Tuning the End Alkyl Chain of the Ether Solvent to Stabilize the Electrode/Electrolyte Interfaces in the NCM-Li Battery.

Lithium metal batteries (LMBs) combined with a high-voltage nickel-rich cathode show great potential in meeting the growing need for high energy density. The lack of advanced electrolytes has been a major obstacle in the commercialization of high-voltage lithium metal batteries (LMBs), as these electrolytes need to effectively support both a stable lithium metal anode (LMA) and a high-voltage cathode (>4 V vs Li+/Li). In this work, by extending the two terminal methyl groups in DIGDME and TEGDME to n-butyl groups, we design a new weakly solvating electrolyte (2 M LIFSI+TEGDBE) that enables the stable cycling of NMC83 (LiNi0.83Co0.12Mn0.05O2) cathodes. The NMC83 cell exhibits a high and stable Coulombic efficiency (CE) of over 99%, as well as capacity retention of approximately 99.8% after 100 cycles at 0.3 C. X-ray photoelectron spectroscopy analysis (XPS) and high-resolution transmission electron microscope (HRTEM) images revealed that the anion species decomposed first, resulting in the formation of a cathode-electrolyte interface (CEI) film predominantly consisting of decomposition products from the anions on the positive electrode surface. This work links the functional group of solvents with the solvation structure and electrochemical performance of ether-based electrolytes, providing a distinctive sight to design advanced electrolytes for high-energy-density LMBs.

Arsenic disturbs neural tube closure involving AMPK/PKB-mTORC1-mediated autophagy in mice.

Arsenic exposure is a significant risk factor for folate-resistant neural tube defects (NTDs), but the potential mechanism is unclear. In this study, a mouse model of arsenic-induced NTDs was established to investigate how arsenic affects early neurogenesis leading to malformations. The results showed that in utero exposure to arsenic caused a decline in the normal embryos, an elevated embryo resorption, and a higher incidence of malformed embryos. Cranial and spinal deformities were the main malformation phenotypes observed. Meanwhile, arsenic-induced NTDs were accompanied by an oxidant/antioxidant imbalance manifested by elevated levels of reactive oxygen species (ROS) and decreased antioxidant activities. In addition, changes in the expression of autophagy-related genes and proteins (ULK1, Atg5, LC3B, p62) as well as an increase in autophagosomes were observed in arsenic-induced aberrant brain vesicles. Also, the components of the upstream pathway regulating autophagy (AMPK, PKB, mTOR, Raptor) were altered accordingly after arsenic exposure. Collectively, our findings propose a mechanism for arsenic-induced NTDs involving AMPK/PKB-mTORC1-mediated autophagy. Blocking autophagic cell death due to excessive autophagy provides a novel strategy for the prevention of folate-resistant NTDs, especially for arsenic-exposed populations.

Research progress on the premature ovarian failure caused by cisplatin therapy.

Cisplatin is a common anticancer drug able to kill tumor cells, but it causes adverse reactions in the kidney, digestive tract, and other systems. The antitumor effects of cisplatin are mainly due to its ability to bind to the DNA in tumor cells to prevent replication, thereby reducing RNA and protein syntheses, leading to cell damage and death. Cisplatin has a wide range of applications; it can be used to treat cervical, thyroid, ovarian, and other cancers. Cisplatin has a beneficial therapeutic effect, but its therapeutic selectivity is poor. In addition to eliminating diseased target cells, cisplatin can damage normal cells; in women of reproductive age being treated for cancer, cisplatin can lead to ovarian function impairment, premature ovarian failure (POF), and/or infertility. Therefore, reducing the adverse effects of cisplatin on ovarian function is an important topic in clinical research. In this paper, we explore the research progress on the POF caused by cisplatin treatment.

The role of PKN1 in glioma pathogenesis and the antiglioma effect of raloxifene targeting PKN1.

