Dissociation of transcription factor MYB94 and histone deacetylases HDA907/908 alleviates oxidative damage in poplar.

Drought is one of the major threats to forest productivity. Oxidation stress is common in drought-stressed plants, and plants need to maintain normal life activities through complex reactive oxygen scavenging mechanisms. However, the molecular links between epigenetics, oxidation stress, and drought in poplar (Populus) remain poorly understood. Here, we found that Populus plants overexpressing PtrMYB94, which encodes a R2R3 MYB transcription factor that regulates the ABA signaling pathway, displayed increased tolerance to extreme drought stress via up-regulation of embryogenic cell phosphoprotein 44 (PtrECPP44) expression. Further investigation revealed that PtrMYB94 could recruit the histone deacetylases PtrHDA907/908 to the promoter of PtrECPP44 and decrease acetylation at lysine residues 9, 14 and 27 of histone H3, leading to relatively low transcriptional expression levels under normal conditions. Drought induced the expression of PtrMYB94 while preventing interaction of PtrMYB94 with PtrHDA907/908, which relaxed the chromatin structure and facilitated the binding of RNA polymerase II to the PtrECPP44 promoter. The upregulation of PtrECPP44 helped poplar alleviate oxidative damage and maintain normal cell activities. This study establishes a PtrMYB94-PtrECPP44 transcriptional regulatory module modified by PtrHDA907/908 in modulating drought-induced oxidative stress recovery. Therefore, our study reveals a oxidative regulatory mechanism in response to drought stress and provides insights into molecular breeding for stress resistance in poplar.

In-Depth Profiling of 4-Hydroxy-2-nonenal Modification via Reversible Thiazolidine Chemistry.

Protein modification by lipid-derived electrophiles (LDEs) is associated with various signaling pathways. Among these LDEs, 4-hydroxy-2-nonenal (HNE) is the most toxic, and protein modified with HNE has been linked to various diseases, including Alzheimer's and Parkinson's. However, due to their low abundance, in-depth profiling of HNE modifications still presents challenges. This study introduces a novel strategy utilizing reversible thiazolidine chemistry to selectively capture HNE-modified proteins and a palladium-mediated cleavage reaction to release them. Thousands of HNE-modified sites in different cell lines were identified. Combined with ABPP, we discovered a set of HNE-sensitive sites that offer a new tool for studying LDE modifications in proteomes.

Global climate change: Effects of future temperatures on emergency department visits for mental disorders in Beijing, China.

Rising temperatures can increase the risk of mental disorders. As climate change intensifies, the future disease burden due to mental disorders may be underestimated. Using data on the number of daily emergency department visits for mental disorders at 30 hospitals in Beijing, China during 2016-2018, the relationship between daily mean temperature and such visits was assessed using a quasi-Poisson model integrated with a distributed lag nonlinear model. Emergency department visits for mental disorders attributed to temperature changes were projected using 26 general circulation models under four climate change scenarios. Stratification analyses were then conducted by disease subtype, sex, and age. The results indicate that the temperature-related health burden from mental disorders was projected to increase consistently throughout the 21st century, mainly driven by high temperatures. The future temperature-related health burden was higher for patients with mental disorders due to the use of psychoactive substances and schizophrenia as well as for women and those aged <65 years. These findings enhance our knowledge of how climate change could affect mental well-being and can be used to advance and refine targeted approaches to mitigating and adapting to climate change with a view on addressing mental disorders.

The impact of apparent temperature on the emergency visits for traumatic fractures in Hangzhou, China.

BACKGROUND: Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. METHODS: Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. RESULTS: A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide "J"-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0-11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132-1.518) and 1.418 (95% CI: 1.191-1.688) at cumulative lag 0-14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0-14 days. The heat effects were higher among male and those aged 18-65 years old. The sensitivity analysis results remained robust. CONCLUSION: Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18-65 years are more susceptible to higher AT.

