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1.
Front Immunol ; 15: 1308238, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660313

RESUMO

Introduction: Limited data were available on the effectivenessfour years after Homo or Hetero prime-boost with 10 µg Hansenulapolymorpha recombinant hepatitis B vaccine (HepB-HP) and 20 µgChinese hamster ovary cell HepB (HepB-CHO). Methods: A crosssectional study was performed in maternalhepatitis B surface antigen (HBsAg)-negative children whoreceived one dose of 10 µg HepB-HP at birth, Homo or Heteroprime-boost with 10 µg HepB-HP and 20 µg HepB-CHO at 1 and 6months. HBsAg and hepatitis B surface antibody (anti-HBs) fouryears after immunization were quantitatively detected by achemiluminescent microparticle immunoassay (CMIA). Results: A total of 359 children were included; 119 childrenreceived two doses of 10 µg HepB-HP and 120 children receivedtwo doses of 20 µg HepB-CHO, called Homo prime-boost; 120children received Hetero prime-boost with 10 µg HepB-HP and 20µg HepB-CHO. All children were HBsAg negative. The geometricmean concentration (GMC) and overall seropositivity rate (SPR) ofanti-HBs were 59.47 (95%CI: 49.00 - 72.16) mIU/ml and 85.51%(307/359). Nearly 15% of the study subjects had an anti-HBsconcentration < 10 mIU/ml and 5.01% had an anti-HBsconcentration ≤ 2.5 mIU/ml. The GMC of the 20 µg CHO Homoprime-boost group [76.05 (95%CI: 54.97 - 105.19) mIU/ml] washigher than that of the 10 µg HP Homo group [45.86 (95%CI:31.94 - 65.84) mIU/ml] (p = 0.035). The GMCs of the Heteroprime-boost groups (10 µg HP-20 µg CHO and 20 µg CHO-10 µgHP) were 75.86 (95% CI: 48.98 - 107.15) mIU/ml and 43.65(95%CI: 27.54 - 69.18) mIU/ml, respectively (p = 0.041). Aftercontrolling for sex influence, the SPR of the 20 µg CHO Homoprime-boost group was 2.087 times than that of the 10 µg HPHomo group. Discussion: The HepB booster was not necessary in the generalchildren, Homo/Hetero prime-boost with 20 µg HepB-CHO wouldincrease the anti-HBs concentration four years after immunization,timely testing and improved knowledge about the self-pay vaccinewould be good for controlling hepatitis B.


Assuntos
Cricetulus , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B , Hepatite B , Imunização Secundária , Vacinas Sintéticas , Humanos , Vacinas contra Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Antígenos de Superfície da Hepatite B/imunologia , Feminino , Animais , Masculino , Hepatite B/prevenção & controle , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Células CHO , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Estudos Transversais , Criança , Lactente , Pré-Escolar , Vírus da Hepatite B/imunologia
2.
J Control Release ; 369: 420-443, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38575075

RESUMO

Wound healing involves distinct phases, including hemostasis, inflammation, proliferation, and remodeling, which is a complex and dynamic process. Conventional preparations often fail to meet multiple demands and provide prompt information about wound status. Here, a pH/ROS dual-responsive hydrogel (OHA-PP@Z-CA@EGF) was constructed based on oxidized hyaluronic acid (OHA), phenylboronic acid-grafted ε-polylysine (PP), chlorogenic acid (CA)-loaded ZIF-8 (Z-CA), and epidermal growth factor (EGF), which possesses intrinsic antibacterial, antioxidant, and angiogenic capacities. Due to the Schiff base and Phenylboronate ester bonds, the hydrogel exhibited excellent mechanical properties, strong adhesion, good biodegradability, high biocompatibility, stable rheological properties, and self-healing ability. Moreover, introducing Z-CA as an initiator and nanofiller led to the additional cross-linking of hydrogel through coordination bonds, which further improved the mechanical properties and antioxidant capabilities. Bleeding models of liver and tail amputations demonstrated rapid hemostatic properties of the hydrogel. Besides, the hydrogel regulated macrophage phenotypes via the NF-κB/JAK-STAT pathways, relieved oxidative stress, promoted cell migration and angiogenesis, and accelerated diabetic wound healing. The hydrogel also enabled real-time monitoring of the wound healing stages by colorimetric detection. This multifunctional hydrogel opens new avenues for the treatment and management of full-thickness diabetic wounds.