PKN1 (protein kinase N1), a serine/threonine protein kinase family member, is associated with various cancers. However, the role of PKN1 in gliomas has rarely been studied. We suggest that PKN1 expression in glioma specimens is considerably upregulated and positively correlates with the histopathological grading of gliomas. Knocking down PKN1 expression in glioblastoma (GBM) cells inhibits GBM cell proliferation, invasion and migration and promotes apoptosis. In addition, yes-associated protein (YAP) expression, an essential effector of the Hippo pathway contributing to the oncogenic role of gliomagenesis, was also downregulated. In contrast, PKN1 upregulation enhances the malignant characteristics of GBM cells and simultaneously upregulates YAP expression. Therefore, PKN1 is a promising therapeutic target for gliomas. Raloxifene (Ralo), a commonly used selective oestrogen-receptor modulator to treat osteoporosis in postmenopausal women, was predicted to target PKN1 according to the bioinformatics team from the School of Mathematics, Tianjin Nankai University. We showed that Ralo effectively targets PKN1, inhibits GBM cells proliferation and migration and sensitizes GBM cells to the major chemotherapeutic drug, Temozolomide. Ralo also reverses the effect of PKN1 on YAP activation. Thus, we confirm that PKN1 contributes to the pathogenesis of gliomas and may be a potential target for Ralo adjuvant glioma therapy.

Retinal cell-targeted liposomal ginsenoside Rg3 attenuates retinal ischemia-reperfusion injury via alleviating oxidative stress and promoting microglia/macrophage M2 polarization.

Retinal ischemia-reperfusion (RIR) injury remains a major challenge that is detrimental to retinal cell survival in a variety of ocular diseases. However, current clinical treatments focus on a single pathological mechanism, making them unable to provide comprehensive retinal protection. A variety of natural products including ginsenoside Rg3 (Rg3) exhibit potent antioxidant and anti-inflammatory activities. Unfortunately, the hydrophobicity of Rg3 and the presence of various intraocular barriers limit its effective application in clinical settings. Hyaluronic acid (HA)- specifically binds to cell surface receptors, CD44, which is widely expressed in retinal pigment epithelial cells and M1-type macrophage. Here, we developed HA-decorated liposomes loaded with Rg3, termed Rg3@HA-Lips, to protect against retinal damage caused by RIR injury. Treatment with Rg3@HA-Lips significantly inhibited the oxidative stress induced by RIR injury. In addition, Rg3@HA-Lips promoted the transition of M1-type macrophage to the M2 type, ultimately reversing the pro-inflammatory microenvironment. The mechanism of Rg3@HA-Lips was further investigated and found that they can regulateSIRT/FOXO3a, NF-κB and STAT3 signaling pathways. Together with as well demonstrated good safety profiles, this CD44-targeted platform loaded with a natural product alleviates RIR injury by modulating the retinal microenvironment and present a potential clinical treatment strategy.

Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia.

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.

Comparison of chemical compositions, antioxidant activities, and acetylcholinesterase inhibitory activities between coffee flowers and leaves as potential novel foods.

This study aimed to compare chemical compositions, antioxidant activities, and acetylcholinesterase inhibitory activities of coffee flowers (ACF) and coffee leaves (ACL) with green coffee beans (ACGB) of Coffea Arabica L. The chemical compositions were determined by employing high-performance liquid chromatography-mass spectroscopy (HPLC-MS) and gas chromatography-mass spectroscopy (GC-MS) techniques. Antioxidant effects of the components were evaluated using DPPH and ABTS radical scavenging assays, and the ferric reducing antioxidant power (FRAP) assay. Their acetylcholinesterase inhibitory activities were also evaluated. The coffee sample extracts contained a total of 214 components identified by HPLC-MS and belonged to 12 classes (such as nucleotides and amino acids and their derivatives, tannins, flavonoids, alkaloids, benzene, phenylpropanoids, and lipids.), where phenylpropanoids were the dominant component (>30%). The contents of flavonoids, alkaloids, saccharides, and carboxylic acid and its derivatives in ACF and ACL varied significantly (p < .05) compared to similar components in ACGB. Meanwhile, 30 differentially changed chemical compositions (variable importance in projection [VIP] > 1, p < .01 and fold change [FC] > 4, or <0.25), that determine the difference in characteristics, were confirmed in the three coffee samples. Furthermore, among 25 volatile chemical components identified by GC-MS, caffeine, n-hexadecanoic acid, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-phenol], and quinic acid were common in these samples with caffeine being the highest in percentage. In addition, ACL showed the significantly highest (p < .05) DPPH radical scavenging capacity with IC50 value of 0.491 ± 0.148 mg/ml, and acetylcholinesterase inhibitory activity with inhibition ratio 25.18 ± 2.96%, whereas ACF showed the significantly highest (p < .05) ABTS radical scavenging activity with 36.413 ± 1.523 mmol trolox/g Ex. The results suggested that ACL and ACF had potential values as novel foods in the future.

