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1.
iScience ; 25(1): 103593, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35005542

RESUMO

The HIV-1 capsid is the target for the antiviral drugs GS-CA1 and Lenacapavir (GS-6207). We investigated the mechanism by which GS-CA1 and GS-6207 inhibit HIV-1 infection. HIV-1 inhibition by GS-CA1 did not require CPSF6 in CD4+ T cells. Contrary to PF74 that accelerates uncoating of HIV-1, GS-CA1 and GS-6207 stabilized the core. GS-CA1, unlike PF74, allowed the core to enter the nucleus, which agrees with the fact that GS-CA1 inhibits infection after reverse transcription. Unlike PF74, GS-CA1 did not disaggregate preformed CPSF6 complexes in nuclear speckles, suggesting that PF74 and GS-CA1 have different mechanisms of action. GS-CA1 stabilized the HIV-1 core, possibly by inducing a conformational shift in the core; in agreement, HIV-1 cores bearing N74D regained their ability to bind CPSF6 in the presence of GS-CA1. We showed that GS-CA1 binds to the HIV-1 core, changes its conformation, stabilizes the core, and thereby prevents viral uncoating and infection.

2.
Cancer Lett ; 529: 100-111, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34990752

RESUMO

The transcription factor B cell lymphoma 6 (BCL6) is an oncogenic driver of diffuse large B cell lymphoma (DLBCL) and mediates lymphomagenesis through transcriptional repression of its target genes by recruiting corepressors to its N-terminal broad-complex/tramtrack/bric-a-brac (BTB) domain. Blocking the protein-protein interactions of BCL6 and its corepressors has been proposed as an effective approach for the treatment of DLBCL. However, BCL6 inhibitors with excellent drug-like properties are rare. Hence, the development of BCL6 inhibitors is worth pursuing. We screened our internal chemical library by luciferase reporter assay and Homogenous Time Resolved Fluorescence (HTRF) assay and a small molecule compound named WK500B was identified. WK500B engaged BCL6 inside cells, blocked BCL6 repression complexes, reactivated BCL6 target genes, killed DLBCL cells and caused apoptosis as well as cell cycle arrest. In animal models, WK500B inhibited germinal center (GC) formation and DLBCL tumour growth without toxic and side effects. Moreover, WK500B displayed strong efficacy and favourable pharmacokinetics and presented superior druggability. Therefore, WK500B is a promising candidate that could be developed as an effective orally available therapeutic agent for DLBCL.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34994328

RESUMO

Background Increased CCKBR expression density or frequency has been reported in many neoplasms. Objective We aimed to investigate whether CCKBR drives the growth of gastric cancer (GC) and its potential as a therapeutic target of immunotoxins. Methods A lentiviral interference system was used to generate CCKBR-knockdown gastric cancer cells. Cell Counting Kit-8 and clonogenic assays were used to evaluate cell proliferation. Wound-healing and cell invasion assays were performed to evaluate cell mobility. Cell cycle was analyzed by flow cytometry. Tumor growth in vivo was investigated using a heterologous tumor transplantation model in nude mice. In addition, we generated the immunotoxin FQ17P and evaluated the combining capacity and tumor cytotoxicity of FQ17P in vitro. Results Stable downregulation of CCKBR expression resulted in reduced proliferation, migration and invasion of BGC-823 and SGC-7901 cells. The impact of CCKBR on gastric cancer cells was further verified through CCKBR overexpression studies. Downregulation of CCKBR expression also inhibited the growth of gastric tumors in vivo. Furthermore, FQ17P killed CCKBR-overexpressing GC cells by specifically binding to CCKBR on the tumor cell surface. Conclusion The CCKBR protein drives the growth, migration, and invasion of gastric cancer cells, and it might be a promising target for immunotoxin therapy based on its aberrant expression, functional binding interactions with gastrin, and subsequent internalization.

