Self-Limiting Phase Transition Enabling Reversible Overstoichiometric Li Storage in Ni-Rich Cathodes.

Ni-rich cathodes are some of the most promising candidates for advanced lithium-ion batteries, but their available capacities have been stagnant due to the intrinsic Li+ storage sites. Extending the voltage window down can induce the phase transition from O3 to 1T of LiNiO2-derived cathodes to accommodate excess Li+ and dramatically increase the capacity. By setting the discharge cutoff voltage of LiNi0.6Co0.2Mn0.2O2 to 1.4 V, we can reach an extremely high capacity of 393 mAh g-1 and an energy density of 1070 Wh kg-1 here. However, the phase transition causes fast capacity decay and related structural evolution is rarely understood, hindering the utilization of this feature. We find that the overlithiated phase transition is self-limiting, which will transform into solid-solution reaction with cycling and make the cathode degradation slow down. This is attributed to the migration of abundant transition metal ions into lithium layers induced by the overlithiation, allowing the intercalation of overstoichiometric Li+ into the crystal without the O3 framework change. Based on this, the wide-potential cycling stability is further improved via a facile charge-discharge protocol. This work provides deep insight into the overstoichiometric Li+ storage behaviors in conventional layered cathodes and opens a new avenue toward high-energy batteries.

Role of C/EBP Homologous Protein in Vascular Stenosis After Carotid Artery Injury.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging.

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients.

Pregnane X receptor (PXR) is a member of nuclear receptor subfamily 1 (NR1I2) that is a transcriptional regulator of several metabolic enzymes involved in clopidogrel metabolism. In this study we identified and evaluated the contributions of single nucleotide polymorphisms (SNPs) in NR1I2 and cytochrome P450 (CYP) 2C19 alleles to clopidogrel resistance (CR) and long-term clinical outcomes in acute ischemic stroke (IS) patients. A total of 634 patients with acute IS were recruited, who received antiplatelet medication (clopidogrel or aspirin) every day and completed a 1-year follow-up. The selected SNPs were genotyped, and platelet function was measured. Modified Rankin Scale (mRS) scores and main adverse cardiovascular and cerebrovascular events (MACCE) were noted to assess the prognosis. We showed that SNPs NR1I2 rs13059232 and CYP2C19 alleles (2*/3*) were related to CR. SNP NR1I2 (rs13059232) was identified as an independent risk factor for the long-term clinical outcomes in the clopidogrel cohorts (P < 0.001), but similar results were not observed in a matched aspirin cohort (P > 0.05). Our results suggest that NR1I2 variant (rs13059232) could serve as biomarker for clopidogrel therapy and individualized antiplatelet medications in the treatment of acute IS patients.

Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy.

AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. METHODS: A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB2 ELISA kit. RESULTS: Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233-0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080-6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than noncarriers (odds ratio=8.233, 95% CI: 1.590-42.638). CONCLUSION: A considerable portion (11.66%) of Chinese ischemic stroke patients are insensitive to aspirin treatment, which may be correlated with the MDR1 C3435T, TBXA2R (rs1131882), and PLA2G7 (rs1051931-rs7756935) polymorphisms.

Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke.

AIM: There is a high incidence of the antiplatelet drug clopidogrel resistance (CR) in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NR1I2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke. METHODS: A total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NR1I2 (rs13059232), CYP3A4(*)1G (rs2242480), CYP2C19(*)2 (rs4244285) and P2RY12 (rs2046934) were genotyped. RESULTS: The CR rate in this population was 36%. The CYP2C19(*)2 variant was a risk factor for CR ((*)2/(*)2+wt/(*)2 vs wt/wt, OR: 2.366, 95% CI: 1.180-4.741, P=0.014), whereas the CYP3A4(*)1G variant had a protective effect on CR ((*)1/(*)1 vs (*)1G/(*)1G+(*)1/(*)1G, OR: 2.360, 95% CI: 1.247-4.468, P=0.008). The NR1I2 (rs13059232) polymorphism was moderately associated with CR (CC vs TT+TC, OR: 0.533, 95% CI: 0.286-0.991, P=0.046). The C allele in P2RY12 (rs2046934) was predicted to be a protective factor for CR (CC+TC vs TT, OR: 0.407, 95% CI: 0.191-0.867, P=0.018). In addition, an association was found between hypertension and CR (P=0.022). CONCLUSION: The individuals with both the CYP2C19(*)2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4(*)1G allele, P2RY12 (rs2046934) C allele and NR1I2 (rs13059232) CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke.

