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1.
Nefrologia (Engl Ed) ; 44(2): 139-149, 2024.
Article En | MEDLINE | ID: mdl-38697694

Losartan is widely used in the treatment of chronic kidney disease (CKD) and has achieved good clinical efficacy, but its exact mechanism is not clear. We performed high-throughput sequencing (HTS) technology to screen the potential target of losartan in treating CKD. According to the HTS results, we found that the tumor necrosis factor (TNF) signal pathway was enriched. Therefore, we conducted in vivo and in vitro experiments to verify it. We found that TNF signal pathway was activated in both unilateral ureteral obstruction (UUO) rats and human proximal renal tubular epithelial cells (HK-2) treated with transforming growth factor-ß1 (TGF-ß1), while losartan can significantly inhibit TNF signal pathway as well as the expression of fibrosis related genes (such as COL-1, α-SMA and Vimentin). These data suggest that losartan may ameliorate renal fibrosis through modulating the TNF pathway.


Fibrosis , Losartan , Signal Transduction , Tumor Necrosis Factor-alpha , Losartan/pharmacology , Losartan/therapeutic use , Animals , Signal Transduction/drug effects , Rats , Male , Humans , Ureteral Obstruction/complications , Ureteral Obstruction/drug therapy , Rats, Sprague-Dawley , Kidney/pathology , Kidney/drug effects , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/etiology
2.
ACS Nano ; 18(19): 12295-12310, 2024 May 14.
Article En | MEDLINE | ID: mdl-38695532

Immune checkpoint blockade (ICB) has brought tremendous clinical progress, but its therapeutic outcome can be limited due to insufficient activation of dendritic cells (DCs) and insufficient infiltration of cytotoxic T lymphocytes (CTLs). Evoking immunogenic cell death (ICD) is one promising strategy to promote DC maturation and elicit T-cell immunity, whereas low levels of ICD induction of solid tumors restrict durable antitumor efficacy. Herein, we report a genetically edited cell membrane-coated cascade nanozyme (gCM@MnAu) for enhanced cancer immunotherapy by inducing ICD and activating the stimulator of the interferon genes (STING) pathway. In the tumor microenvironment (TME), the gCM@MnAu initiates a cascade reaction and generates abundant cytotoxic hydroxyl (•OH), resulting in improved chemodynamic therapy (CDT) and boosted ICD activation. In addition, released Mn2+ during the cascade reaction activates the STING pathway and further promotes the DC maturation. More importantly, activated immunogenicity in the TME significantly improves gCM-mediated PD-1/PD-L1 checkpoint blockade therapy by eliciting systemic antitumor responses. In breast cancer subcutaneous and lung metastasis models, the gCM@MnAu showed synergistically enhanced therapeutic effects and significantly prolonged the survival of mice. This work develops a genetically edited nanozyme-based therapeutic strategy to improve DC-mediated cross-priming of T cells against poorly immunogenic solid tumors.


Immunotherapy , Animals , Mice , Female , Humans , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Mice, Inbred BALB C , Cell Line, Tumor , Immunogenic Cell Death/drug effects , Membrane Proteins/genetics , Membrane Proteins/immunology , Nanoparticles/chemistry
3.
Plant Physiol Biochem ; 210: 108626, 2024 May.
Article En | MEDLINE | ID: mdl-38615443

Stomatal operation is crucial for optimising plant water and gas exchange and represents a major trait conferring abiotic stress tolerance in plants. About 56% of agricultural land around the globe is classified as acidic, and Al toxicity is a major limiting factor affecting plant performance in such soils. While most of the research work in the field discusses the impact of major abiotic stresses such as drought or salinity on stomatal operation, the impact of toxic metals and, specifically aluminium (Al) on stomatal operation receives much less attention. We aim to fill this knowledge gap by summarizing the current knowledge of the adverse effects of acid soils on plant stomatal development and operation. We summarised the knowledge of stomatal responses to both long-term and transient Al exposure, explored molecular mechanisms underlying plant adaptations to Al toxicity, and elucidated regulatory networks that alleviate Al toxicity. It is shown that Al-induced stomatal closure involves regulations of core stomatal signalling components, such as ROS, NO, and CO2 and key elements of ABA signalling. We also discuss possible targets and pathway to modify stomatal operation in plants grown in acid soils thus reducing the impact of Al toxicity on plant growth and yield.


