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1.
Biotechnol J ; 19(4): e2300614, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581093

RESUMO

Poly-γ-glutamic acid (γ-PGA) is a microbial-derived polymer with molecular weight (Mw) from 104 to 107 Da, and the high-Mw (> 7.0 × 105 Da) or ultra-high-Mw (> 5.0 × 106 Da) γ-PGA has important application value as a tissue engineering material, as a flocculant, and as a heavy metal remover. Therefore, how to produce these high-Mw γ-PGAs with low cost and high efficiency has attracted wide attention. In this study, a γ-PGA producer was isolated from the natural environment, and identified and named Bacillus subtilis GXD-20. Then, the ultra-high-Mw (> 6.0 × 106 Da) γ-PGA produced by GXD-20 was characterized. Interestingly, GXD-20 could produce γ-PGA at 42°C, and exhibited a γ-PGA titer of up to 22.29 ± 0.59 g L-1 in a 5-L fermenter after optimization of the fermentation process. Comparative genomic analysis indicated that the specific protein sequence and subcellular localization of PgdS (a γ-PGA-degrading enzyme) were closely related to the ultra-high-Mw of γ-PGA. Transcriptomic analysis revealed that the high γ-PGA titer at 42°C was mainly related to the high expression of genes encoding enzymes for sucrose transportation and utilization, nitrogen transportation, endogenous glutamate synthesis, and γ-PGA synthesis. These results provide new insights into the production of ultra-high-Mw γ-PGA by Bacillus at high temperatures.


Assuntos
Bacillus subtilis , Ácido Glutâmico , Ácido Poliglutâmico/análogos & derivados , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Ácido Glutâmico/metabolismo , Peso Molecular , Ácido Poliglutâmico/genética , Ácido Poliglutâmico/metabolismo , Genômica , Fermentação
2.
Zhongguo Gu Shang ; 37(3): 271-7, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38515414

RESUMO

OBJECTIVE: To establish the finite element model of spinal canal reconstruction and internal fixation,analysis influence of spinal canal reconstruction and internal fixation on spinal stability,and verify the effectiveness and reliability of spinal canal reconstruction and internal fixation in spinal canal surgery. METHODS: A 30-year-old male healthy volunteer with a height of 172 cm and weight of 75 kg was selected and his lumbar CT data were collected to establish a finite element model of normal lumbar L3-L5,and the results were compared with in vitro solid results and published finite element analysis results to verify the validity of the model. They were divided into normal group,laminectomy group and spinal canal reconstruction group according to different treatment methods. Under the same boundary fixation and physiological load conditions,six kinds of activities were performed,including forward bending,backward extension,left bending,right bending,left rotation and right rotation,and the changes of range of motion (ROM) of L3-L4,L4-L5 segments and overall maximum ROM of L3-L5 were analyzed under the six conditions. RESULTS: The ROM displacement range of each segment of the constructed L3-L5 finite element model was consistent with the in vitro solid results and previous literature data,which confirms the validity of the model. In L3-L4,ROM of spinal canal reconstruction group was slightly increased than that of normal group during posterior extension(>5% difference),and ROM of other conditions was similar to that of normal group(<5% difference). ROM in laminectomy group was significantly increase than that in normal group and spinal canal reconstruction group under the condition of flexion,extension,left and right rotation. In L4-L5,ROM in spinal canal reconstruction group was similar to that in normal group(<5% difference),while ROM in laminectomy group was significantly higher than that in normal group and spinal canal reconstruction group(>5% difference). In the overall maximum ROM of L3-L5,spinal canal reconstruction group was only slightly higher than normal group under the condition of posterior extension(>5% difference),while laminectomy was significantly higher than normal group and spinal canal reconstruction group under the condition of anterior flexion,posterior extension,left and right rotation(>5% difference). The changes of each segment ROM and overall ROM of L3-L5 showed laminectomy group>spinal canal reconstruction group>normal group. CONCLUSION: Laminectomy could seriously affect biomechanical stability of the spine,but application of spinal canal reconstruction and internal fixation could effectively reduce ROM displacement of the responsible segment of spine and maintain its biomechanical stability.


