Field-dependent deep learning enables high-throughput whole-cell 3D super-resolution imaging.

Single-molecule localization microscopy in a typical wide-field setup has been widely used for investigating subcellular structures with super resolution; however, field-dependent aberrations restrict the field of view (FOV) to only tens of micrometers. Here, we present a deep-learning method for precise localization of spatially variant point emitters (FD-DeepLoc) over a large FOV covering the full chip of a modern sCMOS camera. Using a graphic processing unit-based vectorial point spread function (PSF) fitter, we can fast and accurately model the spatially variant PSF of a high numerical aperture objective in the entire FOV. Combined with deformable mirror-based optimal PSF engineering, we demonstrate high-accuracy three-dimensional single-molecule localization microscopy over a volume of ~180 × 180 × 5 µm3, allowing us to image mitochondria and nuclear pore complexes in entire cells in a single imaging cycle without hardware scanning; a 100-fold increase in throughput compared to the state of the art.

Multifunctional Heterostructured Fe3 O4 -FeTe@MCM Electrocatalyst Enabling High-Performance Practical Lithium-Sulfur Batteries Via Built-in Electric Field.

The development of capable of simultaneously modulating the sluggish electrochemical kinetics, shuttle effect, and lithium dendrite growth is a promising strategy for the commercialization of lithium-sulfur batteries. Consequently, an elaborate preparation method is employed to create a host material consisting of multi-channel carbon microspheres (MCM) containing highly dispersed heterostructure Fe3 O4 -FeTe nanoparticles. The Fe3 O4 -FeTe@MCM exhibits a spontaneous built-in electric field (BIEF) and possesses both lithophilic and sulfophilic sites, rendering it an appropriate host material for both positive and negative electrodes. Experimental and theoretical results reveal that the existence of spontaneous BIEF leads to interfacial charge redistribution, resulting in moderate polysulfide adsorption which facilitates the transfer of polysulfides and diffusion of electrons at heterogeneous interfaces. Furthermore, the reduced conversion energy barriers enhanced the catalytic activity of Fe3 O4 -FeTe@MCM for expediting the bidirectional sulfur conversion. Moreover, regulated Li deposition behavior is realized because of its high conductivity and remarkable lithiophilicity. Consequently, the battery exhibited long-term stability for 500 cycles with 0.06% capacity decay per cycle at 5 C, and a large areal capacity of 7.3 mAh cm-2 (sulfur loading: 9.73 mg cm-2 ) at 0.1 C. This study provides a novel strategy for the rational fabrication of heterostructure hosts for practical Li-S batteries.

Formation and toxicity alteration of halonitromethanes from Chlorella vulgaris during UV/chloramination process involving bromide ion.

Frequent algal blooms cause algal cells and their algal organic matter (AOM) to become critical precursors of disinfection by-products (DBPs) during water treatment. The presence of bromide ion (Br-) in water has been demonstrated to affect the formation laws and species distribution of DBPs. However, few researchers have addressed the formation and toxicity alteration of halonitromethanes (HNMs) from algae during disinfection in the presence of Br-. Therefore, in this work, Chlorella vulgaris was selected as a representative algal precursor to investigate the formation and toxicity alteration of HNMs during UV/chloramination involving Br-. The results showed that the formation concentration of HNMs increased and then decreased during UV/chloramination. The intracellular organic matter of Chlorella vulgaris was more susceptible to form HNMs than the extracellular organic matter. When the Br-: Cl2 mass ratio was raised from 0.004 to 0.08, the peak of HNMs total concentration increased 33.99%, and the cytotoxicity index and genotoxicity index of HNMs increased 67.94% and 22.80%. Besides, the formation concentration and toxicity of HNMs increased with increasing Chlorella vulgaris concentration but decreased with increasing solution pH. Possible formation pathways of HNMs from Chlorella vulgaris during UV/chloramination involving Br- were proposed based on the alteration of nitrogen species and fluorescence spectrum analysis. Furthermore, the formation laws of HNMs from Chlorella vulgaris in real water samples were similar to those in deionized water samples. This study contributes to a better comprehension of HNMs formation from Chlorella vulgaris and provides valuable information for water managers to reduce hazards associated with the formation of HNMs.

