Mitophagy defect mediates the aging-associated hallmarks in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal disease manifested by premature aging and aging-related phenotypes, making it a disease model for aging. The cellular machinery mediating age-associated phenotypes in HGPS remains largely unknown, resulting in limited therapeutic targets for HGPS. In this study, we showed that mitophagy defects impaired mitochondrial function and contributed to cellular markers associated with aging in mesenchymal stem cells derived from HGPS patients (HGPS-MSCs). Mechanistically, we discovered that mitophagy affected the aging-associated phenotypes of HGPS-MSCs by inhibiting the STING-NF-ĸB pathway and the downstream transcription of senescence-associated secretory phenotypes (SASPs). Furthermore, by utilizing UMI-77, an effective mitophagy inducer, we showed that mitophagy induction alleviated aging-associated phenotypes in HGPS and naturally aged mice. Collectively, our results uncovered that mitophagy defects mediated the aging-associated markers in HGPS, highlighted the function of mitochondrial homeostasis in HGPS progression, and suggested mitophagy as an intervention target for HGPS and aging.

Quasi-Hyperbolic Framework Graphite Foam-Based Composites with High Thermal Conductivity and Electromagnetic Shielding Properties Fabricated by an Electrochemical Expansion Method.

Nowadays, the rapid development of electronic devices requires composites with high thermal conductivity and good electromagnetic shielding properties. The key challenge lies in the construction of high-performance conductive networks. Herein, an electrochemical expansion graphite foam (EEG) with a quasi-hyperbolic framework was prepared by an electrochemical expansion method, and then the epoxy resin (EP) was filled to fabricate the composites. The graphite plate was first electrochemically intercalated and then foamed, in which plasticization was caused by weak oxidation in intercalation and the quasi-hyperbolic framework was induced by foaming during expansion. These processes were characterized by Fourier transform infrared (FTIR), micro-Raman, X-ray photoelectron spectroscopy (XPS), and so on. Based on the highly efficient quasi-hyperbolic framework and high-quality graphite structure, the thermal conductivity of the composite reached 43.523 W/(m·K), and total electromagnetic interference (EMI) shielding (SET) reached 105 dB. The heat transfer behavior was simulated by finite element analysis (FEA) in detail. This method of preparing high thermal conductivity and electromagnetic shielding materials has a good application prospect.

Advances in ionogels for proton-exchange membranes.

To ensure the long-term performance of proton-exchange membrane fuel cells (PEMFCs), proton-exchange membranes (PEMs) have stringent requirements at high temperatures and humidities, as they may lose proton carriers. This issue poses a serious challenge to maintaining their proton conductivity and mechanical performance throughout their service life. Ionogels are ionic liquids (ILs) hybridized with another component (such as organic, inorganic, or organic-inorganic hybrid skeleton). This design is used to maintain the desirable properties of ILs (negligible vapor pressure, thermal stability, and non-flammability), as well as a high ionic conductivity and wide electrochemical stability window with low outflow. Ionogels have opened new routes for designing solid-electrolyte membranes, especially PEMs. This paper reviews recent research progress of ionogels in proton-exchange membranes, focusing on their electrochemical properties and proton transport mechanisms.

Image Recognition and Parameter Analysis of Concrete Vibration State Based on Support Vector Machine.

In this paper, the directional gradient histogram technology is employed to extract the features of concrete image samples captured under different vibration states. The support vector machine (SVM) is utilized to learn the relationship between image features and vibration state. The machine learning results are subsequently used to assess the feasibility of the concrete vibration state. Simultaneously, the influence mechanism of the calculation parameters of the directional gradient histogram on the recognition accuracy is analyzed. The results demonstrate the feasibility of using the directional gradient histogram-SVM technology to identify the vibration state of concrete. The recognition accuracy initially increases and then decreases as the block size of the directional gradient, or the number of statistical intervals increases. The recognition accuracy also decreases linearly with the increase of the binarization threshold. By using sample images with a resolution of 1024 pixels x 1024 pixels and optimizing the feature extraction parameters, a recognition accuracy of 100% can be attained.

Simultaneous deep transcriptome and proteome profiling in a single mouse oocyte.

