Regulation of drought tolerance in Arabidopsis involves the PLATZ4-mediated transcriptional repression of plasma membrane aquaporin PIP2;8.

Plant A/T-rich protein and zinc-binding protein (PLATZ) transcription factors play important roles in plant growth, development and abiotic stress responses. However, how PLATZ influences plant drought tolerance remains poorly understood. The present study showed that PLATZ4 increased drought tolerance in Arabidopsis thaliana by causing stomatal closure. Transcriptional profiling analysis revealed that PLATZ4 affected the expression of a set of genes involved in water and ion transport, antioxidant metabolism, small peptides and abscisic acid (ABA) signaling. Among these genes, the direct binding of PLATZ4 to the A/T-rich sequences in the plasma membrane intrinsic protein 2;8 (PIP2;8) promoter was identified. PIP2;8 consistently reduced drought tolerance in Arabidopsis through inhibiting stomatal closure. PIP2;8 was localized in the plasma membrane, exhibited water channel activity in Xenopus laevis oocytes and acted epistatically to PLATZ4 in regulating the drought stress response in Arabidopsis. PLATZ4 increased ABA sensitivity through upregulating the expression of ABSCISIC ACID INSENSITIVE 3 (ABI3), ABI4 and ABI5. The transcripts of PLATZ4 were induced to high levels in vegetative seedlings under drought and ABA treatments within 6 and 3 h, respectively. Collectively, these findings reveal that PLATZ4 positively influences plant drought tolerance through regulating the expression of PIP2;8 and genes involved in ABA signaling.

A long non-coding RNA functions as a competitive endogenous RNA to modulate TaNAC018 by acting as a decoy for tae-miR6206.

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.

Lysosome-Targeting Bacterial Outer Membrane Vesicles for Tumor Specific Degradation of PD-L1.

Increased expression of immune check point genes, such as PD-L1, is one of the main reasons for immunosuppression, especially for colon cancer. Development of novel therapeutic strategies is of great importance to improve the prognosis. In this study, outer membrane vesicles (OMV) derived from Gram-negative bacteria are engineered to immune checkpoint blockade nanosystem for efficient elicitation of anti-tumor immunity. Briefly, the OMVs are engineered with Lyp1-Traptavidin (S52G, R53D mutant of streptavidin) fusion protein displayed on the surface. The Lyp-1 endows the OMV with the capacity to target tumor tissues, while the Traptavidin ensures easy decoration of biotinylated anti-PD-L1 and biotinylated M6P (mannose 6-phosphate). The simultaneously anchored anti-PD-L1 and M6P (ligand for cation-independent mannose 6-phosphate receptor) on the engineered OMVs coordinately direct the membrane PD-L1 to lysosome for degradation, and thus unleash the anti-tumor immunity. With syngeneic tumor model, the engineered OMVs are confirmed to boost immunity, inhibit cancer growth, and thus prolong survival. Together, A proposed OMV-based modular nanosystem that enables assembly of biotinylated anti-PD-L1 and M6P on the surface for tumor-targeted immune checkpoint blockade.

An efficient genetic transformation system mediated by Rhizobium rhizogenes in fruit trees based on the transgenic hairy root to shoot conversion.

Genetic transformation is a critical tool for gene editing and genetic improvement of plants. Although many model plants and crops can be genetically manipulated, genetic transformation systems for fruit trees are either lacking or perform poorly. We used Rhizobium rhizogenes to transfer the target gene into the hairy roots of Malus domestica and Actinidia chinensis. Transgenic roots were generated within 3 weeks, with a transgenic efficiency of 78.8%. Root to shoot conversion of transgenic hairy roots was achieved within 11 weeks, with a regeneration efficiency of 3.3%. Finally, the regulatory genes involved in stem cell activity were used to improve shoot regeneration efficiency. MdWOX5 exhibited the most significant effects, as it led to an improved regeneration efficiency of 20.6% and a reduced regeneration time of 9 weeks. Phenotypes of the overexpression of RUBY system mediated red roots and overexpression of MdRGF5 mediated longer root hairs were observed within 3 weeks, suggesting that the method can be used to quickly screen genes that influence root phenotype scores through root performance, such as root colour, root hair, and lateral root. Obtaining whole plants of the RUBY system and MdRGF5 overexpression lines highlights the convenience of this technology for studying gene functions in whole plants. Overall, we developed an optimized method to improve the transformation efficiency and stability of transformants in fruit trees.