Aluminum , Plant Stomata , Soil , Aluminum/toxicity , Plant Stomata/drug effects , Plant Stomata/physiology , Soil/chemistry , Crops, Agricultural/metabolism , Crops, Agricultural/drug effects , Crops, Agricultural/growth & development , Adaptation, Physiological/drug effects
4.
Nefrología (Madrid) ; 44(2): 139-149, Mar-Abr. 2024. tab, graf
Article En | IBECS | ID: ibc-231563

Losartan is widely used in the treatment of chronic kidney disease (CKD) and has achieved good clinical efficacy, but its exact mechanism is not clear. We performed high-throughput sequencing (HTS) technology to screen the potential target of losartan in treating CKD. According to the HTS results, we found that the tumor necrosis factor (TNF) signal pathway was enriched. Therefore, we conducted in vivo and in vitro experiments to verify it. We found that TNF signal pathway was activated in both unilateral ureteral obstruction (UUO) rats and human proximal renal tubular epithelial cells (HK-2) treated with transforming growth factor-β1 (TGF-β1), while losartan can significantly inhibit TNF signal pathway as well as the expression of fibrosis related genes (such as COL-1, α-SMA and Vimentin). These data suggest that losartan may ameliorate renal fibrosis through modulating the TNF pathway.(AU)


El Losartán es ampliamente utilizado en el tratamiento de la enfermedad renal crónica (CKD) y ha logrado buenos resultados clínicos, pero su mecanismo exacto aún no está claro. Utilizamos la técnica de secuenciación de alto rendimiento (HTS) para detectar posibles dianas de losartán para el tratamiento de la CKD. Según los resultados de HTS, encontramos un enriquecimiento de la vía de señalización del factor de necrosis tumoral (TNF). Así, realizamos experimentos in vivo e in vitro para verificar esto. Encontramos que, tanto en ratas con obstrucción ureteral unilateral (uuo) como en células epiteliales tubulares renales proximal humanas (HK-2) tratadas con factor de crecimiento transformador β1 (TGF-β1), se activó la vía de señalización del TNF. El losartán inhibe significativamente la expresión de las vías de señalización del TNF y genes relacionados con la fibrosis, como COL-1, α-SMA y vicentin. Estos datos sugieren que el losartán puede mejorar la fibrosis renal regulando la vía del TNF.(AU)


Humans , Male , Female , Tumor Necrosis Factors , Losartan/administration & dosage , Renal Insufficiency, Chronic/drug therapy , Fibrosis/drug therapy , High-Throughput Nucleotide Sequencing , Nephrology , Kidney Diseases
5.
Physiol Plant ; 176(2): e14259, 2024.
Article En | MEDLINE | ID: mdl-38511474

Proteins of the armadillo repeat gene family play important roles in plant pathogen response. Here, 169 armadillo (ARM) genes were identified in upland cotton (Gossypium hirsutum). Phylogenetic analysis grouped these into 11 subfamilies, with conserved protein structures within each subfamily. The results signify that the expansion of the gene family occurred via whole genome duplication and dispersed duplication. Expression profiling and network analysis suggest that GhARM144 may regulate cotton resistance to Verticillium dahliae. GhARM144 was upregulated in roots by V. dahliae infection or salicylic acid treatment. This upregulation indicates a negative regulatory role of GhARM144' in the cotton immune responses, potentially by manipulating salicylic acid biosynthesis. Protein interaction studies found that GhARM144 associates with an osmotin-like protein, GhOSM34, at the plasma membrane. Silencing GhOSM34 reduced the resistance to V. dahliae, suggesting it may play a positive regulatory role. The results demonstrate that GhARM144 modulates cotton immunity through interaction with GhOSM34 and salicylic acid signalling. Further study of these proteins may yield insights into disease resistance mechanisms in cotton and other plants.