Assessment of lower limb alignment: supine weight-bearing CT scanograms compared with a standing full-length radiograph.

PURPOSE: We identified limb misalignment by applying personalized axial force while the limb was in a supine position to mimic a standing posture. This study aimed to confirm the accuracy of evaluating lower limb alignment using supine weight-bearing CT scanograms. METHODS: We prospectively compared measurements of the weight-bearing line ratio (WBL), hip-knee-ankle (HKA) angle, and joint convergence angle (JLCA) in 46 sets of supine weight-bearing CT scanograms with those obtained from full-length standing anteroposterior lower extremity radiographs. We achieved the weight-bearing CT scanograms by applying six different levels of axial force: zero, 1/5 of body weight, 2/5 of body weight, 3/5 of body weight, 4/5 of body weight, and full body weight. We assessed the impact of age, body mass index, HKA, and JLCA on the observed mechanical axis deviation differences between the two methods. RESULT: The average absolute difference between standing radiographs and supine CT scanograms was 4.32% for the WBL ratio (p < 0.05), 1.25° for HKA (p < 0.05), and 0.46 for JLCA (p < 0.05). The mean absolute difference was minimal when applying full body weight axial pressure during CT scanograms (p > 0.05). Age, body mass index, HKA, and JLCA had no effect on the deviation in the mechanical axis measurements obtained through supine weight-bearing CT scanograms with full body weight. CONCLUSION: No significant differences were found in assessing lower limb alignment between standing radiographs and supine weight-bearing CT scanograms with full body weight. Weight-bearing CT scanograms prove to be a valuable method for assessing lower limb alignment while in a supine position.

Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-κB pathway in a chronic migraine model.

BACKGROUND: Neuroinflammation, mediated by the activation of microglia, contributes to central sensitization, which is associated with the development of chronic migraine (CM). TREM1 receptors amplify the inflammatory response. However, their relationship to CM is unclear. Thus, this study endeavoured to elucidate the exact role of TREM1 in CM. METHODS: Nitroglycerin (NTG) was repeatedly administered intraperitoneally to establish the CM model. Mechanical and thermal sensitivities were assessed using von Frey filaments and hot plate assays. Using Western blotting, TREM1, NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were all detected. Immunofluorescence was used to examine the cellular distribution of TREM1 and NLRP3, the number of microglia, immunoreactivity, and morphological changes. We examined the effects of TREM1 antagonists (LR12) and NF-κB inhibitors (PDTC) on pain behaviour, as well as the production of c-fos and CGRP. Additionally, we investigated whether LR12 and PDTC affect the activation of microglia and the NLRP3 inflammasome. We synthesized siRNA and TREM1-overexpressing plasmids to transfect BV2 cells treated with LPS and normal BV2 cells and treated TREM1-overexpressing BV2 cells with PDTC. The NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were quantified using Western blotting. RESULTS: Following NTG administration, the expression of TREM1 was significantly upregulated and exclusively localized in microglia in the TNC, and was well co-localized with NLRP3. Furthermore, activation of the classical NF-κB pathway was observed. Pre-treatment with LR12 and PDTC effectively attenuated mechanical hypersensitivity, suppressed the expression of c-fos and CGRP, and inhibited NF-κB activity in CM mice. Additionally, inhibition of TREM1 and NF-κB activity mitigated NTG-induced microglia and NLRP3 activation, as well as proinflammatory cytokines production. In vitro, knockdown of TREM1 resulted in attenuated activation of the NF-κB pathway following lipopolysaccharide (LPS) treatment and reduced expression of NLRP3 inflammasome components as well as proinflammatory cytokines. After TREM1 overexpression, the NF-κB pathway was activated, NLRP3 inflammasome components and proinflammatory cytokines were upregulated, and PDTC reversed this phenomenon. CONCLUSIONS: Our findings suggest that TREM1 regulates microglia and NLRP3 activation via the NF-κB pathway, thereby contributing to central sensitization and implicating its involvement in chronic migraine pathogenesis.

