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1.
Light Sci Appl ; 13(1): 159, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982066

ABSTRACT

Ultrasound sensors play an important role in biomedical imaging, industrial nondestructive inspection, etc. Traditional ultrasound sensors that use piezoelectric transducers face limitations in sensitivity and spatial resolution when miniaturized, with typical sizes at the millimeter to centimeter scale. To overcome these challenges, optical ultrasound sensors have emerged as a promising alternative, offering both high sensitivity and spatial resolution. In particular, ultrasound sensors utilizing high-quality factor (Q) optical microcavities have achieved unprecedented performance in terms of sensitivity and bandwidth, while also enabling mass production on silicon chips. In this review, we focus on recent advances in ultrasound sensing applications using three types of optical microcavities: Fabry-Perot cavities, π-phase-shifted Bragg gratings, and whispering gallery mode microcavities. We provide an overview of the ultrasound sensing mechanisms employed by these microcavities and discuss the key parameters for optimizing ultrasound sensors. Furthermore, we survey recent advances in ultrasound sensing using these microcavity-based approaches, highlighting their applications in diverse detection scenarios, such as photoacoustic imaging, ranging, and particle detection. The goal of this review is to provide a comprehensive understanding of the latest advances in ultrasound sensing with optical microcavities and their potential for future development in high-performance ultrasound imaging and sensing technologies.

2.
Arch Virol ; 169(8): 163, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990396

ABSTRACT

Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a suspended-MDCK-cell-derived inactivated H7N9 vaccine, which was based on a low-pathogenic H7N9 virus, to assess cross-reactive immunity and cross-protection against antigenically divergent H7N9 viruses. We found that the CRX-527 adjuvant, a synthetic TLR4 agonist, significantly enhanced the humoral immune responses of the suspended-MDCK-cell-derived H7N9 vaccine, with significant antigen-sparing and immune-enhancing effects, including robust virus-specific IgG, hemagglutination-inhibiting (HI), neuraminidase-inhibiting (NI), and virus-neutralizing (VN) antibody responses, which are crucial for protection against influenza virus infection. Moreover, the CRX-527-adjuvanted H7N9 vaccine also elicited cross-protective immunity and cross-protection against a highly pathogenic H7N9 virus with a single vaccination. Notably, NI and VN antibodies might play an important role in cross-protection against lethal influenza virus infections. This study showed that a synthetic TLR4 agonist adjuvant has a potent immunopotentiating effect, which might be considered worth further development as a means of increasing vaccine effectiveness.


Subject(s)
Antibodies, Viral , Immunity, Humoral , Influenza A Virus, H7N9 Subtype , Influenza Vaccines , Mice, Inbred BALB C , Orthomyxoviridae Infections , Toll-Like Receptor 4 , Vaccines, Inactivated , Animals , Influenza A Virus, H7N9 Subtype/immunology , Toll-Like Receptor 4/agonists , Toll-Like Receptor 4/immunology , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , Mice , Antibodies, Viral/immunology , Dogs , Madin Darby Canine Kidney Cells , Vaccines, Inactivated/immunology , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/immunology , Female , Antibodies, Neutralizing/immunology , Cross Protection/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Adjuvants, Vaccine , Immunoglobulin G/immunology , Immunoglobulin G/blood
3.
J Environ Manage ; 366: 121825, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38996604