4.
Front Med (Lausanne) ; 8: 757313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966751

RESUMO

Significance: Perifoveal exudative vascular anomalous complex (PEVAC) is a unique clinical lesion. It manifests as isolated lesions and is easily misdiagnosed. Thus far, few PEVAC case reports have been published. PEVAC is typically inconsistent with other reported macular lesions. Purpose: To report our 24-month follow-up experience on the treatment of PEVAC with a micropulse laser (MPL). Case Report: A 56-year-old Chinese woman with no history of other diseases complained of decreased vision in her left eye that had persisted for more than 1 year. Comprehensive ophthalmic examinations were performed, including a vision test, slit lamp fundus exam, optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA). Intravitreal injection of ranibizumab was ineffective, and bleeding, exudation and visual acuity were not improved. After two rounds of micropulse laser (MPL) treatment, the patient was followed up, and the prognosis was good. Conclusion: PEVAC is very rare, and early diagnosis is important, as the lesions readily cause irreversible damage. Our results indicate that an MPL can be used as an alternative treatment for PEVAC patients.

5.
Clin Cancer Res ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740924

RESUMO

PURPOSE: Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many "cold" tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy. EXPERIMENTAL DESIGN: Analysis of transcriptomic profiles at single-cell resolution was performed in clinical patients' samples, along with integrated analysis of multiple RNA-seq datasets. The antitumor activity of YY001, a novel EP4 antagonist, combined with anti-programmed cell death protein 1 (PD-1) antibody was evaluated both in vitro and in vivo Results: We identified EP4 (PTGER4) as expressed in epithelial cells and various immune cells and involved in modulating the prostate cancer immune microenvironment. YY001, a novel EP4 antagonist, inhibited the differentiation, maturation, and immunosuppressive function of myeloid-derived suppressor cells (MDSCs) while enhancing the proliferation and anticancer functions of T cells. Furthermore, it reversed the infiltration levels of MDSCs and T cells in the tumor microenvironment by overturning the chemokine profile of tumor cells in vitro and in vivo The combined immunotherapy demonstrated a robust antitumor immune response as indicated by the robust accumulation and activation of CD8+ cytotoxic T cells, with a significantly decreased MDSC ratio and reduced MDSC immunosuppression function. CONCLUSIONS: Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti-PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory.

6.
Anal Chem ; 93(41): 13886-13892, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34623153

RESUMO

Given the great harm of pesticide residues to the environment and public health, exploring ultrasensitive and low-cost methods for their quantitative analysis becomes intensely necessary. Herein, we proposed a double-functionalized gold nanoparticle (AuNP) probe as a signal amplification immunoassay for the detection of acetochlor (ATC), metolachlor, and propisochlor. The AuNP was modified with IgG and fluorophore-labeled duplex DNA by a polyadenine-based freezing method. The quenched fluorescence can be effectively recovered via duplex-specific nuclease (DSN) with excellent cleaving activity. This approach provided limits of detection (LODs) down to 0.03 ng/mL for ATC, 0.10 ng/mL for metolachlor, 0.14 ng/mL for propisochlor, and 0.08 ng/mL for their mixture. The average recoveries of ATC, metolachlor, and propisochlor were 93.0-106.6% from a corn sample, which are in good agreement with the commercial kit (R2 = 0.9995). This "turn-off" fluorescence immunoassay presents considerable potential in the analysis of chloroacetamide herbicide due to its simple process of probe preparing and ultrahigh sensitivity.


Assuntos
Ouro , Nanopartículas Metálicas , Acetamidas , Imunoensaio , Toluidinas
7.
Curr Issues Mol Biol ; 43(3): 1529-1547, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34698109