Construction of TiO2/CuPc Heterojunctions for the Efficient Photocatalytic Reduction of CO2 with Water.

Utilizing solar energy for photocatalytic CO2 reduction is an attractive research field because of its convenience, safety, and practicality. The selection of an appropriate photocatalyst is the key to achieve efficient CO2 reduction. Herein, we report the synthesis of TiO2/CuPc heterojunctions by compositing CuPc with TiO2 microspheres via a hydroxyl-induced self-assembly process. The experimental investigations demonstrated that the optimal TiO2/0.5CuPc photocatalyst exhibited a significantly enhanced CO2 photoreduction rate up to 32.4 µmol·g-1·h-1 under 300 W xenon lamp irradiation, which was 3.7 times that of the TiO2 microspheres alone. The results of photoelectrochemical experiments indicated that the construction of the heterojunctions by introducing CuPc effectively promoted the separation and transport of photogenerated carriers, thus enhancing the catalytic effect of the photocatalyst.

Magnetic Titanium Dioxide Nanocomposites as a Recyclable SERRS Substrate for the Ultrasensitive Detection of Histidine.

A highly sensitive, selective and recyclable histidine detection method based on magnetic Fe3O4@mTiO2 (M-TiO2) nanocomposites with SERRS was developed. Mesoporous M-TiO2 nanoparticles were functionalized with 4-aminothiophenol and then coupled with histidine through an azo coupling reaction in 5 min, producing the corresponding azo compound. The strong and specific SERRS response of the azo product allowed for ultrasensitive and selective detection for histidine with an M-TiO2 device loaded with Ag NPs due to the molecular resonance effect and plasmonic effect of Ag NPs under a 532 nm excitation laser. The sensitivity was further enhanced with the magnetic enrichment of M-TiO2. The limit of detection (LOD) was as low as 8.00 × 10-12 mol/L. The M-TiO2 demonstrated applicability towards histidine determination in human urine without any sample pretreatment. Additionally, the M-TiO2 device can be recycled for 3 cycles with the photodegradation of the azo product under UV irradiation due to TiO2-assisted and plasmon-enhanced photocatalysis. In summary, a multifunctional and recyclable M-TiO2 device was synthesized based on azo coupling and SERRS spectroscopy for ultra-sensitive and specific histidine sensing. In addition, the proposed system demonstrated the potential for the multiplex determination of toxic compounds in the fields of food safety, industrial production and environmental protection, which benefit from the fingerprint property and universality of SERRS.

Optimal sampling rate for 3D single molecule localization.

Resolution of single molecule localization microscopy (SMLM) depends on the localization accuracy, which can be improved by utilizing engineered point spread functions (PSF) with delicate shapes. However, the intrinsic pixelation effect of the detector sensor will deteriorate PSFs under different sampling rates. The influence of the pixelation effect to the achieved 3D localization accuracy for different PSF shapes under different signal to background ratio (SBR) and pixel dependent readout noise has not been investigated in detail so far. In this work, we proposed a framework to characterize the 3D localization accuracy of pixelated PSF at different sampling rates. Four different PSFs (astigmatic PSF, double helix (DH) PSF, Tetrapod PSF and 4Pi PSF) were evaluated and the pixel size with optimal 3D localization performance were derived. This work provides a theoretical guide for the optimal design of sampling rate for 3D super resolution imaging.

Near-infrared molecular sensor for visualizing and tracking ONOO- during the process of anti-tuberculosis drug-induced liver damage.