ABSTRACT

Chelator-assisted phytoremediation is an efficacious method for promoting the removal efficiency of heavy metals (HMs). The effects of N, N-bis(carboxymethyl)-L-glutamic acid (GLDA) and polyaspartic acid (PASP) on Cd uptake and pyrene removal by Solanum nigrum L. (S. nigrum) were compared in this study. Using GLDA or PASP, the removal efficiency of pyrene was over 98%. And PASP observably raised the accumulation and transport of Cd by S. nigrum compared with GLDA. Meanwhile, both GLDA and PASP markedly increased soil dehydrogenase activities (DHA) and microbial activities. DHA and microbial activities in the PASP treatment group were 1.05 and 1.06 folds of those in the GLDA treatment group, respectively. Transcriptome analysis revealed that 1206 and 1684 differentially expressed genes (DEGs) were recognized in the GLDA treatment group and PASP treatment group, respectively. Most of the DEGs found in the PASP treatment group were involved in the metabolism of carbohydrates, the biosynthesis of brassinosteroid and flavonoid, and they were up-regulated. The DEGs related to Cd transport were screened, and ABCG3, ABCC4, ABCG9 and Nramp5 were found to be relevant with the reduction of Cd stress in S. nigrum by PASP. Furthermore, with PASP treated, transcription factors (TFs) related to HMs such as WRKY, bHLH, AP2/ERF, MYB were down-regulated, while more MYB and bZIP TFs were up-regulated. These TFs associated with plant stress resistance would work together to induce oxidative stress. The above results indicated that PASP was more conducive for phytoremediation of Cd-pyrene co-contaminated soil than GLDA.

4.
Org Lett ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023054

ABSTRACT

Strategies that fully convert available racemic substrates into valuable enantioenriched products are urgently needed in organic synthesis. Reported herein is the first parallel kinetic asymmetric transformation of racemic cyclohexadienones. Racemic cyclohexadienones are first diastereoselectively converted into a new pair of racemic transient dienol intermediates, which are then parallel protonated by chiral phosphoric acid to deliver two sets of hydroindole products bearing a quaternary stereocenter with generally excellent enantioselectivity.

5.
Sci Rep ; 14(1): 13919, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886464

ABSTRACT

With business process optimization, technological advancement, equipment capability enhancement, and other means, the Railway Passenger Service Department in China is consistently working to improve the efficiency and convenience of passenger entry and exit procedures at railway stations. Concerning passengers' checkout, not only conventional identification approaches based on manual control, identification card, and magnetic thermal paper ticket are supported, but also a recent contactless identification process based on face recognition is applied in some stations. To further improve the contactless identification ability for checkout, an advanced contactless checkout process based on gait-augmented face recognition is innovatively put forward, in which a weakly-supervised body segmentation network named Dwsegnet and an improved GaitSet model are proposed. Through comparison with various models, the effectiveness of both Dwsegnet and the improved GaitSet is validated. Specifically, the contactless identification rate of gait-augmented face recognition is improved by 2.31% when compared to single-modal face recognition, which demonstrates the superiority of the proposed process.

6.
J Hazard Mater ; 476: 134980, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38905978

ABSTRACT

In this investigation, we conducted a detailed analysis of the oxidation of 16 imidazole ionic liquid variants by Fe(VI) under uniform experimental setups, thereby securing a dataset of second-order reaction rate constants (kobs). This methodology ensures superior data consistency and comparability over traditional methods that amalgamate disparate data from varied studies. Utilizing 16 chemical structural parameters obtained via Density Functional Theory (DFT) as descriptors, we developed a Quantitative Structure Activity Relationship (QSAR) model. Through rigorous correlation analysis, Principal Component Analysis (PCA), Multiple Linear Regression (MLR), and Applicability Domain (AD) evaluation, we identified a pronounced negative correlation between the molecular orbital gap energy (Egap) and kobs. MLR analysis further underscored Egap as a pivotal predictive variable, with its lower values indicating heightened oxidative reactivity towards Fe(VI) in the ionic liquids, leading the QSAR model to achieve a predictive accuracy of 0.95. Furthermore, we integrated an advanced machine learning approach - Random Forest Regression (RFR), which adeptly highlighted the critical factors influencing the oxidation efficiency of imidazole ionic liquids by Fe(VI) through elaborate decision trees, feature importance assessment, Recursive Feature Elimination (RFE), and cross-validation strategies. The RFR model demonstrated a remarkable predictive performance of 0.98. Both QSAR and RFR models pinpointed Egap as a key descriptor significantly affecting oxidation efficiency, with the RFR model presenting lower root mean square errors, establishing it as a more reliable predictive tool. The application of the RFR model in this study significantly improved the model's stability and the intuitive display of key influencing factors, introducing promising advanced analytical tools to the field of environmental chemistry.