Acremonium , Ascomycota , Verticillium , Phylogeny , Verticillium/metabolism , Gossypium/genetics , Gossypium/metabolism , Salicylic Acid/metabolism , Disease Resistance/genetics , Plant Diseases/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant
6.
Int Urol Nephrol ; 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38498274

Chronic kidney disease (CKD), including chronic glomerulonephritis, IgA nephropathy and diabetic nephropathy, are common chronic diseases characterized by structural damage and functional decline of the kidneys. The current treatment of CKD is symptom relief. Several studies have reported that the phosphatidylinositol 3 kinases (PI3K)/protein kinase B (Akt) signaling pathway is a pathway closely related to the pathological process of CKD. It can ameliorate kidney damage by inhibiting this signal pathway which is involved with inflammation, oxidative stress, cell apoptosis, epithelial mesenchymal transformation (EMT) and autophagy. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in CKD-induced inflammatory response, apoptosis, autophagy and EMT. We also summarize the latest evidence on treating CKD by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of CKD, and identify potential challenges in developing these clinical therapeutic CKD strategies, and provide appropriate solutions.

7.
Adv Mater ; : e2311803, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38519052

Neuroinflammation has emerged as a major concern in ischemic stroke therapy because it exacebates neurological dysfunction and suppresses neurological recovery after ischemia/reperfusion. Fingolimod hydrochloride (FTY720) is an FDA-approved anti-inflammatory drug which exhibits potential neuroprotective effects in ischemic brain parenchyma. However, delivering a sufficient amount of FTY720 through the blood-brain barrier into brain lesions without inducing severe cardiovascular side effects remains challenging. Here, a neutrophil membrane-camouflaged polyprodrug nanomedicine that can migrate into ischemic brain tissues and in situ release FTY720 in response to elevated levels of reactive oxygen species. This nanomedicine delivers 15.2-fold more FTY720 into the ischemic brain and significantly reduces the risk of cardiotoxicity and infection compared with intravenously administered free drug. In addition, single-cell RNA-sequencing analysis identifies that the nanomedicine attenuates poststroke inflammation by reprogramming microglia toward anti-inflammatory phenotypes, which is realized via modulating Cebpb-regulated activation of NLRP3 inflammasomes and secretion of CXCL2 chemokine. This study offers new insights into the design and fabrication of polyprodrug nanomedicines for effective suppression of inflammation in ischemic stroke therapy.

8.
ACS Appl Mater Interfaces ; 16(13): 16678-16686, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38503721

Photodetectors with a broad-band response range are widely used in many fields and are regarded as pivotal components of the modern miniaturized electronics industry. However, commercial broad-band photodetectors composed of traditional bulk semiconductor materials are still limited by complex preparation techniques, high costs, and a lack of mechanical strength and flexibility, which are difficult to satisfy the increasing demand for flexible and wearable optoelectronics. Therefore, researchers have been devoted to finding new strategies to obtain flexible, stable, and high-performance broad-band photodetectors. In this work, a novel self-assembled BiGaSeAs composite superlattice-structured nanowire was developed with a simple chemical vapor deposition method for easy fabrication. After the device assembling, the photodetector showed outstanding performance in terms of obvious Ion/Ioff (13.9), broad-band photoresponse (365-940 nm), excellent responsivity (1007.67 A/W), high detectivity (9.38 × 109 Jones), and rapid response (21 and 23 ms). The formation of microheterojunctions among various materials inside the nanowires also contributed to their extended broad-spectrum response and outstanding detection ability. These results indicate that the BiGaSeAs nanowires have potential applications in the field of flexible and wearable electronics.