A novel strategy of tannery sludge disposal - converting into biochar and reusing for Cr(VI) removal from tannery wastewater.

Tannery sludge with high chromium content has been identified as hazardous solid waste due to its potential toxic effects. The safety disposal and valorization of the tannery sludge remains a challenge. In this study, the chromium stabilization mechanism was systematically investigated during chromium-rich tannery sludge was converted to biochar and the removal performance of the sludge biochar (SBC) for Cr(VI) from tannery wastewater was also investigated. The results showed that increase in pyrolysis temperature was conductive to the stabilization of Cr and significant reduction of the proportion of Cr(VI) in SBC. It was confirmed that the stabilization of chromium mainly was attributed to the embedding of chromium in the C matrix and the transformation of the chromium-containing substances from the amorphous Cr(OH)3 to the crystalline state, such as (FeMg)Cr2O5. The biochar presented high adsorption capacity of Cr(VI) at low pH and the maximal theoretical adsorption capacity of SBC produced at 800°C can reach 352 mg Cr(VI)/g, the process of which can be well expressed by Langmuir adsorption isotherm and pseudo second order model. The electrostatic effect and reduction reaction were dominantly responsible for the Cr(VI) adsorption by SBC800. Overall, this study provided a novel strategy for the harmless disposal and resource utilization for the solid waste containing chromium in leather industry.

Genome-wide identification and expression analysis of xyloglucan endotransglucosylase/hydrolase genes family in Salicaceae during grafting.

BACKGROUND: Poplar (Populus cathayana)and willow (Salix rehderiana) are important fast-growing trees in China. Grafting plays an important role in improving plant stress resistance and construction of ornamental plants. It is found that willow scions grafted onto poplar rootstocks can form ornamental plants. However, this grafted combination has a low survival rate. Many studies have reported that the xyloglucan endotransglucosylase/hydrolase (XTH) family plays an important role in the healing process of grafts. RESULTS: A total of 38 PtrXTHs and 32 SpuXTHs were identified in poplar and willow respectively, and were classified into three subfamilies. Tandem duplication was the main reason for the expansion of the PtrXTHs. Grafting treatment and Quantitative real time PCR (RT-qPCR) analysis revealed that five XTH genes differentially expressed between self-grafted and reciprocal grafted combinations. Specifically, the high expression levels of SrXTH16, SrXTH17, SrXTH25, PcXTH22 and PcXTH17 may contribute to the high survival rate of the grafted combination with willow scion and poplar rootstock. Subcellular localization identified that the SrXTH16, SrXTH17, SrXTH25, PcXTH17 and PcXTH22 proteins were located on the cell walls. Transcription factors (NAC, MYB and DOF) may regulate the five XTH genes. CONCLUSIONS: This study provides a new understanding of the roles of PcXTH and SrXTH genes and their roles in grafting. Our results will give some hints to explore the molecular mechanisms of PcXTH and SrXTH genes involved in grafting in the future.

Preclinical evaluation of Mito-LND, a targeting mitochondrial metabolism inhibitor, for glioblastoma treatment.

BACKGROUND: Glioblastoma (GBM) is a brain tumor with the highest level of malignancy and the worst prognosis in the central nervous system. Mitochondrial metabolism plays a vital role in the occurrence and development of cancer, which provides critical substances to support tumor anabolism. Mito-LND is a novel small-molecule inhibitor that can selectively inhibit the energy metabolism of tumor cells. However, the therapeutic effect of Mito-LND on GBM remains unclear. METHODS: The present study evaluated the inhibitory effect of Mito-LND on the growth of GBM cells and elucidated its potential mechanism. RESULTS: The results showed that Mito-LND could inhibit the survival, proliferation and colony formation of GBM cells. Moreover, Mito-LND induced cell cycle arrest and apoptosis. Mechanistically, Mito-LND inhibited the activity of mitochondrial respiratory chain complex I and reduced mitochondrial membrane potential, thus promoting ROS generation. Importantly, Mito-LND could inhibit the malignant proliferation of GBM by blocking the Raf/MEK/ERK signaling pathway. In vivo experiments showed that Mito-LND inhibited the growth of GBM xenografts in mice and significantly prolonged the survival time of tumor-bearing mice. CONCLUSION: Taken together, the current findings support that targeting mitochondrial metabolism may be as a potential and promising strategy for GBM therapy, which will lay the theoretical foundation for further clinical trials on Mito-LND in the future.

