USP7 depletion potentiates HIF2α degradation and inhibits clear cell renal cell carcinoma progression.

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel Lindau (VHL) gene loss of function mutation, which leads to the accumulation of hypoxia-inducible factor 2α (HIF2α). HIF2α has been well-established as one of the major oncogenic drivers of ccRCC, however, its therapeutic targeting remains a challenge. Through an analysis of proteomic data from ccRCCs and adjacent non-tumor tissues, we herein revealed that Ubiquitin-Specific Peptidase 7 (USP7) was upregulated in tumor tissues, and its depletion by inhibitors or shRNAs caused significant suppression of tumor progression in vitro and in vivo. Mechanistically, USP7 expression is activated by the transcription factors FUBP1 and FUBP3, and it promotes tumor progression mainly by deubiquitinating and stabilizing HIF2α. Moreover, the combination of USP7 inhibitors and afatinib (an ERBB family inhibitor) coordinately induce cell death and tumor suppression. In mechanism, afatinib indirectly inhibits USP7 transcription and accelerates the degradation of HIF2α protein, and the combination of them caused a more profound suppression of HIF2α abundance. These findings reveal a FUBPs-USP7-HIF2α regulatory axis that underlies the progression of ccRCC and provides a rationale for therapeutic targeting of oncogenic HIF2α via combinational treatment of USP7 inhibitor and afatinib.

Hypoxic glioma-derived exosomal miR-25-3p promotes macrophage M2 polarization by activating the PI3K-AKT-mTOR signaling pathway.

BACKGROUND: Exosomes (EXO) play crucial roles in intercellular communication and glioma microenvironment modulation. Tumor-associated macrophages are more likely to become M2-like type macrophages in the immunosuppressive microenvironment. Here, we aimed to investigate the effects and molecular mechanisms of hypoxic glioma-derived exosomes mediated M2-like macrophage polarization. METHODS: Highly expressed miRNAs in exosomes derived from glioma cells cultured under hypoxia condition compared to normoxic condition were identified through microRNA sequencing. The polarization status of macrophages was determined using qRT-PCR, Western blotting, flow cytometry, and immunohistochemistry. By using RNA-seq, we aimed to identify the downstream target genes regulated by miR-25-3p in macrophages and investigate the mechanistic pathways through which it exerts its effects. The proliferation and migration capabilities of glioma cells were assessed through EdU, Transwell assays, and in vivo experiments. RESULTS: We found that miR-25-3p was upregulated in the exosomes derived from hypoxic glioma cells and can be transferred to the macrophage. In macrophages, miR-25-3p downregulates the expression of PHLPP2, thereby activating the PI3K-AKT-mTOR signaling pathway, ultimately leading to macrophage M2 polarization. As part of a feedback loop, M2-polarized macrophages can, in turn, promote malignant glioma progression. CONCLUSION: Our study reveals that miR-25-3p from hypoxic glioma cells is delivered to macrophages via exosomes as a mediator, promoting M2 polarization of macrophages through the miR-25-3p/PHLPP2/PI3K-AKT signaling pathway. This study suggests that targeted interventions to modulate miR-25-3p expression, transmission, or inhibition of PI3K-AKT pathway activation can disrupt the immune-suppressive microenvironment, providing a novel approach for immunotherapy in gliomas.

Effects of alkaline salt stress on growth, physiological properties and medicinal components of clonal Glechoma longituba (Nakai) Kupr.

