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2.
Int Immunopharmacol ; 142(Pt A): 113089, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39244897

ABSTRACT

Interleukin-10 (IL-10) exerts complex effects on tumor growth, exhibiting both pro- and anti-tumor properties. Recent focus on the anti-inflammatory properties of IL-10 has highlighted its potential anti-tumor properties, particularly through the enhancement of CD8+ T cell activity. However, further research is needed to fully elucidate its other anti-tumor mechanisms. Our study investigates novel anti-tumor mechanisms of IL-10 in a murine mammary carcinoma model (4T1). We found that IL-10 overexpression in mouse 4T1 cells suppressed tumor growth in vivo. This suppression was accompanied by an increase in IFN-γ-secreting CD8+ T cells and a decrease in myeloid-derived suppressor cells (MDSCs) in tumor tissue. In vitro experiments showed that IL-10-rich tumor cell-derived supernatants inhibited myeloid cell differentiation into monocytic and granulocytic MDSCs while reducing MDSCs migration. In addition, IL-10 overexpression downregulated CXCL5 expression in 4T1 cells, resulting in decreased CXCR2+ MDSCs infiltration. Using RAG1-deficient mice and CXCL5 knockdown tumor models, we demonstrated that the anti-tumor effects of IL-10 depend on both CD8+ T cells and reduced MDSC infiltration. IL-10 attenuated the immunosuppressive tumor microenvironment by enhancing CD8+ T cell activity and inhibiting MDSCs infiltration. In human breast cancer, we observed a positive correlation between CXCL5 expression and MDSC infiltration. Our findings reveal a dual mechanism of IL-10-mediated tumor suppression: (1) direct enhancement of CD8+ T cell activity and (2) indirect reduction of immunosuppressive MDSCs through CXCL5 downregulation and inhibition of myeloid cell differentiation. This study provides new insights into the role of IL-10 in anti-tumor immunity and suggests potential strategies for breast cancer immunotherapy by modulating the IL-10-CXCL5-MDSCs axis.

3.
Sci Total Environ ; 954: 176430, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39307360

ABSTRACT

The "memory effect" of polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) in wet scrubber (WS) has become a frequent negative phenomenon in waste incineration field. This work focuses on studying the major influence factors and pathways of memory effect of PCDD/Fs in WS from the aspects of PCDD/F carriers and operating conditions. The PCDD/F contents of fillings used for over three years is 0.098 ng I-TEQ/g, which performs as a stable source of PCDD/Fs for thousands of hours with PCDD/F desorption rates ranged in 0.023-0.116 pg I-TEQ/g·h at 65 °C-93 °C. On the one hand, the filling layer has been the biggest PCDD/F storage part in WS (6845.1 µg). On the other hand, the generated yellow wrapping layer in long-term operation can limit the desorption of inner PCDD/Fs. The solubility of PCDD/Fs in scrubbing water (SW) performs a positive correlation with the content of suspended substances, and the increased temperature and pH value of SW both lead to a higher toxic concentration of PCDD/Fs dissolved from the fly ash to solutions. In addition, the built mass balance of PCDD/Fs around WS suggests the incomplete SW refreshing and sludge cleaning also contribute to the memory effect of PCDD/Fs through enhancing the liquid-phase PCDD/Fs in flue gas from SW. Based on this study, three suggestions are propounded on the operation of WS. The results of this study will provide essential evidence and guidelines for optimizing operation and inhibiting the PCDD/F memory effect in WS.

