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1.
Environ Pollut ; 292(Pt B): 118455, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742817

RESUMO

Facing the challenge of global microplastics (MPs) pollution, full characterization of MPs biohazards is urgent. Recent intensive studies revealed that the toxicity depends on the material, size, and exposure concentration of MP. To better elucidate MPs biohazards, we investigated the impact of polystyrene-MPs of size 0.1 µm at a low dose of 50 µg/L on the neuromuscular, retinal, and reproductive phenotypes of fruit fly model, by voltage-clamped electrophysiology, electroretinogram, and reproductive assay, respectively. We found that MPs decreased the frequency of spontaneous junction currents of synapse and altered the receptor potential amplitude of the retina. Furthermore, MPs lowered the rate of embryo-laying of fruit flies. The differential gene expression of ligand-receptor interaction, endocytosis, phototransduction, and Toll/Imd signaling pathways might underlie these MPs-induced phenotypes. These findings call for further investigation on the potential biohazards of low-dose MPs.


Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Drosophila , Plásticos , Poliestirenos , Retina/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
2.
J Hazard Mater ; 423(Pt A): 127069, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482085

RESUMO

Frequent leaks of hazardous chemicals have a huge impact on human lives, property and the ecological environment. Therefore, the three-dimensional functional porous materials with high absorption efficiency and special wettability for the disposal of hazardous chemical spills is an urgent demand. In this work, a series of spherical beads consisting of partially reduced graphene oxide (prGO) and MXene (Ti3C2Tx) nanosheets were constructed by hydrogen bond induced self-assembly along with freeze-drying and thermal treatment. The lightweight and amphipathic prGO/MXene spherical beads (prGMSBDs) had millimeter-level size, spherical morphology and highly porous internal structure, which were especially suitable for eliminating hazardous chemicals. Because of their excellent thermal stability and fire retardance, the prGMSBDs could be used to absorb flammable organic liquids, reducing the fire risk of the flammable hazardous chemical spills. Indeed, the prGMSBDs exhibited outstanding absorption performances for various hazardous chemicals, including organic solvents and water-based concentrated acid and alkali. Moreover, the prGMSBDs showed relatively stable absorption performance after five absorption-drying cycles. Due to meeting the requirements of both amphipathic characteristic and flame retardancy, the prGMSBDs reported in this work may offer a promising strategy for rapidly cleaning up various hazardous chemicals and open a feasible route to protecting the combustible hazardous chemical spills from fire.

3.
J Colloid Interface Sci ; 607(Pt 2): 1919-1927, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34695740

RESUMO

Schottky-contacted nanosensors have attracted extensive attention due to their high sensitivity and fast response time. In this article, we proved that the construction of Schottky contact by Pt nanoparticles (NPs) decoration can effectively improve the performance of V2O5 nanobelts photodetectors. After modified by Pt NPs, the photocurrent of V2O5 nanobelts is increased by more than two orders of magnitude, and the photoresponse speed is improved by at least three orders of magnitude. Detailed studies have shown that the performance enhancement is attributed to the formation of the Schottky contact at the electrode-semiconductor interface due to the decrease of surface gas adsorption and the increase of V2O5 work function after Pt NPs modification. The strong built-in field in the Schottky barrier region will quickly separate photogenerated carriers, thereby reducing the electron-hole recombination rate, resulting in the fast response time and an increase in the free carrier density. Moreover, it is found that this enhancement effect can be regulated by controlling the pressure to modulating the Schottky barrier height at the interface. Overall, the Pt NPs-modified V2O5 nanobelts photodetector exhibits a broad response spectrum (visible to near infrared), fast rise/fall response time (less than 6.12/6.15 ms), high responsivity (5.6 A/W), and high specific detectivity (6.9 × 108 Jones). This study demonstrates the feasibility of building a Schottky barrier to enhance the photodetection performance, which provides a general and effective strategy towards the construction and its practical application of supersensitive and fast-response nanosensors.

