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1.
Environ Pollut ; 316(Pt 1): 120555, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332709

RESUMO

Due to anthropogenic activities, heavy metals are discharged into the hydrosphere and deposit onto the sediment. Heavy metals remobilize through physical disturbance and change in environmental conditions, posing a risk to environments and human health. Among several remediation methods, active layer capping is considered to be more feasible due to its financial and technical advantages; however, its long-term effects remain unknown. To overcome this problem, this work applied a novel, recoverable amendment, sulfurized magnetic biochar (SMBC), to remediate multiple heavy metal (Cu, Ni, Zn, Cr, Hg, and MeHg) contaminated sediment. Physiochemical characterization shows magnetite (Fe3O4) crystalline in both magnetic biochar (MBC) and SMBC, with such characteristics resulting in a greater surface area (324.9 and 346.3 m2/g) than BC (39.6 m2/g) and SBC (65.0 m2/g). FeS crystalline was also observed in SMBC, which plays an important role in controlling heavy metal release from sediment. Microcosm experiments indicated the effectiveness of SMBC in lowering aquatic Cu, Ni, Zn, Hg, and MeHg releases was significantly greater than the other three biochar materials. Notably, the recovery of SMBC by magnetism was 87%, demonstrating the exceptional recoverability of SMBC from seawater and sediment. Based on its robust capability in lowering Cu, Ni, Zn, Hg, and MeHg release and excellent recoverability from seawater and sediment, this technique represents a practical alternative to conventional approaches for heavy metal immobilization from sediment.

2.
Phytomedicine ; 108: 154538, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36370638

RESUMO

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a clinically commonly-seen slow-progressing cerebral vascular disease. As a classic Chinese formula for the treatment of stroke, Daqinjiao Decoction (DQJD) is now used to treat CSVD with desirable effect. Since the mechanism of action is still unclear, this article will explore the therapeutic effect and mechanism of action of the formula using network pharmacology technology. METHODS: The major chemical components and potential target genes of DQJD were screened by bioinformatics. The key targets in CSVD were identified based on network modules. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Pharmacodynamics of the decoction was evaluated by establishing a rat model with bilateral common carotid artery occlusion in the brain. Molecular docking, Western blot analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to confirm the effectiveness of targets in related pathways. RESULTS: Network pharmacology showed that 16 targets and 30 pathways were involved in the DQJD-targeted pathway network. Results revealed that DQJD might play a role by targeting the key targets including Caspse3 and P53 and regulating the P53 signaling pathway. Cognitive function and neuronal cell changes of rats were evaluated using Morris water maze, open field test and HE staining. It was indicated that DQJD could keep the nerve cells intact and neatly arranged. The decoction could improve the memory and learning ability of rats compared with the model group. It decreased the protein and mRNA expression levels of Caspse3 and P53 significantly (p<0.01). CONCLUSION: The study shows that baicalein, quercetin and wogonin, the effective components of DQJD, may regulate multiple signaling pathways by targeting the targets like Caspse3 and P53 and treat CSVD by reducing the damage to brain nerve cells.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Medicamentos de Ervas Chinesas , Animais , Ratos , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/química , Farmacologia em Rede , Proteína Supressora de Tumor p53 , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Tecnologia
3.
J Ethnopharmacol ; 301: 115802, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36209953