Advancements in nanomedicine: Precision delivery strategies for male pelvic malignancies - Spotlight on prostate and colorectal cancer.

BACKGROUND: Pelvic malignancies consistently pose significant global health challenges, adversely affecting the well-being of the male population. It is anticipated that clinicians will continue to confront these cancers in their practice. Nanomedicine offers promising strategies that revolutionize the treatment of male pelvic malignancies by providing precise delivery methods that aim to improve the efficacy of therapeutic outcomes while minimizing side effects. Nanoparticles are designed to encapsulate therapeutic agents and selectively target cancer cells. They can also be loaded with theragnostic agents, enabling multifunctional capabilities. OBJECTIVE: This review aims to summarize the latest nanomedicine research into clinical applications, focusing on nanotechnology-based treatment strategies for male pelvic malignancies, encompassing chemotherapy, radiotherapy, immunotherapy, and other cutting-edge therapies. The review is structured to assist physicians, particularly those with limited knowledge of biochemistry and bioengineering, in comprehending the functionalities and applications of nanomaterials. METHODS: Multiple databases, including PubMed, the National Library of Medicine, and Embase, were utilized to locate and review recently published articles on advancements in nano-drug delivery for prostate and colorectal cancers. CONCLUSION: Nanomedicine possesses considerable potential in improving therapeutic outcomes and reducing adverse effects for male pelvic malignancies. Through precision delivery methods, this emerging field presents innovative treatment modalities to address these challenging diseases. Nevertheless, the majority of current studies are in the preclinical phase, with a lack of sufficient evidence to fully understand the precise mechanisms of action, absence of comprehensive pharmacotoxicity profiles, and uncertainty surrounding long-term consequences.

Targeted delivery of MerTK protein via cell membrane engineered nanoparticle enhances efferocytosis and attenuates atherosclerosis in diabetic ApoE-/- Mice.

BACKGROUND: Clearance of apoptotic cells by efferocytosis is crucial for prevention of atherosclerosis progress, and impaired efferocytosis contributes to the aggravated atherosclerosis. RESULTS: In this study, we found that diabetic ApoE-/- mice showed aggravated atherosclerosis as hyperglycemia damaged the efferocytosis capacity at least partially due to decreased expression of Mer tyrosine kinase (MerTK) on macrophages. To locally restore MerTK in the macrophages in the plaque, hybrid membrane nanovesicles (HMNVs) were thus developed. Briefly, cell membrane from MerTK overexpressing RAW264.7 cell and transferrin receptor (TfR) overexpressing HEK293T cell were mixed with DOPE polymers to produce nanovesicles designated as HMNVs. HMNVs could fuse with the recipient cell membrane and thus increased MerTK in diabetic macrophages, which in turn restored the efferocytosis capacity. Upon intravenous administration into diabetic ApoE-/- mice, superparamagnetic iron oxide nanoparticles (SMN) decorated HMNVs accumulated at the aorta site significantly under magnetic navigation, where the recipient macrophages cleared the apoptotic cells efficiently and thus decreased the inflammation. CONCLUSIONS:  Our study indicates that MerTK decrease in macrophages contributes to the aggravated atherosclerosis in diabetic ApoE-/- mice and regional restoration of MerTK in macrophages of the plaque via HMNVs could be a promising therapeutic approach.

Salt responsive alternative splicing of a RING finger E3 ligase modulates the salt stress tolerance by fine-tuning the balance of COP9 signalosome subunit 5A.