3.
Nanotechnology ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593758

RESUMO

To break the resolution limitation of traditional resists, more work is needed on non-chemically amplified resists (non-CARs). Non-CARs based on iodonium salt modified polystyrene (PS-I) were prepared with controllable molecular weight and structure. The properties of the resist can be adjusted by the uploading of iodonium salts on the polymer chain, the materials with a higher proportion of iodonium salts show better lithography performance. By comparing contrast curves and quality of the lithographic patterns, the optimum developing condition of 4-methyl-2-pentanone and ethyl alcohol (v:v = 1:7) was selected. The high-resolution stripes of 15 nm half-pitch (HP) can be achieved by PS-I0.58 in e-beam lithography (EBL). PS-I0.58 shows the advanced lithography performance in the patterns of 16 nm HP and 18 nm HP stripes with low line edge roughness (LER) (3.0 nm and 2.4 nm). The resist shows excellent potential for further pattern transfer, the etch selectivity of resist PS-I0.58 to the silicon was close to 12:1. The lithographic mechanism of PS-I was investigated by experimental and theoretical calculation, which indicate the polarity of materials changes resulted in the solubility switch. This work provides a new option and useful guidelines for the development of high-resolution resist.

4.
Org Biomol Chem ; 22(9): 1850-1858, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38345427

RESUMO

ß-Galactosidase (ß-gal), which is responsible for the hydrolysis of the glycosidic bond of lactose to galactose, has been recognized as an important biomarker of cell or organism status, especially cell senescence and primary ovarian cancer. Extensive efforts have been devoted to develop probes for detecting and visualizing ß-gal in cells. Herein, a fluorescent probe gal-HCA which possesses both excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) properties was prepared to monitor ß-gal in living cells. The probe consists of 2-hydroxy-4'-dimethylamino-chalcone (HCA) capped with a D-galactose group. The cleavage of the glycosidic bond in gal-HCA triggered by ß-gal releases HCA, which results in a significant bathochromic shift in fluorescence from 532 to 615 nm. The probe exhibited high selectivity and sensitivity toward ß-gal with a detection limit as low as 0.0122 U mL-1. The confocal imaging investigation demonstrated the potential of gal-HCA in monitoring the endocellular overexpressed ß-gal in senescent cells and ovarian cancer cells. This study provides a straightforward approach for the development of fluorescent probes to monitor ß-gal and detection of ß-gal-associated diseases.


Assuntos
Chalconas , Neoplasias Ovarianas , Feminino , Humanos , Corantes Fluorescentes/química , Prótons , Neoplasias Ovarianas/diagnóstico por imagem , Imagem Óptica/métodos , beta-Galactosidase
5.
Biomed Pharmacother ; 170: 116025, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113625

RESUMO

Trace elements (TEs) are essential for the treatment of rheumatoid arthritis (RA). This study aimed to prepare a TEs solution enriched with various organic states to evaluate its preventive, therapeutic effects, and mechanism of action in RA and to provide a treatment method for RA treatment. The TEs in natural ore were extracted and added to 0.5% (W/V) L-alanyl-L-glutamine (LG) to obtain a TEs solution (LG-WLYS), which was examined for its concentration and quality. The antioxidant properties and effects of LG-WLYS on cell behavior were evaluated at the cellular level. The preventive and therapeutic effects and mechanism of action of LG-WLYS in rats with RA were explored. The LG-WLYS solution was clear, free from visible foreign matter, and had a pH of 5.33 and an osmolality of 305.67 mOsmol/kg. LG-WLYS inhibited cell migration and angiogenesis. LG-WLYS solution induced macrophages to change from M1-type to M2-type, increased the content of antioxidant enzymes (glutathione, superoxide dismutase, and IL-10), decreased the levels of nitric oxide, malondialdehyde, TNF-α, IL-1ß, IL-6, COX-2, and iNOs, scavenging reactive oxygen species from the lesion site, inhibiting the apoptosis of chondrocytes, regulating inflammatory microenvironment, and decreasing inflammation response to exert the therapeutic effect for RA. In conclusion, LG-WLYS has outstanding therapeutic and preventive effects against RA and has enormous potential for further development.