BACKGROUND: Glechoma longituba, recognized as a medicinal plant, provides valuable pharmaceutical raw materials for treating various diseases. Saline-alkali stress may effectively enhance the medicinal quality of G. longituba by promoting the synthesis of secondary metabolites. To investigate the changes in the primary medicinal components of G. longituba under saline-alkali stress and improve the quality of medicinal materials, Na2CO3 was applied to induce short-term stress under different conditions and the biomass, physiologically active substances and primary medicinal components of G. longituba were measured in this study. RESULTS: Under alkaline salt stress, the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX) were elevated in G. longituba, accompanied by increased accumulation of proline (Pro) and malondialdehyde (MDA). Furthermore, analysis of the medicinal constituents revealed that G. longituba produced the highest levels of soluble sugars, flavonoids, ursolic acid, and oleanolic acid under 0.6% Na2CO3 stress for 48 h, 0.2% Na2CO3 stress for 72 h, 0.4% Na2CO3 stress for 12 h, and 0.4% Na2CO3 stress for 8 h, respectively. CONCLUSIONS: Short-term Na2CO3 stress enhances the synthesis of medicinal components in G. longituba. By manipulating stress conditions, the production of various medicinal substances could be optimized. This approach may serve as a basis for the targeted cultivation of G. longituba, offering potential applications in the treatment of diverse diseases.

Flour Treatments Affect Gluten Protein Extractability, Secondary Structure, and Antibody Reactivity.

Commercial Brazilian wheat flour was subjected to extrusion, oven, and microwave treatments. The solubility, monomeric and polymeric proteins, and the glutenin and gliadin profiles of the gluten were analyzed. In addition, in vitro digestibility and response against potential celiac disease immune-stimulatory epitopes were investigated. All treatments resulted in low solubility of the polymeric and monomeric proteins. The amounts of insoluble proteins increased from 5.6% in control flour to approximately 10% for all (treatments), whereas soluble proteins decreased from 6.5% to less than 0.5% post treatment. In addition, the treatments affected glutenin and gliadin profiles. The amount of α/ß-gliadin extracted decreased after all treatments, while that of γ-gliadin was unaffected. Finally, the potential celiac disease immune stimulatory epitopes decreased in oven and microwave treatment using the G12 ELISA, but no change was observed using the R5 antibody. However, the alteration of the gluten structure and complexity was not sufficient to render a product safe for consumption for individuals with celiac disease; the number of potential celiac disease immune-stimulatory epitopes remained high.

Multiomics integrated analysis and experimental validation identify TLR4 and ALOX5 as oxidative stress-related biomarkers in intracranial aneurysms.

BACKGROUND: Intracranial aneurysm (IA) is a severe cerebrovascular disease, and effective gene therapy and drug interventions for its treatment are still lacking. Oxidative stress (OS) is closely associated with the IA, but the key regulatory genes involved are still unclear. Through multiomics analysis and experimental validation, we identified two diagnostic markers for IA associated with OS. METHODS: In this study, we first analyzed the IA dataset GSE75436 and conducted a joint analysis of oxidative stress-related genes (ORGs). Differential analysis, functional enrichment analysis, immune infiltration, WGCNA, PPI, LASSO, and other methods were used to identify IA diagnostic markers related to OS. Next, the functions of TLR4 and ALOX5 expression in IA and their potential targeted therapeutic drugs were analyzed. We also performed single-cell sequencing of patient IA and control (superficial temporal artery, STA) tissues. 23,342 cells were captured from 2 IA and 3 STA samples obtained from our center. Cell clustering and annotation were conducted using R software to observe the distribution of TLR4 and ALOX5 expression in IAs. Finally, the expression of TLR4 and ALOX5 were validated in IA patients and in an elastase-induced mouse IA model using experiments such as WB and immunofluorescence. RESULTS: Through bioinformatics analysis, we identified 16 key ORGs associated with IA pathogenesis. Further screening revealed that ALOX5 and TLR4 were highly expressed to activate a series of inflammatory responses and reduce the production of myocytes. Methotrexate (MTX) may be a potential targeted drug. Single-cell analysis revealed a notable increase in immune cells in the IA group, with ALOX5 and TLR4 primarily localized to monocytes/macrophages. Validation through patient samples and mouse models confirmed high expression of ALOX5 and TLR4 in IAs. CONCLUSIONS: Bioinformatics analysis indicated that ALOX5 and TLR4 are the most significant ORGs associated with the pathogenesis of IA. Single-cell sequencing and experiments revealed that the high expression of ALOX5 and TLR4 are closely related to IA. These two genes are promising new targets for IA therapy.

