Membralin is required for maize development and defines a branch of the endoplasmic reticulum-associated degradation pathway in plants.

Endoplasmic reticulum (ER)-associated degradation (ERAD) plays key roles in controlling protein levels and quality in eukaryotes. The Ring Finger Protein 185 (RNF185)/membralin ubiquitin ligase complex was recently identified as a branch in mammals and is essential for neuronal function, but its function in plant development is unknown. Here, we report the map-based cloning and characterization of Narrow Leaf and Dwarfism 1 (NLD1), which encodes the ER membrane-localized protein membralin and specifically interacts with maize homologs of RNF185 and related components. The nld1 mutant shows defective leaf and root development due to reduced cell number. The defects of nld1 were largely restored by expressing membralin genes from Arabidopsis thaliana and mice, highlighting the conserved roles of membralin proteins in animals and plants. The excessive accumulation of ß-hydroxy ß-methylglutaryl-CoA reductase in nld1 indicates that the enzyme is a membralin-mediated ERAD target. The activation of bZIP60 mRNA splicing-related unfolded protein response signaling and marker gene expression in nld1, as well as DNA fragment and cell viability assays, indicate that membralin deficiency induces ER stress and cell death in maize, thereby affecting organogenesis. Our findings uncover the conserved, indispensable role of the membralin-mediated branch of the ERAD pathway in plants. In addition, ZmNLD1 contributes to plant architecture in a dose-dependent manner, which can serve as a potential target for genetic engineering to shape ideal plant architecture, thereby enhancing high-density maize yields.

Therapeutic potential of mesenchymal stem cells for cerebral small vessel disease.

Cerebral small vessel disease (CSVD), as the most common, chronic and progressive vascular disease on the brain, is a serious neurological disease, whose pathogenesis remains unclear. The disease is a leading cause of stroke and vascular cognitive impairment and dementia, and contributes to about 20% of strokes, including 25% of ischemic strokes and 45% of dementias. Undoubtedly, the high incidence and poor prognosis of CSVD have brought a heavy economic and medical burden to society. The present treatment of CSVD focuses on the management of vascular risk factors. Although vascular risk factors may be important causes or accelerators of CSVD and should always be treated in accordance with best clinical practice, controlling risk factors alone could not curb the progression of CSVD brain injury. Therefore, developing safer and more effective treatment strategies for CSVD is urgently needed. Recently, mesenchymal stem cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of central nervous system disease, given their paracrine properties and immunoregulatory. Herein, we discussed the therapeutic potential of MSCs for CSVD, aiming to enable clinicians and researchers to understand of recent progress and future directions in the field.

A Visualization Method of Knowledge Graphs for the Computation and Comprehension of Ultrasound Reports.

Knowledge graph visualization in ultrasound reports is essential for enhancing medical decision making and the efficiency and accuracy of computer-aided analysis tools. This study aims to propose an intelligent method for analyzing ultrasound reports through knowledge graph visualization. Firstly, we provide a novel method for extracting key term networks from the narrative text in ultrasound reports with high accuracy, enabling the identification and annotation of clinical concepts within the report. Secondly, a knowledge representation framework based on ultrasound reports is proposed, which enables the structured and intuitive visualization of ultrasound report knowledge. Finally, we propose a knowledge graph completion model to address the lack of entities in physicians' writing habits and improve the accuracy of visualizing ultrasound knowledge. In comparison to traditional methods, our proposed approach outperforms the extraction of knowledge from complex ultrasound reports, achieving a significantly higher extraction index (η) of 2.69, surpassing the general pattern-matching method (2.12). In comparison to other state-of-the-art methods, our approach achieves the highest P (0.85), R (0.89), and F1 (0.87) across three testing datasets. The proposed method can effectively utilize the knowledge embedded in ultrasound reports to obtain relevant clinical information and improve the accuracy of using ultrasound knowledge.

Long-Term Imaging of Cys in Cells and Tumor Mice by a Solid-State Fluorescence Probe.