[Water use characteristics and the mechanism of water uptake in two typical sand-fixing species in Mu Us sandy land]. / æ¯›ä¹Œç´ å ¸åž‹å›ºæ²™æ¤ç‰©çš„æ°´åˆ†åˆ©ç”¨ç‰¹æ€§ä¸Žå¸æ°´æœºåˆ¶.

Understanding water absorption mechanisms of sand-fixing plants is important for the rational establishment of plant community structures, thereby providing a scientific basis for desertification control and the efficient utilization of water resources in sandy areas. Based on the hydrogen and oxygen isotopic compositions of precipi-tation, soil water, xylem water, and groundwater, coupled with soil water-heat dynamics, annual water consumption characteristics of vegetation, using the multi-source linear mixing model (IsoSource), we analyzed the differences in water sources between Salix psammophila and Artemisia ordosica, during winter and the growing season. We further examined the effects of groundwater depth (2 m and 10 m), soil freezing-thawing, and drought on their water utilization to elucidate water absorption mechanisms of those species. The results showed that: 1) During soil freezing-thawing period (January to March), S. psammophila mainly utilized soil water in 60-120 cm depths below the frozen layer (69.1%). In the green-up season (April and May), soil water from the 0-60 cm layers could satisfy the water demand of S. psammophila (30.9%-87.6%). During the dry period of the growing season (June), it predominantly utilized soil water at the depth of 120-160 cm (27.4%-40.8%). Over the rainy season (July and September), soil water in 0-60 cm depths provided 59.8%-67.9% of the total water required. A. ordosica, with shallow roots, could not utilize soil water after complete freezing of root zone but could overwinter by storing water in rhizomes during autumn. During the growing season, it primarily relied on 0-40 cm soil layer (23.4%-86.8%). During the dry period, it mainly utilized soil water from 40-80 cm and 80-160 cm soil layers, with utilization rates of 14.6%-74.4% and 21.8%-78.2%, respectively. 2) With decreasing groundwater depth, vegetation shifted its water absorption depth upward, with water source of S. psammophila transitioning from 120-160 cm to 60-160 cm layers, while A. ordosica shifted water absorption depth from 80-160 cm to 0-40 cm. S. psammophila's utilization of soil water is influenced by transpiration, adopting an "on-demand" approach to achieve a balance between water supply and energy conservation, whereas A. ordosica tends to utilize shallow soil water, exhibiting a higher depen-dence on water sources from a single soil layer.

A nano-delivery system expands the insecticidal target of thiamethoxam to include a devastating pest, the fall armyworm.

Nano-delivery systems have been applied to deliver various synthetic/botanical pesticides to increase the efficiency of pesticide use and reduce the volumes of pesticides applied. Previous studies have supported the hypothesis that the nanocarriers can help expand the insecticidal target of pesticides to include non-target pests. However, the potential mechanism underlying this interesting phenomenon remains unclear. Herein, a widely applied star polycation (SPc) nanocarrier was synthesized to construct a thiamethoxam (TMX) nano-delivery system. The SPc-based delivery system could promote the translocation of exogenous substances across the membrane of Sf9 cells, increase the cytotoxicity of TMX against Sf9 cells by nearly 20%, and expand the insecticidal target of TMX to include Spodoptera frugiperda (the fall armyworm), with a 27.5% mortality increase at a concentration of 0.25 mg/mL. Moreover, the RNA-seq analysis demonstrated that the SPc could upregulate various transport-related genes, such as Rab, SORT1, CYTH, and PIKfyve, for the enhanced cellular uptake of TMX. Furthermore, enhanced cell death in larvae treated with the TMX-SPc complex was observed through changes in the expression levels of death-related genes, such as Casp7, BIRC5, MSK1, and PGAM5. The SPc-based nano-delivery system improved the cellular uptake of TMX and expanded its insecticidal target by adjusting the expression levels of death-related genes. The current study mainly identified the transport and cell death genes related to nanocarrier-based insecticidal target expansion, which is beneficial for understanding the bioactivity enhancement of the nano-delivery system.

