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1.
Sci Total Environ ; : 174334, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38955279

RESUMO

High-precision rainfall erosivity mapping is crucial for accurately evaluating regional soil erosion on the Tibetan Plateau (TP) under the backdrop of climate warming and humidification. Although high spatiotemporal resolution gridded precipitation data provides the foundation for rainfall erosivity mapping, the increasing spatial heterogeneity of rainfall with decreasing temporal granularity can lead to greater errors when directly computing rainfall erosivity from gridded precipitation data. In this study, a site-scale conversion coefficient was established so that rainfall erosivity calculated using hourly data can be converted to rainfall erosivity calculated using per-minute data. A revised model was established for calculating the rainfall erosivity based on high-resolution hourly precipitation data from the Third Pole gridded precipitation dataset (TPHiPr). The results revealed a notable underestimation in the original calculation results obtained using the TPHiPr, but strong correlation was observed between the two sets of results. There was a significant improvement in the Nash-Sutcliffe coefficient of efficiency (from -0.39 to 0.80) and the Percent Bias (from -63.95 % to 0.37 %) after model revision. The TPHiPr effectively depict the spatial characteristics of rainfall erosivity on the TP. It accurately reflected the rain shadow area on the northern flank of the Himalayas and the dry-hot valley in the Hengduan Mountains. It also showed high rainfall erosivity values in the tropical rainforest area on the southern flank of the eastern Himalayas. The overall trend of rainfall erosivity has increased on the TP during the period 1981 to 2020, with 65.91 % of the regions exhibiting an increasing trend and 22.25 % showing significant increases, indicating an intensified risk of water erosion. These findings suggest that the 40-year-high spatial resolution rainfall erosivity dataset can provide accurate data support for a quantitative understanding of soil erosion on the TP.

2.
J Nanobiotechnology ; 22(1): 381, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951911

RESUMO

Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Hidrogéis , Neoplasias Hepáticas , Hidrogéis/química , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/terapia , Humanos , Animais , Embolização Terapêutica/métodos
3.
Opt Lett ; 49(13): 3552-3555, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950207

RESUMO

Detecting heavy metal and radioactive elements distributed in the environment and human body is crucial for life and environmental safety. A lens with a high numerical aperture (NA) is used in laser-induced breakdown spectroscopy to collect the plasma fluorescence as much as possible and improve the limit of detection. However, even a lens with NA up to 0.6, only the fluorescence in a solid angle of 0.4π can be collected. In this work, a novel, to our knowledge, fluorescence collecting scheme composed of a parabolic mirror and a lens is proposed which can collect the plasma fluorescence in a solid angle of ∼1.4π for an opaque material and ∼1.9π for a transparent material. Simulation results show that for opaque samples, this method can improve the fluorescence collection ability by 3.8 times compared to a single lens (NA = 0.5) collection scheme, and for transparent samples 4.5 times may be achieved. In experiments, a 2.8-fold enhancement in the fluorescence collection ability is demonstrated, and the signal-to-noise ratio is increased by 2.5 times for opaque samples.

4.
Cancer Lett ; 598: 217095, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964728

RESUMO

Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.

5.
Breastfeed Med ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963776

RESUMO

Background: Gestational weight gain (GWG) may be associated with delayed onset of lactogenesis II (DOL II), but it is still unclear and controversial. Object: The study aims to evaluate the relationship between GWG and DOL II. Methods: A comprehensive search was performed in 10 electronic databases from inception to May 21, 2023, for studies that reported outcomes in breastfeeding. Data were extracted by two independent reviewers. A meta-analysis was conducted to calculate the pooled estimates of association using random-effect models with Review Manager (RevMan) software version 5.4. The primary outcome was the rate of DOL II. Results: In this study, 248,515 women were included in 16 eligible articles. Women with excessive GWG have a higher risk of DOL II (odds ratio [OR] = 1.28; 95% confidence interval [CI]: 1.15-1.43). Specifically, prepregnancy overweight and obese women with GWG above recommendations (OR = 3.01, 95% CI: 1.38-6.57) and underweight women with excessive GWG before pregnancy have a higher risk of DOL II (OR = 3.32, 95% CI: 1.69-6.53). Nonetheless, there is no distinction between women with inadequate GWG and those with adequate GWG in DOL II(OR = 1.08, 95% CI: 0.88-1.33). In addition, the women whose GWG is above the recommendations also tend to stop exclusive breastfeeding 1 month postpartum (OR = 0.82, 95% CI: 0.80-0.85). Conclusion: Excessive GWG has a negative influence on the timing of the onset of lactogenesis and exclusive breastfeeding within 1 month postpartum.