9.
Theor Appl Genet ; 137(4): 86, 2024 Mar 21.
Article En | MEDLINE | ID: mdl-38512498

KEY MESSAGE: Recent developments in understanding the distribution and distinctive features of recombination hotspots are reviewed and approaches are proposed to increase recombination frequency in coldspot regions. Recombination events during meiosis provide the foundation and premise for creating new varieties of crops. The frequency of recombination in different genomic regions differs across eukaryote species, with recombination generally occurring more frequently at the ends of chromosomes. In most crop species, recombination is rare in centromeric regions. If a desired gene variant is linked in repulsion with an undesired variant of a second gene in a region with a low recombination rate, obtaining a recombinant plant combining two favorable alleles will be challenging. Traditional crop breeding involves combining desirable genes from parental plants into offspring. Therefore, understanding the mechanisms of recombination and factors affecting the occurrence of meiotic recombination is important for crop breeding. Here, we review chromosome recombination types, recombination mechanisms, genes and proteins involved in the meiotic recombination process, recombination hotspots and their regulation systems and discuss how to increase recombination frequency in recombination coldspot regions.


Homologous Recombination , Plant Breeding , Genome , Centromere , Crops, Agricultural/genetics , Meiosis/genetics
10.
Phytopathology ; 2024 Mar 07.
Article En | MEDLINE | ID: mdl-38451589

Scald is one of the major economically important foliar diseases in barley, causing susceptible varieties up to 40% of yield loss. The identification of quantitative trait loci (QTL) and elite alleles that confer resistance to scald is imperative in reducing the threats to barley production. In this study, genome-wide association studies (GWAS) were conducted using a panel of 697 barley genotypes to identify QTL for scald resistance. Field experiments were conducted over three consecutive years. Among different models used for GWAS analysis, FarmCPU was shown to be the best-suited model. Nineteen significant marker-trait associations (MTAs) related to scald resistance were identified across six different chromosomes. Eleven of these MTAs correspond to previously reported scald resistance genes Rrs1, Rrs4, and Rrs2, respectively. Eight novel MTAs were identified in this study with the candidate genes encoding a diverse class of proteins including region leucine-rich repeats (LRR), AP2/ERF transcription factor, homeodomain-leucine zipper, and protein kinases family proteins. The combination of identified superior alleles significantly reduces disease severity scores. The results will be valuable for marker-assisted breeding for developing scald-resistant varieties.

11.
Small ; : e2311702, 2024 Mar 08.
Article En | MEDLINE | ID: mdl-38456371

The PD1/PD-L1 immune checkpoint blocking is a promising therapy, while immunosuppressive tumor microenvironment (TME) and poor tumor penetration of therapeutic antibodies limit its efficacy. Repolarization of tumor-associated macrophages (TAMs) offers a potential method to ameliorate immunosuppression of TME and further boost T cell antitumor immunity. Herein, hybrid cell membrane biomimetic nanovesicles (hNVs) are developed by fusing M1 macrophage-derived nanovesicles (M1-NVs) and PD1-overexpressed tumor cell-derived nanovesicles (PD1-NVs) to improve cancer immunotherapy. The M1-NVs promote the transformation of M2-like TAMs to M1-like phenotype and further increase the release of pro-inflammatory cytokines, resulting in improved immunosuppressive TME. Concurrently, the PD1-NVs block PD1/PD-L1 pathway, which boosts cancer immunotherapy when combined with M1-NVs. In a breast cancer mouse model, the hNVs efficiently accumulate at the tumor site after intravenous injection and significantly inhibit the tumor growth. Mechanically, the M1 macrophages and CD8+ T lymphocytes in TME increase by twofold after the treatment, indicating effective immune activation. These results suggest the hNVs as a promising strategy to integrate TME improvement with PD1/PD-L1 blockade for cancer immunotherapy.