Hydroxysafflor Yellow A Exerts Neuroprotective Effect by Reducing Aß Toxicity Through Inhibiting Endoplasmic Reticulum Stress in Oxygen-Glucose Deprivation/Reperfusion Cell Model.

Ischemia stroke is thought to be one of the vascular risks associated with neurodegenerative diseases, such as Alzheimer's disease (AD). Hydroxysafflor yellow A (HSYA) has been reported to protect against stroke and AD, while the underlying mechanism remains unclear. In this study, SH-SY5Y cell model treated with oxygen-glucose deprivation/reperfusion (OGD/R) was used to explore the potential mechanism of HSYA. Results from cell counting kit-8 (CCK-8) showed that 10 µM HSYA restored the cell viability after OGD 2 hours/R 24 hours. HSYA reduced the levels of malondialdehyde and reactive oxygen species, while improved the levels of superoxide dismutase and glutathione peroxidase. Furthermore, apoptosis was inhibited, and the expression of brain-derived neurotrophic factor was improved after HSYA treatment. In addition, the expression levels of amyloid-ß peptides (Aß) and BACE1 were decreased by HSYA, as well as the expression levels of binding immunoglobulin heavy chain protein, PKR-like endoplasmic reticulum (ER) kinase pathway, and activating transcription factor 6 pathway, whereas the expression level of protein disulfide isomerase was increased. Based on these results, HSYA might reduce Aß toxicity after OGD/R by interfering with apoptosis, oxidation, and neurotrophic factors, as well as relieving ER stress.

Icy core-shell composite nanofibers with cooling, antibacterial and healing properties for outdoor burns.

Burns are usually difficult to treat because their susceptibe to bacterial infections. When burns is accompanied by hyperthermia, the heat accumulated on the skin will causes extensive tissue damage. Most dressings focus on the treatment process, while ignoring the first-aid treatment to remove hyperthermia. To make matters worse, when outdoors, it is hard to find clean water to wash and cool the burned area. A dressing which can simultaneously realize first-time cooling and repairing treatment of the burned area can shorten treatment time, and is especially beneficial for outdoor use. In this study, a handheld coaxial electrospinning device is developed for preparing platelet-rich plasma @Polycaprolactone-epsilon polylysine (PRP@PCL/ε-PL) core-shell nanofibers. The nanofibers can be synchronously transformed into ice fibers during the spinning process, and directly deposited on the skin. The whole process is convenient to use outdoor. Via dual cooling mechanisms, first aid can take away the excessive heat in the burn area by nanofibers. These core-shell nanofibers also show its excellent antimicrobial and tissue regeneration-promoting properties. Therefore, it achieves first-time cooling and repair treatment of the burned area at the same time. Moreover, due to direct in-situ deposition of this handheld coaxial electrospinning, better antimicrobial properties, and faster healing performance are achieved. By using this integrated strategy that combines cooling, antibacterial and healing promotion, the burn recovery time is shortened from 21 days to 14 days.

Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via Notch inhibition by competitively binding to Jag1.

Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal angiogenesis has been explored, little is known about its role in pro-angiogenesis and the microglia-endothelia interaction. Here, we report that galectin-3 (Gal3) released by activated microglia functions as a communicator between microglia and endothelia and competitively binds to Jag1, thus inhibiting the Notch signaling pathway and enhancing endothelial angiogenic metabolism to promote angiogenesis. These results suggest that Gal3 may be a novel and effective target in the treatment of retinal angiogenesis.

Poor sleep quality association with higher lung cancer risk: a nested case-control study.

