Incompatible and sterile insect techniques combined eliminate mosquitoes.

The radiation-based sterile insect technique (SIT) has successfully suppressed field populations of several insect pest species, but its effect on mosquito vector control has been limited. The related incompatible insect technique (IIT)-which uses sterilization caused by the maternally inherited endosymbiotic bacteria Wolbachia-is a promising alternative, but can be undermined by accidental release of females infected with the same Wolbachia strain as the released males. Here we show that combining incompatible and sterile insect techniques (IIT-SIT) enables near elimination of field populations of the world's most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT-SIT for mosquito vector control.

Arabidopsis HSFA9 Acts as a Regulator of Heat Response Gene Expression and the Acquisition of Thermotolerance and Seed Longevity.

Heat-shock transcription factors (HSFs) are crucial for regulating plant responses to heat and various stresses, as well as for maintaining normal cellular functions and plant development. HSFA9 and HSFA2 are two of the Arabidopsis class A HSFs and their expressions are dramatically induced in response to heat shock (HS) stress among all 21 Arabidopsis HSFs. However, the detailed biological roles of their cooperation have not been fully characterized. In this study, we employed an integrated approach that combined bioinformatics, molecular genetics and computational analysis to identify and validate the molecular mechanism that controls seed longevity and thermotolerance in Arabidopsis. The acquisition of tolerance to deterioration was accompanied by a significant transcriptional switch that involved the induction of primary metabolism, reactive oxygen species and unfolded protein response, as well as the regulation of genes involved in response to dehydration, heat and hypoxia. In addition, the cis-regulatory motif analysis in normal stored and controlled deterioration treatment (CDT) seeds confirmed the CDT-repressed genes with heat-shock element (HSE) in their promoters. Using a yeast two-hybrid and molecular dynamic interaction assay, it is shown that HSFA9 acted as a potential regulator that can interact with HSFA2. Moreover, the knock-out mutants of both HSFA9 and HSFA2 displayed a significant reduction in seed longevity. These novel findings link HSF transcription factors with seed deterioration tolerance and longevity.

Specific metabolic and cellular mechanisms of the vegetative desiccation tolerance in resurrection plants for adaptation to extreme dryness.

MAIN CONCLUSION: Substantial advancements have been made in our comprehension of vegetative desiccation tolerance in resurrection plants, and further research is still warranted to elucidate the mechanisms governing distinct cellular adaptations. Resurrection plants are commonly referred to as a small group of extremophile vascular plants that exhibit vegetative desiccation tolerance (VDT), meaning that their vegetative tissues can survive extreme drought stress (> 90% water loss) and subsequently recover rapidly upon rehydration. In contrast to most vascular plants, which typically employ water-saving strategies to resist partial water loss and optimize water absorption and utilization to a limited extent under moderate drought stress, ultimately succumbing to cell death when confronted with severe and extreme drought conditions, resurrection plants have evolved unique mechanisms of VDT, enabling them to maintain viability even in the absence of water for extended periods, permitting them to rejuvenate without harm upon water contact. Understanding the mechanisms associated with VDT in resurrection plants holds the promise of expanding our understanding of how plants adapt to exceedingly arid environments, a phenomenon increasingly prevalent due to global warming. This review offers an updated and comprehensive overview of recent advances in VDT within resurrection plants, with particular emphasis on elucidating the metabolic and cellular adaptations during desiccation, including the intricate processes of cell wall folding and the prevention of cell death. Furthermore, this review highlights existing unanswered questions in the field, suggests potential avenues for further research to gain deeper insights into the remarkable VDT adaptations observed in resurrection plants, and highlights the potential application of VDT-derived techniques in crop breeding to enhance tolerance to extreme drought stress.

Alterations of lung microbiota in lung transplant recipients with pneumocystis jirovecii pneumonia.