Assuntos
Vértebras Lombares , Fusão Vertebral , Masculino , Humanos , Adulto , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Análise de Elementos Finitos , Reprodutibilidade dos Testes , Amplitude de Movimento Articular/fisiologia , Fenômenos Biomecânicos , Canal Medular/cirurgia
3.
Physiol Rep ; 12(3): e15929, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307709

RESUMO

Diastolic dysfunction is a major cardiac dysfunction, and an important predisposing factor is age. Although exercise training is often used for the prevention and treatment of cardiovascular disease nowadays, little is currently known about whether exercise interventions associated with the slowing of cardiac aging are related to mtp-related pathways. In the present study, the UAS/Tub-Gal4 system was used to knockdown whole-body mtp expression levels in Drosophila, which underwent 2 weeks of endurance training. By conducting different assays and quantifying different indicators, we sought to investigate the relationship between mtp, exercise, and age-related diastolic dysfunction. We found that (1) Drosophila in the mtpRNAi youth group exhibited age-related diastolic dysfunction and had a significantly shorter mean lifespan. (2) Endurance exercise could improve diastolic dysfunction and prolong lifespan in aged Drosophila. (3) Endurance exercise could increase the expression levels of apolpp and Acox3, and decrease the levels of TC, LDL-C, and TG in the aged group. In summary, aging causes age-associated diastolic dysfunction in Drosophila, and systemic knockdown of mtp causes premature age-associated diastolic dysfunction in young Drosophila. Besides, endurance exercise improves age-related diastolic dysfunction and prolongs lifespan.


Assuntos
Envelhecimento , Drosophila melanogaster , Longevidade , Resistência Física , Animais , Humanos , Envelhecimento/fisiologia , Coração/fisiologia , Resistência Física/fisiologia , Drosophila melanogaster/fisiologia
4.
Funct Integr Genomics ; 24(2): 40, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38383667

RESUMO

As a common malignant tumor, esophageal squamous cell carcinoma (ESCC) is occasionally seen in clinical practice. This type of disease has low incidence rate and mortality. The post-translational modification of small ubiquitin like modifiers (SUMO) can play a crucial role in regulating protein function, and can significantly impact the occurrence and development of diseases. SUMO-specific peptidase (SENP) affects cell activity by regulating the biological function of SUMO. SENP3 belongs to the SENP family, and available data indicate that many malignancies are associated with SENPs, it is currently unclear its role in ESCC. This study indicates that there is a high level of SENP3 expression in ESCC tumor cells. If the expression level of this gene is high, it can have a significant impact on ESCC cell lines and affect physiological activities such as invasion of KYSE170 cells. If the gene is knocked out, this situation will not occur. There is also research data indicating that this gene can effectively activate related signaling pathways, thereby promoting the physiological activities of malignant tumor cells. In a nude mouse xenograft tumor model, KYSE170 cells with SENP3 expression knockdown induced a smaller volume and weight of tumor tissue. Therefore, it can be clearly stated that SENP3 can enable Wnt/ ß- The catenin signaling pathway is stimulated, which in turn affects the physiological activities of ESCC cells, including the invasion process. The results of this article lay the foundation for clinical staff to carry out clinical management.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Wnt/genética
5.
Angew Chem Int Ed Engl ; 63(13): e202319728, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38285535

RESUMO

Organic molecules bearing chiral sulfur stereocenters exert a great impact on asymmetric catalysis and synthesis, chiral drugs, and chiral materials. Compared with acyclic ones, the catalytic asymmetric synthesis of thio-heterocycles has largely lagged behind due to the lack of efficient synthetic strategies. Here we establish the first modular platform to access chiral thio-oxazolidinones via Pd-catalyzed asymmetric [3+2] annulations of vinylethylene carbonates with sulfinylanilines. This protocol is featured by readily available starting materials, and high enantio- and diastereoselectivity. In particular, an unusual effect of a non-chiral supporting ligand on the diastereoselectivity was observed. Possible reaction mechanisms and stereocontrol models were proposed.

