality after noncoronary cardiac surgery. However, limited studies have developed a predictive model for PMI. Therefore, we used hybrid feature selection (FS) methods to establish a predictive model for PMI in noncoronary cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This was a single-center retrospective study conducted at the Fuwai Hospital in China. Patients aged 18-70 years who underwent elective noncoronary surgery with CPB at our institution from December 2018 to April 2021 were enrolled. The primary outcome was PMI, defined as the postoperative cardiac troponin I (cTnI) levels exceeding 220 times of upper reference limit (URL). Statistical analyses were conducted by Python (Python Software Foundation, version 3.9.7 and integrated development environment Jupyter Notebook 1.1.0) and SPSS software version 26.0 (IBM Corp., Armonk, New York, USA). RESULTS: A total of 1130 patients were eventually eligible for this study. The incidence of PMI was 20.3% (229/1130) in the overall patients, 20.6% (163/791) in the training dataset, and 19.5% (66/339) in the testing dataset. The logistic regression model performed the best AUC of 0.6893 (95 CI%: 0.6371-0.7382) by the traditional selection method, and the random forest model performed the best AUC of 0.6937 (95 CI%: 0.6416-0.7423) by the union of Wrapper and Embedded method, and the CatBoost model performed the best AUC of 0.6828 (95 CI%: 0.6304-0.7320) by the union of Embedded and forward logistic regression technique, and the Naïve Bayes model achieved the best AUC with 0.7254 (95 CI%: 0.6746-0.7723) by forwarding logistic regression method. Moreover, the decision tree, KNeighborsClassifier, and support vector machine models performed the worse AUC in all selection forms. Furthermore, the SHapley Additive exPlanations plot showed that prolonged CPB, aortic clamp time, and preoperative low platelets count were strongly related to the PMI risk. CONCLUSIONS: In total, four category feature selection methods were utilized, comprising five individual selection techniques and 15 combined methods. Notably, the combination of logistic regression and embedded methods demonstrated outstanding performance in predicting PMI risk. We also concluded that the machine learning model, including random forest, catboost, and Naive Bayes, were suitable candidates for establishing PMI predictive model. Nevertheless, additional investigation and validation are imperative for substantiating these finding.
BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.
Actins , Meiosis , Oocytes , cdc42 GTP-Binding Protein , Animals , Oocytes/metabolism , Mice , Female , Actins/metabolism , Actins/genetics , cdc42 GTP-Binding Protein/metabolism , cdc42 GTP-Binding Protein/genetics , Phosphorylation , Spindle Apparatus/metabolism
Lymph nodes (LNs) occupy a critical position in initiating and augmenting immune responses, both spatially and functionally. In cancer immunotherapy, tumor-specific vaccines are blooming as a powerful tool to suppress the growth of existing tumors, as well as provide preventative efficacy against tumorigenesis. Delivering these vaccines more efficiently to LNs, where antigen-presenting cells (APCs) and T cells abundantly reside, is under extensive exploration. Formulating vaccines into nanomedicines, optimizing their physiochemical properties, and surface modification to specifically bind molecules expressed on LNs or APCs, are common routes and have brought encouraging outcomes. Alternatively, porous scaffolds can be engineered to attract APCs and provide an environment for them to mature, proliferate and migrate to LNs. A relatively new research direction is inducing the formation of LN-like organoids, which have shown positive relevance to tumor prognosis. Cutting-edge advances in these directions and discussions from a future perspective are given here, from which the up-to-date pattern of cancer vaccination will be drawn to hopefully provide basic guidance to future studies.
Codonopsis radix is the dried root of C. pilosula (Franch.) Nannf., C. pilosula Nannf. var. modesta (Nannf.) L. T. Shen, or C. tangshen Oliv., constitutes a botanical medicine with a profound historical lineage. It encompasses an array of bioactive constituents, including polyacetylenes, phenylpropanoids, alkaloids, triterpenoids, and polysaccharides, conferring upon it substantial medicinal and edible values. Consequently, it has garnered widespread attention from numerous scholars. In recent years, driven by advancements in modern traditional Chinese medicine, considerable strides have been taken in exploring resources utilization, traditional processing, quality evaluation and polysaccharide research of Codonopsis radix. However, there is a lack of systematic and comprehensive reporting on these research results. This paper provides a summary of recent advances in Codonopsis research, identifies existing issues in Codonopsis studies, and offers insights into future research directions. The aim is to provide insights and literature support for forthcoming investigations into Codonopsis.