Isoniazid (INH) and pyrazinamide (PZA) are both the first-line anti-tuberculosis drugs in clinical treatment. It is notable that there are serious side effects of the drugs along with upregulation of reactive nitrogen species, mainly including peripheral neuritis, gastrointestinal reactions, and acute drug-induced liver injury (DILI). Among them, DILI is the most common clinical symptom as well as the basic reason of treatment interruption, protocol change, and drug resistance. As vital reactive nitrogen species (RNS), peroxynitrite (ONOO-) has been demonstrated as a biomarker for evaluation and pre-diagnosis of drug-induced liver injury (DILI). In this work, we developed a red-emitting D-π-A type fluorescence probe DIC-NP which was based on 4'-hydroxy-4-biphenylcarbonitrile modified with dicyanoisophorone as a fluorescent reporter and diphenyl phosphinic chloride group as the reaction site for highly selective and sensitive sensing ONOO-. Probe DIC-NP displayed a low detection limit (14.9 nM) and 60-fold fluorescent enhancement at 669 nm in the sensing of ONOO-. Probe DIC-NP was successfully applied to monitor exogenous and endogenous ONOO- in living HeLa cells and zebrafish. Furthermore, we verified the toxicity of isoniazid (INH) and pyrazinamide (PZA) by taking the oxidative stress induced by APAP as a reference, and successfully imaged anti-tuberculosis drug-induced endogenous ONOO- in HepG2 cells. More importantly, we developed a series of mice models of liver injury and investigated the hepatotoxicity caused by the treatment of anti-tuberculosis drugs. At the same time, H&E of mice organs (heart, liver, spleen, lung, kidney) further confirmed the competence of probe DIC-NP for estimating the degree of drug-induced liver injury, which laid a solid foundation for medical research.

Accuracy and patient-centered results of static and dynamic computer-assisted implant surgery in edentulous jaws: a retrospective cohort study.

OBJECTIVES: This study aimed to compare implant positioning accuracy and patient-centered results between static and dynamic computer-assisted implant surgery (s-CAIS and d-CAIS) in edentulous jaws. MATERIAL AND METHODS: The current study retrospectively evaluated a total of 110 implants placed in 22 fully edentulous patients via s-CAIS or d-CAIS (n = 11). The accuracy of implant positioning was assessed by measuring the implant's angular deviation and deviation at the platform and apex from the preoperative design postoperatively. Patient-centered results, including preoperative and intraoperative patient-reported experiences and postoperative patient-reported outcomes, were extracted from the medical records. The nested t test and chi-square test were used to compare accuracy and patient-centered results between s-CAIS and d-CAIS postoperatively. RESULTS: The implants in the s-CAIS group showed significantly smaller angular deviation (2.32 ± 1.23°) than those in the d-CAIS group (3.87 ± 2.75°). In contrast, the platform and apical deviation were significantly larger in s-CAIS (1.56 ± 1.19 mm and 1.70 ± 1.09 mm, respectively) than d-CAIS (1.02 ± 0.45 mm and 1.00 ± 0.51 mm, respectively). Furthermore, the implants in the s-CAIS group deviated significantly (p < 0.001) more toward the coronal direction than those in the d-CAIS group. Notably, all patients in the s-CAIS group reported an obvious foreign body sensation during surgery, representing a significant difference from the d-CAIS group. CONCLUSIONS: Compared to s-CAIS, d-CAIS is a reliable technique for the placement of multiple implants in fully edentulous patients with less linear deviation and less foreign body sensation. TRIAL REGISTRATION: The retrospective study was registered on the Chinese Clinical Trial Registry on August 8th, 2022, with registration number No. ChiCTR2200062484. CLINICAL RELEVANCE: Despite the increasing use of computer- assisted implant surgery in fully edentulous patients, clinical evidence comparing implant positioning accuracy and patient-centered results between static and dynamic CAIS systems is scarce. Our study demonstrated that compared to s-CAIS, d-CAIS is a reliable technique for the placement of multiple implants in fully edentulous patients with less linear deviation.

Deformable mirror based optimal PSF engineering for 3D super-resolution imaging.

Point spread function (PSF) engineering is an important technique to encode the properties (e.g., 3D positions, color, and orientation) of a single molecule in the shape of the PSF, often with the help of a programmable phase modulator. A deformable mirror (DM) is currently the most widely used phase modulator for fluorescence detection as it shows negligible photon loss. However, it relies on careful calibration for precise wavefront control. Therefore, design of an optimal PSF not only relies on the theoretical calculation of the maximum information content, but also the physical behavior of the phase modulator, which is often ignored during the optimization process. Here, we develop a framework for PSF engineering which could generate a device specific optimal PSF for 3D super-resolution imaging using a DM. We use our method to generate two types of PSFs with depths of field comparable to the widely used astigmatism and tetrapod PSFs, respectively. We demonstrate the superior performance of the DM specific optimal PSF over the conventional astigmatism and tetrapod PSF both theoretically and experimentally.