Cysteine is an important biological thiol and is closely related to cancer. It remains a challenge to develop a probe that can provide long-term fluorescence detection and imaging of Cys in cells as well as in living organisms. Here, a solid-state fluorophore HTPQ is combined with an acrylate group to construct a solid-state fluorescent probe HTPQC for Cys recognition. The fluorescence of the probe is quenched when the photoinduced electron transfer (PET) process is turned on and the excited-state intramolecular proton transfer (ESIPT) process is turned off. In the presence of Cys, an obvious solid-state fluorescence signal can be observed. The double quenching mechanism makes the probe HTPQC have the advantages of high sensitivity, good selectivity, and high contrast of biological imaging. Due to low cytotoxicity, the probe HTPQC can be used to detect exogenous and endogenous Cys in living cells and is capable of imaging over long periods of time. By making full use of long wavelengths, the probe can be applied for the detection of Cys levels in tumor mice and equipped with the ability to conduct long-term imaging in vivo.

Maize MITOGEN-ACTIVATED PROTEIN KINASE 20 mediates high-temperature-regulated stomatal movement.

High temperature induces stomatal opening; however, uncontrolled stomatal opening is dangerous for plants in response to high temperature. We identified a high-temperature sensitive (hts) mutant from the ethyl methane sulfonate (EMS)-induced maize (Zea mays) mutant library that is linked to a single base change in MITOGEN-ACTIVATED PROTEIN KINASE 20 (ZmMPK20). Our data demonstrated that hts mutants exhibit substantially increased stomatal opening and water loss rate, as well as decreased thermotolerance, compared to wild-type plants under high temperature. ZmMPK20-knockout mutants showed similar phenotypes as hts mutants. Overexpression of ZmMPK20 decreased stomatal apertures, water loss rate, and enhanced plant thermotolerance. Additional experiments showed that ZmMPK20 interacts with MAP KINASE KINASE 9 (ZmMKK9) and E3 ubiquitin ligase RPM1 INTERACTING PROTEIN 2 (ZmRIN2), a maize homolog of Arabidopsis (Arabidopsis thaliana) RIN2. ZmMPK20 prevented ZmRIN2 degradation by inhibiting ZmRIN2 self-ubiquitination. ZmMKK9 phosphorylated ZmMPK20 and enhanced the inhibitory effect of ZmMPK20 on ZmRIN2 degradation. Moreover, we employed virus-induced gene silencing (VIGS) to silence ZmMKK9 and ZmRIN2 in maize and heterologously overexpressed ZmMKK9 or ZmRIN2 in Arabidopsis. Our findings demonstrated that ZmMKK9 and ZmRIN2 play negative regulatory roles in high-temperature-induced stomatal opening. Accordingly, we propose that the ZmMKK9-ZmMPK20-ZmRIN2 cascade negatively regulates high-temperature-induced stomatal opening and balances water loss and leaf temperature, thus enhancing plant thermotolerance.

Case report: MELAS and T3271C mitochondrial mutation in an adult woman.

