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1.
ChemistryOpen ; 12(1): e202200192, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36627171

RESUMO

Surface-enhanced Raman spectroscopy (SERS) has shown strength in non-invasive, rapid, trace analysis and has been used in many fields in medicine. Machine learning (ML) is an algorithm that can imitate human learning styles and structure existing content with the knowledge to effectively improve learning efficiency. Integrating SERS and ML can have a promising future in the medical field. In this review, we summarize the applications of SERS combined with ML in recent years, such as the recognition of biological molecules, rapid diagnosis of diseases, developing of new immunoassay techniques, and enhancing SERS capabilities in semi-quantitative measurements. Ultimately, the possible opportunities and challenges of combining SERS with ML are addressed.


Assuntos
Técnicas Biossensoriais , Análise Espectral Raman , Humanos , Análise Espectral Raman/métodos , Imunoensaio/métodos , Aprendizado de Máquina , Algoritmos
2.
Plant Sci ; 329: 111594, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36642105

RESUMO

Genetic control of fruit flesh color in watermelon is complex, and significant knowledge gaps still exist. In the present study, we investigated the genetic basis of canary-yellow flesh color in watermelon inbred line PI 635597 using a segregating population derived from a cross between PI 635597 and another inbred line, Cream of Saskatchewan (pale yellow flesh color). We showed that a single dominant gene controls the canary-yellow flesh color for the Cyf (canary-yellow flesh) trait. Bulk segregant analysis (BSA) and fine genetic mapping narrowed down the Cyf locus to a 79.62-kb region on chromosome 6, which harbors 10 predicted genes. Sequence variation analysis in the promoter and coding regions and gene expression analysis in both parental lines and selected watermelon accessions with diverse fruit flesh colors support Cla97C06G122050 (unknown protein) and Cla97C06G122120 (pentatricopeptide repeat) as predicted candidate genes for the Cyf locus. Marker-assisted selection and sequence alignment showed that the Cyf locus could differentiate canary-yellow flesh and pale-yellow flesh. Our results indicate that the Cyf locus might be responsible for canary-yellow flesh color and carotenoid accumulation levels.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36693188

RESUMO

Serum alpha fetoprotein (AFP) is a "gold-standard" biomarker for the diagnosis of hepatocellular carcinoma (HCC). Available pieces of evidence suggest that the ratio of AFP-L3 isoform in the total AFP may provide more accurate prediction for the incidence of HCC. In this work, we design an electrochemical aptasensor for high-accuracy assay of AFP-L3 ratio based on differentiated labeling of AFP isoforms in an orderly fashion. Specifically, total AFP is first captured by an AFP aptamer-functionalized electrode and labeled with quantum dots-functionalized DNA probes via mild reduction. Then, AFP-L3 isoform that strongly binds to Lens culinaris agglutinin is labeled with silver nanoparticles after the exonuclease-catalyzed removal of DNA probes. By tracing the electrochemical responses of quantum dots and silver nanoparticles, respectively, the amounts of total AFP and AFP-L3 isoforms are determined and the AFP-L3 ratio is accordingly calculated to favor the accurate HCC diagnosis. Experimental results prove the high-accuracy assay of AFP-L3 ratio based on the AFP quantitation in a linear range of 0.0008-40 ng mL-1 and AFP-L3 quantitation in a linear range of 0.004-40 ng mL-1. The aptasensor also displays satisfactory specificity and good recoveries even in the complex serum samples. Therefore, the aptasensor may provide a valuable tool for the assay of the AFP-L3 ratio and have a great potential use in early warning of HCC for clinical application.