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Thousands of years of clinical practice in the treatment of joint-related diseases support the efficacy and safety of Wutou decoction (WTD). Nevertheless, the lack of pharmacological evidence and unclear mechanisms make it difficult for WTD to become a recognized complementary therapy for the treatment of rheumatoid arthritis (RA). AIM OF THE STUDY: This study aimed to investigate the effect of WTD against synovial inflammation in RA and whether this effect depends on the regulation of macrophage polarization. MATERIALS AND METHODS: Sprague-Dawley rats were used to establish the collagen-induced arthritis (CIA) model. WTD with low and high doses was administered for 45 days. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) or interleukin (IL)-4 to polarize M1 and M2 macrophages, which were pre-treated with WTD extract for 4 h. The anti-arthritic and anti-inflammatory effects of WTD were studied using arthritis score, histopathological staining, immunostaining, and enzyme-linked immunosorbent assay (ELISA). The polarization state of RAW264.7 cells and related pro/anti-inflammatory cytokines was detected by ELISA, reverse transcription quantitative polymerase chain reaction and western blotting. Western blotting and immunofluorescence were used to investigate the effect of WTD on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptors γ (PPARγ) activation both in vivo and in vitro. RESULTS: WTD significantly reduced the arthritis score and the pathological damage of the knee joint and decreased the expression of tumor necrosis factor alpha (TNF-α), IL-6 in serum, TNF-α, IL-1ß, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-3 (MMP3) in the knee synovium. WTD inhibited M1 type polarization and promoted M2 type polarization, both in vitro and in vivo, and reduced the expression of pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines. Experiments showed that WTD inhibited the phosphorylation of NF-κB and downstream p38 in the synovium of CIA rats and LPS-induced M1 type polarized RAW264.7 cells. In addition, PPARγ expression in the synovium of CIA rats was mainly located in the cytoplasm, and WTD treatment increased the nuclear translocation of PPARγ, which was further verified in RAW264.7 cells. CONCLUSIONS: NF-κB and PPARγ regulating M1 and M2 macrophage polarization and subsequent secretion of pro-inflammatory and anti-inflammatory cytokines are the underlying mechanisms of WTD that ameliorate RA synovial inflammation.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Ratos , Anti-Inflamatórios , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Macrófagos , NF-kappa B/metabolismo , PPAR gama/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
4.
Food Chem ; 404(Pt B): 134683, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36323028

RESUMO

This study investigated the impact of multiple thermal treatments (explosion-puffing, microwave, and roasting) on the processing qualities of sesame seeds and cold-pressed oil. The scanning electron microscopy (SEM) showed fissures and cavities of sesame seed surface upon thermal treatments. The microwave treatment promoted the maximum conversion of sesamolin into sesamol in the sesame oil. Compared with other treatments, explosion-puffing treatment resulted in most significant increases in the multiple beneficial phytochemicals, as well as in vitro antioxidant properties determined by 2,2-dipheny1-1-picrylhydrazyl radical (DPPH) radical scavenging activity, Ferric reducing antioxidant power (FRAP) and oxidative stability index (OSI). Additionally, thermal treatment processing caused varying degrees of damage of crude protein, total amino acids (TAA) and protein structure (tertiary and second structure). In which, explosion-puffing achieved minimal reduction in the first two indicators. Collectively, explosion-puffing might be a preferable thermal treatment method for industrial sesame processing with improved quality specifications.


Assuntos
Sesamum , Sesamum/química , Antioxidantes , Óleo de Gergelim/química , Oxirredução , Sementes
5.
Sci Total Environ ; 856(Pt 1): 158910, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36152852

RESUMO

Evaluating the embodied environmental impact of solar photovoltaic (PV) technology has been an important topic in addressing the sustainable development of renewable energy. While monetization of environmental externality is a remaining issue, which should be carried out in order to allow for an easy-to-understand comparison between direct economic and external cost. In this study, the environmental impact of solar PV power is monetized through conversion factors between midpoint and endpoint categories of life cycle analysis and the monetization weighting factor. Then, the power generation capacity and generation life of PV and coal-fired power plants are assumed to be consistent in order to compare the total cost of PV and coal-fired power generation. Results show that the cost of PV technology is higher than coal-fired form the base year from 2026 until 2030, taking into account environmental external costs and production costs. However, by 2030, the total cost of coal-fired power will be higher than that of solar PV. The life span cost per kWh is $3.55 for solar PV and $116.25 for coal-fired power. Although solar PV power seems more environmentally effective than coal-fired power in the life span, our results reveal the high environmental external cost of producing solar photovoltaic modules, which reminds us to pay more attention to the environmental impact when conducting cost-benefit analysis of renewable technologies. Without incorporating the environmental cost, the real cost of renewable technology will be underestimated.