7.
Eur J Med Chem ; 273: 116519, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38795519

ABSTRACT

Anticancer peptides (ACPs) have regarded as a new generation of promising antitumor drugs due to the unique mode of action. The main challenge is to develop potential anticancer peptides with satisfied antitumor activity and low toxicity. Here, a series of new α-helical anticancer peptides were designed and synthesized based on the regular repeat motif KLLK. The optimal peptides 14E and 14Aad were successfully derived from the new short α-helical peptide KL-8. Our results demonstrated that 14E and 14Aad had good antitumor activity and low toxicity, exhibiting excellent selectivity index. This result highlighted that the desirable modification position and appropriate hydrophobic side-chain structure of acidic amino acids played critical roles in regulating the antitumor activity/toxicity of new peptides. Further studies indicated that they could induce tumor cell death via the multiple actions of efficient membrane disruption and intracellular mechanisms, displaying apparent superiority in combination with PTX. In addition, the new peptides 14E and 14Aad showed excellent antitumor efficacy in vivo and low toxicity in mice compared to KL-8 and PTX. Particularly, 14Aad with the longer side chain at the 14th site exhibited the best therapeutic performance. In conclusion, our work provided a new avenue to develop promising anticancer peptides with good selectivity for tumor therapy.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Drug Design , Drug Screening Assays, Antitumor , Peptides , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Animals , Humans , Mice , Peptides/chemistry , Peptides/pharmacology , Peptides/chemical synthesis , Structure-Activity Relationship , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Molecular Structure , Cell Line, Tumor , Mice, Inbred BALB C , Apoptosis/drug effects , Female
8.
Vaccines (Basel) ; 12(5)2024 May 15.
Article in English | MEDLINE | ID: mdl-38793795

ABSTRACT

Background:Streptococcus suis (S. suis) is a Gram-positive bacterium that causes substantial disease in pigs. S. suis is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of S. suis epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. Methods: In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of S. suis, was examined in mice for evaluation as a universal vaccine candidate. Results: S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 S. suis strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to S. suis serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with S. suis serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with S. suis serotype 7. Conclusions: These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against S. suis.

9.
Virology ; 595: 110083, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38696887

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibits swine leukocyte antigen class I (SLA-I) expression in pigs, resulting in inefficient antigen presentation and subsequent low levels of cellular PRRSV-specific immunity as well as persistent viremia. We previously observed that the non-structural protein 4 (nsp4) of PRRSV contributed to inhibition of the ß2-microglobulin (ß2M) and SLA-I expression in cells. Here, we constructed a series of nsp4 mutants with different combination of amino acid mutations to attenuate the inhibitory effect of nsp4 on ß2M and SLA-I expression. Almost all nsp4 mutants exogenously expressed in cells showed an attenuated effect on inhibition of ß2M and SLA-I expression, but the recombinant PRRSV harboring these nsp4 mutants failed to be rescued with exception of the rPRRSV-nsp4-mut10 harboring three amino acid mutations. However, infection of rPRRSV-nsp4-mut10 not only enhanced ß2M and SLA-I expression in both cells and pigs but also promoted the DCs to active the CD3+CD8+T lymphocytes more efficiently, as compared with its parental PRRSV (rPRRVS-nsp4-wt). These data suggested that the inhibition of nsp4-mediated ß2M downregulation improved ß2M/SLA-I expression in pigs.