4.
J Environ Manage ; 330: 117190, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36603263

RESUMO

An ambitious new Post-2020 Global Biodiversity Framework "Kunming-Montreal Global Biodiversity Framework" has been developed. However, the combined effects of climate change and human modification can undermine the potential benefits of the global post-2020 conservation efforts. The co-benefits of stabilizing the climate, conserving biodiversity, and maintaining intact wilderness areas may help to persuade the general public of the need to quickly expand existing protected areas (PAs). To maximize the co-benefits after 2020, the careful optimization of existing (PAs) network and scientific identification of conservation targets are both essential. Here, we mapped hotspots of biodiversity, climate vulnerability, and wilderness in Southwest China (SWC). By analyzing the representativeness and gaps of the existing PAs network in SWC, we devised post-2020 conservation targets and highlighted their implications for decision-makers. Our results showed that the incongruence between hotspots of different species exists, indicating that habitats suitable for one taxon may not fully harbor other taxa. According to our assessment, the five jurisdictions of SWC have warmed on average by 0.4°C-1.1 °C over the past 60 years alone. In particular, biodiversity hotspots in SWC are undergoing stark climatic changes. We uncovered prominent conservation gaps in SWC's network of PAs, especially in terms of climate vulnerability and biodiversity. Due to their insufficient number and unreasonable spatial distribution, the PAs network in SWC may be not capable of meeting its biodiversity, climate vulnerability, and wilderness conservation objectives. To rectify this, we proposed a 3-step mission: milestone 2025, milestone 2030, and goal 2050, which aims to protect 23%, 28%, and 60% of the terrestrial area in SWC, respectively. Taken together, our study derived conservation priority areas with relatively clear spatial boundaries and importance levels, thus providing detailed, timely information for decision-makers to expand the PAs network and implement conservation measures varying in strictness in post-2020 conservation practice.

5.
J Mater Chem B ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629834

RESUMO

Although photodynamic therapy (PDT) has exhibited good potential in therapy of gliomas, the limited penetration depth of light and the obstacle of the blood-brain barrier (BBB) lead to unsatisfactory treatment effects. Herein, a multifunctional nanodrug (UMD) was constructed with up-conversion nanoparticles (NaGdF4:Yb,Tm@NaYF4:Yb,Nd@NaYF4, UCNPs) as the core, the photosensitizer NH2-MIL-53 (Fe) as the shell and a carrier for loading chemotherapy drug doxorubicin hydrochloride (Dox) for synergistic therapy of gliomas. Lactoferrin (LF) was finally modified on the surface of the UMD to endow it with the ability to traverse the BBB and target cells (UMDL). The UCNP core can convert 808 nm near-infrared (NIR) light to ultraviolet light (UV light) for exciting NH2-MIL-53 (Fe), achieving NIR-mediated PDT. In addition, Fe3+ on the surface of the NH2-MIL-53 (Fe) shell could be reduced to Fe2+ in a tumor microenvironment (TME), and then reacted with over-expressed H2O2 in the TME to generate hydroxyl radicals (˙OH) for chemodynamic therapy (CDT). The Dox drug could be released in response to acidic conditions in the TME, inhibiting the growth of gliomas with low side effects. The synergistic effect of PDT/CDT/chemotherapy leads to effective suppression of orthotopic gliomas.

6.
Opt Lett ; 48(2): 407-410, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638469

RESUMO

With the extensive research on the Pancharatnam-Berry phase, metasurfaces have been widely designed as various cross-polarized nanodevices for circularly polarized (CP) illumination. However, co- and cross-polarized lights are rarely co-modulated by the metasurface. To fully utilize the transmitted light, we propose a spin-selected bifunctional metasurface composed of arrayed silver nanorods, integrating an amplitude-based grayscale imaging for co-polarized transmission and a phase-based metalens for cross-polarized transmission, under left-handed CP incidence. Moreover, such dual functionalities work well under right-handed CP incidence. Both experiments and simulations demonstrate the bifunctional performance as potential meta-devices.

7.
Environ Sci Technol ; 57(1): 190-200, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36521032

RESUMO

Phytate as a root exudate is rare in plants as it mainly serves as a P storage in the seeds; however, As-hyperaccumulator Pteris vittata effectively secretes phytate and utilizes phytate-P, especially under As exposure. This study investigated the effects of As on its phytate and phytase exudation and the impacts of As and/or phytate on each other's uptake in P. vittata through two hydroponic experiments. Under 10-100 µM arsenate (AsV), the exudation of phytate and phytase by P. vittata was increased by 50-72% to 20.4-23.4 µmol h-1 g-1 and by 28-104% to 18.6-29.5 nmol h-1 plant-1, but they were undetected in non-hyperaccumulator Pteris ensiformis at 10 µM AsV. Furthermore, compared to 500 µM phytate, the phytate concentration in the growth media was reduced by 69% to 155 µM, whereas the P and As contents in P. vittata fronds and roots were enhanced by 68-134% and 44-81% to 2423-2954 and 82-407 mg kg-1 under 500 µM phytate plus 50 µM AsV. The increased P/As uptake in P. vittata was probably attributed to 3.0-4.5-fold increase in expressions of P transporters PvPht1;3-1;4. Besides, under As exposure, plant P may be converted to phytate in P. vittata roots, thereby increasing phytate's contents by 84% to 840 mg kg-1. Overall, our results suggest that As-induced phytate/phytase exudation and phytate-P uptake stimulate its growth and As hyperaccumulation by P. vittata.