4.
Ann Rheum Dis ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853001

RESUMO

OBJECTIVES: Dysregulated chondrocyte metabolism is closely associated with the pathogenesis of osteoarthritis (OA). Suppressing chondrocyte catabolism to restore cartilage homeostasis has been extensively explored, whereas far less effort has been invested toward enhancing chondrocyte anabolism. This study aimed to repurpose clinically approved drugs as potential stimulators of chondrocyte anabolism in treating OA. METHODS: Screening of a Food and Drug Administration-approved drug library; Assays for examining the chondroprotective effects of digoxin in vitro; Assays for defining the therapeutic effects of digoxin using a surgically-induced OA model; A propensity-score matched cohort study using The Health Improvement Network to examine the relationship between digoxin use and the risk of joint OA-associated replacement among patients with atrial fibrillation; identification and characterisation of the binding of digoxin to low-density lipoprotein receptor-related protein 4 (LRP4); various assays, including use of CRISPR-Cas9 genome editing to delete LRP4 in human chondrocytes, for examining the dependence on LRP4 of digoxin regulation of chondrocytes. RESULTS: Serial screenings led to the identification of ouabain and digoxin as stimulators of chondrocyte differentiation and anabolism. Ouabain and digoxin protected against OA and relieved OA-associated pain. The cohort study of 56 794 patients revealed that digoxin use was associated with reduced risk of OA-associated joint replacement. LRP4 was isolated as a novel target of digoxin, and deletion of LRP4 abolished digoxin's regulations of chondrocytes. CONCLUSIONS: These findings not only provide new insights into the understanding of digoxin's chondroprotective action and underlying mechanisms, but also present new evidence for repurposing digoxin for OA.

5.
Environ Technol ; : 1-11, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34727838

RESUMO

Spent petroleum catalyst (SPC) is a highly toxic material since it contains heavy metals and hazardous substances. A novel recycling technology based on the cooperative smelting-vitrification process by using coal fly ash (CFA) as a fluxing material was proposed. The benefits of employing CFA in this cooperative smelting-vitrification process of SPC have been demonstrated via the results of lab-scale and scale-up experiments. The experimental results indicated that with a collector iron (Fe) addition of 26 wt%, a C/O molar ration of 1.4, and an H3BO3 addition of 14 wt%, the maximum nickel (Ni) recovery was ∼98% by controlling the CFA addition of 40-50 wt%, basicity of 0.4-0.5, smelting temperature of 1550°C, and smelting time of 60 min, respectively. In this process, a ferronickel (Ni-Fe) alloy with a high Ni grade of 10 wt% was successfully obtained, which could be directly further produced stainless steel. Meanwhile, a glass slag with a low Ni content (below 0.12 wt%) was also obtained, and its leaching characteristics further confirmed it is a non-hazardous slag because heavy metals were successfully encapsulated in glass slag, and thereby, this proposed method achieved the transformation from hazardous solid waste to general solid waste. The results of the 10 kg scale-up experiment indicated the possibility of industrialization of this new technology. Therefore, the process proposed in this study is a practical and promising process for Ni recovery from SPC and reutilization of CFA.

6.
Mol Immunol ; 140: 196-205, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34735868

RESUMO

BACKGROUND: Gastric cancer (GC) derived exosomes (Exos) aggravate GC development by facilitating M2 macrophage polarization and long non-coding RNA (lncRNA) HCG18 was highly expressed in GC. This study aimed to investigate whether the exosomal lncRNA HCG18 regulated the M2 macrophage polarization in GC and the possible mechanism. METHODS: The isolated GC cells (GCCs)-Exos were identified using transmission electron microscopy, Nanoparticle Tracking Analysis and Western blot. The GCCs-Exos function was verified by enzyme-linked immunosorbent assay and flow cytometry. Meanwhile, the exosomal lncRNA HCG18 function was determined using thein vitro assays. Furthermore, the underlying mechanism of the exosomal lncRNA HCG18 that regulated M2 macrophage polarization in GC was investigated using dual-luciferase reporter gene assay and RNA pull-down. RESULTS: After the validation of GCCs-Exos, the GCCs-Exos facilitated the M2 macrophage polarization. The in vitro assays confirmed that the exosomal lncRNA HCG18 positively regulated the M2 macrophage polarization. Mechanistically, lncRNA HCG18 bound to miR-875-3p, miR-875-3p bound to KLF4. Furthermore, GCCs-exosomal lncRNA HCG18 elevated the KLF4 expression by decreasing miR-875-3p in macrophages to facilitate M2 macrophage polarization, thus alleviating GC. The in vivo assays clarified that the GCCs-exosomal lncRNA HCG18 restrained the tumor growth of GC induced by M2 macrophages. CONCLUSION: GCCs-exosomal lncRNA HCG18 elevated KLF4 expression by decreasing miR-875-3p in macrophages to facilitate the M2 macrophage polarization.

