A calcium-dependent protein kinase regulates the defense response in Citrus sinensis.

Citrus Huanglongbing (HLB), which is caused by Candidatus Liberibacter asiaticus (CLas), is one of the most destructive citrus diseases worldwide, and defense-related Citrus sinensis gene resources remain largely unexplored. Calcium signaling plays an important role in diverse biological processes. In plants, a few calcium-dependent protein kinases (CDPKs/CPKs) have been shown to contribute to defense against pathogenic microbes. The genome of Citrus sinensis encodes dozens of CPKs. In this study, the role of CsCPKs in Citrus sinensis defense was investigated. Silencing of CsCPK6 compromised the induction of defense-related genes in Citrus sinensis. Expression of a constitutively active form of CsCPK6 (CsCPK6CA) triggers the activation of defense-related genes in Citrus sinensis. Complementation of CsCPK6 rescued the defense-related gene induction in an Arabidopsis thaliana cpk4/11 mutant, indicating that CsCPK6 carries CPK activity and is capable of functioning as a CPK in Arabidopsis. Moreover, an effector derived from CLas inhibits defense induced by the expression of CsCPK6CA and autophosphorylation of CsCPK6, which suggests the involvement of CsCPK6 and calcium signaling in defense. These results support the positive role of CsCPK6 in Citrus sinensis defense against CLas, and the auto-inhibitory regulation of CsCPK6 provides a potential genome-editing target for improving the defense of Citrus sinensis.

How users make judgements about the quality of online health information: a cross-sectional survey study.

BACKGROUND: People increasingly use the Internet to seek health information. However, the overall quality of online health information remains low. This situation is exacerbated by the unprecedented "infodemic", which has had negative consequences for patients. Therefore, it is important to understand how users make judgements about health information by applying different judgement criteria. OBJECTIVE: The objective of this study is to determine how patients apply different criteria in their judgement of the quality of online health information during the pandemic. In particular, we investigate whether there is consistency between the likelihood of using a particular judgement criterion and its perceived importance among different groups of users. METHODS: A cross-sectional survey was conducted in one of the leading hospitals in a coastal province of China with a population of forty million. Combined-strategy sampling was used to balance the randomness and the practicality of the recruiting process. A total of 1063 patients were recruited for this study. Chi-square and Kruskal-Wallis analyses were used to analyse the survey data. RESULTS: In general, patients make quality judgement of health information more frequently based on whether it is familiar, aesthetic, and with expertise. In comparison, they put more weights on whether health information is secure, trustworthy, and with expertise when determining its quality. Criteria that were considered more important were not always those with a higher likelihood of being used. Patients may not use particular criteria, such as familiarity, identification, and readability, more frequently than others even if they consider them to be more important than other do and vice versa. Surprisingly, patients with a primary school degree put more weight on whether health information is comprehensive than those with higher degrees do in determining its quality. However, they are less likely to use this guideline in practice. CONCLUSIONS: To the best of our knowledge, this is the first study to investigate the consistency between the likelihood of using certain quality judgement criteria and their perceived importance among patients grouped by different demographic variables and eHealth literacy levels. The findings highlight how to improve online health information services and provide fine-grained customization of information for users.

Student Reflections on Shared Trauma: One Year Later.

In March of 2021, as the world marked the first anniversary since COVID-19 altered our reality, graduate social work students in Dr. Carol Tosone's Evidence-Based Trauma class at NYU considered the challenges of learning about trauma treatment while simultaneously living through a global trauma. Students reflected on their home lives, school experiences, field placements, mental health challenges, feelings of burnout, and the added complexities of racial disparities and injustices. Students also shared their coping mechanisms and hope for the future. This paper aims to provide insight into their varied experiences while relating their struggles and demonstrating their pathways toward resiliency.

Advanced Driving Assistance Based on the Fusion of Infrared and Visible Images.

Obtaining key and rich visual information under sophisticated road conditions is one of the key requirements for advanced driving assistance. In this paper, a newfangled end-to-end model is proposed for advanced driving assistance based on the fusion of infrared and visible images, termed as FusionADA. In our model, we are committed to extracting and fusing the optimal texture details and salient thermal targets from the source images. To achieve this goal, our model constitutes an adversarial framework between the generator and the discriminator. Specifically, the generator aims to generate a fused image with basic intensity information together with the optimal texture details from source images, while the discriminator aims to force the fused image to restore the salient thermal targets from the source infrared image. In addition, our FusionADA is a fully end-to-end model, solving the issues of manually designing complicated activity level measurements and fusion rules existing in traditional methods. Qualitative and quantitative experiments on publicly available datasets RoadScene and TNO demonstrate the superiority of our FusionADA over the state-of-the-art approaches.

Design, synthesis and evaluation of 3-amide-5-aryl benzoic acid derivatives as novel P2Y14R antagonists with potential high efficiency against acute gouty arthritis.

P2Y14 nucleotide receptor plays important roles in series of physiological and pathologic events especially associated with immune and inflammation. Based on the 3-amide benzoic acid scaffold reported by our group previously, a series of 5-aryl-3-amide benzoic acid derivatives were designed as novel P2Y14 antagonists with improved pharmacokinetic properties. Among which compound 11m showed most potent P2Y14 antagonizing activity with an IC50 value of 2.18 nM, furnishing greatly improved water solubility and bioavailability compared with PPTN. In MSU-induced acute gouty arthritis model in mice, 11m exerted promising in vivo efficacy in alleviating mice paw swelling and inflammatory infiltration. Mechanistically, compound 11m notably blocked pyroptosis of macrophages through inhibiting NLRP3 inflammasome activation. This work may contribute to the identification of potential therapeutic agents to intervene in acute gouty arthritis.

Regulation of Female Germline Specification via Small RNA Mobility in Arabidopsis.