RESUMO

Melanocortin 1 receptor (MC1R) is thought to be a marker of poor prognosis and a potential target for the treatment of melanoma. Studies have found that MC1R promotes several tumor behaviors, including cell proliferation and differentiation, pigment formation, and genome damage repair. Some single-nucleotide polymorphisms (SNPs) of MC1R are involved in the occurrence and development of melanoma. A few studies have reported a relationship between MC1R and colorectal cancer (CRC). In this research, our objective was to examine MC1R expression and MC1R SNPs and investigate their correlation with the clinicopathological features of human CRC tissues. We evaluated MC1R mRNA expression by performing bioinformatic analyses on human CRC expression datasets. We used Western blotting and RT-qPCR to compare MC1R expression in CRC tissues with that in normal tissues, and MC1R SNPs in CRC tissues were detected by PCR-direct sequencing (DS). The expression of MC1R was significantly decreased in CRC tissues compared with normal tissue, and its expression was negatively associated with P53 expression, MLH1 expression, and PMS2 expression, and high MC1R expression was significantly associated with microsatellite instability (MSI). MC1R SNPs were also associated with the clinicopathological characteristics of CRC; for example, the rs2228479 locus genotype was correlated with Ki67 status, and the rs885479 locus genotype was correlated with age and T stage. In conclusion, MC1R plays a crucial role in the progression of CRC and may be a marker of poor prognosis in CRC.

8.
Ann Palliat Med ; 10(8): 8963-8971, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488383

RESUMO

BACKGROUND: The incidence of ischemic cerebrovascular disease (ICVD) has been increasing, leading to disability and deaths among middle-aged and elderly people. Digital subtraction angiography (DSA) is the gold standard for diagnosing ICVD, but it is invasive, expensive, and complex to operate. Transcranial Doppler (TCD) ultrasound is characterized by high accuracy, simplicity, and low cost, and thus became the focus of this study. METHODS: The databases of PubMed, Web of Science, Embase, and The Cochrane Library were searched from January 2000 to September 2020, for literature involving the use of TCD to diagnose ICVD. The software RevMan 5.3 was used for quality assessment, and forest plots and summary receiver operating characteristic (SROC) curves were drawn. The software STATA12.0 was adopted for publication bias analysis. RESULTS: A total of 11 references were included, and the combined sensitivity, specificity, and 95% confidence interval (CI) of TCD were 0.93 (0.75 to 1.00) and 0.95 (0.78 to 1.00), respectively. The area under the curve (AUC) of SROC was 0.887. DISCUSSION: Superb capabilities in diagnosing ICVD have been demonstrated by TCD, and it should therefore be applied in the clinic. The results are important to realize early diagnosis of ICVD and improve the prognosis of patients.


Assuntos
Transtornos Cerebrovasculares , Ultrassonografia Doppler Transcraniana , Idoso , Transtornos Cerebrovasculares/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Prognóstico
9.
J Environ Manage ; 296: 113218, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34246906

RESUMO

Coagulation/flocculation is an extensive and effective pretreatment technology for improving the sludge dewaterability. A series of hydrophobically associated cationic starch-based flocculants (CS-DMRs) with different degrees of hydrophobicity but similar charge densities were designed and synthesized. The CS-DMRs exhibited excellent sludge dewatering performance. The dewaterability of sludge increased with the hydrophobicity of the CS-DMRs, and the filter cake moisture content (FCMC) and specific resistance to filtration (SRF) could be reduced from 95.47% and 7.09 × 1012 m/kg to 79.26% and 2.258 × 1012 m/kg, respectively, at a constant pressure of 0.05 MPa after conditioned by the starch-based flocculant with the highest hydrophobicity at its optimal dose. Moreover, due to their amphiphilic structures, CS-DMRs could closely interact with the negatively charged extracellular polymeric substances (EPS), efficiently compress the protein and polysaccharide in EPS, and release the bound water. A second-order polynomial model was proposed according to the phenomenological theory to quantitatively analyze the effect of hydrophobicity in these starch-based flocculants on the sludge dewaterability. The structure-activity relationship was built, and the optimal dose and corresponding FCMC could be theoretically estimated accordingly. The results were in good agreement with the experimental results. The dewatering mechanisms were also discussed in detail on the basis of the changes in the FCMC, SRF, capillary suction time, properties of sludge flocs, compression coefficient, microstructures of sludge cakes, EPS fractions and components, and spatial distributions of the proteins and polysaccharides. In addition to charge neutralization, the hydrophobic association effects of CS-DMRs played an important role in the formation of drainage channels and net-like porous structures in the sludge cake to improve its permeability and filterability. This study thus provided a good understanding of the structural effects of the starch-based flocculants on the sludge dewaterability. The results are greatly beneficial to the fabrication and utilization of environment-friendly and high-performance natural polymeric conditioners for sludge treatment.