BACKGROUND: Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow. METHODS: In this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii, and analyzed the related clinical variables. RESULTS: BALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus, and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus, Pseudomonas guariconensis, Paracandidimonas soli, Acinetobacter colistiniresistens, and Castellaniella defragrans, which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3+CD45+, CD3+CD4+ and CD3+CD8+ T cells were deeply implicated in the alterations of lung microbiota in LTRs. CONCLUSIONS: This study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.

Trade-offs between root-secreted acid phosphatase and root morphology traits, and their contribution to phosphorus acquisition in Brassica napus.

Oilseed rape (Brassica napus) is one of the most important oil crops in the world and shows sensitivity to low phosphorus (P) availability. In many soils, organic P (Po) is the main component of the soil P pool. Po must be mineralised to Pi through phosphatases, and then taken up by plants. However, the relationship between root-secreted acid phosphatases (APase) and root morphology traits, two important P-acquisition strategies in response to P deficiency, is unclear among B. napus genotypes. This study aimed to understand their relationship and how they affect P acquisition, which is crucial for the sustainable utilisation of agricultural P resources. This study showed significant genotypic variations in root-secreted APase activity per unit root fresh weight (SAP) and total root-secreted APase activity per plant (total SAP) among 350 B. napus genotypes. Seed yield was positively correlated with total SAP but not significantly correlated with SAP. Six root traits of 18 B. napus genotypes with contrasting root biomass were compared under normal Pi, low Pi and Po. Genotypes with longer total root length (TRL) reduced SAP, but those with shorter TRL increased SAP under P deficiency. Additionally, TRL was important in P-acquisition under three P treatments, and total SAP was also important in P-acquisition under Po treatment. In conclusion, trade-offs existed between the two P-acquisition strategies among B. napus genotypes under P-deficient conditions. Total SAP was an important root trait under Po conditions. These results might help to breed B. napus with greater P-acquisition ability under low P availability conditions.

Aberrant HO-1/NQO1-Reactive Oxygen Species-ERK Signaling Pathway Contributes to Aggravation of TPA-Induced Irritant Contact Dermatitis in Nrf2-Deficient Mice.

NF-erythroid 2-related factor 2 (Nrf2) is a major transcription factor to protect cells against reactive oxygen species (ROS) and reactive toxicants. Meanwhile, Nrf2 can inhibit contact dermatitis through redox-dependent and -independent pathways. However, the underlying mechanisms of how Nrf2 mediates irritant contact dermatitis (ICD) are still unclear. In this article, we elucidated the role of Nrf2 in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute ICD. Our study demonstrated that the ear thickness, redness, swelling, and neutrophil infiltration were significantly increased, accompanied by increased expression of inflammatory cytokines (IL-1α, IL-1ß, IL-6, etc.) and decreased expression of antioxidant genes (HO-1 and NQO1) in Nrf2 knockout mice. Moreover, ERK phosphorylation was elevated in mouse embryonic fibroblasts (MEFs) from Nrf2 knockout mouse. Inhibition of ERK significantly alleviated TPA-induced cutaneous inflammation and ROS accumulation in MEFs derived from mouse. Conversely, ROS scavenging inhibited the ERK activation and TPA-induced inflammation in MEFs. Taken together, the findings illustrate the key role of the Nrf2/ROS/ERK signaling pathway in TPA-induced acute ICD.

Retracted: Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Rongfeng Zhang, Jianwei Liu, Shengpeng Yu, Dong Sun, Xiaohua Wang, Jingshu Fu, Jie Shen, Zhao Xie. Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair. Med Sci Monit, 2019; 25: 5572-5579. DOI: 10.12659/MSM.916838.

Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes.