Assuntos
Energia Solar , Animais , Centrais Elétricas , Carvão Mineral , Custos e Análise de Custo , Estágios do Ciclo de Vida
6.
J Oncol ; 2022: 7913067, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457717

RESUMO

Breast cancer is one of the most frequently diagnosed cancer in women and is the major cause of most cancer-related deaths. We previously reported that Brachyury, as a sensitive and specific marker, has been verified to involve in the process of carcinogenesis and progression of breast cancer, but the mechanism by which Brachyury promotes breast cancer cells proliferation and migration still remains less clear. In this study, we identified that Brachyury was markedly increased in breast cancer compared with the adjacent tissues. We have also shown that Brachyury knockdown could decrease the proliferation and migration capability in breast cancer cells both in vitro and in vivo. Finally, we found an important transcriptional factor, E2F3, which is a direct downstream target gene of Brachyury by chromatin immunoprecipitation (ChIP) analysis. Knockdown of E2F3 also decreased breast cancer cell proliferation and migration. Taken together, we reported that Brachyury may act as an oncogenic role in the progression of breast cancer by positively-regulating E2F3 expression.

7.
Plant Physiol ; 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36459587

RESUMO

Intracellular movement is an important step for the initial spread of virus in plants during infection. This process requires virus-encoded movement protein(s) [MP(s)] and their interaction with host factors. Despite the large number of known host factors involved in the movement of different viruses, little is known about host proteins that interact with one of the MPs encoded by potexviruses, the triple-gene-block protein 3 (TGBp3). The main obstacle lies in the relatively low expression level of potexviral TGBp3 in hosts and the weak or transient nature of interactions. Here, we used TurboID-based proximity labeling to identify the network of proteins directly or indirectly interacting with the TGBp3 of a potexvirus, Bamboo mosaic virus (BaMV). Endoplasmic reticulum (ER) luminal binding protein 4 and calreticulin 3 of Nicotiana benthamiana (NbBiP4 and NbCRT3, respectively) associated with the functional TGBp3-containing BaMV movement complexes, but not the movement-defective mutant, TGBp3M. Fluorescent microscopy revealed that TGBp3 colocalizes with NbBiP4 or NbCRT3 and the complexes move together along ER networks to cell periphery in N. benthamiana. Loss- and gain-of-function experiments revealed that NbBiP4 or NbCRT3 is required for the efficient spread and accumulation of BaMV in infected leaves. In addition, overexpression of NbBiP4 or NbCRT3 enhanced the targeting of BaMV TGBp1 to plasmodesmata (PD), indicating that NbBiP4 and NbCRT3 interact with TGBp3 to promote the intracellular transport of virion cargo to PD that facilitates virus cell-to-cell movement. Our findings revealed additional roles for NbBiP4 and NbCRT3 in BaMV intracellular movement through ER networks or ER-derived vesicles to PD, which enhances the spread of BaMV in N. benthamiana.

8.
Food Res Int ; 162(Pt A): 111948, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461283

RESUMO

To enhance physiological activity and probiotic availability of sea buckthorn juice, sea buckthorn juice pulp (BHJ) went through fermentation to the fermented (FHJ). In vitro, FHJ displayed better antioxidant and antidiabetic capacities. To further study effects of FHJ on diet-induced metabolic syndrome (MS) and possible mechanisms in vivo, C57BL/6 mice were fed on BHJ and FHJ under high fat diet (HFD). FHJ, rather BHJ, displayed better performance on ameliorating hyperlipidemia, insulin resistance, and oxidative stress in MS. Mechanistically, FHJ intervention significantly reversed the microorganism dysbiosis by restoring the microbial diversity, and modulating obesogenic bacteria abundance, like Oscillospira. Furthermore, fermentation altered FHJ's metabolomics, especially flavonoids, contributing to interactions between FHJ and probiotics, like Akkermansia and Lachnospiraceae. Furthermore, short-chain fatty acids, related to ameliorations of MS, were increased by FHJ. This study demonstrated that interactions between metabolomic alterations in FHJ and microorganisms were vital to attenuate MS.


Assuntos
Microbioma Gastrointestinal , Hippophae , Síndrome Metabólica , Probióticos , Camundongos , Animais , Fermentação , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Metaboloma
9.
BMC Cancer ; 22(1): 1246, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457074

