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1.
Cell Commun Signal ; 22(1): 269, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745240

ABSTRACT

BACKGROUND: The pathway involving PTEN-induced putative kinase 1 (PINK1) and PARKIN plays a crucial role in mitophagy, a process activated by artesunate (ART). We propose that patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis exhibit insufficient mitophagy, and ART enhances mitophagy via the PINK1/PARKIN pathway, thereby providing neuroprotection. METHODS: Adult female mice aged 8-10 weeks were selected to create a passive transfer model of anti-NMDAR encephalitis. We conducted behavioral tests on these mice within a set timeframe. Techniques such as immunohistochemistry, immunofluorescence, and western blotting were employed to assess markers including PINK1, PARKIN, LC3B, p62, caspase3, and cleaved caspase3. The TUNEL assay was utilized to detect neuronal apoptosis, while transmission electron microscopy (TEM) was used to examine mitochondrial autophagosomes. Primary hippocampal neurons were cultured, treated, and then analyzed through immunofluorescence for mtDNA, mtROS, TMRM. RESULTS: In comparison to the control group, mitophagy levels in the experimental group were not significantly altered, yet there was a notable increase in apoptotic neurons. Furthermore, markers indicative of mitochondrial leakage and damage were found to be elevated in the experimental group compared to the control group, but these markers showed improvement following ART treatment. ART was effective in activating the PINK1/PARKIN pathway, enhancing mitophagy, and diminishing neuronal apoptosis. Behavioral assessments revealed that ART ameliorated symptoms in mice with anti-NMDAR encephalitis in the passive transfer model (PTM). The knockdown of PINK1 led to a reduction in mitophagy levels, and subsequent ART intervention did not alleviate symptoms in the anti-NMDAR encephalitis PTM mice, indicating that ART's therapeutic efficacy is mediated through the activation of the PINK1/PARKIN pathway. CONCLUSIONS: At the onset of anti-NMDAR encephalitis, mitochondrial damage is observed; however, this damage is mitigated by the activation of mitophagy via the PINK1/PARKIN pathway. This regulatory feedback mechanism facilitates the removal of damaged mitochondria, prevents neuronal apoptosis, and consequently safeguards neural tissue. ART activates the PINK1/PARKIN pathway to enhance mitophagy, thereby exerting neuroprotective effects and may achieve therapeutic goals in treating anti-NMDAR encephalitis.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Artesunate , Disease Models, Animal , Neuroprotective Agents , Protein Kinases , Animals , Artesunate/pharmacology , Artesunate/therapeutic use , Mice , Female , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/pathology , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/drug therapy , Protein Kinases/metabolism , Neurons/drug effects , Neurons/pathology , Neurons/metabolism , Microscopy, Electron, Transmission , Mitophagy/drug effects , Apoptosis/drug effects , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/ultrastructure , Hippocampus/pathology , Hippocampus/drug effects , Hippocampus/metabolism
2.
Mol Neurobiol ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38421467

ABSTRACT

Microglial activation plays a crucial role in the disease progression in amyotrophic lateral sclerosis (ALS). Interleukin receptor-associated kinases-M (IRAK-M) is an important negative regulatory factor in the Toll-like receptor 4 (TLR4) pathway during microglia activation, and its mechanism in this process is still unclear. In the present study, we aimed to investigate the dynamic changes of IRAK-M and its protective effects for motor neurons in SOD1-G93A mouse model of ALS. qPCR (Real-time Quantitative PCR Detecting System) were used to examine the mRNA levels of IRAK-M in the spinal cord in both SOD1-G93A mice and their age-matched wild type (WT) littermates at 60, 100 and 140 days of age. We established an adeno-associated virus 9 (AAV9)-based platform by which IRAK-M was targeted mostly to microglial cells to investigate whether this approach could provide a protection in the SOD1-G93A mouse. Compared with age-matched WT mice, IRAK-M mRNA level was elevated at 100 and 140 days in the anterior horn region of spinal cords in the SOD1-G93A mouse. AAV9-IRAK-M treated SOD1-G93A mice showed reduction of IL-1ß mRNA levels and significant improvements in the numbers of spinal motor neurons in spinal cord. Mice also showed previously reduction of muscle atrophy. Our data revealed the dynamic changes of IRAK-M during ALS pathological progression and demonstrated that an AAV9-IRAK-M delivery was an effective and translatable therapeutic approach for ALS. These findings may help identify potential molecular targets for ALS therapy.