Structural Characteristics, Rheological Properties, and Antioxidant and Anti-Glycosylation Activities of Pectin Polysaccharides from Arabica Coffee Husks.

As primary coffee by-products, Arabica coffee husks are largely discarded during coffee-drying, posing a serious environmental threat. However, coffee husks could be used as potential material for extracting pectin polysaccharides, with high bioactivities and excellent processing properties. Thus, the present study aimed to extract the pectin polysaccharide from Arabica coffee husk(s) (CHP). The CHP yield was calculated after vacuum freeze-drying, and its average molecular weight (Mw) was detected by gel permeation chromatography (GPC). The structural characteristics of CHP were determined by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM). Additionally, the rheological and antioxidant properties of CHP and the inhibition capacities of advanced glycation end products (AGEs) with different concentrations were evaluated. The interaction mechanisms between galacturonic acid (GalA) and the AGE receptor were analyzed using molecular docking. The results demonstrated that the CHP yield was 19.13 ± 0.85%, and its Mw was 1.04 × 106 Da. The results of the structural characteristics results revealed that CHP was an amorphous and low-methoxyl pectic polysaccharide linked with an α-(1→6) glycosidic bond, and mainly composed of rhamnose (Rha, 2.55%), galacturonic acid (GalA, 45.01%), ß-N-acetyl glucosamine (GlcNAc, 5.17%), glucose (Glc, 32.29%), galactose (Gal, 6.80%), xylose (Xyl, 0.76%), and arabinose (Ara, 7.42%). The surface microstructure of CHP was rough with cracks, and its aqueous belonged to non-Newtonian fluid with a higher elastic modulus (G'). Furthermore, the results of the antioxidant properties indicated that CHP possessed vigorous antioxidant activities in a dose manner, and the inhibition capacities of AGEs reached their highest of 66.0 ± 0.35% at 1.5 mg/mL of CHP. The molecular docking prediction demonstrated that GalA had a good affinity toward AGE receptors by -6.20 kcal/mol of binding energy. Overall, the study results provide a theoretical basis for broadening the application of CHP in the food industry.

Metabolomics Provides Insights into Renoprotective Effects of Semaglutide in Obese Mice.

Purpose: Semaglutide, a new long-acting glucagon-like peptide-1 analogue, has shown benefits for renal diseases, but its direct role on kidney metabolism under obesity remains unclear. The study aims to elucidate the protective effect and metabolic modulation mechanism of semaglutide on obesity-related kidney injury. Methods: Male C57BL/6J mice were divided into control and obesity groups. Mice in the obesity group had a high-fat diet and were treated with or without semaglutide (30nmol/kg/day). The study assayed blood biochemistry and then evaluated renal pathological injury through Periodic Acid-Schiff staining and electron microscopy. Metabolomics was utilized to analyze obesity-related metabolites in kidney samples. Results: Semaglutide significantly improved glucose homeostasis, insulin resistance, and kidney injury in obese mice. We successfully identified 377 altered metabolites (P<0.05). It was suggested that semaglutide directly improved oxidative stress and inflammation-related metabolites such as nicotinamide adenine dinucleotide (NAD+) and adenosine in the kidney of obese mice, which have not been documented in obesity-related kidney injury. Relevant enriched pathways were included phospholipids and lysophospholipids metabolism, purine metabolism, NAD+ metabolism, and insulin resistance-related metabolism. They could serve as potential targets for intervention of obesity-related kidney injury. Conclusion: Our study revealed the metabolomics-based renoprotective mechanism of semaglutide in obese mice for the first time. The innovation lied in the identified metabolites such as NAD+ and adenosine targeted by semaglutide, which have not been documented in obesity-related kidney injury. Semaglutide may be a promising therapy for obesity-related kidney diseases.