6.
Appl Biochem Biotechnol ; 196(3): 1527-1543, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37432638

RESUMO

In this study, the production of poly-γ-glutamic acid (PGA) by Bacillus subtilis using stage-controlled fermentation and viscosity reduction strategy was investigated in detail. Based on the single-factor optimization experiment, temperature (42 °C and 37 °C), pH (7.0 and uncontrolled), aeration rate (1.2 vvm and 1.0 vvm), and agitation speed (700 rpm and 500 rpm) were selected for the two-stage controlled fermentation (TSCF). The time points for the TSCF of temperature, pH, aeration rate, and agitation speed were set at 18.52 h, 2.82 h, 5.92 h, and 3.62 h, respectively, based on the kinetic analysis. A PGA titer of 19.79 ~ 22.17 g/L was obtained from the TSCF, which did not increase significantly than that (21.25 ± 1.26 g/L) of non-stage controlled fermentation (NSCF). This may be due to the high viscosity and low dissolved oxygen of the PGA fermentation broth. Thus, the TSCF combined with a viscosity reduction strategy was developed to further improve the production of PGA. The PGA titer reached 25.00 ~ 30.67 g/L, which increased by 17.66 ~ 32.94% to that of NSCF. This study provided a valuable reference for the development of process control strategies for high-viscosity fermentation systems.


Assuntos
Bacillus subtilis , Ácido Glutâmico , Fermentação , Viscosidade , Cinética , Ácido Poliglutâmico
7.
RSC Adv ; 13(51): 36200-36208, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38090065

RESUMO

Actinomycins are known for their anti-tumor, antibacterial and antiviral activities, and in particular for the ability of actinomycin D as a clinical drug to treat a variety of cancers. In our ongoing work to obtain novel natural products from endophytic actinomycetes derived from traditional Chinese herbs, we identified the potential to produce actinomycins in YINM00002, a Kitasatospora strain derived from Polygonatum kingianum. According to genome mining, we isolated actinomycins D and V (1 and 2) and small amounts of 4-methyl-3-hydroxyanthranilic acid (4-MHA) derivates (3 and 4) from strain fermentation broth. The presence of actinrhater A (3) and actinrhater B (4) reveals a mysterious shunt pathway in the early stages of actinomycin D biosynthesis. Our study provides a fresh perspective for further discovery and modification of novel actinomycins.

8.
BMC Infect Dis ; 23(1): 874, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093214

RESUMO

BACKGROUND: The sensitivity of HIV screening assays often leads to a high rate of false-positive results, requiring retests and confirmatory tests. This study aimed to analyze the capability of signal-to-cutoff (S/CO) ratios of HIV screening assay to predict HIV infection. METHODS: A retrospective study on the HIV screening-positive population was performed at Zhongshan Hospital, Xiamen University, the correlation between HIV screening assay S/CO ratios and HIV infection was assessed, and plotted Receiver Operating Characteristic (ROC) curves were generated to establish the optimal cutoff value for predicting HIV infection. RESULTS: Out of 396,679 patients, 836 were confirmed to be HIV-infected, with an HIV prevalence of 0.21%. The median S/CO ratios in HIV infection were significantly higher than that in non-HIV infection (296.9 vs. 2.41, P < 0.001). The rate of confirmed HIV infection was increased with higher S/CO ratios in the screening assay. The ROC curve based on the HIV screening assay S/CO ratio achieved a sensitivity of 93.78% and a specificity of 93.12% with an optimal cutoff value of 14.09. The area under the ROC curve was 0.9612. Further analysis of the ROC curve indicated that the S/CO ratio thresholds yielding positive predictive values of 99%, 99.5%, and 100% for HIV infection were 26.25, 285.7, and 354.5, respectively. CONCLUSION: Using HIV screening assay S/CO ratio to predict HIV infection can largely reduce necessitating retests and confirmatory tests. Incorporating the S/CO ratio into HIV testing algorithms can have significant implications for medical and public health practices.