Assuntos
Esgotos , Eliminação de Resíduos Líquidos , Filtração , Floculação , Interações Hidrofóbicas e Hidrofílicas , Amido , Água
10.
Theor Appl Genet ; 134(9): 2991-3011, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34095960

RESUMO

KEY MESSAGE: The genetic basis of 27 seedling traits under normal and salt treatments was fully analyzed in a RIL wheat population, and seven QTL intervals were validated in two other genetic populations. Soil salinity seriously constrains wheat (Triticum aestivum L.) production globally by influencing its growth and development. To explore the genetic basis of salt tolerance in wheat, a recombinant inbred line (RIL) population derived from a cross between high-yield wheat cultivar Zhongmai 175 (ZM175) and salt-tolerant cultivar Xiaoyan 60 (XY60) was used to map QTL for seedling traits under normal and salt treatments based on a high-density genetic linkage map. A total of 158 stable additive QTL for 27 morphological and physiological traits were identified and distributed on all wheat chromosomes except 3A and 4D. They explained 2.35-46.43% of the phenotypic variation with a LOD score range of 2.61-40.38. The alleles from XY60 increased corresponding traits for 100 QTL, while the alleles from ZM175 had positive effects for the other 58 QTL. Nearly half of the QTL (78/158) were mapped in nine QTL clusters on chromosomes 2A, 2B, 2D, 4B, 5A, 5B, 5D, and 7D (2), respectively. To prove the reliability and potentiality in molecular marker-assisted selection (MAS), seven QTL intervals were validated in two other genetic populations. Besides additive QTL, 94 pairs of loci were detected with significant epistatic effect and 20 QTL were found to interact with treatment. This study provides a full elucidation of the genetic basis of seedling traits (especially root system-related traits) associated with salt tolerance in wheat, and the developed kompetitive allele-specific PCR markers closely linked to stable QTL would supply strong supports to MAS in salt-tolerant wheat breeding.


Assuntos
Cromossomos de Plantas/genética , Proteínas de Plantas/metabolismo , Locos de Características Quantitativas , Tolerância ao Sal , Plântula/fisiologia , Triticum/fisiologia , Mapeamento Cromossômico/métodos , Regulação da Expressão Gênica de Plantas , Fenótipo , Melhoramento Vegetal , Proteínas de Plantas/genética , Polimorfismo de Nucleotídeo Único , Plântula/genética , Triticum/genética
11.
Sci Rep ; 11(1): 11819, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083668

RESUMO

Two series of binary graft cationic starch-based flocculants (CS-DMCs and CS-DMLs) with different hydrophilicity and charge density (CD) were prepared by graft copolymerization of acrylamide with 2-(Methacryloyloxy)-N,N,N-trimethylethanaminium chloride and methacrylic acid 2-(benzyldimethylaminio) ethyl chloride, respectively, on the starch (St) backbone. The sludge dewatering performance of CS-DMCs and CS-DMLs were evaluated and compared based on the changes in filter cake moisture content (FCMC), specific resistance of filtration (SRF), fractions and components of extracellular polymeric substances, and various physiochemical characteristics of sludge flocs and cakes. Increase in CD of the St-based flocculants caused improved sludge dewaterability. Under the similar CD, CS-DML with relatively high hydrophobicity exhibited lower FCMC and SRF, larger and denser sludge flocs, and better permeability of sludge cakes than CS-DMCs due to the synergistic effects of charge neutralization, bridging flocculation and hydrophobic association. Furthermore, a second-order polynomial model on the basis of phenomenological theory was successfully applied to quantitatively evaluate the influences of the two important structural factors of these St-based flocculants, i.e., hydrophobicity and CD, on the sludge dewaterability. The structure-activity relationship of the St-based flocculants in sludge dewatering was obtained according to the theoretic simulation. The dewatering mechanisms was discussed in depth on the basis of the experimental and simulated results; besides, the FCMC and optimal dose can be predicted by the established structure-activity relationship. This current work offered a novel and valuable way to exploit and design of low-cost and high-performance graft natural polymeric flocculants applied in efficient conditioning of sludge.