Assuntos
6-Fitase , Arsênio , Pteris , Poluentes do Solo , 6-Fitase/metabolismo , Pteris/metabolismo , Ácido Fítico/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Biodegradação Ambiental
8.
J Med Imaging (Bellingham) ; 9(6): 064503, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36466078

RESUMO

Purpose: Building accurate and robust artificial intelligence systems for medical image assessment requires the creation of large sets of annotated training examples. However, constructing such datasets is very costly due to the complex nature of annotation tasks, which often require expert knowledge (e.g., a radiologist). To counter this limitation, we propose a method to learn from medical images at scale in a self-supervised way. Approach: Our approach, based on contrastive learning and online feature clustering, leverages training datasets of over 100,000,000 medical images of various modalities, including radiography, computed tomography (CT), magnetic resonance (MR) imaging, and ultrasonography (US). We propose to use the learned features to guide model training in supervised and hybrid self-supervised/supervised regime on various downstream tasks. Results: We highlight a number of advantages of this strategy on challenging image assessment problems in radiography, CT, and MR: (1) significant increase in accuracy compared to the state-of-the-art (e.g., area under the curve boost of 3% to 7% for detection of abnormalities from chest radiography scans and hemorrhage detection on brain CT); (2) acceleration of model convergence during training by up to 85% compared with using no pretraining (e.g., 83% when training a model for detection of brain metastases in MR scans); and (3) increase in robustness to various image augmentations, such as intensity variations, rotations or scaling reflective of data variation seen in the field. Conclusions: The proposed approach enables large gains in accuracy and robustness on challenging image assessment problems. The improvement is significant compared with other state-of-the-art approaches trained on medical or vision images (e.g., ImageNet).

9.
Forensic Toxicol ; 40(2): 332-339, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36454415

RESUMO

PURPOSE: This study aimed to develop and validate an ultraperformance liquid chromatography-tandem mass spectrometry to simultaneously determine diquat (DQ) and its two primary metabolites in rat plasma and its application to the toxicokinetic study. METHOD: The chromatographic separation of DQ and its two primary metabolites was performed with hydrophilic interaction chromatography column by adding formic acid and ammonium acetate in mobile phase in stepwise elution mode. DQ and its two primary metabolites were detected by liquid chromatography-tandem mass spectrometry in positive mode. RESULTS: The lower limit of quantification ranging from 0.3 to 3.0 ng/mL for DQ and its two primary metabolites was achieved by using only 50 µL of rat plasma. The maximum concentration (Cmax) was 977 ng/mL, half-life (t1/2) was 13.1 h, and area under the plasma concentration-time curve (AUC0-t) was 2770 h*ng/mL for DQ, Cmax was 47.1 ng/mL, t1/2 was 25.1 h, and AUC0-t was 180 h·ng/mL for diquat monopyridone (DQ-M) and Cmax was 246 ng/mL, t1/2 was 8.2 h, and AUC0-t was 2430 h·ng/mL for diquat dipyridone (DQ-D), respectively. CONCLUSIONS: The validated method was shown to be suitable for simultaneous determination of diquat and its two primary metabolites in rat plasma. This study is the first to study the toxicokinetics of DQ and its two primary metabolites.