Assuntos
Infecções por HIV , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Sensibilidade e Especificidade , Estudos Retrospectivos , Curva ROC , Teste de HIV , Programas de Rastreamento/métodos
9.
Nat Commun ; 14(1): 8357, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102128

RESUMO

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed 'subgenome dominance' remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.


Assuntos
Carpas , Evolução Molecular , Animais , Poliploidia , Genoma/genética , Epigênese Genética , Genoma de Planta
10.
J Magn Reson Imaging ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38131254

RESUMO

BACKGROUND: Progression of intracranial atherosclerotic disease (ICAD) is associated with ischemic stroke events and can be quantified with three-dimensional (3D) intracranial vessel wall (IVW) MRI. However, longitudinal 3D IVW studies are limited and ICAD evolution remains relatively unknown. PURPOSE: To evaluate ICAD changes longitudinally and to characterize the imaging patterns of atherosclerotic plaque evolution. STUDY TYPE: Prospective. POPULATION: 37 patients (69 ± 12 years old, 12 females) with angiography confirmed ICAD. FIELD STRENGTH/SEQUENCE: 3.0T/3D time-of-flight gradient echo sequence and T1- and proton density-weighted fast spin echo sequences. ASSESSMENT: Each patient underwent baseline and 1-year follow-up IVW. Then, IVW data from both time points were jointly preprocessed using a multitime point, multicontrast, and multiplanar viewing workflow (known as MOCHA). Lumen and outer wall of plaques were traced and measured, and plaques were then categorized into progression, stable, and regression groups based on changes in plaque wall thickness. Patient demographic and clinical data were collected. Culprit plaques were identified based on cerebral ischemic infarcts. STATISTICAL TESTS: Generalized estimating equations-based linear and logistic regressions were used to assess associations between vascular risk factors, medications, luminal stenosis, IVW plaque imaging features, and longitudinal changes. A two-sided P-value<0.05 was considered statistically significant. RESULTS: Diabetes was significantly associated with ICAD progression, resulting in 6.6% decrease in lumen area and 6.7% increase in wall thickness at 1-year follow-up. After accounting for arterial segments, baseline contrast enhancement predicted plaque progression (odds ratio = 3.61). Culprit plaques experienced an average luminal expansion of 10.9% after 1 year. 74% of the plaques remained stable during follow-up. The regression group (18 plaques) showed significant increase in minimum lumen area (from 7.4 to 8.3 mm2 ), while the progression group (13 plaques) showed significant decrease in minimum lumen area (from 5.4 to 4.3 mm2 ). DATA CONCLUSION: Longitudinal 3D IVW showed ICAD remodeling on the lumen side. Culprit plaques demonstrated longitudinal luminal expansion compared with their non-culprit counterparts. Baseline plaque contrast enhancement and diabetes mellitus were found to be significantly associated with ICAD changes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

11.
Invest Ophthalmol Vis Sci ; 64(15): 34, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38133502

RESUMO

Purpose: To evaluate the influencing factors of parapapillary ßBM and γ zones incidence in young adolescents and to explore their associations with axial length progression. Methods: In this prospective cohort study, 976 seventh-grade students from nine secondary schools in Beijing, China, were enrolled and followed up 1 year later. Parapapillary ßBM zone was defined as retinal pigment epithelium loss while Bruch's membrane was present. Parapapillary γ zone was defined as the absence of retinal pigment epithelium and Bruch's membrane. Logistic regression model was used to analyze the influencing factors of ßBM and γ zone incidence. A linear mixed model was used to analyze the associations between parapapillary zones and axial elongation. Results: Of the 976 participants, 139 (14.2%) had only ßBM zone, 398 (40.8%) had only γ zone, and 171 (17.5%) had both. At follow-up, the incidence of ßBM zone was 11.5% (76/659), and the incidence of γ zone was 9.7% (39/404). Optic disc tilt, thinner subfoveal choroid, and longer axial length at baseline showed a higher risk of γ zone incidence. The absence of γ zone at baseline showed a faster axial length progression. When the baseline axial length was 25 mm or longer, the ßBM zone was also related to the axial elongation. Conclusions: The γ zone was associated with axial length progression, and the ßBM zone was also associated with the axial length progression when the axial length exceeded 25 mm, which was consistent with the notion that excessive axial length growth not only is the extension of the eyeball but also has its own pathologic changes.