Epsins oversee smooth muscle cell reprograming by influencing master regulators KLF4 and OCT4.

Smooth muscle cells in major arteries play a crucial role in regulating coronary artery disease. Conversion of smooth muscle cells into other adverse cell types in the artery propels the pathogenesis of the disease. Curtailing artery plaque buildup by modulating smooth muscle cell reprograming presents us a new opportunity to thwart coronary artery disease. Here, our report how Epsins, a family of endocytic adaptor proteins oversee the smooth muscle cell reprograming by influencing master regulators OCT4 and KLF4. Using single-cell RNA sequencing, we characterized the phenotype of modulated smooth muscle cells in mouse atherosclerotic plaque and found that smooth muscle cells lacking epsins undergo profound reprogramming into not only beneficial myofibroblasts but also endothelial cells for injury repair of diseased endothelium. Our work lays concrete groundwork to explore an uncharted territory as we show that depleting Epsins bolsters smooth muscle cells reprograming to endothelial cells by augmenting OCT4 activity but restrain them from reprograming to harmful foam cells by destabilizing KLF4, a master regulator of adverse reprograming of smooth muscle cells. Moreover, the expression of Epsins in smooth muscle cells positively correlates with the severity of both human and mouse coronary artery disease. Integrating our scRNA-seq data with human Genome-Wide Association Studies (GWAS) identifies pivotal roles Epsins play in smooth muscle cells in the pathological process leading to coronary artery disease. Our findings reveal a previously unexplored direction for smooth muscle cell phenotypic modulation in the development and progression of coronary artery disease and unveil Epsins and their downstream new targets as promising novel therapeutic targets for mitigating metabolic disorders.

All-Solid-State Lithium-Sulfur Batteries of High Cycling Stability and Rate Capability Enabled by a Self-Lithiated Sn-C Interlayer.

All-solid-state lithium-sulfur batteries (ASSLSBs) have attracted intense interest due to their high theoretical energy density and intrinsic safety. However, constructing durable lithium (Li) metal anodes with high cycling efficiency in ASSLSBs remains challenging due to poor interface stability. Here, a compositionally stable, self-lithiated tin (Sn)-carbon (C) composite interlayer (LSCI) between Li anode and solid-state electrolyte (SSE), capable of homogenizing Li-ion transport across the interlayer, mitigating decomposition of SSE, and enhancing electrochemical/structural stability of interface, is developed for ASSLSBs. The LSCI-mediated Li metal anode enables stable Li plating/stripping over 7000 h without Li dendrite penetration. The ASSLSBs equipped with LSCI thus exhibit excellent cycling stability of over 300 cycles (capacity retention of ≈80%) under low applied pressure (<8 MPa) and demonstrate improved rate capability even at 3C. The enhanced electrochemical performance and corresponding insights of the designed LSCI broaden the spectrum of advanced interlayers for interface manipulation, advancing the practical application of ASSLSBs.

Enhancing the Structural Stability and Electrochemical Performance of High-Nickel Cathode Materials through Ti Doping with an Exothermic Non-oxide Precursor.