Background: Little is known about the relationship between sleep quality and lung cancer incidence. Thus, this study was conducted to investigate the potential connection between sleep quality and lung cancer incidence. Methods: We performed and selected a nested case-control study that included 150 lung cancer cases and 150 matched controls based on the Lianyungang cohort. Univariate and multivariate logistic regression was utilized to investigate the connection between potential risk factors and lung cancer incidence risk. Results: In this study, the average age of participants was 66.5 ± 9.1 years, with 58.7% being male, and 52.7% reportedly experiencing sleep quality problems. The results of multivariate logistic regression showed that poor sleep quality was connected to an increased lung cancer incidence risk (P = 0.033, odds ratio = 1.83, 95% confidence interval = [1.05-3.19]) compared with those with good sleep quality. The stratified analyses showed a significantly positive connection between poor sleep quality (vs. good sleep quality) and cancer risk in smokers (vs. non-smoker, P for interaction = 0.085). The combined effect analysis indicated that smokers with poor sleep quality suffered from a 2.79-fold increase in cancer incidence rates when compared with non-smokers with good sleep quality. Conclusions: Poor sleep quality was positively connected to an increased lung cancer incidence risk. In addition, among those individuals with poor sleep quality, smoking increased the lung cancer incidence risk.

The Significance of the Ocular Adverse Effect Induced by Systemic Taxane Application.

In recent years, in-depth research on anti-tumor therapy has brought the emergence of new active chemotherapeutic agents and combination regimens. However, as one of them, taxane drugs are widely used in clinical practice, but it should be noted that many side reactions caused by their application bring some difficulties to routine management. Among the side reactions related to taxane anti-tumor therapy, ocular adverse reactions are occasionally reported and are not life-threatening but may seriously affect patients' life quality. Thus, the continuation, reduction and cessation of taxane chemotherapy still need to be further evaluated by ophthalmologists and oncologists once the side effects show up. To prevent ocular side reactions, close attention should be paid to complications during medication. To facilitate the oncology department and ophthalmologists to comprehensively understand the ophthalmic adverse reactions of taxane drugs and their possible mechanisms and improve drug use efficiency, we collected relevant literature and reviewed and provided some suggestions for the monitoring and managing of ophthalmic toxicity.

Impact of partial bile duct ligation with or without repeated magnetic resonance imaging examinations in mice.

Partial bile duct ligation (pBDL) is considered a well-tolerated cholestatic model. Magnetic resonance imaging (MRI) is one of the most widely used tools in noninvasive imaging. However, no systematic studies have reported the possible effects of repeated MRI assessments in the pBDL model. Sixty BALB/C mice were investigated. MRI images of each mouse were recorded once every 2 weeks for 6 weeks after pBDL or sham surgery. The reproducibility of the pBDL model and the reliability of MRI were examined by behavioral, physiological, biochemical, and pathological parameters. The mice showed no alterations on behavioral and physiological tests (P > 0.05) at 2, 4, and 6 weeks after pBDL. Repeated general anesthesia did not result in any impairment after pBDL (P > 0.05). The behavioral and biochemical parameters were not affected by repeated MRIs or repeated contrast-enhanced MRIs (P > 0.05). Pathological staining showed the homogeneous formation of collagenous fiber in the pBDL mice and did not indicate any influence of repeated contrast-enhanced MRI on the number of inflammatory cells or fibrotic formation (P > 0.05). Thus, pBDL is a reproducible model with many advantages for animal welfare and scientific research. Additionally, MRI, as a safe tool for longitudinal evaluation and is well tolerated in mice with cholestasis.

Associations between psycho-behavioral risk factors and diabetic retinopathy: NHANES (2005-2018).

Introduction: Diabetes mellitus (DM) and diabetic retinopathy (DR) increase the global burden. Since their pathogenesis is complex, it is necessary to use the biopsychosocial model to discover the most effective strategies. The study is aimed to investigate the psycho-behavioral factors of DR and confirm the discrepancies from previous studies. Research design and methods: The study comprised seven cycles of cross-sectional data of the National Health and Nutrition Examination Survey (NHANES) from 2005-2006 to 2017-2018. Samples of DM were selected from this complex multi-stage probability sample and divided into the non-DR and DR groups, where 4,426 samples represented 18,990,825 individuals after weighting. This study comprehensively explored the biological, social, and psychological risk factors of DR, among which the biological factors included blood pressure, blood routine, HbA1c%, blood glucose, the duration of DM, family history, comorbidities, and treatment methods. Social aspects include gender, education, income, insurance, smoking, drinking, sleep habits, and recreational activities. The Patient Health Questionnaire-9 (PHQ-9) was used to assess the psychological state. Taylor series regression was used to examine the connection between factors and DR. Results: Men accounted for 55.5% of the DR group (P = 0.0174). Lymphocyte count, insulin treatment, heart failure, stroke, liver condition, and renal failure showed significant differences in DR (P < 0.05). The incidence of depression in DR was 40.5%. Mild to moderate depression [odds ratio was associated with DR [(OR) = 1.37, 95% confidence interval (CI): 1.06-1.79], but there was no statistical difference in severe depression (OR = 1.34, 95% CI: 0.83-2.17). Although ≤ 6 h of sleep was associated with DR (OR = 1.38, 95% CI: 1.01-1.88), we found no statistical differences in alcohol consumption, recreational activities, or sedentary time between the two groups in our current study (P > 0.05). Conclusions: The biological risk factors of DR are significant. It showed that stroke is associated with DR, and retinal exams have the potential value as a screening tool for the brain. Besides, psycho-behavioral risk factors of DR should also be paid attention. Our study highlights that mild and moderate depression and ≤6 h of sleep are distinguishably associated with DM complicated with DR. It indicates that psycho-behavioral risk factors confer a vital influence on diabetic health care and DR.