3.
Fish Shellfish Immunol ; 146: 109428, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38325594

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease in the world. Immunity is the major contributing factor in NAFLD; however, the interaction of immune cells and hepatocytes in disease progression has not been fully elucidated. As a popular species for studying NAFLD, zebrafish, whose liver is a complex immune system mediated by immune cells and non-immune cells in maintaining immune tolerance and homeostasis. Understanding the cellular composition and immune environment of zebrafish liver is of great significance for its application in NAFLD. Here, we established a liver atlas that consists of 10 cell types using single-cell RNA sequencing (scRNA-seq). By examining the heterogeneity of hepatocytes and analyzing the expression of NAFLD-associated genes in the specific cluster, we provide a potential target cell model to study NAFLD. Additionally, our analysis identified two subtypes of distinct resident macrophages with inflammatory and non-inflammatory functions and characterized the successive stepwise development of T cell subclusters in the liver. Importantly, we uncovered the possible regulation of macrophages and T cells on target cells of fatty liver by analyzing the cellular interaction between hepatocytes and immune cells. Our data provide valuable information for an in-depth study of immune cells targeting hepatocytes to regulate the immune balance in NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Zebrafish/genetics , Transcriptome , Liver/metabolism , Hepatocytes/metabolism , Cell Communication
4.
Gene ; 901: 148199, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38253299

ABSTRACT

SET (SuVar3-9, Enhancer of Zeste, Trithorax) domain bifurcated histone lysine methyltransferase 1, setdb1, is the predominant histone lysine methyltransferase catalyzing H3K9me3. Prior studies have illustrated that setdb1 and H3K9me3 critically regulate sex differentiation and gametogenesis. However, the molecular details by which setdb1 is involved in these processes in fish have been poorly reported. Here, we cloned and characterized the setdb1 ORF (open reading frame) sequence from Chinese tongue sole (Cynoglossus semilaevis). The setdb1 ORF sequence was 3,669 bp, encoding a 1,222-amino-acid protein. Phylogenetic analysis showed that setdb1 was structurally conserved. qRT-PCR revealed that setdb1 had a high expression level in the testes at 12 mpf (months post fertilization). Single-cell RNA-seq data at 24 mpf indicated that setdb1 was generally expressed in spermatogenic cells at each stage except for sperm and was centrally expressed in oogonia. H3K9me3 modification was observed in gonads with the immunofluorescence technique. Furthermore, the overexpression experiment suggested that sox5 was a candidate target of setdb1. sox5 was abundantly expressed in male and pseudomale gonads at 24 mpf. Single-cell RNA-seq data showed that sox5 was mainly expressed in spermatogonia and its expression gradually declined with differentiation. Taken together, our findings imply that setdb1 regulates sox5 transcription in gonads, which provides molecular clues into histone modification-mediated orchestration of sex differentiation and gametogenesis.


Subject(s)
Fish Proteins , Flounder , Histone Code , Histone-Lysine N-Methyltransferase , SOXD Transcription Factors , Animals , Male , Flounder/genetics , Gonads/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Phylogeny , Semen/metabolism , SOXD Transcription Factors/metabolism , Fish Proteins/metabolism
5.
Food Res Int ; 174(Pt 1): 113615, 2023 12.
Article in English | MEDLINE | ID: mdl-37986470