RESUMO

BACKGROUND: Lateral neck is not recommended for dissection in patients with pN1a papillary thyroid cancer (PTC), but its recurrence risk has not been well stratified. We aimed to develop a risk stratification system for lateral neck recurrence in patients with pN1a PTC. METHODS: Patients with pN1a PTC who underwent thyroidectomy and unilateral central compartment dissection from 2000-2016 were enrolled. The association between number of central lymph node metastases (CLNMs) and lateral neck recurrence was comprehensively assessed using a Cox proportional hazards model with restricted cubic spline. Stratification was then performed based on CLNMs and other significant risk factors selected by multivariate analysis. Lateral neck recurrent-free survival (LRFS) rate of each stratification was estimated with Kaplan-Meier curve and comparison was performed using log-rank test. RESULTS: Ninety-six (3.8%) lateral neck recurrences were identified during a median follow-up of 62 months among a total of 2500 admitted cases. An increasing number of CLNMs was associated with compromised LRFS for up to 6 CLNMs (P < 0.001), and CLNMs > 3 indicated significantly worse 5-year LRFS than that of CLNM ≤ 3 (90.6% vs. 98.1%, P < 0.001). When stratification with CLNMs and primary tumor size (selected by multivariate analysis, HR (95%CI) = 4.225(2.460-7.256), P < 0.001), 5-year LRFS rates of high- (CLNMs > 3 and primary tumor size > 2 cm), intermediate- (CLNMs > 3 and primary tumor size 1-2 cm) and low-risk (primary tumor size ≤ 1 cm or CLNMs ≤ 3) groups were 78.5%, 90.0% and 97.9%, respectively (P < 0.05). CONCLUSIONS: The number of CLNMs combined with primary tumor size seems to effectively stratify lateral neck recurrence risk for patients with pN1a PTC.


Assuntos
Pescoço , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Metástase Linfática , Neoplasias da Glândula Tireoide/cirurgia , Medição de Risco
10.
Medicine (Baltimore) ; 101(47): e31882, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451472

RESUMO

BACKGROUND: Atherosclerotic acute carotid occlusion is a specific type of stroke, and controversy exists regarding the surgical strategy, that is, whether an internal carotid artery stent should be placed immediately after opening the occluded vessel. There is no objective evaluation system for this procedure. In a previous study, we summarized an evaluation decision system Emergent Carotid Artery Stent placement decision Evaluation System (ECASES) for emergency stent placement. STUDY DESIGN: This is a prospective, single-center, randomized controlled trial. Patients with acute ischemic stroke caused by atherosclerotic carotid artery occlusion confirmed by imaging (computed tomography/magnetic resonance angiography/digital subtraction angiography) will be randomly divided into the study and control groups, with 101 patients in each group. The study group will undergo surgery according to the ECASES system and the control group will undergo surgery according to the operator's experience. The postoperative outcomes of the 2 groups will be compared. STUDY OUTCOMES: Primary outcome: Neurological functional status (modified Rankin Scale and National Institutes of Health Stroke Scale scores) of patients 90 days postoperatively. Secondary outcomes: neurological function changes, hemorrhage events, cerebral edema, postoperative modified treatment in cerebral infarction grade, new cerebral infarction, and reocclusion of responsible vessels. DISCUSSION: Currently, no prospective controlled data exist regarding the efficacy and safety of carotid stenting in the acute phase. Previously, we had developed an ECASES stent placement system for acute carotid artery occlusion. The present study will evaluate the efficacy and safety of ECASES in a randomized, double-blind prospective study and clarify its guiding significance in acute atherosclerotic carotid artery occlusion surgery.


Assuntos
Doenças das Artérias Carótidas , AVC Isquêmico , Acidente Vascular Cerebral , Estados Unidos , Humanos , Estudos Prospectivos , Stents , Angiografia Digital , Infarto Cerebral , Acidente Vascular Cerebral/etiologia
11.
ACS Appl Mater Interfaces ; 14(47): 52634-52642, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36383430

RESUMO

Neoantigen vaccines have opened a new paradigm for cancer immunotherapy. Here, we constructed a neoantigen nanovaccine-HemoMap, with the ability to target lymph nodes and activate immune cells. We propose a HemoMap nanovaccine consisting of the mouse melanoma highly expressed antigenic peptide Tyrp1 and a magnesium nanoadjuvant-HemoM. By immunofluorescence labeling of the nanovaccine, the lymph node targeting of the vaccine was observed and verified by a mouse near-infrared imaging system. About two-fold higher effective retention of HemoMap induces the internalization of Tyrp1 in DCs than that of free Tyrp1 in draining lymph nodes (DLNs) for 48 h. A mouse melanoma subcutaneous model was established to evaluate neoantigen-specific antitumor immune responses. In comparison to the control group, the tumor growth rate was dramatically slowed down by HemoMap treatment, and the median survival time was extended by 7 days. We discovered that effective co-delivery of Tyrp1 antigen and magnesium (Mg2+) to lymph nodes (LNs) boosted cellular internalization and activated immune cells, such as CD11c+ DCs and CD8+ T lymphocytes. Spleen lymphocytes from the HemoMap group displayed much more antitumor activity than those from the other groups. Our findings highlight that HemoMap is promising to trigger T cell responses and to provide novel nanoadjuvants strategies for cancer immunotherapy.