Assuntos
Disco Óptico , Humanos , Adolescente , Disco Óptico/patologia , Tomografia de Coerência Óptica/métodos , Estudos Prospectivos , Comprimento Axial do Olho/patologia , Corioide
12.
Fa Yi Xue Za Zhi ; 39(4): 406-416, 2023 Aug 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37859481

RESUMO

In recent years, the types and quantities of fentanyl analogs have increased rapidly. It has become a hotspot in the illicit drug control field of how to quickly identify novel fentanyl analogs and to shorten the blank regulatory period. At present, the identification methods of fentanyl analogs that have been developed mostly rely on reference materials to target fentanyl analogs or their metabolites with known chemical structures, but these methods face challenges when analyzing new compounds with unknown structures. In recent years, emerging machine learning technology can quickly and automatically extract valuable features from massive data, which provides inspiration for the non-targeted screening of fentanyl analogs. For example, the wide application of instruments like Raman spectroscopy, nuclear magnetic resonance spectroscopy, high resolution mass spectrometry, and other instruments can maximize the mining of the characteristic data related to fentanyl analogs in samples. Combining this data with an appropriate machine learning model, researchers may create a variety of high-performance non-targeted fentanyl identification methods. This paper reviews the recent research on the application of machine learning assisted non-targeted screening strategy for the identification of fentanyl analogs, and looks forward to the future development trend in this field.


Assuntos
Fentanila , Drogas Ilícitas , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas/métodos , Drogas Ilícitas/análise
13.
Front Psychiatry ; 14: 1093106, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37621972

RESUMO

Objective: This study aimed to investigate the effect of 8 months of high-intensity interval training (HIIT) on physical fitness and health-related quality of life in substance use disorder. Methods: Sixty substance use disorder were randomly assigned to either the HIIT group or the control group according to a random sampling method. The HIIT group received 8 months of four 60-min sessions per week under supervision. Weight, waist circumference, body fat percentage, heart rate, blood pressure, VO2max, reaction time, grip strength, standing on one foot with eyes closed, sitting forward flexion, and quadrant jumping, standing on one foot with eyes closed, the number of push-ups, quality of life (SF-36) score, and craving (VAS) scored were monitored in the HIIT and control groups at baseline, 4 months, and 8 months. SPSS 22.0 was used to conduct repeated measurement analysis of variance and Pearson correlation analysis on the collected subject data. Results: Compared with baseline, weight (p < 0.001), waist circumference (p < 0.001), body fat percentage (p < 0.001), heart rate (p < 0.05), Systolic blood pressure (p < 0.01), systolic blood pressure (p < 0.05), reaction time (p < 0.001),PSQI (p < 0.001), Total cholesterol (p < 0.001), Triglyceride (p < 0.001), Blood sugar (p < 0.001) and VAS score (p < 0.001) were significantly decreased after 8 months of exercise intervention. Contrastingly, VO2max (p < 0.05), grip strength (p < 0.05), eyes closed and one foot Standing (p < 0.001), sitting forward flexion (p < 0.001), quadrant jumping (p < 0.001), push-ups (p < 0.001), PCS (p < 0.001), and MCS (p < 0.001) were significantly increased. VO2max was significantly negatively correlated with VAS (r = -0.434, p < 0.001), and significantly positively correlated with PCS (r = 0.425, p < 0.001). There was a positive correlation between standing on one foot with closed eyes and MCS (r = 0.283, p < 0.05). Conclusion: Eight months of HIIT can comprehensively improve the physical health level and health-related quality of life of men with substance use disorders, reduce the desire for drugs, and lay the foundation for better starting a happy life.