ABSTRACT

Long-term storage of Liupao tea (LPT) is usually believed to enhance its quality and commercial value. The non-volatile metabolites variations and the fungal succession play a key role for organoleptic qualities during the storage procedure. To gain in-depth understanding the impact of storage time on the quality of LPT, two different brands of LPT with different storage time, including Maosheng LPTs (MS) with 0, 5, 10 and 15 years and Tianyu LPTs (TY) with 0, 3, 5, 8 and 10 years, were resorted to investigate the changes of non-volatile metabolites and fungi as well as their correlation by multi-omics. A total of 154 and 119 differential metabolites were identified in these two different brands of MS and TY, respectively, with the aid of high-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry. In both categories of LPTs, the transformation of differential metabolites in the various stages referred to the formation of alkaloids, increase of organic acids, biosynthesis of terpenoids as well as glycosylation and methylation of flavonoids. Thereinto, glycosylation and methylation of flavonoids were the critical stages for distinguishing MS and TY, which were discovered in MS and TY stored for about 10 and 8 years, respectively. Moreover, the results of high-throughput sequencing showed that the key fungal genera in the storage of LPTs consisted of Eurotium, Aspergillus, Blastobotrys, Talaromyces, Thermomyces and Trichomonascus. It was confirmed on the basis of multivariate analysis that the specific fungal genera promoted the transformation of metabolites, affecting the tea quality to some extent. Therefore, this study provided a theoretical basis for the process optimization of LPT storage.


Subject(s)
Mycobiome , Tea , Chromatography, Liquid , Tea/chemistry , Tandem Mass Spectrometry , Flavonoids/chemistry , High-Throughput Nucleotide Sequencing
6.
ACS Omega ; 8(16): 14520-14530, 2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37125115

ABSTRACT

The karst depression with a natural negative landform is favorable for reservoir construction with less excavation work. The underground air-water pressure would be complicated after the construction of a reservoir that blocks the natural air-water channel (sinkhole, karst channel, etc.). To develop a monitoring system for the reservoir, a large-scale laboratory simulation test was carried out to study the air-pressure evolution and water migration process during water table fluctuation after the blockage of the sinkhole in a karst depression. The results are as follows. (1) The positive pressure jacking effect and the negative pressure sucking effect were observed in the karst channel and inside the model during groundwater table fluctuation. (2) A water imbibition test on the rock-like material was carried out with layered resistivity and layered NMR measurement. The relationship of resistivity and water saturation was developed based on Archie's equation. (3) The resistivity evolution during the test was monitored using the high-density electronic resistivity imaging method. The resistivity of the measured profile was sensitive to the variation of the water level, and the water migration process was quantified by the resistivity to water saturation conversion. (4) The suitability of many techniques for monitoring a reservoir built on the karst depression was discussed. The resistivity monitoring technique combined with the air-water pressure monitoring technique could provide useful information for safety and reliability assessment.

7.
Eur Radiol ; 33(11): 7686-7696, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37219618

ABSTRACT

OBJECTIVE: To compare examination time and image quality between artificial intelligence (AI)-assisted compressed sensing (ACS) technique and parallel imaging (PI) technique in MRI of patients with nasopharyngeal carcinoma (NPC). METHODS: Sixty-six patients with pathologically confirmed NPC underwent nasopharynx and neck examination using a 3.0-T MRI system. Transverse T2-weighted fast spin-echo (FSE) sequence, transverse T1-weighted FSE sequence, post-contrast transverse T1-weighted FSE sequence, and post-contrast coronal T1-weighted FSE were obtained by both ACS and PI techniques, respectively. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and duration of scanning of both sets of images analyzed by ACS and PI techniques were compared. The images from the ACS and PI techniques were scored for lesion detection, margin sharpness of lesions, artifacts, and overall image quality using the 5-point Likert scale. RESULTS: The examination time with ACS technique was significantly shorter than that with PI technique (p < 0.0001). The comparison of SNR and CNR showed that ACS technique was significantly superior with PI technique (p < 0.005). Qualitative image analysis showed that the scores of lesion detection, margin sharpness of lesions, artifacts, and overall image quality were higher in the ACS sequences than those in the PI sequences (p < 0.0001). Inter-observer agreement was evaluated for all qualitative indicators for each method, in which the results showed satisfactory-to-excellent agreement (p < 0.0001). CONCLUSION: Compared with the PI technique, the ACS technique for MR examination of NPC can not only shorten scanning time but also improve image quality. CLINICAL RELEVANCE STATEMENT: The artificial intelligence (AI)-assisted compressed sensing (ACS) technique shortens examination time for patients with nasopharyngeal carcinoma, while improving the image quality and examination success rate, which will benefit more patients. KEY POINTS: • Compared with the parallel imaging (PI) technique, the artificial intelligence (AI)-assisted compressed sensing (ACS) technique not only reduced examination time, but also improved image quality. • Artificial intelligence (AI)-assisted compressed sensing (ACS) pulls the state-of-the-art deep learning technique into the reconstruction procedure and helps find an optimal balance of imaging speed and image quality.