Assuntos
Vacinas Anticâncer , Melanoma , Camundongos , Animais , Magnésio , Imunoterapia/métodos , Melanoma/terapia , Imunidade , Células Dendríticas , Camundongos Endogâmicos C57BL
12.
Sensors (Basel) ; 22(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36433456

RESUMO

Forest fire prevention is very important for the protection of the ecological environment, which requires effective prevention and timely suppression. The opening of the firebreaks barrier contributes significantly to forest fire prevention. The development of an artificial intelligence algorithm makes it possible for an intelligent belt opener to create the opening of the firebreak barrier. This paper introduces an innovative vision system of an intelligent belt opener to monitor the environment during the creation of the opening of the firebreak barrier. It can provide precise geometric and location information on trees through the combination of LIDAR data and deep learning methods. Four deep learning networks including PointRCNN, PointPillars, SECOND, and PV-RCNN were investigated in this paper, and we train each of the four networks using our stand tree detection dataset which is built on the KITTI point cloud dataset. Among them, the PointRCNN showed the highest detection accuracy followed by PV-RCNN and PV-RCNN. SECOND showed less detection accuracy but can detect the most targets.


Assuntos
Aprendizado Profundo , Algoritmos , Inteligência Artificial
13.
J Mol Model ; 28(12): 406, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36451058

RESUMO

3-nitro-1,2,4-triazol-5-one (NTO)-based polymer-bonded explosives (PBXs) have been widely used in insensitive munitions, but the main properties of NTO-based PBXs such as compatibility, safety performance, and mechanical properties are rarely reported. In this work, molecular dynamics simulation was carried out to study interface interactions of NTO-based PBXs, in which hydroxy-terminated polybutadiene (HTPB), ethylene-vinyl acetate copolymer (EVA), glycidyl azide polymer (GAP), poly-3-nitratomethyl-3-methyl oxetane (Poly-NIMMO), and ester urethane (Estane5703) are selected as binders. The binding energy analysis indicates that the order of compatibility is NTO/GAP > NTO/Estane5703 > NTO/HTPB > NTO/Poly-NIMMO > NTO/EVA. Radial distribution function analysis results show that the interface interaction is mainly the hydrogen bond between H atoms of NTO and O atoms of Estane5703, HTPB, EVA, and Poly-NIMMO or N atoms of GAP. The values of cohesive energy density verify that the safety is NTO/GAP > NTO/Poly-NIMMO > NTO/HTPB > NTO/EVA > NTO/Estane5703. Mechanical properties results show that GAP and EVA would improve the plasticity of the systems effectively. Furthermore, it can be found that the most favorable interactions occur between the NTO (1 0 0) crystal face and binders.

14.
Cell Death Dis ; 13(11): 1004, 2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36437247

RESUMO

Blocked cellular differentiation is a critical pathologic hallmark of acute myeloid leukemia (AML). Here, we showed that genetic activation of the orphan GPCR GPR132 significantly induced cell differentiation of AML both in vitro and in vivo, indicating that GPR132 is a potential trigger of myeloid differentiation. To explore the therapeutic potential of GPR132 signaling, we screened and validated a natural product 8-gingerol (8GL) as a GPR132 agonist. Notably, GPR132 activation by 8GL promoted differentiation and reduced colony formation in human AML cell lines with diverse genetic profiles. Mechanistic studies revealed that 8GL treatment inhibits the activation of the mammalian target of rapamycin (mTOR), a regulator of AML cell differentiation blockade, via activating GPR132-Gs-PKA pathway. We further showed that the combination of 8GL and an mTOR inhibitor synergistically elicited AML cell differentiation in vitro. Importantly, 8GL alone or in combination with an mTOR inhibitor remarkably impaired tumor growth and extended mouse survival in an AML xenograft model accompanied by enhanced cell differentiation. Notably, genetic or pharmacological activation of GPR132 triggered the differentiation of human primary AML cells. In summary, this study demonstrated that activation of orphan GPR132 represents a potential strategy for inducing myeloid differentiation in AML patients.


