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1.
J Phys Chem Lett ; : 4297-4308, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35532545

RESUMO

Molecular cross-scale gridization and polygridization of organic π-backbones make it possible to install 0/1/2/3-dimensional organic wide-bandgap semiconductors (OWBGSs) with potentially ZnO-like fascinating multifunctionality such as optoelectronic and piezoelectronic features. However, gridization effects are limited to uncover, because the establishment of gridochemistry still requires a long time, which offers a chance to understand the effects with a theoretical method, together with data statistics and machine learning. Herein, we demonstrate a state-of-the-art 3D cubic nanogridon with a size of ∼2 × 2 × 1.5 nm3 to examine its multigridization of π-segments on the bandgap, molecular strain energy (MSE), as well as reorganization energy (ROE). A cubic gridon (CG) consists of a four-armed bifluorene skeleton and a thiophene-containing fused arene plane with the Csp3 spiro-linkage, which can be deinstalled into face-on or edge-on monogrids. As a result, multigridization does not significantly reduce bandgaps (Eg ≥ 4.03 eV), while the MSE increases gradually from 4.72 to 23.83 kcal/mol. Very importantly, the ROE of a CG exhibits an extreme reduction down to ∼28 meV (λ+) that is near the thermal fluctuation energy (∼26 meV). Our multigridization results break through the limitation of the basic positively proportional relationship between reorganization energies and bandgaps in organic semiconductors. Furthermore, multigridization makes it possible to keep the ROE small under the condition of a high MSE in OWBGS that will guide the cross-scale design of multifunctional OWBGSs with both inorganics' optoelectronic performance and organics' mechanical flexibility.

2.
PLoS One ; 17(5): e0268779, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35594278

RESUMO

BACKGROUND: The efficacy and safety of stereotactic body radiotherapy (SBRT) plus transcatheter arterial chemoembolization (TACE) versus SBRT or TACE alone(monotherapy) for hepatocellular carcinoma (HCC) patients with portal vein tumour thrombus (PVTT) remains controversial. This meta-analysis was performed to provide more powerful evidence for clinical strategies in inoperable HCC with PVTT. METHODS: We searched the PubMed, EMBASE, Web of Science, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), VIP Journal Integration Platform (VIP), and WanFang databases for eligible studies. We pooled the results of 1- and 2-year overall survival rates (OSRs), objective response rates (ORRs), and adverse events (AEs) between the two groups and performed a subgroup meta-analysis for study type, control group, treatment order, and the interval between SBRT and TACE. RESULTS: Nine studies with 10 cohorts involving 938 patients were included in our meta-analysis. SBRT plus TACE yielded significantly higher 1-year OSR (RR, 1.52[95% CI, 1.33-1.74]), 2-year OSR (RR, 2.00 [95% CI: 1.48-2.70]), ORR (RR = 1.22 [95% CI, 1.08-1.37]), and a lower progression disease (PD) rate (RR = 0.45 [95% CI:0.26-0.79]) than monotherapy. No significant differences were detected in CR, PR, SD, or AEs between the two groups. Subgroup analysis regarding study type, control group, and treatment order indicated that compared with monotherapy, the combination of SBRT with TACE was associated with an increase in 1- and 2-year OSRs but not in ORR. In regard to the interval between SBRT and TACE, subgroup analysis found that the combination therapy for patients with an SBRT-TACE interval <28 days was preferable to monotherapy in the 1- and 2-year OSRs, and ORR. However, for patients with an SBRT-TACE interval ≥28 days, no obvious distinctions were observed in the 1-year OSR, 2-year OSR, or ORR between the two groups. CONCLUSION: The combination of SBRT with TACE appears to be better than monotherapy in treating HCC with PVTT and should be recommended for inoperable HCC patients with PVTT.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Radiocirurgia , Trombose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Veia Porta/patologia , Trombose/etiologia , Resultado do Tratamento
3.
J Colloid Interface Sci ; 623: 500-512, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35597019