Subject(s)
Artificial Intelligence , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/diagnostic imaging , Magnetic Resonance Imaging/methods , Signal-To-Noise Ratio , Nasopharyngeal Neoplasms/diagnostic imaging , Artifacts
8.
BMC Oral Health ; 23(1): 141, 2023 03 11.
Article in English | MEDLINE | ID: mdl-36906526

ABSTRACT

BACKGROUND: Intrafibrillar remineralization within the hybrid layers (HLs) has recently attracted extensive attention in achieving durable resin-dentin bonds. The polyhydroxy-terminated poly(amidoamine) dendrimer (PAMAM-OH) at fourth generation becomes a desirable candidate to induce intrafibrillar remineralization to protect exposed collagen fibrils within HLs based on the size exclusion effect of fibrillar collagen. However, the remineralization process in vivo is time-consuming, during which the exposed collagen fibrils are vulnerable to enzymatic degradation, resulting in unsatisfactory remineralization. Thereby, if PAMAM-OH itself possesses concomitant anti-proteolytic activity during the induction of remineralization, it would be very beneficial to obtain satisfactory remineralization. METHODS: Binding capacity tests using adsorption isotherm and confocal laser scanning microscopy (CLSM) were performed to assess if the PAMAM-OH had adsorption capacity on dentin. Anti-proteolytic testings were detected by MMPs assay kit, in-situ zymography and ICTP assay. Adhesive infiltration of resin-dentin interface and tensile bond strength before and after thermomechanical cycling were implemented to assess if the PAMAM-OH adversely affected resin-dentin bonds. RESULTS: Anti-proteolytic testings performed using MMPs assay kit, in-situ zymography and ICTP assay indicated that PAMAM-OH inhibited exogenous soluble MMP-9 as well as had inhibitory effect on the endogenous proteases. Adhesive infiltration of resin-dentin interface and tensile bond strength before and after thermomechanical cycling were implemented to indicate that the PAMAM-OH pretreatment had no adverse effects on immediate dentin bonding and prolonged the durability of resin-dentin bonds. CONCLUSIONS: PAMAM-OH possesses anti-proteolytic activity and prevents exposed collagen fibrils within HLs from degradation, which lays the foundation for the satisfactory intrafibrillar remineralization induced by PAMAM-OH within HLs to achieve durable resin-dentin bonds in the next work.


Subject(s)
Dendrimers , Dental Bonding , Collagen/metabolism , Dendrimers/analysis , Dendrimers/metabolism , Dental Bonding/methods , Dentin/metabolism , Dentin-Bonding Agents/chemistry , Materials Testing , Matrix Metalloproteinases/metabolism , Tensile Strength
9.
Sci China Life Sci ; 66(5): 1151-1169, 2023 05.
Article in English | MEDLINE | ID: mdl-36437386

ABSTRACT

Female-to-male sex reversals (pseudomales) are common in lower vertebrates and have been found in natural populations, which is a concern under rapid changes in environmental conditions. Pseudomales can exhibit altered spermatogenesis. However, the regulatory mechanisms underlying pseudomale spermatogenesis remain unclear. Here, we characterized spermatogenesis in Chinese tongue sole (Cynoglossus semilaevis), a species with genetic and environmental sex determination, based on a high-resolution single-cell RNA-seq atlas of cells derived from the testes of genotypic males and pseudomales. We identified five germ cell types and six somatic cell types and obtained a single-cell atlas of dynamic changes in gene expression during spermatogenesis in Chinese tongue sole, including alterations in pseudomales. We detected decreased levels of Ca2+ signaling pathway-related genes in spermatogonia, insufficient meiotic initiation in spermatocytes, and a malfunction of somatic niche cells in pseudomales. However, a cluster of CaSR genes and MAPK signaling factors were upregulated in undifferentiated spermatogonia of pseudomales. Additionally, we revealed that Z chromosome-specific genes, such as piwil2, dhx37, and ehmt1, were important for spermatogenesis. These results improve our understanding of reproduction after female-to-male sex-reversal and provide new insights into the adaptability of reproductive strategies in lower vertebrates.