Introduction: Patients with mitochondrial disorders always show neurological deficits. However, the diversity of clinical manifestations, genetic heterogeneity and threshold effect caused by maternal heredity make its diagnosis very challenging. Case presentation: A 30-year-old female presented to our neurology department with a recurrence of symmetrical weakness proximally in the lower extremities. Seven years ago, the patient had a sudden onset of persistent weakness in bilateral proximal lower extremities, along with elevated creatinine kinase (CK) and CK-MB. Given the diagnosis of Guillain-Barre syndrome, she was treated with high-dose glucocorticoid (GC) therapy at the local hospital and recovered. After admission to our hospital, laboratory analysis revealed elevated CK and alpha-hydroxybutyrate dehydrogenase in serum. Electrocardiography showed sinus tachycardia and left high ventricular voltage. Electromyography (EMG) and evoked potential (EP) suggested peripheral neurogenic damage of the upper and lower extremities with myogenic wear. Chronic inflammatory demyelinating polyneuropathy (CIDP) was initially considered, but neurological symptoms were not significantly improved with glucocorticoid shock therapy. An elevated level of lactate was found. The short-tau inversion recovery (STIR) axial magnetic resonance image (MRI) revealed mild hyperintensities, indicating muscle edema. Meanwhile, muscle biopsies suggested pathological changes in mitochondrial disorders (MIDs) and neuronal damage. Further mitochondrial genome analysis revealed a heteroplasmic m3271 T>C mutation in the mitochondrial tRNA-Leu gene (UUR). Collectively, the patient was finally diagnosed with mitochondrial disorder and apparently improved after the corresponding treatment to regulate energy metabolism. Conclusions: To our knowledge, it's the first report about MELAS with 3271 mutation that have only shown peripheral nerve motion impairment. Proximal weakness is also common in CIDP. In the context of this patient's experience, mitochondrial genome analysis provides an auxiliary criterion for differential diagnosis between MIDs and CIDP. In the meantime, we discussed the clinical effect of GCs on MIDs.

The cysteine-rich receptor-like kinase CRK4 contributes to the different drought stress response between Columbia and Landsberg erecta.

The natural variation between Arabidopsis (Arabidopsis thaliana) ecotypes Columbia (Col) and Landsberg erecta (Ler) strongly affects abscisic acid (ABA) signalling and drought tolerance. Here, we report that the cysteine-rich receptor-like protein kinase CRK4 is involved in regulating ABA signalling, which contributes to the differences in drought stress tolerance between Col-0 and Ler-0. Loss-of-function crk4 mutants in the Col-0 background were less drought tolerant than Col-0, whereas overexpressing CRK4 in the Ler-0 background partially to completely restored the drought-sensitive phenotype of Ler-0. F1 plants derived from a cross between the crk4 mutant and Ler-0 showed an ABA-insensitive phenotype with respect to stomatal movement, along with reduced drought tolerance like Ler-0. We demonstrate that CRK4 interacts with the U-box E3 ligase PUB13 and enhances its abundance, thus promoting the degradation of ABA-INSENSITIVE 1 (ABI1), a negative regulator of ABA signalling. Together, these findings reveal an important regulatory mechanism for modulating ABI1 levels by the CRK4-PUB13 module to fine-tune drought tolerance in Arabidopsis.

COVID-19 Vaccine Adverse Event Detection Based on Multi-Label Classification With Various Label Selection Strategies.

Analyzing massive VAERS reports without medical context may lead to incorrect conclusions about vaccine adverse events (VAE). Facilitating VAE detection promotes continual safety improvement for new vaccines. This study proposes a multi-label classification method with various term-and topic-based label selection strategies to improve the accuracy and efficiency of VAE detection. Topic modeling methods are first used to generate rule-based label dependencies from Medical Dictionary for Regulatory Activities terms in VAE reports with two hyper-parameters. Multiple label selection strategies, namely one-vs-rest (OvsR), problem transformation (PT), algorithm adaption (AA), and deep learning (DL) methods, are used in multi-label classification to examine the model performance, respectively. Experimental results indicated that the topic-based PT methods improve the accuracy by up to 33.69% using a COVID-19 VAE reporting data set, which improves the robustness and interpretability of our models. In addition, the topic-based OvsR methods achieve an optimal accuracy of up to 98.88%. The accuracy of the AA methods with topic-based labels increased by up to 87.36%. By contrast, the state-of-art LSTM- and BERT-based DL methods have relatively poor performance with accuracy rates of 71.89% and 64.63%, respectively. Our findings reveal that the proposed method effectively improves the model accuracy and strengthens VAE interpretability by using different label selection strategies and domain knowledge in multi-label classification for VAE detection.

A dual-channel fluorescent nanoprobe for accurate cancer diagnosis by sequential detection of adenosine triphosphate and sulfur dioxide.