4.
Environ Pollut ; 361: 124750, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39151785

ABSTRACT

Calcium oxide (CaO), utilized in semi-dry/dry desulfurization systems at municipal solid waste incineration (MSWI) plants, demonstrates some capability to remove polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). This study assessed the gas-phase PCDD/F removal performance of CaO, activated carbon (AC) and CaO-AC mixtures. Alone, CaO achieved removal efficiencies of only 31.9% for mass and 50.8% for I-TEQ concentration. However, CaO-AC mixtures exhibited significantly higher efficiencies, reaching 96.0% and 92.5% for mass and I-TEQ concentrations, respectively, surpassing those of AC alone, which were 74.7% and 58.5%. BET analysis indicated that CaO's limited surface area and pore structure are major constraints on its adsorption performance. Density functional theory (DFT) calculations revealed that the π-π electron donor-acceptor (EDA) interaction enhances the adsorption between AC and PCDD/F, with adsorption energies ranging from -1.02 to -1.24 eV. Additionally, the induced dipole interactions between CaO and PCDD/F contribute to adsorption energies ranging from -1.13 to -1.43 eV. Moreover, with increasing chlorination levels, PCDD/F molecules are more predisposed to accept electron transfers from the surfaces of AC or CaO, thereby facilitating adsorption. The calculation for mixed AC and CaO showed that CaO modifies AC's properties, enhancing its ability to adsorb gas phase PCDD/Fs, with the higher adsorption energy and more electrons transfer, aligning with gas phase PCDD/Fs adsorption experiments. This study provides a comprehensive understanding of how CaO influences the PCDD/F adsorption performance of AC.

5.
Sci Total Environ ; 948: 174959, 2024 Oct 20.
Article in English | MEDLINE | ID: mdl-39059654

ABSTRACT

High ammonia pollution is a common problem in water bodies. However, research on the mechanisms underlying the toxic effects on organisms at different nutritional levels is still insufficient. Herein, based on the environmental concentration, the toxic effects of high ammonia pollution on Daphnia magna were investigated. Overall, the feeding and filtration rates of D. magna were significantly decreased by ammonia. Growth inhibition of D. magna by ammonia was confirmed by the decreased body length. After ammonia exposure, the metabolic status of D. magna changed, the correlation network weakened, and the correlations between metabolites were disrupted. Changes occurred in metabolites primarily involved in oxidative stress, fatty acid oxidation, tricarboxylic acid cycle, and protein digestion, absorption, and synthesis, which were validated through alterations in multiple biomarkers. In addition, mitochondrial function was evaluated and was found to inhibit mitochondrial activity, which was accompanied by a decreased marker of mitochondrial activity contents and ATPase activity. Thus, the results suggested that energy metabolism and oxidative stress were involved in ammonia-induced growth toxicity. This study provides new insights into the impact of ammonia on aquatic ecological health.


Subject(s)
Ammonia , Daphnia magna , Energy Metabolism , Oxidative Stress , Water Pollutants, Chemical , Animals , Ammonia/toxicity , Daphnia magna/drug effects , Daphnia magna/physiology , Energy Metabolism/drug effects , Oxidative Stress/drug effects , Water Pollutants, Chemical/toxicity
6.
J Nanobiotechnology ; 22(1): 375, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926721

ABSTRACT

As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3'-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.


Subject(s)
Carcinoma, Hepatocellular , Copper , Liver Neoplasms , Photochemotherapy , Photosensitizing Agents , Copper/chemistry , Copper/pharmacology , Animals , Carcinoma, Hepatocellular/drug therapy , Photochemotherapy/methods , Liver Neoplasms/drug therapy , Mice , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Mice, Inbred BALB C , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/chemistry , Porphyrins/chemistry , Porphyrins/pharmacology , Chlorophyllides , Glutathione/metabolism , Nanoparticles/chemistry , Catalysis , Metal Nanoparticles/chemistry , Drug Liberation , Mice, Nude , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
7.
Environ Int ; 188: 108746, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38776653