Increasing evidence points to the tight relationship between alternative splicing (AS) and the salt stress response in plants. However, the mechanisms linking these two phenomena remain unclear. In this study, we have found that Salt-Responsive Alternatively Spliced gene 1 (SRAS1), encoding a RING-Type E3 ligase, generates two splicing variants: SRAS1.1 and SRAS1.2, which exhibit opposing responses to salt stress. The salt stress-responsive AS event resulted in greater accumulation of SRAS1.1 and a lower level of SRAS1.2. Comprehensive phenotype analysis showed that overexpression of SRAS1.1 made the plants more tolerant to salt stress, whereas overexpression of SRAS1.2 made them more sensitive. In addition, we successfully identified the COP9 signalosome 5A (CSN5A) as the target of SRAS1. CSN5A is an essential player in the regulation of plant development and stress. The full-length SRAS1.1 promoted degradation of CSN5A by the 26S proteasome. By contrast, SRAS1.2 protected CSN5A by competing with SRAS1.1 on the same binding site. Thus, the salt stress-triggered AS controls the ratio of SRAS1.1/SRAS1.2 and switches on and off the degradation of CSN5A to balance the plant development and salt tolerance. Together, these results provide insights that salt-responsive AS acts as post-transcriptional regulation in mediating the function of E3 ligase.

Efficient Delivery of GSDMD-N mRNA by Engineered Extracellular Vesicles Induces Pyroptosis for Enhanced Immunotherapy.

Pyroptosis is a newly discovered inflammatory form of programmed cell death, which promotes systemic immune response in cancer immunotherapy. GSDMD is one of the key molecules executing pyroptosis, while therapeutical delivery of GSDMD to tumor cells is of great challenge. In this study, an extracellular vesicles-based GSDMD-N mRNA delivery system (namely EVTx ) is developed for enhanced cancer immunotherapy, with GSDMD-N mRNA encapsulated inside, Ce6 (Chlorin e6 (Ce6), a hydrophilic sensitizer) incorporated into extracellular vesicular membrane, and HER2 antibody displayed onto the surface. Briefly, GSDMD-N mRNA is translationally repressed in donor cells by optimized puromycin, ensuring the cell viability and facilitating the mRNA encapsulation into extracellular vesicles. When targeted and delivered into HER2+ breast cancer cells by the engineered extracellular vesicles, the translational repression is unleashed in the recipient cells as the puromycin is diluted and additionally inactivated by sonodynamic treatment as the extracellular vesicles are armed with Ce6, allowing GSDMD-N translation and pyroptosis induction. In addition, sonodynamic treatment also induces cell death in the recipient cells. In the SKBR3- and HER2 transfected 4T1- inoculated breast tumor mouse models, the engineered EVTx efficiently induces a powerful tumor immune response and suppressed tumor growth, providing a nanoplatform for cancer immunotherapy.

Plasmonic Metal Mediated Charge Transfer in Stacked Core-Shell Semiconductor Heterojunction for Significantly Enhanced CO2 Photoreduction.

Construction of core-shell semiconductor heterojunctions and plasmonic metal/semiconductor heterostructures represents two promising routes to improved light harvesting and promoted charge separation, but their photocatalytic activities are respectively limited by sluggish consumption of charge carriers confined in the cores, and contradictory migration directions of plasmon-induced hot electrons and semiconductor-generated electrons. Herein, a semiconductor/metal/semiconductor stacked core-shell design is demonstrated to overcome these limitations and significantly boost the photoactivity in CO2  reduction. In this smart design, sandwiched Au serves as a "stone", which "kills two birds" by inducing localized surface plasmon resonance for hot electron generation and mediating unidirectional transmission of conduction band electrons and hot electrons from TiO2  core to MoS2  shell. Meanwhile, upward band bending of TiO2  drives core-to-shell migration of holes through TiO2 -MoS2  interface. The co-existence of TiO2  â†’ Au â†’ MoS2  electron flow and TiO2  â†’ MoS2  hole flow contributes to spatial charge separation on different locations of MoS2  outer layer for overall redox reactions. Additionally, reduction potential of photoelectrons participating in the CO2  reduction is elaborately adjusted by tuning the thickness of MoS2  shell, and thus the product selectivity is delicately regulated. This work provides fresh hints for rationally controlling the charge transfer pathways toward high-efficiency CO2  photoreduction.

