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1.
Proc Natl Acad Sci U S A ; 121(8): e2316716121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38349874

RESUMO

Understanding the molecular-level mechanisms involved in transmembrane ion selectivity is essential for optimizing membrane separation performance. In this study, we reveal our observations regarding the transmembrane behavior of Li+ and Mg2+ ions as a response to the changing pore solvation abilities of the covalent-organic-framework (COF) membranes. These abilities were manipulated by adjusting the lengths of the oligoether segments attached to the pore channels. Through comparative experiments, we were able to unravel the relationships between pore solvation ability and various ion transport properties, such as partitioning, conduction, and selectivity. We also emphasize the significance of the competition between Li+ and Mg2+ with the solvating segments in modulating selectivity. We found that increasing the length of the oligoether chain facilitated ion transport; however, it was the COF membrane with oligoether chains containing two ethylene oxide units that exhibited the most pronounced discrepancy in transmembrane energy barrier between Li+ and Mg2+, resulting in the highest separation factor among all the evaluated membranes. Remarkably, under electro-driven binary-salt conditions, this specific COF membrane achieved an exceptional Li+/Mg2+ selectivity of up to 1352, making it one of the most effective membranes available for Li+/Mg2+ separation. The insights gained from this study significantly contribute to advancing our understanding of selective ion transport within confined nanospaces and provide valuable design principles for developing highly selective COF membranes.

2.
J Immunol ; 212(1): 57-68, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38019127

RESUMO

Salmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm-infected C57BL6/J mice were used to demonstrate the therapeutic benefits of the Bacillus velezensis JT3-1 (B. velezensis/JT3-1) strain or its cell-free supernatant in enhancing Trp metabolism. Targeted Trp metabolomic analyses indicated the predominance of indole-3-lactic acid (ILA), an indole derivative and ligand for aryl hydrocarbon receptor (AHR). Based on the 16S amplicon sequencing and correlation analysis of metabolites, we found that B. velezensis supported the relative abundance of Lactobacillus and Ligilactobacillus in mouse gut and showed positive correlations with ILA levels. Moreover, AHR and its downstream genes (especially IL-22) significantly increased in mouse colons after B. velezensis or cell-free supernatant treatment, suggesting the importance of AHR pathway activation. In addition, ILA was found to stimulate primary mouse macrophages to secrete IL-22, which was antagonized by CH-223191. Furthermore, ILA could protect mice from S. Tm infection by increasing IL-22 in Ahr+/- mice, but not in Ahr-/- mice. Finally, Trp-rich feeding showed amelioration of S. Tm infection in mice, and the effect depended on gut microbiota. Taken together, these results suggest that B. velezensis-associated ILA contributes to protecting mice against S. Tm infection by activating the AHR/IL-22 pathway. This study provides insights into the involvement of microbiota-derived Trp catabolites in protecting against Salmonella infection.


Assuntos
Microbioma Gastrointestinal , Microbiota , Infecções por Salmonella , Animais , Camundongos , Salmonella typhimurium , Triptofano/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo
3.
Plant Physiol ; 195(1): 617-639, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38285060

RESUMO

Revealing the genetic basis for stress-resistant traits in extremophile plants will yield important information for crop improvement. Zygophyllum xanthoxylum, an extant species of the ancient Mediterranean, is a succulent xerophyte that can maintain a favorable water status under desert habitats; however, the genetic basis of this adaptive trait is poorly understood. Furthermore, the phylogenetic position of Zygophyllales, to which Z. xanthoxylum belongs, remains controversial. In this study, we sequenced and assembled the chromosome-level genome of Z. xanthoxylum. Phylogenetic analysis showed that Zygophyllales and Myrtales form a separated taxon as a sister to the clade comprising fabids and malvids, clarifying the phylogenetic position of Zygophyllales at whole-genome scale. Analysis of genomic and transcriptomic data revealed multiple critical mechanisms underlying the efficient osmotic adjustment using Na+ and K+ as "cheap" osmolytes that Z. xanthoxylum has evolved through the expansion and synchronized expression of genes encoding key transporters/channels and their regulators involved in Na+/K+ uptake, transport, and compartmentation. It is worth noting that ZxCNGC1;1 (cyclic nucleotide-gated channels) and ZxCNGC1;2 constituted a previously undiscovered energy-saving pathway for Na+ uptake. Meanwhile, the core genes involved in biosynthesis of cuticular wax also featured an expansion and upregulated expression, contributing to the water retention capacity of Z. xanthoxylum under desert environments. Overall, these findings boost the understanding of evolutionary relationships of eudicots, illustrate the unique water retention mechanism in the succulent xerophyte that is distinct from glycophyte, and thus provide valuable genetic resources for the improvement of stress tolerance in crops and insights into the remediation of sodic lands.