12.
Theor Appl Genet ; 137(3): 50, 2024 Feb 16.
Article En | MEDLINE | ID: mdl-38363421

KEY MESSAGE: Two new major QTL were identified for powdery mildew resistance. We confirmed that the QTL on 7HS contributed mainly to the adult-plant resistance, while another one on chromosome arm 1HS made a significant contribution to the seedling resistance. Powdery mildew (PM), caused by Blumeria hordei, can occur at all post emergent stages of barley and constantly threatens crop production. To identify more genes for effective resistance to powdery mildew for use in breeding programs, 696 barley accessions collected from different regions of the world were evaluated for PM resistance at seedling and adult growth stages in three different states of Australia. These barley accessions were genotyped using DArTSeq with over 18,000 markers for a genome-wide association study (GWAS). Using the FarmCPU model, 54 markers showed significant associations with PM resistance scored at the seedling and adult-plant stages in different states of Australia. Another 40 markers showed tentative associations (LOD > 4.0) with resistance. These markers are distributed across all seven barley chromosomes. Most of them were grouped into eleven QTL regions, coinciding with the locations of most of the reported resistance genes. Two major MTAs were identified on chromosome arms 3HS and 5HL, with one on 3HS contributing to adult plant resistance and the one on 5HL to both seedling and adult plant resistance. An MTA on 7HS contributed mainly to the adult-plant resistance, while another one on chromosome arm 1HS made a significant contribution to the seedling resistance.


Ascomycota , Hordeum , Hordeum/genetics , Genome-Wide Association Study , Seedlings/genetics , Genetic Markers , Ascomycota/genetics , Plant Breeding , Plant Diseases/genetics , Disease Resistance/genetics
13.
Dalton Trans ; 53(9): 4291-4298, 2024 Feb 27.
Article En | MEDLINE | ID: mdl-38345325

Studying the effect of morphology on the circularly polarized luminescence (CPL) of chiral molecular materials is important for the development of CPL-active materials for applications. Herein, we report that the morphology of Gd(NO3)3/R-,S-AnempH2 [AnempH2 = (1-anthrylethylamino)methylphosphonic acid] assemblies can be controlled by solvent modulation to form spiral bundles Gd(R-,S-AnempH)3·2H2O (R-,S-1), crystals Gd(R-,S-AnempH)3·2H2O (R-,S-2) and spindle-shaped particles Gd(R-,S-AnempH)3·3H2O·0.5DMF (R-,S-3) with similar chain structures. Interestingly, R-,S-1 are CPL active and show the highest value of dissymmetric factor among the three pairs of enantiomers (|glum| = 2.1 × 10-3), which is 2.8 times larger than that of R-,S-2, while R-,S-3 are CPL inactive with |glum| ≈ 0. This work provides a new route to control the morphology of chiral coordination polymers and improve their CPL performance.

14.
Neurochem Int ; 175: 105676, 2024 May.
Article En | MEDLINE | ID: mdl-38336256

BACKGROUND: Microglia-mediated neuroinflammation is the major contributor to the secondary brain injury of ischemic stroke. NLRP3 is one of the major components of ischemia-induced microglial activation. Echinatin, a chalcone found in licorice, was reported to have the activity of anti-inflammation and antioxidant. However, the relative study of echinatin in microglia or ischemic stroke is still unclear. METHODS: We intravenously injected echinatin or vehicle into adult ischemic male C57/BL6J mice induced by 60-min transient middle cerebral artery occlusion (tMCAO). The intraperitoneal injection was performed 4.5 h after reperfusion and then daily for 2 more days. Infarct size, blood brain barrier (BBB) leakage, neurobehavioral tests, and microglial-mediated inflammatory reaction were examined to assess the outcomes of echinatin treatment. LPS and LPS/ATP stimulation on primary microglia were used to explore the underlying anti-inflammatory mechanism of echinatin. RESULTS: Echinatin treatment efficiently decreased the infarct size, alleviated blood brain barrier (BBB) damage, suppressed microglial activation, reduced the production of inflammatory factors (e.g., IL-1ß, IL-6, IL-18, TNF-α, iNOS, COX2), and relieved post-stroke neurological defects in tMCAO mice. Mechanistically, we found that echinatin could suppress the NLRP3 assembly and reduce the production of inflammatory mediators independently of NF-κB and monoamine oxidase (MAO). CONCLUSION: Based on our study, we have identified echinatin as a promising therapeutic strategy for the treatment of ischemic stroke.