ABSTRACT

Despite increasing waste-to-energy (WtE) capacities, there remain deficiencies in comprehension of 136 kinds of tetra- through octa-chlorinated dibenzo-p-dioxin and dibenzofurans (136 PCDD/Fs) originating from incineration sources. Samples from twenty typical WtE plants, encompassing coal-fired power plants (CPP), grate incinerators (GI), fluidized bed incinerators (FBI), and rotary kilns (RK), yielded extensive PCDD/F datasets. Research was conducted on fingerprint mapping, formation pathways, emission profiles, and diagnostic analysis of PCDD/Fs in WtE plants. Fingerprints revealed a prevalence of TCDF, followed by PeCDF, while CPP and RK respectively generated more PCDD and HxCDD. De novo synthesis was the predominant formation pathway except one plant, where CP-route dominated. DD/DF chlorination also facilitated PCDD/F formation, showing general trends of FBI > GI > CPP > RK. The PCDD/F emission intensities emitted in air pollution control system inlet (APCSI) and outlet (APCSO) followed the statistical sequence of RK > FBI > GI > CPP, with the average I-TEQ concentrations in APCSO reaching 0.18, 0.08, 0.11, and 0.04 ng I-TEQ·Nm-3. Emission spectrum were accordingly formed. Four clusters were segmented for diagnosis analysis, where PCDD/Fs in GI and FBI were similar, grouped as a single cluster. PCDD/Fs in CPP and RK demonstrated distinctive features in TCDD, HxCDD, and HxCDF. The WtE plants exceeding the limit value tended to generate and retain fewer TCDD and TCDF yet had higher fractions of HxCDD and HxCDF. The failure of APCS coupled with the intrinsic source strength of PCDD/Fs directly led to exceedance, highlighting safe operational practices. This study motivated source tracing and precise evaluation of 136 PCDD/Fs based on the revealed fingerprint profiles for WtE processes.


Subject(s)
Air Pollutants , Dioxins , Environmental Monitoring , Incineration , Air Pollutants/analysis , Environmental Monitoring/methods , Dioxins/analysis , Power Plants , Polychlorinated Dibenzodioxins/analysis , Benzofurans/analysis
8.
Protein Expr Purif ; 221: 106518, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38821452

ABSTRACT

Chiral amino acids and their deamination products, α-keto acids, have important applications in food, medicine, and fine chemicals. In this study, two l-amino acid deaminase genes from Proteus mirabilis, PM473 of type Ⅰ and PM471 of type Ⅱ were cloned and expressed in Escherichia coli respectively, expected to achieve the chiral separation of amino acids. Extensive substrate preference testing showed that both deaminases had catalytic effects on the d-amino acid component of the D, l-amino acids, and PM473 has a wider catalytic range for amino acids. When D, L-Cys was used as the substrate, all L-Cys components and 75.1 % of D-Cys were converted to mercapto pyruvate, and the remaining D-Cys was a single chiral enantiomer. Molecular docking analysis showed that the interaction between the substrate and the key residues affected the stereoselectivity of enzymes. The compatibility of hydrophobicity between the binding pocket and substrate may be the basic factor that affects the substrate selectivity. This work provides an alternative method for the production of α-keto acids and the resolution of chiral amino acids.


Subject(s)
Escherichia coli , Keto Acids , Molecular Docking Simulation , Proteus mirabilis , Proteus mirabilis/enzymology , Proteus mirabilis/genetics , Keto Acids/metabolism , Keto Acids/chemistry , Escherichia coli/genetics , Escherichia coli/metabolism , Stereoisomerism , Substrate Specificity , Amino Acids/genetics , Amino Acids/chemistry , Amino Acids/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Recombinant Proteins/biosynthesis , Cloning, Molecular
9.
J AOAC Int ; 107(5): 801-810, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38733574

ABSTRACT

BACKGROUND: The identification of the geographical origin of Polygonatum cyrtonema Hua is of particular importance because the quality and market value of Polygonatum cyrtonema Hua from different production areas are highly variable due to differences in the growing environment and climatic conditions. OBJECTIVE: This study utilized near-infrared spectra (NIR) of Polygonatum cyrtonema Hua (n = 400) to develop qualitative models for effective differentiation of Polygonatum cyrtonema Hua from various regions. METHODS: The models were produced under different conditions to distinguish the origins distinctly. Ten preprocessing methods have been used to preprocess the original spectra (OS) and to select the most optimal spectral preprocessing method. Principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to determine appropriate models. For simplicity, the pretreated full spectrum was calculated by different wavelength selection methods, and the four most significant variables were selected as discriminant indicator variables. RESULTS: The results show that Polygonatum cyrtonema Hua from different regions can be effectively distinguished using spectra from a series of samples analyzed by OPLS-DA. The accuracy of the OPLS-DA model is also satisfactory, with a good differentiation rate. CONCLUSION: The study findings indicate the feasibility of using spectroscopy in combination with multivariate analysis to identify the geographical origins of Polygonatum cyrtonema Hua. HIGHLIGHTS: The utilization of NIR spectroscopy combined with chemometrics exhibits high efficacy in discerning the provenance of herbal medicines and foods, thereby facilitating QA measures.