Subject(s)
Testis , Transcriptome , Animals , Male , Female , Testis/metabolism , Spermatogenesis/genetics , Germ Cells , Fishes/genetics
10.
Medicine (Baltimore) ; 101(45): e31399, 2022 Nov 11.
Article in English | MEDLINE | ID: mdl-36397445

ABSTRACT

Our study aimed to develop a prediction model to predict the short-term mortality of hepatocellular carcinoma (HCC) patients with lung metastasis. The retrospective data of HCC patients with lung metastasis was from the Surveillance, Epidemiology, and End Results registration database between 2010 and 2015. 1905 patients were randomly divided into training set (n = 1333) and validation set (n = 572). There were 1092 patients extracted from the Surveillance, Epidemiology, and End Results database 2015 to 2019 as the validation set. The variable importance was calculated to screen predictors. The constructed prediction models of logistic regression, random forest, broad learning system, deep neural network, support vector machine, and naïve Bayes were compared through the predictive performance. The mortality of HCC patients with lung metastasis was 51.65% within 1 month. The screened prognostic factors (age, N stage, T stage, tumor size, surgery, grade, radiation, and chemotherapy) and gender were used to construct prediction models. The area under curve (0.853 vs. 0.771) of random forest model was more optimized than that of logistic regression model in the training set. But, there were no significant differences in testing and validation sets between random forest and logistic regression models. The value of area under curve in the logistic regression model was significantly higher than that of the broad learning system model (0.763 vs. 0.745), support vector machine model (0.763 vs. 0.689) in the validation set, and higher than that of the naïve Bayes model (0.775 vs. 0.744) in the testing model. We further chose the logistic regression prediction model and built the prognostic nomogram. We have developed a prediction model for predicting short-term mortality with 9 easily acquired predictors of HCC patients with lung metastasis, which performed well in the internal and external validation. It could assist clinicians to adjust treatment strategies in time to improve the prognosis.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Lung Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/secondary , Retrospective Studies , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Bayes Theorem , Prognosis
11.
Front Cell Dev Biol ; 10: 828124, 2022.
Article in English | MEDLINE | ID: mdl-35300429

ABSTRACT

Oogenesis is a highly orchestrated process that depends on regulation by autocrine/paracrine hormones and growth factors. However, many details of the molecular mechanisms that regulate fish oogenesis remain elusive. Here, we performed a single-cell RNA sequencing (scRNA-seq) analysis of the molecular signatures of distinct ovarian cell categories in adult Chinese tongue sole (Cynoglossus semilaevis). We characterized the successive stepwise development of three germ cell subtypes. Notably, we identified the cellular composition of fish follicle walls, including four granulosa cell types and one theca cell type, and we proposed important transcription factors (TFs) showing high activity in the regulation of cell identity. Moreover, we found that the extensive niche-germline bidirectional communications regulate fish oogenesis, whereas ovulation in fish is accompanied by the coordination of simultaneous and tightly sequential processes across different granulosa cells. Additionally, a systems biology analysis of the homologous genes shared by Chinese tongue sole and macaques revealed remarkably conserved biological processes in germ cells and granulosa cells across vertebrates. Our results provide key insights into the cell-type-specific mechanisms underlying fish oogenesis at a single-cell resolution, which offers important clues for exploring fish breeding mechanisms and the evolution of vertebrate reproductive systems.