Subject(s)
Down-Regulation , Histocompatibility Antigens Class I , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Viral Nonstructural Proteins , beta 2-Microglobulin , Porcine respiratory and reproductive syndrome virus/genetics , Porcine respiratory and reproductive syndrome virus/physiology , Porcine respiratory and reproductive syndrome virus/immunology , Animals , Swine , Porcine Reproductive and Respiratory Syndrome/virology , Porcine Reproductive and Respiratory Syndrome/immunology , Porcine Reproductive and Respiratory Syndrome/genetics , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism , Viral Nonstructural Proteins/immunology , beta 2-Microglobulin/genetics , beta 2-Microglobulin/metabolism , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/metabolism , Histocompatibility Antigens Class II/immunology , Cell Line , CD8-Positive T-Lymphocytes/immunology , Mutation
10.
Eur J Med Chem ; 271: 116451, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38691892

ABSTRACT

The potent antibacterial activity and low resistance of antimicrobial peptides (AMPs) render them potential candidates for treating multidrug-resistant bacterial infections. Herein, a minimalist design strategy was proposed employing the "golden partner" combination of arginine (R) and tryptophan (W), along with a dendritic structure to design AMPs. By extension, the α/ε-amino group and the carboxyl group of lysine (K) were utilized to link R and W, forming dendritic peptide templates αRn(εRn)KWm-NH2 and αWn(εWn)KRm-NH2, respectively. The corresponding linear peptide templates R2nKWm-NH2 and W2nKRm-NH2 were used as controls. Their physicochemical properties, activity, toxicity, and stability were compared. Among these new peptides, the dendritic peptide R2(R2)KW4 was screened as a prospective candidate owing to its preferable antibacterial properties, biocompatibility, and stability. Additionally, R2(R2)KW4 not only effectively restrained the progression of antibiotic resistance, but also demonstrated synergistic utility when combined with conventional antibiotics due to its unique membrane-disruptive mechanism. Furthermore, R2(R2)KW4 possessed low toxicity (LD50 = 109.31 mg/kg) in vivo, while efficiently clearing E. coli in pulmonary-infected mice. In conclusion, R2(R2)KW4 has the potential to become an antimicrobial regent or adjuvant, and the minimalist design strategy of dendritic peptides provides innovative and encouraging thoughts in designing AMPs.


Subject(s)
Anti-Bacterial Agents , Arginine , Microbial Sensitivity Tests , Tryptophan , Tryptophan/chemistry , Tryptophan/pharmacology , Animals , Arginine/chemistry , Arginine/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Mice , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Cell Membrane/drug effects , Dose-Response Relationship, Drug , Bacterial Infections/drug therapy , Humans , Escherichia coli/drug effects
11.
Front Microbiol ; 15: 1359970, 2024.
Article in English | MEDLINE | ID: mdl-38800747

ABSTRACT

Introduction: Porcine Reproductive and Respiratory Syndrome virus (PRRSV) causes high abortion rates in gestating sows and stillbirths, as well as high piglet mortality, seriously jeopardizing the pig industry in China and worldwide. Methods: In this study, an infectious clone containing the full-length genome of NADC34-like PRRSV was constructed for the first time using reverse genetic techniques. The gene was amplified segmentally onto a plasmid, transfected into BHK-21 cells, and the transfected supernatant was harvested and transfected into PAM cells, which showed classical cytopathic effects (CPE). Results: The virus rJS-KS/2021 was successfully rescued which could be demonstrated by Western Blot and indirect immunofluorescence assays. Its growth curve was similar to the original strain. Replace the 5'UTR and 3'UTR of rJS-KS/2021 with 5'UTR and 3'UTR of HP-PRRSV (strain SH1) also failed to propagate on MARC-145. Discussion: In this study, an infectious clone of NADC34-like was constructed by reverse genetics, replacing the UTR and changing the cellular tropism of the virus. These findings provide a solid foundation for studying the recombination of different PRRSVs and the adaption of PRRSVs on MARC-145 in the future.