Dual blockade of EGFR and PI3K signaling pathways offers a therapeutic strategy for glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is a devastating disease that lacks effective drugs for targeted therapy. Previously, we found that the third-generation epidermal growth factor receptor (EGFR) inhibitor AZD-9291 persistently blocked the activation of the ERK pathway but had no inhibitory effect on the phosphoinositide 3-kinase (PI3K)/Akt pathway. Given that the PI3K inhibitor GDC-0084 is being evaluated in phase I/II clinical trials of GBM treatment, we hypothesized that combined inhibition of the EGFR/ERK and PI3K/Akt pathways may have a synergistic effect in the treatment of GBM. METHODS: The synergistic effects of cotreatment with AZD-9291 and GDC-0084 were validated using cell viability assays in GBM and primary GBM cell lines. Moreover, the underlying inhibitory mechanisms were assessed through colony formation, EdU proliferation, and cell cycle assays, as well as RNA-seq analyses and western blot. The therapeutic effects of the drug combination on tumor growth and survival were investigated in mice bearing tumors using subcutaneously or intracranially injected LN229 xenografts. RESULTS: Combined treatment with AZD-9291 and GDC-0084 synergistically inhibited the proliferation and clonogenic survival, as well as induced cell cycle arrest of GBM cells and primary GBM cells, compared to monotherapy. Moreover, AZD-9291 plus GDC-0084 combination therapy significantly inhibited the growth of subcutaneous tumors and orthotopic brain tumor xenografts, thus prolonging the survival of tumor-bearing mice. More importantly, the combination of AZD-9291 and GDC-0084 simultaneously blocked the activation of the EGFR/MEK/ERK and PI3K/AKT/mTOR signaling pathways, thereby exerting significant antitumor activity. CONCLUSION: Our findings demonstrate that the combined blockade of the EGFR/MEK/ERK and PI3K/AKT/mTOR pathways is more effective against GBM than inhibition of each pathway alone, both in vitro and in vivo. Our results suggest that AZD-9291 combined with GDC-0084 may be considered as a potential treatment strategy in future clinical trials. Video Abstract.

CDC20 promotes bone formation via APC/C dependent ubiquitination and degradation of p65.

The E3 ubiquitin ligase complex CDC20-activated anaphase-promoting complex/Cyclosome (APC/CCDC20 ) plays a critical role in governing mitotic progression by targeting key cell cycle regulators for degradation. Cell division cycle protein 20 homolog (CDC20), the co-activator of APC/C, is required for full ubiquitin ligase activity. In addition to its well-known cell cycle-related functions, we demonstrate that CDC20 plays an essential role in osteogenic commitment of bone marrow mesenchymal stromal/stem cells (BMSCs). Cdc20 conditional knockout mice exhibit decreased bone formation and impaired bone regeneration after injury. Mechanistically, we discovered a functional interaction between the WD40 domain of CDC20 and the DNA-binding domain of p65. Moreover, CDC20 promotes the ubiquitination and degradation of p65 in an APC11-dependent manner. More importantly, knockdown of p65 rescues the bone loss in Cdc20 conditional knockout mice. Our current work reveals a cell cycle-independent function of CDC20, establishes APC11CDC20 as a pivotal regulator for bone formation by governing the ubiquitination and degradation of p65, and may pave the way for treatment of bone-related diseases.

Short-term effect of particulate matter on lung function and impulse oscillometry system (IOS) parameters of chronic obstructive pulmonary disease (COPD) in Beijing, China.