Subject(s)
Polygonatum , Principal Component Analysis , Spectroscopy, Near-Infrared , Spectroscopy, Near-Infrared/methods , Polygonatum/chemistry , Least-Squares Analysis , Discriminant Analysis , Chemometrics/methods
10.
Reprod Toxicol ; 126: 108596, 2024 06.
Article in English | MEDLINE | ID: mdl-38641015

ABSTRACT

This study replicated a mouse model of sperm DNA damage induced by benzo(a)pyrene (BaP), and the transcriptomic and proteomic features of the model were examined to clarify the pathways related to BaP-induced damage to sperm DNA. Male mice in the BaP group were subjected to BaP at a dosage of 100 mg/kg/d or an equivalent quantity of saline solution in the control group for 60 days. Subsequently, the DNA fragmentation index (DFI) in sperm was assessed using a sperm chromatin structure assay (SCSA). RNA-seq and data-independent acquisition (DIA) were used to identify the mRNA and protein expression patterns in the testis. The sperm DFI significantly increased in the BaP group. Compared to the control group, the BaP group exhibited differential expression of 240 genes (referred to as DEGs) and 616 proteins (referred to as DEPs). These molecules included Aldh1a1, Cyb5r3, Fads1, Oxsm, Rcn3, and Prss45. Pathways in cancer, the PI3K-Akt signaling pathway, metabolic pathways, and the MAPK signaling pathway were the primary areas where these genes showed enrichment. BaP can damage the DNA of sperm and affect metabolism, the PI3K-Akt pathway, and pathways associated with cancer signaling.


Subject(s)
Benzo(a)pyrene , DNA Damage , Spermatozoa , Transcriptome , Animals , Male , Benzo(a)pyrene/toxicity , Spermatozoa/drug effects , Spermatozoa/metabolism , Transcriptome/drug effects , Mice , Proteome/drug effects , Proteomics , Testis/drug effects , Testis/metabolism , Testis/pathology , DNA Fragmentation/drug effects
11.
Arch Insect Biochem Physiol ; 115(4): e22114, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38659314

ABSTRACT

The insect cuticle plays a key role in maintaining the insect's physiological function and behavior. Herein, the yellow-y protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. However, yellow-y can also have other functions, for instance, in insect behavior, but not much is known. In this study, we have studied the yellow-y gene in one important model and pest species, namely the German cockroach (Blattella germanica), which is to our knowledge the first time reported. In essence, we identified the yellow-y gene (BgY-y) and characterized its function by using RNA interference (RNAi). Silencing of BgY-y gene led to different developmental abnormalities (body weight and wings) in both genders. Specifically, there was an abundant decrease in melanin, turning the body color in pale yellow and the cuticle softer and more transparent. Interestingly, we also observed that the knockdown of BgY-y impaired the male cockroaches to display a weaker response to female-emitted contact sex pheromones, and also that the oviposition ability was weakened in the RNAi females. This study comprehensively analyzed the biological functions of the yellow-y gene in German cockroaches from the perspectives of development, body color, courtship behavior and oviposition, and as a consequence, this may opens new avenues to explore it as a novel pest control gene.


Subject(s)
Blattellidae , Insect Proteins , Oviposition , Pigmentation , RNA Interference , Animals , Blattellidae/genetics , Blattellidae/physiology , Female , Insect Proteins/genetics , Insect Proteins/metabolism , Male , Pigmentation/genetics , Courtship , Melanins/metabolism , Sexual Behavior, Animal
12.
Scand J Immunol ; 99(5): e13356, 2024 May.
Article in English | MEDLINE | ID: mdl-38605549

ABSTRACT

In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in-depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra-tumoural T-cell ratios or in the functionality of T-cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8+ T cells by elevating IFN-γ and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single-agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro-immunogenic conditions. This assertion is backed by a raised CD8+/CD4+ T-cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T-cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T-cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti-tumour immunity through the application of innovative therapeutic strategies.


