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1.
World J Urol ; 42(1): 321, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744781

RESUMO

PURPOSE: Utilize magnetic resonance defecography (MRD) to analyze the primary pelvic floor dysfunctions in patients with stress urinary incontinence (SUI) associated with pelvic organ prolapse (POP), and in SUI patients with asymptomatic POP. METHOD: We performed MRD in both SUI and POP subjects. As a primary analysis, the functional MR parameters were compared between the isolated POP and POP combined SUI groups. As a secondary analysis, the functional MR data were compared between the POP combined SUI and the SUI with asymptomatic POP (isolated SUI) groups. RESULTS: MRD noted the main characteristics of SUI combined moderate or severe POP, including the shorter closed urethra length (1.87 cm vs. 2.50 cm, p < 0.001), more prevalent urethral hypermobility (112.31° vs. 85.67°, p = 0.003), bladder neck funneling (48.28% vs. 20.51%, p = 0.020), lower position of vesicourethral junction (2.11 cm vs. 1.67 cm, p = 0.030), and more severe prolapse of the posterior bladder wall (6.26 cm vs. 4.35 cm, p = 0.008). The isolated SUI patients showed the shortest length of the closed urethra (1.56 cm vs. 1.87 cm, p = 0.029), a larger vesicourethral angle (153.80° vs. 107.58°, p < 0.001), the more positive bladder funneling (84.85% vs. 48.28%, p = 0.002) and a special urethral opening sign (45.45% vs. 3.45%, p < 0.001). CONCLUSIONS: Patients with SUI accompanying POP primarily exhibit excessive urethral mobility and a shortened urethral closure. SUI patients with asymptomatic POP mainly show dysfunction of the urethra and bladder neck, characterized by the opening of the urethra and bladder neck and a shortened urethral closure.


Assuntos
Defecografia , Imageamento por Ressonância Magnética , Prolapso de Órgão Pélvico , Incontinência Urinária por Estresse , Humanos , Incontinência Urinária por Estresse/diagnóstico por imagem , Prolapso de Órgão Pélvico/diagnóstico por imagem , Prolapso de Órgão Pélvico/complicações , Feminino , Pessoa de Meia-Idade , Idoso , Adulto
2.
Neuroradiology ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592454

RESUMO

PURPOSE: Posterior circulation ischemic stroke (PCIS) possesses unique features. However, previous studies have primarily or exclusively relied on anterior circulation stroke cases to build machine learning (ML) models for predicting onset time. To date, there is no research reporting the effectiveness and stability of ML in identifying PCIS onset time. We aimed to build diffusion-weighted imaging-based ML models to identify the onset time of PCIS patients. METHODS: Consecutive PCIS patients within 24 h of definite symptom onset were included (112 in the training set and 49 in the independent test set). Images were processed as follows: volume of interest segmentation, image feature extraction, and feature selection. Five ML models, naïve Bayes, logistic regression, tree ensemble, k-nearest neighbor, and random forest, were built based on the training set to estimate the stroke onset time (binary classification: ≤ 4.5 h or > 4.5 h). Relative standard deviations (RSD), receiver operating characteristic (ROC) curves, and the calibration plot was performed to evaluate the stability and performance of the five models. RESULTS: The random forest model had the best performance in the test set, with the highest area under the curve (AUC, 0.840; 95% CI: 0.706, 0.974). This model also achieved the highest accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (83.7%, 64.3%, 91.4%, 75.0%, and 86.5%, respectively). Furthermore, the model had high stability (RSD = 0.0094). CONCLUSION: The PCIS case-based ML model was effective for estimating the symptom onset time and achieved considerably high specificity and stability.