6.
Pharmacol Res ; : 107293, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971271

RESUMO

Colorectal cancer (CRC) presents a complex landscape, characterized by both inter-tumor and intra-tumor heterogeneity. RUNX1, a gene implicated in modulating tumor cell growth, survival, and differentiation, remains incompletely understood regarding its impact on CRC prognosis. In our investigation, we discerned a positive correlation between elevated RUNX1 expression and aggressive phenotypes across various CRC subtypes. Notably, knockdown of RUNX1 demonstrated efficacy in restraining CRC proliferation both in vitro and in vivo, primarily through inducing apoptosis and impeding cell proliferation. Mechanistically, we unveiled a direct regulatory link between RUNX1 and cholesterol synthesis, mediated by its control over HMGCR expression. Knockdown of RUNX1 in CRC cells triggered HMGCR transcriptional activation, culminating in elevated cholesterol levels that subsequently hindered cancer progression. Clinically, heightened RUNX1 expression emerged as a prognostic marker for adverse outcomes in CRC patients. Our findings underscore the pivotal involvement of RUNX1 in CRC advancement and its potential as a therapeutic target. The unique influence of RUNX1 on cholesterol synthesis and HMGCR transcriptional regulation uncovers a novel pathway contributing to CRC progression.

7.
Nat Commun ; 15(1): 5668, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971832

RESUMO

The creation of well-defined hollow two-dimensional structures from small organic molecules, particularly those with controlled widths and numbers of segments, remains a formidable challenge. Here we report the fabrication of the well-defined concentric hollow two-dimensional platelets with programmable widths and numbers of segments through constructing a concentric multiblock two-dimensional precursor followed by post-processing. The fabrication of concentric multi-hexagons two-dimensional platelets is realized by the alternative heteroepitaxial growth of two donor-acceptor molecules. Upon ultraviolet irradiation, one of the two donor-acceptor molecules can be selectively oxidized by singlet oxygen generated during the process, and the oxidized product becomes more soluble due to increased polarity. This allows for selective removal of the oxidized segments simply by solvent dissolution, yielding hollow multiblock two-dimensional structures. The hollow two-dimensional platelets can be utilized as templates to lithograph complex electrodes with precisely controlled gap sizes, thereby offering a platform for examining the optoelectronic performance of functional materials.

8.
Artigo em Chinês | MEDLINE | ID: mdl-38973039

RESUMO

Objective:To analyze the clinical characteristics of middle ear mastoiditis combined with sigmoid sinus thrombophlebitis in children. Methods:Author retrospectively analyzed the clinical data of 6 children with middle ear mastoiditis combined with sigmoid sinus thrombophlebitis who were hospitalized in the Department of Infectious Diseases and Department of Neurology with first diagnosis of fever/headache, and subsequently underwent middle ear mastoidectomy in our department. All patients underwent comprehensive otoscopic, audiologic, imaging, and pathogenetic examinations. Clinical manifestations, pathogenetic features, treatment methods and prognosis were summarized, and the follow-up period was 3-6 months. Results:All 6 cases were first diagnosed with intracranial complications such as fever and headache in the internal medicine department. Within one month, all patients developed ear symptoms including pain, discharge, and hearing loss. Audiologic examination revealed conductive hearing loss in five cases and total deafness in one case. MRI, MRV and MRA examinations suggested that there were 6 cases of middle ear infection combined with thrombophlebitis of the ethmoid sinus, of which 3 cases had thrombus in the ethmoid sinus. 6 cases received surgical treatments: 2 cases of radical mastoidectomy+grommet Insertion, and 4 cases of radical mastoidectomy. Pathogenetic examination identified Streptococcus pneumoniae in three cases, Pseudomonas aeruginosa in one case, Enterobacter cloacae complex in one case, and no pathogens were detected in one case. Postoperative pathology was inflammatory granulation in all 6 cases. Follow-up was 3-6 months with no recurrence of intracranial and middle ear lesions on regular review. Conclusion:Children with recurrent fever, headache, and a recent history of acute and chronic otitis media should be evaluated for the possibility of sigmoid sinus thrombophlebitis, and imaging tests should be performed in a timely manner to clarify the diagnosis. Once diagnosed, surgery to remove the lesions around the ethmoid sinus, smooth drainage combined with antibiotic therapy is the most direct and effective treatment, and anticoagulation therapy is given when necessary. Timely diagnosis, multidisciplinary collaboration, and accurate timing of the management of primary foci and comorbidities are crucial to the treatment of the disease.