12.
Am J Orthod Dentofacial Orthop ; 161(1): 92-102, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34452789

ABSTRACT

INTRODUCTION: The space on each side of the mouth, between the commissure of the mouth and the buccal surface of the last visible tooth, is called the buccal corridor. The size of the buccal corridor can affect perceptions of facial esthetics. We analyzed the perceptions of orthodontists, laypersons, and orthodontic patients regarding the size of buccal corridors in people with brachyfacial, mesofacial, and dolichofacial types. METHODS: Photographs of 1 male and 1 female model were modified digitally into brachyfacial, mesofacial, and dolichofacial types. Each facial type was further modified to create 5 sizes of buccal corridors. Orthodontists, adult orthodontic patients, and laypersons were invited to rate the photographs. RESULTS: Orthodontists rated lower than the other groups of raters when they evaluated the female model with the buccal corridors of 20% (P <0.05). Laypersons could not distinguish the changes of the buccal corridors when evaluating the male model with brachyfacial and mesofacial (P >0.05). Orthodontic patients rated significantly higher than the orthodontists and the laypersons when evaluating the dolichofacial type of both models (P <0.05). CONCLUSIONS: Orthodontists are more sensitive to the buccal corridors than are orthodontic patients and laypersons. It is only necessary to consider eliminating the patient's buccal corridors when the buccal corridor area ratio is over 15%.


Subject(s)
Orthodontists , Smiling , Adult , Attitude of Health Personnel , Esthetics, Dental , Face , Female , Humans , Male
13.
Phys Rev Lett ; 127(22): 227001, 2021 Nov 24.
Article in English | MEDLINE | ID: mdl-34889620

ABSTRACT

Charge-4e superconductivity as a novel phase of matter remains elusive so far. Here, we show that charge-4e phase can arise as a vestigial order above the nematic superconducting transition temperature in time-reversal-invariant nematic superconductors. On the one hand, the nontrivial topological defect-nematic vortex-is energetically favored over the superconducting phase vortex when the nematic stiffness is less than the superfluid stiffness; consequently the charge-4e phase emerges by proliferation of nematic vortices upon increasing temperatures. On the other hand, the Ginzburg-Landau theory of the nematic superconductors has two distinct decoupling channels to either charge-4e orders or nematic orders; by analyzing the competition between the effective mass of the charge-4e order and the cubic potential of the nematic order, we find a sizable regime where the charge-4e order is favored. These two analyses consistently show that nematic superconductors can provide a promising route to realize charge-4e phases, which may apply to candidate nematic superconductors such as PbTaSe_{2} and twisted bilayer graphene.

14.
Nat Commun ; 12(1): 5375, 2021 09 10.
Article in English | MEDLINE | ID: mdl-34508070

ABSTRACT

The viability of lithium-sulfur batteries as an energy storage technology depends on unlocking long-term cycle stability. Most instability stems from the release and transport of polysulfides from the cathode, which causes mossy growth on the lithium anode, leading to continuous consumption of electrolyte. Therefore, development of a durable cathode with minimal polysulfide escape is critical. Here, we present a saccharide-based binder system that has a capacity for the regulation of polysulfides due to its reducing properties. Furthermore, the binder promotes the formation of viscoelastic filaments during casting which endows the sulfur cathode with a desirable web-like microstructure. Taken together this leads to 97% sulfur utilisation with a cycle life of 1000 cycles (9 months) and capacity retention (around 700 mAh g-1 after 1000 cycles). A pouch cell prototype with a specific energy of up to 206 Wh kg-1 is produced, demonstrating the promising potential for practical applications.

15.
Hum Immunol ; 81(12): 702-708, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32950268

ABSTRACT

To discover immune factors that can predict the progression of COVID-19, we evaluated circulating immune cells and plasma cytokines in COVID-19 patients. We found that T cells, including CD4+ T cells and CD8+ T cells, were significantly decreased in severe COVID-19 symptoms but not in mild symptoms, in comparison with healthy people. T cells remained at a low level after recovery from severe COVID-19. CD4+CD25+CD127low Treg-enriched cells were significantly increased in either mild or severe COVID-19 patients, regardless of recovery or not. Moreover, in either mild or severe COVID-19 patients, Treg-enriched cells up-regulated CD25 and down-regulated CD127. After recovery, CD25 was partially down-regulated but still higher than the normal level, while CD127 returned to the normal level in mild patients but not severe patients. B cells were decreased in mild patients and further decreased in severe patients, and remained low after recovery. NK cells were decreased only in severe COVID-19, with a tendency to return to the normal level after recovery. Plasma IL-6 and IL-10 were both elevated in severe patients but not in mild patients. After recovery, IL-6 remained higher than its normal level, while IL-10 returned to the normal level. Binary logistic regression analysis indicated that CD4+ T cells, B cells, IL-6, and IL-10 were significantly associated with COVID-19 severity. Therefore, these parameters are indicators of COVID-19 severity. Dynamic monitoring of these parameters would benefit therapy planning and prognosis evaluation.