7.
Sci Rep ; 11(1): 22966, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824364

RESUMO

High tumor regulatory T (Treg) cell infiltration is associated with poor prognosis of many cancers. CD25 is highly expressed on tumor Treg cells and is a potential target for Treg deletion. Previously characterized anti-CD25 antibodies appear to have limited efficacy in tumor inhibition. Here we identified two human anti-CD25 antibodies, BA9 and BT942, which did not prevent the activation of IL-2R signaling pathway by IL-2. BT942 had weaker binding and cytotoxic activity to human CD25-expressing cell lines than BA9. But both demonstrated significant tumor growth inhibition in early and late-stage animal cancer models. BT942 resulted in a higher expansion of CD8+ T cells and CD4+ T cells in tumor microenvironment in mouse MC38 model compared to BA9. BT942 also demonstrated significant higher tumor growth inhibition and higher expansion of CD8+ T cells and CD4+ T cells in combination with an anti-PD1 antibody. Pharmacokinetic study of BT942 in cynomolgus monkeys demonstrated a half-life of 206.97 ± 19.03 h. Structural analysis by cryo-EM revealed that BT942 recognizes an epitope on opposite side of the CD25-IL-2 binding site, consistent with no IL-2 signaling blockade in vitro. BT942 appears to be an excellent candidate for cancer immunotherapy.

8.
Biomolecules ; 11(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34827557

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all Pinteraction: <0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06-2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34739560

RESUMO

Immune checkpoint inhibitors (ICIs) for programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have become preferred treatment strategies for several advanced cancers. However, response rates for these treatments are limited, which encourages the search for new ICI candidates. Recent reports have underscored significant roles of B7 homolog 3 protein (B7-H3) in tumor immunity and disease progression. While its multifaceted roles are being elucidated, B7-H3 has already entered clinical trials as a therapeutic target. In this review, we overview the recent results of clinical trials evaluating the antitumor activity and safety of B7-H3 targeting drugs. On this basis, we also discuss the challenges and opportunities arising from the application of these drugs. Finally, we point out current gaps to address in the understanding of B7-H3 function and regulation in order to fully unleash the future clinical utility of B7-H3-based therapies for the treatment of cancer.

10.
Front Chem ; 9: 768854, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746098

RESUMO

Asparaginyl endopeptidases (AEPs) or legumains are Asn/Asp (Asx)-specific proteases that break peptide bonds, but also function as peptide asparaginyl ligases (PALs) that make peptide bonds. This ligase activity can be used for site-specific protein modifications in biochemical and biotechnological applications. Although AEPs are common, PALs are rare. We previously proposed ligase activity determinants (LADs) of these enzymes that could determine whether they catalyze formation or breakage of peptide bonds. LADs are key residues forming the S2 and S1' substrate-binding pockets flanking the S1 active site. Here, we build on the LAD hypothesis with the engineering of ligases from proteases by mutating the S2 and S1' pockets of VcAEP, an AEP from Viola canadensis. Wild type VcAEP yields <5% cyclic product from a linear substrate at pH 6.5, whereas the single mutants VcAEP-V238A (Vc1a) and VcAEP-Y168A (Vc1b) targeting the S2 and S1' substrate-binding pockets yielded 34 and 61% cyclic products, respectively. The double mutant VcAEP-V238A/Y168A (Vc1c) targeting both the S2 and S1' substrate-binding pockets yielded >90% cyclic products. Vc1c had cyclization efficiency of 917,759 M-1s-1, which is one of the fastest rates for ligases yet reported. Vc1c is useful for protein engineering applications, including labeling of DARPins and cell surface MCF-7, as well as producing cyclic protein sfGFP. Together, our work validates the importance of LADs for AEP ligase activity and provides valuable tools for site-specific modification of proteins and biologics.