Cancer is one of the major diseases that seriously endanger the health of all mankind. Accurate diagnosis of early cancer is the most promising way to reduce cancer harm and improve patient survival. However, many developed fluorescent probes for cancer imaging only have the function of identifying one marker, which cannot meet the needs of accurate diagnosis. Here, a fluorescent nanoprobe (CPH@ZIF-90) utilizing ZIF-90 to encapsulate SO2-sensitive dye (CPH) is synthesized for the sequential detection of ATP and SO2. The nanoprobe first interacts with ATP to release CPH, thus increasing the fluorescence at 685 nm and realizing the near-infrared (NIR) fluorescence detection of ATP. Then, SO2 acts on the released CPH through nucleophilic addition, affecting the π-conjugated structure of CPH and resulting in enhanced fluorescence at 580 nm. CPH@ZIF-90 exhibits satisfactory sensitivity and selectivity for sequential detection of ATP and SO2. Excitedly, CPH@ZIF-90 can sequentially image the endogenous ATP and SO2 in cells, showing sensitive fluorescence changes in dual channels (red and green). Due to the NIR emission properties of CPH@ZIF-90 and its ability to enrich in tumor, it is applied to monitor ATP and SO2 in mice and distinguish normal mice from tumor mice. The ability of CPH@ZIF-90 to sequentially detect two cancer-related biomarkers makes it provide meaningful assistance in accurate early diagnosis of cancer.

A near-infrared fluorescent probe for monitoring abnormal mitochondrial viscosity in cancer and fatty-liver mice model.

Viscosity is an important component of cell microenvironment, and abnormal mitochondrial viscosity is associated with many diseases such as tumor and fatty liver. Herein, a near-infrared fluorescence probe (QX-V) based on quinoline-xanthene dye for detecting viscosity is constructed. In high viscosity medium, the free rotation of single bond is inhibited and the fluorescence is released. The probe shows high sensitivity together with good selectivity. Notably, QX-V has a long excitation wavelength (710 nm) and emission wavelength (786 nm). At the same time, the probe is a positively charged molecule that can target mitochondria. QX-V can not only distinguish cancer cells from normal cells, but also make a distinction between normal cells and fatty hepatocytes. In addition, QX-V is used to image viscosity abnormality in tumor-bearing mice. The probe also has a good ability to image viscosity abnormality caused by liver injury in fatty-liver mice.

Joint Power and Time Allocation in Hybrid NoMA/OMA IoT Networks for Two-Way Communications.

This article investigates two-way communications between an access point (AP) and multiple terminals in low-cost Internet of Things (IoT) networks. The main issues considered are the asymmetric transmission traffic on the uplink (UL) and downlink (DL), and the unbalanced receivers processing capability at the AP and the terminals. As a solution, a hybrid non-orthogonal multiple access/orthogonal multiple access (NoMA/OMA) scheme together with a joint power and time allocation method is proposed to address these issues. For the system design, we formulated the optimization problem with the aim of minimizing the system power and satisfying the UL and DL transmission rate constraints. Due to the coupling of power and time variables in the objective function and the multi-user interference (MUI) in the UL transmission rate constraints, the formulated problem is shown to be non-linear and non-convex and thus is hard to solve. To obtain a numerical, efficient solution, the original problem is first reformulated to be a convex one relying on the successive convex approximation (SCA) method, and then a numerical efficient solution is thus obtained by using an iterative routine. The proposed transmission scheme is shown to be not only physically feasible but also power-efficient.

A mesoporous silica-based probe with a molecularly imprinted polymer recognition and Mn:ZnS QDs@rhodamine B ratiometric fluorescence sensing strategy for the analysis of 4-nitrophenol.

