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1.
Neural Regen Res ; 18(2): 244-252, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900398

RESUMO

Subarachnoid hemorrhage (SAH) is a dominant cause of death and disability worldwide. A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neurons, which subsequently promotes a series of pathophysiological responses leading to neuronal death. Many previous experimental studies have reported that excitotoxicity, mitochondrial death pathways, the release of free radicals, protein misfolding, apoptosis, necrosis, autophagy, and inflammation are involved solely or in combination in this disorder. Among them, irreversible neuronal apoptosis plays a key role in both short- and long-term prognoses after SAH. Neuronal apoptosis occurs through multiple pathways including extrinsic, mitochondrial, endoplasmic reticulum, p53 and oxidative stress. Meanwhile, a large number of blood contents enter the subarachnoid space after SAH, and the secondary metabolites, including oxygenated hemoglobin and heme, further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema, causing early brain injury and delayed cerebral ischemia, and ultimately increasing neuronal apoptosis. Even there is no clear and effective therapeutic strategy for SAH thus far, but by understanding apoptosis, we might excavate new ideas and approaches, as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH. In this review, we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH, which provides a possible target or new strategy for the treatment of SAH.

2.
J Environ Sci (China) ; 124: 350-359, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182144

RESUMO

Sulfite (SO32-) activation is one of the most potential sulfate-radical-based advanced oxidation processes, and the catalysts with high efficiency and low-cost are greatly desired. In this study, the cobalt nanoparticles embedded in nitrogen-doped graphite layers (Co@NC), were used to activate SO32- for removal of Methyl Orange in aqueous solution. The Co@NC catalysts were synthesized via pyrolysis of Co2+-based metal-organic framework (Co-MOF), where CoO was firstly formed at 400℃ and then partially reduced to Co nanoparticles embedded in carbon layers at 800℃. The Co@NC catalysts were more active than other cobalt-based catalysts such as Co2+, Co3O4 and CoFe2O4, due to the synergistic effect of metallic Co and CoxOy. A series of chain reaction between Co species and dissolved oxygen was established, with the production and transformation of SO3•-, SO52-, and subsequent active radicals SO4•- and HO•. In addition, HCO3- was found to play a key role in the reaction by complexing with Co species on the surface of the catalysts. The results provide a new promising strategy by using the Co@NC catalyst for SO32- oxidation to promote organic pollutants degradation.


Assuntos
Poluentes Ambientais , Grafite , Estruturas Metalorgânicas , Nanopartículas , Carbono , Cobalto , Nitrogênio , Óxidos , Oxigênio , Sulfatos , Sulfitos
3.
Neural Regen Res ; 18(5): 1090-1098, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36254998

RESUMO

Neural progenitor cells (NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox (VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR (0.5 mM valproic acid, 3 µM CHIR99021, and 1 µM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition (5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6 (Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs (ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson's disease.

4.
J Hazard Mater ; 443(Pt B): 130289, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36345059

RESUMO

Ultrasensitive real-time detection of trace Pb2+ in continuous flow is vital to effectively and timely eliminate the potential hazards to ecosystem health and sustainability. This work reports on a micro-structured smart hydrogel grating with ultra-sensitivity, high selectivity, good transparency and mechanical property for real-time detection of Pb2+ in continuous flow. The hydrogel grating possesses uniform surface relief microstructures with periodic nano-height ridges made of poly(acrylamide-co-benzo-18-crown-6-acrylamide) networks that crosslinked by tetra-arm star poly(ethylene glycol)acrylamide. The hydrogel grating with good optical transparency and mechanical property can change its height via selective host-guest complexation with Pb2+ to output a changed diffraction efficiency. Meanwhile, the periodic nano-ridges with large specific area benefit the contact with Pb2+ for fast Pb2+-induced height change. Thus, with such rationally designed molecular structures and surface relief microstructures, the hydrogel grating integrated in a glass-based mini-chip allows real-time detection of Pb2+ in continuous flow with ultra-sensitivity and high selectivity. The hydrogel grating detector can achieve ultralow detection limit (10-9 M Pb2+), fast response (2 min), and selective detection of Pb2+ from dozens of interfering ions even with high concentrations. This high-performance hydrogel grating detector is general and can be extended to detect many analytes due to the wide choice of responsive hydrogels, thus opening new areas for creating advanced smart detectors in analytical science.