11.
Int J Biochem Cell Biol ; 141: 106100, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34678458

RESUMO

BACKGROUND: The occurrence of recurrence and metastasis after treatment is a major challenge in the treatment of gastric cancer. This study was based on the methionine (Met)-dependent characteristics of gastric cancer cells to explore the effect of Met deficiency on the occurrence and development of gastric cancer. METHODS: Human gastric cancer cell lines MKN45 and AGS and nude mice model were used to explore how Met affects gastric cancer by regulating lncRNA PVT1. RESULTS: The levels of lncRNA PVT1 in gastric cancer cells and human gastric cancer xenografts of nude mice were down-regulated under the condition of Met deficiency. The cell viability and cell proliferation were declined after MKN45 and SGC-790 cells were cultured in Met-deficient medium. LncRNA PVT1 could affect BNIP3 promoter DNA methylation level through its interaction with DNMT1. Moreover, the silence of lncRNA PVT1 and the up-regulation of BNIP3 level inhibited the gastric cancer cell proliferation. Met deficiency could up-regulate BNIP3 expression by inhibiting the binding of lncRNA PVT1 to DNMT1, and activate mitophagy, thus inhibiting gastric cancer cell proliferation. CONCLUSION: Our study suggested that Met deficiency could down-regulate the expression of lncRNA PVT1, further demethylated the promoter of BNIP3, thus inhibiting the proliferation of gastric cancer cells by activating mitophagy.

12.
J Biol Chem ; 297(6): 101325, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34710371

RESUMO

Legumains, also known as asparaginyl endopeptidases (AEPs), cleave peptide bonds after Asn/Asp (Asx) residues. In plants, certain legumains also have ligase activity that catalyzes biosynthesis of Asx-containing cyclic peptides. An example is the biosynthesis of MCoTI-I/II, a squash family-derived cyclic trypsin inhibitor, which involves splicing to remove the N-terminal prodomain and then N-to-C-terminal cyclization of the mature domain. To identify plant legumains responsible for the maturation of these cyclic peptides, we have isolated and characterized a legumain involved in splicing, McPAL1, from Momordica cochinchinensis (Cucurbitaceae) seeds. Functional studies show that recombinantly expressed McPAL1 displays a pH-dependent, trimodal enzymatic profile. At pH 4 to 6, McPAL1 selectively catalyzed Asp-ligation and Asn-cleavage, but at pH 6.5 to 8, Asn-ligation predominated. With peptide substrates containing N-terminal Asn and C-terminal Asp, such as is found in precursors of MCoTI-I/II, McPAL1 mediates proteolysis at the Asn site and then ligation at the Asp site at pH 5 to 6. Also, McPAL1 is an unusually stable legumain that is tolerant of heat and high pH. Together, our results support that McPAL1 is a splicing legumain at acidic pH that can mediate biosynthesis of MCoTI-I/II. We purport that the high thermal and pH stability of McPAL1 could have applications for protein engineering.

13.
BMC Musculoskelet Disord ; 22(1): 845, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600519

RESUMO

BACKGROUND: Anterior shoulder dislocation remains a clinical challenge. This study aimed to assess the graft position and clinical outcomes of the arthroscopic Latarjet procedure and capsular repair for the treatment of recurrent anterior shoulder dislocation with significant glenoid bone loss in 37 patients. METHODS: Between 2017 and 2017, 37 patients underwent arthroscopic Latarjet plus capsular repair procedure for recurrent anterior shoulder dislocation combined with significant glenoid bone loss. In follow-up examinations, Walch-Duplay scores, subjective shoulder value (SSV) scores, Rowe scores, and active range of motion (AROM) were assessed. Three-dimensional computed tomography (CT) was used to evaluate coracoid graft position and bone resorption. A new method of evaluating the position of the coracoid bone block after Latarjet (H-Z method) was developed. RESULTS: Thirty-seven patients were included in this study. Follow-up ranged from 6 to 36 months postoperatively (with an average of 13 months). No recurrent dislocation occurred at the final follow-up, and there was no significant effect on the AROM (all p > 0.05). Rowe (from 42.2 ± 5.6 to 91.1 ± 3.3), Walch-Duplay (from 31.5 ± 8.0 to 92.6 ± 3.7), and SSV (from 63.9 ± 6.1 to 79.3% ± 5.0%) scores were improved significantly after surgery (all p < 0.001). CT showed that the 29 patients had varying degrees of bone resorption, and 23 recovered to the preinjury level of motional function within 6-12 months after surgery. CONCLUSIONS: In active patients with recurrent anterior shoulder dislocations and significant glenoid bone loss, the arthroscopic Latarjet procedure plus capsular repair could restore shoulder stability satisfactory.