12.
Int J Mol Sci ; 25(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38791443

ABSTRACT

Broad-spectrum antibiotics are frequently used to treat bacteria-induced infections, but the overuse of antibiotics may induce the gut microbiota dysbiosis and disrupt gastrointestinal tract function. Probiotics can be applied to restore disturbed gut microbiota and repair abnormal intestinal metabolism. In the present study, two strains of Enterococcus faecium (named DC-K7 and DC-K9) were isolated and characterized from the fecal samples of infant dogs. The genomic features of E. faecium DC-K7 and DC-K9 were analyzed, the carbohydrate-active enzyme (CAZyme)-encoding genes were predicted, and their abilities to produce short-chain fatty acids (SCFAs) were investigated. The bacteriocin-encoding genes in the genome sequences of E. faecium DC-K7 and DC-K9 were analyzed, and the gene cluster of Enterolysin-A, which encoded a 401-amino-acid peptide, was predicted. Moreover, the modulating effects of E. faecium DC-K7 and DC-K9 on the gut microbiota dysbiosis induced by antibiotics were analyzed. The current results demonstrated that oral administrations of E. faecium DC-K7 and DC-K9 could enhance the relative abundances of beneficial microbes and decrease the relative abundances of harmful microbes. Therefore, the isolated E. faecium DC-K7 and DC-K9 were proven to be able to alter the gut microbiota dysbiosis induced by antibiotic treatment.


Subject(s)
Anti-Bacterial Agents , Dysbiosis , Enterococcus faecium , Gastrointestinal Microbiome , Animals , Dysbiosis/microbiology , Gastrointestinal Microbiome/drug effects , Anti-Bacterial Agents/pharmacology , Mice , Feces/microbiology , Fatty Acids, Volatile/metabolism , Probiotics/pharmacology , Dogs , Bacteriocins/pharmacology
13.
Int J Biol Macromol ; 268(Pt 1): 131804, 2024 May.
Article in English | MEDLINE | ID: mdl-38670186

ABSTRACT

Cold stress significantly threatens grape quality, yield, and geographical distribution. Although ethylene-responsive factors (ERFs) are recognized for their pivotal roles in cold stress, the regulatory mechanisms of many ERFs contributing to tolerance remain unclear. In this study, we identified the cold-responsive gene VvERF117 and elucidated its positive regulatory function in cold tolerance. VvERF117 exhibits transcriptional activity and localizes to the nucleus. VvERF117 overexpression improved cold tolerance in transgenic Arabidopsis, grape calli, and grape leaves, whereas VvERF117 silencing increased cold sensitivity in grape calli and leaves. Furthermore, VvERF117 overexpression remarkably upregulated the expression of several stress-related genes. Importantly, BAS1, encoding a 2-Cys peroxidase (POD), was confirmed as a direct target gene of VvERF117. Meanwhile, compared to the wild-type, POD activity and H2O2 content were remarkably increased and decreased in VvERF117-overexpressing grape calli and leaves, respectively. Conversely, VvERF117 silencing displayed the opposite trend in grape calli and leaves under cold stress. These findings indicate that VvERF117 plays a positive role in cold resistance by, at least in part, enhancing antioxidant capacity through regulating the POD-encoding gene VvBAS1, leading to effective mitigation of reactive oxygen species.


Subject(s)
Antioxidants , Gene Expression Regulation, Plant , Plant Proteins , Vitis , Vitis/genetics , Vitis/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Antioxidants/metabolism , Cold Temperature , Cold-Shock Response/genetics , Arabidopsis/genetics , Plants, Genetically Modified/genetics , Plant Leaves/genetics , Plant Leaves/metabolism , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/metabolism
14.
Am J Cancer Res ; 14(3): 1338-1352, 2024.
Article in English | MEDLINE | ID: mdl-38590417