Assuntos
Hidrogéis , Chumbo , Hidrogéis/química , Ecossistema , Íons/química , Acrilamida
5.
Int J Cancer ; 152(1): 90-99, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36111424

RESUMO

Clinically effective methods to predict the efficacy of sunitinib, for patients with metastatic or locally advanced pancreatic neuroendocrine tumors (panNET) are scarce, making precision treatment difficult. This study aimed to develop and validate a computed tomography (CT)-based method to predict the efficacy of sunitinib in patients with panNET. Pretreatment CT images of 171 lesions from 38 patients with panNET were included. CT value ratio (CT value of tumor/CT value of abdominal aorta from the same patient) and radiomics features were extracted for model development. Receiver operating curve (ROC) with area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the proposed model. Tumor shrinkage of >10% at first follow-up after sunitinib treatment was significantly associated with longer progression-free survival (PFS; P < .001) and was used as the major treatment outcome. The CT value ratio could predict tumor shrinkage with AUC of 0.759 (95% confidence interval [CI], 0.685-0.833). We then developed a radiomics signature, which showed significantly higher AUC in training (0.915; 95% CI, 0.866-0.964) and validation (0.770; 95% CI, 0.584-0.956) sets than CT value ratio. DCA also confirmed the clinical utility of the model. Subgroup analysis showed that this radiomics signature had a high accuracy in predicting tumor shrinkage both for primary and metastatic tumors, and for treatment-naive and pretreated tumors. Survival analysis showed that radiomics signature correlated with PFS (P = .020). The proposed radiomics-based model accurately predicted tumor shrinkage and PFS in patients with panNET receiving sunitinib and may help select patients suitable for sunitinib treatment.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Sunitinibe/uso terapêutico , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia
6.
Sci Total Environ ; 857(Pt 3): 159675, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36280051

RESUMO

The sustainability of estuarine ecosystem functions depends on the stabilization of microbial ecological processes. However, due to the unique and variable habitat characteristics of estuarine areas, in-depth studies on ecological processes such as the spatial distribution and assembly patterns of microbial community structure are lacking. As methods to elucidate this structure, we used 16S rDNA, 18S rDNA and ITS sequencing technologies to study the composition, diversity, spatial pattern and aggregation mechanism of the bacterial, protist and fungal communities in the tidal zones of the Pearl River Estuary (PRETZ). The abundance of bacterial communities was much higher than that of protists and fungi, and the spatial pattern was obvious in PRETZ. The application of neutral and null models revealed the assembly process of three microbial communities dominated by stochastic processes. Among the stochastic processes, undominated processes (64.03 %, 62.45 %, and 59.29 %) were the most critical processes in the assembly of bacterial, fungal and protist communities. Meanwhile, environmental variables, geographic locations, and biological factors were associated with the composition and assembly of bacterial, protist, and fungal communities. Among the environmental variables, dissolved oxygen and salinity were the main predictors that jointly affected the differences in the community structure of the three microorganisms, and geographic location was the second predictor affecting the community structure of the three microorganisms and had a more pronounced effect on the diversity and network structure of the bacterial and fungal communities. However, biological factors exerted a weaker effect on the microbial community structure than spatial factors and only affected bacteria and protists; the invasive species Mytilopsis sallei only affected the process of protist community assembly. In addition, environmental variables affected the relative importance of stochastic processes. In summary, the formation of microbial communities in the PRETZ was affected by random processes, environmental variables, geographic location, and invasive species.


Assuntos
Bivalves , Microbiota , Animais , Estuários , Rios , Bactérias , Bivalves/genética , Eucariotos , Espécies Introduzidas , DNA Ribossômico , Fatores Biológicos
7.
Transl Pediatr ; 11(10): 1615-1623, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36345448

RESUMO

Background: Genetic epilepsy with febrile seizures plus (GEFS+) is a type of epileptic syndrome closely related to heredity factors, which can be caused by gene mutations. However, it still remains unclear how these mutations result in seizures. Previously, we identified a new heterozygous missense mutation of the KCNAB3 gene, H258R, in the GEFS+ family; the electric currents of the human embryonic kidney 293 (HEK293) cells co-expressing Kvß3 (H258R) and Kv1.1 showed obvious inactivation. This study sought to examine the effects of this mutation on the potassium channels in the mammalian brain. Methods: Mutant mice were generated by introducing the human H258R missense mutation within exon 10 at an equivalent position in the mouse KCNAB3 gene via CRISPR/Cas9 and homologous recombination. A patch clamp was used to detect the potassium currents in the pyramidal cells of the hippocampal CA1 region of the mutant mice. The total potassium currents of the pyramidal cells in the hippocampal CA1 region of KCNAB3 [wild-type (WT)] and KCNAB3 (H258R) adult mice were recorded with increased voltage. Results: We found a decreased total potassium current in the H258R group but no significant differences at a maximum voltage (+80 mV; P>0.05). Conclusions: These results suggest that the KCNAB3 mutation reduced hippocampal potassium currents in this mouse model.

