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1.
Mol Cancer Ther ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36723609

RESUMO

Monomethyl auristatin E (MMAE) is a potent tubulin inhibitor that is used as the payload for four FDA-approved antibody drug conjugates (ADCs). Deconjugated MMAE readily diffuses into untargeted cells resulting in off-target toxicity. Here we report the development and evaluation of a humanized Fab fragment (ABC3315) that enhances the therapeutic selectivity of MMAE ADCs. ABC3315 increased the IC50 of MMAE against human cancer cell-lines by >500-fold with no impact on the cytotoxicity of MMAE ADCs, including polatuzumab vedotin and trastuzumab-vc-MMAE (TvcMMAE). Co-administration of ABC3315 did not reduce the efficacy of polatuzumab vedotin or TvcMMAE in xenograft tumor models. Co-administration of ABC3315 with 80 mg/kg TvcMMAE significantly (p<0.0001) increased the cumulative amount of MMAE that was excreted in urine 0-4-days after administration from 789.4 ±19.0 nanograms (TvcMMAE alone) to 2625±206.8 nanograms (for mice receiving TvcMMAE with co-administration of ABC3315). Mice receiving 80 mg/kg TvcMMAE and PBS exhibited a significant drop in white blood cell counts (p=0.025) and red blood cell counts (p=0.0083) in comparison to control mice. No significant differences, relative to control mice, were found for white blood cell counts (p=0.15) or for red blood cell counts (p=0.23) for mice treated with 80 mg/kg TvcMMAE and ABC3315. Co-administration of ABC3315 with 120 mg/kg polatuzumab vedotin significantly (p=0.045) decreased the percentage body weight loss at nadir for treated mice from 11.9 ± 7.0% to 4.1 ± 2.1%. Our results demonstrate that ABC3315, an anti-MMAE Fab fragment, decreases off-target toxicity while not decreasing anti-tumor efficacy, increasing the therapeutic window of MMAE ADCs.

2.
Global Health ; 19(1): 1, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597129

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has induced a significant global concern on mental health. However few studies have measured the ability of individuals to "withstand setbacks, adapt positively, and bounce back from adversity" on a global scale. We aimed to examine the level of resilience, its determinants, and its association with maladaptive coping behaviours during the pandemic. METHODS: The Association of Pacific Rim Universities (APRU) conducted a global survey involving 26 countries by online, self-administered questionnaire (October 2020-December 2021). It was piloted-tested and validated by an expert panel of epidemiologists and primary care professionals. We collected data on socio-demographics, socioeconomic status, clinical information, lifestyle habits, and resilience levels measured by the Brief Resilience Scale (BRS) among adults aged ≥ 18 years. We examined factors associated with low resilience level, and evaluated whether low resilience was correlated with engagement of maladaptive coping behaviours. RESULTS: From 1,762 surveys, the prevalence of low resilience level (BRS score 1.00-2.99) was 36.4% (America/Europe) and 24.1% (Asia Pacific). Young age (18-29 years; adjusted odds ratio [aOR] = 0.31-0.58 in older age groups), female gender (aOR = 1.72, 95% C.I. = 1.34-2.20), poorer financial situation in the past 6 months (aOR = 2.32, 95% C.I. = 1.62-3.34), the presence of one (aOR = 1.56, 95% C.I. = 1.19-2.04) and more than two (aOR = 2.32, 95% C.I. = 1.59-3.39) medical conditions were associated with low resilience level. Individuals with low resilience were significantly more likely to consume substantially more alcohol than usual (aOR = 3.84, 95% C.I. = 1.62-9.08), take considerably more drugs (aOR = 12.1, 95% C.I. = 2.72-54.3), buy supplements believed to be good for treating COVID-19 (aOR = 3.34, 95% C.I. = 1.56-7.16), exercise less than before the pandemic (aOR = 1.76, 95% C.I. = 1.09-2.85), consume more unhealthy food than before the pandemic (aOR = 2.84, 95% C.I. = 1.72-4.67), self-isolate to stay away from others to avoid infection (aOR = 1.83, 95% C.I. = 1.09-3.08), have an excessive urge to disinfect hands for avoidance of disease (aOR = 3.08, 95% C.I. = 1.90-4.99) and transmission (aOR = 2.54, 95% C.I. = 1.57-4.10). CONCLUSIONS: We found an association between low resilience and maladaptive coping behaviours in the COVID-19 pandemic. The risk factors identified for low resilience in this study were also conditions known to be related to globalization-related economic and social inequalities. Our findings could inform design of population-based, resilience-enhancing intervention programmes.