Assuntos
Diquat , Espectrometria de Massas em Tandem , Ratos , Animais , Diquat/toxicidade , Toxicocinética , Cromatografia Líquida , Plasma
10.
Forensic Toxicol ; 40(1): 102-110, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36454496

RESUMO

PURPOSE: Paraquat and diquat are well-known toxic herbicides, at least responsible for hundreds of fatal poisoning events worldwide. However, the determination of diquat and paraquat in plasma and urine is very challenging because of their high polarity and double charge characteristics. In this study, we aim to develop a rapid and reliable method for the determination of paraquat and diquat in human plasma and urine by ultraperformance liquid chromatography-tandem mass spectrometry. METHOD: The chromatographic separation of paraquat and diquat was tested with different chromatographic columns and different mobile phase conditions. The mass parameters were optimized by product ions, source gas flow, cone flow, desolvation temperature, and capillary voltage. The isocratic elution mode gave rapid appearance of peak of paraquat and diquat. RESULTS: The sharp peak shapes for paraquat and diquat were achieved with CORTECS® UPLC® HILIC (100 × 2.1 mm, 1.6 µm) column by adding formic acid and ammonium acetate in mobile phase in isocratic elution mode. The lower limit of quantification of 1.0 ng/mL for paraquat and diquat were achieved using only 50 µL of human plasma or urine. The running time for analysis of both paraquat and diquat was as short as 3.5 min per sample. CONCLUSIONS: A rapid and reliable method for the determination of paraquat and diquat was developed and applied to 387 clinical poisoning cases and 22 poisoning cases were found to be paraquat or diquat poisoning.


Assuntos
Diquat , Paraquat , Humanos , Espectrometria de Massas em Tandem , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão , Hospitais , Serviço Hospitalar de Emergência
11.
Forensic Toxicol ; 40(1): 111-118, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36454499

RESUMO

PURPOSE: Lepiota brunneoincarnata is a well-known poisonous mushroom and is responsible for fatal mushroom poisoning cases worldwide. α-Amanitin and ß-amanitin are the main amatoxin compounds of Lepiota brunneoincarnata. However, there are no published toxicokinetic studies of Lepiota brunneoincarnata. To study the toxicokinetics of Lepiota brunneoincarnata, we developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of α-amanitin and ß-amanitin in rat plasma. METHODS: UPLC-MS/MS analyses were performed with a triple quadrupole mass spectrometer in positive-ion mode. The sensitivity of α-amanitin and ß-amanitin detection was increased by inhibiting the production of [M + Na]+ adducts. α-Amanitin and ß-amanitin were separated and quantified on an UPLC octadecyl silyl column in only 2.5 min. RESULTS: The linear ranges were 3.0-3000 ng/mL for α-amanitin and 1.8-1800 ng/mL for ß-amanitin with a correlation coefficient r > 0.99 for both analytes. The lower limit of quantification of 3.0 ng/mL for α-amanitin and 1.8 ng/mL for ß-amanitin was achieved using only 50 µL of rat plasma. The accuracy of α-amanitin and ß-amanitin was between - 9.5 and 7.0% with the precision ranged from 2.2 to 12.5%. The developed method was then applied for Lepiota brunneoincarnata toxicokinetic study after intravenous administration of Lepiota brunneoincarnata extracts. CONCLUSIONS: Establishing UPLC-MS/MS method for quantifying amanitines in rat plasma successfully enabled toxicokinetic study of Lepiota brunneoincarnata extracts.


Assuntos
Agaricales , Alfa-Amanitina , Ratos , Animais , Alfa-Amanitina/toxicidade , Cromatografia Líquida , Toxicocinética , Espectrometria de Massas em Tandem
12.
Chaos ; 32(11): 113123, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36456319

RESUMO

This paper studies the sliding mode control method for coupled delayed fractional reaction-diffusion Cohen-Grossberg neural networks on a directed non-strongly connected topology. A novel fractional integral sliding mode surface and the corresponding control law are designed to realize global Mittag-Leffler synchronization. The sufficient conditions for synchronization and reachability of the sliding mode surface are derived via the hierarchical method and the Lyapunov method. Finally, simulations are provided to verify our theoretical findings.