RESUMO

In this paper, a novel Step-scheme MoS2/Bi4O5Br2 heterojunction was fabricated through the in-situ mechanical agitation method and the photocatalytic activity of that was examined by the photocatalytic degradation Rhodamine B (RhB) and inactivation of E.coli under visible light irradiation (λ > 420 nm). The Step-scheme MoS2/Bi4O5Br2 heterojunctions displayed the enhanced photocatalytic ability compared to pure Bi4O5Br2 and MoS2 and the MoS2/Bi4O5Br2-3% (MS/BOB-3) heterojunction exhibited the strongest photocatalytic activity which can completely inactivate the 1 × 107 cfu/mL with 180 min and degrade RhB (10 mg/L) with 24 min visible light irradiation, respectively. The photocatalytic mechanism of the MoS2/Bi4O5Br2 heterojunction is was attributed to the generated active species (h+, ·O2- and ·OH) which can effectively destroy RhB molecular and cell-membrane of bacterial as demonstrated by multiple techniques such as LC-MS and fluorescence stain. Additionally, characterization results disclosed that the transfer pathway of charge carriers of constructed MoS2/Bi4O5Br2 heterojunction followed the Step-scheme channel, which not only facilitated the separation and migration of the photo-generated charge carriers, but also improved the light absorption ability of the samples and resulting in the promoted photocatalytic performance of MoS2/Bi4O5Br2 heterojunction. This work paves a new idea to develop novel bismuth oxyhalide-based photocatalytic system for wastewater purification.

4.
Clin Chem Lab Med ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35607280

RESUMO

OBJECTIVES: Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs. METHODS: The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines. RESULTS: Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults. CONCLUSIONS: The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.

5.
Acta Pharmacol Sin ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513432

RESUMO

Monoacylglycerol lipase (MAGL) constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA). As such, selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders, metabolic diseases and cancers. Based on a unique 4-piperidinyl azetidine diamide scaffold, we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand [18F]FEPAD. Pharmacokinetics and binding studies on [18F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue (BAT) - a tissue that is known to be metabolically active. We employed [18F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT, which was confirmed by post-mortem tissue analysis. Given the negative regulation of endocannabinoids on the metabolic BAT activity, our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders. Further, we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits, thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system (ECS)-related pathologies.

6.
Comput Intell Neurosci ; 2022: 1003243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528361

RESUMO

Heilongjiang Province is the main grain producing region in China and an important part of Northeast China Plain, which is one of the three black soil belts in the world. The cultivated region of black soil accounts for 50.6% of the black soil region in Northeast China. Due to the obvious rise of temperature and uneven distribution of precipitation in the 20th century, it has been considered to be one of the important reasons for agricultural drought and aridity. Under the background of climate change, understanding the multiyear changes and occurrence characteristics of cultivated land drought in different agricultural regions in Heilongjiang Province is of great significance for the establishment of agricultural drought prediction and early warning system in the future, guiding agricultural high-standard farmland irrigation in different regions, promoting black soil protection, and then improving grain yield. This paper calculates the temperature vegetation drought index (TVDI) based on the normalized difference vegetation index (NDVI) and surface temperature (TS) product data of MODIS from 2000 to 2021. Taking TVDI as the drought evaluation index, this paper studies the temporal and spatial variation distribution characteristics and occurrence frequency of drought in the whole region and four agricultural regions of Heilongjiang Province: Daxing an Mountain and Xiaoxing an Mountain (region I), Sanjiang Plain (region II), Zhangguangcai Mountains (region III), and Songnen Plain (region IV). The results show that medium drought generally occurred in Heilongjiang Province from 2000 to 2021, accounting for about 70% of the total cultivated land. The drought was severe from 2000 to 2009 and weakened from 2010 to 2021. In the 110 months of the crop growing season from 2000 to 2021, about 63.84% of the region suffered more than 60 droughts. It is found that the frequency of drought varies from region to region. More than 80 droughts occurred in the west of region IV and the middle of region II. The characteristics of region IV are large sandstorm, less precipitation, and lack of water conservancy facilities, resulting in frequent and strong drought. It is also found that the occurrence frequency, degree grade and regional distribution of drought are closely related to seasonal changes. In spring, the occurrence grade and frequency of drought in region IV are the strongest and the drought phenomenon is serious. In autumn, drought is frequent and distributed in all regions, but the grade is not strong (mainly medium drought), and the drought phenomenon is medium. It is humid in summer. Crops in Heilongjiang Province are one crop per annual. Spring drought seriously restricts the water content of crops. Long-term drought will lead to poor crop development and reduce yield. Therefore, only by clarifying the characteristics of regional time drought, monitoring accurate drought events and accurately predicting the occurrence of drought, can we guide high-standard farmland precision irrigation, improve crop yield and ensure national food security. At the same time, severe drought will affect the terrestrial ecosystem, resulting in the distribution of crops and microorganisms, and the transformation between carbon sink and carbon source.