Brain Injuries , Brain Ischemia , Chalcones , Ischemic Stroke , Reperfusion Injury , Mice , Male , Animals , NLR Family, Pyrin Domain-Containing 3 Protein , Neuroinflammatory Diseases , Lipopolysaccharides , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/complications , Infarction/complications , Infarction/drug therapy , Anti-Inflammatory Agents/therapeutic use , Brain Injuries/drug therapy , Ischemic Stroke/drug therapy , Brain Ischemia/drug therapy , Brain Ischemia/prevention & control , Brain Ischemia/complications , Microglia , Reperfusion Injury/drug therapy
15.
Adv Healthc Mater ; : e2400068, 2024 Feb 06.
Article En | MEDLINE | ID: mdl-38320299

Cancer nanovaccines have attracted widespread attention by inducing potent cytotoxic T cell responses to improve immune checkpoint blockade (ICB) therapy, while the lack of co-stimulatory molecules limits their clinical applications. Here, a genetically engineered cancer cytomembrane nanovaccine is reported that simultaneously overexpresses co-stimulatory molecule CD40L and immune checkpoint inhibitor PD1 to elicit robust antitumor immunity for cancer immunotherapy. The CD40L and tumor antigens inherited from cancer cytomembranes effectively stimulate dendritic cell (DC)-mediated immune activation of cytotoxic T cells, while the PD1 on cancer cytomembranes significantly blocks PD1/PD-L1 signaling pathway, synergistically stimulating antitumor immune responses. Benefiting from the targeting ability of cancer cytomembranes, this nanovaccines formula shows an enhanced lymph node trafficking and retention. Compared with original cancer cytomembranes, this genetically engineered nanovaccine induces twofold DC maturation and shows satisfactory precaution efficacy in a breast tumor mouse model. This genetically engineered cytomembrane nanovaccine offers a simple, safe, and robust strategy by incorporating cytomembrane components and co-stimulatory molecules for enhanced cancer immunotherapy.

16.
ACS Appl Bio Mater ; 7(2): 1125-1134, 2024 Feb 19.
Article En | MEDLINE | ID: mdl-38319146

Cutaneous trauma repair is still a challenge in the clinic due to the scar formation and slow healing rate, especially for diabetic patients. Various drug-loading wound dressings have been explored to solve this problem. Mesenchymal stem cell (MSC)-derived exosomes have been considered as a potential cell-free drug because of their anti-inflammation function and tissue repair property that are comparable to that of MSCs. Herein, a composite wound dressing (Exo/Gel) consisting of the chitosan hydrogel and adipose MSC-derived exosome (ADMSC-Exo) was designed and fabricated by a physical mixing method to promote the skin full-thickness wound repair. The exosomes were slowly released from the Exo/Gel dressing with the degradation of the chitosan hydrogel. The Exo/Gel displayed enhanced cell migration and angiogenic properties in vitro. And the results in the rat skin wound model showed that the Exo/Gel could promote the regular collagen deposition, angiogenesis, and hair follicle mosaicism regeneration. These results proved that the hydrogel dressing with ADMSCs-derived exosomes can accelerate skin wound healing, which is a strategy for developing wound dressings.