OBJECTIVE: This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. METHODS: In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants' residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity . RESULTS: The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: -3.047 to - 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: -258 to - 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: -1.518 to - 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p < 0.05). CONCLUSION: Short-term exposure to PM2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM2.5, the more severe of COPD.

8-O-acetyl shanzhiside methylester protects against sleep deprivation-induced cognitive deficits and anxiety-like behaviors by regulating NLRP3 and Nrf2 pathways in mice.

Sleep deprivation (SD) is prevalent throughout the world, which has negative effects on cognitive abilities, and causing mood alterations. 8-O-acetyl shanzhiside methylester (8-OaS), a chief component in Lamiophlomis rotata (L. rotata) Kudo, possesses potent neuroprotective properties and analgesic effects. Here, we evaluated the alleviative effects of 8-OaS on memory impairment and anxiety in mice subjected to SD (for 72-h). Our results demonstrated that 8-OaS (0.2, 2, 20 mg/kg) administration dose-dependently ameliorated behavioral abnormalities in SD mice, accompanied with restored synaptic plasticity and reduced shrinkage and loss of hippocampal neurons. 8-OaS reduced the inflammatory response and oxidative stress injury in hippocampus caused by SD, which may be related to inhibition of NLRP3 inflammasome-mediated inflammatory process and activation of the Nrf2/HO-1 pathway. SD also led to increases in the expressions of TLR-4/MyD88, active NF-κB, pro-IL-1ß, TNFα and MDA, as well as a decrease in the level of SOD in mice hippocampus, which were reversed by 8-OaS administration. Moreover, our molecular docking analyses showed that 8-OaS also has good affinity for NLRP3 and Nrf2 signaling pathways. These results suggested that 8-OaS could be used as a novel herbal medicine for the treatment of sleep loss and for use as a structural base for developing new drugs.

Conductive and self-healing hydrogel for flexible electrochemiluminescence sensor.

A flexible electrochemiluminescence (ECL) hydrogel sensor exhibiting good self-healing was constructed. A transparent self-healing oxidized sodium alginate/hydrazide polyethylene glycol (OSA/PEG-DH) hydrogel was prepared by crosslinking dynamic covalent acylhydrazone bond. The introduction of 4-amino-DL-phenylalanine, a catalyst with good biocompatibility, allows rapid gelation and self-healing of hydrogel under mild conditions. Using the hydrogel as the sensing substrate, the ionic liquid (IL) 2-hydroxy-N,N,N-trimethylethanaminium chloride and the luminescent reagent N-(aminobutyl)-N-(ethylisoluminol) (ABEI) were simultaneously immobilized in the OSA/PEG-DH hydrogel to obtain the ABEI/IL/OSA/PEG-DH hydrogel. The ABEI/IL/OSA/PEG-DH hydrogel can be directly used as a semi-solid electrolyte for constructing a flexible ECL hydrogel sensor for the detection of H2O2, which acted as a coreactant of ABEI. The prepared flexible ECL sensor showed good self-healing performance, can restore ECL signal intensity within 20 min after physical damage, and showed high accuracy in the analysis of complex serum samples. This research shed new light on the development of flexible ECL sensor for bioanalytical applications.

Sn Anodes Protected by Intermetallic FeSn2 Layers for Long-lifespan Sodium-ion Batteries with High Initial Coulombic Efficiency of 93.8.