Assuntos
Mastoidite , Humanos , Estudos Retrospectivos , Mastoidite/complicações , Criança , Masculino , Feminino , Pré-Escolar , Mastoidectomia , Trombose dos Seios Intracranianos/complicações
9.
Adv Sci (Weinh) ; : e2400229, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973266

RESUMO

Inflammatory responses play a central role in coordinating biomaterial-mediated tissue regeneration. However, precise modulation of dynamic variations in microenvironmental inflammation post-implantation remains challenging. In this study, the traditional ß-tricalcium phosphate-based scaffold is remodeled via ultrathin MXene-Ti3C2 decoration and Zn2+/Sr2+ ion-substitution, endowing the scaffold with excellent reactive oxygen species-scavenging ability, near-infrared responsivity, and enhanced mechanical properties. The induction of mild hyperthermia around the implant via periodic near-infrared irradiation facilitates spatiotemporal regulation of inflammatory cytokines secreted by a spectrum of macrophage phenotypes. The process initially amplifies the pro-inflammatory response, then accelerates M1-to-M2 macrophage polarization transition, yielding a satisfactory pattern of osteo-immunomodulation during the natural bone healing process. Later, sustained release of Zn2+/Sr2+ ions with gradual degradation of the 3D scaffold maintains the favorable reparative M2-dominated immunological microenvironment that supports new bone mineralization. Precise temporal immunoregulation of the bone healing process by the intelligent 3D scaffold enhances bone regeneration in a rat cranial defect model. This strategy paves the way for the application of ß-tricalcium phosphate-based materials to guide the dynamic inflammatory and bone tissue responses toward a favorable outcome, making clinical treatment more predictable and durable. The findings also demonstrate that near-infrared irradiation-derived mild hyperthermia is a promising method of immunomodulation.

10.
RSC Adv ; 14(30): 21241-21249, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38974227

RESUMO

Cardiovascular diseases caused by atherosclerosis (AS) seriously damage human health. Nano-photothermal technology has been proven to inhibit the development of vascular inflammation by inhibiting the proliferation of inflammatory macrophages. However, photothermal therapy can inhibit the enrichment of AS macrophages in the early stage, but the inhibitory effect is insufficient in the later stage. Herein, we designed and prepared CoS1.097 nanocrystals by a simple hydrothermal method as new nanoplatforms for efficient photothermal therapy of arterial inflammation. CoS1.097 nanocrystals exhibited the degradability to release the cobalt ions, and can inhibit the proliferation of macrophages both in vitro and in vivo resulting from the slowly released cobalt ions. Moreover, CoS1.097 nanocrystals showed intense absorption in the NIR region, thus showing excellent photothermal performance. When irradiated by an 808 nm laser, the photothermal effect of CoS1.097 nanocrystals can more efficiently kill the macrophages which play an important role in the development of atherosclerosis. As far as we know, this is the first work on CoS1.097 nanocrystals for photothermal therapy of arterial inflammation.

11.
Int J Cardiol Heart Vasc ; 53: 101434, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38974459

RESUMO

Coronary heart disease (CHD) is a serious cardiovascular illness, for which an elevated uric acid (UA) level presents as a considerable risk factor. This can be treated with UA-lowering drugs such as allopurinol and benzbromarone, which can reduce UA levels by the inhibition of UA production or by promoting its excretion. Such drugs can also be beneficial to CHD in other ways, such as reducing the degree of coronary arteriosclerosis, improving myocardial blood supply and alleviating ventricular remodeling. Different UA-lowering drugs are used in different ways: allopurinol is preferred as a single agent in clinical application, but in absence of the desired response, a combination of drugs such as benzbromarone with ACE inhibitors may be used. Patients must be monitored regularly to adjust the medication regimen. Appropriate use of UA-lowering drugs has great significance for the prevention and treatment of CHD. However, the specific mechanisms of the drugs and individualized drug use need further research. This review article expounds the mechanisms of UA-lowering drugs on CHD and their clinical application strategy, thereby providing a reference for further optimization of treatment.