Assuntos
Diferenciação Celular , Leucemia Mieloide Aguda , Receptores Acoplados a Proteínas G , Animais , Humanos , Camundongos , Proteínas de Transporte/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Mamíferos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
15.
Neural Netw ; 157: 323-335, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36379102

RESUMO

Deep learning based facial landmark detection (FLD) has made rapid progress. However, the accuracy and robustness of FLD algorithms are degraded heavily when the face is subject to diverse expressions, posture deflection, partial occlusion and other uncertain circumstances. To learn more discriminative representations and reduce the negative effect caused by outliers, a stacked attention hourglass network (SAHN) is proposed for FLD, where new attention mechanism is introduced. Basically, in the design of SAHN, a spatial attention residual (SAR) unit is constructed such that relevant areas of facial landmarks are specially emphasized and essential features of different scales can be well extracted, and a channel attention branch (CAB) is introduced to better guide the next-level hourglass network for feature extraction. Due to the introduction of SAR and CAB, only two hourglass networks are stacked as the proposed SAHN with fewer parameters, which is different from traditional SHNs stacked by four hourglass networks. Furthermore, a variable robustness (VR) loss function is introduced for the training of SAHN. The robustness of the proposed model for FLD is guaranteed with the help of the VR loss by adaptively adjusting a continuous parameter. Extensive experimental results on three public datasets including 300W, WFLW and COFW confirm that our method is superior to some previous ones.

16.
JAMA Surg ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36449303

RESUMO

Importance: Surgical treatment of patients with papillary thyroid cancer (PTC) by either lobectomy or total thyroidectomy (TT) has long been a topic of debate, especially for patients with intermediate-risk PTC. Objective: To compare recurrence-free survival (RFS) for patients with PTC and lymph node metastasis after lobectomy vs TT. Design, Setting, and Participants: This retrospective cohort study included a review of patients with PTC treated from January 1, 2000, to December 31, 2017. Propensity score matching (PSM) was performed between patients treated with lobectomy and TT. This study involved a single institute in a cancer referral center. Enrolled were adult patients (aged 18-75 years) with unilateral PTC and ipsilateral clinical lateral neck metastasis (cN1b). Patients with the following characteristics were excluded: a lymph node yield less than 20, primary tumor size greater than 4 cm, gross extrathyroidal extension, metastatic lymph node size greater than 3 cm, and distant metastasis. Data analysis was performed from April 1 to April 30, 2022. Exposures: Lobectomy and TT. Main Outcomes and Measures: The primary outcome was the association between extent of surgery and RFS, assessed using Cox proportional hazards regression models. Results: A total of 946 patients with PTC (mean [SD] age, 37.0 [12.1] years, 630 female individuals [66.6%]) were analyzed. Lobectomy (624 [66.0%]) was negatively correlated with the frequencies of older age (≥65 years, 17 [2.7%]), female sex (393 [63.0%]), multifocality (132 [21.2%]), minor extrathyroidal extension (259 [41.5%]), number of metastatic lymph nodes (median [range], 9 [6-14] nodes), and radioactive iodine ablation (0). After PSM with treatment period and potential prognostic factors (age, sex, primary tumor size, multifocality, minor extrathyroidal extension, number of lymph node metastases and lymph node ratio), 265 pairs of patients were available for analysis. After a median (range) follow-up of 60 (9-150) months in the lobectomy group and 58 (8-161) months in the TT group, 21 (7.9%) and 17 (6.4%) structural recurrences were identified in the lobectomy and TT groups, respectively. Lobectomy was not associated with significantly compromised 5-year RFS rate (lobectomy, 92.3% vs TT, 93.7%; adjusted hazard ratio, 1.10; 95% CI, 0.58-2.11; P = .77). Power analysis indicated that the test had 90% power to detect a more than 4.9% RFS difference. No significant difference in RFS was observed between patients treated with TT and radioactive iodine ablation (n = 75) and their counterparts (adjusted hazard ratio, 0.59; 95% CI, 0.14-2.41; P = .46). Conclusions and Relevance: Results of this cohort study suggest that patients with PTC and lymph node metastasis had a similar RFS after lobectomy vs those who had TT. If radioactive iodine ablation is not going to be performed, lobectomy may be an effective alternative option.