12.
Orthop Surg ; 13(5): 1513-1520, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34075690

RESUMO

OBJECTIVE: To using finite element analysis to investigate the effects of the traditional titanium alloy Gamma nail and a biodegradable magnesium alloy bionic Gamma nail for treating intertrochanteric fractures. METHODS: Computed tomography images of an adult male volunteer of appropriate age and in good physical condition were used to establish a three-dimensional model of the proximal femur. Then, a model of a type 31A1 intertrochanteric fracture of the proximal femur was established, and the traditional titanium alloy Gamma nails and biodegradable magnesium alloy bionic Gamma nails were used for fixation, respectively. The von Mises stress, the maximum principal stress, and the minimum principal stress were calculated to evaluate the effect of bone ingrowth on stress distribution of the proximal femur after fixation. RESULTS: In the intact model, the maximum stress was 5.8 MPa, the minimum stress was -11.7 MPa, and the von Mises stress was 11.4 MPa. The maximum principal stress distribution of the cancellous bone in the intact model appears in a position consistent with the growth direction of the principal and secondary tensile zones. After traditional Gamma nail healing, the maximum stress was 32 MPa, the minimum stress was -23.5 MPa, and the von Mises stress was 31.3 MPa. The stress concentration was quite obvious compared with the intact model. It was assumed that the nail would biodegrade completely within 12 months postoperatively. The maximum stress was 18.7 MPa, the minimum stress was -12.6 MPa, and the von Mises stress was 14.0 MPa. For the minimum principal stress, the region of minimum stress value less than -10 MPa was significantly improved compared with the traditional titanium alloy Gamma nail models. Meanwhile, the stress distribution of the bionic Gamma nail model in the proximal femur was closer to that of the intact bone, which significantly reduced the stress concentration of the implant. CONCLUSION: The biodegradable magnesium alloy bionic Gamma nail implant can improve the stress distribution of fractured bone close to that of intact bone while reducing the risk of postoperative complications associated with traditional internal fixation techniques, and it has promising clinical value in the future.


Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas/instrumentação , Fraturas do Quadril/cirurgia , Desenho de Prótese , Adulto , Ligas , Cadáver , Análise de Elementos Finitos , Humanos , Magnésio , Masculino , Titânio
13.
Artigo em Inglês | MEDLINE | ID: mdl-34117780

RESUMO

OBJECTIVE: To explore the safety and efficiency of modified sacrospinous ligament fixation (MSSF) for apical prolapse. METHODS: A retrospective cohort study. Patients diagnosed with apical prolapse from 2014 to 2019 were recruited and divided into three groups: sacrospinous ligament fixation (SSF), MSSF, and laparoscopic sacral hysteropexy (LSH). All surgical characteristics were obtained and information concerning complications was collected and compared among these three groups. RESULTS: A total of 710 patients were included: 108 in the SSF group, 260 in the LSH group, and 342 in the MSSF group. The MSSF and SSF groups took less surgical time (P < 0.001) and had shorter hospital stays (P < 0.001). All three methods can significantly change prolapses to point C on the POP quantification score (P < 0.001). Prevalence of vaginal and pelvic pain after surgery was higher in the SSF group (8/108; 7.41%) (P = 0.028), and urinary incontinence was higher in the LSH group (22/260; 8.46%) (P = 0.010). In the LSH group more patients experienced constipation and dyschezia after surgery (prevalence 18/260; 6.92%; P = 0.048). Recurrence of pelvic organ prolapse in the MSSF group (15/324; 4.39%) and LSH group (12/260; 4.62%) was much lower than in the SSF group (16/108; 14.81%) (P < 0.001). CONCLUSION: The efficacy of MSSF is commendable with low recurrence of POP and few complications in long-term follow up.