Embedding Nano-Piezoelectrics into Heterointerfaces of S-Scheme Heterojunctions for Boosting Photocatalysis and Piezophotocatalysis.

Step-scheme (S-scheme) heterojunctions have exhibited great potential in photocatalysis due to their extraordinary light harvesting and high redox capacities. However, inadequate S-scheme recombination of useless carriers in weak redox abilities increases the probability of their recombination with useful ones in strong redox capabilities. Herein, a versatile protocol is demonstrated to overcome this impediment based on the insertion of nano-piezoelectrics into the heterointerfaces of S-scheme heterojunctions. Under light excitation, the piezoelectric inserter promotes interfacial charge transfer and produces additional photocarriers to recombine with useless electrons and holes, ensuring a more thorough separation of powerful ones for CO2 reduction and H2 O oxidation. When introducing extra ultrasonic vibration, a piezoelectric polarization field is established, which allows efficient separation of charges generated by the embedded piezoelectrics and expedites their recombination with weak carriers, further increasing the number of strong ones participating in the redox reactions. Encouraged by the greatly improved charge utilization, significantly enhanced photocatalytic and piezophotocatalytic activities in CH4 , CO, and O2 production are achieved by the designed stacked catalyst. This work highlights the importance in strengthening the necessary charge recombination in S-scheme heterojunctions and presents an efficient and novel strategy to synergize photocatalysis and piezocatalysis for renewable fuels and value-added chemicals production.

Intronic microRNA-directed regulation of mitochondrial reactive oxygen species enhances plant stress tolerance in Arabidopsis.

MicroRNAs (miRNAs) play crucial roles in regulating plant development and stress responses. However, the functions and mechanism of intronic miRNAs in plants are poorly understood. This study reports a stress-responsive RNA splicing mechanism for intronic miR400 production, whereby miR400 modulates reactive oxygen species (ROS) accumulation and improves plant tolerance by downregulating its target expression. To monitor the intron splicing events, we used an intronic miR400 splicing-dependent luciferase transgenic line. Luciferase activity was observed to decrease after high cadmium concentration treatment due to the retention of the miR400-containing intron, which inhibited the production of mature miR400. Furthermore, we demonstrated that under Cd treatments, Pentatricopeptide Repeat Protein 1 (PPR1), the target of miR400, acts as a positive regulator by inducing ROS accumulation. Ppr1 mutation affected the Complex III activity in the electron transport chain and RNA editing of the mitochondrial gene ccmB. This study illustrates intron splicing as a key step in intronic miR400 production and highlights the function of intronic miRNAs as a 'signal transducer' in enhancing plant stress tolerance.

Construction and external validation of a nomogram model for predicting the risk of esophageal stricture after endoscopic submucosal dissection: a multicenter case-control study.