14.
Org Lett ; 25(35): 6506-6510, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37624728

RESUMO

A phosphine-promoted tandem Diels-Alder reaction using pentadienyl 4-nitrobenzoate (α-vinyl MBH adduct) as a diene precursor with 3-olefinic oxindoles or CF3-activated ketones as dienophiles has been developed. The reaction proceeds through the formation of a pentadienyl phosphonium intermediate via SN2'' addition, which acts as both a D-A diene and a precursor for the exomethylene moiety. This method offers a metal-free and step-efficient approach for synthesizing exomethylene-bearing spirooxindoles and dihydropyrans, which are privileged structures found in natural products.

16.
Fa Yi Xue Za Zhi ; 39(2): 144-150, 2023 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37277377

RESUMO

OBJECTIVES: To identify 1-(4-fluorophenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-α-PVP) analog 1-(4-fluoro-3-methyl phenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-3-Methyl-α-PVP) hydrochloride without reference substance. METHODS: The direct-injection electron ionization-mass spectrometry (EI-MS), GC-MS, electrospray ionization-high resolution mass spectrometry (ESI-HRMS), ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (UPLC-HRMS/MS), nuclear magnetic resonance (NMR), ion chromatography and Fourier transform infrared spectroscopy (FTIR) were integrated utilized to achieve the structural analysis and characterization of the unknown compound in the sample, and the cleavage mechanism of the fragment ions was deduced by EI-MS and UPLC-HRMS/MS. RESULTS: By analyzing the direct-injection EI-MS, GC-MS, ESI-HRMS and UPLC-HRMS/MS of the compound in the samples, it was concluded that the unknown compound was a structural analog of 4-F-α-PVP, possibly with one more methyl group in the benzene ring. According to the analysis results of 1H-NMR and 13C-NMR, it was further proved that the methyl group is located at the 3-position of the benzene ring. Since the actual number of hydrogen in 1H-NMR analysis was one more than 4-F-3-Methyl-α-PVP neutral molecule, it was inferred that the compound existed in the form of salt. Ion chromatography analysis results showed that the compound contained chlorine anion (content 11.14%-11.16%), with the structural analysis of main functional group information by FTIR, the unknown compound was finally determined to be 4-F-3-Methyl-α-PVP hydrochloride. CONCLUSIONS: A comprehensive method using EI-MS, GC-MS, ESI-HRMS, UPLC-HRMS/MS, NMR, ion chromatography and FTIR to identify 4-F-3-Methyl-α-PVP hydrochloride in samples is established, which will be helpful for the forensic science laboratory to identify this compound or other analog compounds.


Assuntos
Benzeno , Espectrometria de Massas por Ionização por Electrospray , Cromatografia Gasosa-Espectrometria de Massas/métodos , Cromatografia Líquida de Alta Pressão/métodos
17.
Adv Mater ; 35(51): e2302559, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37142810

RESUMO

Recently, 2D transition metal carbide, nitride, and carbonitrides (MXenes) materials stand out in the field of tumor therapy, particularly in the construction of functional platforms for optimal antitumor therapy due to their high specific surface area, tunable performance, strong absorption of near-infrared light as well as preferable surface plasmon resonance effect. In this review, the progress of MXene-mediated antitumor therapy is summarized after appropriate modifications or integration procedures. The enhanced antitumor treatments directly performed by MXenes, the significant improving effect of MXenes on different antitumor therapies, as well as the MXene-mediated imaging-guided antitumor strategies are discussed in detail. Moreover, the existing challenges and future development directions of MXenes in tumor therapy are presented.


