ABSTRACT
Crop improvement by genome editing involves the targeted alteration of genes to improve plant traits, such as stress tolerance, disease resistance or nutritional content. Techniques for the targeted modification of genomes have evolved from generating random mutations to precise base substitutions, followed by insertions, substitutions and deletions of small DNA fragments, and are finally starting to achieve precision manipulation of large DNA segments. Recent developments in base editing, prime editing and other CRISPR-associated systems have laid a solid technological foundation to enable plant basic research and precise molecular breeding. In this Review, we systematically outline the technological principles underlying precise and targeted genome-modification methods. We also review methods for the delivery of genome-editing reagents in plants and outline emerging crop-breeding strategies based on targeted genome modification. Finally, we consider potential future developments in precise genome-editing technologies, delivery methods and crop-breeding approaches, as well as regulatory policies for genome-editing products.
Subject(s)
CRISPR-Cas Systems , Crops, Agricultural , Gene Editing , Genome, Plant , Plant Breeding , Gene Editing/methods , Plant Breeding/methods , Crops, Agricultural/genetics , Plants, Genetically Modified/geneticsABSTRACT
Forming mutualistic symbioses with arbuscular mycorrhizae (AMs) improves the acquisition of mineral nutrients for most terrestrial plants. However, the formation of AM symbiosis usually occurs under phosphate (Pi)-deficient conditions. Here, we identify SlSPX1 (SYG1 (suppressor of yeast GPA1)/Pho81(phosphate 81)/XPR1 (xenotropic and polytropic retrovirus receptor 1) as the major repressor of the AM symbiosis in tomato (Solanum lycopersicum) under phosphate-replete conditions. Loss of SlSPX1 function promotes direct Pi uptake and enhances AM colonization under phosphate-replete conditions. We determine that SlSPX1 integrates Pi signaling and AM symbiosis by directly interacting with a set of arbuscule-induced SlPHR proteins (SlPHR1, SlPHR4, SlPHR10, SlPHR11, and SlPHR12). The association with SlSPX1 represses the ability of SlPHR proteins to activate AM marker genes required for the arbuscular mycorrhizal symbiosis. SlPHR proteins exhibit functional redundancy, and no defective AM symbiosis was detected in the single mutant of SlPHR proteins. However, silencing SlPHR4 in the Slphr1 mutant background led to reduced AM colonization. Therefore, our results support the conclusion that SlSPX1-SlPHRs form a Pi-sensing module to coordinate the AM symbiosis under different Pi-availability conditions.
Subject(s)
Mycorrhizae , Solanum lycopersicum , Gene Expression Regulation, Plant , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Minerals/metabolism , Mycorrhizae/physiology , Phosphates/metabolism , Plant Roots/metabolism , Symbiosis/physiologyABSTRACT
Systematic control and design of solid-state chemical reactions are required for modifying materials properties and in novel synthesis. Understanding chemical dynamics at the nanoscale is therefore essential to revealing the key reactive pathways. Herein, we combine focused ion beam-scanning electron microscopy (FIB-SEM) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) to track the migration of sodium from a borate coating to the oxide scale during in situ hot corrosion testing. We map the changing distribution of chemical elements and compounds from 50 to 850 °C to reveal how sodium diffusion induces corrosion. The results are validated by in situ X-ray diffraction and post-mortem TOF-SIMS. We additionally retrieve the through-solid sodium diffusion rate by fitting measurements to a Fickian diffusion model. This study presents a step change in analyzing microscopic diffusion mechanics with high chemical sensitivity and selectivity, a widespread analytical challenge that underpins the defining rates and mechanisms of solid-state reactions.
ABSTRACT
The dynamics of ion transport at the interface is the critical factor for determining the performance of an electrochemical energy storage device. While practical applications are realized in concentrated electrolytes and nanopores, there is a limited understanding of their ion dynamic features. Herein, we studied the interfacial ion dynamics in room-temperature ionic liquids by transient single-particle imaging with microsecond-scale resolution. We observed slowed-down dynamics at lower potential while acceleration was observed at higher potential. Combined with simulation, we found that the microstructure evolution of the electric double layer (EDL) results in potential-dependent kinetics. Then, we established a correspondence between the ion dynamics and interfacial ion composition. Besides, the ordered ion orientation within EDL is also an essential factor for accelerating interfacial ion transport. These results inspire us with a new possibility to optimize electrochemical energy storage through the good control of the rational design of the interfacial ion structures.