Assuntos
Filogenia , Água , Zygophyllum , Água/metabolismo , Zygophyllum/genética , Zygophyllum/metabolismo , Genoma de Planta , Regulação da Expressão Gênica de Plantas , Genômica/métodos
4.
FASEB J ; 38(10): e23708, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38805151

RESUMO

Metacestodiasis is an infectious disease caused by the larval stage of cestode parasites. This disease poses a serious health hazard to wildlife, livestock, and humans, and it incurs substantial economic losses by impacting the safety of the livestock industry, the quality of meat production, and public health security. Unfortunately, there is currently no available molecular diagnostic method capable of distinguishing cysticercus- and Echinococcus-derived microRNAs (miRNAs) from other helminthes and hosts in the plasma of metacestode-infected animals. This study aims to develop a specific, sensitive, and cost-efficient molecular diagnostic method for cysticercosis and echinococcosis, particularly for early detection. The study developed a rolling circular amplification (RCA)-assisted CRISPR/Cas9 detection method based on parasite-derived miRNA let-7-5p. Using a series of dilutions of the let-7 standard, the limit of detection (LOD) of the qPCR, RCA, and RCA-assisted CRISPR/Cas9 methods was compared. The specificity of qPCR and CRISPR/Cas9 was evaluated using four artificially synthesized let-7 standards from different species. A total of 151 plasma samples were used to evaluate the diagnostic performance. Additionally, the study also assessed the correlation between plasma levels of let-7-5p, the number of Taenia pisiformis cysticerci, and the weight of Echinococcus multilocularis cysts. The results demonstrated that the RCA-assisted CRISPR/Cas9 assay could significantly distinguish let-7 from cestodes and other species, achieving a LOD of 10 aM; the diagnostic sensitivity and specificity for rabbit cysticercosis and mouse E. multilocularis were 100% and 97.67%, and 100% and 100%, respectively. Notably, let-7-5p gradually increased in the plasma of T. pisiformis-infected rabbits from 15 days post infection (dpi), peaked at 60 dpi, and persisted until 120 dpi. In E. multilocularis-infected mice, let-7-5p gradually increased from 15 dpi and persisted until 90 dpi. Furthermore, the expression of let-7-5p positively correlated with the number of cysticerci and cyst weight. These results indicated that the let-7-5p-based RCA-assisted CRISPR/Cas9 assay is a sensitive and specific detection method that can be used as a universal diagnostic method for metacestodiasis, particularly for early diagnosis (15 dpi).


Assuntos
Sistemas CRISPR-Cas , Cisticercose , MicroRNAs , Animais , MicroRNAs/genética , MicroRNAs/sangue , Camundongos , Cisticercose/diagnóstico , Cisticercose/veterinária , Cisticercose/parasitologia , Equinococose/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e Especificidade , Humanos
5.
Infect Immun ; 92(8): e0023224, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39037247

RESUMO

Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin (Emu-serpin), within the larval stage of Echinococcus multilocularis. Our observations indicate that Emu-serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu-serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu-serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu-serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu-serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.


Assuntos
Colite , Disbiose , Echinococcus multilocularis , Microbioma Gastrointestinal , Macrófagos , Serpinas , Animais , Camundongos , Serpinas/metabolismo , Colite/microbiologia , Macrófagos/imunologia , Macrófagos/metabolismo , Echinococcus multilocularis/imunologia , Proteínas de Helminto/metabolismo , Células RAW 264.7 , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Feminino
6.
BMC Genomics ; 25(1): 804, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187768