Notch-Regulated c-Kit-Positive Liver Sinusoidal Endothelial Cells Contribute to Liver Zonation and Regeneration.

BACKGROUND & AIMS: Liver sinusoidal endothelial cells (SECs) promote the proliferation of hepatocytes during liver regeneration. However, the specific subset of SECs and its mechanisms during the process remain unclear. In this study, we investigated the potential role of c-kit+ SECs, a newly identified subset of SECs in liver regeneration. METHODS: Partial hepatectomy mice models were established to induce liver regeneration. Hepatic c-kit expression was detected by quantitative reverse-transcription polymerase chain reaction, immunofluorescent staining, and fluorescence-activated cell sorting. VE-cadherin-cyclization recombinase-estrogen receptor (Cdh5-Cre-ERT) Notch intracellular domain and Cdh5-Cre recombination signal binding protein Jκfloxp mice were introduced to mutate Notch signaling. c-Kit+ SECs were isolated by magnetic beads. Single-cell RNA sequencing was performed on isolated SECs. Liver injuries were induced by CCl4 or quantitative polymerase chain reaction injection. RESULTS: Hepatic c-kit is expressed predominantly in SECs. Liver resident SECs contribute to the increase of c-kit during partial hepatectomy-induced liver regeneration. Isolated c-kit+ SECs promote hepatocyte proliferation in vivo and in vitro by facilitating angiocrine. The distribution of c-kit shows distinct spatial differences that are highly coincident with the liver zonation marker wingless-type MMTV integration site family, member2 (Wnt2). Notch mutation reshapes the c-kit distribution and liver zonation, resulting in altered hepatocyte proliferation. c-Kit+ SECs were shown to regulate hepatocyte regeneration through angiocrine in a Wnt2-dependent manner. Activation of the Notch signaling pathway weakens liver regeneration by inhibiting positive regulatory effects of c-kit+ SECs on hepatocytes. Furthermore, c-kit+ SEC infusion attenuates toxin-induced liver injuries in mice. CONCLUSIONS: Our results suggest that c-kit+ SECs contributes to liver zonation and regeneration through Wnt2 and is regulated by Notch signaling, providing opportunities for novel therapeutic approaches to liver injury in the future. Transcript profiling: GEO (accession number: GSE134037).

PFKFB3: A Potential Key to Ocular Angiogenesis.

The current treatment for ocular pathological angiogenesis mainly focuses on anti-VEGF signals. This treatment has been confirmed as effective despite the unfavorable side effects and unsatisfactory efficiency. Recently, endothelial cell metabolism, especially glycolysis, has been attracting attention as a potential treatment by an increasing number of researchers. Emerging evidence has shown that regulation of endothelial glycolysis can influence vessel sprouting. This new evidence has raised the potential for novel treatment targets that have been overlooked for a long time. In this review, we discuss the process of endothelial glycolysis as a promising target and consider regulation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as treatment for ocular pathological angiogenesis.

Multiparameter magnetic resonance imaging of liver fibrosis in a bile duct ligation mouse model.