The foreseeable global cobalt (Co) crisis has driven the demand for cathode materials with less Co dependence, where high-nickel layered oxides are a promising solution due to their high energy density and low cost. However, these materials suffer from poor cycling stability and rapid voltage decay due to lattice displacement and nanostrain accumulation. Here, we introduced an exothermic TiN dopant via a scalable coating method to stabilize LiNi0.917Co0.056Mn0.026O2 (NCM92) materials. The exothermic reaction of TiN conversion generates extra heat during the calcination process on the cathode surface, promotes the lithiation process, and tunes the morphology of the cathode material, resulting in compact and conformal smaller particle sizes to provide better particle integration and lithium diffusion coefficient. Moreover, the Ti dopant substitutes the Ni3+ site to generate stronger Ti-O bonding, leading to higher structural stability and extended cycle life. The Ti-doped NCM (NCM92_TiN) shows a remarkable cycling stability of maintaining 80% capacity retention for 400 cycles, while bare NCM92 can only reach 88 cycles. Furthermore, the NCM92_TiN cathodes demonstrate an enhanced rate capability and achieve a discharge capacity of over 168 mAh g-1 at 5C.

A Weakly Solvating Ether Electrolyte Enables Fast-Charging and Wide-Temperature Lithium-Ion Pouch Cells.

Graphite-based lithium-ion batteries have succeeded greatly in the electric vehicle market. However, they suffer from performance deterioration, especially at fast charging and low temperatures. Traditional electrolytes based on carbonated esters have sluggish desolvation kinetics, recognized as the rate-determining step. Here, a weakly solvating ether electrolyte with tetrahydropyran (THP) as the solvent is designed to enable reversible and fast lithium-ion (Li+) intercalation in the graphite anode. Unlike traditional ether-based electrolytes which easily cointercalate into the graphite layers, the THP-based electrolyte shows fast desolvation ability and can match well with the graphite anode. In addition, the weak interconnection between Li+ and THP allows more anions to come into the solvating shell of Li+, inducing an inorganic-rich interface and thus suppressing the side reactions. As a result, the lithium iron phosphate/graphite pouch cell (3 Ah) with the THP electrolyte shows a capacity retention of 80.3% after 500 cycles at 2 C charging, much higher than that of the ester electrolyte system (7.6% after 200 cycles). At 4 C charging, the discharging capacity is increased from 2.29 Ah of esters to 2.96 Ah of THP. Furthermore, the cell can work normally over wide working temperatures (-20 to 60 °C). Our electrolyte design provides some understanding of lithium-ion batteries at fast charging and wide temperatures.

Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS.

BACKGROUND: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. METHODS AND RESULTS: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). CONCLUSIONS: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Potential of BMI as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial.

BACKGROUND: To investigate the association between BMI and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial-intracranial bypass surgery. MATERIALS AND METHODS: The authors analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, the authors compared the primary endpoint of CMOSS-stroke or death within 30 days, or IIS after 30 days up to 2 years-among patients with varying BMIs who underwent either surgery or medical treatment. RESULTS: Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within 2 years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m 2 ; 95% CI: 1.06-1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m 2 . Patients with BMI ≥24.5 kg/m 2 experienced a higher incidence of IIS compared to those with BMI <24.5 kg/m 2 (17.4 vs. 0.0%, P <0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m 2 (5.3 vs. 19.8%, P <0.01) and those with BMI <24.5 kg/m 2 (10.6 vs. 1.4%; P =0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m 2 . CONCLUSION: Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m 2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.

Phonon Engineering in Solid Polymer Electrolyte toward High Safety for Solid-State Lithium Batteries.

Extensively-used rechargeable lithium-ion batteries (LIBs) face challenges in achieving high safety and long cycle life. To address such challenges, ultrathin solid polymer electrolyte (SPE) is fabricated with reduced phonon scattering by depositing the composites of ionic-liquid (1-ethyl-3-methylimidazolium dicyamide, EMIM:DCA), polyurethane (PU) and lithium salt on the polyethylene separator. The robust and flexible separator matrix not only reduces the electrolyte thickness and improves the mobility of Li+, but more importantly provides a relatively regular thermal diffusion channel for SPE and reduces the external phonon scattering. Moreover, the introduction of EMIM:DCA successfully breaks the random intermolecular attraction of the PU polymer chain and significantly decreases phonon scattering to enhance the internal thermal conductivity of the polymer. Thus, the thermal conductivity of the as-obtained SPE increases by approximately six times, and the thermal runaway (TR) of the battery is effectively inhibited. This work demonstrates that optimizing thermal safety of the battery by phonon engineering sheds a new light on the design principle for high-safety Li-ion batteries.