Assuntos
COVID-19 , Adulto , Humanos , Feminino , Idoso , COVID-19/epidemiologia , Pandemias , Adaptação Psicológica , Inquéritos e Questionários , Saúde Mental
3.
Eur J Med Res ; 28(1): 12, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611184

RESUMO

OBJECTIVES: To investigate whether intravenous thrombolysis (IVT) with alteplase (a recombinant tissue plasminogen activator, rt-PA) before endovascular treatment (EVT) is beneficial for acute ischemic stroke (AIS) patients in different periods. METHODS: This study enrolled a total of 140 patients hospitalized between 2019 and 2022 with AIS from large vessel occlusion (LVO) in the anterior circulation. Those patients were divided into the EVT alone group and IVT + EVT group, in which EVT was preceded by intravenous rt-PA. According to the time from onset to femoral artery puncture, the above two groups were divided into the following subgroups: < 4.5 h, between 4.5 and 6 h, between 6 and 8 h, and between 8 and 10 h. There were 78 patients in the EVT alone group and 62 patients in the IVT + EVT group. RESULTS: There was no statistically significant difference in functional independence, recanalization rate, favorable outcome rate, or mortality between the EVT and IVT + EVT groups (P > 0.05). After adjusting for confounding factors, a lower incidence of intracerebral hemorrhage was observed in the EVT group (P < 0.05). A comparison of time-dependent efficacy between the two groups showed that within 6-8 h, there were statistically significant differences between admission and postoperation in the National Institutes of Health Stroke Scale scores at 24 h (P = 0.01) or 7 days (P = 0.02). CONCLUSIONS: Although there was no difference in clinical efficacy and safety between the abovementioned two groups, treatment with IVT + EVT could increase the risk of bleeding compared to EVT. Moreover, in the 6-8 h subgroup, the efficacy of EVT alone was better than that of IVT + EVT.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Estados Unidos , Humanos , Ativador de Plasminogênio Tecidual/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , AVC Isquêmico/complicações , Terapia Trombolítica/efeitos adversos , Resultado do Tratamento
4.
ACS Nano ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629747

RESUMO

A robust neural interface with intimate electrical coupling between neural electrodes and neural tissues is critical for stable chronic neuromodulation. The development of bioadhesive hydrogel neural electrodes is a potential approach for tightly fixing the neural electrodes on the epineurium surface to construct a robust neural interface. Herein, we construct a photopatternable, antifouling, conductive (∼6 S cm-1), bioadhesive (interfacial toughness ∼100 J m-2), soft, and elastic (∼290% strain, Young's modulus of 7.25 kPa) hydrogel to establish a robust neural interface for bioelectronics. The UV-sensitive zwitterionic monomer can facilitate the formation of an electrostatic-assembled conductive polymer PEDOT:PSS network, and it can be further photo-cross-linked into elastic polymer network. Such a semi-interpenetrating network endows the hydrogel electrodes with good conductivity. Especially, the photopatternable feature enables the facile microfabrication processes of multifunctional hydrogel (MH) interface with a characteristic size of 50 µm. The MH neural electrodes, which show improved performance of impedance, charge storage capacity, and charge injection capability, can produce effective electrical stimulation with high current density (1 mA cm-2) at ultralow voltages (±25 mV). The MH interface could realize high-efficient electrical communication at the chronic neural interface for stable recording and stimulation of a sciatic nerve in the rat model.

5.
Adv Mater ; : e2210179, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36630669

RESUMO

Phototheranostics have emerged and flourished as a promising pattern for cancer theranostics owing to their precise photoinduced diagnosis and therapeutic to meet the demands of precision medicine. The diagnosis information and therapeutic effect are directly determined by the fluorescence imaging ability and photothermal conversion efficiency (PCE) of phototheranostic agents. Hence, how to balance the competitive radiative and nonradiative processes of phototheranostic agents is the key factor to evaluate the phototheranostic effect. Herein, we rationally designed molecules named ICRs with fluorescence emission in the second near-infrared (NIR-II, 1000-1700 nm), exhibiting high photostability and high PCE. The optimized D-A interaction and reorganization energy of ICRs were considered to be the key factors for their high PCE. Noteworthily, ICR-Qu with stronger D-A interaction and large-sized conjugated unit encapsulated in nanoparticles exhibited high PCE (81.1%). Besides, ICR-QuNPs were used for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to guide deep-tissue photonic hyperthermia, achieving precise removal and inhibition of breast cancer. Furthermore, combined with α-PD-1, ICR-QuNPs showed huge potential to be a facile and efficient tool for photo-immunotherapy. More importantly, this study not only reported an "all-in-one" polymethine-based phototheranostic agent but also shed light on the exploration of versatile organic molecules for future practical applications. This article is protected by copyright. All rights reserved.