Although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces great challenges. Here, we developed a single-cell simultaneous transcriptome and proteome (scSTAP) analysis platform based on microfluidics, high-throughput sequencing, and mass spectrometry technology to achieve deep and joint quantitative analysis of transcriptome and proteome at the single-cell level, providing an important resource for understanding the relationship between transcription and translation in cells. This platform was applied to analyze single mouse oocytes at different meiotic maturation stages, reaching an average quantification depth of 19,948 genes and 2,663 protein groups in single mouse oocytes. In particular, we analyzed the correlation of individual RNA and protein pairs, as well as the meiosis regulatory network with unprecedented depth, and identified 30 transcript-protein pairs as specific oocyte maturational signatures, which could be productive for exploring transcriptional and translational regulatory features during oocyte meiosis.

Comparison of Two Representative Methods for Differentiation of Human Induced Pluripotent Stem Cells into Mesenchymal Stromal Cells.

Mesenchymal stromal cells (MSCs) are adult pluripotent stem cells which have been widely used in regenerative medicine. As somatic tissue-derived MSCs are restricted by limited donation, quality variations, and biosafety, the past 10 years have seen a great rise in efforts to generate MSCs from human induced pluripotent stem cells (hiPSCs). Past and recent efforts in the differentiation of hiPSCs into MSCs have been centered around two culture methodologies: (1) the formation of embryoid bodies (EBs) and (2) the use of monolayer culture. This protocol describes these two representative methods in deriving MSC from hiPSCs. Each method presents its advantages and disadvantages, including time, cost, cell proliferation ability, the expression of MSC markers, and their capability of differentiation in vitro. This protocol demonstrates that both methods can derive mature and functional MSCs from hiPSCs. The monolayer method is characterized by lower cost, simpler operation, and easier osteogenic differentiation, while the EB method is characterized by lower time consumption.

Modeling feedback processes between soil detachment and sediment transport along hillslopes on the Loess Plateau of China.

A dynamic model of soil erosion along hillslopes considering soil detachment and sediment transport is still a major challenge in terms of its applicability to field conditions. Data availability for model calibration and validation is very limited for physically process models. An improved hillslope erosion dynamic model (HED) with a simple structure and strong application on field plots was established based on the sediment feedback mechanism in this study. Observed runoff and sediment data from field plots with slope gradients of 14.1 %-62.5 % and slope lengths of 7.9-64.7 m within runoff events for the Chagagou catchment on the Loess Plateau of China were used to evaluate the HED. We confirmed that the power function can reproduce the soil detachment capacity (Φ) and sediment transport capacity (Tc) under varying field slope conditions (gradients and lengths). The two parameters associated with the power function of Φ or Tc are consistent across the variable conditions. When the HED model simulates the process and event sediment discharge, the unified model parameters could be obtained. The simulation precision of above results ranged from 0.44 to 0.95 for Nash-Sutcliffe simulation efficiency (NSE), from 0.65 to 0.96 for R2 and from -32.37 % to 31.61 % for relative error (RE). The feedback term of HED was close to one as the slope length approached zero. Decreasing of sediment yield as slope length increased was quite consistent with the measured data due to the reasonable sediment feedback term. The critical slope lengths were more easily reached, and the feedback term value along the slope decreased more rapidly at steeper slopes and higher runoff events. HED can be further integrated into distributed watershed models for predicting sediment discharge within runoff events.

Effects of white matter hyperintensity on cognitive function in PD patients: a meta-analysis.