Somatic hypermutation (SHM) and class-switch recombination (CSR) of the immunoglobulin (Ig) genes allow B cells to make antibodies that protect us against a wide variety of pathogens. SHM is mediated by activation-induced deaminase (AID), occurs at a million times higher frequency than other mutations in the mammalian genome, and is largely restricted to the variable (V) and switch (S) regions of Ig genes. Using the Ramos human Burkitt's lymphoma cell line, we find that H3K79me2/3 and its methyltransferase Dot1L are more abundant on the V region than on the constant (C) region, which does not undergo mutation. In primary naïve mouse B cells examined ex vivo, the H3K79me2/3 modification appears constitutively in the donor Sµ and is inducible in the recipient Sγ1 upon CSR stimulation. Knockout and inhibition of Dot1L in Ramos cells significantly reduces V region mutation and the abundance of H3K79me2/3 on the V region and is associated with a decrease of polymerase II (Pol II) and its S2 phosphorylated form at the IgH locus. Knockout of Dot1L also decreases the abundance of BRD4 and CDK9 (a subunit of the P-TEFb complex) on the V region, and this is accompanied by decreased nascent transcripts throughout the IgH gene. Treatment with JQ1 (inhibitor of BRD4) or DRB (inhibitor of CDK9) decreases SHM and the abundance of Pol II S2P at the IgH locus. Since all these factors play a role in transcription elongation, our studies reinforce the idea that the chromatin context and dynamics of transcription are critical for SHM.

DLL1 orchestrates CD8+ T cells to induce long-term vascular normalization and tumor regression.

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.

Lightweight Detection Method for X-ray Security Inspection with Occlusion.

Identifying the classes and locations of prohibited items is the target of security inspection. However, X-ray security inspection images with insufficient feature extraction, imbalance between easy and hard samples, and occlusion lead to poor detection accuracy. To address the above problems, an object-detection method based on YOLOv8 is proposed. Firstly, an ASFF (adaptive spatial feature fusion) and a weighted feature concatenation algorithm are introduced to fully extract the scale features from input images. In this way, the model can learn further details in training. Secondly, CoordAtt (coordinate attention module), which belongs to the hybrid attention mechanism, is embedded to enhance the learning of features of interest. Then, the slide loss function is introduced to balance the simple samples and the difficult samples. Finally, Soft-NMS (non-maximum suppression) is introduced to resist the conditions containing occlusion. The experimental result shows that mAP (mean average precision) achieves 90.2%, 90.5%, 79.1%, and 91.4% on the Easy, Hard, and Hidden sets of the PIDray and SIXray public test set, respectively. Contrasted with original model, the mAP of our proposed YOLOv8n model increased by 2.7%, 3.1%, 9.3%, and 2.4%, respectively. Furthermore, the parameter count of the modified YOLOv8n model is roughly only 3 million.

Construction of an Early Risk Prediction Model for Type 2 Diabetic Peripheral Neuropathy Based on Random Forest.

Diabetic peripheral neuropathy is a major cause of disability and death in the later stages of diabetes. A retrospective chart review was performed using a hospital-based electronic medical record database to identify 1020 patients who met the criteria. The objective of this study was to explore and analyze the early risk factors for peripheral neuropathy in patients with type 2 diabetes, even in the absence of specific clinical symptoms or signs. Finally, the random forest algorithm was used to rank the influencing factors and construct a predictive model, and then the model performance was evaluated. Logistic regression analysis revealed that vitamin D plays a crucial protective role in preventing diabetic peripheral neuropathy. The top three risk factors with significant contributions to the model in the random forest algorithm eigenvalue ranking were glycosylated hemoglobin, disease duration, and vitamin D. The areas under the receiver operating characteristic curve of the model ware 0.90. The accuracy, precision, specificity, and sensitivity were 0.85, 0.83, 0.92, and 0.71, respectively. The predictive model, which is based on the random forest algorithm, is intended to support clinical decision-making by healthcare professionals and help them target timely interventions to key factors in early diabetic peripheral neuropathy.

CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-ß-catenin signalling pathway in serous ovarian cancer.