6.
Sci Rep ; 13(1): 1454, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702838

RESUMO

All oxide-based transparent flexible memristor is prioritized for the potential application in artificially simulated biological optoelectronic synaptic devices. SnOx memristor with HfOx layer is found to enable a significant effect on synaptic properties. The memristor exhibits good reliability with long retention, 104 s, and high endurance, 104 cycles. The optimized 6 nm thick HfOx layer in SnOx-based memristor possesses the excellent synaptic properties of stable 350 epochs training, multi-level conductance (MLC) behaviour, and the nonlinearity of 1.53 and 1.46 for long-term potentiation and depression, respectively, and faster image recognition accuracy of 100% after 23 iterations. The maximum weight changes of -73.12 and 79.91% for the potentiation and depression of the synaptic device, respectively, are observed from the spike-timing-dependent plasticity (STDP) characteristics making it suitable for biological applications. The flexibility of the device on the PEN substrate is confirmed by the acceptable change of nonlinearities up to 4 mm bending. Such a synaptic device is expected to be used as a vision photo-receptor.

7.
Chem Commun (Camb) ; 59(8): 1054-1057, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36606455

RESUMO

A scalable, and cost-effective method was employed to prepare self-supported CuSn bimetallic catalyst on carbon paper. The obtained CuSn catalyst demonstrates high faradaic efficiency of CO around or above 90% at a broad potential range from -0.7 to -1.8 V vs. reversible hydrogen electrode, greatly surpassing Cu or Sn counterparts.


Assuntos
Dióxido de Carbono , Papel , Eletrodos
8.
Sci Rep ; 13(1): 1035, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658236

RESUMO

Smoking is a trigger for asthma, which has led to an increase in asthma incidence in China. In smokers, asthma management starts with smoking cessation. Data on predictors of smoking cessation in Chinese patients with asthma are scarce. The objective of this study was to find the differences in clinical characteristics between current smokers and former smokers with asthma in order to identify factors associated with smoking cessation. Eligible adults with diagnosed asthma and smoking from the hospital outpatient clinics (n = 2312) were enrolled and underwent a clinical evaluation, asthma control test (ACT), and pulmonary function test. Information on demographic and sociological data, lung function, laboratory tests, ACT and asthma control questionnaire (ACQ) scores was recorded. Patients were divided into a current smokers group and a former smokers group based on whether they had quit smoking. Logistic regression analysis was used to analyze the factors associated with smoking cessation. Of all patients with asthma, 34.6% were smokers and 65.4% were former smokers, and the mean age was 54.5 ± 11.5 years. Compared with current smokers, the former smokers were older, had longer duration of asthma, had higher ICS dose, had more partially controlled and uncontrolled asthma, had more pack-years, had smoked for longer, and had worse asthma control. The logistic regression model showed that smoking cessation was positively correlated with age, female sex, pack-years, years of smoking, partially controlled asthma, uncontrolled asthma, and body mass index (BMI), but was negatively correlated with ACT, FEV1, FEV1%predicted, and widowed status. More than 30% of asthma patients in the study were still smoking. Among those who quit smoking, many quit late, often not realizing they need to quit until they have significant breathing difficulties. The related factors of smoking cessation identified in this study indicate that there are still differences between continuing smokers and former smokers, and these factors should be focused on in asthma smoking cessation interventions to improve the prognosis of patients with asthma.