12.
Ultrason Sonochem ; 107: 106935, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850642

RESUMO

Myofibrillar proteins (MPs) have a notable impact on the firmness and flexibility of gel-based products. Therefore, enhancing the gelation and emulsification properties of scallop MPs is of paramount significance for producing high-quality scallop surimi products. In this study, we investigated the effects of high-intensity ultrasound on the physicochemical and gelation properties of MPs from bay scallops (Argopecten irradians). The carbonyl content of MPs significantly increased with an increase in ultrasound power (150, 350, and 550 W), indicating ultrasound-induced MP oxidation. Meanwhile, high-intensity ultrasound treatment (550 W) enhanced the emulsifying capacity and the short-term stability of MPs (up to 72.05 m2/g and 153.05 min, respectively). As the ultrasound power increased, the disulfide bond content and surface hydrophobicity of MPs exhibited a notable increase, indicating conformational changes in MPs. Moreover, in the secondary structure of MPs, the α-helix content significantly decreased, whereas the ß-sheet content increased, thereby suggesting the ultrasound-induced stretching and flexibility of MP molecules. Sodium-dodecyl sulfate-polyacrylamide gel electrophoresis and scanning electron microscopy analysis further elucidated that high-intensity ultrasound induced MP oxidation, leading to modification of amino acid side chains, intra- and intermolecular cross-linking, and MP aggregation. Consequently, high-intensity ultrasound treatment was found to augment the viscoelasticity, gel strength, and water-holding capacity of MP gels, because ultrasound treatment facilitated the formation of a stable network structure in protein gels. Thus, this study offers theoretical insights into the functional modification of bay scallop MPs and the processing of its surimi products.


Assuntos
Géis , Proteínas Musculares , Pectinidae , Pectinidae/química , Animais , Géis/química , Proteínas Musculares/química , Ondas Ultrassônicas , Fenômenos Químicos , Interações Hidrofóbicas e Hidrofílicas , Emulsões/química
13.
Membranes (Basel) ; 14(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38921495

RESUMO

This study investigated the use of chicken egg white (CEW) waste immobilized on weak acidic nanofiber membranes for removing the anionic acid orange 7 (AO7) dye in batch and continuous flow modes. Different experiments were conducted to evaluate the effectiveness of CEW-modified nanofiber membranes for AO7 removal, focusing on CEW immobilization conditions, adsorption kinetics, and thermodynamics. The CEW-modified nanofiber membrane (namely NM-COOH-CEW) exhibited a maximum AO7 adsorption capacity of 589.11 mg/g within approximately 30 min. The Freundlich isotherm model best represented the equilibrium adsorption data, while the adsorption kinetics followed a pseudo-second-order rate model. Breakthrough curve analysis using the Thomas model and the bed depth service time (BDST) model showed that the BDST model accurately described the curve, with an error percentage under 5%. To investigate AO7 elution efficiency, different concentrations of organic solvents or salts were tested as eluents. The NM-COOH-CEW nanofiber membrane exhibited promising performance as an effective adsorbent for removing AO7 dye from contaminated water.

14.
Proc Natl Acad Sci U S A ; 121(25): e2406788121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38865267

RESUMO

Heritable symbionts are common among animals in nature, but the molecular mechanisms underpinning symbiont invasions of host populations have been elusive. In this study, we demonstrate the spread of Rickettsia in an invasive agricultural pest, the whitefly Bemisia tabaci Mediterranean (MED), across northeastern China from 2018 to 2023. Here, we show that the beneficial symbiont Rickettsia spreads by manipulating host hormone signals. Our analyses suggest that Rickettsia have been horizontally acquired by B. tabaci MED from another invasive whitefly B. tabaci Middle East-Asia Minor 1 during periods of coexistence. Rickettsia is transmitted maternally and horizontally from female B. tabaci MED individuals. Rickettsia infection enhances fecundity and results in female bias among whiteflies. Our findings reveal that Rickettsia infection stimulates juvenile hormone (JH) synthesis, in turn enhancing fecundity, copulation events, and the female ratio of the offspring. Consequently, Rickettsia infection results in increased whitefly fecundity and female bias by modulating the JH pathway. More female progeny facilitates the transmission of Rickettsia. This study illustrates that the spread of Rickettsia among invasive whiteflies in northeastern China is propelled by host hormone regulation. Such symbiont invasions lead to rapid physiological and molecular evolution in the host, influencing the biology and ecology of an invasive species.