ABSTRACT
BACKGROUND: Plant U-box (PUB) E3 ubiquitin ligases have vital effects on various biological processes. Therefore, a comprehensive and systematic identification of the members of the U-box gene family in potato will help to understand the evolution and function of U-box E3 ubiquitin ligases in plants. RESULTS: This work identified altogether 74 PUBs in the potato (StPUBs) and examined their gene structures, chromosomal distributions, and conserved motifs. There were seventy-four StPUB genes on ten chromosomes with diverse densities. As revealed by phylogenetic analysis on PUBs within potato, Arabidopsis, tomato (Solanum lycopersicum), cabbage (Brassica oleracea), rice (Oryza sativa), and corn (Zea mays), were clustered into eight subclasses (C1-C8). According to synteny analysis, there were 40 orthologous StPUB genes to Arabidopsis, 58 to tomato, 28 to cabbage, 7 to rice, and 8 to corn. In addition, RNA-seq data downloaded from PGSC were utilized to reveal StPUBs' abiotic stress responses and tissue-specific expression in the doubled-monoploid potato (DM). Inaddition, we performed RNA-seq on the 'Atlantic' (drought-sensitive cultivar, DS) and the 'Qingshu NO.9' (drought-tolerant cultivar, DT) in early flowering, full-blooming, along with flower-falling stages to detect genes that might be involved in response to drought stress. Finally, quantitative real-time PCR (qPCR) was carried out to analyze three candidate genes for their expression levels within 100 mM NaCl- and 10% PEG 6000 (w/v)-treated potato plantlets for a 24-h period. Furthermore, we analyzed the drought tolerance of StPUB25 transgenic plants and found that overexpression of StPUB25 significantly increased peroxidase (POD) activity, reduced ROS (reactive oxygen species) and MDA (malondialdehyde) accumulation compared with wild-type (WT) plants, and enhancing drought tolerance of the transgenic plants. CONCLUSION: In this study, three candidate genes related to drought tolerance in potato were excavated, and the function of StPUB25 under drought stress was verified. These results should provide valuable information to understand the potato StPUB gene family and investigate the molecular mechanisms of StPUBs regulating potato drought tolerance.
Subject(s)
Arabidopsis , Solanum tuberosum , Ubiquitin-Protein Ligases/genetics , Solanum tuberosum/genetics , Solanum tuberosum/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Drought Resistance , Phylogeny , Droughts , Ubiquitins/genetics , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolismABSTRACT
Bronchopulmonary dysplasia (BPD) is a serious disease that occurs in premature and low-birth-weight infants. In recent years, the incidence of BPD has not decreased, and there is no effective treatment for it. Oridonin (Ori) is a traditional Chinese medicine with a wide range of biological activities, especially pharmacological and anti-inflammatory. It is well known that inflammation plays a key role in BPD. However, the therapeutic effect of Ori on BPD has not been studied. Therefore, in the present study, we will observe the anti-inflammatory activity of Ori in an experimental animal model of BPD. Here, we showed that Ori could significantly decrease hyperoxia-induced alveolar injury, inhibit neutrophil recruitment, myeloperoxidase concentrations, and release inflammatory factors in BPD neonatal rats. Taken together, the experimental results suggested that Ori can significantly improve BPD in neonatal rats by inhibiting inflammatory response.
ABSTRACT
It has been widely recognized that the pH environment influences the nanobubble dynamics and hydroxide ions adsorbed on the surface may be responsible for the long-term survival of the nanobubbles. However, understanding the distribution of hydronium and hydroxide ions in the vicinity of a bulk nanobubble surface at a microscopic scale and the consequent impact of these ions on the nanobubble behavior remains a challenging endeavor. In this study, we carried out deep potential molecular dynamics simulations to explore the behavior of a nitrogen nanobubble under neutral, acidic, and alkaline conditions and the inherent mechanism, and we also conducted a theoretical thermodynamic and dynamic analysis to address constraints related to simulation duration. Our simulations and theoretical analyses demonstrate a trend of nanobubble dissolution similar to that observed experimentally, emphasizing the limited dissolution of bulk nanobubbles in alkaline conditions, where hydroxide ions tend to reside slightly farther from the nanobubble surface than hydronium ions, forming more stable hydrogen bond networks that shield the nanobubble from dissolution. In acidic conditions, the hydronium ions preferentially accumulating at the nanobubble surface in an orderly manner drive nanobubble dissolution to increase the entropy of the system, and the dissolved nitrogen molecules further strengthen the hydrogen bond networks of systems by providing a hydrophobic environment for hydronium ions, suggesting both entropy and enthalpy effects contribute to the instability of nanobubbles under acidic conditions. These results offer fresh insights into the double-layer distribution of hydroxide and hydronium near the nitrogen-water interface that influences the dynamic behavior of bulk nanobubbles.