A high performance oxide composite electrode is obtained with a two-step solid state calcined titanium niobium oxide TiNb2O7 (TNO) anode and super P-carbon nanotube (SP-CNT) binary conductive agents. The solid state synthesized TNO-0.2C (the proportion of CNTs in the binary conductive agent is 20% wt) anode exhibits a high reversible discharge capacity of 278.6 mA h g-1 at 0.5C, a competitive rate capability with reported works that employed wet chemical methods at moderate rates (178.1 mA h g-1 at 10C), and an excellent capacity retention of 92.2% after 200 cycles at 1.5C/1.5C. The enhancement in electrochemical properties of the TNO-0.2C anode is mainly attributed to the combination of the short range and long range conductive agents in the SP-CNT binary conductive system, which guarantees an efficient electronic conductive network. The Li|Li1.3Al0.3Ti1.7(PO4)3 composite polymer electrolyte (LATPCPEs)|TNO-0.2C solid state batteries are also assembled, which deliver a high initial reversible discharge capacity of 241.3 mA h g-1 at 1C and a good capacity retention rate of 93% after 50 cycles. This work provides an efficient way to improve the electrochemical properties of TNO anodes in lithium ion batteries, especially for solid state batteries.
Zero-dimensional (0D) hybrid metal halides (HMHs) have emerged as a promising platform for exploring excitation-dependent multicolor luminescent materials owing to their diverse crystal structures and chemical compositions. Nevertheless, understanding the mechanism behind excitation-dependent emissions (EDEs) in 0D HMHs and achieving precise modulation remains challenging. In this work, the delicate regulations on the EDE of 0D (DMEDABr)4SnBr3I3 (DMEDA: N, N'-dimethylethylenediamine) with mixed halogens are achieved under low temperature and high pressure, respectively. The inhomogeneous halogen occupation at the atomic scale leads to the formation of Br-rich and I-rich SnX6 (X = Br, I) octahedra, which act as distinct luminescent centers upon photoexcitation. At low temperatures, the narrowed photoluminescence spectra could distinguish the individual emissions from different luminescent centers, resulting in a pronounced EDE of (DMEDABr)4SnBr3I3. In addition, the contraction and distortion of the luminescent SnX6 (X = Br, I) centers at high pressure further result in different degrees of emission shifts, giving rise to the gradual emergence and disappearance of EDE. This work elucidates the underlying mechanism of EDE in 0D HMHs and highlights the crucial role of halogens in determining the optical properties of metal halides.
OBJECTIVE: The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians' awareness of and attention to this disease. METHODS: We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes. RESULTS: All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G). CONCLUSION: Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.
Chloride Channels , Dent Disease , Phosphoric Monoester Hydrolases , Humans , Male , Child , Chloride Channels/genetics , Retrospective Studies , Child, Preschool , China/epidemiology , Dent Disease/genetics , Dent Disease/diagnosis , Phosphoric Monoester Hydrolases/genetics , Mutation , Proteinuria/genetics , Adolescent , Hypercalciuria/genetics , Nephrocalcinosis/genetics , Nephrolithiasis/genetics , Infant , Genetic Testing , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/diagnosis , Mutation, Missense , Female , Glomerulosclerosis, Focal Segmental/genetics , Kidney/pathology , East Asian People
Ischemic stroke rapidly increases the expression level of vascular endothelial growth factor (VEGF), which promotes neovascularization during hypoxia. However, the effect and mechanism of VEGF intervention on cerebrovascular formation remain unclear. Therefore, our research discussed the protective effect of exogenous VEGF on cells in hypoxia environment in cerebral microvascular endothelial cells, simulating ischemic stroke in hypoxic environment. Firstly, we detected the proliferation and apoptosis of cerebral microvascular endothelial cells under hypoxia environment, as well the expression levels of VEGF-E, vascular endothelial growth factor re-ceptor-2 (VEGFR-2), BCL2, PRKCE and PINK1. Moreover, immunofluorescence and western blotting were used to verify the regulation of exogenous VEGF-E on VEGFR-2 expression in hypoxic or normal oxygen environment. Lastly, we manipulated the concentration of VEGF-E in the culture medium to investigate its impact on phospholipase Cγ1 (PLCγ1)/extracellular signaling regulatory protein kinase (ERK) -1/2 and protein kinase B (AKT) pathways. Additionally, we employed a PLCγ1 inhibitor (U73122) to investigate its impact on proliferation and PLCγ1/ERK pathways. The results show that hypoxia inhibited the proliferation of cerebral microvascular endothelial cells, promoted cell apoptosis, significantly up-regulated the expression of VEGF-E, VEGFR-2, PRKCE and PINK1, but down-regulated the expression of BCL2. Interference from exogenous VEGF-E activated PLCγ1/ERK-1/2 and AKT pathways, promoting cell proliferation and inhibiting apoptosis of hypoxic brain microvascular endothelial cells. In summary, exogenous VEGF-E prevents hypoxia-induced damage to cerebral microvascular endothelial cells by activating the PLCγ1/ERK and AKT pathways. This action inhibits the apoptosis pathway in hypoxic cerebral microvascular endothelial cells, thereby safeguarding the blood-brain barrier and the nervous system.