Assuntos
Redes Neurais de Computação , Difusão
13.
Artigo em Inglês | MEDLINE | ID: mdl-36493631

RESUMO

Polyploid breeding can produce new species with a faster growth rate, higher disease resistance, and higher survival rate, and has achieved significant economic benefits. This study investigated the protein differences in the body wall of triploid Apostichopus japonicus and diploid A. japonicus using isotope-labeled relative and absolute quantitative Tandem Mass Tag technology. A total of 21,096 independent peptides and 4621 proteins were identified. Among them, there were 723 proteins with significant expression differences, including 413 up-regulated proteins and 310 down-regulated proteins. The differentially expressed proteins (DEPs) were enriched in 4519 Gene Ontology enrichment pathways and 320 Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Twenty-two key DEPs related to important functions such as growth and immunity of triploid A. japonicus were screened from the results, among which 20 were up-regulated, such as cathepsin L2 cysteine protease and fibrinogen-like protein A. Arylsulfatase A and zonadhesin were down-regulated. The up-regulated proteins were mainly involved in oxidative stress response, innate immune response, and collagen synthesis in triploid A. japonicus, and the down-regulated proteins were mainly associated with the sterility of triploid A. japonicus. In addition, the transcriptome and proteome were analyzed jointly to support proteome data. In this study, the differences in protein composition between triploid and diploid A. japonicus were analyzed for the first time, and the results revealed the underlying reasons for the growth advantage of triploid A. japonicus.

14.
Ital J Pediatr ; 48(1): 198, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36510285

RESUMO

BACKGROUND: It is reported that the adverse impact of nonpharmaceutical interventions (NPIs) on the mental health of children and adolescents may lead to psychologically related disorders during the coronavirus disease 2019 (COVID-19) period. Subject symptoms such as chest pain, chest tightness, and palpitation may be related to increased stress and anxiety in children and adolescents. The present research aimed to determine the number of pediatric consults and etiology of subject symptoms during the COVID-19 pandemic period and compared it with the same timelines in 2019 and 2021 to discuss the impact of different periods on the organic disease onset of children with subject symptoms, especially in cardiac involvement. METHODS: Children who visited Qingdao Women and Children's Hospital, Qingdao University between January 23 to April 30, 2019 (pre-COVID-19 period), January 23 to April 30, 2020 (COVID-19 period), and January 23 to April 30, 2021 (post-COVID-19 period) presenting chest pain, chest tightness, and palpitation were recruited. Information to determine gender, age, medical history, department for the initial visit, clinical manifestations, time from the latest onset to the visit, and diagnosis were recorded. RESULT: A total of 891 patients were enrolled in the present study (514 males; median age: 7.72). One hundred twenty-three patients presented during the pre-COVID-19 period while 130 during the COVID-19 period, nevertheless, the number substantially increased during the post-COVID-19 period (n = 638). Cardiac etiology accounted for 1.68% (n = 15) of the patient population, including arrhythmias (n = 10, 1.12%), myocarditis (n = 4, 0.44%), and atrial septal defect (n = 1, 0.11%). There was no significant difference among groups in the distribution of organic etiology. The median time from the latest onset to the visit during the pre-COVID-19 period was 7 days compared to 10 days during the COVID-19 period and 3 days during the post-COVID period. CONCLUSION: During the post-COVID-19 period, the median time from the latest onset to the visit was significantly shorter than that in the pre-COVID-19 period or COVID-19 period. The pediatric consult of children with subject symptoms presented increased substantially during the post-COVID-19 period, while there was no significant difference in the number of patients involving the cardiac disease. Clinicians ought to be more careful to screen heart diseases to prevent missed diagnosis and misdiagnosis during special periods.


Assuntos
COVID-19 , Cardiopatias , Adolescente , Masculino , Humanos , Feminino , Criança , Pandemias , COVID-19/epidemiologia , SARS-CoV-2 , Encaminhamento e Consulta , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Dor no Peito/diagnóstico , Dor no Peito/epidemiologia , Dor no Peito/etiologia , Arritmias Cardíacas
15.
Sci Rep ; 12(1): 18373, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319826