Assuntos
Raios Infravermelhos , Neoplasias , Humanos , Nitritos , Ressonância de Plasmônio de Superfície , Neoplasias/tratamento farmacológico
18.
Talanta ; 259: 124508, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37043878

RESUMO

Ultrasonic sample introduction combined with flame assisted thermal ionization mass spectrometry (USI-FATI-MS) was developed to monitor the fractions of preparative liquid chromatography. Recently, ultrasound-based sample introduction techniques have achieved great advance in the field of high-throughput analysis. However, it is still a challenge to directly apply these existing techniques to the analysis of macro volume samples (mL level). In this work, ultrasonic sample introduction combined with flame assisted thermal ionization was used for pretreatment-free direct mass spectrometry analysis of micro to macro volume samples (µL-mL level). Utilizing this unique design of ultrasonic sample introduction, liquid sample in the container can be quickly atomized to the gas phase without contact. Then, due to the flame assisted thermal ionization source, desolvation and ionization of the sample droplets will occur immediately. USI-FATI-MS has shown excellent sensitivity, repeatability and great compatibility to solvents and compounds with a wide range of polarity. As a proof of concept, USI-FATI-MS has been applied for rapid monitoring and identification of purified synthetic and natural products in fractions.

19.
J Med Chem ; 66(6): 4025-4044, 2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-36912866

RESUMO

Bruton's tyrosine kinase (BTK) plays an essential role in B-cell receptor (BCR)-mediated signaling as well as the downstream signaling pathway for Fc receptors (FcRs). Targeting BTK for B-cell malignancies by interfering with BCR signaling has been clinically validated by some covalent inhibitors, but suboptimal kinase selectivity may lead to some adverse effects, which also makes the clinical development of autoimmune disease therapy more challenging. The structure-activity relationship (SAR) starting from zanubrutinib (BGB-3111) leads to a series of highly selective BTK inhibitors, in which BGB-8035 is located in the ATP binding pocket and has similar hinge binding to ATP but exhibits high selectivity over other kinases (EGFR, Tec, etc.). With an excellent pharmacokinetic profile as well as demonstrated efficacy studies in oncology and autoimmune disease models, BGB-8035 has been declared a preclinical candidate. However, BGB-8035 showed an inferior toxicity profile compared to that of BGB-3111.


Assuntos
Doenças Autoimunes , Neoplasias , Humanos , Tirosina Quinase da Agamaglobulinemia , Relação Estrutura-Atividade , Doenças Autoimunes/tratamento farmacológico , Neoplasias/tratamento farmacológico , Trifosfato de Adenosina , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética
20.
Pak J Med Sci ; 39(1): 280-284, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36694778

RESUMO

Objective: To investigate the value of serum procalcitonin(PCT), C-reactive protein(CRP), and neutrophil gelatinase-associated lipocalin(NGAL) in the early diagnosis of acute kidney injury(AKI) after upper urinary tract calculi(UUTC). Methods: The clinical data of 86 patients who underwent UUTC surgery in our hospital from March 2020 to April 2021 were analyzed retrospectively(Approval number: 20211205L, Date: 2021-12-21). Patients were divided into an AKI group (AKI≥7 days after the operation) and a Non-AKI group. PCT, CRP, and NGAL concentrations were compared before and two hours after the operation. Multivariate logistic regression analysis was used to identify risk factors affecting the early occurrence of AKI post-operation. The receiver operating characteristic curve evaluated PCT, CRP, and NGAL in the early AKI diagnosis. Results: A total of 86 patients (30 with AKI and 56 with Non-AKI) were included. Kidney injury molecule-1(KIM-1) and urinary microalbumin(mAlb) concentrations were significantly higher in the AKI group (P<0.05). PCT, CRP, and NGAL concentrations were significantly higher two hours after the operation than before the operation (P<0.05). KIM-1 levels and elevated PCT, CRP and NGAL concentrations affected the establishment of AKI after UUTC. The sensitivity of PCT, CRP, and NGAL in evaluating AKI after UUTC were 81.17%, 84.42%, and 79.02%; the specificity was 62.31%, 71.48%, and 73.32%; and the AUC was 0.812, 0.885 and 0.804 respectively. Conclusions: PCT, CRP, and NGAL concentrations in patients with AKI after UUTC were significantly increased two hours after the operation, which can be used for the early diagnosis of AKI after UUTC operation.

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