Chitosan , Exosomes , Mesenchymal Stem Cells , Humans , Rats , Animals , Wound Healing , Hydrogels/metabolism , Exosomes/metabolism , Mesenchymal Stem Cells/metabolism , Bandages
17.
Adv Sci (Weinh) ; 11(13): e2309293, 2024 Apr.
Article En | MEDLINE | ID: mdl-38258489

The efficiency of photocatalytic hydrogen evolution is currently limited by poor light adsorption, rapid recombination of photogenerated carriers, and ineffective surface reaction rate. Although heterojunctions with innovative morphologies and structures can strengthen built-in electric fields and maximize the separation of photogenerated charges. However, how to rational design of novel multidimensional structures to simultaneously improve the above three bottleneck problems is still a research imperative. Herein, a unique Cu2O─S@graphene oxide (GO)@Zn0.67Cd0.33S Three dimensional (3D) hollow heterostructure is designed and synthesized, which greatly extends the carrier lifetime and effectively promotes the separation of photogenerated charges. The H2 production rate reached 48.5 mmol g-1 h-1 under visible light after loading Ni2+ on the heterojunction surface, which is 97 times higher than that of pure Zn0.67Cd0.33S nanospheres. Furthermore, the H2 production rate can reach 77.3 mmol g-1 h-1 without cooling, verifying the effectiveness of the photothermal effect. Meanwhile, in situ characterization and density flooding theory calculations reveal the efficient charge transfer at the p-n 3D hollow heterojunction interface. This study not only reveals the detailed mechanism of photocatalytic hydrogen evolution in depth but also rationalizes the construction of superior 3D hollow heterojunctions, thus providing a universal strategy for the materials-by-design of high-performance heterojunctions.

18.
J Virol ; 98(2): e0168223, 2024 Feb 20.
Article En | MEDLINE | ID: mdl-38289117

Porcine deltacoronavirus (PDCoV) has caused enormous economic losses to the global pig industry. However, the immune escape mechanism of PDCoV remains to be fully clarified. Transcriptomic analysis revealed a high abundance of interferon (IFN)-induced protein with tetratricopeptide repeats 3 (IFIT3) transcripts after PDCoV infection, which initially implied a correlation between IFIT3 and PDCoV. Further studies showed that PDCoV nsp5 could antagonize the host type I interferon signaling pathway by cleaving IFIT3. We demonstrated that PDCoV nsp5 cleaved porcine IFIT3 (pIFIT3) at Gln-406. Similar cleavage of endogenous IFIT3 has also been observed in PDCoV-infected cells. The pIFIT3-Q406A mutant was resistant to nsp5-mediated cleavage and exhibited a greater ability to inhibit PDCoV infection than wild-type pIFIT3. Furthermore, we found that cleavage of IFIT3 is a common characteristic of nsp5 proteins of human coronaviruses, albeit not alphacoronavirus. This finding suggests that the cleavage of IFIT3 is an important mechanism by which PDCoV nsp5 antagonizes IFN signaling. Our study provides new insights into the mechanisms by which PDCoV antagonizes the host innate immune response.IMPORTANCEPorcine deltacoronavirus (PDCoV) is a potential emerging zoonotic pathogen, and studies on the prevalence and pathogenesis of PDCoV are ongoing. The main protease (nsp5) of PDCoV provides an excellent target for antivirals due to its essential and conserved function in the viral replication cycle. Previous studies have revealed that nsp5 of PDCoV antagonizes type I interferon (IFN) production by targeting the interferon-stimulated genes. Here, we provide the first demonstration that nsp5 of PDCoV antagonizes IFN signaling by cleaving IFIT3, which affects the IFN response after PDCoV infection. Our findings reveal that PDCoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by deltacoronaviruses.