3.
Magn Reson Imaging ; 110: 23-28, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38552748

RESUMO

OBJECTIVE: To evaluate the effect of stent implantation for vertebrobasilar artery stenosis,by using 3D arterial spin labeling (3D ASL) technique. METHODS: A retrospective analysis was conducted on the clinical and 3D ASL data of 48 patients who underwent vertebral-basilar artery stenting. Post-labeling delay times (PLD) of 1.5 s and 2.5 s were chosen, and the average regional cerebral blood flow (rCBF) values were measured in nine brain regions of the posterior circulation: bilateral thalamus, bilateral occipital lobes, bilateral cerebellar hemispheres, midbrain, pons, and medulla. The 48 patients were divided into two groups based on the presence or absence of acute ischemic stroke in the posterior cerebral circulation region detected by diffusion-weighted imaging (DWI). The preoperative and postoperative rCBF results were statistically analyzed. RESULTS: In the infarct group, there were significant increases in rCBF values of all nine brain regions at both PLD = 1.5 s and 2.5 s postoperatively compared to preoperatively. At PLD = 1.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were found in the right thalamus, left cerebellum, midbrain, and pons regions (P < 0.05). At PLD = 2.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were observed in the left occipital lobe, right cerebellum, midbrain, and pons regions (P < 0.05). When analyzing the rCBF values of the brain regions with recent infarcts in the infarct group, there was a significant increase in postoperative rCBF values compared to preoperative values (P < 0.05). After excluding the data from brain regions with recent infarcts, the CBF values in the remaining brain regions were also increased postoperatively, and some brain regions showed statistically significant differences in rCBF values between the preoperative and postoperative periods (P < 0.05). In the non-infarct group, there were no statistically significant differences in the preoperative and postoperative rCBF values in all brain regions at both PLD = 1.5 s and 2.5 s (P > 0.05). CONCLUSION: The application of 3D ASL technology shows significant value in assessing the surgical efficacy of vertebral-basilar artery stenting, especially in patients with acute posterior circulation infarction.


Assuntos
Circulação Cerebrovascular , Imageamento Tridimensional , Stents , Insuficiência Vertebrobasilar , Humanos , Masculino , Feminino , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Imageamento Tridimensional/métodos , Resultado do Tratamento , Marcadores de Spin , Imagem de Difusão por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Encéfalo/cirurgia , Adulto
4.
Plants (Basel) ; 13(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38337927

RESUMO

This investigation focused on the suppressive impact of varying NaHCO3 concentrations on cucumber seed germination and the ameliorative effects of 2,4-Epibrassinolide (EBR). The findings revealed a negative correlation between NaHCO3 concentration and cucumber seed germination, with increased NaHCO3 concentrations leading to a notable decline in germination. Crucially, the application of exogenous EBR significantly counteracted this inhibition, effectively enhancing germination rates and seed vigor. Exogenous EBR was observed to substantially elevate the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), thereby mitigating oxidative damage triggered under NaHCO3 stress conditions. Additionally, EBR improved enzyme activity under alkaline stress conditions and reduced starch content in the seeds. Pertinently, EBR upregulated genes that were associated with gibberellin (GA) synthesis (GA20ox and GA3ox), and downregulated genes that were linked to abscisic acid (ABA) synthesis (NCED1 and NCED2). This led to an elevation in GA3 concentration and a reduction in ABA concentration within the cucumber seeds. Therefore, this study elucidates that alleviating oxidative stress, promoting starch catabolism, and regulating the GA and ABA balance are key mechanisms through which exogenous EBR mitigates the suppression of cucumber seed germination resulting from alkaline stress.

5.
Protein Expr Purif ; 218: 106441, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38367654

RESUMO

Nanobodies (Nbs) represent a class of single-domain antibodies with great potential application value across diverse biotechnology fields, including therapy and diagnostics. Thymic Stromal Lymphopoietin (TSLP) is an epithelial cell-derived cytokine, playing a crucial role in the regulation of type 2 immune responses at barrier surfaces such as skin and the respiratory/gastrointestinal tract. In this study, a method for the expression and purification of anti-TSLP nanobody (Nb3341) was established at 7 L scale and subsequently scaled up to 100 L scale. Key parameters, including induction temperature, methanol feed and induction pH were identified as key factors by Plackett-Burman design (PBD) and were optimized in 7 L bioreactor, yielding optimal values of 24 °C, 8.5 mL/L/h and 6.5, respectively. Furthermore, Diamond Mix-A and Diamond MMC were demonstrated to be the optimal capture and polishing resins. The expression and purification process of Nb3341 at 100L scale resulted in 22.97 g/L titer, 98.7% SEC-HPLC purity, 95.7% AEX-HPLC purity, 4 ppm of HCP content and 1 pg/mg of HCD residue. The parameters of the scaling-up process were consistent with the results of the optimized process, further demonstrating the feasibility and stability of this method. This study provides a highly promising and competitive approach for transitioning from laboratory-scale to commercial production-scale of nanobodies.