Assuntos
Secas , Ecossistema , China , Solo , Temperatura , Água
7.
Eur J Med Chem ; 236: 114309, 2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35398730

RESUMO

The formation of biofilm enables Staphylococcus aureus to resist antibiotics and causes chronic infections. Several compounds of pyrrolomycins are potent antibacterial agents which display inhibition upon staphylococcal biofilms. We designed and synthesized two series of substituted pyrazoles as pyrrolomycin analogues. Compounds 17a, 17d and 17h displayed potent antibacterial activity against various vancomycin-resistant Enterococcus faecalis (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), and 17d showed the most potent activity against MRSA (MIC = 0.0625 µg/mL), vancomycin-intermediate Staphylococcus aureus (VISA) (MIC = 0.0313 µg/mL). Further study indicated that compound 17h could significantly reduce the biofilm formation of MRSA and exhibited promising selectivity. In vitro liver microsomal stability was also evaluated and the results manifested that 17h was metabolically stable in human liver microsomes.

8.
Bioinformatics ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35485740

RESUMO

MOTIVATION: Single-cell RNA sequencing (scRNA-seq) technologies have been testified revolutionary for their promotion on the profiling of single-cell transcriptomes at single-cell resolution. Excess zeros due to various technical noises, called dropouts, will mislead downstream analyses. Therefore, it is crucial to have accurate imputation methods to address the dropout problem. RESULTS: In this paper, we develop a new dropout imputation method for scRNA-seq data based on multi-objective optimization. Our method is different from existing ones, which assume that the underlying data has a preconceived structure and impute the dropouts according to the information learned from such structure. We assume that the data combines three types of latent structures, including the horizontal structure (genes are similar to each other), the vertical structure (cells are similar to each other), and the low-rank structure. The combination weights and latent structures are learned using multi-objective optimization. And, the weighted average of the observed data and the imputation results learned from the three types of structures are considered as the final result. Comprehensive downstream experiments show the superiority of our method in terms of recovery of true gene expression profiles, differential expression analysis, cell clustering and cell trajectory inference. AVAILABILITY: The R package is available at https://github.com/Zhangxf-ccnu/scMOO and https://zenodo.org/record/5785195. The codes to reproduce the downstream analyses in this paper can be found at https://github.com/Zhangxf-ccnu/scMOO_experiments_codes and https://zenodo.org/record/5786211. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

9.
ACS Appl Mater Interfaces ; 14(16): 19067-19075, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35420410

RESUMO

In the selective enrichment of phosphorylated proteins (PPs) from biological samples, the non-phosphorylated proteins (NPPs) adhered onto enrichment adsorbents due to the hydrophobic interaction, resulting in poor selectivity and low recovery of target PPs. Herein, superhydrophilic TiO2-coated porous SiO2 microspheres are prepared and boost remarkable selectivity toward standard PP spiked with 2000 mass-fold NPP interference. The outstanding performance of the superhydrophilic microspheres is attributed to the coordination interaction between TiO2 and PPs, and the confined water layer generated from superhydrophilicity avoids the irreversible adsorption of NPPs by keeping NPP inner hydrophobic regions in a compact structure, which is verified by single molecule force spectroscopy, circular dichroism, and quartz crystal microbalance. This strategy for enrichment is expected to solve the challenge in proteomics and sheds light on the interactions between biomolecules and superwettability.


Assuntos
Dióxido de Silício , Água , Microesferas , Dióxido de Silício/química , Titânio/química
10.
ACS Appl Mater Interfaces ; 14(16): 18634-18645, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35412801

RESUMO

Commercialization of high-energy Li-S batteries is greatly restricted by their unsatisfactory cycle retention and poor cycling life originated from the notorious "shuttling effect" of lithium polysulfides. Modification of a commercial separator with a functional coating layer is a facile and efficient strategy beyond nanostructured composite cathodes for suppressing polysulfide shuttling. Herein, a multilayered functional CeO2-x@C-rGO/CNT separator was successfully achieved by alternately depositing conductive carbon nanotubes (CNTs) and synthetic CeO2-x@C-rGO onto the surface of the commercial separator. The cooperation of multiple components including Ce-MOF-derived CeO2-x@C, rGO, and CNTs enables the as-built CeO2-x@C-rGO/CNT separator to perform multifunctions from the separator surface: (i) to hinder the diffusion of polysulfide species through physical blocking or chemical adsorption, (ii) to accelerate the sluggish redox reactions of sulfur species, and (iii) to enhance the conductivity for sulfur re-activation and efficient utilization. Serving as a multilayer and powerful barrier, the CeO2-x@C-rGO/CNT separator greatly constrains and reutilizes the polysulfide species. Thus, the Li-S battery assembled with the CeO2-x@C-rGO/CNT separator demonstrates an excellent combination of capacity, rate capability, and cycling performances (an initial capacity of 1107 mA h g-1 with a low decay rate of 0.060% per cycle over 500 cycles at 1 C, 651 mA h g-1 at 5 C) together with remarkably mitigated self-discharge and anode corrosion. This work provides guidelines for functional separator design as well as rare-earth material applications for Li-S batteries and other energy storage systems.