RESUMO

Although aplastic anemia (AA) does not come under the category of blood malignant diseases, the infection that frequently occurs in this bone marrow failure can make it worse. Pulmonary infection is the most prevalent but limiting clinical diagnosis. To find biomarkers predicting bacterial or bacterial-combined fungal infections in the lungs, we reviewed 287 AA medical records including 151 without any infection, 87 with pure pulmonary bacterial infection, and 49 with bacterial and fungal infection were reviewed. There were substantial changes in IL-17F, IL-17A, IFN-γ, IL-6, IL-8, and IL-10 levels between the non-infected and lung bacterial infection groups (P < 0.05). Further, a significant variation in IL-17A, TNF-ß, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-22, and IL-12p70, between the uninfected group and the pulmonary bacterial and fungal infection group (P < 0.05) was observed. The results further revealed significant differences in TNF-ß, IL-12p70, IL-6, IL-8, and IL-10 between the pulmonary bacterial infection group and the fungal infection group (P < 0.05). Moreover, by calculating ROC and cut-off values, we determined that IL-6 (AUC = 0.98, Cut-off = 14.28 pg/ml, P = 0.0000) had a significant advantage than other cytokines, body temperature (AUC = 0.61, P = 0.0050), PCT (AUC = 0.57, P = 0.0592), and CRP (AUC = 0.60, P = 0.0147) in the detection of lungs bacterial infections. In addition, IL-6 (AUC = 1.00, Cut-off = 51.50 pg/ml, P = 0.000) and IL-8 (AUC = 0.87, Cut-off = 60.53 pg/ml, P = 0.0000) showed stronger advantages than other cytokines, body temperature (AUC = 0.60, P = 0.0324), PCT (AUC = 0.72, Cut-off = 0.63 ng/ml, P = 0.0000) and CRP (AUC = 0.79, Cut-off = 5.79 mg/l, P = 0.0000) in distinguishing bacteria from fungi. This may suggest that IL-8 may play a role in differentiating co-infected bacteria and fungi. Such advantages are repeated in severe aplastic anemia (SAA) and very severe aplastic anemia (VSAA).In conclusion, aberrant IL-6 elevations in AA patients may predict the likelihood of bacterial lung infection. The concurrent increase of IL-6 and IL-8, on the other hand, should signal bacterial and fungal infections in patients.These findings may help to suggest bacterial or fungal co-infection in patients with AA (Focus on VSAA and SAA).


Assuntos
Anemia Aplástica , Infecções Bacterianas , Coinfecção , Micoses , Humanos , Bactérias , Citocinas , Interleucina-10 , Interleucina-12 , Interleucina-17 , Interleucina-6 , Interleucina-8 , Pulmão , Linfotoxina-alfa
16.
Int J Antimicrob Agents ; : 106691, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36372344

RESUMO

BACKGROUND: There is uncertainty about whether piperacillin/tazobactam (PT) increases the risk of AKI in patients without concomitant use of vancomycin. We compared risk of hospital-acquired acute kidney injury (HA-AKI) among adults treated with PT or anti-pseudomonal ß-lactams (meropenem, ceftazidime), without concomitant use of vancomycin. METHODS: This real-world study analyzed the data from China Renal Data System (CRDS) and assessed the HA-AKI risk in adults hospitalized with infection after exposure to PT or meropenem or ceftazidime, in the absence of concomitant vancomycin. The primary outcome was any stage of HA-AKI according to the Kidney Disease Improving Global Outcomes guidelines. A multivariable cox regression model and different propensity score matching models were used. RESULTS: Among the 29,441 adults (mean [SD] age, 62.44 [16.84] years; 17,980 female [61.1%]) included in this study, 14,721 (50%) used PT, 9,081 (31%) used meropenem and 5,639 (19%) ceftazidime. During a median follow-up period of 8 days, 3,476 (6.9%) developed HA-AKI. Use of PT was not associated with statistically increased risk of HA-AKI compared with meropenem [adjusted hazard ratio [aHR]: 1.07, 95%CI 0.97-1.19], ceftazidime [aHR: 1.09, 95%CI 0.92-1.3] or both agents (aHR: 1.07, 95% CI 0.97-1.17) after adjusting for confounders. Results were consistent in stratified analyses, propensity score (PS) matching using logistics regression or random forest methods to generate a PS, and in an analysis restricting outcomes to AKI stage 2-3. CONCLUSIONS: Without concomitant vancomycin use, the risk of AKI following PT therapy is comparable with that of meropenem or ceftazidime among adults hospitalized with infection.