ABSTRACT
Designing and synthesizing fullerene bisadducts with a higher-lying conduction band minimum is promising to further improve the device performance of tin-based perovskite solar cells (TPSCs). However, the commonly obtained fullerene bisadduct products are isomeric mixtures and require complicated separation. Moreover, the isomeric mixtures are prone to resulting in energy alignment disorders, interfacial charge loss, and limited device performance improvement. Herein, we synthesized single-isomer C60- and C70-based diethylmalonate functionalized bisadducts (C60BB and C70BB) by utilizing the steric-hindrance-assisted strategy and determined all molecular structures involved by single crystal diffraction. Meanwhile, we found that the different solvents used for processing the fullerene bisadducts can effectively regulate the molecular packing in their films. The dense and amorphous fullerene bisadduct films prepared by using anisole exhibited the highest electron mobility. Finally, C60BB- and C70BB-based TPSCs showed impressive efficiencies up to 14.51 and 14.28%, respectively. These devices also exhibited excellent long-term stability. This work highlights the importance of developing strategies to synthesize single-isomer fullerene bisadducts and regulate their molecular packing to improve TPSCs' performance.
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Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide-releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.
Subject(s)
Kidney Transplantation , Kidney , Organ Preservation , Organometallic Compounds , Perfusion , Warm Ischemia , Animals , Warm Ischemia/adverse effects , Kidney/blood supply , Kidney/pathology , Kidney/drug effects , Perfusion/methods , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Humans , Organ Preservation/methods , Male , Organometallic Compounds/administration & dosage , Organometallic Compounds/pharmacology , Reperfusion Injury/prevention & control , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Rats , Oxygen/metabolism , Oxidative Stress/drug effects , Apoptosis/drug effects , Microcirculation/drug effects , Time Factors , Human Umbilical Vein Endothelial Cells/drug effectsABSTRACT
The locular gel, produced by the placenta, is important for fruit flavor and seed development in tomato. However, the mechanism underlying locule and placenta development is not fully understood yet. Here, we show that two SlARF transcription factors, SlARF8B and SlARF8A (SlARF8A/B), promote the development of locular and placenta tissues. The expression of both SlARF8A and SlARF8B is repressed by sly-microRNA167 (sly-miR167), allowing for the activation of auxin downstream genes. In slarf8a, slarf8b, and slarf8a/b mutants, the auxin (IAA) levels are decreased, whereas the levels of inactive IAA conjugates including IAA-Ala, IAA-Asp, and IAA-Glu are increased. We further find that SlARF8B directly inhibits the expression of SlGH3.4, an acyl acid amino synthetase that conjugates the amino acids to IAA. Disruption of such auxin balance by the increased expression of SlGH3.4 or SlGH3.2 results in defective locular and placental tissues. Taken together, our findings reveal an important regulatory module constituted by sly-miR167-SlARF8A/B-SlGH3.4 during the development of locular and placenta tissues of tomato fruits.
Subject(s)
Fruit , Solanum lycopersicum , Pregnancy , Female , Humans , Solanum lycopersicum/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Feedback , Placenta/metabolism , Indoleacetic Acids/metabolism , Homeostasis , Gene Expression Regulation, PlantABSTRACT
Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management.
Subject(s)
Chitinases , Houseflies , Animals , Houseflies/genetics , Houseflies/metabolism , Chitinases/metabolism , Larva , Recombinant Proteins/genetics , Chitin/metabolismABSTRACT
BACKGROUND: Esophageal cancer is a significant global health concern, ranking seventh in incidence and sixth in mortality. It encompasses two pathological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, with ESCC being more prevalent globally and associated with higher mortality rates. The POU (Pit-Oct-Unc) domain family transcription factors, comprising 15 members, play important roles in embryonic development and organ formation. Aberrant expression of POUs has been observed in several human cancers, influencing cell proliferation, tumor invasion, and drug resistance. However, their specific role in ESCC remains unknown. METHODS: We analyzed TCGA and GEO databases to assess POUs expression in ESCC tissues. Kaplan-Meier and ROC analyses were used to evaluate the prognostic value of POUs. Gene Set Enrichment Analysis and Protein-Protein interaction network were used to explore the potential pathway. Functional assays (Cell Counting Kit-8, EdU Staining assay, and cloning formation assay) and mechanism analyses (RNA-seq, flow cytometry, and Western blot) were conducted to determine the effects of POU4F1 knockdown on ESCC cell phenotypes and signaling pathways. RESULTS: POU4F1 and POU6F2 were upregulated in various cancer tissues, including ESCC, compared to normal tissues. POU4F1 expression was significantly correlated with patient survival and superior to previous models (AUC = 0.776). Knockdown of POU4F1 inhibited ESCC cell proliferation and affected cell cycle, autophagy, and DNA damage pathways in ESCC cells. CONCLUSION: POU4F1 is a novel and promising prognostic and therapeutic target for ESCC patients, providing insights into potential treatment strategies.