11.
COPD ; 19(1): 99-108, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35385365

RESUMO

This study aimed to explore the relationship between body mass index (BMI) and abdominal obesity and the risk of airflow obstruction, based on the data from the 2007-2012 National Health and Nutrition Survey (NHANES). Logistic regression was applied to assess the relationships between BMI or abdominal obesity and the risk of airflow obstruction by the fixed ratio method and the lower limit of normal (LLN) method. We further used the restricted cubic splines with 3 knots located at the 5th, 50th, and 95th percentiles of the distribution to evaluate the dose-response relationship. A total of 12,865 individuals aged 20-80 years old were included. In the fixed ratio method, underweight was positively correlated with the risk of airflow obstruction, and overweight and obesity were negatively correlated with the risk of airflow obstruction. In the LLN method, the results were consistent with the fixed ratio method. Abdominal obesity was positively associated with the risk of airflow obstruction only in the fixed ratio method (OR: 1.41, 95% CI: 1.04-1.90). There was an additive interaction between underweight and smoking on airflow obstruction in both methods. Abdominal obesity and smoking had additive interactions in the LLN method. Dose-response analysis indicated that there was a non-linear trend between BMI and the risk of airflow obstruction (Pfor nonlinearity < 0.01). Our study suggested that underweight and abdominal obesity were associated with the increased risk of airflow obstruction, and overweight and general obesity were associated with the decreased risk of airflow obstruction.


Assuntos
Sobrepeso , Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Volume Expiratório Forçado/fisiologia , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/complicações , Obesidade/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores de Risco , Magreza/complicações , Magreza/epidemiologia , Adulto Jovem
12.
J Orthop Surg Res ; 17(1): 243, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440065

RESUMO

BACKGROUND: Despite Vast improvements in technology and surgical technique in total knee arthroplasty (TKA), approximately 15-25% TKAs, have suboptimal subjective clinical outcomes. Our study sought to evaluate if sensor-guided balancing improves postoperative clinical outcomes compared to a conventional gap balancing technique. METHODS: We searched Web of Science, Embase, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database in March 2022 to identify studies involving sensor-guided balancing versus conventional gap balancing technique in TKA. Finally, we identified 2147 knees assessed in nine studies. RESULTS: Compared with manual gap balancing, Sensor-guided gap balancing resulted in less rate of Manipulation under anesthesia (MUA) (P = 0.02), however more rate of intraoperative additional procedures (P = 0.0003). There were no significant differences in terms of KSS (P = 0.21), KSS Function score (P = 0.36), OKS (P = 0.61), KOOS (P = 0.78), operative time (P = 0.17), Mechanical axis (P = 0.69) and rate of reoperation between two groups. CONCLUSION: Compared with conventional manual gap balancing techniques, sensors have more balancing procedures being performed. However, it did result in a reduction in the rate of MUA. More extensive, high-quality RCTs are required to verify our findings further.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/métodos , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Amplitude de Movimento Articular
13.
Aging (Albany NY) ; 14(8): 3597-3606, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468095