RESUMO

BACKGROUND: SET domain-containing histone lysine methyltransferases (HKMTs) and JmjC domain-containing histone demethylases (JHDMs) are essential for maintaining dynamic changes in histone methylation across parasite development and infection. However, information on the HKMTs and JHDMs in human pathogenic piroplasms, such as Babesia duncani and Babesia microti, and in veterinary important pathogens, including Babesia bigemina, Babesia bovis, Theileria annulata and Theileria parva, is limited. RESULTS: A total of 38 putative KMTs and eight JHDMs were identified using a comparative genomics approach. Phylogenetic analysis revealed that the putative KMTs can be divided into eight subgroups, while the JHDMs belong to the JARID subfamily, except for BdJmjC1 (BdWA1_000016) and TpJmjC1 (Tp Muguga_02g00471) which cluster with JmjC domain only subfamily members. The motifs of SET and JmjC domains are highly conserved among piroplasm species. Interspecies collinearity analysis provided insight into the evolutionary duplication events of some SET domain and JmjC domain gene families. Moreover, relative gene expression analysis by RT‒qPCR demonstrated that the putative KMT and JHDM gene families were differentially expressed in different intraerythrocytic developmental stages of B. duncani, suggesting their role in Apicomplexa parasite development. CONCLUSIONS: Our study provides a theoretical foundation and guidance for understanding the basic characteristics of several important piroplasm KMT and JHDM families and their biological roles in parasite differentiation.


Assuntos
Babesia , Filogenia , Babesia/genética , Babesia/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/química , Genômica , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/química , Animais , Humanos , Genoma de Protozoário , Domínios PR-SET/genética
7.
J Clin Microbiol ; : e0046324, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235247

RESUMO

Serological assays for antibody detection have contributed significantly to the diagnosis and control of infectious diseases. African swine fever is the most devastating infectious disease of domestic pigs and wild boars, severely threatening the global pig industry in recent years. Here, we developed a rapid, simple, and sensitive immunoassay based on the split-luciferase system to detect IgG antibodies against African swine fever virus (ASFV). In this assay, the p30 protein of ASFV was genetically coupled to the LgBiT and SmBiT subunits of nanoluciferase, which were used as fusion probes for specific antibodies. Target engagement of the probes results in the reconstitution of a functional nanoluciferase, which further catalyzes bioluminescent reactions. Different orientations of the LgBiT and SmBiT-p30 fusion sensors were designed and investigated, and N-LgBiT/p30 and N-SmBiT/p30 were identified as a promising sensor pair for reforming active nanoluciferase in the presence of specific antibodies. After optimization, this split-luciferase complementation assay showed high sensitivity and specificity for the detection of ASFV antibodies. The analytical sensitivity of the assay was 16 times greater than that of the blocking enzyme-linked immunosorbent assay (ELISA) by the detection of serial dilutions of serum, and no cross-reaction was observed with other swine pathogens. As demonstrated in clinical samples, its performance is highly consistent with that of a commercial ELISA kit, with a concordance rate of 98.19%. This assay is simple and easy to perform, providing a more flexible and efficient approach for the measurement of ASFV antibodies in clinical applications. IMPORTANCE: The study is about a homogeneous split-luciferase assay for antibody detection. Split nanoluciferase biosensors for the detection of ASFV antibodies were designed. This sensor platform enables the sensitive and specific detection of antibodies. The split-luciferase assay is simple, rapid, and easy to use.

8.
J Virol ; 97(10): e0121723, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37815352

RESUMO

IMPORTANCE: African swine fever virus (ASFV) completes the replication process by resisting host antiviral response via inhibiting interferon (IFN) secretion and interferon-stimulated genes (ISGs) function. 2', 5'-Oligoadenylate synthetase gene 1 (OAS1) has been reported to inhibit the replication of various RNA and some DNA viruses. However, the regulatory mechanisms involved in the ASFV-induced IFN-related pathway still need to be fully elucidated. Here, we found that OAS1, as a critical host factor, inhibits ASFV replication in an RNaseL-dependent manner. Furthermore, overexpression of OAS1 can promote the activation of the JAK-STAT pathway promoting innate immune responses. In addition, OAS1 plays a new function, which could interact with ASFV P72 protein to suppress ASFV infection. Mechanistically, OAS1 enhances the proteasomal degradation of P72 by promoting TRIM21-mediated ubiquitination. Meanwhile, P72 inhibits the production of avSG and affects the interaction between OAS1 and DDX6. Our findings demonstrated OAS1 as an important target against ASFV replication and revealed the mechanisms and intrinsic regulatory relationships during ASFV infection.