Esophageal stricture is a common complication after endoscopic submucosal dissection (ESD) for superficial esophageal cancer and precancerous lesions, we intend to investigate the independent risk factors of esophageal stricture after ESD by adding the data of included living habits, established a nomogram model to predict the risk of esophageal stricture, and verified it by external data. The clinical data and living habits of patients with early esophageal cancer and precancerous lesions who underwent ESD in the Affiliated Hospital of North Sichuan Medical College and Langzhong People's Hospital from March 2017 to August 2021 were retrospectively collected. The data collected from the two hospitals were used as the development group (n = 256) and the validation group (n = 105), respectively. Univariate and multivariate logistic regression analyses were used to determine independent risk factors for esophageal stricture after ESD and establish a nomogram model for the development group. The prediction performance of the nomogram model is internally and externally verified by calculating C-Index and plotting the receiver operating characteristic curve (ROC) and calibration curve, respectively. The results showed that Age, drinking water temperature, neutrophil-lymphocyte ratio, the extent of esophageal mucosal defect, longitudinal diameter of resected mucosa, and depth of tissue invasion (P < 0.05) were independent risk factors for esophageal stricture after ESD. The C-Index of the development group and validation group was 0.925 and 0.861, respectively. The ROC curve and area under the curve (AUC) of the two groups suggested that the discrimination and prediction performance of the model were good. The two groups of calibration curves are consistent and almost overlap with the ideal calibration curve, indicating that the predicted results of this model are in good agreement with the actual observed results. In conclusion, this nomogram model has a high accuracy for predicting the risk of esophageal stricture after ESD, providing a theoretical basis for reducing or avoiding esophageal stricture and guiding clinical practice.

Hydrogel armed with Bmp2 mRNA-enriched exosomes enhances bone regeneration.

BACKGROUND: Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life of BMP2 at protein level cannot meet the clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel to achieve sustained release for more efficient and safe bone regeneration. RESULTS: Bmp2 mRNA was enriched into exosomes by selective inhibition of translation in donor cells, in which NoBody (non-annotated P-body dissociating polypeptide, a protein that inhibits mRNA translation) and modified engineered BMP2 plasmids were co-transfected. The derived exosomes were named ExoBMP2+NoBody. In vitro experiments confirmed that ExoBMP2+NoBody had higher abundance of Bmp2 mRNA and thus stronger osteogenic induction capacity. When loaded into GelMA hydrogel via ally-L-glycine modified CP05 linker, the exosomes could be slowly released and thus ensure prolonged effect of BMP2 when endocytosed by the recipient cells. In the in vivo calvarial defect model, ExoBMP2+NoBody-loaded GelMA displayed great capacity in promoting bone regeneration. CONCLUSIONS: Together, the proposed ExoBMP2+NoBody-loaded GelMA can provide an efficient and innovative strategy for bone regeneration.

Safe femoral tunnel drilling angles avoid injury to the medial and posteromedial femoral anatomic structures during single-bundle posterior cruciate ligament reconstruction with the inside-out technique.

PURPOSE: To investigate the relationship between the medial and posteromedial femoral anatomic structures and the femoral tunnel exit produced by different tunnel orientations when creating the femoral tunnel for posterior cruciate ligament reconstruction (PCLR) using the inside-out (IO) technique and to estimate safe tunnel orientations to minimize the risk of iatrogenic injury to these structures. METHODS: Eleven cadaveric knees were used. The medial and posteromedial aspects of each knee joint were dissected to reveal the "safe zone," which is a bony area that avoids the distribution or attachment of at-risk structures (MCL, PMC structures, and articular cartilage), while remaining 10 mm away from the articular cartilage. The hypothesis of this study was that by creating the femoral tunnel at specific angles using the IO technique, the tunnel outlet would be as close to the safe zone as possible, protecting the at-risk structures from damage. Femoral tunnels were drilled at 20 different angle combinations on each specimen: 0°, 15°, 30°, 45°, and 60° relative to a line parallel to the transepicondylar axis in the axial plane, as well as 15°, 30°, 45°, and 60° relative to a line parallel to the femoral axis in the coronal plane. The positional relationship between each tunnel exit and the safe zone was recorded, and the shortest distance between the exit center and the safe zone boundary was measured. RESULTS: The risk of iatrogenic injury differed depending on the drilling orientation (χ2 = 168.880, P < 0.001). Femoral drilling angle combinations of 45/45°, 45/60°, 60/30°, 60/45°, and 60/60° (axial/coronal) were considered relatively safer than other orientations (P < 0.05). The shortest distance between the tunnel exit and the safe zone boundary was negatively correlated with the angle in the axial plane (P < 0.001, r = - 0.810). CONCLUSIONS: When creating the IO femoral tunnel for single-bundle PCL reconstruction, angle combinations of 45/45°, 45/60°, 60/30°, 60/45°, and 60/60° (axial/oblique coronal) could be utilized to prevent at-risk structures from being damaged. The drilling angles and the safe zone can be employed to optimize the femoral tunnel in PCLR.