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy and lacks effective therapeutic targets. Trametinib is considered to be a promising potential indirectly targeted KRAS inhibitor in PDAC. However, the clinical outcomes were poor. JQ1 displayed a significant synergistic effect when combined with chemotherapy or potential targeted therapy in pancreatic cancer. The impact of Trametinib and JQ1 combination treatment in PDAC remains to be fully elucidated. METHODS: The efficacy of trametinib and JQ1 on cell proliferation and cytotoxicity was assayed in 7 KRAS mutant pancreatic cancer cell lines. The cytotoxic effects of drugs either alone or in combination were evaluated using a luminescent cell viability assay. Immunoblot analysis was carried out to investigate changes in p62 and autophagy. RESULTS: We found that either trametinib or JQ1 alone inhibited the proliferation of some pancreatic cancer cell lines with KRAS alterations, irrespective of the mutational loci of KRAS and the aberrant status of the other driver genes. The synergistic effects of combination treatment of trametinib and JQ1 were observed in both trametinib-resistant and trametinib-sensitive cells. In trametinib-sensitive PDAC cells, the combined treatment definitely inhibited p62 expression compared with trametinib alone, while LC3 expression at high levels changed little. In trametinib-resistant PDAC cells, the combination of MEK/BET inhibitor dramatically decreased p62 expression compared with single agent, while p62 expression increased after anti-autophagic therapy was added. CONCLUSIONS: Blocking RAS downstream signaling and epigenetic pathway synergistically increases the antiproliferative activity in KRAS mutant PDAC cells. Combination therapeutic synergism may induce different cell death modes in different pancreatic cancer subtypes.


Assuntos
Antineoplásicos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Antineoplásicos/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética , Humanos , Mutação , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Int Med Res ; 50(4): 3000605221091095, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35469480

RESUMO

Gastric hepatoid adenocarcinoma (GHAC) is a highly aggressive histological subtype of gastric cancer (GC) with similar tissue morphology to hepatocellular carcinoma. GHAC frequently produces alpha-fetoprotein (AFP) and has a poor prognosis; however, standardized treatment remains elusive. We report a male patient in his early 60s with GHAC who received immunotherapy, and the curative effect was evaluated. He was admitted because of progressive fatigue and dizziness for 2 months. He had experienced spontaneous epigastric pain with muscular defense of the epigastrium and accompanying tenderness 1 year earlier and underwent radical gastrectomy. Immunohistochemistry showed that hepatocyte-specific marker (Hep) was highly-expressed, indicating probable GHAC. Additionally, imaging suggested GC recurrence or gastric stump cancer. Radioimmunoassay indicated an AFP level of >1210.00 µg/L, and liver biopsy was performed following abdominal contrast-enhanced computed tomography. Pathology showed a few hepatocytes and proliferative fibrous connective tissue. The patient received three cycles of chemotherapy, with no obvious improvement. The possibility of surgical treatment was excluded, and immunotherapy or palliative treatment was selected. He received 11 cycles of a programed death-1 (PD-1) monoclonal antibody, and the effect of treatment was satisfactory. The mechanism of action of immunotherapy in GHAC warrants further investigation.


Assuntos
Adenocarcinoma , Neoplasias Hepáticas , Neoplasias Gástricas , Adenocarcinoma/patologia , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/patologia , Masculino , Recidiva Local de Neoplasia , Neoplasias Gástricas/patologia , alfa-Fetoproteínas
15.
Artigo em Inglês | MEDLINE | ID: mdl-35476574

RESUMO

The single cell RNA sequencing (scRNA-seq) technique begins a new era by revealing gene expression patterns at single-cell resolution, enabling studies of heterogeneity and transcriptome dynamics of complex tissues at single-cell resolution. However, existing large proportion of dropout events may hinder downstream analyses. Thus imputation of dropout events is an important step in analyzing scRNA-seq data. We develop scTSSR2, a new imputation method which combines matrix decomposition with the previously developed two-side sparse self-representation, leading to fast two-side sparse self-representation to impute dropout events in scRNA-seq data. The comparisons of computational speed and memory usage among different imputation methods show that scTSSR2 has distinct advantages in terms of computational speed and memory usage. Comprehensive downstream experiments show that scTSSR2 outperforms the state-of-the-art imputation methods. A user-friendly R package scTSSR2 is developed to denoise the scRNA-seq data to improve the data quality.

16.
ACG Case Rep J ; 9(3): e00753, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35359752

RESUMO

Liver injury is a common manifestation of coronavirus disease 2019 (COVID-19), with most injuries manifesting as transient mild hepatocellular injury. Cholestatic injury occurs less commonly and is typically mild. Severe cholestatic injury is rare, with only 4 cases reported in the literature. We present a 70-year-old woman with no known liver disease who presented with severe COVID-19 and developed severe cholestatic hepatitis. A liver biopsy was performed demonstrating bile duct injury, uncommonly reported in patients with COVID-19. This complication needs greater awareness because it has been known to cause progressive liver disease requiring transplantation.