Assuntos
Asma , Abandono do Hábito de Fumar , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Asma/epidemiologia , Estudos Transversais , Fumantes , Fumar/efeitos adversos , Fumar/epidemiologia , Masculino
9.
Cells ; 12(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36672266

RESUMO

Radiotherapy with proton therapy (PT) has dosimetric advantages over photon therapy, which helps to enlarge the therapeutic window of radiotherapy for hepatocellular carcinoma (HCC). We evaluated the response of HCC to PT and examined the underlying mechanisms. The human liver cancer cell lines HepG2 and HuH7 and the murine liver cancer cell line Hepa1-6 were selected for cell and animal experiments to examine the response induced by PT irradiation. Biological changes and the immunological response following PT irradiation were examined. In vitro experiments showed no significant difference in cell survival following PT compared with photon radiotherapy. In a murine tumor model, the tumors were obviously smaller in size 12 days after PT irradiation. The underlying changes included increased DNA damage, upregulated IL-6 levels, and a regulated immune tumor microenvironment. Protein analysis in vitro and in vivo showed that PT increased the level of programmed cell death ligand 1 (PD-L1) expressed in tumor cells and recruited myeloid-derived suppressor cells (MDSCs). The increase in PD-L1 was positively correlated with the irradiation dose. In Hepa1-6 syngeneic mouse models, the combination of PT with anti-PD-L1 increased tumor growth delay compared with PT alone, which was associated with increased tumor-infiltrating T cells and attenuated MDSC recruitment in the microenvironment. Furthermore, when PT was applied to the primary HCC tumor, anti-PD-L1 antibody-treated mice showed smaller synchronous unirradiated tumors. In conclusion, the response of HCC to PT was determined by tumor cell killing and the immunological response in the tumor microenvironment. The combination with the anti-PD-L1 antibody to enhance antitumor immunity was responsible for the therapeutic synergism for HCC treated with PT. Based on our results, we suggest that PT combined with anti-PD-L1 may be a promising therapeutic policy for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Supressoras Mieloides , Terapia com Prótons , Humanos , Camundongos , Animais , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/metabolismo , Células Supressoras Mieloides/metabolismo , Morte Celular , Microambiente Tumoral
10.
Healthcare (Basel) ; 11(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36673599

RESUMO

This study examined patient unpunctuality's effect on patient appointment scheduling in the ultrasound department of a hospital. The study created a simulation system incorporating the formulated F3 distribution to describe patient unpunctuality. After the simulation model passed verification and validation processes, what-if scenarios were conducted under two policies: The preempt policy and the wait policy. A comparison of the total cost of each policy showed that the preempt policy performed better than the wait policy in the presence of unpunctuality. The study used sensitivity analyses to identify the different effects of patient unpunctuality on the system. The weights of the cost coefficient of both radiological technician's idle time and patient waiting time must be equal in order to achieve a lower cost. The patient's inter-arrival time must be close to the average total time in the system to achieve lower costs. Moreover, utilization decreases as the patient's inter-arrival increases. Therefore, the patient's inter-arrival time should be higher than, but close to, the service time to ensure less radiological technician's idle time and patient waiting time.

11.
Gastroenterol Res Pract ; 2023: 6973723, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36691432

RESUMO

Long noncoding RNAs are a novel class of regulators in human cancers. It has been reported that small nucleolar RNA hostgene 7 (SNHG7) can sponge microRNAs to regulate colorectal cancer (CRC) progression. Given its important regulatory role in cancer biology, we wondered whether SNHG7 is involved in drug resistance to anlotinib (ATB) in CRC. To answer this, we quantified the expression of SNHG7 by quantitative real-time PCR. We performed the Cell Counting Kit-8 and Colony formation assay, flow cytometric analysis, RNA pull-down, RNA-binding protein immunoprecipitation assay, and Luciferase reporter assay to confirm the interaction among SNHG7, miR-181a-5p, and GATA6. We found that SNHG7 was significantly upregulated in CRC tissues and cell lines and ATB-resistant cell lines, which was closely related to the poor overall survival of patients. Loss-of-function studies demonstrated that SNHG7 knockdown can inhibit CRC cell proliferation, increase apoptosis, and sensitize CRC cells to resist ATB. Mechanistic studies showed that SNHG7 acted as a competitive endogenous RNA to sponge miR-181a-5p to regulate the expression of GATA6, thereby promoting ATB resistance in ATB-resistant cell lines. In conclusion, SNHG7 plays an important role in ATB resistance, and it may be used to monitor ATB resistance in CRC.