Assuntos
Artrite Reumatoide , Oligoelementos , Ratos , Animais , Oligoelementos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Macrófagos , Fator de Necrose Tumoral alfa/farmacologia
6.
Adv Sci (Weinh) ; 10(31): e2303167, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37740428

RESUMO

Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri-cross-linked inflammatory microenvironment-responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment-responsive hydrogel (OD-PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano-fillers into the hydrogel results in extra cross-linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple-network is achieved. The hydrogel has injectable, self-healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli-responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH-regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF-κB and MAPK pathways, exerting anti-inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple-network structure provides an effective strategy to treat IDs, holding great promise in clinical application.


Assuntos
Nanopartículas , Selênio , Animais , Ratos , NF-kappa B , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Hidrogéis , Espécies Reativas de Oxigênio , Staphylococcus aureus , Sistema de Sinalização das MAP Quinases
7.
ACS Omega ; 8(30): 26739-26748, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37546582

RESUMO

2-Aminoanthracene was used as a nucleophilic additive in a molecular glass photoresist, bisphenol A derivative (BPA-6-epoxy), to improve advanced lithography performance. The effect of 2-aminoanthracene on BPA-6-epoxy was studied by electron beam lithography (EBL) and extreme ultraviolet lithography (EUVL). The result indicates that the additive can optimize the pattern outline by regulating epoxy cross-linking reaction, avoiding photoresist footing effectively in EBL. The EUVL result demonstrates that 2-aminoanthracene can significantly reduce line width roughness (LWR) for HP (Half-Pitch) 25 nm (from 4.9 to 3.8 nm) and HP 22 nm (from 6.9 to 3.0 nm). The power spectrum density (PSD) curve further confirms the reduction of roughness at medium and high frequency for HP 25 nm and the whole range of frequency for HP 22 nm, respectively. The study offers useful guidelines to improve the roughness of a chemically amplified molecular glass photoresist with epoxy groups for electron beam lithography and extreme ultraviolet lithography.

8.
Pharmaceutics ; 15(8)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37631371

RESUMO

A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of -27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box-Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development.

10.
Nanoscale Horiz ; 8(8): 1090-1097, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37272286

RESUMO

Organic-inorganic nanocomposite films formed from blends of small-molecule organic semiconductors and colloidal quantum dots are attractive candidates for high efficiency, low-cost solar energy harvesting devices. Understanding and controlling the self-assembly of the resulting organic-inorganic nanocomposite films is crucial in optimising device performance, not only at a lab-scale but for large-scale, high-throughput printing and coating methods. Here, in situ grazing incidence X-ray scattering (GIXS) gives direct insights into how small-molecule organic semiconductors and colloidal quantum dots self-assemble during blade coating. Results show that for two blends separated only by a small difference in the structure of the small molecule forming the organic phase, crystallisation may proceed down two distinct routes. It either occurs spontaneously or is mediated by the formation of quantum dot aggregates. Irrespective of the initial crystallisation route, the small-molecule crystallisation acts to exclude the quantum dot inclusions from the growing crystalline matrix phase. These results provide important fundamental understanding of structure formation in nanocomposite films of organic small molecules and colloidal quantum dots prepared via solution processing routes. It highlights the fundamental difference to structural evolution which can be made by seemingly small changes in system composition. It provides routes for the structural design and optimisation of solution-processed nanocomposites that are compatible with the large-scale deposition manufacturing techniques that are crucial in driving their wider adoption in energy harvesting applications.

11.
J Phys Chem Lett ; 14(26): 6135-6142, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37364284

RESUMO

Singlet exciton fission is the spin-allowed generation of two triplet electronic excited states from a singlet state. Intramolecular singlet fission has been suggested to occur on individual carotenoid molecules within protein complexes provided that the conjugated backbone is twisted out of plane. However, this hypothesis has been forwarded only in protein complexes containing multiple carotenoids and bacteriochlorophylls in close contact. To test the hypothesis on twisted carotenoids in a "minimal" one-carotenoid system, we study the orange carotenoid protein (OCP). OCP exists in two forms: in its orange form (OCPo), the single bound carotenoid is twisted, whereas in its red form (OCPr), the carotenoid is planar. To enable room-temperature spectroscopy on canthaxanthin-binding OCPo and OCPr without laser-induced photoconversion, we trap them in a trehalose glass. Using transient absorption spectroscopy, we show that there is no evidence of long-lived triplet generation through intramolecular singlet fission despite the canthaxanthin twist in OCPo.