17.
Sci Adv ; 8(46): eabq4659, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36399575

RESUMO

Directly delivering therapeutic proteins to their intracellular targets remains a great challenge. Here, we apply CD8+ T cells to form pores on the tumor cells' plasma membranes, enabling perfusion of ribonuclease A (RNase A) and granzyme B into cells, therefore effectively inducing tumor apoptosis and pyroptosis by activating caspase 3 and gasdermin E pathways to potentiate the CD8+ T cell-mediated immunotherapy. Then, RNase A, programmed cell death ligand 1 antibody, and a photothermal agent were further loaded into an injectable hydrogel to treat the low immunogenic murine breast cancer. Notably, three courses of laser irradiation induced efficient cell apoptosis and immune activation, resulting in a notable therapeutic efficacy that 75% of the tumors were ablated without relapse.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Camundongos , Animais , Ribonuclease Pancreático , Piroptose/fisiologia , Imunoterapia , Apoptose , Neoplasias/terapia
18.
Stat Med ; 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36404417

RESUMO

In vaccine research towards the prevention of infectious diseases, immune response biomarkers serve as an important tool for comparing and ranking vaccine candidates based on their immunogenicity and predicted protective effect. However, analyses of immune response outcomes can be complicated by differences across assays when immune response data are acquired from multiple groups/laboratories. Motivated by a real-world problem to accommodate the use of two different neutralization assays in COVID-19 vaccine trials, we propose methods based on left-censored multivariate normal model assuming common assay differences across settings, to adjust for differences between assays with respect to measurement error and the lower limit of detection. Our proposed methods integrate external paired-sample data with bridging assumptions to achieve two objectives, both using pooled data acquired from different assays: (i) comparing immunogenicity between vaccine regimens, and (ii) evaluating correlates of risk. In simulation studies, for the first objective, our method leads to unbiased calibrated assay mean with good coverage of bootstrap confidence interval, as well as valid test for immunogenicity comparison, while the alternative method assuming constant calibration model between assays leads to biased estimate of assay mean with undercoverage problem and invalid test with inflated type-I error; for the second objective, in the presence of noticeable left-censoring rate, our proposed method can drastically outperform the existing method that ignores left-censoring, in terms of reduced bias and improved precision. We apply the proposed methods to SARS-CoV-2 spike-pseudotyped virus neutralization assay data generated in vaccine and convalescent samples by two different laboratories.

19.
Gynecol Endocrinol ; : 1-4, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36342905

RESUMO

OBJECTIVE: To investigate the effects of blood lipid concentration and blood lipid growth rate in the first and third trimesters of pregnancy on adverse pregnancy outcomes. METHODS: The study subjects were 1051 singleton pregnant women who established archives in Chengdu Maternity and Child Specialty Hospital. The pregnancy information was continuously recorded until the pregnant woman gave birth, and lipid biochemical indicators were performed every three months. RESULTS: The average age of the pregnant women recruited was 27.82 ± 3.07 years. Compared with the first trimester, the concentration of triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in the third trimester were increased significantly (all p < .05). The growth rate of triglyceride was closely related to the occurrence of gestational diabetes mellitus and large for gestational, and the growth rate of total cholesterol and low-density lipoprotein cholesterol was closely related to gestational diabetes mellitus and cholestasis of pregnancy. For every unit increase in triglyceride growth rate, the risk of gestational diabetes mellitus and large for gestational age increases by 1.237 times and 1.317 times, respectively. CONCLUSION: Among non-high-risk pregnant women, blood lipid concentration is generally high among pregnant women with complications during pregnancy. It is necessary to combine a single blood lipid test concentration during pregnancy with the blood lipid growth rate to assess the condition of pregnant women and provide better guidance during pregnancy.