Association between c-type lectin-like receptor 2 and microsatellite instability in colorectal cancer: a cross-sectional study.

BACKGROUND: As a transmembrane protein, C-type lectin-like receptor 2 (CLEC-2) is mainly expressed on platelets and released into plasma after platelet activation. Activated platelets participate in the regulation of innate immune cells. Patients with different microsatellite statuses have distinct immune profiles. This study aimed to investigate the association of plasma CLEC-2 levels with microsatellite status among colorectal cancer (CRC) patients. METHODS: A cross-sectional analysis of 430 CRC patients from Harbin Medical University Cancer Hospital was conducted. CLEC-2 levels were measured with fasting venous blood samples drawn from each participant before any treatment. The microsatellite status was evaluated with DNA obtained from fresh frozen tumor tissue samples. The other clinical data were collected and recorded based on the medical system records. RESULTS: CLEC-2 levels were significantly higher among patients with high microsatellite instability phenotype than the stable microsatellite group, adjusting for other confounding variables. CONCLUSIONS: The increased CLEC-2 is associated with the high microsatellite instability subtype of CRC.

Incidence of oxygen desaturation using a high-flow nasal cannula versus a facemask during flexible bronchoscopy in patients at risk of hypoxemia: a randomised controlled trial.

BACKGROUND: Patients with obstructive sleep apnoea (OSA), male sex, obesity, older age or hypertension are prone to hypoxemia during flexible bronchoscopy. This study investigated whether using a high-flow nasal cannula (HFNC) could reduce the incidence of oxygen desaturation during bronchoscopy under deep sedation in patients at risk of hypoxemia. METHODS: A total of 176 patients at risk of hypoxemia who underwent flexible bronchoscopy under deep sedation were randomly assigned to two groups: the HFNC group (humidified oxygen was supplied via a high-flow nasal cannula at a rate of 60 L/min and a concentration of 100%, n = 87) and the facemask group (oxygen was supplied via a tight-fitting facemask at a rate of 6 L/min and a concentration of 100%, n = 89). RESULTS: Oxygen desaturation occurred in 4 (4.6%) patients in the HFNC group and 26 (29.2%) patients in the facemask group (P < 0.001). The facemask group required more jaw thrust manoeuvres than the HFNC group (43[48.3%] vs. 5[5.7%], P < 0.001). 8 patients (9.0%) in the facemask group and none in the HFNC group required bag-mask ventilation (P = 0.012). CONCLUSION: The use of an HFNC can reduce the incidence of oxygen desaturation and the requirement for airway intervention in patients at risk of hypoxemia during flexible bronchoscopy under deep sedation. TRIAL REGISTRATION: www.chiCTR.org.cn Identifier: ChiCTR2100044105. Registered 11/03/2021.

Alternation of Organ-Specific Exposure in LPS-Induced Pneumonia Mice after the Inhalation of Tetrandrine Is Governed by Metabolizing Enzyme Suppression and Lysosomal Trapping.

The objective of the present study was to define whether inhaled tetrandrine (TET) could be a promising way to achieve the local effect on its therapeutic efficacy based on biodistribution features using the LPS-treated acute lung injury (ALI) model. The tissue distribution profiles of inhaled TET in normal and ALI mouse models showed that pulmonary inflammation led to an altered distribution in a tissue-specific way. More TET accumulated in almost all tissues including in the blood. Among them, the increased exposure in the lungs was significantly higher than in the other tissues. However, there was a negative increase in the brain. In vitro turnover rates of TET in mouse liver microsomes (MLM) from normal and LPS-treated mice showed significant differences. In the presence of NADPH, TET demonstrated relatively low hepatic clearance (89 mL/h/kg) in that of normal MLM (140 mL/h/kg). Intracellular uptakes of TET in A549, HepG2, RAW264.7, and C8-D1A cells were significantly inhibited by monensin, indicating that the intracellular accumulation of TET is driven by lysosomal trapping. However, in the presence of LPS, only the lysosomal pH partitioning of TET in A549 cell lines increased (~30%). Bidirectional transport of TET across LLC-PK1 cell expressing MDR1 showed that MDR1 is responsible for the low brain exposure via effluxion (ER = 32.46). From the observed overall agreement between the in vitro and in vivo results, we concluded that the downregulation of the CYP3A together with strengthened pulmometry lysosomal trapping magnified the retention of inhaled TET in the lung. These results therefore open the possibility of prolonging the duration of the local anti-inflammation effect against respiratory disorders.