BREVIPEDICELLUS Positively Regulates Salt-Stress Tolerance in Arabidopsis thaliana.

Salt stress is one of the major environmental threats to plant growth and development. However, the mechanisms of plants responding to salt stress are not fully understood. Through genetic screening, we identified and characterized a salt-sensitive mutant, ses5 (sensitive to salt 5), in Arabidopsis thaliana. Positional cloning revealed that the decreased salt-tolerance of ses5 was caused by a mutation in the transcription factor BP (BREVIPEDICELLUS). BP regulates various developmental processes in plants. However, the biological function of BP in abiotic stress-signaling and tolerance are still not clear. Compared with wild-type plants, the bp mutant exhibited a much shorter primary-root and lower survival rate under salt treatment, while the BP overexpressors were more tolerant. Further analysis showed that BP could directly bind to the promoter of XTH7 (xyloglucan endotransglucosylase/hydrolase 7) and activate its expression. Resembling the bp mutant, the disruption of XTH7 gave rise to salt sensitivity. These results uncovered novel roles of BP in positively modulating salt-stress tolerance, and illustrated a putative working mechanism.

Tyrosylprotein sulfotransferase suppresses ABA signaling via sulfation of SnRK2.2/2.3/2.6.

Phytohormone abscisic acid (ABA) plays vital roles in stress tolerance, while long-term overactivation of ABA signaling suppresses plant growth and development. However, the braking mechanism of ABA responses is not clear. Protein tyrosine sulfation catalyzed by tyrosylprotein sulfotransferase (TPST) is a critical post-translational modification. Through genetic screening, we identified a tpst mutant in Arabidopsis that was hypersensitive to ABA. In-depth analysis revealed that TPST could interact with and sulfate SnRK2.2/2.3/2.6, which accelerated their degradation and weakened the ABA signaling. Taken together, these findings uncovered a novel mechanism of desensitizing ABA responses via protein sulfation.

Emerging Stacked Photocatalyst Design Enables Spatially Separated Ni(OH)2 Redox Cocatalysts for Overall CO2 Reduction and H2 O Oxidation.

Construction of photocatalytic systems with spatially separated dual cocatalysts is considered as a promising route to modulate charge separation/transfer, promote surface redox reactivities, and prevent unwanted reverse reactions. However, past efforts on the loading of spatially separated double-cocatalysts are limited to hollow structured semiconductors with inner/outer surface and monocrystalline semiconductors with different exposed facets. To overcome this limitation, herein, enabled by a unique stacked photocatalyst design, a facile and versatile strategy for spatial separation of redox cocatalysts on various semiconductors without structural and morphological restriction is demonstrated. The smart design begins with the deposition of light-harvesting semiconductors on reduced graphene oxide (rGO) nanosheets, followed with the coverage of Ni(OH)2 outer layer. The ternary photocatalysts exhibit superior activities and stabilities of H2 O oxidation and selective CO2 -to-CO reduction, remarkably surpassing other counterparts. The origin of the enhanced performance is attributed to the synergistic interplay of rGO@Ni(OH)2 reduction cocatalysts surrounding the semiconductors and Ni(OH)2 oxidation cocatalysts directly supported by the semiconductors, which mitigates the charge recombination, supplies highly active and selective sites for overall reactions, and preserves the semiconductors from photocorrosion. This work presents a new approach to regulating the position of dual cocatalysts and ameliorating the net efficiency of photoredox catalysis.