14.
Mol Pharm ; 18(6): 2285-2297, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33998814

RESUMO

Cholecystokinin-2 receptor (CCK2R) has been proven to be a specific biomarker for colorectal malignancies. Immunotoxins are a valuable class of immunotherapy agents consisting of a targeting element and a bacterial or plant toxin. Previous work demonstrated that targeting CCK2R is a good therapeutic strategy for the treatment of colorectal cancer (CRC). In the present study, we developed a new version of CCK2R-targeting immunotoxin GD9P using a targeted peptide, GD9, as the binding motif and a truncated Pseudomonas exotoxin A (PE38) as the cytokiller. BALB/c nude mice were treated with different doses of GD9P, and pharmacodynamics, pharmacokinetic, and toxicological data were obtained throughout this study. Compared to the parental immunotoxin rCCK8PE38, GD9P exhibited about 1.5-fold yield, higher fluorescence intensity, and increased antitumor activity against human CRC in vitro and in vivo. The IC50 values of GD9P in vitro ranged from 1.61 to 4.55 nM. Pharmacokinetic studies were conducted in mice with a T1/2 of 69.315 min. When tumor-bearing nude mice were treated with GD9P at doses ≥2 mg/kg for five doses, a rapid shrinkage in tumor volume and, in some cases, complete remission was observed. A preliminary safety evaluation demonstrated a good safety profile of GD9P as a Pseudomonas exotoxin A-based immunotherapy. The therapy in combination with oxaliplatin can increase the antitumor efficacy and reduce the toxic side effects caused by chemotherapy. In conclusion, the data support the use of GD9P as a promising immunotherapy targeting CCK2R-expressing colorectal malignancies.

15.
Ultraschall Med ; 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34015837

RESUMO

PURPOSE: To determine the association between levator avulsion and urinary stress incontinence (USI) by 3/4D transperineal ultrasound. MATERIALS AND METHODS: 842 patients who were admitted to our hospital from 2016 to 2019 were recruited for our study. 3D/4D transperineal ultrasound was performed. After standard interview and clinical evaluation, general conditions and levator hiatus data were collected and measured to compare with each group. The odds ratio (OR) of USI symptoms or ultrasound features with levator avulsion were calculated. RESULTS: A total of 593 women were studied: 204 suffered from levator avulsion (96 cases of left-side avulsion, 80 cases of right-side avulsion and 28 cases of bilateral avulsion) and 389 women had no avulsion. The gravidity and episiotomy conditions of the avulsion groups were significantly different from the no-avulsion group. Significant differences were found in the transverse diameters and anteroposterior diameters between the levator avulsion group and the no-avulsion group, but there was no difference among the avulsion groups, regardless of whether the patient was at rest or performing the Valsalva maneuver. Interestingly, a significant difference was found in the presence of USI symptoms between the uni-avulsion group and the no-avulsion group. The odds ratio (OR) of USI symptoms in the uni-avulsion group is 2.786 (95 %CI, 1.663-4.669), but 0.939 (95 %CI, 0.276-3.199) for the bilateral avulsion and no-avulsion groups. CONCLUSION: Unilateral levator avulsion may be a risk factor for urinary stress incontinence.