Assuntos
Luxações Articulares , Instabilidade Articular , Articulação do Ombro , Artroscopia , Humanos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/cirurgia , Ombro , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia
14.
Nano Lett ; 21(20): 8609-8618, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34661419

RESUMO

Tumor heterogeneity, often leading to metastasis, limits the development of tumor therapy. Personalized therapy is promising to address tumor heterogeneity. Here, a vesicle system was designed to enhance innate immune response and amplify personalized immunotherapy. Briefly, the bacterial outer membrane vesicle (OMV) was hybridized with the cell membrane originated from the tumor (mT) to form new functional vesicles (mTOMV). In vitro experiments revealed that the mTOMV strengthened the activation of innate immune cells and increased the specific lysis ability of T cells in homogeneous tumors. In vivo experiments showed that the mTOMV effectively accumulated in inguinal lymph nodes, then inhibited lung metastasis. Besides, the mTOMV evoked adaptive immune response in homologous tumor rather than the heterogeneous tumor, reversibly demonstrating the effects of personalized immunotherapy. The functions to inhibit tumor growth and metastasis accompanying good biocompatibility and simple preparation procedure of mTOMV provide their great potential for clinical applications.


Assuntos
Membrana Externa Bacteriana , Imunoterapia , Membrana Celular , Imunidade Inata , Linfócitos T
15.
EMBO Rep ; : e52124, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647680

RESUMO

This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues and tumor-associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2-polarized macrophage-derived exosomes (M2-exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2-exo reverses the promotional effect of M2-exo on cell proliferation in CDDP-treated GC cells and homograft tumor growth in CDDP-treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1)-mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2-exo enhances the CDDP sensitivity of GC cells treated with M2-exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM-derived exosomes.

16.
J Orthop Surg Res ; 16(1): 619, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663388

RESUMO

BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) is a safe and noninvasive rehabilitative physical therapy with anti-inflammatory effects. The current study investigated the effect of LIPUS on the inflammation of nucleus pulposus (NP) cells and its underlying mechanism. METHODS: Human NP cells were acquired from lumbar disc herniation tissue samples and cultured for experiments. Human NP cells were treated with LPS and then exposed to LIPUS (15 mW/cm2, 30 mW/cm2 and 60 mW/cm2) for 20 min daily for 3 days to determine the appropriate intensity to inhibit the expression of the inflammatory factors TNF-α and IL-1ß. The gene and protein expression of aggrecan, collagen II, MMP-3 and MMP-9 was measured by real-time PCR and western blotting, respectively. The activity of the nuclear factor-kappa B (NF-κB) pathway was examined by western blotting and immunofluorescence. After pretreatment with the NF-κB inhibitor PDTC, the expression of TNF-α, IL-1ß, MMP-3 and MMP-9 was measured by real-time PCR. RESULTS: LIPUS at intensities of 15 mW/cm2, 30 mW/cm2 and 60 mW/cm2 inhibited LPS-induced NP cell expression of the inflammatory factors TNF-α and IL-1ß, especially at 30 mW/cm2. LIPUS significantly upregulated the gene and protein expression of aggrecan and collagen II and downregulated the gene and protein expression of MMP-3 and MMP-9 in LPS-induced NP cells. The NF-κB signaling pathway was inhibited by LIPUS through inhibiting the protein expression of p-P65 and the translocation of P65 into the nucleus in LPS-induced NP cells. In addition, LIPUS had similar effects as the NF-κB inhibitor PDTC by inhibiting the NF-κB signaling pathway, inflammation and catabolism in LPS-induced human degenerative nucleus pulposus cells. CONCLUSION: LIPUS inhibited inflammation and catabolism through the NF-κB pathway in human degenerative nucleus pulposus cells.