Assuntos
2',5'-Oligoadenilato Sintetase , Vírus da Febre Suína Africana , Febre Suína Africana , Proteínas com Motivo Tripartido , Replicação Viral , Animais , Vírus da Febre Suína Africana/fisiologia , Proteínas do Capsídeo/metabolismo , Interferons/metabolismo , Janus Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Suínos , Proteínas com Motivo Tripartido/metabolismo , 2',5'-Oligoadenilato Sintetase/metabolismo
9.
Plant Cell Environ ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39286958

RESUMO

Verticillium wilt (VW) caused by the soil-borne fungal pathogen Verticillium dahliae reduces cotton productivity and quality. Numerous studies have explored the genetic and molecular mechanisms regulating VW resistance in cotton, but the role and mechanism of strigolactone (SL) is still elusive. We investigated the function of SL in cotton's immune response to V. dahliae infection by exogenously applying SL analog, blocking or enhancing biosynthesis of endogenous SLs in combination with comparative transcriptome analysis and by exploring cross-talk between SL and other phytohormones. Silencing GhDWARF27 and applying the SL analog GR24 or overexpressing GhDWARF27 decreased and enhanced V. dahliae resistance, respectively. Transcriptome analysis revealed SL-mediated activation of abscisic acid (ABA) and jasmonic acid (JA) biosynthesis and signaling pathways. Enhanced ABA biosynthesis and signaling led to increased activity of antioxidant enzymes and reduced buildup of excess reactive oxygen species. Enhanced JA biosynthesis and signaling facilitated transcription of JA-dependent disease resistance genes. One of the components of the SL signal transduction pathway, GhD53, was found to interact with GhNCED5 and GhLOX2, the key enzymes of ABA and JA biosynthesis, respectively. We revealed the molecular mechanism underlying SL-enabled V. dahliae resistance and provided potential solutions for improving VW resistance in cotton.

10.
Infection ; 52(3): 787-800, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38717734

RESUMO

PURPOSE: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. METHODS: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. RESULTS: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug-drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. CONCLUSION: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option.


Assuntos
Antibacterianos , Infecções por Bactérias Gram-Positivas , Oxazolidinonas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Oxazolidinonas/farmacologia , Oxazolidinonas/uso terapêutico , Humanos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Animais , Piridonas
11.
Inorg Chem ; 63(23): 10481-10489, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38783831

RESUMO

Achieving high-efficiency tunable emission in a single phosphor remains a significant challenge. Herein, we report a series of Sb3+-doped all-inorganic double perovskites, Sb3+:Cs2NaScCl6, with efficient excitation-dependent emission. In 0.5%Sb3+:Cs2NaScCl6, strong blue emission with a high photoluminescence quantum yield (PLQY) of 85% is obtained under 265 nm light irradiation, which turns into bright neutral white light with a PLQY of 56% when excited at 303 nm. Spectroscopic and computational investigations were performed to reveal the mechanism of this excitation-dependent emission. Sb3+ doping induces two different excitation channels: the internal transition of Sb3+: 5s2 → 5s5p and the electron transfer transition of Sb3+: 5s → Sc3+ 3d. The former one generates excited Sb3+ ions, which can undergo efficient energy transfer to populate the host self-trapped exciton (STE) state, yielding enhanced blue emission. The latter one leads to the formation of a new STE state with the hole localized on Sb3+ and the electron delocalized on the nearest Sc3+, which accounts for the newly exhibited low-energy emission. The difference in the excitation pathways of the two emitting STE states results in the highly efficient excitation-dependent emission, making the doped systems promising anticounterfeiting materials.