16.
Nanotechnology ; 32(35)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34034240

RESUMO

Plasmonic nanostructures are successfully demonstrated in solar cells due to their broad spectra-selective resonance in the range of ultraviolet to near-infrared, and thus light absorption can be mostly improved and power conversion efficiency (PCE) further. Here, we demonstrate plasmonic dye-sensitized solar cells (DSSCs) using collapsible Au nanofingers to build photoanode to enhance light absorption. In this plasmonic DSSCs, by balancing local field enhancement due to gap-plasmon resonance and dye fluorescence quenching, the optimal gap size in collapsed Au/Al2O3/Au nanofingers is designed by twice the Al2O3thickness and then deposited a TiO2layer as photoanode. The results show that the PCE of DSSCs is mostly improved as compared to DSSCs with photoanode of Au/Al2O3/TiO2films, which can be ascribed to the coupled local field enhancement within the sub-nanometer gaps. In addition, fluorescence of dyes on plasmonic nanofingers is nearly 10 times higher than plain Au/Al2O3/TiO2films, which further proves the dye absorption enhancement. These plasmonic nanofingers enable the precise engineering of gap-plasmon modes and can be scaled up to wafer scale with low cost by the nanoimprint lithography technique, which suggests the feasibility of applying our result in constructing the photoanode for other types of solar cells.

17.
Onco Targets Ther ; 14: 2489-2495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883903

RESUMO

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) complicated with angioimmunoblastic T-cell lymphoma (AITL) is extremely rare and typically shows an aggressive clinical course and unsatisfactory prognosis. Here, we describe the case of a 77-year-old man who was referred to the hospital because of repeated fever, night sweats, and weight loss. He was finally diagnosed with a discordant lymphoma consisting of AITL and DLBCL, with significantly different maximum standardized uptake values on positron emission tomography/computed tomography. Based on his complex illness and poor performance status, the patient received six cycles of lenalidomide combined with R-miniCHOP regimen and achieved complete remission with tolerable and controlled toxicity. He subsequently received lenalidomide maintenance therapy and achieved sustained remission. We consider the possible causes of this discordance involved AITL and EBV-positive DLBCL, and the possible mechanism of lenalidomide action in both T-cell and B-cell non-Hodgkin lymphomas. Lenalidomide-combination therapy may be a preferable choice in patients with an EBV-associated discordant lymphoma.

18.
Int Orthop ; 45(7): 1827-1835, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33876255

RESUMO

OBJECTIVE: Post-operative femoral shaft fractures are often accompanied by a residual varus/valgus deformity, which can result in osteoarthritis in severe cases. The purpose of this study was to investigate the biomechanical effects of residual varus/valgus deformities after middle and lower femoral fracture on the stress distribution and contact area of knee joint. METHODS: Thin-slice CT scanning of lower extremities and MRI imaging of knee joints were obtained from a healthy adult male to establish normal lower limb model (neutral position). Then, the models of 3°, 5°, and 10° of varus/valgus were established respectively by modifying middle and lower femur of normal model. To validate the modifying, a patient-specific model, whose BMI was same to former and had 10° of varus deformity of tibia, was built and simulated under the same boundary conditions. RESULT: The contact area and maximum stress of modified models were similar to those of patient-specific model. The contact area and maximum stress of medial tibial cartilage in normal neutral position were 244.36 mm2 and 0.64 MPa, while those of lateral were 196.25 mm2 and 0.76 MPa. From 10° of valgus neutral position to 10° of varus, the contact area and maximum stress of medial tibial cartilage increased, and the lateral gradually decreased. The contact area and maximum stress of medial meniscus in normal neutral position were 110.91 mm2 and 3.24 MPa, while those of lateral were 135.83 mm2 and 3.45 MPa. The maximum stress of medial tibia subchondral bone in normal neutral position was 1.47 MPa, while that of lateral was 0.65 MPa. The variation trend of medial/lateral meniscus and subchondral bone was consistent with that of tibial plateau cartilage in the contact area and maximum stress. CONCLUSION: This study suggested that varus/valgus deformity of femur had an obvious effect on the contact area and stress distribution of knee joint, providing biomechanical evidence and deepening understanding when performing orthopedic trauma surgery or surgical correction of the already existing varus/valgus deformity.