With a theoretical capacity of 847 mAh g-1 , Sn has emerged as promising anode material for sodium-ion batteries (SIBs). However, enormous volume expansion and agglomeration of nano Sn lead to low Coulombic efficiency and poor cycling stability. Herein, an intermetallic FeSn2 layer is designed via thermal reduction of polymer-Fe2 O3 coated hollow SnO2 spheres to construct a yolk-shell structured Sn/FeSn2 @C. The FeSn2 layer can relieve internal stress, avoid the agglomeration of Sn to accelerate the Na+ transport, and enable fast electronic conduction, which endows quick electrochemical dynamics and long-term stability. As a result, the Sn/FeSn2 @C anode exhibits high initial Coulombic efficiency (ICE=93.8 %) and a high reversible capacity of 409 mAh g-1 at 1 A g-1 after 1500 cycles, corresponding to an 80 % capacity retention. In addition, NVP//Sn/FeSn2 @C sodium-ion full cell shows outstanding cycle stability (capacity retaining rate of 89.7 % after 200 cycles at 1 C).

Identification of TIFY gene family in walnut and analysis of its expression under abiotic stresses.

BACKGROUND: Walnuts (Juglans regia L.) are known for their nutrient-rich nuts and are one of the important economic tree species in the world. However, due to global warming and soil salinization, walnuts suffer from various abiotic stresses. TIFY (TIF[F/Y]XG) proteins play an essential role in the growth and development of plants, signal transduction, and stress response in plants. At present, although the TIFY gene family of a number of plants has been identified and studied, how TIFY takes part in stress tolerance remains obscure and many functions of TIFY require further investigation. RESULT: In this study, twenty-one TIFY transcription factors were identified in the walnut genome database, and they were divided into four subfamilies (TIFY, JAZ, ZML, and PPD) by bioinformatics analysis. Chromosome location revealed tandem duplication of some genes. Phylogenetic tree analysis showed JrTIFYs were closely related to the TIFY gene family of Arabidopsis thaliana (A. thaliana). qRT-PCR (quantitative real-time PCR) analysis revealed the TIFY genes have different expression patterns in 'Qingxiang' and 'Xiangling' walnut varieties under drought, heat, and salt stress. JAZ subfamily was more expressed in different abiotic stress than other subfamilies. The expressions of JrTIFY14 under heat and salt stress were significantly higher than those under drought stress. However, the expression of JrTIFYs was not significant in 'Xiangling'. CONCLUSION: This study reveals the TIFY gene family plays an important role in walnuts facing abiotic stresses and provides a theoretical basis for walnut breeding.

Fully Integrated Microfluidic Biosensor with Finger Actuation for the Ultrasensitive Detection of Escherichia coli O157:H7.

A portable microfluidic biosensor was developed for the detection of E. coli O157:H7 using finger actuation. The chip was assembled with three functional zones, immunomagnetic separation, nucleic acid extraction and purification, and signal detection. First, antibody-modified magnetic nanoparticles (MNPs) were used to separate the target bacteria from the sample. The captured bacteria were then lysed and silica-coated MNPs were used to absorb DNA, followed by washing and eluting to obtain purified DNA. The obtained DNA was subjected to amplification and fluorescence detection based on the recombinase polymerase amplification-clustered regularly interspaced short palindromic repeat-associated protein/Cas12a reaction. The fluorescence images were collected and analyzed using a smartphone app under a 3D-printed detection device. It could quantitatively detect E. coli O157:H7 from 102 to 108 CFU/mL in 2.5 h with a limit of detection (LOD) of 10 CFU/mL. The recovery rate ranged from 104 to 120%. Overall, the biosensor realizes "sample-in and answer-out" assay for E. coli O157:H7 and eliminates the need for external pumps and skilled personnel.

DUSP5 promotes osteogenic differentiation through SCP1/2-dependent phosphorylation of SMAD1.