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OBJECTIVE: To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome (ASS). METHODS: This study included 115 anti-Jo-1-positive patients with ASS who were admitted to China-Japan Friendship Hospital between 2009 and 2019. Anti-Jo-1 antibody serum levels at initial admission and follow-up were determined by enzyme-linked immunosorbent assay (ELISA). Global and organ disease activity was assessed at baseline and follow-up according to the International Myositis Assessment and Clinical Studies guidelines. RESULTS: Among enrolled patients, 70 (60.9%) patients initially presented with interstitial lung disease (ILD), and 46 (40%) patients presented with with muscle weakness at initial admission. At baseline, patients with ILD had lower levels of anti-Jo-1 antibodies than those without ILD (p = 0.012). Baseline anti-Jo-1 antibody levels were higher in patients with muscle weakness, skin involvement, and arthritis (all p < 0.05) compared to those without these manifestations. Baseline anti-Jo-1 antibody levels were positively correlated with skin visual analogue scale (VAS) scores (r = 0.25, p = 0.006), but not with disease activity in other organs. However, changes in anti-Jo-1 antibody levels were significantly positively correlated with the changes in PGA (ß = 0.002, p = 0.001), muscle (ß = 0.003, p < 0.0001), and pulmonary (ß = 0.002, p = 0.013) VAS scores, but not with skin and joint VAS scores. Older age of onset (hazard ratio [HR] 1.069, 95% confidence interval [CI]:1.010-1.133, p = 0.022) and higher C-reactive protein (CRP) levels (HR 1.333, 95% CI: 1.035-1.717, p = 0.026) were risk factors for death. CONCLUSION: Anti-Jo-1 titers appear to correlate more with disease activity changes over time rather than with organ involvement at baseline, which provides better clinical guidance for assessing the disease course using anti-Jo-1 levels.
Subject(s)
Antibodies, Antinuclear , Myositis , Humans , Myositis/blood , Myositis/immunology , Myositis/diagnosis , Male , Female , Middle Aged , Prognosis , Adult , Antibodies, Antinuclear/blood , Follow-Up Studies , Aged , Retrospective Studies , Biomarkers/blood , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/diagnosisABSTRACT
The pathogenesis of schizophrenia is believed to involve combined dysfunctions of many proteins including microtubule-associated protein 6 (MAP6) and Kv3.1 voltage-gated K+ (Kv) channel, but their relationship and functions in behavioral regulation are often not known. Here we report that MAP6 stabilizes Kv3.1 channels in parvalbumin-positive (PV+ ) fast-spiking GABAergic interneurons, regulating behavior. MAP6-/- and Kv3.1-/- mice display similar hyperactivity and avoidance reduction. Their proteins colocalize in PV+ interneurons and MAP6 deletion markedly reduces Kv3.1 protein level. We further show that two microtubule-binding modules of MAP6 bind the Kv3.1 tetramerization domain with high affinity, maintaining the channel level in both neuronal soma and axons. MAP6 knockdown by AAV-shRNA in the amygdala or the hippocampus reduces avoidance or causes hyperactivity and recognition memory deficit, respectively, through elevating projection neuron activity. Finally, knocking down Kv3.1 or disrupting the MAP6-Kv3.1 binding in these brain regions causes avoidance reduction and hyperactivity, consistent with the effects of MAP6 knockdown. Thus, disrupting this conserved cytoskeleton-membrane interaction in fast-spiking neurons causes different degrees of functional vulnerability in various neural circuits.