Subject(s)
Antibodies , Mucin-1 , Neoplasms , Programmed Cell Death 1 Receptor , Vaccines, DNA , Animals , Mice , Antibodies/metabolism , CD8-Positive T-Lymphocytes , Cell Line, Tumor , Mucin-1/genetics , Neoplasms/metabolism , Programmed Cell Death 1 Receptor/metabolism , Tumor Microenvironment
13.
Bull Entomol Res ; 114(2): 271-280, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38623047

ABSTRACT

Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.


Subject(s)
Blattellidae , Melanins , Pigmentation , Animals , Blattellidae/genetics , Blattellidae/physiology , Male , Female , Pigmentation/genetics , Melanins/metabolism , Insect Proteins/genetics , Insect Proteins/metabolism , Sexual Behavior, Animal , RNA Interference
14.
Mol Immunol ; 170: 46-56, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38615627

ABSTRACT

Peritoneal B cells can be divided into B1 cells (CD11b+CD19+) and B2 cells (CD11b-CD19+) based on CD11b expression. B1 cells play a crucial role in the innate immune response by producing natural antibodies and cytokines. B2 cells share similar traits with B1 cells, influenced by the peritoneal environment. However, the response of both B1 and B2 cells to the same stimuli in the peritoneum remains uncertain. We isolated peritoneal B1 and B2 cells from mice and assessed differences in Interleukin-10(IL-10) secretion, apoptosis, and surface molecule expression following exposure to LPS and Interleukin-21(IL-21). Our findings indicate that B1 cells are potent IL-10 producers, possessing surface molecules with an IgMhiCD43+CD21low profile, and exhibit a propensity for apoptosis in vitro. Conversely, B2 cells exhibit lower IL-10 production and surface markers characterized as IgMlowCD43-CD21hi, indicative of some resistance to apoptosis. LPS stimulates MAPK phosphorylation in B1 and B2 cells, causing IL-10 production. Furthermore, LPS inhibits peritoneal B2 cell apoptosis by enhancing Bcl-xL expression. Conversely, IL-21 has no impact on IL-10 production in these cells. Nevertheless, impeding STAT3 phosphorylation permits IL-21 to increase IL-10 production in peritoneal B cells. Moreover, IL-21 significantly raises apoptosis levels in these cells, a process independent of STAT3 phosphorylation and possibly linked to reduced Bcl-xL expression. This study elucidates the distinct functional and response profiles of B1 and B2 cells in the peritoneum to stimuli like LPS and IL-21, highlighting their differential roles in immunological responses and B cell diversity.


Subject(s)
Apoptosis , B-Lymphocyte Subsets , Interleukin-10 , Interleukins , Lipopolysaccharides , Peritoneum , Animals , Mice , Antigens, CD19/immunology , Antigens, CD19/metabolism , Apoptosis/drug effects , Apoptosis/immunology , B-Lymphocyte Subsets/drug effects , B-Lymphocyte Subsets/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , bcl-X Protein/metabolism , bcl-X Protein/immunology , CD11b Antigen/metabolism , CD11b Antigen/immunology , Interleukin-10/immunology , Interleukin-10/metabolism , Interleukins/immunology , Interleukins/pharmacology , Lipopolysaccharides/pharmacology , Lipopolysaccharides/immunology , Mice, Inbred C57BL , Peritoneum/immunology , Peritoneum/cytology , Phosphorylation/drug effects , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/immunology
15.
Sci Total Environ ; 926: 171286, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38428617