ABSTRACT

Cistanche deserticola, known for its extensive history in Traditional Chinese Medicine (TCM), is valued for its therapeutic properties. Recent studies have identified its anticancer capabilities, yet the mechanisms underlying these properties remain to be fully elucidated. In this study, we determined that a mixture of four cistanche-derived phenylethanoid glycosides (CPhGs), echinacoside, acteoside, 2-acetylacteoside, and cistanoside A, which are among the main bioactive compounds in C. deserticola, eliminated T-cell lymphoma (TCL) cells by inducing apoptosis and pyroptosis in vitro and attenuated tumor growth in vivo in a xenograft mouse model. At the molecular level, these CPhGs elevated P53 by inhibiting the SIRT2-MDM2/P300 and PI3K/AKT carcinogenic axes and activating PTEN-Bax tumor-suppressing signaling. Moreover, CPhGs activated noncanonical and alternative pathways to trigger pyroptosis. Interestingly, CPhGs did not activate canonical NLRP3-caspase-1 pyroptotic signaling pathway; instead, CPhGs suppressed the inflammasome factor NLRP3 and the maturation of IL-1ß. Treatment with a caspase-1/4 inhibitor and silencing of Gasdermin D (GSDMD) or Gasdermin E (GSDME) partially rescued CPhG-induced cell death. Conversely, forced expression of NLRP3 restored cell proliferation. In summary, our results indicate that CPhGs modulate multiple signaling pathways to achieve their anticancer properties and perform dual roles in pyroptosis and NLRP3-driven proliferation. This study offers experimental support for the potential application of CPhGs in the treatment of TCL.

15.
Cartilage ; : 19476035241245805, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38641989

ABSTRACT

OBJECTIVE: Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may modulate the M1/M2 polarization of macrophages during osteoarthritis (OA). However, the underlying mechanisms of BMSC-Exos in this process still need to be elucidated. In this study, we explored the role of BMSC-Exos in the polarization of macrophages in vitro and the OA rats in vivo. METHODS: The effects of BMSC-Exos on RAW264.7 cells were determined, including the production of reactive oxygen species (ROS) and the protein expression of Akt, PINK1, and Parkin. We prepared an OA model by resecting the anterior cruciate ligament and medial meniscus of Sprague-Dawley (SD) rats. Hematoxylin-eosin (H&E) and safranin O-fast green staining, immunohistochemistry and immunofluorescence analyses, and the examination of interleukin 6 (IL-6), interleukin 1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were performed to assess changes in cartilage and synovium. RESULTS: BMSC-Exos inhibited mitochondrial membrane damage, ROS production, and the protein expression of PINK1 and Parkin. Akt phosphorylation was downregulated under lipopolysaccharide (LPS) induction but significantly recovered after treatment with BMSC-Exos. BMSC-Exos alleviated cartilage damage, inhibited M1 polarization, and promoted M2 polarization in the synovium in OA rats. The expression of PINK1 and Parkin in the synovium and the levels of IL-6, IL-1ß, and TNF-α in the serum decreased, but the level of IL-10 increased when BMSC-Exos were used in OA rats. CONCLUSION: BMSC-Exos ameliorate OA development by regulating synovial macrophage polarization, and one of the underlying mechanisms may be through inhibiting PINK1/Parkin signaling.

16.
Front Neurol ; 15: 1353275, 2024.
Article in English | MEDLINE | ID: mdl-38682035

ABSTRACT

Introduction: Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed. Methods: In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case-control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments. Results: A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis. Discussion: In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.