Blueberry fruit valorization and valuable constituents: A review.

Blueberry (Vaccinium spp.) is one of the five major healthy foods for humans and is recognized as the "king of the world fruit", which has attracted great interest in the phytogenic prebiotics market. Blueberry fruit is favored for its delicious taste and its various functional ingredients (organic acids, phenolics, minerals and vitamins) with multitherapeutic value (antioxidant, anti-inflammatory, anticancer, neuroprotective and vision improvement properties). However, fresh blueberries are highly perishable since they are vulnerable to mechanical damage and microbial decay, resulting in a short shelf life and inevitable subsequent economic losses. Due to the strong seasonal availability and limited storage period of blueberries, their derived bioactive products have emerged as functional foods. Novel food developments that are currently available include blueberry fruit juice, wine, vinegar, jam, dried fruit, pulp powder, colorant and flavoring additives used in cake, biscuit, bread, yogurt, and jelly. This review systematically describes the current status of blueberry fruit as bioactive ingredients and valuable food products with greater nutraceutical health potential of blueberries.

Photodynamic Antimicrobial Therapy Based on Conjugated Polymers.

Pathogenic microorganisms have been a serious threat to human life and have become a public health problem of global concern. However, in the actual treatment there is a lack of efficient antimicrobial strategies which do not easily develop drug resistance; this can lead to inaccurate drug treatment that worsens the infection and even threatens life. With the emergence of a variety of drug-resistant bacteria and fungi, photodynamic therapy has gradually become one of the most promising treatment methods for drug-resistant bacteria infection; this is because it is controllable, non-invasive, and not prone to cause the development of drug resistance. Organic conjugated polymers that possess high fluorescence intensity, a large molar extinction coefficient, excellent light stability, an adjustable energy band, easy modification, good biocompatibility, and the ability to photosensitize oxygen to produce reactive oxygen species have been widely used in the fields of solar cells, highly sensitive detection systems, biological imaging, and anti-cancer and anti-microbial treatment. Photodynamic therapy is non-invasive and has high temporal and spatial resolution and is a highly effective antimicrobial treatment that does not easily induce drug resistance; it has also stimulated the scientific research enthusiasm of researchers and has become a research hotspot in the antimicrobial field. In this review, the photodynamic antibacterial applications of conjugated polymers with different structure types are summarized, and their development directions are considered.

Single-cell transcriptome reveals effects of semaglutide on non-cardiomyocytes of obese mice.

Non-cardiomyocytes (nonCMs) play an important part in cardiac fibrosis pathophysiology, but the underlying molecular pathways are unknown. Semaglutide has cardioprotective properties, but it is still unclear whether it helps with cardiac fibrosis and what the processes are. The goal of this study is to use single cell transcriptomics approaches to investigate the molecular mechanism of semaglutide's cardioprotective action in obese mice. We found 15 non-CMs, with fibroblasts making up the majority of them. We found eight DEGs that altered significantly following semaglutide treatment by screening for differentially expressed genes (DEGs). DEGs were shown to have biological activities primarily related to extracellular matrix and collagen synthesis and distribution, with Serpinh1 and Pcolce expression being the most dramatically altered. Serpinh1 and Pcolce were mostly found in fibroblasts, which play a key role in the fibrosis of the heart. Furthermore, we discovered that semaglutide lowered cardiac collagen content and alleviated obesity-induced ventricular wall hypertrophy. As a result, our findings show that Serpinh1 and Pcolce, which are expressed by fibroblasts, may play a role in the development of obese cardiac fibrosis. By reducing Serpinh1 and Pcolce expression and delaying cardiac fibrosis, semaglutide may have a cardioprotective effect.

A metabonomics-based renoprotective mechanism analysis of empagliflozin in obese mice.