Risk Factors, Antithrombotic Management, and Long-Term Outcomes of Patients Undergoing Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND: Patients receiving endovascular treatment for unruptured intracranial aneurysms (UIAs) face varying risks and benefits with antithrombotic management. This study aimed to evaluate the perioperative and long-term effects of antithrombotic strategies, identify the populations that would benefit, and explore the predictive factors affecting the long-term outcomes. METHODS: UIA patients undergoing endovascular treatment including stent-assisted coiling or flow diversion between June 2019 and June 2022 were enrolled. We compared perioperative and long-term complications between tirofiban and dual antiplatelet therapy groups. Optimal candidates for each antithrombotic treatment were identified using multivariate logistic regression. Nomograms were developed to determine the significant predictors for thromboembolic complications during follow-up. RESULTS: Among 181 propensity-score matched pairs, the tirofiban group showed a trend toward a lower rate of thromboembolic complications than the DAPT group without elevating major bleeding risk in either period. Homocysteine (Hcy) level ≥10 µmol/L was a significant independent factor associated with thromboembolic complication in both periods. Subgroup analysis highlighted that in patients with high Hcy levels, tirofiban and sustained antiplatelet treatment for ≥12 months were protective factors, while a history of stroke was an independent risk factor for thromboembolic events in follow-up. Four variables were selected to construct a prognostic nomogram, history of hypertension, prior stroke, Hcy level, and the duration of antiplatelet therapy. CONCLUSION: Perioperative low-dose tirofiban and extended antiplatelet therapy demonstrated a favorable trend in long-term outcomes for UIA patients with preoperative Hcy levels ≥10 µmol/L undergoing endovascular treatment. The prognostic model offers reliable risk prediction and guides antithrombotic strategy decisions.

Biomechanical analysis of adjacent segments after correction surgery for adult idiopathic scoliosis: a finite element analysis.

The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1-S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.

Preclinical testing of CT1113, a novel USP28 inhibitor, for the treatment of T-cell acute lymphoblastic leukaemia.

T-cell acute lymphoblastic leukaemia (T-ALL) is a highly aggressive and heterogeneous lymphoid malignancy with poor prognosis in adult patients. Aberrant activation of the NOTCH1 signalling pathway is involved in the pathogenesis of over 60% of T-ALL cases. Ubiquitin-specific protease 28 (USP28) is a deubiquitinase known to regulate the stability of NOTCH1. Here, we report that genetic depletion of USP28 or using CT1113, a potent small molecule targeting USP28, can strongly destabilize NOTCH1 and inhibit the growth of T-ALL cells. Moreover, we show that USP28 also regulates the stability of sterol regulatory element binding protein 1 (SREBP1), which has been reported to mediate increased lipogenesis in tumour cells. As the most critical transcription factor involved in regulating lipogenesis, SREBP1 plays an important role in the metabolism of T-ALL. Therefore, USP28 may be a potential therapeutic target, and CT1113 may be a promising novel drug for T-ALL with or without mutant NOTCH1.

Transcriptome Analysis of Tomato Leaves Reveals Candidate Genes Responsive to Tomato Brown Rugose Fruit Virus Infection.