17.
Nano Lett ; 24(17): 5154-5164, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38602357

ABSTRACT

Developing novel strategies for defeating osteoporosis has become a world-wide challenge with the aging of the population. In this work, novel supramolecular nanoagonists (NAs), constructed from alkaloids and phenolic acids, emerge as a carrier-free nanotherapy for efficacious osteoporosis treatment. These precision nanoagonists are formed through the self-assembly of berberine (BER) and chlorogenic acid (CGA), utilizing noncovalent electrostatic, π-π, and hydrophobic interactions. This assembly results in a 100% drug loading capacity and stable nanostructure. Furthermore, the resulting weights and proportions of CGA and BER within the NAs are meticulously controlled with strong consistency when the CGA/BER assembly feed ratio is altered from 1:1 to 1:4. As anticipated, our NAs themselves could passively target osteoporotic bone tissues following prolonged blood circulation, modulate Wnt signaling, regulate osteogenic differentiation, and ameliorate bone loss in ovariectomy-induced osteoporotic mice. We hope this work will open a new strategy to design efficient herbal-derived Wnt NAs for dealing with intractable osteoporosis.


Subject(s)
Berberine , Chlorogenic Acid , Osteoporosis , Osteoporosis/drug therapy , Animals , Mice , Berberine/pharmacology , Berberine/therapeutic use , Berberine/chemistry , Berberine/administration & dosage , Berberine/pharmacokinetics , Chlorogenic Acid/chemistry , Chlorogenic Acid/pharmacology , Chlorogenic Acid/therapeutic use , Chlorogenic Acid/administration & dosage , Female , Humans , Osteogenesis/drug effects , Bone and Bones/drug effects , Bone and Bones/pathology , Nanostructures/chemistry , Nanostructures/therapeutic use
18.
Nat Commun ; 15(1): 3124, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600164

ABSTRACT

Crop wild relatives offer natural variations of disease resistance for crop improvement. Here, we report the isolation of broad-spectrum powdery mildew resistance gene Pm36, originated from wild emmer wheat, that encodes a tandem kinase with a transmembrane domain (WTK7-TM) through the combination of map-based cloning, PacBio SMRT long-read genome sequencing, mutagenesis, and transformation. Mutagenesis assay reveals that the two kinase domains and the transmembrane domain of WTK7-TM are critical for the powdery mildew resistance function. Consistently, in vitro phosphorylation assay shows that two kinase domains are indispensable for the kinase activity of WTK7-TM. Haplotype analysis uncovers that Pm36 is an orphan gene only present in a few wild emmer wheat, indicating its single ancient origin and potential contribution to the current wheat gene pool. Overall, our findings not only provide a powdery mildew resistance gene with great potential in wheat breeding but also sheds light into the mechanism underlying broad-spectrum resistance.


Subject(s)
Ascomycota , Triticum , Triticum/genetics , Plant Breeding , Genes, Plant , Ascomycota/genetics , Chromosome Mapping , Disease Resistance/genetics , Plant Diseases/genetics
20.
Comp Immunol Microbiol Infect Dis ; 109: 102179, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636297

ABSTRACT

porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV) infection, is an important swine infectious disease that causes substantial losses worldwide each year. PRRSV is a positive-sense single-stranded RNA virus that is highly susceptible to mutation and recombination, making vaccine and drug research for the disease extremely difficult. In this study, the binding of PRRSV nsp2 to HSP71 protein was detected by using the IP/MS technique. And the inhibitory effect of HSP71 on nsp2 antagonistic activity was validated by measuring NF-kB luciferase reporter. According to stress from inhibitory effects, the amino acid variation profile of PRRSV nsp2 under HSP71 stress was further analyzed using second-generation sequencing. Surprisingly, the results indicated that HSP71 pressure limits the random mutations of PRRSV nsp2 and maintains the dominant PRRSV strain within the population. Mutant strain showed weaker antagonistic activity and replication capability in cell. These results imply the binding of HSP71 with PRRSV nsp2 may lead to maintain the stability of highly virulent strains of PRRSV.


Subject(s)
Mutation , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Viral Nonstructural Proteins , Virus Replication , Porcine respiratory and reproductive syndrome virus/genetics , Animals , Swine , Porcine Reproductive and Respiratory Syndrome/virology , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism , Cell Line , Protein Binding , NF-kappa B/metabolism , NF-kappa B/genetics
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