With an increasing prevalence of obesity related kidney disease, exploring the mechanisms of therapeutic method is of critical importance. Empagliflozin is a new antidiabetic agent with broad clinical application prospect in cardiovascular and renal diseases. However, a metabonomics-based renoprotective mechanism of empagliflozin in obesity remains unclear. Our results showed that empagliflozin significantly alleviated the deposition of lipid droplet, glomerular and tubular injury. The innovation lied in detection of empagliflozin-targeted differential metabolites in kidneys. Compared with normal control mice, obese mice showed higher levels of All-trans-heptaprenyl diphosphate, Biliverdin, Galabiose, Galabiosylceramide (d18:1/16:0), Inosine, Methylisocitric acid, Uric acid, Xanthosine, O-glutarylcarnitine, PG(20:3(8Z,11Z,14Z)/0:0), PG(20:4(5Z,8Z,11Z,14Z)/0:0), PE(O-16:0/0:0), PG(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0), and lower level of Adenosine. Empagliflozin regulated these metabolites in the opposite direction. Associated metabolic pathways were Phospholipids metabolism, Purine metabolism, and Biliverdin metabolism. Most of metabolites were associated with inflammatory response and oxidative stress. Empagliflozin improved the oxidative stress and inflammation imbalance. Our study revealed the metabonomics-based renoprotective mechanism of empagliflozin in obese mice for the first time. Empagliflozin may be a promising tool to delay the progression of obesity-related kidney disease.

Correlation of Body Mass Index with Clinicopathologic Parameters in Patients with Idiopathic Membranous Nephropathy.

Objective: To investigate the association between body mass index (BMI) and clinicopathologic parameters in patients with idiopathic membranous nephropathy (IMN). Methods: This study was retrospective and included patients with biopsy-proven IMN from 2018 to 2021 in Hebei General Hospital. Patients were categorized into two groups based on BMI. Clinical and histopathologic data were analyzed at the time of renal biopsy. Pathological data included immunofluorescence staining, glomerulosclerosis (GS, 0-2), mesangial cell proliferation (MCP, 0-1), tubular atrophy (TA, 0-1), interstitial fibrosis (IF, 0-1), vascular wall thickness (VWT, 0-1) and a combination score (GMTIV) graded from 0 to 5. Results: Our study revealed that the obese group had a higher prevalence of hypertension and diabetes than the overweight/normal weight group (P=0.001, P=0.002). Systolic blood pressure (P=0.005), diastolic blood pressure (P<0.001), haemoglobin (P=0.006), triglycerides (P<0.001), serum uric acid (P=0.05), 24 h urine proteinuria concentration (UP) (P=0.012), MCP (P=0.042), IF (P=0.033), and GMITV (P=0.033) score were higher in obese group compared to the other group, while the high-density lipoprotein-cholesterol (P=0.034) and immunoglobulin A deposition score (P=0.005) were lower. Factors significantly associated with UP were the ratio of lymphocyte count to white blood cell count, serum pre-albumin, immunoglobulin G, microscopic hematuria, anti-phospholipase A2 receptor (anti-PLA2R), C3 deposit on multivariable analysis (adjusted R 2=0.343). Binary logistic regression analysis illustrated that MCP was correlated to BMI (OR=2.528, P=0.036). Ordinal logistic regression analysis demonstrated that GMTIV was associated with BMI (OR=1.114, P=0.010) and C3 deposit (OR=1.655, P=0.001). Conclusion: High BMI was associated with MCP and GMTIV score in IMN patients. Obesity may play an essential role in mesangial lesions of IMN. This study emphasized the relation between BMI and histological parameters under the universal usage of anti-PLA2R antibodies for diagnosis and prognosis in IMN.

UTP14A, DKC1, DDX10, PinX1, and ESF1 Modulate Cardiac Angiogenesis Leading to Obesity-Induced Cardiac Injury.

Background: This study is aimed at exploring the key genes and the possible mechanism of heart damage caused by obesity. Methods: We analyzed the GSE98226 dataset. Firstly, differentially expressed genes (DEGs) were identified in heart tissues of obese and normal mice. Then, we analyzed DEGs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Thirdly, we constructed a protein-protein interaction (PPI) network and key modules and searched hub genes. Finally, we observed the pathological changes associated with obesity through histopathology. Results: A total of 763 DEGs were discovered, including 629 upregulated and 134 downregulated genes. GO enrichment analysis showed that these DEGs were mainly related to the regulation of transcription, DNA-templated, nucleic acid binding, and metal ion binding. KEGG pathway analysis revealed that the DEGs were enriched in long-term depression, gap junction, and sphingolipid signaling pathways. Finally, we identified UTP14A, DKC1, DDX10, PinX1, and ESF1 as the hub genes. Histopathologic analysis showed that obesity increased the number of collagen fibers and decreased the number of microvessels and proliferation of the endothelium and increased endothelial cell damage which further leads to dysfunction of cardiac microcirculation. Conclusion: UTP14A, DKC1, DDX10, PinX1, and ESF1 have been identified as hub genes in obesity-induced pathological changes in the heart and may be involved in obesity-induced cardiac injury by affecting cardiac microcirculatory function.