Tomato brown rugose fruit virus (ToBRFV) is a newly-emerging tobamovirus which was first reported on tomatoes in Israel and Jordan, and which has now spread rapidly in Asia, Europe, North America, and Africa. ToBRFV can overcome the resistance to other tobamoviruses conferred by tomato Tm-1, Tm-2, and Tm-22 genes, and it has seriously affected global crop production. The rapid and comprehensive transcription reprogramming of host plant cells is the key to resisting virus attack, but there have been no studies of the transcriptome changes induced by ToBRFV in tomatoes. Here, we made a comparative transcriptome analysis between tomato leaves infected with ToBRFV for 21 days and those mock-inoculated as controls. A total of 522 differentially expressed genes were identified after ToBRFV infection, of which 270 were up-regulated and 252 were down-regulated. Functional analysis showed that DEGs were involved in biological processes such as response to wounding, response to stress, protein folding, and defense response. Ten DEGs were selected and verified by qRT-PCR, confirming the reliability of the high-throughput sequencing data. These results provide candidate genes or signal pathways for the response of tomato leaves to ToBRFV infection.

Feasibility and efficiency of a new classification based on high-resolution MRI for carotid artery pseudo-occlusion and occlusion: Hybrid revascularization pilot study.

BACKGROUND AND PURPOSE: Studies on changes in the distal internal carotid artery based on high resolution magnetic resonance imaging (HRMRI) are scarce. Herein, we propose a histological classification system for patients with carotid artery pseudo-occlusion or occlusion based on preoperative HRMRI, for which we evaluated the feasibility and clinical implications. MATERIALS AND METHODS: From January 2017 to June 2021, 40 patients with Doppler ultrasound, CTA or MRA suggesting carotid artery occlusion were enrolled in this study. A new classification system based on HRMRI was established and subsequently verified by postoperative specimens. We recorded and analyzed patient characteristics, HRMRI data, recanalization rate, requirements of additional endovascular procedures, complications, and outcomes. RESULTS: Four histological classifications (type Ⅰ-Ⅳ) were identified. According to our classification system, 20 patients (50.00%) were type I, nine (22.50%) were type II, 7 (17.50%) were type III, and four (10.00%) were type Ⅳ. The success rate of recanalization was 88.89% (32/36) in type I-III patients. Four (44.44%) type Ⅱ patients and five (71.43%) type Ⅲ patients suffered from intraoperative dissection. CONCLUSION: Patients identified as types I (pseudo-occlusion) and II (thrombotic-occlusion) were able to be treated via hybrid revascularization with relatively low risk, while patients identified as type III (fibrous-occlusion) required more careful treatment. Recanalization is not suitable for patients identified as type Ⅳ. Our proposed classification system based on HRMRI data can be used as an adjunctive guide to predict the technical feasibility and success of revascularization via a hybrid technique.

Diabetes prediction model for unbalanced community follow-up data set based on optimal feature selection and scorecard.

Objectives: Diabetes is a metabolic disease and early detection is crucial to ensuring a healthy life for people with prediabetes. Community care plays an important role in public health, but the association between community follow-up of key life characteristics and diabetes risk remains unclear. Based on the method of optimal feature selection and risk scorecard, follow-up data of diabetes patients are modeled to assess diabetes risk. Methods: We conducted a study on the diabetes risk assessment model and risk scorecard using follow-up data from diabetes patients in Haizhu District, Guangzhou, from 2016 to 2023. The raw data underwent preprocessing and imbalance handling. Subsequently, features relevant to diabetes were selected and optimized to determine the optimal subset of features associated with community follow-up and diabetes risk. We established the diabetes risk assessment model. Furthermore, for a comprehensible and interpretable risk expression, the Weight of Evidence transformation method was applied to features. The transformed features were discretized using the quantile binning method to design the risk scorecard, mapping the model's output to five risk levels. Results: In constructing the diabetes risk assessment model, the Random Forest classifier achieved the highest accuracy. The risk scorecard obtained an accuracy of 85.16%, precision of 87.30%, recall of 80.26%, and an F1 score of 83.27% on the unbalanced research dataset. The performance loss compared to the diabetes risk assessment model was minimal, suggesting that the binning method used for constructing the diabetes risk scorecard is reasonable, with very low feature information loss. Conclusion: The methods provided in this article demonstrate effectiveness and reliability in the assessment of diabetes risk. The assessment model and scorecard can be directly applied to community doctors for large-scale risk identification and early warning and can also be used for individual self-examination to reduce risk factor levels.