Assuntos
Cantaxantina , Carotenoides , Carotenoides/química , Análise Espectral/métodos , Proteínas de Bactérias/química , Luz
12.
ACS Omega ; 8(13): 12173-12182, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37033792

RESUMO

A novel molecular glass (TPSiS) with photoacid generator (sulfonium salt group) binding to tetraphenylsilane derivatives was synthesized and characterized. The physical properties such as solubility, film-forming ability, and thermal stability of TPSiS were examined to assess the suitability for application as a candidate for photoresist materials. The sulfonium salt unit underwent photolysis to effectively generate photoacid on UV irradiation, which catalyzed the deprotection of the t-butyloxycarbonyl groups. It demonstrates that the TPSiS can be used as a 'single-component' molecular resist without any additives. The lithographic performance of the TPSiS resist was evaluated by electron beam lithography. The TPSiS resist can resolve 25 nm dense line/space patterns and 16 nm L/4S semidense line/space patterns at a dose of 45 and 85 µC/cm2 for negative-tone development (NTD). The etching selectivity of the TPSiS resist to Si substrate is 8.6 under SF6/O2 plasma, indicating a potential application. Contrast analysis suggests that the significant solubility switch within a narrow exposure dose range (18-47 µC/cm2) by NTD is favorable for high-resolution patterns. This study supplies useful guidelines for the optimization and development of single-component molecular glass resists with high lithographic performance.

13.
Pharmaceutics ; 15(3)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36986680

RESUMO

Drug degradation at low pH and rapid clearance from intestinal absorption sites are the main factors limiting the development of oral macromolecular delivery systems. Based on the pH responsiveness and mucosal adhesion of hyaluronic acid (HA) and poly[2-(dimethylamino)ethyl methacrylate] (PDM), we prepared three HA-PDM nano-delivery systems loaded with insulin (INS) using three different molecular weights (MW) of HA (L, M, H), respectively. The three types of nanoparticles (L/H/M-HA-PDM-INS) had uniform particle sizes and negatively charged surfaces. The optimal drug loadings of the L-HA-PDM-INS, M-HA-PDM-INS, H-HA-PDM-INS were 8.69 ± 0.94%, 9.11 ± 1.03%, and 10.61 ± 1.16% (w/w), respectively. The structural characteristics of HA-PDM-INS were determined using FT-IR, and the effect of the MW of HA on the properties of HA-PDM-INS was investigated. The release of INS from H-HA-PDM-INS was 22.01 ± 3.84% at pH 1.2 and 63.23 ± 4.10% at pH 7.4. The protective ability of HA-PDM-INS with different MW against INS was verified by circular dichroism spectroscopy and protease resistance experiments. H-HA-PDM-INS retained 45.67 ± 5.03% INS at pH 1.2 at 2 h. The biocompatibility of HA-PDM-INS, regardless of the MW of HA, was demonstrated using CCK-8 and live-dead cell staining. Compared with the INS solution, the transport efficiencies of L-HA-PDM-INS, M-HA-PDM-INS, and H-HA-PDM-INS increased 4.16, 3.81, and 3.10 times, respectively. In vivo pharmacodynamic and pharmacokinetic studies were performed in diabetic rats following oral administration. H-HA-PDM-INS exhibited an effective hypoglycemic effect over a long period, with relative bioavailability of 14.62%. In conclusion, these simple, environmentally friendly, pH-responsive, and mucoadhesive nanoparticles have the potential for industrial development. This study provides preliminary data support for oral INS delivery.

14.
Food Chem ; 418: 135939, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36948024

RESUMO

Epigallocatechin gallate (EGCG) has attracted the increasing attention of many researchers, especially in the field of tumor therapy. However, EGCG has poor fat solubility, low stability, low bioavailability, and a high effective dose in vivo. Traditional drug delivery methods are difficult to deliver the water-soluble EGCG efficiently and in high doses to tumor sites. To address these issues, a new type of strategy has been tried in this study to transform EGCG from a "Bioactive natural ingredient" into a "Bioactive drug carrier". Briefly, the EGCG was modified with a fat-soluble 9-fluorene methoxy carbonyl (Fmoc) motif, and the obtained EGCG-Fmoc showed a considerable improvement in lipid solubility and stability. Interestingly, EGCG-Fmoc obtained the characteristic of self-assembly in water, making it easier to take up by tumor cells. Furthermore, the self-assembled nanocomplex exhibited paclitaxel encapsulation performance and could achieve the dual delivery of EGCG and paclitaxel.