Subject(s)
Neurons , Potassium Channels, Voltage-Gated , Mice , Animals , Neurons/metabolism , Potassium Channels, Voltage-Gated/pharmacology , Cytoskeleton/metabolism , Microtubules/metabolism , Emotions , Shaw Potassium Channels/metabolismABSTRACT
Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM), and cell death plays an important role. Ferroptosis is a recently discovered type of iron-dependent cell death and one that is different from other kinds of cell death including apoptosis and necrosis. However, ferroptosis has not been described in the context of DN. This study explored the role of ferroptosis in DN pathophysiology and aimed to confirm the efficacy of the ferroptosis inhibitor SRS 16-86 on DN. Streptozotocin injection was used to establish the DM and DN animal models. To investigate the presence or occurrence of ferroptosis in DN, we assessed the concentrations of iron, reactive oxygen species and specific markers associated with ferroptosis in a rat model of DN. Additionally, we performed haematoxylin-eosin staining, blood biochemistry, urine biochemistry and kidney function analysis to evaluate the efficacy of the ferroptosis inhibitor SRS 16-86 in ameliorating DN. We found that SRS 16-86 could improve the recovery of renal function after DN by upregulating glutathione peroxidase 4, glutathione and system xc -light chain and by downregulating the lipid peroxidation markers and 4-hydroxynonenal. SRS 16-86 treatment could improve renal organization after DN. The inflammatory cytokines interleukin 1ß and tumour necrosis factor α and intercellular adhesion molecule 1 were significantly decreased following SRS 16-86 treatment after DN. The results indicate that there is a strong connection between ferroptosis and the pathological mechanism of DN. The efficacy of the ferroptosis inhibitor SRS 16-86 in DN repair supports its use as a new therapeutic treatment for DN.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Ferroptosis , Rats, Sprague-Dawley , Ferroptosis/drug effects , Ferroptosis/physiology , Animals , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/physiopathology , Male , Rats , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Reactive Oxygen Species/metabolism , Lipid Peroxidation/drug effects , Kidney/metabolism , Kidney/drug effects , Kidney/pathology , Iron/metabolismABSTRACT
An antibody-drug conjugate (ADC) of human epidermal growth factor receptor-2 (HER2) provides effective treatment for patients with HER2-positive non-small cell lung cancer (NSCLC). Exon 20 insertion mutations are the most common among HER2 mutations. This mutant subtype is highly drug-resistant, and patients receiving conventional treatment often have a poor prognosis. Trastuzumab deruxtecan (T-DXd), a novel anti-HER2 ADC, has emerged as a novel treatment option for HER2-positive (mutated, expressed, amplified, alternated) NSCLC, based on several studies and reported results. Herein, we report a case of stage IV NSCLC with HER2 exon 20 mutation in a 52-year-old male patient whose tumor recurred after radical resection of pulmonary carcinoma, who could not tolerate chemotherapy, and presented with bone metastasis. After treatment with T-DXd, the tumor significantly regressed and bone metastasis improved, maintaining a state of no progression for 21 months. This case report evidences the use of T-DXd in the treatment of NSCLC with HER2 exon 20 insertion mutation.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Immunoconjugates , Lung Neoplasms , Male , Humans , Middle Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Mutagenesis, Insertional , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Trastuzumab/therapeutic use , Camptothecin , Receptor, ErbB-2/genetics , ExonsABSTRACT
The transportation behaviors of compound droplets in confined channels are widespread phenomena while the physical mechanisms are far from being completely unraveled. In this work, behaviors of double emulsions flowing through bifurcation microchannels are experimentally studied with the aim of building universal flow pattern maps. Three flow patterns are categorized according to different features of daughter droplets in terms of size, uniformity, and shell thickness. A detailed analysis of the dynamics of interfacial evolutions in different patterns is carried out and the coupling interaction between interfaces is found to affect the minimum tail distance during transportation. It is feasible to obtain the threshold of the occurrence of the coupling interaction, due to the different variation tendencies in the two states, which relies on three dimensionless parameters, i.e. droplet length, length ratio, and capillary number. Furthermore, a novel physical model is proposed to build the flow pattern map, with the two transition boundaries being expressed as different relationships in terms of the three identified parameters. The physical mechanisms are summarized with the aid of force analysis. An excellent agreement is shown between the model and experimental results in different liquid systems and bifurcation structures, indicating the generality of the proposed model.