In the ovules of most sexually reproducing plants, one hypodermal cell differentiates into a megaspore mother cell (MMC), which gives rise to the female germline. Trans-acting small interfering RNAs known as tasiR-ARFs have been suggested to act non-cell-autonomously to prevent the formation of multiple MMCs by repressing AUXIN RESPONSE FACTOR3 (ARF3) expression in Arabidopsis (Arabidopsis thaliana), but the underlying mechanisms are unknown. Here, we examined tasiR-ARF-related intercellular regulatory mechanisms. Expression analysis revealed that components of the tasiR-ARF biogenesis pathway are restricted to distinct ovule cell types, thus limiting tasiR-ARF production to the nucellar epidermis. We also provide data suggesting tasiR-ARF movement along the mediolateral axis into the hypodermal cells and basipetally into the chalaza. Furthermore, we used cell type-specific promoters to express ARF3m, which is resistant to tasiR-ARF regulation, in different ovule cell layers. ARF3m expression in hypodermal cells surrounding the MMC, but not in epidermal cells, led to a multiple-MMC phenotype, suggesting that tasiR-ARFs repress ARF3 in these hypodermal cells to suppress ectopic MMC fate. RNA sequencing analyses in plants with hypodermally expressed ARF3m showed that ARF3 potentially regulates MMC specification through phytohormone pathways. Our findings uncover intricate spatial restriction of tasiR-ARF biogenesis, which together with tasiR-ARF mobility enables cell-cell communication in MMC differentiation.

Effectiveness of Yi-Zhi-An-Shen granules on cognition and sleep quality in older adults with amnestic mild cognitive impairment: protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is a syndrome characterized by significant forgetfulness that does not meet the criteria of dementia. Individuals with aMCI are at greater risk of progressing to dementia. Current studies suggest that good sleep quality is linked with preserved cognition in the elderly, and sleep complaints are common among the elderly with amnesia. Therefore, improving their sleep may be helpful for maintaining and improving their cognitive capacity. According to the theory of traditional Chinese medicine, Yi-Zhi-An-Shen is an herbal compound which may ameliorate forgetfulness and sleep disorders. As growing evidence indicates that the gut microbiome is associated with major mental symptoms, a hypothesis was proposed that Yi-Zhi-An-Shen granules (YZASG) might work by alternating microbial abundance and diversity. In this study, the investigators intend to assess the efficacy of YZASG on global cognition in the elderly suffering from aMCI and evaluate its safety as well as its potential mechanisms via sleep quality, fecal microbial 16S ribosomal DNA and metagenomics analyses, and serum markers. METHODS/DESIGN: This study is a randomized, double-blind, placebo-controlled clinical trial. A total of 80 patients (aged 60-85 years) will be recruited and allocated randomly to a treatment group and a placebo group in a 1:1 ratio and will then be administered YZASG or isodose placebo three times a day. The intervention course is 16 weeks, with an 18 months follow-up. The primary outcome is the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Secondary outcome measures are the Mini-Mental State Examination, Montreal Cognitive Assessment, Pittsburgh Sleep Quality Index, serum concentrations of immunological factors and inflammatory cytokines, and fecal microbiota. Fecal microbiota will only be collected at the baseline and endpoint of the intervention. DISCUSSION: The results of this trial will be conducive to assessing the safety and effectiveness on cognition of YZASG in intervening aMCI among the elderly and determining if it takes effect via the improvement of sleep quality, regulation of gut microbiota, and concentration of certain serum markers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03601000 . Registered on 26 July 2018.

Design, synthesis and anti-inflammatory evaluation of 3-amide benzoic acid derivatives as novel P2Y14 receptor antagonists.

The P2Y14 receptor (P2Y14R) plays a key role in the modulation of inflammatory process, but very few classes of antagonists have been reported. A series of 3-amide benzoic acid derivatives were identified as novel and potent P2Y14R antagonists. The most potent antagonist, 16c, showed comparable activity (IC50 = 1.77 nM) to PPTN, the most potent P2Y14R antagonist reported. Compound 16c demonstrated dramatically improved aqueous solubility and excellent metabolic stability in rat and human microsomes. Investigation of the anti-inflammatory effect of 16c was performed in MSU treated THP-1 cells by flow cytometry, Western Blot and immunofluorescence labeling technology, which exhibited that 16c might be a promising candidate for further research.

Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy.

Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O'1,O1-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction. Our study showed that the MLP could deliver polo-like kinase 1 siRNA (siPLK1) into glioma cells and effectively enhance the cellular uptake of MLP/siPLK1 because of increased positive charges induced by hypoxia and low pH. Moreover, MLP/siPLK1 was shown to be very effective in inhibiting the growth of glioma cells both in vitro and in vivo. Therefore, the MLP is a promising siRNA delivery system for tumor therapy.

Development of a hypoxia-triggered and hypoxic radiosensitized liposome as a doxorubicin carrier to promote synergetic chemo-/radio-therapy for glioma.

The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma. In this study, hypoxic radiosensitizer nitroimidazoles were conjugated with lipid molecules with a hydrolysable ester bond to form MDH. MDH was mixed together with DSPE-PEG2000 and cholesterol to make MLP liposomes, which were found to have strong radiosensitivity and to promote cargo release under hypoxic conditions, due to the properties of nitroimidazoles under hypoxic conditions. MLP/DOX was found to have distinct advantages, including precise and stealthy pharmacokinetics and efficient passive uptake by the tumor. Furthermore, the combination of MLP/DOX and radiotherapy (RT) significantly inhibited glioma growth as assessed by in vivo bioluminescence imaging. These findings suggest that MLP is a promising candidate as a DOX delivery system to enhance the antitumor treatment effects on glioma, owing to synergistic chemo-/radiotherapy.