ABSTRACT

Vacuolar-type (H+)-ATPase (vATPase) is a conserved multi-subunit eukaryotic enzyme composed of 14 subunits that form a functional complex consisting of an ATP-hydrolytic domain (V1) and a proton-translocation domain (V0). ATP hydrolysis and subsequent H+ translocation rely heavily on a fully assembled V1/V0 complex. Since vATPase is crucial for insect survival, it is a viable molecular target for pest control. However, detailed functional analyses of the 14 subunits and their suitability for pest control have not been fully explored in a single insect species. In this study, we identified 22 vATPase subunit transcripts that correspond to 13 subunits (A1, A2, B, C, D, E, F, G, H, a1, a2, c and d) in the white-backed planthopper (WBPH), Sogatella furcifera, a major hemipteran pest of rice. RNAi screens using microinjection and spray-based methods revealed that the SfVHA-F, SfVHA-a2 and SfVHA-c2 subunits are critical. Furthermore, star polymer (SPc) nanoparticles were utilized to conduct spray-induced and nanoparticle-delivered gene silencing (SI-NDGS) to evaluate the pest control efficacy of RNAi targeting the SfVHA-F, SfVHA-a2 and SfVHA-c2 transcripts. Target mRNA levels and vATPase enzymatic activity were both reduced. Honeydew excreta was likewise reduced in WBPH treated with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. To assess the environmental safety of the nanoparticle-wrapped dsRNAs, Cyrtorhinus lividipennis Reuter, a major natural enemy of planthoppers, was also sprayed with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. Post-spray effects of dsSfVHA-a2 and dsSfVHA-c2 on C. lividipennis were innocuous. This study identifies SfVHA-a2 and SfVHA-c2 as promising targets for biorational control of WBPH and lays the foundation for developing environment-friendly RNAi biopesticides.


Subject(s)
Hemiptera , Heteroptera , Oryza , Pesticides , Animals , Oryza/genetics , RNA Interference , Risk Assessment , Adenosine Triphosphate
16.
Diagnostics (Basel) ; 14(4)2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38396428

ABSTRACT

Major depressive disorder (MDD) and bipolar disorder (BD) share clinical features, which complicates their differentiation in clinical settings. This study proposes an innovative approach that integrates structural connectome analysis with machine learning models to discern individuals with MDD from individuals with BD. High-resolution MRI images were obtained from individuals diagnosed with MDD or BD and from HCs. Structural connectomes were constructed to represent the complex interplay of brain regions using advanced graph theory techniques. Machine learning models were employed to discern unique connectivity patterns associated with MDD and BD. At the global level, both BD and MDD patients exhibited increased small-worldness compared to the HC group. At the nodal level, patients with BD and MDD showed common differences in nodal parameters primarily in the right amygdala and the right parahippocampal gyrus when compared with HCs. Distinctive differences were found mainly in prefrontal regions for BD, whereas MDD was characterized by abnormalities in the left thalamus and default mode network. Additionally, the BD group demonstrated altered nodal parameters predominantly in the fronto-limbic network when compared with the MDD group. Moreover, the application of machine learning models utilizing structural brain parameters demonstrated an impressive 90.3% accuracy in distinguishing individuals with BD from individuals with MDD. These findings demonstrate that combined structural connectome and machine learning enhance diagnostic accuracy and may contribute valuable insights to the understanding of the distinctive neurobiological signatures of these psychiatric disorders.

17.
Adv Clin Exp Med ; 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38315382

ABSTRACT

B10 cells, a specialized subset of regulatory B cells, have been identified in both mice and humans. These cells are characterized by their regulatory impact on immune dynamics, principally through their secretion of interleukin-10 (IL-10), a cytokine known for its anti-inflammatory properties. The pivotal role of immune mediators such as B10 cells is to maintain a delicate equilibrium between antitumor immunity and tumor-promoting responses. Emerging studies have cast B10 cells as key suppressors in the antitumor immune arsenal. They operate in synergy with a spectrum of immune cells within the innate and adaptive spectrums, contributing to a milieu that favors tumor progression and metastatic spread. In this comprehensive review, we will discuss the ontogeny, phenotype and effector functions of B10 cells in murine systems. We will also review the role of B10 cells in oncological models in animal studies and extend these findings to the human clinical context, elucidating their role in facilitating tumor immune evasion. A thorough understanding of these processes is imperative for the strategic targeting and attenuation of B10 cell activity, which is anticipated to be a cornerstone in the advancement of effective cancer immunotherapy strategies.