Assuntos
Fertilidade , Hemípteros , Rickettsia , Razão de Masculinidade , Simbiose , Animais , Rickettsia/fisiologia , Hemípteros/microbiologia , Hemípteros/fisiologia , Feminino , Masculino , Hormônios Juvenis/metabolismo , China
15.
J Chem Phys ; 160(24)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38916267

RESUMO

We report the free energy barriers for the elementary reactions in the 2e- and 4e- oxygen reduction reaction (ORR) steps on Au(100) in an alkaline solution. Due to the weak adsorption energy of O2 on Au(100), the barrier for the association channel is very low, and the 2e- pathway is clearly favored, while the barrier for the O-O dissociation channel is significantly higher at 0.5 eV. Above 0.7 V reversible hydrogen electrode (RHE), the association channel becomes thermodynamically unfavorable, which opens up the O-O dissociation channel, leading to the 4e- pathway. The low adsorption energy of oxygenated species on Au is now an advantage, and residue ORR current can be observed up to the 1.0-1.2 V region (RHE). In contrast, the O-O dissociation barrier on Au(111) is significantly higher, at close to 0.9 eV, due to coupling with surface reorganization, which explains the lower ORR activity on Au(111) than that on Au(100). In combination with the previously suggested outer sphere electron transfer to O2 for its initial adsorption, these results provide a consistent explanation for the features in the experimentally measured polarization curve for the alkaline ORR on Au(100) and demonstrate an ORR mechanism distinct from that on Pt(111). It also highlights the importance to consider the spin state of O2 in ORR and to understand the activation barriers, in addition to the adsorption energies, to account for the features observed in electrochemical measurements.

16.
Int J Biol Macromol ; 273(Pt 1): 132735, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38825293

RESUMO

Polysaccharides extracted from Hericium erinaceus (HEP) exhibit hepatoprotective activity in the alleviation of non-alcoholic fatty liver disease (NAFLD); however, the mechanisms underlying whether and how HEP regulation of the gut microbiota to alleviate liver-associated metabolic disorders are not well understood. This study used an aged laying hen model to explore the mechanisms through which HEP alleviates NAFLD, with a focus on regulatory function of HEP in the gut microbiome. The results showed that HEP ameliorated hepatic damage and metabolic disorders by improving intestinal barrier function and shaping the gut microbiota and tryptophan metabolic profiles. HEP increased the abundance of Lactobacillus and certain tryptophan metabolites, including indole-3-carboxylic acid, kynurenic acid, and tryptamine in the cecum. These metabolites upregulated the expression of ZO-1 and Occludin by activating the AhR and restoring the intestinal barrier integrity. The increased intestinal barrier functions decreased LPS transferring from the intestine to the liver, inhibited hepatic LPS/TLR4/MyD88/NF-κB pathway activation, and reduced hepatic inflammatory response and apoptosis. Fecal microbiota transplantation experiments further confirmed that the hepatoprotective effect is likely mediated by HEP-altered gut microbiota and their metabolites. Overall, dietary HEP could ameliorate the hepatic damage and metabolic disorders of NAFLD through regulating the "gut-liver" axis.


Assuntos
Galinhas , Modelos Animais de Doenças , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Polissacarídeos , Triptofano , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Triptofano/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/química , Feminino , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia
17.
Eur J Pharmacol ; 978: 176775, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925288

RESUMO

The development of multitarget opioid drugs has emerged as an attractive approach for innovative pain management with reduced side effects. In the present study, a novel hybrid peptide BNT12 containing the opioid and neurotensin (NT)-like fragments was synthesized and pharmacologically characterized. In acute radiant heat paw withdrawal test, intracerebroventricular (i.c.v.) administration of BNT12 produced potent antinociception in mice. The central antinociceptive activity of BNT12 was mainly mediated by µ-, δ-opioid receptor, neurotensin receptor type 1 (NTSR1) and 2 (NTSR2), supporting a multifunctional agonism of BNT12 in the functional assays. BNT12 also exhibited significant antinociceptive effects in spared nerve injury (SNI)-neuropathic pain, complete Freund's adjuvant (CFA)-induced inflammatory pain, acetic acid-induced visceral and formalin-induced pain after i.c.v. administration. Furthermore, BNT12 exhibited substantial reduction of acute antinociceptive tolerance, shifted the dose-response curve to the right by only 1.3-fold. It is noteworthy that BNT12 showed insignificant chronic antinociceptive tolerance at the supraspinal level. In addition, BNT12 exhibited reduced or no opioid-like side effects on conditioned place preference (CPP) response, naloxone-precipitated withdrawal response, acute hyperlocomotion, motor coordination, gastrointestinal transit, and cardiovascular responses. The present investigation demonstrated that the novel hybrid peptide BNT12 might serve as a promising analgesic candidate with limited opioid-like side effects.