Neuronal ferroptosis plays a key role in neurologic deficits post intracerebral hemorrhage (ICH). However, the endogenous regulation of rescuing ferroptotic neurons is largely unexplored. Here, we analyzed the integrated alteration of metabolomic landscape after ICH using LC-MS and MALDI-TOF/TOF MS, and demonstrated that aconitate decarboxylase 1 (Irg1) and its product itaconate, a derivative of the tricarboxylic acid cycle, were protectively upregulated. Deficiency of Irg1 or depletion of neuronal Irg1 in striatal neurons was shown to exaggerate neuronal loss and behavioral dysfunction in an ICH mouse model using transgenic mice. Administration of 4-Octyl itaconate (4-OI), a cell-permeable itaconate derivative, and neuronal Irg1 overexpression protected neurons in vivo. In addition, itaconate inhibited ferroptosis in cortical neurons derived from mouse and human induced pluripotent stem cells in vitro. Mechanistically, we demonstrated that itaconate alkylated glutathione peroxidase 4 (GPx4) on its cysteine 66 and the modification allosterically enhanced GPx4's enzymatic activity by using a bioorthogonal probe, itaconate-alkyne (ITalk), and a GPx4 activity assay using phosphatidylcholine hydroperoxide. Altogether, our research suggested that Irg1/itaconate-GPx4 axis may be a future therapeutic strategy for protecting neurons from ferroptosis post ICH.
Coalbed methane (CBM) reservoirs constitute a distinct class of dense organic rocks characterized by extremely low porosity and permeability. Conducting an in-depth investigation into pore heterogeneity assumes paramount importance for the exploration and development of CBM. This study focuses on the multifractal analysis of the pores with diameters below 300 nm in six coal samples sourced from the Junggar Basin and the Qinshui Basin in China. The analysis is based on a series of experiments involving CO2 adsorption, low-temperature N2 adsorption/desorption, and CH4 isothermal adsorption. This work delves into the influence of pore heterogeneity on gas adsorption capacity by linking the structural parameters to CH4 adsorption properties. The results indicate that both the micropores, as assessed through CO2 adsorption, and mesopores to macropores, measured via N2 adsorption, exhibit multifractal behavior. In contrast to micropores, the mesopores and macropores display stronger heterogeneity and lower connectivity. Generally, uniform and well-connected nanopores are anticipated to positively contribute to gas adsorption. However, there is a positive correlation between the Langmuir volume and the heterogeneity degree of micropores. This phenomenon is ascribed to the fact that the greater surface complexity in micropores involves a larger specific surface area and a higher abundance of adsorption sites. This research contributes to a more profound and precise comprehension of the heterogeneous pore structure within CBM reservoirs, thereby establishing a theoretical foundation for the sustainable exploitation of CBM.