8.
JTO Clin Res Rep ; 3(12): 100416, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36426287

RESUMO

Introduction: Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC. Methods: This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)-resistant NSCLC, with crossover permitted on disease progression. The primary end point was the objective response rate, and the secondary end points included progression-free survival, overall survival, and safety of ICI after EGFR TKI. Results: Recruitment ceased owing to futility after 31 of 184 planned patients were treated. A total of 15 patients received N and 16 received NI combination. There were 16 patients (51.6%) who had programmed death-ligand (PDL1) 1 greater than or equal to 1%, and 15 (45.2%) harbored EGFR T790M. Five patients derived clinical benefits from ICI with one objective response (objective response rate 3.2%), and median progression-free survival was 1.22 months (95% confidence interval: 1.15-1.35) for the overall cohort. None of the four patients who crossed over achieved salvage response by NI. PDL1 and tumor mutational burden (TMB) were not able to predict ICI response. Rates of all grade immune-related adverse events were similar (80% versus 75%), with only two grade 3 events. Conclusions: Immune checkpoint inhibition is ineffective in EGFR TKI-resistant NSCLC. Whereas a small subgroup of EGFR-mutant NSCLC may be immunogenic and responsive to ICI, better biomarkers are needed to select appropriate patients.

9.
J Pain Res ; 15: 3509-3521, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36394058

RESUMO

Purpose: To evaluate the efficacy of different non-pharmacologic therapies (NPTs) on relieving depressive symptoms and pain intensity in individuals living with chronic low back pain (LBP) and associated depression. Methods: A comprehensive search of seven English databases and two Chinese databases from inception to the search date will be undertaken. The reference lists of previously published relevant reviews and included trials will also be searched. Only peer-reviewed and published moderate-to-high quality randomized controlled trials (RCTs) for chronic LBP and associated depression treated with NPTs will be considered. Two independent reviewers will identify studies, extract data, assess risk of bias, and evaluate the strength of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis will be conducted to estimate the treatment effect of various NPTs. Heterogeneity will be assessed using Cochrane's Q and the I-squared statistics. Subgroup and sensitivity analyses will be performed to assess the robustness of findings. A funnel plot will be developed to evaluate reporting bias, and Begg's and Egger's tests will be used to assess funnel plot symmetries. Results: This protocol outlines the planned scope and methodology for an upcoming systematic review and meta-analysis, which will provide up-to-date evidence on 1) which NPTs are associated with improvements in depressive symptoms and pain intensity and 2) whether the effects of NPTs on chronic LBP and associated depression vary according to clinical condition, participant, and treatment characteristics. Conclusion: Our meta-analyses of moderate-to-high quality RCTs will help to develop specific recommendations on prescribing NPTs in patients with chronic LBP and associated depression. Study Registration: This protocol is registered on the International Platform of Registered Systematic Review and Meta-analysis (INPLASY) protocols platform as record No. INPLASY202260055.

10.
Inorg Chem ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36417706

RESUMO

Three polyoxometalate-based metal-organic frameworks were synthesized by the thermal reaction of pyridyl-Anderson polyoxometalate linker and lanthanide ions. With the help of [Ru(bpy)3]2+ photosensitizer, these frameworks exhibited excellent photocatalytic sulfide oxidation performance with sulfoxide selectivity. The reactive oxygen species as well as the photooxidation mechanism were also explored.