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OBJECTIVES: To investigate the prevalence and characteristics of typical polymyositis (PM) in Chinese patients with idiopathic inflammatory myopathy (IIM). METHODS: Patients diagnosed with IIM according to the 2017 EULAR/ACR criteria were included. Serological aspects including myositis-specific antibodies (MSA) and pathological data were re-evaluated. The diagnosis of typical PM was strictly done using the pathological criteria, while excluding other IIM subtypes such as dermatomyositis (DM), immune-mediated necrotising myopathies (IMNM), anti-synthetase syndrome (ASS), and sporadic inclusion body myositis (sIBM), based on their respective diagnostic criteria. RESULTS: A total of 544 IIM patients with muscle biopsy were involved, and 129 of them were diagnosed with initial PM according to the 2017 EULAR/ACR criteria. Only 6 (1.1%, 6/544) patients met the strict definition of typical PM after re-evaluation. Patients with typical PM were MSA-negative (100% vs. 35.7%, p=0.003) and had CD8+ T cells surrounding or invading non-necrotic muscle fibres in muscle biopsies (100% vs. 7.8%, p<0.001) compared to the initially diagnosed PM patients. All typical PM patients achieved clinical remission at the second-year follow-up. Typical PM patients had a favourable prognosis compared to MSA-negative IMNM and unspecific myositis patients. CONCLUSIONS: Strictly defined typical PM is a rare clinical subtype in Chinese IIM patients. Typical PM patients with classical pathology were MSA-negative and responded well to treatment and had a favourable prognosis. It is crucial for clinicians to combine clinical, serological, and pathological features to properly distinguish PM from other IIM subtypes.
Subject(s)
Autoimmune Diseases , Myositis, Inclusion Body , Myositis , Polymyositis , Humans , Myositis/diagnosis , Myositis/epidemiology , Myositis/therapy , Polymyositis/diagnosis , Polymyositis/epidemiology , Antibodies , China/epidemiology , AutoantibodiesABSTRACT
The purpose of this study is to describe the morbidity and mortality of children during the entire COVID-19 pandemic. Age-disaggregated data of 108,003,741 cases and 560,426 deaths were collected from Canada, France, Germany, and Italy. The number of cases and deaths per million people per week, as well as case fatality rates (CFRs), were calculated for patients aged 0-14 and ≥ 15 years. During the first pandemic period in the four countries, starting from weeks 4 to 11 (in 2020) and ending at week 22 (in 2021), the number of deaths per million people per week and the CFRs in the ≥ 15 years age group were 500 to 2513 and 442 to 1662 times greater, respectively, than those in the 0-14 years age group. The number of deaths per million people per week was significantly lower in the first pandemic period than in the second pandemic period, which started at week 23 (2021) and ended from week 22 to week 25 (2023). During the second pandemic period in the four countries, the disparities between the ≥ 15 years and 0-14 years age groups decreased, and the number of deaths per million people per week in the ≥ 15 years age group was 76 to 180 times greater than it in the 0-14 years age group. CONCLUSION: Children aged 0-14 years had a far lower mortality risk during the entire COVID-19 pandemic, and the impact of viral variants and/or vaccination on the mortality rate is difficult to distinguish. WHAT IS KNOWN: ⢠Although extensive studies have focused on COVID-19-induced mortality, most of them are provisional reports performed during the unfolding of the pandemic and provide imprecise conclusion. WHAT IS NEW: ⢠We described the morbidity and mortality for children aged 0-14 years using complete survey data recorded during the entire COVID-19 pandemic. ⢠The number of deaths per million people per week was far lower in children aged 0-14 years, while the number of deaths per million people per week in children aged 0-14 years was significantly higher in the second period which starting from week 23 (2021) and ending at week 22 to 25 (2023) than in the first period which starting from week 1 to 11 (2020) and ending at week 22 (2021).
Subject(s)
COVID-19 , Humans , COVID-19/mortality , COVID-19/epidemiology , Child , Adolescent , Infant , Child, Preschool , Infant, Newborn , Male , Female , SARS-CoV-2 , Pandemics , France/epidemiology , Italy/epidemiology , Age DistributionABSTRACT
Freezing of gait (FoG) is one of the most distressing symptoms of Parkinson's Disease (PD), commonly occurring in patients at middle and late stages of the disease. Automatic and accurate FoG detection and prediction have emerged as a promising tool for long-term monitoring of PD and implementation of gait assistance systems. This paper reviews the recent development of FoG detection and prediction using wearable sensors, with attention on identifying knowledge gaps that need to be filled in future research. This review searched the PubMed and Web of Science databases to collect studies that detect or predict FoG with wearable sensors. After screening, 89 of 270 articles were included. The data description, extracted features, detection/prediction methods, and classification performance were extracted from the articles. As the number of papers of this area is increasing, the performance has been steadily improved. However, small datasets and inconsistent evaluation processes still hinder the application of FoG detection and prediction with wearable sensors in clinical practice.