BACKGROUND: Bile duct ligation (BDL) in animals is a classical method for mimicking cholestatic fibrosis. Although different surgical techniques have been described in rats and rabbits, mouse models can be more cost-effective and reproducible for investigating cholestatic fibrosis. Magnetic resonance imaging (MRI) has made great advances for noninvasive assessment of liver fibrosis. More comprehensive liver fibrotic features of BDL on MRI are important. However, the utility of multiparameter MRI to detect liver fibrosis in a BDL mouse model has not been assessed. AIM: To evaluate the correlation between the pathological changes and multiparameter MRI characteristics of liver fibrosis in a BDL mouse model. METHODS: Twenty-eight healthy adult male balb/c mice were randomly divided into four groups: sham, week 2 BDL, week 4 BDL, and week 6 BDL. Multiparameter MRI sequences, included magnetic resonance cholangiopancreatography, T1-weighted, T2-weighted, T2 mapping, and pre- and post-enhanced T1 mapping, were performed after sham and BDL surgery. Peripheral blood and liver tissue were collected after MRI. For statistical analysis, Student's t-test and Pearson's correlation coefficient were used. RESULTS: Four mice died after BDL surgery; seven, six, five and six mice were included separately from the four groups. Signal intensities of liver parenchyma showed no difference on TI- and T2-weighted images. Bile duct volume, ΔT1 value, T2 value, and the rate of liver fibrosis increased steadily in week 2 BDL, week 4 BDL and week 6 BDL groups compared with those in the sham group (P < 0.01). Alanine aminotransferase and aspartate transaminase levels initially surged after surgery, followed by a gradual decline over time. Strong correlations were found between bile duct volume (r = 0.84), T2 value (r = 0.78), ΔT1 value (r = 0.62), and hepatic fibrosis rate (all P < 0.01) in the BDL groups. CONCLUSION: The BDL mouse model induces changes that can be observed on MRI. The MRI parameters correlate with the hepatic fibrosis rate and allow for detection of cholestatic fibrosis.

Apocynum venetum leaf extract protects rat cortical neurons from injury induced by oxygen and glucose deprivation in vitro.

This study aimed to investigate the protective effect of Apocynum venetum leaf extract (AVLE) on an in vitro model of ischemia-reperfusion induced by oxygen and glucose deprivation (OGD) and further explored the possible mechanisms underlying protection. Cell injury was assessed by morphological examination using phase-contrast microscopy and quantified by measuring the amount of lactate dehydrogenase (LDH) leakage; cell viability was measured by XTT reduction. Neuronal apoptosis was determined by flow cytometry, and electron microscopy was used to study morphological changes of neurons. Caspase-3, -8, and -9 activation and Bcl-2/Bax protein expression were determined by Western blot analysis. We report that treatment with AVLE (5 and 50 µg/mL) effectively reduced neuronal cell death and relieved cell injury induced by OGD. Moreover, AVLE decreased the percentage of apoptotic neurons, relieved neuronal morphological damage, suppressed overexpression of active caspase-3 and -8 and Bax, and inhibited the reduction of Bcl-2 expression. These findings indicate that AVLE protects against OGD-induced injury by inhibiting apoptosis in rat cortical neurons by down-regulating caspase-3 activation and modulating the Bcl-2/Bax ratio.

Research on Standard Compliance Test Algorithm Based on Electronic Medical Records of Traditional Chinese Medicine Outpatients.

Objectives: To effectively evaluate the compliance degree between the electronic medical records of Traditional Chinese Medicine (TCM) hospitals, as well as the information platform, and the related information standards of electronic medical records, a standard compliance testing scheme based on electronic medical records of TCM outpatients is proposed. Methods: This research selected the data of clinical outpatients accumulated in 10 years by the Digital Medicine Institute of Chengdu University of TCM and processed the data through security check and desensitization process. And then 28348 cases of processed electronic medical records of TCM outpatients were inputted into the standard compliance testing platform for assessment. The result was then outputted. Results: There are 924 cases among the 28348 that can be rated as five-star medical records, 84 cases four-star, 132 cases three-star, 12460 cases two-star, 13488 one-star, and 1260 cases zero-star through the integrity and standardization test. Conclusion: By the way of assessing the integrity and standardization of data, the standard compliance test algorithm scheme for electronic medical records of TCM outpatients introduced in this paper can solve the problems such as data unavailability caused by ununified codes and incomplete data in the data-sharing process and provides technical support for the construction of data standardization testing in electronic medical records of TCM outpatients.