Background: Parkinson's disease (PD) is often accompanied by cognitive dysfunction, which imposes a heavy burden on patients, their families, and society. Early identification and intervention are particularly important, but reliable biomarkers for identifying PD-related cognitive impairment at an early stage are currently lacking. Although numerous clinical studies have investigated the association between brain white matter hyperintensity (WMH) and cognitive decline, the findings regarding the relationships between WMH and cognitive dysfunction in PD patients have been inconsistent. Therefore, this study aims to conduct a meta-analysis of the effect of WMH on PD cognitive function. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We systematically searched relevant literature from databases such as PubMed, Web of Science, EMBASE, CNKI, and CBM. The retrieval time was limited to database records created up until December 31, 2022. Additionally, we manually retrieved references for full-text reading. Statistical data analysis was performed using RevMan 5.3 and Stata 15.0 software. Results: This study encompassed 23 individual studies and involved 2,429 patients with PD. The group of PD with mild cognitive impairment (PD-MCI) exhibited a significantly higher overall level of WMH than the group of PD with normal cognitive function (PD-NC) (SMD = 0.37, 95% CI: 0.21-0.52, p < 0.01). This finding was consistent across subgroup analyses based on different ethnicities (Asian or Caucasian), WMH assessment methods (visual rating scale or volumetry), and age matching. In addition to the overall differences in WMH load between the PD-MCI and PD-NC groups, the study found that specific brain regions, including periventricular white matter hyperintensity (PVH) and deep white matter hyperintensity (DWMH), had significantly higher WMH load in the PD-MCI group compared to the PD-NC group. The study also conducted a meta-analysis of WMH load data for PD with dementia (PDD) and PD without dementia (PDND), revealing that the overall WMH load in the PDD group was significantly higher than that in the PDND group (SMD = 0.98, 95% CI: 0.56-1.41, p < 0.01). This finding was consistent across subgroup analyses based on different ethnicities and age matching. Moreover, regarding specific brain regions (PVH or DWMH), the study found that the PDD group had significantly higher WMH load than the PDND group (p < 0.01). Conclusion: WMH was associated with PD cognitive dysfunction. The early appearance of WMH may indicate PD with MCI.

Multiple functions of stress granules in viral infection at a glance.

Stress granules (SGs) are distinct RNA granules induced by various stresses, which are evolutionarily conserved across species. In general, SGs act as a conservative and essential self-protection mechanism during stress responses. Viruses have a long evolutionary history and viral infections can trigger a series of cellular stress responses, which may interact with SG formation. Targeting SGs is believed as one of the critical and conservative measures for viruses to tackle the inhibition of host cells. In this systematic review, we have summarized the role of SGs in viral infection and categorized their relationships into three tables, with a particular focus on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Moreover, we have outlined several kinds of drugs targeting SGs according to different pathways, most of which are potentially effective against SARS-CoV-2. We believe this review would offer a new view for the researchers and clinicians to attempt to develop more efficacious treatments for virus infection, particularly for the treatment of SARS-CoV-2 infection.

Reconstructed eight-century streamflow in the Tibetan Plateau reveals contrasting regional variability and strong nonstationarity.

Short instrumental streamflow records in the South and East Tibetan Plateau (SETP) limit understanding of the full range and long-term variability in streamflow, which could greatly impact freshwater resources for about one billion people downstream. Here we reconstruct eight centuries (1200-2012 C.E.) of annual streamflow from the Monsoon Asia Drought Atlas in five headwater regions across the SETP. We find two regional patterns, including northern (Yellow, Yangtze, and Lancang-Mekong) and southern (Nu-Salween and Yarlung Zangbo-Brahmaputra) SETP regions showing ten contrasting wet and dry periods, with a dividing line of regional moisture regimes at ~32°-33°N identified. We demonstrate strong temporal nonstationarity in streamflow variability, and reveal much greater high/low mean flow periods in terms of duration and magnitude: mostly pre-instrumental wetter conditions in the Yarlung Zangbo-Brahmaputra and drier conditions in other rivers. By contrast, the frequency of extreme flows during the instrumental periods for the Yangtze, Nu-Salween, and Yarlung Zangbo-Brahmaputra has increased by ~18% relative to the pre-instrumental periods.

Poyang and Dongting Lakes, Yangtze River: tributary lakes blocked by main-stem aggradation.

During its 6,300-km course from the Tibetan Plateau to the ocean, the Yangtze River is joined by two large lakes: Dongting Lake and Poyang Lake. We explain why these lakes exist. Deglaciation forced the ocean adjacent to the Yangtze mouth to rise ∼120 m. This forced a wave of rising water surface elevation and concomitant bed aggradation upstream. While aggradation attenuated upstream, the low bed slope of the Middle-Lower Yangtze River (∼2 × 10-5 near Wuhan) made it susceptible to sea level rise. The main stem, sourced at 5,054 m above sea level, had a substantial sediment load to "fight" against water surface level rise by means of bed aggradation. The tributaries of the Middle-Lower Yangtze have reliefs of approximately hundreds of meters, and did not have enough sediment supply to fill the tributary accommodation space created by main-stem aggradation. We show that the resulting tributary blockage likely gave rise to the lakes. We justify this using field data and numerical modeling, and derive a dimensionless number capturing the critical rate of water surface rise for blockage versus nonblockage.