17.
J Transl Med ; 20(1): 135, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35303878

RESUMO

Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.


Assuntos
Neoplasias , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Humanos , Neoplasias/terapia , Prognóstico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Transdução de Sinais , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-35230503

RESUMO

INTRODUCTION: The lateral femoral notch sign (LFNS) and the kissing contusion (KC) are two indirect signs of anterior cruciate ligament (ACL) injuries. They can be used to diagnose ACL injuries. MATERIALS AND METHODS: A total of 1000 patients were enrolled in this study, including 500 patients with ACL injuries who assigned to experimental group and 500 patients with meniscal tear (MT) who allocated to control group. All the patients underwent magnetic resonance imaging (MRI) preoperatively, and the diagnosis was confirmed with the aid of arthroscopy. The depth of LFNS and the presence of KC were determined on MRI findings. The relationship and characteristics between these two indicators was explored. RESULTS: The notch depth of lateral femoral condyle in the experimental group (0.99 ± 0.56 mm) was significantly greater than that in the control group (0.49 ± 0.28 mm) (P < 0.05). The positive rate of KC in the experimental group (183/500) was markedly higher than that in the control group (3/500) (P < 0.05). The values of notch depth in patients who had ACL rupture concomitant lateral MT injuries and medial collateral ligament (MCL) injuries were 1.12 ± 0.64 and 1.23 ± 0.74 mm, respectively, which were significantly higher than those in patients with only ACL injury (0.89 ± 0.49 mm) (P < 0.05). It also was revealed that when the optimal cut-off point of LFNS was 0.72 mm (area under the curve (AUC) = 81%), the values of specificity and sensitivity were 67% and 84%, respectively. For KC, the corresponding values were 36.6% and 99.4%, respectively. The diagnostic outcome of LFNS was not in agreement with that of KC, as there was a poor coincidence according to the Kappa coefficient (Kappa = 0.155 < 0.4, P = 0.035). CONCLUSION: The LFNS and KC have strong clinical significance in the diagnosis of ACL injuries. A deeper notch often indicates a more complex knee injury. Notch depth equal to 0.72 mm can be basically considered as the optimal cut-off point for LFNS in statistics.

19.
Genomics ; 114(3): 110348, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35339630

RESUMO

Single nucleotide polymorphisms (SNPs) are widely used in genetic research and molecular breeding. To date, the genomes of many vegetable crops have been assembled, and hundreds of core germplasms for each vegetable have been sequenced. However, these data are not currently easily accessible because they are stored on different public databases. Therefore, a vegetable crop SNP database should be developed that hosts SNPs demonstrated to have a high success rate in genotyping for genetic research (herein, "alpha SNPs"). We constructed a database (VegSNPDB, http://www.vegsnpdb.cn/) containing the sequence data of 2032 germplasms from 16 vegetable crop species. VegSNPDB hosts 118,725,944 SNPs of which 4,877,305 were alpha SNPs. SNPs can be searched by chromosome number, position, SNP type, genetic population, or specific individuals, as well as the values of MAF, PIC, and heterozygosity. We hope that VegSNPDB will become an important SNP database for the vegetable research community.

20.
Clin Chim Acta ; 531: 120-125, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35358470

RESUMO

BACKGROUND: Bartter syndrome is an inherited renal tubular disorder that is characterized by hypokalemic, hypochloremic metabolic alkalosis in which the primary defect is a deficiency of transporters involved in sodium chloride reabsorption. Bartter syndrome type 1 is caused by SLC12A1 mutations. METHODS: The patients were from two unrelated non-consanguineous Chinese families. Both patients presented with intrauterine growth retardation, premature delivery, failure to thrive, polyuria and metabolic alkalosis. Whole-exome sequencing was used to identify the causative gene. RESULTS: Exome sequencing identified three novel SLC12A1 mutations in our patients. And we found the two patients had significantly different outcomes when they were two years of age. Moreover, we identified four novel variants of SLC12A1 that were likely to be pathogenic, from our in-house database. A review of the whole-exome sequencing data of patient 1 lead to her brother being genetically diagnosed with pulmonary alveolar microlithiasis, which was caused by compound heterozygous SLC34A2 variations. CONCLUSION: We reported two children from one family who were affected by different rare conditions. This study expanded the mutation spectra of the SLC12A1 and SLC34A2 genes. We showed the important role of early genetic testing for disease diagnosis and emphasized the importance of standardized treatment and management.

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