BACKGROUND: Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC. METHODS: The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-ß-catenin signalling pathway. RESULTS: Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-ß-catenin signalling pathway. CONCLUSIONS: The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-ß-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Serous ovarian cancer is a type of gynecological malignant tumour with high mortality rates. Understanding this disease is crucial for improving treatments and enhancing patient survival. In our study, we investigated a protein called CST2 and its role in serous ovarian cancer. We found that CST2 levels vary among patients and are associated with the progression of cancer and the prognosis of the patient, which could be valuable for future diagnosis and treatment strategies. However, further research is needed to validate these findings. Despite its limitations, our findings suggest that CST2 holds promise as a potential biomarker for detecting serous ovarian cancer and as a therapeutic target in the management of patients with this type of cancer.

[Advance of research on Hereditary spastic paraplegia type 4].

Spastic paraplegia type 4 (SPG4) is the most common type of autosomally inherited spastic paraplegia. Its main clinical features include typical simple hereditary spastic paraplegia, with neurological impairments limited to lower limb spasticity, hypertonic bladder dysfunction, and mild weakening of lower limb vibration sensation, without accompanying features such as nerve atrophy, ataxia, cognitive impairment, seizures, and muscle tone disorders. SPAST is the main pathogenic gene underlying SPG4, and various pathogenic SPAST variants have been discovered. This disease has featured a high degree of clinical heterogeneity, and the same pathogenic variant can have different age of onset and severity among different patients and even within the same family. There is a lack of systematic research on the correlation between the genotype and phenotype of SPG4, and the pathogenic mechanism has remained controversial. This article has provided a review for the clinical characteristics, pathogenic gene characteristics, correlation between the genotype and phenotype, and pathogenic mechanism of this disease, with an aim to provide reference for its clinical diagnosis and treatment.

YAP promotes AP-1 expression in tubular epithelial cells in the kidney.

Chronic kidney disease (CKD) is a major health problem. Kidney fibrosis is a hallmark and final common pathway of CKD. The Hippo/yes-associated protein (YAP) pathway regulates organ size, inflammation, and tumorigenesis. Our previous study demonstrated tubular YAP activation by tubule-specific double knockout of mammalian STE20-like protein kinase 1/2 (Mst1/2) induced CKD in mice, but the underlying mechanisms remain to be fully elucidated. Activator protein (AP)-1 activation was found to promote tubular atrophy and tubulointerstitial fibrosis. Therefore, we studied whether YAP regulates AP-1 expression in the kidney. We found that expression of various AP-1 components was induced in kidneys subjected to unilateral ureteric obstruction and in Mst1/2 double knockout kidneys, and these inductions were blocked by deletion of Yap in tubular cells, with Fosl1 being most affected compared with other AP-1 genes. Inhibition of Yap also most highly suppressed Fosl1 expression among AP-1 genes in HK-2 and IMCD3 renal tubular cells. YAP bound to the Fosl1 promoter and promoted Fosl1 promoter-luciferase activity. Our results suggest that YAP controls AP-1 expression and that Fosl1 is the primary target of YAP in renal tubular cells.NEW & NOTEWORTHY Yes-associated protein (YAP) activation leads to tubular injury, renal inflammation, and fibrosis, but the underlying mechanisms are not fully understood. We now provide genetic evidence that YAP promotes activator protein-1 expression and that Fosl1 is the primary target of YAP in renal tubular cells.

Dynamics of chromatin accessibility and genome wide control of desiccation tolerance in the resurrection plant Haberlea rhodopensis.