Assuntos
Catequina , Portadores de Fármacos , Micelas , Paclitaxel , Água
15.
Hum Vaccin Immunother ; 19(1): 2163813, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36704960

RESUMO

Limited data are available on the effectiveness of COVID-19 vaccines used in China in real-world outbreaks - especially against Omicron variants in vaccinated individuals. Two outbreaks of SARS-CoV-2 Omicron variants - the first involving the sub-lineage BA.2 and the second the BA.1 variant - occurred in Quzhou. Infected people and their close contacts were divided according to vaccination status: unvaccinated, partially vaccinated, fully vaccinated, and boosted. The Cox proportional-hazard regression model was used to estimate the evolving hazard for vaccinated individuals after their first immunization. 138 people had been infected with the SARS-CoV-2 Omicron BA.2 variant and 13 with the BA.1 variant. Of the 151 infections, 99.34% (150/151) were mild or asymptomatic and 90.07% (136/151) were vaccine breakthrough cases. The total vaccine effectiveness (VE) of partial, full, and booster vaccinations during the two outbreaks was 47.4% (95%CI: 0-93.1%), 28.9% (95%CI: 0-60.2%), and 27.5% (95%CI: 0-58.3%). The VE of booster vaccination against the Omicron BA.1 variant was higher than that for the BA.2 variant. The cumulative hazard began to increase 220 days after the first immunization. The transmissibility of the Omicron BA.2 variant as for BA.1 did not increase in vaccinated individuals; booster vaccination after a primary course substantially increased protection. Our study found that the SARS-CoV-2 Omicron variant caused less severe illness and that the VE of boosters against the Omicron variant was less than 30%. Timely administration of the booster dose was important, especially for individuals aged over 80 years old.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Idoso de 80 Anos ou mais , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Surtos de Doenças/prevenção & controle
17.
ACS Appl Mater Interfaces ; 15(1): 2289-2300, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36578201

RESUMO

Nonchemically amplified resists based on triphenyl sulfonium triflate-modified polystyrene (PSTS) were prepared by a facile method of modification of polystyrene with sulfonium groups. The uploading of the sulfonium group can be well-controlled by changing the feed ratio of raw materials, resulting in PSTS0.5 and PSTS0.7 resists with sulfonium ratios of 50 and 70%, respectively. The optimum developer (methyl isobutyl ketone/ethanol = 1:7) is obtained by analyzing contrast curves of electron beam lithography (EBL). PSTS0.7 exhibits a better resolution (18 nm half-pitch (HP)) than the PSTS0.5 resist (20 nm HP) at the same developing conditions for EBL. This novel resist platform was further evaluated by extreme ultraviolet lithography, and patterning performance down to 13 nm HP at a dose of 186 mJ cm-2 with a line edge roughness of 2.8 nm was achieved. Our detailed study of the reaction and patterning mechanism suggests that the decomposition of the polar triflate and triphenyl sulfonium groups into nonpolar sulfide or polystyrene plays an important role in the solubility switch.

18.
Front Public Health ; 11: 1333178, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38274546

RESUMO

Background: Hemorrhagic fever with renal syndrome (HFRS) is one of the 10 major infectious diseases that jeopardize human health and is distributed in more than 30 countries around the world. China is the country with the highest number of reported HFRS cases worldwide, accounting for 90% of global cases. The incidence level of HFRS in Quzhou is at the forefront of Zhejiang Province, and there is no specific treatment for it yet. Therefore, it is crucial to grasp the epidemiological characteristics of HFRS in Quzhou and establish a prediction model for HFRS to lay the foundation for early warning of HFRS. Methods: Descriptive epidemiological methods were used to analyze the epidemic characteristics of HFRS, the incidence map was drawn by ArcGIS software, the Seasonal AutoRegressive Integrated Moving Average (SARIMA) and Prophet model were established by R software. Then, root mean square error (RMSE) and mean absolute error (MAE) were used to evaluate the fitting and prediction performances of the model. Results: A total of 843 HFRS cases were reported in Quzhou City from 2005 to 2022, with the highest annual incidence rate in 2007 (3.93/100,000) and the lowest in 2022 (1.05/100,000) (P trend<0.001). The incidence is distributed in a seasonal double-peak distribution, with the first peak from October to January and the second peak from May to July. The incidence rate in males (2.87/100,000) was significantly higher than in females (1.32/100,000). Farmers had the highest number of cases, accounting for 79.95% of the total number of cases. The incidence is high in the northwest of Quzhou City, with cases concentrated on cultivated land and artificial land. The RMSE and MAE values of the Prophet model are smaller than those of the SARIMA (1,0,1) (2,1,0)12 model. Conclusion: From 2005 to 2022, the incidence of HFRS in Quzhou City showed an overall downward trend, but the epidemic in high-incidence areas was still serious. In the future, the dynamics of HFRS outbreaks and host animal surveillance should be continuously strengthened in combination with the Prophet model. During the peak season, HFRS vaccination and health education are promoted with farmers as the key groups.