18.
Pestic Biochem Physiol ; 202: 105913, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879317

RESUMO

Bacterial leaf blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), poses a significant threat to rice cultivation across diverse regions. Growing concerns about pesticide resistance and environmental impact underscore the urgent necessity for eco-friendly biopesticides. Here, the complete genome sequence of Streptomyces albidoflavus strain ML27 revealed substantial antimicrobial activity and secondary metabolite production potential through genome mining. 3,4-dimethoxyphenol (purity 97%) was successfully isolated from the fermentation broth of S. albidoflavus strain ML27, exhibiting broad and pronounced inhibitory effects on the growth of seven different fungi and five tested bacteria. The efficacy of 3,4-dimethoxyphenol in controlling rice bacterial leaf blight was evaluated through pot tests, demonstrating substantial therapeutic (69.39%) and protective (84.53%) effects. Application of 3,4-dimethoxyphenol to Xoo resulted in cells displayed notable surface depressions, wrinkles, distortions, or even ruptures compared to their typical morphology. Transcriptome analysis revealed significant inhibition of membrane structures, protein synthesis and secretion, bacterial secretion system, two-component system, flagellar assembly, as well as various metabolic and biosynthetic pathways by 3,4-dimethoxyphenol. Notably, the down-regulation of the type III secretion system (T3SS) expression was a pivotal finding. Furthermore, validation via quantitative real-time polymerase chain reaction (qRT-PCR) analysis confirmed significant downregulation of 10 genes related to T3SS upon 3,4-dimethoxyphenol treatment. Based on these results, it is promising to develop 3,4-dimethoxyphenol as a novel biopesticide targeting the T3SS of Xoo for controlling bacterial leaf blight in rice.


Assuntos
Streptomyces , Xanthomonas , Xanthomonas/efeitos dos fármacos , Xanthomonas/genética , Streptomyces/genética , Streptomyces/metabolismo , Doenças das Plantas/microbiologia , Perfilação da Expressão Gênica , Oryza/microbiologia , Antibacterianos/farmacologia
19.
J Nanobiotechnology ; 22(1): 308, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825711

RESUMO

Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.


Assuntos
Adjuvantes Imunológicos , Vacinas Anticâncer , Nanotecnologia , Neoplasias , Vacinas de mRNA , Humanos , Vacinas Anticâncer/imunologia , Nanotecnologia/métodos , Neoplasias/terapia , Neoplasias/imunologia , Animais , Sistemas de Liberação de Medicamentos/métodos , COVID-19/prevenção & controle , Adjuvantes de Vacinas , RNA Mensageiro/genética , SARS-CoV-2/imunologia , Vacinas Sintéticas/imunologia
20.
Plast Reconstr Surg Glob Open ; 12(6): e5853, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38841525

RESUMO

Background: With the popularity of microbotox, pain caused by multiple microdroplets and subcutaneous injection of botulinum toxin is increasing. This study presents a new, refined, three-point nerve block technique that provides effective pain relief during minimally invasive injection therapy targeting the middle and upper face. Methods: Fifty volunteers underwent facial ultrasonography to measure the locations of the supraorbital and infraorbital foramen. Following microdrop Botox injection of the middle and upper face, 100 patients underwent a self-controlled study to analyze whether a three-point nerve block surpasses topical anesthesia for reducing injection pain. The visual analog scale pain score, the time of the three-point method and botulinum toxin injection, and side effects were recorded. Results: Among the volunteers, the location of the supraorbital and infraorbital foramen showed no statistical difference between the left and right sides. For the 100 patients (13 men, 87 women) who underwent the three-point nerve block, the visual analog scale pain scores on the experimental side were significantly lower than those on the control side, except in the frontotemporal region (2.46 ± 0.50, 2.42 ± 0.47, P > 0.05). The duration of the unilateral three-point nerve block was 74.8 ± 5.64 seconds. The total injection time was 189.86 ± 26.79 seconds (range 148-286 s). Conclusions: The three-point method exerted prominent analgesic effects during middle and upper facial treatments, with benefits including a precise block region, high satisfaction, and simple operation technique. Therefore, clinicians can easily master and apply this method.

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