BACKGROUND: Drought is one of the main consequences of global climate change and this problem is expected to intensify in the future. Resurrection plants evolved the ability to withstand the negative impact of long periods of almost complete desiccation and to recover at rewatering. In this respect, many physiological, transcriptomic, proteomic and genomic investigations have been performed in recent years, however, few epigenetic control studies have been performed on these valuable desiccation-tolerant plants so far. RESULTS: In the present study, for the first time for resurrection plants we provide evidences about the differential chromatin accessibility of Haberlea rhodopensis during desiccation stress by ATAC-seq (Assay for Transposase Accessible Chromatin with high-throughput sequencing). Based on gene similarity between species, we used the available genome of the closely related resurrection plant Dorcoceras hygrometricum to identify approximately nine hundred transposase hypersensitive sites (THSs) in H. rhodopensis. The majority of them corresponds to proximal and distal regulatory elements of different genes involved in photosynthesis, carbon metabolism, synthesis of secondary metabolites, cell signalling and transcriptional regulation, cell growth, cell wall, stomata conditioning, chaperons, oxidative stress, autophagy and others. Various types of binding motifs recognized by several families of transcription factors have been enriched from the THSs found in different stages of drought. Further, we used the previously published RNA-seq data from H. rhodopensis to evaluate the expression of transcription factors putatively interacting with the enriched motifs, and the potential correlation between the identified THS and the expression of their corresponding genes. CONCLUSIONS: These results provide a blueprint for investigating the epigenetic regulation of desiccation tolerance in resurrection plant H. rhodopensis and comparative genomics between resurrection and non-resurrection species with available genome information.

Electrostatic discharge induced degradation of optical-electrical properties and defect evolution of GaAs-based oxide-confined VCSELs.

GaAs-based oxide-confined vertical-cavity surface-emitting lasers (VCSELs) exhibit relatively low resistance against reliability-related damage. In order to gain a deeper understanding of the degradation and failure mechanism in oxide-confined VCSELs caused by electrostatic discharge (ESD)-induced defect proliferation, we investigated the effects of ESD stress on the degradation of optical-electrical characteristics and the evolution of defects in VCSELs under human body model test condition. The degradation threshold values for forward and reverse ESD pulse amplitudes were estimated to be 200 V and -50 V, respectively. Notably, VCSELs demonstrated greater sensitivity to reverse bias ESD compared to forward bias ESD. Analysis of optical emission and microstructure provided evidence that the device failure is attributed to an increase in ESD current density, leading to the multiplication of dark line defects (DLDs) originating from the edge of the device's oxide aperture. The formation of defects occurred suddenly in discrete events within small regions, rather than progressing gradually and uniformly. These defects propagated and led to damage across the entire active region. We believe that our results would be meaningful for improving the reliability of VCSEL in the future.

Above 20†GHz high frequency operation of mid-infrared doughnut-shaped microcavity quantum cascade lasers.

Microresonator-based high-speed single-mode quantum cascade lasers are ideal candidates for on-chip optical data interconnection and high sensitivity gas sensing in the mid-infrared spectral range. In this paper, we propose a high frequency operation of single-mode doughnut-shaped microcavity quantum cascade laser at ∼4.6 µm. By leveraging compact micro-ring resonators and integrating with grounded coplanar waveguide transmission lines, we have greatly reduced the parasitics originating from both the device and wire bonding. In addition, a selective heat dissipation scheme was introduced to improve the thermal characteristics of the device by semi-insulating InP infill regrowth. The highest continuous wave operating temperature of the device reaches 288 K. A maximum -3 dB bandwidth of 11 GHz and a cut-off frequency exceeding 20 GHz in a microwave rectification technique are obtained. Benefiting from the notch at the short axis of the microcavity resonator, a highly customized far-field profile with an in-plane beam divergence angle of 2.4° is achieved.

Genetic variation in the glycine-rich protein gene BnGRP1 contributes to low phosphorus tolerance in Brassica napus.