12.
Inorg Chem ; 63(1): 621-634, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38100652

RESUMO

In this paper, the synthesis, photophysics, electrochemistry, and intramolecular energy transfer of two series of dinuclear and tetranuclear metallic complexes [(bpy)2M1LxM2(bpy)2]4+ (x = 1, 2; M1 = Ru, M2 = Ru/Os; M1 = Os, M2 = Ru) and {[Ru(bpy)2(Lx)]3Ru}8+ based on new heteroditopic bridging ligands (L1 = 6-phenyl-4-Hpip-2-2'-bipyridine, L2 = 6-Hpip-2-2'-bipyridine, Hpip = 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline) are reported. The dimetallic and tetrametallic complexes exhibit rich redox properties with successive reversible metal-centered oxidation and ligand-centered reduction couples. All complexes display intense absorption in the entire ultraviolet-visible spectral regions. The mononuclear [LxRu(bpy)2]2+ and homodinuclear [(bpy)2RuLxRu(bpy)2]4+ complexes display strong Ru-based characteristic emission at room temperature. Interestingly, the optical studies of heterodinuclear complexes reveal almost complete quenching of the RuII-based emission and efficient photoinduced energy transfer, resulting in an OsII-based emission in the near-infrared region. As a result of the intramolecular energy transfer from the center to the periphery and steric hindrance quenching of the peripheral RuII-centered emissive triplet metal-to-ligand charge transfer states, the tetranuclear complexes exhibit weak RuII-based emission with a short lifetime. Since the light absorbed by several chromophores is efficiently directed to the subunit with the lowest-energy excited state, the present multinuclear complexes can be used as well-visible-light-absorption antennas.

13.
BMC Infect Dis ; 24(1): 219, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374030

RESUMO

OBJECTIVE: In the present study, we aimed to compare the clinical efficacy and safety of omadacycline (OMC) with its comparators for the treatment of complicated skin and soft tissue infections (cSSTIs) in adult patients. METHODS: Randomized controlled trials (RCTs) evaluating OMC for cSSTIs were searched in databases of PubMed, Embase, Cochrane, Web of Science, and Clinical Trial, up to July 2022. The primary outcomes were clinical efficacy and microbiological response, with secondary outcome was safety. RESULTS: Four RCTs consisting of 1,757 patients were included, with linezolid (LZD) as a comparator drug. For clinical efficacy, OMC was not inferior to LZD in the modified intent-to-treat (MITT) (OR: 1.24, 95% Cl: [0.93, 1.66], P = 0.15) and clinically evaluable (CE) populations (OR: 1.92, 95% Cl: [0.94, 3.92], P = 0.07). For microbiological response, OMC was numerically higher than LZD in the microbiologically evaluable (ME) (OR: 1.74, 95% Cl: [0.81, 3.74], P = 0.16) and microbiological MITT (micro-MITT) populations (OR: 1.27, 95% Cl: [0.92, 1.76], P = 0.14). No significant difference was found in subpopulations of monomicrobial or polymicrobial mixed infection populations. The mortality and adverse event rates were similar between OMC and LZD. CONCLUSIONS: OMC was as good as LZD in terms of clinical efficacy and microbiological response, and has similar safety issues in treating cSSTIs. OMC might be a promising option for treating cSSTIs in adult patients.


Assuntos
Infecções dos Tecidos Moles , Adulto , Humanos , Antibacterianos/efeitos adversos , Linezolida/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções dos Tecidos Moles/microbiologia , Tetraciclinas/efeitos adversos , Resultado do Tratamento
14.
Bioorg Chem ; 144: 107108, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38244379

RESUMO

Molecules containing C-N bonds are of paramount importance in a diverse array of organic-based materials, natural products, pharmaceutical compounds, and agricultural chemicals. Biocatalytic C-N bond-forming reactions represent powerful strategies for producing these valuable targets, and their significance in the field of synthetic chemistry has steadily increased over the past decade. In this review, we provide a concise overview of recent advancements in the development of C-N bond-forming enzymes, with a particular emphasis on the inherent chemistry involved in these enzymatic processes. Overall, these enzymatic systems have proven their potential in addressing long-standing challenges in traditional small-molecule catalysis.


Assuntos
Compostos Orgânicos , Biocatálise , Compostos Orgânicos/química , Catálise
15.
Artigo em Inglês | MEDLINE | ID: mdl-38982736

RESUMO

Circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. This study aimed to investigate the role and molecular mechanisms of circMYO1C in OA. CircMYO1C was upregulated in OA- and interleukin-1ß (IL-1ß)-exposed chondrocytes. The results indicated that circMYO1C knockdown repressed the inflammatory factors (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], interleukin-8 [IL-8], etc.) and apoptosis of chondrocytes following IL-1ß exposure. CircMYO1C was an N6-methyladenosine (m6A)-modified circRNA with m6A characteristics. High mobility group box 1 (HMGB1) was a target of circMYO1C. IL-1ß exposure increased the stability and half-life (t1/2) of HMGB1 mRNA, while silencing circMYO1C reduced HMGB1 mRNA stability. Taken together, circMYO1C targets the m6A/HMGB1 axis to promote chondrocyte apoptosis and inflammation. The present study demonstrates that the circMYO1C/m6A/HMGB1 axis is essential for OA progression, highlighting a novel potential therapeutic target for clinical OA.