Subject(s)
B-Lymphocytes/immunology , COVID-19/immunology , Interleukin-10/blood , Interleukin-6/blood , Killer Cells, Natural/immunology , SARS-CoV-2/genetics , T-Lymphocytes, Regulatory/immunology , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Female , Humans , Inflammation/immunology , Lymphocyte Count , Male , Middle Aged , Prognosis , Severity of Illness Index , Up-Regulation/immunology
16.
Sci Adv ; 6(9): eaay0443, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32158938

ABSTRACT

The iron-based superconductor FeTe x Se1-x is one of the material candidates hosting Majorana vortex modes residing in the vortex cores. It has been observed by recent scanning tunneling spectroscopy measurement that the fraction of vortex cores having zero-bias peaks decreases with increasing magnetic field on the surface of FeTe x Se1-x . The hybridization of two Majorana vortex modes cannot simply explain this phenomenon. We construct a three-dimensional tight-binding model simulating the physics of over a hundred Majorana vortex modes in FeTe x Se1-x . Our simulation shows that the Majorana hybridization and disordered vortex distribution can explain the decreasing fraction of the zero-bias peaks observed in the experiment; the statistics of the energy peaks off zero energy in our Majorana simulation are in agreement with the experiment. These agreements lead to an important indication of scalable Majorana vortex modes in FeTe x Se1-x . Thus, FeTe x Se1-x can be one promising platform having scalable Majorana qubits for quantum computing.

17.
Radiol Med ; 125(7): 647-653, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32072391

ABSTRACT

INTRODUCTION: To determine the value of whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating nasopharyngeal carcinoma (NPC) from lymphoma (NPL) at the primary site METHOD AND MATERIALS: One hundred forty-seven patients with nasopharyngeal tumors (89 NPCs and 38 NPLs) who had undergone magnetic resonance imaging (MRI) and diffusion-weighted imaging were retrospectively analyzed. ADC histogram-derived parameters were compared between the NPC and NPL groups by using the Mann-Whitney U test. Receiver operating characteristic (ROC) curves of the histogram parameters were plotted for diagnostic accuracy. Sensitivity and specificity were calculated for each histogram parameter. RESULTS: In whole-tumor histogram analysis, the mean, median, and 10th and 25th percentiles of ADC were all significantly higher in NPC than NPL (P = 0.045, P = 0.035, P = 0.005, and P = 0.016, respectively). Uniformity was significantly higher in NPC than NPL (P = 0.001). Skewness was significantly lower in NPC than NPL (P = 0.039). For the conventional ROI-based method, ADCmean values were significantly higher in NPC than in NPL (P = 0.009). The ROC curve analysis showed that uniformity yielded the largest area under the curve (AUC = 0.768) for differentiating NPC from NPL among all ADC metrics, followed by 10th percentiles of ADC (AUC = 0.725); sensitivity and specificity were 76.5% and 71.4%, respectively. CONCLUSION: Whole-tumor histogram analysis of ADC maps could be helpful for differentiating NPC from NPL.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Lymphoma/diagnostic imaging , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Lymphoma/pathology , Male , Middle Aged , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Retrospective Studies , Sensitivity and Specificity
18.
Zhonghua Liu Xing Bing Xue Za Zhi ; 35(1): 61-5, 2014 Jan.
Article in Chinese | MEDLINE | ID: mdl-24685040