DNMT1 Mediated CAHM Repression Promotes Glioma Invasion via SPAK/JNK Pathway.

Gliomas are the most common and fatal brain tumors worldwide. Abnormal DNA promoter methylation is an important mechanism for gene loss of tumor suppressors. A long non-coding RNA colorectal adenocarcinoma hypermethylated (CAHM) has been reported to be nearly deleted in glioblastomas (GBMs). Nevertheless, the roles of CAHM in gliomas remain unknown up to now. In the present study, 969 glioma samples downloaded from the CGGA and Gravendeel databases were included. We found that CAHM expression was correlated with glioma grades, molecular subtype, IDH mutation status, and 1q/19p codel status. In glioma cells, CAHM is hypermethylated by DNA methyltransferase1 (DNMT1) and the loss of CAHM expression could be reversed by 5-Aza-2'-deoxycytidine (5-Aza), a specific inhibitor of DNA methyltransferases. Besides, the expression of CAHM was negatively associated with overall survival in both primary and recurrent gliomas. Moreover, the result of Gene Ontology (GO) analysis suggested that CAHM participated in negatively regulating cell development, nervous system development, neurogenesis, and integrin-mediated signaling pathway. Overexpression of CAHM inhibited glioma cell proliferation, clone formation, and invasion. Further exploring results showed that CAHM overexpression suppressed glioma migration and invasion through SPAK/MAPK pathway. Collectively, this study disclosed that CAHM might be a suppressor in gliomas.

Size-Dependent Cytotoxicity and Reactive Oxygen Species of Cerium Oxide Nanoparticles in Human Retinal Pigment Epithelia Cells.

PURPOSE: The use of cerium oxide nanoparticles (CeO2 NPs), a lanthanide element oxide and bivalent compound, has been growing continuously in industry and biomedicine. Due to their wide application, the potential human health problems of CeO2 NPs have attracted attention, but studies on the toxicity of this compound to human eyes are lacking. This study investigated the cytotoxicity and reactive oxygen species (ROS) of CeO2 NPs in human retinal pigment epithelial cells (ARPE-19 cells). METHODS: Using the transmission electron microscope (TEM), the size distribution and shape of CeO2 NPs were characterized. To explore the effect of CeO2 NP size on ophthalmic toxicity in vitro, three sizes (15, 30 and 45 nm) of CeO2 NPs were investigated using ATP content measurement, LDH release measurement and cell proliferation assay in ARPE-19 cells. ROS values and mitochondrial membrane potential depolarization were evaluated by H2DCF-DA staining and JC-1 staining. Morphology changes were detected using a phase-contrast microscope. RESULTS: The cytotoxicity of 15 nm CeO2 NPs was found to be the highest and hence was further explored. Treatment with 15 nm CeO2 NPs caused the morphology of ARPE-19 cells to change in a dose- and time-dependent manner. Moreover, the treatment induced excessive ROS generation and mitochondrial membrane potential depolarization. In addition, cytotoxicity was attenuated by the application of a ROS scavenger N-acetyl-L- cysteine (NAC). CONCLUSION: CeO2 NPs induced cytotoxicity in ARPE-19 cells and excessive production of ROS and decreasing mitochondrial membrane potential. The Overproduction of ROS partially contributes to CeO2 NP-induced cytotoxicity.

Poly(p-phenylenevinylene) nanoparticles modified with antiEGFRvIII for specific glioblastoma therapy.

