ABSTRACT
Drought and low temperature are two key environmental factors that induce adult citrus flowering. However, the underlying regulation mechanism is poorly understood. The bZIP transcription ...factor FD is a key component of the florigen activation complex (FAC) which is composed of FLOWERING LOCUS T (FT), FD, and 14‐3‐3 proteins. In this study, isolation and characterization of CiFD in citrus found that there was alternative splicing (AS) of CiFD, forming two different proteins (CiFDα and CiFDβ). Further investigation found that their expression patterns were similar in different tissues of citrus, but the subcellular localization and transcriptional activity were different. Overexpression of the CiFD DNA sequence (CiFD‐DNA), CiFDα, or CiFDβ in tobacco and citrus showed early flowering, and CiFD‐DNA transgenic plants were the earliest, followed by CiFDβ and CiFDα. Interestingly, CiFDα and CiFDβ were induced by low temperature and drought, respectively. Further analysis showed that CiFDα can form a FAC complex with CiFT, Ci14‐3‐3, and then bind to the citrus APETALA1 (CiAP1) promoter and promote its expression. However, CiFDβ can directly bind to the CiAP1 promoter independently of CiFT and Ci14‐3‐3. These results showed that CiFDβ can form a more direct and simplified pathway that is independent of the FAC complex to regulate drought‐induced flowering through AS. In addition, a bHLH transcription factor (CibHLH96) binds to CiFD promoter and promotes the expression of CiFD under drought condition. Transgenic analysis found that CibHLH96 can promote flowering in transgenic tobacco. These results suggest that CiFD is involved in drought‐ and low‐temperature‐induced citrus flowering through different regulatory patterns.
In citrus, alternative splicing of the transcription factor gene CiFD produces two different proteins, CiFDα and CiFDβ At low temperature, CiFDα forms a complex with CiFLOWERING LOCUS T and Ci14‐3‐3 to activate the expression of CiAPETALA1. Under drought conditions, CiFDβ directly binds to the CiAPETALA1 promoter to induce flowering.
MADS-box genes are involved in various developmental processes including vegetative development, flower architecture, flowering, pollen formation, seed and fruit development. However, the function of ...most MADS-box genes and their regulation mechanism are still unclear in woody plants compared with model plants. In this study, a MADS-box gene (CiMADS43) was identified in citrus. Phylogenetic and sequence analysis showed that CiMADS43 is a GOA-like Bsister MADS-box gene. It was localized in the nucleus and as a transcriptional activator. Overexpression of CiMADS43 promoted early flowering and leaves curling in transgenic Arabidopsis. Besides, overexpression or knockout of CiMADS43 also showed leaf curl phenotype in citrus similar to that of CiMADS43 overexpressed in Arabidopsis. Protein–protein interaction found that a SEPALLATA (SEP)-like protein (CiAGL9) interacted with CiMADS43 protein. Interestingly, CiAGL9 also can bind to the CiMADS43 promoter and promote its transcription. Expression analysis also showed that these two genes were closely related to seasonal flowering and the development of the leaf in citrus. Our findings revealed the multifunctional roles of CiMADS43 in the vegetative and reproductive development of citrus. These results will facilitate our understanding of the evolution and molecular mechanisms of MADS-box genes in citrus.
Background and aims
The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has recently spread worldwide and been ...declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases.
Methods
Electronic medical records of 11 patients with COVID‐19 were collected, and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed.
Results
The clinical course of the eleven cases demonstrated the complexity of the COVID‐19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe.
Conclusion
All different clinical characteristics of COVID‐19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.
Clinical manifestations of COVID‐19 range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe.
The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and ...high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.
Optical properties are among the most fascinating and useful properties of nanomaterials and have been extensively studied using a variety of optical spectroscopic techniques. A basic understanding ...of the optical properties and related spectroscopic techniques is essential for anyone who is interested in learning about nanomaterials of semiconductors, insulators or metal. This is partly because optical properties are intimately related to other properties and functionalities (e.g. electronic, magnetic, and thermal) that are of fundamental importance to many technological applications, such as energy conversion, chemical analysis, biomedicine, optoelectronics, communication, and radiation detection.
Aim
Transcutaneous electrical cranial‐auricular acupoint stimulation (TECAS) is a novel non‐invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An ...assessor‐blinded, randomized, non‐inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild‐to‐moderate major depressive disorder.
Methods
468 participants received two TECAS sessions per day at home (n = 233) or approximately 10–13 mg/day escitalopram (n = 235) for 8 weeks plus 4‐week follow‐up. The primary outcome was clinical response, defined as a baseline‐to‐endpoint ≥50% reduction in Montgomery‐Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality.
Results
The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval CI, −5.9% to 12.9%) in intention‐to‐treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, −6.9% to 11.4%) in per‐protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non‐inferiority margin of −10% (P ≤ 0.004 for non‐inferiority). Most secondary outcomes did not differ between the two groups. TECAS‐treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram.
Conclusions
TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma‐associated depression. It could serve an effective portable therapy for mild‐to‐moderate depression.
Background
Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has been widely spread. We aim to investigate the clinical ...characteristic and allergy status of patients infected with SARS‐CoV‐2.
Methods
Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID‐19 patients, with confirmed result of SARS‐CoV‐2 viral infection, were extracted and analyzed.