ABSTRACT

OBJECTIVE: To identify the pathogen and characteristics on a case of hand-foot-mouth disease (HFMD) caused by coxsackie-virus A6 (CA6) associated with vaccine-derived poliovirus (VDPV) co-infection. METHODS: Field epidemiological study at the epidemic area was conducted and 16 stool samples including from the patient and close contacts were collected for isolation and identification of the enterovirus (EV). 21 stool samples from patients diagnosed as HFMD were collected in the same hospital at the same month to detect CA16,EV71, CA6 and PV by real-time RT-PCR or RT-PCR. The VP1 gene of the CA6 was amplified by RT-PCR and PCR products were sequenced and analyzed. RESULTS: The patient showed only HFMD symptoms, but no symptoms related to acute flaccid paralysis (AFP). No EVs were isolated from 16 samples collected from the patient and close contacts. And no AFP cases were found by an active search. A total of 21 samples from patients diagnosed as HFMD were collected in the same hospital at the same month and 4 were found to be EV71, 2 were CA16 and 15 (include the patient)were CA6. Only this patient was found to have had VDPV II infection. The CA6 VP1 gene was amplified from the HFMD patient and 9 other cases from the same hospital at the same month. Nucleotide sequences of the VP1 gene among the 9 strains shared 98.9%-100.0% in homology and 96.0%-100.0% in the deduced amino acid sequences. Phylogenetic analysis of the VP1 sequences categorized the 9 strains into the same branch. There were 6 nucleotides changes including U2909A between the VP1 region of the VDPV strain of the case and Sabin II. Results from phylogenetic analysis on the VP1 sequences indicated that the VDPV strain of the case was different from other VDPVs strains isolated in the world. CONCLUSION: This case was a HFMD which caused by CA6 co-infection with VDPV II and the VDPV was newly discovered. HFMD symptoms of the case were caused by CA6. The reason why this case did not have AFP symptoms was probably due the protective effect of IPV vaccine. No AFP cases were found by the active search for AFP cases conducted in the area, which indicated that VDPV did not cause virus circulation in this area.


Subject(s)
Coinfection , Enterovirus A, Human/isolation & purification , Hand, Foot and Mouth Disease/complications , Hand, Foot and Mouth Disease/virology , Poliovirus Vaccines/adverse effects , Child, Preschool , Female , Humans
19.
Ann Bot ; 110(3): 743-56, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22751653

ABSTRACT

BACKGROUND AND AIMS: Abscisic acid (ABA) plays crucial roles in plants' responses to abiotic stresses. ABA 8'-hydroxylation controlled by CYP707A genes has been well studied in Arabidopsis and rice, but not in legumes. The aims of the present study were to identify and functionally analyse the soybean CYP707A gene family, and to explore their expression patterns under dehydration and salt stresses. METHODS: A complementation experiment was employed to verify the function of soybean CYP707A1a in ABA catabolism. Genomic and cDNA sequences of other soybean CYP707A genes were isolated from the Phytozome database based on soybean CYP707A1a. The structure and phylogenetic relationship of this gene family was further analysed. The expression patterns of soybean CYP707A genes under dehydration and salt stress were analysed via quantitative real-time PCR. KEY RESULTS: Over-expression of GmCYP707A1a in the atcyp707a2 T-DNA insertion mutant decreased its sensitivity to ABA, indicating that GmCYP707A1a indeed functions as an ABA 8'-hydroxylase in higher plants. The soybean genome contains ten CYP707A genes. Gene structure and phylogenetic analysis showed high conservation of ten GmCYP707A genes to the other CYP707A genes from monocots and dicots. Seed imbibition induced expression of A1a, A1b, A2a, A2b, A2c, A3a and A5 in embryo, and expression of A1a, A1b, A2a and A2b in cotyledon. Dehydration induced expression of A1a, A1b, A2b, A2c, A3a, A3b, A4a, A4b and A5 both in roots and in leaves, whereas rehydration stimulated transcription of A2a, A2b, A3b, A4a and A5 in roots, and only A3b and A5 in leaves. Expression of all soybean CYP707A genes was induced either by short- or by long-term salt stress. CONCLUSIONS: The first biological evidence is provided that GmCYP7071a encodes an ABA 8'-hydroxylase through transgenic studies. Ten soybean GmCYP707A genes were identified, most of them expressed in multiple soybean tissues, and were induced by imbibition, dehydration and salinity.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , Droughts , Gene Expression Regulation, Plant/drug effects , Glycine max/genetics , Glycine max/metabolism , Sodium Chloride/pharmacology , Water/metabolism , Adaptation, Physiological/genetics , Genes, Plant , Plant Proteins , Plants, Genetically Modified , Salinity , Stress, Physiological/genetics
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