16.
J Chem Phys ; 160(15)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38624113

RESUMO

Boron carbonitride (BCN) films containing hybridized bonds involving B, C, and N over wide compositional ranges enable an abundant variety of new materials, properties, and applications; however, their electronic performance is still limited by the presence of structural and electronic defects, yielding sluggish mobility and electrical conductivity. This work reports on mechanically stable BCN films and their corresponding optical and electronic properties. The ternary BCN films consisting of hybridized B-C-N bonds have been achieved by varying N2 flow by the radio frequency magnetron sputtering method. The BCN films show a bandgap value ranging from 3.32 to 3.82 eV. Hall effect measurements reveal an n-type conductivity with an improved hall mobility of 226 cm2/V s at room temperature for the optimal film. The n-BCN/p-Si heterojunctions exhibit a nonlinear rectifying characteristic, where the tunneling behavior dominates the injection regimes due to the density of defects, i.e., structural disorder and impurities. Our work demonstrates the tunable electrical properties of BCN/Si p-n diodes and, thus, is beneficial for the potential application in the fields of optics, optoelectronics, and electrics.

17.
Exp Parasitol ; 265: 108813, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39117169

RESUMO

Babesia duncani, responsible for human babesiosis, is one of the most important tick-borne intraerythrocytic pathogens. Traditionally, babesiosis is definitively diagnosed by detecting parasite DNA in blood samples and examining Babesia parasites in Giemsa-stained peripheral blood smears. Although these techniques are valuable for determining Babesia duncani, they are often time-consuming and laborious. Therefore, developing rapid and reliable B. duncani identification assays is essential for subsequent epidemiological investigations and prevention and control. In this study, a cross-priming amplification (CPA) assay was developed, combined with a vertical flow visualization strip, to rapidly and accurately detect B. duncani infection. The detection limit of this method was as low as 0.98 pg/µl of genomic DNA from B. duncani merozoites per reaction at 59 °C for 60 min. There were no cross-reactions between B. duncani and other piroplasms infective to humans and mammals. A total of 592 blood samples from patients bitten by ticks and experimental infected hamsters were accurately assessed using CPA assay. The average cost of the CPA assay is as low as approximately $ 0.2 per person. These findings indicate that the CPA assay may therefore be a rapid screening tool for detection B. duncani infection, based on its accuracy, speed, and cost-effectiveness, particularly in resource-limited regions with a high prevalence of human babesiosis.


Assuntos
Babesia , Babesiose , DNA de Protozoário , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e Especificidade , Animais , Babesiose/diagnóstico , Babesiose/parasitologia , Babesia/isolamento & purificação , Babesia/genética , Babesia/classificação , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/economia , Técnicas de Amplificação de Ácido Nucleico/normas , DNA de Protozoário/isolamento & purificação , DNA de Protozoário/sangue , DNA de Protozoário/análise , Cricetinae , Limite de Detecção
18.
BMC Anesthesiol ; 24(1): 37, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263038

RESUMO

OBJECTIVE: This study was aimed to explore the protective effect of electroacupuncture (EA) pretreatment at Zusanli point (ST36) on ventilation-induced lung injury (VILI) and its potential anti-inflammatory mechanism. METHODS: High tidal volume ventilation was used to induce the VILI in mice, and EA pretreatment at ST36 was given for 7 consecutive days. The wet/dry ratio and pathological injury score of lung tissue, and total protein content of pulmonary alveolar lavage fluid (BALF) were detected after 4 h of mechanical ventilation (MV). Meanwhile, the expressions of TLR4 and NF- κB in lung tissue were evaluated by Western Blot, and the inflammatory factors in lung tissue were detected by ELISA. RESULTS: After four hours of mechanical ventilation, mice with ventilator-induced lung injury showed significant increases in lung wet/dry ratio, tissue damage scores, and protein content in bronchoalveolar lavage fluid. Pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α) and TLR4/NF-κB expression levels in the lung were also markedly elevated (P < 0.05). Conversely, ST36 acupuncture point pre-treatment significantly reduced these parameters (P < 0.05). CONCLUSION: EA pretreatment at ST36 could alleviate the inflammatory response for VILI via inhibiting TLR4/NF- κB pathway.