SIRT6 silencing overcomes resistance to sorafenib by promoting ferroptosis in gastric cancer.

Sorafenib is a tyrosine kinase inhibitor that shows anti-tumour effects against various cancers including gastric cancer (GC). However, the clinical application of sorafenib is often hampered by drug resistance. Sirtuins 6 (SIRT6) is a member of the Sirtuin family of NAD (+)-dependent enzymes that are critically involved in various biological activities. This study presents that SIRT6 silencing overcomes sorafenib resistance by promoting ferroptosis, which is a novel form of cell death. Mechanistically, SIRT6 inhibition led to the inactivation of the Keap1/Nrf2 signalling pathway and downregulation of GPX4. The overexpression of GPX4 or activation of Keap1/Nrf2 reverses the effects of the downregulation of SIRT6 on sorafenib-induced ferroptosis. Thus, targeting the SIRT6/Keap1/Nrf2/GPX4 signalling pathway may be a potential strategy for overcoming sorafenib resistance in GC.

Abnormal expression of TGFBR2, EGF, LRP10, and IQGAP1 is involved in the pathogenesis of coronary artery disease.

Coronary artery disease (CAD) is the most common cardiovascular disease worldwide. In this study, we investigated the pathogenesis of CAD. We downloaded the GSE98583 dataset, including 12 CAD samples and 6 normal samples, from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs) in CAD versus normal samples. Next, we performed functional enrichment analysis, protein-protein interaction (PPI) network, and functional module analyses to explore potential functions and regulatory functions of identified DEGs. Next, transcription factors (TFs) and microRNAs (miRNAs) targeting DEGs were predicted. In total, 456 DEGs were identified in CAD and normal samples, including 175 upregulated and 281 downregulated genes. These genes were enriched in the intestinal immune network for immunoglobulin A production and the mitogen-activated protein kinase signaling pathway (e.g., TGFBR2 and EGF). The PPI network contained 212 genes, and HIST1H2BJ, HIST1H2AC, EGF, and EP300 were hub genes with degrees higher than 10. Four significant modules were identified from the PPI network, with genes in the modules mainly enriched in the inflammatory response, protein ubiquitination involved in ubiquitin-dependent protein catabolic processes, protein transport, and mitochondrial translational elongation, respectively. Two TFs (E2F1 and FOXK1) and five miRNAs (miR-122A, miR-516-5P, miR-507, miR-342, and miR-520F) were predicted to target 112 DEGs. miR-122A reportedly targets both LRP10 and IQGAP1 in the TF-miRNA target regulatory network. The abnormal expression of TGFBR2, EGF, LRP10, and IQGAP1 may be implicated in CAD pathogenesis. Our study provides targets and potential regulators for investigating CAD pathogenesis.

Antimicrobial and antitumor activity of peptidomimetics synthesized from amino acids.

Thirteen cationic peptidomimetics derived from amino acids bearing an alkyl or ethynylphenyl moiety that mimic the structure of cationic antibacterial peptides were designed and synthesized using a simple coupling reaction of an amino acid with a substituted amine. Antibacterial activities of the resulting peptidomimetics against drug-sensitive bacteria, such as Gram-positive Staphylococcus aureus (S. aureus) and Bacillus subtilis, Gram-negative Escherichia coli (E. coli) and Salmonella enterica, and a drug-resistant bacterium, methicillin-resistant S. aureus (MRSA), were systematically evaluated. Most peptidomimetics show significant broad-spectrum antibacterial activity. A-L-Iso-C12 (isoleucine derivative bearing a dodecyl moiety) show MICs of 2.5 µg/mL against S. aureus and 4 µg/mL against MRSA and A-L-Val-C12 (valine derivative bearing a dodecyl moiety) show MICs of 1.67 µg/mL against E. coli and 8.3 µg/mL against MRSA. A-L-Val-C12 showed low cytotoxicity toward L929 cells in comparison with SGC 7901 cells, indicating tumor-directed killing by peptidomimetics while avoiding toxicity to normal cells. The influences of type of amino acid and substituent, length of substituent, and stereochemistry of amino acids on antibacterial activity and cytotoxicity of peptidomimetics were systematically investigated. The results indicate that this series of cationic peptidomimetics derived from amino acids display antitumor activity and may be useful for treatment of bacterial infections.