12.
Biosens Bioelectron ; 225: 115084, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36693286

RESUMO

The microRNA21 (miR-21), a specific tumor biomarker, is crucial for the diagnosis of several cancer types, and investigation of its overexpression pattern is important for cancer diagnosis. Herein, we report a low-cost, rapid, ultrasensitive, and convenient biosensing strategy for the detection of miR-21 using a nanoplasmonic array chip coupled with gold nanoparticles (AuNPs). This sensing platform combines the surface plasmon resonance effect of nanoplasmonics (NanoSPR) and the localized surface plasmon resonance (LSPR) effect, which allows the real-time monitoring of the subtle optical density (OD) changes caused by the variations in the dielectric constant in the process of the hybridization of the target miRNA. Using this method, the miRNA achieves a broad detection range from 100 aM to 1 µM, and with a limit of detection (LoD) of 1.85 aM. Furthermore, this assay also has a single-base resolution to discriminate the highly homologous miRNAs. More importantly, this platform has high throughput characteristics (96 samples can be detected simultaneously). This strategy exhibits more than 86.5 times enhancement in terms of sensitivity compared to that of traditional biosensors.

14.
J Phys Chem Lett ; : 1265-1271, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719712

RESUMO

The photodissociation and photoionization behaviors of haloalkanes in the VUV regime are important to fully understand the mechanism of ozone depletion in the stratosphere. The ionization of dichloromethane (CH2Cl2) under the irradiation of 10.0 and 10.6 eV light was investigated. CH2Cl+ was observed at 10 Pa, while both CH2Cl+ and CHCl2+ were observed at higher pressure. The production efficiency of CH2Cl+ decreased with the increasing number density of CH2Cl2, while that of CHCl2+ increased. A kinetic model was successfully derived to quantitatively describe the variation trends of CH2Cl+ and CHCl2+, in which the competition between photoinduced ion-pair and photodissociation-assisted photoionization (PD-PI) were included. The ion-pair channel was quenched efficiently at higher pressure or concentration, which reduced its contribution. Our study proposed new insights into the complicated photoexcitation behaviors of CH2Cl2 in the VUV regime and revealed the important role of photodissociation in photoionization at low photon flux.

15.
Cancer Cell Int ; 23(1): 12, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707875

RESUMO

The NF-κB signaling pathway is overactivated in tumor cells, and the activation of the NF-κB signaling pathway releases a large number of inflammatory factors, which enhance tumor immunosuppression and promote tumor metastasis. The cytochrome P450 (CYP450) system consists of important metabolic enzymes present in different tissues and progressive tumors, which may lead to changes in the pharmacological action of drugs in inflammatory diseases such as tumors. In this study, the anticancer effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on breast cancer cells and the underlying mechanism were investigated. Result showed that THC selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner. Moreover, THC-induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species (ROS) induction. In addition, THC could affect the CYP450 enzyme metabolic pathway and inhibit the expression of CYP1A1 and activation of the NF-κB pathway, thereby inhibiting the migration and invasion of breast cancer cells. Furthermore, after overexpression of CYP1A1, the inhibitory effects of THC on the proliferation, metastasis, and induction of apoptosis in breast cancer cells were weakened. The knockdown of CYP1A1 significantly enhanced the inhibitory effect of THC on the proliferation, metastasis, and apoptosis induction of breast cancer cells. Notably, THC exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MCF-7 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Collectively, these results showed that TH could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the CYP1A1/NF-κB signaling pathway, indicating that THC serves as a potential candidate drug for the treatment of breast cancer.

17.
Behav Neurosci ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633988

RESUMO

Interaction between Pavlovian and instrumental control systems is key for adaptive motivated behavior, but also plays an important role in various neuropsychiatric disorders, including depression, addiction, and anxiety. Here, we employed the flouorodopa positron emission tomography ([¹8F]-DOPA PET) in healthy participants (N = 100) to assess whether dopamine synthesis capacity (Ki), specifically in the ventral striatum, accounts for individual variation in Pavlovian-to-instrumental transfer (PIT). Surprisingly, this was not the case. Rather, the relationship of ventral striatal Ki with PIT depended on working memory (WM) capacity. Ventral striatal dopamine boosted the effects of Pavlovian cues on instrumental responding to a greater degree in participants with higher WM capacity. Caution is warranted to interpret this post hoc four-way interaction given the modest sample size. Nonetheless, these results chime with prior findings demonstrating that dopaminergic drugs boost Pavlovian biases to a greater degree in participants with greater WM capacity and highlight the importance of interactions between striatal dopamine and WM capacity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