Assuntos
Febre Hemorrágica com Síndrome Renal , Masculino , Feminino , Humanos , Febre Hemorrágica com Síndrome Renal/epidemiologia , Estações do Ano , China/epidemiologia , Surtos de Doenças , Incidência
19.
Int J Nanomedicine ; 17: 6377-6398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36545220

RESUMO

Introduction: The blood-brain barrier (BBB) is a key obstacle to the delivery of drugs into the brain. Therefore, it is essential to develop an advanced drug delivery nanoplatform to solve this problem. We previously screened a small rabies virus glycoprotein 15 (RVG15) peptide with 15 amino acids and observed that most of the RVG15-modified nanoparticles entered the brain within 1 h of administration. The high BBB penetrability gives RVG15 great potential for brain-targeted drug delivery systems. Moreover, a multifunctional integrated nanoplatform with a high drug-loading capacity, tunable functionality, and controlled drug release is crucial for tumor treatment. Zeolitic imidazolate framework (ZIF-8) is a promising nanodrug delivery system. Methods: Inspired by the biomimetic concept, we designed RVG15-coated biomimetic ZIF-8 nanoparticles (RVG15-PEG@DTX@ZIF-8) for docetaxel (DTX) delivery to achieve efficient glioblastoma elimination in mice. This bionic nanotherapeutic system was prepared by one-pot encapsulation, followed by coating with RVG15-PEG conjugates. The size, morphology, stability, drug-loading capacity, and release of RVG15-PEG@DTX@ZIF-8 were thoroughly investigated. Additionally, we performed in vitro evaluation, cell uptake capacity, BBB penetration, and anti-migratory ability. We also conducted an in vivo evaluation of the biodistribution and anti-glioma efficacy of this bionic nanotherapeutic system in a mouse mode. Results: In vitro studies showed that, this bionic nanotherapeutic system exhibited excellent targeting efficiency and safety in HBMECs and C6 cells and high efficiency in crossing the BBB. Furthermore, the nanoparticles cause rapid DTX accumulation in the brain, allowing deeper penetration into glioma tumors. In vivo antitumor assay results indicated that RVG15-PEG@DTX@ZIF-8 significantly inhibited glioma growth and metastasis, thereby improving the survival of tumor-bearing mice. Conclusion: Our study demonstrates that our bionic nanotherapeutic system using RVG15 peptides is a promising and powerful tool for crossing the BBB and treating glioblastoma.


Assuntos
Glioblastoma , Glioma , Nanopartículas , Camundongos , Animais , Barreira Hematoencefálica/metabolismo , Distribuição Tecidual , Biomimética , Linhagem Celular Tumoral , Glioblastoma/patologia , Sistemas de Liberação de Medicamentos/métodos , Glioma/tratamento farmacológico , Docetaxel/farmacologia , Peptídeos/química , Nanopartículas/química
20.
Analyst ; 147(23): 5264-5268, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36330961

RESUMO

NAD(P)H quinone oxidoreductase1 (NQO1) is a flavoenzyme that regulates the redox potential level in cells. Overexpression of NQO1 has been proven to be relevant to some malignant tumors. Herein a bioluminescent probe NQO1-Luc equipped with an NQO1-targeting group, trimethyl-locked quinone propionic acid (QPA), was constructed. The reduction of NQO1-Luc could be triggered by NQO1, resulting in the release of free D-luciferin, and concomitantly a bright bioluminescence emission. NQO1-Luc exhibits high selectivity and sensitivity toward NQO1 activity and the capability of distinguishing NQO1-overexpressing cells in vitro and in vivo, which offers a promising tool for investigations of NQO1 related biological processes including tumors in living organisms.


Assuntos
NAD(P)H Desidrogenase (Quinona) , Neoplasias , Humanos , NAD(P)H Desidrogenase (Quinona)/genética , Quinonas , Benzoquinonas
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