Glioblastoma is the most common primary brain cancer and it is nearly impossible to remove the entire tumor with surgery or a single drug. EGFRvIII is the most frequent genetic change associated with glioblastoma, so EGFRvIII-based targeting therapies provide promise for treating glioblastoma. Herein, poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylenevinylene] (PPV) was used as the core to prepare a conjugated polymer nanoparticle (PPVN) modified with anti-EGFRvIII (PPVN-A) that exhibited high ROS generation ability under white light irradiation. PPVN-A could target EGFRvIII-overexpressed tumor cells and damaged more than 90% of tumor cells with the light illumination while PPVN without modification exhibited no obvious cytotoxicity toward these cells under the same condition. Thus, the photodynamic treatment of glioblastoma cells using PPVN-A could be achieved, indicating the potential of anti-EGFRvIII-modified nanoparticles as a therapeutic material for treating glioblastoma in clinic.

Prospectively Assigned AAST Grade versus Modified Hinchey Class and Acute Diverticulitis Outcomes.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) recently developed a classification system to standardize outcomes analyses for several emergency general surgery conditions. To highlight this system's full potential, we conducted a study integrating prospective AAST grade assignment within the electronic medical record. METHODS: Our institution integrated AAST grade assignment into our clinical workflow in July 2018. Patients with acute diverticulitis were prospectively assigned AAST grades and modified Hinchey classes at the time of surgical consultation. Support vector machine-a machine learning algorithm attuned for small sample sizes-was used to compare the associations between the two classification systems and decision to operate and incidence of complications. RESULTS: 67 patients were included (median age of 62 y, 40% male) for analysis. The decision for operative management, hospital length of stay, intensive care unit admission, and intensive care unit length of stay were associated with both increasing AAST grade and increasing modified Hinchey class (all P < 0.001). AAST grade additionally showed a correlation with complication severity (P = 0.02). Compared with modified Hinchey class, AAST grade better predicted decision to operate (88.2% versus 82.4%). CONCLUSIONS: This study showed the feasibility of electronic medical record integration to support the full potential of AAST classification system's utility as a clinical decision-making tool. Prospectively assigned AAST grade may be an accurate and pragmatic method to find associations with outcomes, yet validation requires further study.

Management protocol for emergency aneurysm craniotomy clipping in non-major COVID-19 epidemic areas in Beijing, China.

BACKGROUND: An epidemic of COVID-19 broke out in Wuhan, China, since December 2019. The ordinary medical services were hindered. However, the emergency cases, including aneurysmal subarachnoid hemorrhage (aSAH), still required timely intervention. Thus, it provoked challenges to the routine management protocol. In this study, we summarized our experience in the emergency management of aSAH (Beijing Tiantan Protocol, BTP) in Beijing, China. METHODS: Demographic, clinical, and imaging data of consecutive emergency aSAH patients who underwent craniotomy clipping during the COVID-19 epidemic season were reviewed and compared with the retrospective period last year. Subgroup analysis was further performed to assess the outcomes of different screening results and several detailed protocols. Neurological outcomes were evaluated by the modified Rankin Scale (mRS). RESULTS: A total of 127 aSAH were referred to our emergency department, and 42 (33.1%) underwent craniotomy clipping between January 20, 2020, and March 25, 2020. The incidence of preoperative hospitalized adverse events and the perioperative outcomes were similar (- 0.1, 95% CI - 1.0 to 0.8, P = 0.779) to the retrospective period last year (January 2019-March 2019). After the propensity score matching (PSM), there were still no statistical differences in prognostic parameters between the two groups. Eight (19.0%) of the 42 individuals were initially screened as preliminary undetermined COVID-19 cases, in which 2 of them underwent craniotomy clipping in the negative pressure operating room (OR). The prognosis of patients with varied COVID-19 screening results was similar (F(2, 39) = 0.393, P = 0.678). Since February 28, 12 cases (28.6%) received COVID-19 nucleic acid testing (NAT) upon admission, and all showed negative. The false-negative rate was 0.0%. The preoperative hospitalized adverse events and postoperative prognosis were still similar between patients with and without COVID-19 NAT (- 0.3, 95% CI - 1.4 to 0.9, P = 0.653). CONCLUSIONS: Our emergency surgery management protocol (BTP) is reliable for scheduling emergency aneurysm craniotomy clipping in non-major epidemic areas.