In this study, a mesoporous silica fluorescence probe co-doped with manganese-doped zinc sulfide quantum dots (Mn:ZnS QDs) and rhodamine B (RB) and coated with molecularly imprinted polymer (MIP) has been prepared by sol-gel methods. The morphology and structure were characterized in detail by transmission electron microscopy (TEM), Fourier transform-infrared absorption spectroscopy (FT-IR) and ultraviolet-visible absorption spectroscopy (UV-vis). The probe exhibited two characteristic emission peaks at 411 nm and 582 nm, and the synchronous ratiometric fluorescence responses F411/F582 to different concentrations of 4-nitrophenol (4-NP) showed a good linear correlation in the range of 0.01-10 µmol L-1 besides achieving the sensitive detection of 4-NP with a detection limit as low as 3.0 nmol L-1 (3σ). The probe possesses the advantages of selectivity toward the target molecular structure, self-stability in the detection time domain and anti-interference ability, exhibiting excellent potential for application in 4-NP detection in different water environments.

A nitrobenzoxadiazole-based near-infrared fluorescent probe for the specific imaging of H2S in inflammatory and tumor mice.

As a common gaseous signaling molecule, hydrogen sulfide (H2S) plays a vital role in physiology and pathology. The development of fluorescent probes for detecting H2S has attracted widespread attention. However, most of the reported fluorescent probes with nitrobenzoxadiazole (NBD) as the recognition group have been widely used to simultaneously detect biothiols and H2S, instead of specifically detecting H2S. Herein, a novel NBD-based near-infrared (NIR) fluorescent probe named CX-N for the detection of H2S is synthesized. The selectivity of CX-N for H2S is significantly higher than that for biothiols and other potential interferences. After reacting with H2S, CX-N shows a significant increase in NIR fluorescence (75-fold), large Stokes shift (155 nm) and fast response (4 min). And the possible response mechanism of CX-N to H2S is given and confirmed by HPLC and HRMS. Based on the low cytotoxicity of CX-N, it has been used for H2S imaging in live cells and zebrafish. More importantly, CX-N has also been successfully applied for the real-time imaging of H2S in inflammatory and tumor mice based on its NIR emission, which provides a reliable platform for the specific recognition of H2S in complex biological systems.

A peroxyoxalate chemiluminescence recovery system based on the interaction of N-doped graphene oxide nanosheets and an oligopeptide for ultra-sensitive and selective copper(II) ion detection.

In this paper, a peroxyoxalate chemiluminescence (CL) recovery system based on the interaction of N-doped graphene oxide nanosheets (N-GONs) and an oligopeptide for copper(II) ion detection has been reported. N-GONs as an excellent CL enhancer are prepared by the hydrothermal method using citric acid and ammonia, and the morphology and structure are characterized in detail by TEM, XPS, FT-IR and UV/vis, etc. In the bis(2,4,6-trichlorophenyl)oxalate (TCPO) and hydrogen peroxide (TCPO + H2O2) CL reaction system, the addition of N-GONs gives a remarkable CL emission, which can be quenched by an oligopeptide composed of ten amino acid residues due to the interaction between the N-GON plane and the oligopeptide strand. While in the presence of copper(II) ion, the quenched CL is recovered gradually along with the addition of copper(II) ion in the system. Based on the above CL reactions, a TCPO + H2O2 + N-GONs + oligopeptide CL system is constructed, achieving an ultra-sensitive and selective detection of copper(II) ion in environmental water samples. The detection limit of this method is as low as 0.2 pmol L-1, which is at least three orders of magnitude lower than other CL methods. The N-GONs and oligopeptide involved in the CL system are environmentally friendly, making it possess potential in the detection of copper(II) ion in environmental water samples.

The Impact of Artificial Intelligence on Firm Performance: An Application of the Resource-Based View to e-Commerce Firms.