Assuntos
Eletroacupuntura , Lesão Pulmonar Induzida por Ventilação Mecânica , Animais , Camundongos , NF-kappa B , Receptor 4 Toll-Like , Transdução de Sinais
19.
Arch Gynecol Obstet ; 310(2): 855-861, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38280055

RESUMO

OBJECTIVE: This study aims to assess the feasibility and effectiveness of color doppler flow imaging (CDFI) technology and the Slow Flow HD imaging technique in identifying fetal pulmonary veins (PVs) in the first trimester (11-13 + 6 weeks), and further explore the factors affecting fetal pulmonary vein identification in early pregnancy. METHODS: Echocardiography and scanning of PVs were performed in 240 normal singleton fetuses in early pregnancy by using CDFI and slow flow HD techniques, to compare the ability of two methods to identify the PVs. Slow Flow HD technology was used to further investigate the difference of PVs identification at different gestational ages [group I (11-11 + 6 weeks), group II (12-12 + 6 weeks), group III (13-13 + 6 weeks)] and with different maternal body mass indices (BMI) (≥ 25 and < 25). In 31 cases of 240 fetuses, transvaginal ultrasonography was added due to maternal habitus or significant retroversion of the uterus, and the difference in PVs identification between transabdominal and transvaginal examination was analyzed. RESULTS: Successful PVs identification rates via CDFI and Slow Flow HD were 32.0% and 88.3%, respectively (p < 0.05). The identification rate of at least one and two pulmonary veins in Slow Flow HD was 88.3% and 76.2%, and all four pulmonary veins in 11.6% (p < 0.05). The identification rate of group I, II and III were 76.4%, 88.9% and 96.0%, respectively. The identification rate was 45.1% in the transabdominal ultrasound group and 83.8% in the transvaginal ultrasound group. The identification rate was 62.5% in the BMI ≥ 25 group and 94.7% in the BMI < 25 group (p < 0.05). CONCLUSIONS: Slow Flow HD can detect PVs in early pregnancy more often than using CDFI. Slow Flow HD is a feasible and effective imaging technique for evaluating PVs in early pregnancy.


Assuntos
Estudos de Viabilidade , Primeiro Trimestre da Gravidez , Veias Pulmonares , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Adulto , Ultrassonografia Pré-Natal/métodos , Veias Pulmonares/diagnóstico por imagem , Idade Gestacional , Índice de Massa Corporal
20.
Mikrochim Acta ; 191(10): 589, 2024 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256238

RESUMO

Rapid and reliable detection method for African swine fever virus (ASFV) is proposed by surface-enhanced Raman spectroscopy (SERS). The ASFV target DNA can be specifically captured by sandwich hybridization between nanomagnetic beads and a SERS probe. Experimental results show that the significant Raman signal of the SERS probe with gold nanoparticles and a molecular reporter DTNB (5,5'-dimercapto-bis (2-nitrobenzoic acid)) can be adopted for detecting the hybridization chain reaction of ASFV DNA. The advantage of the SERS sandwich hybridization assay is the large response range from the single molecule level to 108 copies per mL, which not only can overcome the tedious time required for the amplification reaction but also provides a comparative method to polymerase chain reaction. Furthermore, real samples of African swine fever virus were detected from different subjects of swine fever virus including porcine reproductive respiratory syndrome virus and Japanese encephalitis virus. The proposed biosensor method can rapidly detect ASFV correctly within 15 min as a simple, convenient, low-cost detection approach. The biosensor can be used as a platform for the determination in biological, food, and environmental analytical fields.


Assuntos
Vírus da Febre Suína Africana , Ouro , Nanopartículas Metálicas , Hibridização de Ácido Nucleico , Análise Espectral Raman , Vírus da Febre Suína Africana/isolamento & purificação , Vírus da Febre Suína Africana/genética , Análise Espectral Raman/métodos , Nanopartículas Metálicas/química , Animais , Ouro/química , Técnicas Biossensoriais/métodos , Suínos , DNA Viral/análise , DNA Viral/genética , Limite de Detecção , Febre Suína Africana/diagnóstico , Febre Suína Africana/virologia
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