Amplification of downstream flood stage due to damming of fine-grained rivers.

River dams provide many benefits, including flood control. However, due to constantly evolving channel morphology, downstream conveyance of floodwaters following dam closure is difficult to predict. Here, we test the hypothesis that the incised, enlarged channel downstream of dams provides enhanced water conveyance, using a case study from the lower Yellow River, China. We find that, although flood stage is lowered for small floods, counterintuitively, flood stage downstream of a dam can be amplified for moderate and large floods. This arises because bed incision is accompanied by sediment coarsening, which facilitates development of large dunes that increase flow resistance and reduce velocity relative to pre-dam conditions. Our findings indicate the underlying mechanism for such flood amplification may occur in >80% of fine-grained rivers, and suggest the need to reconsider flood control strategies in such rivers worldwide.

Zfp281 Inhibits the Pluripotent-to-Totipotent State Transition in Mouse Embryonic Stem Cells.

The cell-fate transition between pluripotent and totipotent states determines embryonic development and the first cell-lineage segregation. However, limited by the scarcity of totipotent embryos, regulators on this transition remain largely elusive. A novel model to study the transition has been recently established, named the 2-cell-like (2C-like) model. The 2C-like cells are rare totipotent-like cells in the mouse embryonic stem cell (mESC) culture. Pluripotent mESCs can spontaneously transit into and out of the 2C-like state. We previously dissected the transcriptional roadmap of the transition. In this study, we revealed that Zfp281 is a novel regulator for the pluripotent-to-totipotent transition in mESCs. Zfp281 is a transcriptional factor involved in the cell-fate transition. Our study shows that Zfp281 represses transcripts upregulated during the 2C-like transition via Tet1 and consequentially inhibits mESCs from transiting into the 2C-like state. Interestingly, we found that the inhibitory effect of Zfp281 on the 2C-like transition leads to an impaired 2C-like-transition ability in primed-state mESCs. Altogether, our study reveals a novel mediator for the pluripotent-to-totipotent state transition in mESCs and provides insights into the dynamic transcriptional control of the transition.

Study on the serum level of CoQ10B in patients with Moyamoya disease and its mechanism of affecting disease progression.

BACKGROUND: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD. OBJECTIVE: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients. METHODS: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level. RESULTS: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001). CONCLUSIONS: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.

SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer.

The suppressor of cytokine signaling (SOCS) family contains eight members, including SOCS1-7 and CIS, and SOCS3 has been shown to inhibit cytokine signal transduction in various signaling pathways. Although several studies have currently shown the correlations between SOCS3 and several types of cancer, no pan-cancer analysis is available to date. We used various computational tools to explore the expression and pathogenic roles of SOCS3 in several types of cancer, assessing its potential role in the pathogenesis of cancer, in tumor immune infiltration, tumor progression, immune evasion, therapeutic response, and prognostic. The results showed that SOCS3 was downregulated in most The Cancer Genome Atlas (TCGA) cancer datasets but was highly expressed in brain tumors, breast cancer, esophageal cancer, colorectal cancer, and lymphoma. High SOCS3 expression in glioblastoma multiforme (GBM) and brain lower-grade glioma (LGG) were verified through immunohistochemical experiments. GEPIA and Kaplan-Meier Plotter were used, and this bioinformatics analysis showed that high SOCS3 expression was associated with a poor prognosis in the majority of cancers, including LGG and GBM. Our analysis also indicated that SOCS3 may be involved in tumor immune evasion via immune cell infiltration or T-cell exclusion across different types of cancer. In addition, SOCS3 methylation was negatively correlated with mRNA expression levels, worse prognoses, and dysfunctional T-cell phenotypes in various types of cancer. Next, different analytical methods were used to select genes related to SOCS3 gene alterations and carcinogenic characteristics, such as STAT3, SNAI1, NFKBIA, BCL10, TK1, PGS1, BIRC5, TMC8, and AFMID, and several biological functions were identified between them. We found that SOCS3 was involved in cancer development primarily through the JAK/STAT signaling pathway and cytokine receptor activity. Furthermore, SOCS3 expression levels were associated with immunotherapy or chemotherapy for numerous types of cancer. In conclusion, this study showed that SOCS3 is an immune-oncogenic molecule that may possess value as a biomarker for diagnosis, treatment, and prognosis of several types of cancer in the future.