Assuntos
Fraturas do Fêmur , Osteoartrite do Joelho , Adulto , Fenômenos Biomecânicos , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Análise de Elementos Finitos , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Masculino , Osteoartrite do Joelho/cirurgia , Tíbia/diagnóstico por imagem , Tíbia/cirurgia
19.
Am J Emerg Med ; 46: 38-44, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33714053

RESUMO

INTRODUCTION: Rhabdomyolysis (RM) is a complex set of clinical syndromes involving the rapid dissolution of skeletal muscles. The early detection of patients who need renal replacement therapy (RRT) is very important and may aid in delivering proper care and optimizing the use of limited resources. METHODS: Retrospective analyses of the following three databases were performed: the eICU Collaborative Research Database (eICU-CRD), the Medical Information Mart for Intensive Care III (MIMIC-III) database and electronic medical records from the First Medical Centre of the Chinese People's Liberation Army General Hospital (PLAGH). The data from the eICU-CRD and MIMIC-III datasets were merged to form the derivation cohort. The data collected from the Chinese PLAGH were used for external validation. The factors predictive of the need for RRT were selected using a LASSO regression analysis. A logistic regression was selected as the algorithm. The model was built in Python using the ML library scikit-learn. The accuracy of the model was measured by the area under the receiver operating characteristic curve (AUC). R software was used for the LASSO regression analysis, nomogram, concordance index, calibration, and decision and clinical impact curves. RESULTS: In total, 1259 patients with RM (614 patients from eICU-CRD, 324 patients from the MIMIC-III database and 321 patients from the Chinese PLAGH) were eligible for this analysis. The rate of RRT was 15.0% (92/614) in the eICU-CRD database, 17.6% (57/324) in the MIMIC-III database and 5.6% in the Chinese PLAGH (18/321). After the LASSO regression selection, eight variables were included in the RRT prediction model. The AUC of the model in the training dataset was 0.818 (95% CI 0.78-0.87), the AUC in the test dataset was 0.794 (95% CI 0.72-0.86), and the AUC in the Chinese PLAGH dataset (external validation dataset) was 0.820 (95% CI 0.70-0.86). CONCLUSIONS: We developed and validated a model for the early prediction of the RRT requirement among patients with RM based on 8 variables commonly measured during the first 24 h after admission. Predicting the need for RRT could help ensure appropriate treatment and facilitate the optimization of the use of medical resources.


Assuntos
Regras de Decisão Clínica , Terapia de Substituição Renal , Rabdomiólise/terapia , Adulto , Idoso , Algoritmos , Diagnóstico Precoce , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Rabdomiólise/diagnóstico , Fatores de Risco
20.
Med Sci Sports Exerc ; 53(9): 1826-1834, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33787533

RESUMO

PURPOSE: Rhabdomyolysis (RM) is a complex set of clinical syndromes that involves the rapid dissolution of skeletal muscles. Mortality from RM is approximately 10%. This study aimed to develop an interpretable and generalizable model for early mortality prediction in RM patients. METHOD: Retrospective analyses were performed on two electronic medical record databases: the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care III database. We extracted data from the first 24 h after patient ICU admission. Data from the two data sets were merged for further analysis. The merged data sets were randomly divided, with 70% used for training and 30% for validation. We used the machine learning model extreme gradient boosting (XGBoost) with the Shapley additive explanation method to conduct early and interpretable predictions of patient mortality. Five typical evaluation indexes were adopted to develop a generalizable model. RESULTS: In total, 938 patients with RM were eligible for this analysis. The area under the receiver operating characteristic curve (AUC) of the XGBoost model in predicting hospital mortality was 0.871, the sensitivity was 0.885, the specificity was 0.816, the accuracy was 0.915, and the F1 score was 0.624. The XGBoost model performance was superior to that of other models (logistic regression, AUC = 0.862; support vector machine, AUC = 0.843; random forest, AUC = 0.825; and naive Bayesian, AUC = 0.805) and clinical scores (Sequential Organ Failure Assessment, AUC = 0.747; Acute Physiology Score III, AUC = 0.721). CONCLUSIONS: Although the XGBoost model is still not great from an absolute performance perspective, it provides better predictive performance than other models for estimating the mortality of patients with RM based on patient characteristics in the first 24 h of admission to the ICU.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva , Aprendizado de Máquina , Rabdomiólise/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos
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