Dual-specificity phosphatases (DUSPs) are defined by their capability to dephosphorylate both phosphoserine/phosphothreonine (pSer/pThr) and phosphotyrosine (pTyr). DUSP5, a member of DUSPs superfamily, is located in the nucleus and plays crucially regulatory roles in the signaling pathway transduction. In our present study, we discover that DUSP5 significantly promotes osteogenic differentiation of mesenchymal stromal cells (MSCs) by activating SMAD1 signaling pathway. Mechanistically, DUSP5 physically interacts with the phosphatase domain of small C-terminal phosphatase 1/2 (SCP1/2, SMAD1 phosphatases) by the linker region. In addition, we further confirm that DUSP5 activates SMAD1 signaling through a SCP1/2-dependent manner. Specifically, DUSP5 attenuates the SCP1/2-SMAD1 interaction by competitively binding to SCP1/2, which is responsible for the SMAD1 dephosphorylation, and thus results in the activation of SMAD1 signaling. Importantly, DUSP5 expression in mouse bone marrow MSCs is significantly reduced in ovariectomized (OVX) mice in which osteogenesis is highly passive, and overexpression of Dusp5 via tail vein injection reverses the bone loss of OVX mice efficiently. Collectively, this work demonstrates that the linker region of DUSP5 maybe a novel chemically modifiable target for controlling MSCs fate choices and for osteoporosis treatment.

Risk factors for and clinical outcomes of ceftazidime-avibactam-resistant carbapenem-resistant Klebsiella pneumoniae nosocomial infections: a single-center retrospective study.

PURPOSE: The emergence of ceftazidime-avibactam (CZA) resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported in recent years. We aimed to identify the risk factors of CZA-resistant CRKP infection and assess clinical outcomes of the patients. METHODS: The study retrospectively analyzed the clinical and microbiological data of patients with CRKP infection to identify risk factors, clinical features, and outcomes using multivariate logistic regression analysis. RESULTS: A total of 103 patients with CRKP infection were enrolled in this study. Multivariate analysis showed previous renal replacement therapy (OR 3.966, 95% CI 1.301-12.090, P = 0.015) was an independent risk factor for CZA-resistant CRKP infection. The 28-day mortality was higher in patients infected with CZA-resistant CRKP (27.9%) than those with CZA-susceptible CRKP (7.1%) (P = 0.009). CZA-resistant CRKP infection (OR 20.308, 95% CI 1.461-282.293, P = 0.025), and mechanical ventilation (OR 14.950, 95% CI 1.034-216.212, P = 0.047) were independent predictors for 28-day mortality in patients with CRKP infection. Lower level of platelet count (OR 0.987, 95% CI 0.975-0.999, P = 0.032) on the day of CRKP infection onset was related to 28-day mortality. Kaplan-Meier curves showed that the CZA-resistant CRKP group had a shorter survival time than the CZA-susceptible CRKP group. CONCLUSION: The prevalence and mortality of CZA-resistant CRKP are still increasing. Strengthening the hospital infection control of renal replacement therapy and mechanical ventilation may help to prevent CZA-resistant CRKP.

Plagiodera versicolora feeding induces systemic and sexually differential defense responses in poplars.

Dioecious plants have evolved effective defense strategies to deal with various biotic and abiotic stresses. However, little is known regarding sexual differences in their defense against herbivores. In this study, we investigated the mechanism of systemic defense responses in male and female Populus cathayana attacked by Plagiodera versicolora Laicharting. The results revealed that P. cathayana exhibits sexually differential responses to a defoliator. The percentage of damaged leaf area was greater in males than in females. Furthermore, the observed saccharide changes imply that males and females exhibit different response times to defoliators. The contents of flavonoids and anthocyanins were significantly increased in both sexes but were higher in females. Specifically, the jasmonic acid (JA) pathway plays an important role. Expression of pest-related genes further revealed that hormones induce changes in downstream genes and metabolites, and upregulation of JA ZIM-domain (JAZ) and CORONATINE INSENSITIVE 1 (COI1) was more significant in females. In the undamaged adjacent leaves, metabolite and gene changes displayed similar patterns to the damaged local leaves, but levels of JA, JAZ1, and COI1 were higher in females. Therefore, our data confirmed that plants initiate the JA pathway to defend against herbivores, that there is systematic signal transduction, and that this ability is stronger in females than in males. This study provides new insights into the resistance of dioecious plants to herbivory and adds a new theoretical basis for the systemic signal transduction of plants in response to biotic stress.