Maize HEAT UP-REGULATED GENE 1 plays vital roles in heat stress tolerance.

Increasing temperature is one of the major threats to maize growth and yield globally. Under heat stress conditions, intracellular protein homeostasis is seriously disturbed, leading to accumulation of abnormally folded proteins, especially in the endoplasmic reticulum (ER). Molecular chaperones are vital players in the renaturation process and in preventing protein aggregation. However, heat stress tolerance-associated chaperones are not well documented in maize. Here, we characterized the biological roles of HEAT UP-REGULATED GENE 1 (ZmHUG1) in maize. ZmHUG1 encodes a heat-inducible holdase-type molecular chaperone localized in the ER. Knockout mutant of ZmHUG1 exhibited remarkably enhanced sensitivity to heat stress. Accordingly, the zmhug1 mutant showed severe ER stress under high temperature. MAIZE PRENYLATED RAB ACCEPTOR 1.C1 (ZmPRA1.C1) was identified as a client of ZmHUG1, and heat-induced aggregation of ZmPRA1.C1 was accelerated in the zmhug1 mutant. Furthermore, the expression of ZmHUG1 was rapidly transactivated by ER stress sensor BASIC LEUCINE ZIPPER DOMAIN 60 (bZIP60) when heat stress occurred. This study reveals a ZmHUG1-based thermo-protective mechanism in maize.

Twenty-year span of global acute pancreatitis trends: A bibliometric analysis.

OBJECTIVE: This study aims to investigate the global research routine and trends of acute pancreatitis over the last twenty years based on the production, hotspots, and frontiers of published articles as well as to provide the global health system with a bibliometric reference. METHODS: The Web of Science core collection database was retrieved for acute pancreatitis original articles and review articles published from January 1, 1999 to May 17, 2020. Duplicates and discrete papers were excluded. Articles were evaluated for several characteristics including number of citations, publication time, country of origin, institution, journal and authorship. RESULTS: A total of 7001 articles originated from 94 countries and were published in 1263 journals. The China contributed most articles (1752) followed by USA (1214). The research was major published in specialized journals including the Pancreas (511) and pancreatology (351). Universities were the main institutions of science progress. High-impact articles focused on the fields of clinical medicine. A steady growth was observed in the last 20 years from 1999 to 2020. CONCLUSION: This comprehensive bibliometric study indicates that severe acute pancreatitis and necrotizing pancreatitis are significant topic in the acute pancreatitis research. The structured information may be helpful in understanding research trends, and locating research hot spots and gaps in this domain.

Trimethylamine N-oxide promotes hyperlipidemia acute pancreatitis via inflammatory response.

Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is involved in the regulation of lipid metabolism and inflammatory response; however, the role of TMAO in hyperlipidemia acute pancreatitis (HAP) is not clear. In this study, HAP mice were used as an animal model to explore the effects and possible mechanism of TMAO on HAP, which may provide new ideas for the treatment of HAP. Results found that the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, nonestesterified fatty acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, α-amylase, TMAO, and flavin-containing monooxygenase 3 were significantly increased, the levels of high-density lipoprotein cholesterol and insulin were significantly decreased, and there was an obvious pancreatic injury and inflammatory response in the model group. The choline analogue 3,3-dimethyl-1-butanol (DMB) treatment reversed the changes of serum biochemical parameters, alleviated the pancreatic tissue injury, and reduced the levels of inflammatory cytokines. Further studies of toll-like receptor (TLR)/p-glycoprotein 65 (p65) pathway found that the expressions of TLR2, TLR4, and p-p65/p65 in the model group were significantly increased, which was more obvious after Escherichia coli (Migula) Castellani & Chalmers treatment, while activation of the TLR/p65 pathway was inhibited by DMB. The results indicated that TMAO promotes HAP by promoting inflammatory response through TLR/p65 signaling pathway, suggesting that TMAO may be a potential target of HAP.