18.
ACS Appl Mater Interfaces ; 14(45): 50616-50625, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36332001

RESUMO

The unsatisfactory therapeutic effect and long-term adverse effect markedly prevent inorganic nanomaterials from clinical transformation. In light of this, we developed a novel biodegradable theranostic agent (MnCO3:Ho3+@DOX/Ca3(PO4)2@BSA, HMCDB) based on the sonosensitizer manganese carbonate (MnCO3) coating with calcium phosphate (Ca3(PO4)2) and simultaneously loaded it with the chemotherapeutic drug doxorubicin (DOX). Due to the mild acidity of the tumor microenvironment (TME), the Ca3(PO4)2 shell degraded first, releasing substantial quantities of calcium ions (Ca2+) and DOX. Meanwhile, with the ultrasound (US) irradiation, MnCO3 produced enough reactive oxygen species (ROS) to cause oxidative stress in the cells, resulting in accumulation of Ca2+. Consequently, the cascade effect significantly amplified the therapeutic effect. Importantly, the nanocomposite can be completely degraded and cleared from the body, demonstrating that it was a promising theranostic agent for tumor therapy. Furthermore, the doped holmium ions (Ho3+) and in situ generation of manganese ions (Mn2+) in TME endow the nanoagent with the ability for tumor-specific bimodality T1/T2-weighted magnetic resonance imaging (MRI). This novel nanoplatform with low toxicity and biodegradability holds great potential for cancer diagnosis and treatment.


Assuntos
Nanopartículas , Neoplasias , Humanos , Microambiente Tumoral , Nanopartículas/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imageamento por Ressonância Magnética , Linhagem Celular Tumoral , Nanomedicina Teranóstica
19.
Eur J Pharm Sci ; 180: 106319, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36328086

RESUMO

Glioblastoma (GBM) is a common malignant tumor in brain, and the treatment is still a challenge owing to the high invasiveness and the existence of blood-brain barrier (BBB). Although temozolomide (TMZ) is the first line medication, its efficacy is not ideal, which is related to the defect of dose distribution and drug resistance. It is urgent to develop a novel BBB-permeable nanoagent with multiple therapeutic modalities for improving the treatment effect of GBM. In this work, we constructed an intelligent BBB-permeable nanoplatform (CTHG-Lf NPs) with hollow mesoporous copper sulfide nanoparticles (HM-CuS NPs) as temozolomide (TMZ) carrier and hyaluronic acid (HA) as gatekeeper, as well as further modification with glucose oxidase (GOx) and lactoferrin (Lf) for highly efficient synergistic therapy of orthotopic GBM. The modification of Lf endows CTHG-Lf NPs with good target and BBB-permeable ability. HA not only prevents the TMZ leakage during circulation, but also achieves responsive drug release at tumor site for effective chemotherapy (CT). GOx provides high hydrogen peroxide (H2O2) and gluconic acid for improving the treatment effect of chemodynamic therapy (CDT), and realizes the starvation therapy (ST) by consuming glucose. The good photothermal effect of CTHG-Lf NPs achieves the "mild" photothermal therapy (PTT), while enhancing the efficiency of Fenton-like reaction. The synergistic strategy with CT/CDT/PTT/ST can not only promote brain drug delivery, but also realize the combination of multiple mechanisms for effective tumor growth suppression in vivo.

20.
Adv Sci (Weinh) ; : e2204937, 2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36437111

RESUMO

Gliomas are common and refractory primary tumors closely associated with the fine structures of the brain. Photothermal therapy (PTT) has recently shown promise as an effective treatment for gliomas. However, nonspecific accumulation of photothermal agents may affect adjacent normal brain structures, and the inflammatory response induced during PTT may result in an increased risk of brain tumor recurrence or metastasis. Here, the design and fabrication of an intelligent nanomachine is reported based on Gd2 O3 @Ir/TMB-RVG29 (G@IT-R) hybrid nanomaterials. These nanomaterials enable tumor-specific PTT and eliminate inflammation to protect normal brain tissue. The mechanism involves the rabies virus glycopeptide-29 peptide (RVG29) passing through the blood-brain barrier (BBB) and targeting gliomas. In the tumor microenvironment, Ir nanozymes can act as logic control systems to trigger chromogenic reaction amplification of 3,3',5,5'-tetramethylbenzidine (TMB) for tumor-specific PTT, whereas in normal brain tissues, they scavenge reactive oxygen species (ROS) generated by poor therapy and function as protective agents. Autophagy inhibition of Gd2 O3 enables excellent photothermal therapeutic effects on orthotopic gliomas and protection against inflammation in normal cells. The results of this study may prove useful in developing highly efficient nanomedicines for glioma treatment.

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