11.
Anal Chem ; 94(46): 16237-16245, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36346897

RESUMO

Herein, an innovative fluorescent sensor was courageously empoldered for precise and ultrasensitive detection and imaging of target miRNA-21 through the agency of a dextrous target-motivated polymerization/nicking DNA nanomachineries based on a hyperbranched rolling circle amplification (HB-RCA)-assisted multiposition strand displacement reaction (SDR) signal amplification approach. Impressively, the ingenious technique not only realized target recycling via polymerization/nicking DNA nanomachineries but also involved HB-RCA amplification induced by the released transformation target as the repeated signal amplification. Most importantly, HB-RCA was firstly exploited to remarkably increase the local concentration and collision efficiency of the templates and primers, which could simultaneously generate multiple repeated DNA sequences as initiators to supply substantial banding positions for SDR, removing the massive fluorescence-resonance-energy-transfer (FRET) DNA duplexes from the repeated DNA sequences to remarkably avert the self-quenching of the fluorescence signal due to self-aggregation caused by the winding of the HB-RCA products, thereby leading to a conspicuously improved signal amplification multiplier. As proof of concept, an ingenious technique effectively and accurately distinguished target miRNA-21 even with a tiny change in cells compared to the conventional fluorescence in situ hybridization (FISH) approach. Moreover, the proposed fluorescent method apparently discriminated drug-manipulative miRNA expression level abnormities. Therefore, the proposed cascade nucleic acid amplification strategy could provide an epigamic avenue for ultrasensitive imaging of diverse biomarkers, which help researchers to better study the tumor mechanism, thereby unambiguously increasing cancer cure rates and reducing the risk of recurrence.


Assuntos
Técnicas Biossensoriais , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Hibridização in Situ Fluorescente , Técnicas de Amplificação de Ácido Nucleico/métodos , DNA/genética , Espectrometria de Fluorescência/métodos , Limite de Detecção , Técnicas Biossensoriais/métodos
12.
Comput Math Methods Med ; 2022: 2974126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388159

RESUMO

Background: Hypoxia was considered to be a prognostic indicator in a variety of solid tumors. This study aims at identifying the hypoxia-related genes (HRGs) in breast cancer (BC) and the feasibility of HRGs as a prognostic indicator. Methods: We downloaded the mRNA expression data of BC patients from TCGA and GEO databases. The LASSO Cox regression analysis was applied to screen the hub HRGs to establish a prognostic Risk Score. The independence of Risk Score was assessed by multivariate Cox regression analysis. And the immune checkpoint analysis was also performed. In addition, we also detected the expression level of hub HRGs in MCF-10A cells, MCF-7 cells, and SK-BR-3 cells by RT-qPCR. Results: Three HRGs were identified as hub genes with prognostic value in BC, including CA9, PGK1, and SDC1. The Risk Score constructed by these three genes could efficiently distinguish the prognosis of different BC patients and has been shown to be an independent prognostic indicator. In the high-risk group, patients had lower overall survival and poorer prognosis. In addition, the expression levels of five immune checkpoints (PD1, CTLA4, TIGIT, LAG3, and TIM3) in the high-risk group were significantly higher than those in the low-risk group. Moreover, the expression levels of PGK1 and SDC1 in BC cells were significantly increased. Conclusion: In this study, we established an efficiently model based on three optimal HRGs (CA9, PGK1, and SDC1) could clearly distinguish the prognosis of different BC patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Prognóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Perfilação da Expressão Gênica , Hipóxia/genética
13.
J Am Heart Assoc ; 11(22): e027578, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36346048

RESUMO

Background Dilated cardiomyopathy (DCM), characterized by progressive left ventricular enlargement and systolic dysfunction, is the most common type of cardiomyopathy and a leading cause of heart failure and cardiac death. Accumulating evidence underscores the critical role of genetic defects in the pathogenesis of DCM, and >250 genes have been implicated in DCM to date. However, DCM is of substantial genetic heterogeneity, and the genetic basis underpinning DCM remains elusive in most cases. Methods and Results By genome-wide scan with microsatellite markers and genetic linkage analysis in a 4-generation family inflicted with autosomal-dominant DCM, a new locus for DCM was mapped on chromosome 15q13.1-q13.3, a 4.77-cM (≈3.43 Mbp) interval between markers D15S1019 and D15S1010, with the largest 2-point logarithm of odds score of 5.1175 for the marker D15S165 at recombination fraction (θ)=0.00. Whole-exome sequencing analyses revealed that within the mapping chromosomal region, only the mutation in the KLF13 gene, c.430G>T (p.E144X), cosegregated with DCM in the family. In addition, sequencing analyses of KLF13 in another cohort of 266 unrelated patients with DCM and their available family members unveiled 2 new mutations, c.580G>T (p.E194X) and c.595T>C (p.C199R), which cosegregated with DCM in 2 families, respectively. The 3 mutations were absent from 418 healthy subjects. Functional assays demonstrated that the 3 mutants had no transactivation on the target genes ACTC1 and MYH7 (2 genes causally linked to DCM), alone or together with GATA4 (another gene contributing to DCM), and a diminished ability to bind the promoters of ACTC1 and MYH7. Add, the E144X-mutant KLF13 showed a defect in intracellular distribution. Conclusions This investigation indicates KLF13 as a new gene predisposing to DCM, which adds novel insight to the molecular pathogenesis underlying DCM, implying potential implications for prenatal prevention and precision treatment of DCM in a subset of patients.