18.
BMC Musculoskelet Disord ; 24(1): 54, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681804

RESUMO

BACKGROUND: A consensus regarding the optimal approach for treating femoral neck fractures is lacking. We aimed to investigate the biomechanical outcomes of Femoral Neck System (FNS) internal fixation components in the treatment of nonanatomically reduced femoral neck fractures. METHOD: We constructed two types of femoral neck fractures of the Pauwels classification with angles of 30° and 50°, and three models of anatomic reduction, positive buttress reduction and negative buttress reduction were constructed. Subgroups of 1 to 4 mm were divided according to the distance of displacement in the positive buttress reduction and negative buttress reduction models. The von Mises stress and displacements of the femur and FNS internal fixation components were measured for each fracture group under 2100-N axial loads. RESULTS: When the Pauwels angle was 30°, the positive 1-mm and 2-mm models had lower FNS stress than the negative buttress model. The positive 3- and 4-mm models showed FNS stress similar to that of the negative buttress model. But the four positive buttress models had similar stresses on the femur as the negative buttress model. When the Pauwels angle was 50°, the four positive buttress models had higher FNS stress than the negative buttress model. Three positive buttress models (2 mm, 3 and 4 mm) resulted in lower stress of the femur than the negative buttress model, though the 1-mm model did not. When the Pauwels angle was 30°, the positive buttress model had a lower displacement of the FNS than the negative buttress model and a similar displacement of the femur with the negative buttress model. When the Pauwels angle was 50°, the positive buttress model had a higher displacement of the FNS and femur than the negative buttress model. Our study also showed that the von Mises stress and displacement of the internal fixation and the femur increased as the fracture angle increased. CONCLUSION: From the perspective of biomechanics, when the Pauwels angle was 30°, positive buttress was more stable to negative buttress. However, when the Pauwels angle was 50°, this advantage weakens. In our opinion, the clinical efficacy of FNS internal fixation with positive buttress may be related to the fracture angle, neck-shaft angle and alignment in the lateral view. This result needs verification in further clinical studies.


Assuntos
Fraturas do Colo Femoral , Colo do Fêmur , Humanos , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/cirurgia , Análise de Elementos Finitos , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Fenômenos Biomecânicos
19.
Food Chem ; 410: 135435, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36641913

RESUMO

Detrimental contamination of zearalenone (ZEN) in crops and foodstuffs has drawn intensive public attention since it poses an ongoing threat to global food security and human health. Highly sensitive and rapid response ZEN trace analysis suitable for complex matrices at different processing stages is an indispensable part of food production. Conventional detection methods for ZEN encounter many deficiencies and demerits such as sophisticated equipment and heavy labor intensity. Alternatively, the nanomaterial-based biosensors featured with high sensitivity, portability, and miniaturization are springing up and emerging as superb substitutes to monitor ZEN in recent years. Herein, we predominantly devoted to overview the progress in the fabrication strategies and applications of various nanomaterial-based biosensors, highlighting rationales on sensing mechanisms, response types, and practical analytical performance. Synchronously, the versatile nanomaterials integrating with diverse recognition elements for augmenting sensing capabilities are emphasized. Finally, critical challenges and perspectives to expedite ZEN detection are outlooked.

20.
Cancer Gene Ther ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36653483

RESUMO

Multiple primary lung cancer (MPLC) with lymph node metastasis (LNM) is a rare phenomenon of multifocal lung cancer. The genomic landscapes of MPLC and the clonal evolution pattern between primary lung lesions and lymph node metastasis haven't been fully illustrated. We performed whole-exome sequencing (WES) on 52 FFPE (Formalin-fixed Paraffin-Embedded) samples from 11 patients diagnosed with MPLC with LNM. Genomic profiling and phylogenetic analysis were conducted to infer the evolutional trajectory within each patient. The top 5 most frequently mutated genes in our study were TTN (76.74%), MUC16 (62.79%), MUC19 (55.81%), FRG1 (46.51%), and NBPF20 (46.51%). For most patients in our study, a substantial of genetic alterations were mutually exclusive among the multiple pulmonary tumors of the same patient, suggesting their heterogenous origins. Individually, the genetic profile of lymph node metastatic lesions overlapped with that of multiple lung cancers in different degrees but are more genetically related to specific pulmonary lesions. SETD2 was a potential metastasis biomarker of MPLC. The mean putative neo-antigen number of the primary tumor (646.5) is higher than that of lymph node metastases (300, p = 0.2416). Primary lung tumors and lymph node metastases are highly heterogenous in immune repertoires. Our findings portrayed the comprehensive genomic landscape of MPLC with LNM. We characterized the genomic heterogeneity among different tumors. We offered novel clues to the clonal evolution between MPLC and their lymphatic metastases, thus advancing the treatment strategies and preventions of MPLC with LNM.

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