Value of carotid intima thickness in assessing advanced carotid plaque vulnerability: a study based on carotid artery ultrasonography and carotid plaque histology.

Background: Research has shown that carotid intima-media thickness (CIMT) could help to predict carotid plaque (CP) progression in patients with mild carotid stenosis. However, the debate continues as to the value of carotid intima thickness (CIT) in monitoring the development of CP in patients with severe carotid stenosis. This study sought to evaluate the relationships between CIT and the ultrasonic characteristics of CP and to analyze the value of CIT and the ultrasonic parameters of CP in assessing plaque vulnerability in advanced human carotid atherosclerosis. Methods: A total of 55 individuals who underwent carotid endarterectomy (CEA) were included in the study (mean age: 65±7 years; female: 9.1%). CIMT and CIT were examined at the common carotid artery (CCA). Plaque textural features, such as the gray-scale median (GSM), superb microvascular imaging (SMI) level, and total plaque area (TPA), were also identified. A Spearman correlation coefficient analysis was performed to examine the relationship between CIT and the ultrasonic parameters of CP. The CIT of various plaque types was compared. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic values of the ultrasound characteristics to evaluate CP vulnerability. Results: The mean CIT of all the participants was 0.382±0.095 mm, the mean CIT of the participants with stable plaques was 0.328±0.031 mm, and the mean CIT of participants with vulnerable plaques was 0.424±0.106 mm (P<0.001). CIT was associated with the SMI level (Spearman's correlation coefficient: r=0.392, P=0.005), TPA (Spearman's correlation coefficient: r=0.337, P=0.012). Patients with thicker CIT had larger lipid cores, higher levels of plaque vulnerability, and more intraplaque hemorrhages (IPHs). The areas under the ROCs (AUCs) with 95% confidence interval (CI) for CIMT, CIT, the SMI level, the GSM, the TPA, and the combined model for identifying vulnerable plaques were 0.673 (0.533-0.793), 0.849 (0.727-0.932), 0.771 (0.629-0.879), 0.669 (0.529-0.790), 0.858 (0.738-0.938), and 0.949 (0.854-0.990), respectively. Conclusions: CIT was associated with both the histology and ultrasonic features of CP. CIT may be helpful in the detection of severe CP development.

Physicochemical properties of esterified/crosslinked quinoa starches and their influence on bread quality.

BACKGROUND: Starch is the main component of quinoa seeds. However, quinoa starch has poor solubility in cold water and poor mechanical resistance and is easily aged, which limit its application. Therefore, modification of its structure to improve its functional properties is necessary. RESULTS: This research used acetic anhydride and sodium trimetaphosphate to modify the structure of starch molecules and investigated their influence on bread quality. The results showed that both esterification and crosslinking prevented the aggregation behavior of starch molecules. Moreover, they both decreased the gelatinization enthalpy change and relative crystallinity of the starch. Compared with native starch, modification significantly decreased the gelatinization temperature from 57.01 to 52.01 °C and the esterified starch exhibited the lowest enthalpy change with a 44.2% decrease. Modified starch increased the specific volume and decreased the hardness and chewiness of bread. Modification did not influence the moisture content in bread but impacted the water retention capacity, depending on the degree of modification. Low and medium degrees of modification improved the water retention capacity during storage. By contrast, a high degree of modification (10 g kg-1 crosslinking agent) decreased the water retention capacity. The dually modified quinoa starch (esterified and crosslinked) showed no influence on the textural properties of bread. CONCLUSION: This study demonstrated that both esterification and crosslinking significantly improved the functional properties of quinoa starch. Crosslinked or esterified quinoa starches have the potential to improve the textural properties of bakery products. © 2024 Society of Chemical Industry.