SIGNIFICANCE: Hemoporfin-mediated photodynamic therapy (HMME-PDT) has been recognized as a safe and effective treatment for port wine stain (PWS). However, some patients show limited improvement even after multiple treatments. Herein, we aim to explore the effect of autophagy on HMME-PDT in human umbilical vein endothelial cells (HUVECs), so as to provide theoretical basis and treatment strategies to enhance clinical effectiveness. METHODS: Establish the in vitro HMME-PDT system by HUVECs. Apoptosis and necrosis were identified by Annexin â ¤-FITC/PI flow cytometry, and autophagy flux was detected by monitoring RFP-GFP-LC3 under the fluorescence microscope. Hydroxychloroquine and rapamycin were employed in the mechanism study. Specifically, the certain genes and proteins were qualified by qPCR and Western Blot, respectively. The cytotoxicity was measured by CCK8, VEGF-A secretion was determined by ELISA, and the tube formation of HUVECs was observed by angiogenesis assay. RESULTS: In vitro experiments revealed that autophagy and apoptosis coexisted in HUVECs treated by HMME-PDT. Apoptosis was dominant in early stage, while autophagy gradually increased in the middle and late stage. AMPK, AKT and mTOR participated in the regulation of autophagy induced by HMME-PDT, in which AMPK was positive regulation, while AKT and mTOR were negative regulation. Hydroxychloroquine could not inhibit HMME-PDT-induced autophagy, but capable of blocking the fusion of autophagosomes with lysosome. Rapamycin might cooperate with HMME-PDT to enhance autophagy in HUVECs, leading to increased cytotoxicity, reduced VEGF-A secretion, and weakened angiogenesis ability. CONCLUSIONS: Both autophagy and apoptosis contribute to HMME-PDT-induced HUVECs death. Pretreatment of HUVECs with rapamycin to induce autophagy might enhance the photodynamic killing effect of HMME-PDT on HUVECs. The combination of Rapamycin and HMME-PDT is expected to further improve the clinical efficacy.
AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.
STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.
Artificial peroxisomes (AP) with enzyme-mimetic catalytic activity and recruitment ability have drawn a great deal of attention in fabricating protocell systems for scavenging reactive oxygen species (ROS), modulating the inflammatory microenvironment, and reprogramming macrophages, which is of great potential in treating inflammatory diseases such as rheumatoid arthritis (RA). Herein, a macrophage membrane-cloaked Cu-coordinated polyphthalocyanine-based AP (CuAP) is prepared with a macrocyclic conjugated polymerized network and embedded Cu-single atomic active center, which mimics the catalytic activity and coordination environment of natural superoxide dismutase and catalase, possesses the inflammatory recruitment ability of macrophages, and performs photoacoustic imaging (PAI)-guided treatment. The results of both in vitro cellular and in vivo animal experiments demonstrated that the CuAP under ultrasound and microbubbles could efficiently scavenge excess ROS in cells and tissues, modulate microenvironmental inflammatory cytokines such as interleukin-1ß, tumor necrosis factor-α, and arginase-1, and reprogram macrophages by polarization of M1 (proinflammatory phenotype) to M2 (anti-inflammatory phenotype). We believe this study offers a proof of concept for engineering multifaceted AP and a promising approach for a PAI-guided treatment platform for RA.
Pigmented and non-pigmented rice varieties (grown in different areas) were collected in China, Yunnan, to investigate the content of macro-, trace elements and potentially toxic elements (PTEs), and to assess the health risk associated with dietary intake. The order of elemental concentrations in rice was Mn > Zn > Fe > Cu > Se for trace elements, P > K > Mg > Ca > Na for macro elements, and Cr > As > Cd for PTEs. Rice with a high concentration of essential elements also associated with a high content of PTEs. In addition, higher content of Cr, Mn and Na were found in pigmented rice. The health risk assessment showed that the daily intake of all elements was below the tolerable limit (UL). Moreover the intake of Fe, Zn and Se was far from sufficient for the nutrient requirement. The PTEs in rice dominated the health risk. Of concern is that this rice consumption is likely to contribute to carcinogenic risks in the long term and that adults are at higher health risk from pigmented rice compared to non-pigmented rice. This study confirms that the lack of essential micronutrients in rice and the health risk associated with rice diets should remain a concern.
Oryza , Trace Elements , Oryza/chemistry , Trace Elements/analysis , Trace Elements/toxicity , Humans , China , Risk Assessment , Pigmentation
Hindered ethers are ubiquitous in natural products and bioactive molecules. However, developing an efficient method for the stereocontrolled synthesis of all stereoisomers of chiral hindered ethers is highly desirable but challenging. Here we show a strategy that utilizes in situ-generated water as a nucleophile in an asymmetric cascade reaction involving two highly reactive intermediates, 3-furyl methyl cations and ortho-quinone methides (o-QMs), to synthesize chiral hindered ethers. The Ca(II)/Au(I) synergistic catalytic system enables the control of diastereoselectivity and enantioselectivity by selecting suitable chiral phosphine ligands in this cascade hydration/1,4-addition reaction, affording all four stereoisomers of a diverse range of chiral tetra-aryl substituted ethers with high diastereoselectivities (up to >20/1) and enantioselectivities (up to 95% ee). This work provides an example of chiral Ca(II)/Au(I) bimetallic catalytic system controlling two stereogenic centers via a cascade reaction in a single operation.