Assuntos
Cardiomiopatia Dilatada , Humanos , Cardiomiopatia Dilatada/metabolismo , Mutação , Linhagem , Proteínas Repressoras/genética , Proteínas de Ciclo Celular/genética , Fatores de Transcrição Kruppel-Like/genética
14.
Nat Commun ; 13(1): 6951, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376293

RESUMO

Immune checkpoint blockade therapies targeting the PD-L1/PD-1 axis have demonstrated clear clinical benefits. Improved understanding of the underlying regulatory mechanisms might contribute new insights into immunotherapy. Here, we identify transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) as a modulator of PD-L1 post-translational modifications in tumor cells. Mechanistically, TMUB1 competes with HECT, UBA and WWE domain-containing protein 1 (HUWE1), a E3 ubiquitin ligase, to interact with PD-L1 and inhibit its polyubiquitination at K281 in the endoplasmic reticulum. Moreover, TMUB1 enhances PD-L1 N-glycosylation and stability by recruiting STT3A, thereby promoting PD-L1 maturation and tumor immune evasion. TMUB1 protein levels correlate with PD-L1 expression in human tumor tissue, with high expression being associated with poor patient survival rates. A synthetic peptide engineered to compete with TMUB1 significantly promotes antitumor immunity and suppresses tumor growth in mice. These findings identify TMUB1 as a promising immunotherapeutic target.


Assuntos
Antígeno B7-H1 , Neoplasias , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Glicosilação , Imunoterapia , Neoplasias/genética , Neoplasias/terapia , Evasão Tumoral , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
15.
Pathol Res Pract ; 240: 154187, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36327821

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor. It has a poor 5-year survival rate, a high recurrence rate, and few therapeutic options. Exploring the molecular processes underlying the formation and progression of GBM, as well as identifying novel therapeutic targets, is critical for improving GBM therapy and prognosis. METHODS: We extracted primary GSCs (glioblastoma stem cells) from patient-derived samples. Different levels of CSNK1D were evaluated through immunohistochemistry, western blot and real-time PCR assays. A Transwell assay was used to detect invasive ability of cell lines. Tumorsphere formation assay was performed to detect cancer stemness properties. Orthotopic xenograft models were used to evaluate the effect of CSNK1D on GSC tumorigenesis. RESULTS: We found the expression levels of CSNK1D was elevated in GBM tissues compared with normal brain. CSNK1D expression had an increased tendency among WHO grades (G2-G4), and was higher in IDH wildtype group than in mutation group. The prognosis of the CSNK1D high expression group was significantly worse than that of the low expression group. Cox multivariate analysis showed that CSNK1D was also an independent prognostic factor in GBM patients. In primary GBM cells, we observed increased levels of CSNK1D in GSCs compared to non-stem tumor cells (NSTCs). In addition, the change of stemness markers expression and proliferation of GSCs were in coordinate with CSNK1D overexpression or knockdown. Furthermore, CSNK1D could affect the epithelial-mesenchymal transition (EMT) markers and MMPs expression in GSCs. Finally, disruption of CSNK1D expression impairs GSC survival and GBM tumor propagation in orthotopic xenograft models. CONCLUSION: Our results suggest that CSNK1D correlated with GBM prognosis and might influence the stemness and invasiveness of GSCs, which represented a potential therapeutic target in GBM patients.