Lack of phosphorus (P) is a major environmental factor affecting rapeseed (Brassica napus. L) root growth and development. For breeding purposes, it is crucial to identify the molecular mechanisms underlying root system architecture traits that confer low-P tolerance in rapeseed. Natural variations in the glycine-rich protein gene BnGRP1 were analysed in the natural population of 400 rapeseed cultivars under low-P stress through genome-wide association study and transcriptome analysis. Based on 11 single nucleotide polymorphism mutations in the BnGRP1 sequence, 10 haplotypes (Hap) were formed. Compared with the other types, the cultivar BnGRP1Hap1 in the panel demonstrated the longest root length and heaviest root weight. BnGRP1Hap1 overexpression in rapeseed led to enhanced low-P tolerance. CRISPR/Cas9-derived BnGRP1Hap4 knockout mutations in rapeseed can lead to sensitivity to low-P stress. Furthermore, BnGRP1Hap1 influences the expression of the phosphate transporter 1 gene (PHT1) associated with P absorption. Overall, the findings of this study highlight new insights into the mechanisms of GRP1 enhancement of low-P tolerance in rapeseed.

Plasmodesmal endoplasmic reticulum proteins regulate intercellular trafficking of cucumber mosaic virus in Arabidopsis.

Plasmodesmata (PD) are plasma membrane-lined cytoplasmic nanochannels that mediate cell-to-cell communication across the cell wall. A range of proteins are embedded in the PD plasma membrane and endoplasmic reticulum (ER), and function in regulating PD-mediated symplasmic trafficking. However, knowledge of the nature and function of the ER-embedded proteins in the intercellular movement of non-cell-autonomous proteins is limited. Here, we report the functional characterization of two ER luminal proteins, AtBiP1/2, and two ER integral membrane proteins, AtERdj2A/B, which are located within the PD. These PD proteins were identified as interacting proteins with cucumber mosaic virus (CMV) movement protein (MP) in co-immunoprecipitation studies using an Arabidopsis-derived plasmodesmal-enriched cell wall protein preparation (PECP). The AtBiP1/2 PD location was confirmed by TEM-based immunolocalization, and their AtBiP1/2 signal peptides (SPs) function in PD targeting. In vitro/in vivo pull-down assays revealed the association between AtBiP1/2 and CMV MP, mediated by AtERdj2A, through the formation of an AtBiP1/2-AtERdj2-CMV MP complex within PD. The role of this complex in CMV infection was established, as systemic infection was retarded in bip1/bip2w and erdj2b mutants. Our findings provide a model for a mechanism by which the CMV MP mediates cell-to-cell trafficking of its viral ribonucleoprotein complex.

Dihydromyricetin attenuates cisplatin-induced acute kidney injury by reducing oxidative stress, inflammation and ferroptosis.

BACKGROUND: Cisplatin is effective against various types of cancers. However, its clinical application is limited owing to its adverse effects, especially acute kidney injury (AKI). Dihydromyricetin (DHM), a flavonoid derived from Ampelopsis grossedentata, has varied pharmacological activities. This research aimed to determine the molecular mechanism for cisplatin-induced AKI. METHODS: A murine model of cisplatin-induced AKI (22 mg/kg, I.P.) and a HK-2 cell model of cisplatin-induced damage (30 µM) were established to evaluate the protective function of DHM. Renal dysfunction markers, renal morphology and potential signaling pathways were investigated. RESULTS: DHM decreased the levels of renal function biomarkers (blood urea nitrogen and serum creatinine), mitigated renal morphological damage, and downregulated the protein levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. It upregulated the expression levels of antioxidant enzymes (superoxide dismutase and catalase expression), nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream proteins, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, thus eventually reducing cisplatin-induced reactive oxygen species (ROS) production. Moreover, DHM partially inhibited the phosphorylation of the active fragments of caspase-8 and -3 and mitogen-activated protein kinase and restored glutathione peroxidase 4 expression, which attenuated renal apoptosis and ferroptosis in cisplatin-treated animals. DHM also mitigated the activation of NLRP3 inflammasome and nuclear factor (NF)-κB, attenuating the inflammatory response. In addition, it reduced cisplatin-induced HK-2 cell apoptosis and ROS production, both of which were blocked by the Nrf2 inhibitor ML385. CONCLUSIONS: DHM suppressed cisplatin-induced oxidative stress, inflammation and ferroptosis probably through regulating of Nrf2/HO-1, MAPK and NF-κB signaling pathways.