The application of artificial intelligence (AI) technology has evolved into an influential endeavor to improve firm performance, but little research considers the relationship among artificial intelligence capability (AIC), management (AIM), driven decision making (AIDDM), and firm performance. Based on the resource-based view (RBV) and existing findings, this paper constructs a higher-order model of AIC and suggests a research model of e-commerce firm AIC and firm performance. We collected 394 valid questionnaires and conducted data analysis using partial least squares structural equation modeling (PLS-SEM). As a second-order variable, AIC was formed by three first-order variables: basic, proclivity, and skills. AIC indirectly affects firm performance through creativity, AIM, and AI-driven decision making. Firm creativity, AIM, and AIDDM are essential variables between AIC and firm performance. Innovation culture (IC) positive moderates the relationship between firm creativity and AIDDM as well as the relationship between AIDDM and firm performance. Environmental dynamism (ED) positive mediates the connection between AIM and AIDDM. Among the control variables, firm age negatively affects firm performance, and employee size does not. This study helps enterprises leverage AI to improve firm performance, achieve a competitive advantage, and contribute to theory and management practice.

SORTING NEXIN2 proteins mediate stomatal movement and the response to drought stress by modulating trafficking and protein levels of the ABA exporter ABCG25.

The phytohormone abscisic acid (ABA) regulates ion channel activity and stomatal movement in response to drought stress. Cellular ABA levels change depending on cellular and environmental conditions via modulation of its biosynthesis, catabolism and transport. Although factors involved in ABA biosynthesis and degradation have been studied extensively, how ABA transporters are modulated to fine-tune ABA levels, especially under drought stress, remains elusive. Here, we show that Arabidopsis thaliana SORTING NEXIN 2 (SNX2) proteins play a critical role in endosomal trafficking of the ABA exporter ATP BINDING CASETTE G25 (ABCG25) via direct interaction at endosomes, leading to its degradation in the vacuole. In agreement, snx2a and snx2b mutant plants showed enhanced recycling of GFP-ABCG25 from early endosomes to the plasma membrane and higher accumulation of GFP-ABCG25. Phenotypically, snx2a and snx2b plants were highly sensitive to exogenous ABA and displayed enhanced ABA-mediated inhibition of inward K+ currents and ABA-mediated activation of slow anion currents in guard cells, resulting in an increased tolerance to drought stress. Based on these results, we propose that SNX2 proteins play a crucial role in stomatal movement and tolerance to drought stress by modulating the endosomal trafficking of ABCG25 and thus cellular ABA levels.

Cryo-Electron Microscopy Structure and Interactions of the Human Cytomegalovirus gHgLgO Trimer with Platelet-Derived Growth Factor Receptor Alpha.

Human cytomegalovirus (HCMV) is a herpesvirus that produces disease in transplant patients and newborn children. Entry of HCMV into cells relies on gH/gL trimer (gHgLgO) and pentamer (gHgLUL128-131) complexes that bind cellular receptors. Here, we studied the structure and interactions of the HCMV trimer, formed by AD169 strain gH and gL and TR strain gO proteins, with the human platelet-derived growth factor receptor alpha (PDGFRα). Three trimer surfaces make extensive contacts with three PDGFRα N-terminal domains, causing PDGFRα to wrap around gO in a structure similar to a human hand, explaining the high-affinity interaction. gO is among the least conserved HCMV proteins, with 8 distinct genotypes. We observed high conservation of residues mediating gO-gL interactions but more extensive gO variability in the PDGFRα interface. Comparisons between our trimer structure and a previously determined structure composed of different subunit genotypes indicate that gO variability is accommodated by adjustments in the gO-PDGFRα interface. We identified two loops within gO that were disordered and apparently glycosylated, which could be deleted without disrupting PDGFRα binding. We also identified four gO residues that contact PDGFRα, which when mutated produced markedly reduced receptor binding. These residues fall within conserved contact sites of gO with PDGFRα and may represent key targets for anti-trimer neutralizing antibodies and HCMV vaccines. Finally, we observe that gO mutations distant from the gL interaction site impact trimer expression, suggesting that the intrinsic folding or stability of gO can impact the efficiency of trimer assembly. IMPORTANCE HCMV is a herpesvirus that infects a large percentage of the adult population and causes significant levels of disease in immunocompromised individuals and birth defects in the developing fetus. The virus encodes a complex protein machinery that coordinates infection of different cell types in the body, including a trimer formed of gH, gL, and gO subunits. Here, we studied the interactions of the HCMV trimer with its receptor on cells, the platelet derived growth factor receptor α (PDGFRα), to better understand how HCMV coordinates virus entry into cells. Our results add to our understanding of HCMV strain-specific differences and identify sites on the trimer that represent potential targets for therapeutic antibodies or vaccine development.