20.
Plant Dis ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36383992

RESUMO

Sugarcane (Saccharum officinarum) is an economically important crop and is extensively planted across China. In August 2020, leaf midribs with red lesions were observed on cultivar 'Yunzhe 081609' in Kaiyuan (103.27°E, 23.71°N), Yunnan, Southwestern China. In July to August 2021, similar symptoms were observed on cultivar 'Liucheng 05-136' in Hechi (108.48°E, 24.47°N), Guangxi, and on cultivars 'Yingyu 91-59' and 'Yunzhe 081609' in Lingcang (99.45°E, 23.33°N), Yunnan. Initially symptoms appeared as red spots on the leaf midribs, which gradually expanded, forming elongated red lesions. At high severity, the leaves broke and hung down. Disease incidence of leaves was estimated at 30 to 50% across the locations. To identify the etiology of this disease, three symptomatic leaves were collected from cultivars 'Liucheng 05-136', 'Yingyu 91-59', and 'Yunzhe 081609', respectively. Symptomatic leaf midribs were cut to small fragments (3 × 5 mm), surface sterilized with 70% ethanol for 30 s followed by 1% NaClO for 1 min, rinsed with sterilized distilled water three times, air dried on sterile filter paper, plated on potato dextrose agar (PDA), and incubated at 28°C in the dark. Ten isolates with similar morphological characteristics were obtained. Colonies on PDA were white to grayish-white with aerial mycelium growing initially upward and then forming clusters. After 10 days, mycelia turned to grayish black. Immature conidia were initially hyaline, aseptate, and ellipsoid. Mature conidia became dark brown, septate, longitudinal striate, and measured 21.2 to 25.8 × 11.4 to 16.4 µm (n = 30). Morphologically, the isolates were identified as Lasiodiplodia theobromae (Alves et al. 2008). For molecular identification, genomic DNA of four representative isolates (LTGX1, LTGX2, LTYN1 and LTYN2) was extracted using the Ezup Column Fungi Genomic DNA Purification kit. The internal transcribed spacer (ITS) region of rDNA, translation elongation factor 1-alpha (TEF-1α) gene, and ß-tubulin (TUB) gene were amplified with primer pairs ITS1/ITS4 for ITS, EF1-728F/EF1-986R for TEF-1α, and Bt2a/Bt2b for TUB, respectively (Glass and Donaldson 1995; Carbone and Kohn 1999; White et al. 1990), and then sequenced. The ITS (ON533336-ON533339), TEF-1α (ON939550-ON939553) and TUB (OP747306-OP747309) sequences were deposited in GenBank. BLAST searches showed >99% nucleotide identity to the sequences of ex-type isolate CBS 164.96 of L. theobromae (ITS, 99.8% to AY640255; TEF-1α, 99.9% to AY640258; TBU, 100% to EU673110). Phylogenetic analysis using maximum likelihood based on the combined ITS, TEF-1α, and TUB sequences of the isolates and reference sequences of Lasiodiplodia spp. downloaded from the GenBank indicated the isolates obtained in this study formed a clade strongly supported based on bootstrap values (100%) to the ex-type isolate CBS 164.96 sequences of L. theobromae. For pathogenicity tests, three healthy 6-month-old potted sugarcane leaf midribs of cultivar 'Yunzhe 081609' were wounded with a sterile needle, then inoculated using 8-mm mycelial agar plugs from a 10-day-old culture of strain LTYN1, and covered with wet cotton to maintain high relative humidity. Sterile PDA plugs were used as controls. Plants were placed in a greenhouse at 28 to 32°C. The test was conducted twice. Five days after inoculation, red lesions appeared on the inoculated leaf midribs. These symptoms were similar to those observed in the field. The leaves used for negative controls remained symptomless. The same fungus (L. theobromae) was re-isolated from all inoculated-symptomatic tissues; and isolates had the same morphological traits mentioned above. The DNA sequence data of these isolates was also similar than the original isolates. The association of L. theobromae with S. officinarum was recorded earlier in Cuba (Urtiaga, 1986), Myanmar (Thaung, 2008) and the Philippines (Reinking, 1919). Leaf midribs with red lesions caused by Colletotrichum falcatum has already been described around the world (Costa et al. 2021; Hossain et al. 2021; Xie et al. 2019). All together, this information indicates that L. theobromae is one of the causal agent of the red lesions symptoms on the sugarcane leaf midribs. To our knowledge, this is the first report of L. theobromae causing red lesions on leaf midribs of sugarcane in China. Further research will focus on developing management strategies to control this disease effectively.

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