16.
Pathol Res Pract ; 240: 154235, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36434856

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a special kind of breast cancer with strong ability of invasion and metastasis. UCHL1 belongs to the ubiquitin carboxy-terminal hydrolase family and is found to be increased in a variety of malignancies, but its expression in TNBC is unknown. METHODS: First, we analyzed the expression of UCHL1 in 128 TNBC specimens and paired adjacent normal tissues from 17 TNBC patients undergoing curative resection by immunohistochemistry. Then, the relationship between UCHL1 and cancer stemness was investigated by cell flow cytometry, spheroid formation assays and western blot. Moreover, cell scratch assay and Transwell assays were performed to explore whether UCHL1 promotes the migration and invasion of TNBC cells. Finally, we constructed a xenografts model of TNBC cell lines to observe the effect of UCHL1 on tumorigenesis in vivo. RESULTS: UCHL1 was overexpressed in TNBC tissues and associated with poor prognosis. UCHL1 promoted stem cancer cells properties, including the percentage of CD44+/CD24- cells, sphere-forming ability and CSCs related markers. Furthermore, Scratch assay and Transwell assay proved that UCHL1 enhanced the migration and invasion of TNBC cells. The experimental results of xenografts model in nude mice showed that UCHL1 promoted tumorigenesis of TNBC in vivo. CONCLUSION: UCHL1 may play a role in the malignant progression of TNBC by maintaining the stemness and promoting cell invasion and is expected to become a potential therapeutic target for TNBC patients.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36440597

RESUMO

The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid-electrolyte interface (SEI) growth would deteriorate its stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.

18.
Water Res ; 227: 119319, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368087

RESUMO

Functionalized antibiofouling membranes have attracted increasing attention in water and wastewater treatment. Among them, contact-killing antibiofouling membranes deliver a long-lasting effect with no leaching or release, thus providing distinctive advantages. However, the antibiofouling mechanism especially in the vicinity of the membrane surface remains unclear. Herein, we demonstrate that mazEF-mediated programmed cell death (PCD) is critical for the antibiofouling behaviors of quaternary ammonium compounds modified membranes (QM). The viability of wild type Escherichia coli (WT E. coli) upon exposure to QM for 1 h was decreased dramatically (31.5 ± 1.4% of the control). In contrast, the bacterial activity of E. coli with the knockout of mazEF gene (KO E. coli) largely remained (85.8 ± 5.2%). Through addition of quorum sensing factor, i.e., extracellular death factor (EDF), the antibacterial activity was significantly enhanced in a dilute culture, indicating that the density-dependent bacterial communication played an important role in the mazEF-mediated PCD system in biofouling control. Long-term study further showed that QM exhibited a better antibiofouling performance to treat feedwater containing WT E. coli, especially when EDF was dosed. Results of this study suggested that the bacteria on the membrane surface subject to contact killing could modulate the population growth in the vicinity via quorum-sensing mazEF-mediated PCD, paving a way to develop efficient antibiofouling materials based on contact-killing scenarios.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Compostos de Amônio Quaternário/farmacologia , Proteínas de Escherichia coli/genética , Percepção de Quorum , Apoptose , Membranas Artificiais
19.
Int J Med Robot ; : e2480, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396620

RESUMO

BACKGROUND: The single port surgical robot causes only one incision and brings many benefits to patients. It is very challenging to design a single port surgical robot that causes a smaller incision than current products. METHODS: This paper presents a highly compact single port laparoscopy surgical robot, which makes full use of the space of the port and only needs a 15 mm-diameter port. The robot is composed of a camera manipulator and two operating manipulators. The non-fully cylindrical manipulators enter the port sequentially, and the equivalent diameter of each operating manipulator is 12 mm. An additional 9 mm-diameter channel is left for other surgical tools to pass through after all manipulators entering the port. RESULTS: The kinematics model of the robot is established, including detailed forward kinematics model and inverse kinematics solution based on geometric iteration method. The teleoperation experiment shows that the manipulator can complete the object-grasping, object-transfer and weight-lifting tasks. CONCLUSIONS: The proposed single port surgical robot design concept can also be extended to the field of natural orifice transluminal endoscopic surgical robots.

20.
Zool Stud ; 61: e20, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330024

RESUMO

This study presents a new species of free-living marine nematode, Ptycholaimellus luoyang sp. nov., from mangrove wetlands in China. The identification was confirmed by analyzing morphological characteristics and three genes: COI, 18S rDNA, and 28S rDNA. This species is distinguished from allied species by its short cephalic setae, cylindrical pharynx with anterior swelling, sclerotized transverse ridges occurring near the dorsal tooth, rod-like gubernaculum and proximal, arch-like, slightly waved, middle curved, and distally pointed spicules. The Bayesian topology was regarded as morphological evidence of P. luoyang sp. nov. being a distinct species. Interspecific and intrageneric thresholds of the K2P distance divergence have been presented here for the first time.

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