Sub-3 Å Cryo-EM Structures of Necrosis Virus Particles via the Use of Multipurpose TEM with Electron Counting Camera.

During this global pandemic, cryo-EM has made a great impact on the structure determination of COVID-19 proteins. However, nearly all high-resolution results are based on data acquired on state-of-the-art microscopes where their availability is restricted to a number of centers across the globe with the studies on infectious viruses being further regulated or forbidden. One potential remedy is to employ multipurpose microscopes. Here, we investigated the capability of 200 kV multipurpose microscopes equipped with a direct electron camera in determining the structures of infectious particles. We used 30 nm particles of the grouper nerve necrosis virus as a test sample and obtained the cryo-EM structure with a resolution as high as ∼2.7 Šfrom a setting that used electron counting. For comparison, we tested a high-end cryo-EM (Talos Arctica) using a similar virus (Macrobrachium rosenbergii nodavirus) to obtain virtually the same resolution. Those results revealed that the resolution is ultimately limited by the depth of field. Our work updates the density maps of these viruses at the sub-3Šlevel to allow for building accurate atomic models from de novo to provide structural insights into the assembly of the capsids. Importantly, this study demonstrated that multipurpose TEMs are capable of the high-resolution cryo-EM structure determination of infectious particles and is thus germane to the research on pandemics.

A novel framework for bringing smart big data to proactive decision making in healthcare.

Big data have shown their great potential value to serve many aspects of human life. Due to complexity of the medical and healthcare big data in real life, traditional big data analysis methods are difficult to be dealt with. Therefore, a single method is unable to analyze and manage heterogeneous big data sources. To utilize data fully from the perspective of decision-making, we propose a novel framework which guides the healthcare big data to be smartly and proactively processed for decision-making without user interventions. The framework contains five stages, which are intelligent data cleaning, customized data fusion, analysis mapping, exploratory visualization analysis, and generation of decision-making reports. It also enables learning from the data and correlating them with the existing human knowledge. Subsequently, a smart big data-driven application exhibits innovative management in intelligent healthcare. The proposed framework provides the guidelines of the best practices of big data-driven analysis for intelligent healthcare according to our practical applications. The platform provides the appropriate reference for the big data-driven innovation of management in intelligent healthcare.

The Cyclophilin ROC3 Regulates ABA-Induced Stomatal Closure and the Drought Stress Response of Arabidopsis thaliana.

Drought causes a major constraint on plant growth, development, and crop productivity. Drought stress enhances the synthesis and mobilization of the phytohormone abscisic acid (ABA). Enhanced cellular levels of ABA promote the production of reactive oxygen species (ROS), which in turn induce anion channel activity in guard cells that consequently leads to stomatal closure. Although Cyclophilins (CYPs) are known to participate in the biotic stress response, their involvement in guard cell ABA signaling and the drought response remains to be established. The Arabidopsis thaliana gene ROC3 encodes a CYP. Arabidopsis roc3 T-DNA mutants showed a reduced level of ABA-activated S-type anion currents, and stomatal closure than wild type (WT). Also, roc3 mutants exhibited rapid loss of water in leaf than wild type. Two complementation lines of roc3 mutants showed similar stomatal response to ABA as observed for WT. Both complementation lines also showed similar water loss as WT by leaf detached assay. Biochemical assay suggested that ROC3 positively regulates ROS accumulation by inhibiting catalase activity. In response to ABA treatment or drought stress, roc3 mutant show down regulation of a number of stress responsive genes. All findings indicate that ROC3 positively regulates ABA-induced stomatal closure and the drought response by regulating ROS homeostasis and the expression of various stress-activated genes.