Study on the serum level of CoQ10B in patients with Moyamoya disease and its mechanism of affecting disease progression / Estudo sobre o nível sérico de CoQ10B em pacientes com doença de Moyamoya e seu mecanismo de afetar a progressão da doença

ABSTRACT Background: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD. Objective: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients. Methods: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level. Results: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001). Conclusions: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.

RESUMO Antecedentes: No momento, a etiologia e a patogênese da doença de Moyamoya (DMM) não são completamente claras. Os pacientes geralmente são diagnosticados após eventos cerebrovasculares. Sendo assim, é de grande importância clínica explorar os fatores preditivos de DMM. Objetivo: Este estudo teve como objetivo investigar o nível sérico de CoQ10B, a quantidade de células progenitoras endoteliais (CPE) e a função mitocondrial de CPE em pacientes com DMM. Métodos: Quarenta e um pacientes com DMM e 20 controles saudáveis foram recrutados neste estudo. Aqueles com DMM foram divididos em dois grupos: tipo isquêmico (n=23) e tipo hemorrágico (n=18). Amostras de sangue foram coletadas da veia antecubital e analisadas por CoQ10B Ensaio de Imunoadsorção Enzimática (ELISA) e citometria de fluxo. As medidas da função mitocondrial de CPE incluem taxa de consumo de oxigênio (TCO), potencial de membrana mitocondrial, concentração de Ca2+, atividade de adenosina trifosfatases (ATPase) e nível de espécies reativas de oxigênio (ROS). Resultados: O nível sérico de CoQ10B em pacientes com DMM foi significativamente menor do que em controles saudáveis (p<0,001). O número relativo de CPE em pacientes com MMD foi significativamente maior do que em controles saudáveis (p<0,001). Além disso, a TCO, o potencial de membrana mitocondrial e a atividade ATPase diminuíram e os níveis de Ca2+e ROS aumentaram em pacientes com MMD (p<0,001). Conclusões: Nossos resultados mostraram obviamente diminuição do nível sérico de CoQ10B e aumento do número de CPE em pacientes com DMM em comparação com pacientes saudáveis, e a função mitocondrial de CPE em pacientes com DMM estava anormal.

Clinical Significance and Immune Landscape of a Pyroptosis-Derived LncRNA Signature for Glioblastoma.

Introduction: Pyroptosis was recently implicated in the initiation and progression of tumors, including glioblastoma (GBM). This study aimed to explore the clinical significance of pyroptosis-related lncRNAs (PRLs) in GBM. Methods: Three independent cohorts were retrieved from the TCGA and CGGA databases. The consensus clustering and weighted gene coexpression network analysis (WGCNA) were applied to identify PRLs. The LASSO algorithm was employed to develop and validate a pyroptosis-related lncRNA signature (PRLS) in three independent cohorts. The molecular characteristics, clinical significances, tumor microenvironment, immune checkpoints profiles, and benefits of chemotherapy and immunotherapy regarding to PRLS were also explored. Results: In the WGCNA framework, a key module that highly correlated with pyroptosis was extracted for identifying PRLs. Univariate Cox analysis further revealed the associations between PRLs and overall survival. Based on the expression profiles of PRLs, the PRLS was initially developed in TCGA cohort (n = 143) and then validated in two CGGA cohorts (n = 374). Multivariate Cox analysis demonstrated that our PRLS model was an independent risk factor. More importantly, this signature displayed a stable and accurate performance in predicting prognosis at 1, 3, and 5 years, with all AUCs above 0.7. The decision curve analysis also indicated that our signature had promising clinical application. In addition, patients with high PRLS score suggested a more abundant immune infiltration, higher expression of immune checkpoint genes, and better response to immunotherapy but worse to chemotherapy. Conclusion: A novel pyroptosis-related lncRNA signature with a robust performance was constructed and validated in multiple cohorts. This signature provided new perspectives for clinical management and precise treatments of GBM.