Coronavirus 3C Proteases , Coronavirus Infections , Deltacoronavirus , Interferon Type I , Intracellular Signaling Peptides and Proteins , Swine Diseases , Swine , Animals , Humans , Coronavirus 3C Proteases/metabolism , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Deltacoronavirus/enzymology , Deltacoronavirus/metabolism , Deltacoronavirus/pathogenicity , Immunity, Innate , Interferon Type I/antagonists & inhibitors , Interferon Type I/biosynthesis , Interferon Type I/immunology , Intracellular Signaling Peptides and Proteins/chemistry , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Proteolysis , Signal Transduction/immunology , Swine/immunology , Swine/virology , Swine Diseases/immunology , Swine Diseases/metabolism , Swine Diseases/virology , Transcription Factors/metabolism , Viral Zoonoses/immunology , Viral Zoonoses/virology , Virus Replication
19.
Insects ; 15(1)2024 Jan 18.
Article En | MEDLINE | ID: mdl-38249076

Mosquitoes, as disease vectors causing global morbidity and mortality through diseases like malaria, dengue, and Zika, necessitate mosquito population control methods. This study investigated the efficacy of nano-formulated insecticide-based sugar baits in controlling Anopheles gambiae populations and assessed their potential non-target impact on Coccinella septempunctata. This laboratory-based study employed thiolated polymer-coated attractive toxic sugar bait (ATSB) nano-formulations, delivering pesticides via nano-carriers. Adult and larvae populations of insects were collected from rice and cotton fields subjected to bioassays with 0.5% and 1% concentrations of each nano-formulated and conventional insecticide within ATSB solution, alongside a control 100% attractive sugar bait (ASB). Mosquitoes interacted overnight with insecticide-treated baits, and mortality was assessed. Further observations up to 72 h were conducted for potential delayed toxic effects. Results highlighted nano-ATSB carbosulfan's effectiveness, particularly among organophosphates and pyrethroids. Among pyrethroids, nano-ATSB cypermethrin exhibited high efficacy, while Deltamethrin displayed lower mortality. Among organophosphates, nano-ATSB chlorpyrifos induced substantial mortality. The nano-formulations of insecticide were harmless against C. septempunctata compared to their conventional form. Nano-formulations demonstrated enhanced mortality rates and prolonged efficacy against mosquitoes, having a benign impact on non-target beetles. We expect these results to aid in developing effective plant protection products suitable for IPM practices.

20.
Plant J ; 117(6): 1815-1835, 2024 Mar.
Article En | MEDLINE | ID: mdl-37967090

Developing climate-resilient crops is critical for future food security and sustainable agriculture under current climate scenarios. Of specific importance are drought and soil salinity. Tolerance traits to these stresses are highly complex, and the progress in improving crop tolerance is too slow to cope with the growing demand in food production unless a major paradigm shift in crop breeding occurs. In this work, we combined bioinformatics and physiological approaches to compare some of the key traits that may differentiate between xerophytes (naturally drought-tolerant plants) and mesophytes (to which the majority of the crops belong). We show that both xerophytes and salt-tolerant mesophytes have a much larger number of copies in key gene families conferring some of the key traits related to plant osmotic adjustment, abscisic acid (ABA) sensing and signalling, and stomata development. We show that drought and salt-tolerant species have (i) higher reliance on Na for osmotic adjustment via more diversified and efficient operation of Na+ /H+ tonoplast exchangers (NHXs) and vacuolar H+ - pyrophosphatase (VPPases); (ii) fewer and faster stomata; (iii) intrinsically lower ABA content; (iv) altered structure of pyrabactin resistance/pyrabactin resistance-like (PYR/PYL) ABA receptors; and (v) higher number of gene copies for protein phosphatase 2C (PP2C) and sucrose non-fermenting 1 (SNF1)-related protein kinase 2/open stomata 1 (SnRK2/OST1) ABA signalling components. We also show that the past trends in crop breeding for Na+ exclusion to improve salinity stress tolerance are counterproductive and compromise their drought tolerance. Incorporating these genetic insights into breeding practices could pave the way for more drought-tolerant and salt-resistant crops, securing agricultural yields in an era of climate unpredictability.


Crops, Agricultural , Plant Breeding , Crops, Agricultural/genetics , Crops, Agricultural/metabolism , Sulfonamides , Naphthalenes , Abscisic Acid/metabolism , Droughts
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