Design, Synthesis, Antibacterial, and Antitumor Activity of Linear Polyisocyanide Quaternary Ammonium Salts with Different Structures and Chain Lengths.

The development of organic polymer materials for disinfection and sterilization is thought of as one of the most promising avenues to solve the growth and spread of harmful microorganisms. Here, a series of linear polyisocyanide quaternary ammonium salts (L-PQASs) with different structures and chain lengths were designed and synthesized by polymerization of phenyl isocyanide monomer containing a 4-chloro-1-butyl side chain followed by quaternary amination salinization. The resultant compounds were characterized by 1H NMR and FT-IR. The antibacterial activity of L-PQASs with different structures and chain lengths against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was evaluated by determining the minimum inhibitory concentrations (MICs). The L-POcQAS-M50 has the strongest antimicrobial activity with MICs of 27 µg/mL against E. coli and 32 µg/mL against S. aureus. When the L-PQASs had the same polymerization degree, the order of the antibacterial activity of the L-PQASs was L-POcQAS-Mn > L-PBuQAS-Mn > L-PBnQAS-Mn > L-PDBQAS-Mn (linear, polyisocyanide quaternary ammonium salt, monomer, n = 50,100). However, when L-PQASs had the same side chain, the antibacterial activity reduced with the increase of the molecular weight of the main chain. These results demonstrated that the antibacterial activity of L-PQASs was dependent on the structure of the main chain and the length of the side chain. In addition, we also found that the L-POcQAS-M50 had a significant killing effect on MK-28 gastric cancer cells.

Spatiotemporal variations of ambient air pollutants and meteorological influences over typical urban agglomerations in China during the COVID-19 lockdown.

To investigate the air quality change during the COVID-19 pandemic, we analyzed spatiotemporal variations of six criteria pollutants in nine typical urban agglomerations in China using ground-based data and examined meteorological influences through correlation analysis and backward trajectory analysis under different responses. Concentrations of PM2.5, PM10, NO2, SO2 and CO in urban agglomerations respectively decreased by 18%-45% (30%-62%), 17%-53% (22%-39%), 47%-64% (14%-41%), 9%-34% (0%-53%) and 16%-52% (23%-56%) during Lockdown (Post-lockdown) period relative to Pre-lockdown period. PM2.5 pollution events occurred during Lockdown in Beijing-Tianjin-Hebe (BTH) and Middle and South Liaoning (MSL), and daily O3 concentration rose to grade Ⅱ standard in Post-lockdown period. Distinct from the nationwide slump of NO2 during Lockdown period, a rebound (∼40%) in Post-lockdown period was observed in Cheng-Yu (CY), Yangtze River Middle-Reach (YRMR), Yangtze River Delta (YRD) and Pearl River Delta (PRD). With slightly higher wind speed compared with 2019, the reduction of PM2.5 (51%-62%) in Post-lockdown period is more than 2019 (15%-46%) in HC (Harbin-Changchun), MSL, BTH, CP (Central Plain) and SP (Shandong-Peninsula), suggesting lockdown measures are effective to PM2.5 alleviation. Although O3 concentrations generally increased during the lockdown, its increment rate declined compared with 2019 under similar sunlight duration and temperature. Additionally, unlike HC, MSL and BTH, which suffered from additional (> 30%) air masses from surrounding areas after the lockdown, the polluted air masses reaching YRD and PRD mostly originated from the long-distance transport, highlighting the importance of joint regional governance.

MicroRNA-128-1-5p attenuates myocardial ischemia/reperfusion injury by suppressing Gadd45g-mediated apoptotic signaling.