17.
Natl Sci Rev ; 8(2): nwaa172, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34691573

RESUMO

Compared to human vision, conventional machine vision composed of an image sensor and processor suffers from high latency and large power consumption due to physically separated image sensing and processing. A neuromorphic vision system with brain-inspired visual perception provides a promising solution to the problem. Here we propose and demonstrate a prototype neuromorphic vision system by networking a retinomorphic sensor with a memristive crossbar. We fabricate the retinomorphic sensor by using WSe2/h-BN/Al2O3 van der Waals heterostructures with gate-tunable photoresponses, to closely mimic the human retinal capabilities in simultaneously sensing and processing images. We then network the sensor with a large-scale Pt/Ta/HfO2/Ta one-transistor-one-resistor (1T1R) memristive crossbar, which plays a similar role to the visual cortex in the human brain. The realized neuromorphic vision system allows for fast letter recognition and object tracking, indicating the capabilities of image sensing, processing and recognition in the full analog regime. Our work suggests that such a neuromorphic vision system may open up unprecedented opportunities in future visual perception applications.

19.
Colorectal Dis ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34611964

RESUMO

AIM: Systemic chemotherapy combining biological targeted therapies is the standard therapy for patients with metastatic colorectal cancer (mCRC), but effective markers are needed to identify clinical responders. Circulating tumour cells (CTCs) have been associated with prognosis in patients with mCRC. This study aimed to explore the relationship between CTC number and the clinical response of patients with advanced CRC. METHOD: Epithelial cell adhesion molecule-independent enrichment and CD45- fluorescence in situ hybridization immunofluorescence were used to detect peripheral blood CTCs in 79 patients with advanced CRC. Fisher's exact test and Spearman's rank correlation coefficient were used to analyse the correlation between CTC number and efficacy of chemotherapy. Kaplan-Meier and Cox regression analyses were used to evaluate progression-free survival (PFS). RESULTS: Among the evaluable patients, CTCs were significantly correlated with clinical response (r =4.891, p = 0.031). High CTC numbers were associated with a poor treatment response (r = -0.250, p = 0.027). Dynamic decrease in CTC number was associated with clinical response (p = 0.046). High baseline CTC number and carcinoembryonic antigen levels were prognostic factors for unfavourable PFS in multivariable analysis [hazard ratio (HR) = 3.30, p = 0.011 and HR = 2.04, p = 0.044, respectively]. Compared with the CTC-positive group, the CTC-negative group showed superior PFS (median PFS 15.53 vs. 9.43 months, p = 0.041) among CRC patients receiving first-line treatment. CONCLUSION: CTC number is a feasible biomarker for predicting outcomes in mCRC patients receiving systemic chemotherapy.

20.
Travel Med Infect Dis ; 44: 102166, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34555515

RESUMO

BACKGROUND: Acute mountain sickness (AMS) may cause life-threatening conditions. This study aimed to screen echocardiographic parameters at sea level (SL) to identify predictors of AMS development. METHODS: Overall, 106 healthy men were recruited at SL and ascended to 4100 m within 7 days by bus. Basic characteristics, physiological data, and echocardiographic parameters were collected both at SL and 4100 m above SL. AMS was identified by 2018 Lake Louise Questionnaire Score. RESULTS: After acute high altitude exposure (AHAE), 33 subjects were diagnosed with AMS and exhibited lower lateral mitral valve tissue motion annular displacement (MV TMADlateral) at SL than AMS-free subjects (13.09 vs. 13.89 mm, p = 0.022). MV TMADlateral at SL was significantly correlated with AMS occurrence (OR = 0.717, 95% CI: 0.534-0.964, p = 0.028). The MV TMADlateral<13.30-mm group showed over 4-fold risk for AMS development versus the MV TMADlateral≥13.30-mm group. After AHAE, the MV TMADlateral<13.30-mm group had increased HR (64 vs. 74 bpm, p = 0.001) and right-ventricular myocardial performance index (0.54 vs. 0.69, p = 0.009) and decreased left ventricular global longitudinal strain (-21.50 vs. -20.23%, p = 0.002), tricuspid valve E/A ratio (2.11 vs. 1.89, p = 0.019), and MV E-wave deceleration time (169.60 vs. 156.90 ms, p = 0.035). CONCLUSION: MV TMADlateral at SL was a potential predictor of AMS occurrence and might be associated with differential alterations of ventricular systolic and diastolic functions in subjects with different MV TMADlateral levels at SL after AHAE.

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