Loss of FBXW7 Correlates with Increased IDH1 Expression in Glioma and Enhances IDH1-Mutant Cancer Cell Sensitivity to Radiation.

F-box and WD repeat domain containing 7 (FBXW7) is a substrate receptor of the ubiquitin ligase SKP1-Cullin1-F-box complex and a potent tumor suppressor that prevents unregulated cell growth and tumorigenesis. However, little is known about FBXW7-mediated control of cell metabolism and related functions in cancer therapy. Here, we report that FBXW7 expression inversely correlates with the expression levels of the key metabolic enzyme isocitrate dehydrogenase 1 (IDH1) in patients with glioma and public glioma datasets. Deletion of FBXW7 significantly increased both wild-type (WT) and mutant IDH1 expression, which was mediated by blocking degradation of sterol regulatory element binding protein 1 (SREBP1). The upregulation of neomorphic mutant IDH1 by FBXW7 deletion stimulated production of the oncometabolite 2-hydroxyglutarate at the expense of increasing pentose phosphate pathway activity and NADPH consumption, limiting the buffering ability against radiation-induced oxidative stress. In addition, FBXW7 knockout and IDH1 mutations induced nonhomologous end joining and homologous recombination defects, respectively. In vitro and in vivo, loss of FBXW7 dramatically enhanced the efficacy of radiation treatment in IDH1-mutant cancer cells. Taken together, this work identifies FBXW7 deficiency as a potential biomarker representing both DNA repair and metabolic vulnerabilities that sensitizes IDH1-mutant cancers to radiotherapy. SIGNIFICANCE: Deficiency of FBXW7 causes defects in DNA repair and disrupts NADPH homeostasis in IDH1-mutant glioma cells, conferring high sensitivity to radiotherapy.

The role of ubiquitin-specific peptidases in glioma progression.

The balance between ubiquitination and deubiquitination is crucial for protein stability, function and location under physiological conditions. Dysregulation of E1/E2/E3 ligases or deubiquitinases (DUBs) results in malfunction of the ubiquitin system and is involved in many diseases. Increasing reports have indicated that ubiquitin-specific peptidases (USPs) play a part in the progression of many kinds of cancers and could be good targets for anticancer treatment. Glioma is the most common malignant tumor in the central nervous system. Clinical treatment for high-grade glioma is unsatisfactory thus far. Multiple USPs are dysregulated in glioma and have the potential to be therapeutic targets. In this review, we collected studies on the roles of USPs in glioma progression and summarized the mechanisms of USPs in glioma tumorigenesis, malignancy and chemoradiotherapy resistance.

Diagnosis of TCM symptoms and analysis of risk factors of mild cognitive impairment in patients with type 2 diabetes mellitus.

OBJECTIVE: To explore the diagnosis of traditional Chinese medicine (TCM) syndrome and analyze the risk factors of mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM). METHODS: 141 T2DM patients, who were hospitalized in department of endocrinology of our hospital from February 2020 to December 2020, were chosen as research subjects. The patients were divided into an observation group (n=65, T2DM with MCI) and a control group (n=76, T2DM with normal cognitive function) according to the Montreal Cognitive Assessment (MoCA) score and diagnostic criteria of MCI. Pearson correlation analysis was used to study the correlation between MoCA score and influencing factors, and multiple logistic regression analyses were applied to analyze the risk factors of T2DM patients. RESULTS: Deficiency of kidney essence (34/65, 52.31%) and phlegm obstructing orifices (16/65, 2.62%) were common in T2DM patients with MCI. The observation group had apparently lower MoCA scores than the control group (23.46±3.12 points vs. 27.39±2.56 points, t=8.2150, P=0.0000). According to the results of multivariate logistic regression analysis, age, course of diabetes, homocysteine (HCY) and glycosylated hemoglobin (HbAlc) were the independent risk factors of MCI, and the education level was a protective factor. CONCLUSION: Mental deficiency and phlegm obstruction are common in T2DM patients complicated with MCI. The factors such as age, diabetes course, education degree, HCY and HbAlc are closely related to MCI. The occurrence of MCI in T2DM patients can be prevented by improving the education degree of patients, effective control of blood glucose and reduction of HCY level.