Myocardial ischemia/reperfusion (I/R) injury is a clinically fatal disease, caused by restoring myocardial blood supply after a period of ischemia or hypoxia. However, the underlying mechanism remains unclear. Recently, increasing evidence reveal that microRNAs (miRs) participate in myocardial I/R injury. This study aimed to investigate whether miR-128-1-5p contributed to cardiomyocyte apoptosis induced by myocardial I/R injury. Here, we showed that the expression of miR-128-1-5p was decreased in mice following myocardial I/R injury. Down-regulation of miR-128-1-5p was also showed in H9c2 cardiomyocytes after hypoxia/reoxygenation (H/R), and in neonatal rat cardiomyocytes (NRCMs) with H2O2 treatment. Importantly, we found that overexpression of miR-128-1-5p ameliorates cardiomyocyte apoptosis both in H9c2 cardiomyocytes and NRCMs. Moreover, we also found that growth arrest DNA damage-inducible gene 45 gamma (Gadd45g) is identified as a direct target of miR-128-1-5p, which negatively regulated Gadd45g expression. Additionally, silencing of Gadd45g inhibits cardiomyocyte apoptosis in H9c2 cardiomyocytes and NRCMs. These results reveal a novel mechanism by which miR-128-1-5p regulates Gadd45g-mediated cardiomyocyte apoptosis in myocardial I/R injury.

SG2-Type R2R3-MYB Transcription Factor MYB15 Controls Defense-Induced Lignification and Basal Immunity in Arabidopsis.

Lignification of cell wall appositions is a conserved basal defense mechanism in the plant innate immune response. However, the genetic pathway controlling defense-induced lignification remains unknown. Here, we demonstrate the Arabidopsis thaliana SG2-type R2R3-MYB transcription factor MYB15 as a regulator of defense-induced lignification and basal immunity. Loss of MYB15 reduces the content but not the composition of defense-induced lignin, whereas constitutive expression of MYB15 increases lignin content independently of immune activation. Comparative transcriptional and metabolomics analyses implicate MYB15 as necessary for the defense-induced synthesis of guaiacyl lignin and the basal synthesis of the coumarin metabolite scopoletin. MYB15 directly binds to the secondary wall MYB-responsive element consensus sequence, which encompasses the AC elements, to drive lignification. The myb15 and lignin biosynthetic mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with defense-induced lignin having a major role in basal immunity. A scopoletin biosynthetic mutant also shows increased susceptibility independently of immune activation, consistent with a role in preformed defense. Our results support a role for phenylalanine-derived small molecules in preformed and inducible Arabidopsis defense, a role previously dominated by tryptophan-derived small molecules. Understanding the regulatory network linking lignin biosynthesis to plant growth and defense will help lignin engineering efforts to improve the production of biofuels and aromatic industrial products as well as increase disease resistance in energy and agricultural crops.

Genome-wide identification and expression analysis of the calmodulin-binding transcription activator (CAMTA) gene family in wheat (Triticum aestivum L.).

BACKGROUND: Plant calmodulin-binding transcription activator (CAMTA) proteins play important roles in hormone signal transduction, developmental regulation, and environmental stress tolerance. However, in wheat, the CAMTA gene family has not been systematically characterized. RESULTS: In this work, 15 wheat CAMTA genes were identified using a genome-wide search method. Their chromosome location, physicochemical properties, subcellular localization, gene structure, protein domain, and promoter cis-elements were systematically analyzed. Phylogenetic analysis classified the TaCAMTA genes into three groups (groups A, B, and C), numbered 7, 6, and 2, respectively. The results showed that most TaCAMTA genes contained stress-related cis-elements. Finally, to obtain tissue-specific and stress-responsive candidates, the expression profiles of the TaCAMTAs in various tissues and under biotic and abiotic stresses were investigated. Tissue-specific expression analysis showed that all of the 15 TaCAMTA genes were expressed in multiple tissues with different expression levels, as well as under abiotic stress, the expressions of each TaCAMTA gene could respond to at least one abiotic stress. It also found that 584 genes in wheat genome were predicted to be potential target genes by CAMTA, demonstrating that CAMTA can be widely involved in plant development and growth, as well as coping with stresses. CONCLUSIONS: This work systematically identified the CAMTA gene family in wheat at the whole-genome-wide level, providing important candidates for further functional analysis in developmental regulation and the stress response in wheat.