18.
Org Biomol Chem ; 22(5): 932-939, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38180250

ABSTRACT

A rapid and mild protocol for the exhaustive deoxygenation of various aromatic ketones to corresponding alkanes was described, which was mediated by TiCl4 and used ammonia borane (AB) as the reductant. This reduction protocol applies to a wide range of substrates in moderate to excellent yields at room temperature. The gram-scale reaction and syntheses of some key building blocks for SGLT2 inhibitors demonstrated the practicability of this methodology. Preliminary mechanistic studies revealed that the ketone is first converted into an alcohol, which then undergoes a carbocation to give the alkane via hydrogenolysis.

19.
Drug Deliv Transl Res ; 14(7): 1954-1968, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38191781

ABSTRACT

To improve treatment compliance and reach sustained and controlled drug release in the colon, we developed a hollow mesoporous silica nano-suppository that responded to both pH and redox stimuli. Firstly, we prepared hollow mesoporous silica nanoparticles containing disulfide bonds (HMSN-SS) and loaded them with 5-ASA. Secondly, we modified the surface of HMSN-SS with polydopamine (PDA) and chitosan (CS) and molded the suppository, which we named 5-ASA@HMSN-SS-PDA-CS (5-ASA@HSPC). By administering 5-ASA@HSPC rectally, it acted directly on the affected area. CS helped the nanoparticles adhere to the colon's surface, while PDA dissociates from HMSN-SS due to protonation in the acidic environment of the ulcerative colon. The disulfide bonds were destroyed by the reducing environment of the colon, leading to a stable and slow release of encapsulated 5-ASA from the pores of HMSN. Finally, in vitro release experiments and in vivo pharmacokinetic and pharmacodynamic experiments had demonstrated that 5-ASA@HSPC exhibited a slow and steady action at the colonic site, with an excellent safety profile. This novel approach showed great potential in the treatment of ulcerative colitis.


Subject(s)
Chitosan , Colitis, Ulcerative , Drug Liberation , Indoles , Mesalamine , Nanoparticles , Oxidation-Reduction , Polymers , Silicon Dioxide , Colitis, Ulcerative/drug therapy , Hydrogen-Ion Concentration , Chitosan/chemistry , Chitosan/administration & dosage , Animals , Nanoparticles/chemistry , Nanoparticles/administration & dosage , Mesalamine/chemistry , Mesalamine/administration & dosage , Mesalamine/pharmacokinetics , Silicon Dioxide/chemistry , Silicon Dioxide/administration & dosage , Polymers/chemistry , Polymers/administration & dosage , Indoles/administration & dosage , Indoles/chemistry , Indoles/pharmacokinetics , Suppositories/chemistry , Male , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/pharmacokinetics , Colon/drug effects , Colon/metabolism , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Porosity
20.
J Agric Food Chem ; 72(2): 1007-1016, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38166405

ABSTRACT

RNA interference (RNAi) is a widespread post-transcriptional silencing mechanism that targets homologous mRNA sequences for specific degradation. An RNAi-based pest management strategy is target-specific and considered a sustainable biopesticide. However, the specific genes targeted and the efficiency of the delivery methods can vary widely across species. In this study, a spray-induced and nanocarrier-delivered gene silencing (SI-NDGS) system that incorporated gene-specific dsRNAs targeting conserved genes was used to evaluate phenotypic effects in white-backed planthopper (WBPH). At 2 days postspraying, transcript levels for all target genes were significantly reduced and knockdown of two gene orthologs, hsc70-3 and PP-α, resulted in an elevated mortality (>60%) and impaired ecdysis. These results highlight the utility of the SI-NDGS system for identifying genes involved in WBPH growth and development that could be potentially exploitable as high mortality target genes to develop an alternative method for WBPH control.


Subject(s)
Genes, Lethal , Hemiptera , Animals , RNA Interference , Gene Silencing , Hemiptera/genetics
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