Results
An approximately 1:1 ratio of male (50.7%) and female COVID‐19 patients was found, with an overall median age of 57.0 years. All patients were community‐acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self‐reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground‐glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r = .486, P < .001) and nonsevere (r = .469, P < .001) patients after hospital admission. Significantly higher levels of D‐dimer, C‐reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P < .001).
Conclusion
Detailed clinical investigation of 140 hospitalized COVID‐19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS‐CoV‐2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.
Decreased eosinophil count, which was positively correlated with lymphocyte counts, may be a potential biological indicator for diagnosing
COVID‐19 patients. Low prevalence of allergic diseases, COPD and patients with smoking history indicated they may not be the predisposing
factors of COVID‐19. Elder age, high number of comorbidities and more prominent laboratory abnormalities were associated with severe
patientsz.
The clinical application of central nervous system (CNS) drugs is limited by their poor bioavailability due to the blood-brain barrier (BBB). Borneol is a naturally occurring compound in a class of ...'orifice-opening' agents often used for resuscitative purposes in traditional Chinese medicine. A growing body of evidence confirms that the 'orifice-opening' effect of borneol is principally derived from opening the BBB. Borneol is therefore believed to be an effective adjuvant that can improve drug delivery to the brain. The purpose of this paper is to provide a comprehensive review of information accumulated over the past two decades on borneol's chemical features, sources, toxic and kinetic profiles, enhancing effects on BBB permeability and their putative mechanisms, improvements in CNS drug delivery, and pharmaceutical forms. The BBB-opening effect of borneol is a reversible physiological process characterized by rapid and transient penetration of the BBB and highly specific brain regional distribution. Borneol also protects the structural integrity of the BBB against pathological damage. The enhancement of the BBB permeability is associated with the modulation of multiple ATP-binding cassette transporters, including P-glycoprotein; tight junction proteins; and predominant enhancement of vasodilatory neurotransmitters. Systemic co-administration with borneol improves drug delivery to the brain in a region-, dose- and time-dependent manner. Several pharmaceutical forms of borneol have been developed to improve the kinetic and toxic profiles of co-administered drugs and enhance their delivery to the brain. Borneol is a promising novel agent that deserves further development as a BBB permeation enhancer for CNS drug delivery.
Background
The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has made widespread impact recently. We aim to ...investigate the clinical characteristics of COVID‐19 children with different severities and allergic status.
Methods
Data extracted from the electronic medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results, and radiological images of 182 hospitalized COVID‐19 children, were summarized and analyzed.
Results
The median age was 6 years, ranging from 3 days to 15 years, and there were more boys (male‐female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort, and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground‐glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia (manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase, and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10, and TNF‐α. There were no differences in treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing, and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID‐19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID‐19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy, and asthma. Demographics and clinical features were not significantly different between allergic and nonallergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D‐dimer, and aspartate aminotransferase levels compared with all patients. Immunological profiles including circulating T, B, and NK lymphocyte subsets, total immunoglobulin and complement levels, and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subset numbers, and serum cytokine levels.
Conclusion
Pediatric COVID‐19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and nonallergic COVID‐19 children in disease incidence, clinical features, and laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS‐CoV‐2 infection and hardly influenced the disease course of COVID‐19 in children.
There is no difference between allergic and nonallergic children in clinical features and laboratory/immunological findings, and allergy is not a risk factor for COVID‐19. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) was observed. Higher proportion of patients with pneumonia have fever, cough, comorbidities, and increased inflammatory biomarkers (procalcitonin, alkaline phosphatase and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10, and TNF‐α) than those without pneumonia. Abbreviations: AD, atopic dermatitis; AR, allergic rhinitis; AST, aspartate aminotransferase, AURI, acute upper respiratory infection; COVID‐19, coronavirus disease 2019; DA, drug allergy; FA, food allergy; PCT, procalcitonin; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; TNF, tumor necrosis factor.
The fidelity of intracellular signaling hinges on the organization of dynamic activity architectures. Spatial compartmentation was first proposed over 30 years ago to explain how diverse G ...protein-coupled receptors achieve specificity despite converging on a ubiquitous messenger, cyclic adenosine monophosphate (cAMP). However, the mechanisms responsible for spatially constraining this diffusible messenger remain elusive. Here, we reveal that the type I regulatory subunit of cAMP-dependent protein kinase (PKA), RIα, undergoes liquid-liquid phase separation (LLPS) as a function of cAMP signaling to form biomolecular condensates enriched in cAMP and PKA activity, critical for effective cAMP compartmentation. We further show that a PKA fusion oncoprotein associated with an atypical liver cancer potently blocks RIα LLPS and induces aberrant cAMP signaling. Loss of RIα LLPS in normal cells increases cell proliferation and induces cell transformation. Our work reveals LLPS as a principal organizer of signaling compartments and highlights the pathological consequences of dysregulating this activity architecture.
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•PKA RIα undergoes liquid-liquid phase separation in response to cAMP dynamics•RIα condensates dynamically sequester cAMP and retain high PKA activity•RIα phase separation is necessary for effective cAMP compartmentation•A PKA oncoprotein disrupts RIα bodies, leading to aberrant signaling and growth
cAMP-responsive condensate formation by PKA’s RIα subunit controls local signaling, and disruption of phase separation in this context contributes to tumorigenesis.
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