Assuntos
Anticorpos de Domínio Único , Linfopoietina do Estroma do Timo , Anticorpos de Domínio Único/genética , Anticorpos de Domínio Único/metabolismo , Citocinas/metabolismo , Células Epiteliais , Diamante/metabolismo
6.
Angew Chem Int Ed Engl ; 63(6): e202313859, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38055195

RESUMO

Exploitation of key protected wild plant resources makes great sense, but their limited populations become the major barrier. A particular strategy for breaking this barrier was inspired by the exploration of a resource-saving fungal endophyte Penicillium sp. DG23, which inhabits the key protected wild plant Schisandra macrocarpa. Chemical studies on the cultures of this strain afforded eight novel indole diterpenoids, schipenindolenes A-H (1-8), belonging to six diverse skeleton types. Importantly, semisyntheses suggested some key nonenzymatic reactions constructing these molecules and provided targeted compounds, in particular schipenindolene A (Spid A, 1) with low natural abundance. Remarkably, Spid A was the most potent HMG-CoA reductase (HMGCR) degrader among the indole diterpenoid family. It degraded statin-induced accumulation of HMGCR protein, decreased cholesterol levels and acted synergistically with statin to further lower cholesterol. Mechanistically, transcriptomic and proteomic profiling suggested that Spid A potentially activated the endoplasmic reticulum-associated degradation (ERAD) pathway to enhance the degradation of HMGCR, while simultaneously inhibiting the statin-activated expression of many key enzymes in the cholesterol and fatty acid synthesis pathways, thereby strengthening the efficacy of statins and potentially reducing the side effects of statins. Collectively, this study suggests the potential of Spid A for treating cardiovascular disease.


Assuntos
Acil Coenzima A , Inibidores de Hidroximetilglutaril-CoA Redutases , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Degradação Associada com o Retículo Endoplasmático , Proteômica , Colesterol/metabolismo , Indóis
7.
J Nanobiotechnology ; 21(1): 410, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932752

RESUMO

BACKGROUND: Pancreatic cancer is a highly aggressive malignancy with limited treatment options and a poor prognosis. Trophoblast cell surface antigen 2 (TROP2), a cell surface antigen overexpressed in the tumors of more than half of pancreatic cancer patients, has been identified as a potential target for antibody-drug conjugates (ADCs). Almost all reported TROP2-targeted ADCs are of the IgG type and have been poorly studied in pancreatic cancer. Here, we aimed to develop a novel nanobody-drug conjugate (NDC) targeting TROP2 for the treatment of pancreatic cancer. RESULTS: In this study, we developed a novel TROP2-targeted NDC, HuNbTROP2-HSA-MMAE, for the treatment of TROP2-positive pancreatic cancer. HuNbTROP2-HSA-MMAE is characterized by the use of nanobodies against TROP2 and human serum albumin (HSA) and has a drug-antibody ratio of 1. HuNbTROP2-HSA-MMAE exhibited specific binding to TROP2 and was internalized into tumor cells with high endocytosis efficiency within 5 h, followed by intracellular translocation to lysosomes and release of MMAE to induce cell apoptosis in TROP2-positive pancreatic cancer cells through the caspase-3/9 pathway. In a xenograft model of pancreatic cancer, doses of 0.2 mg/kg and 1 mg/kg HuNbTROP2-HSA-MMAE demonstrated significant antitumor effects, and a dose of 5 mg/kg even eradicated the tumor. CONCLUSION: HuNbTROP2-HSA-MMAE has desirable affinity, internalization efficiency and antitumor activity. It holds significant promise as a potential therapeutic option for the treatment of TROP2-positive pancreatic cancer.


Assuntos
Imunoconjugados , Neoplasias Pancreáticas , Humanos , Antígenos de Superfície , Linhagem Celular Tumoral , Imunoconjugados/química , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Neoplasias Pancreáticas
9.
Front Oncol ; 13: 1211027, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576903

RESUMO

Objective: The aim of this study is to investigate the clinical characteristics and diagnostic and therapeutic methods of bladder metastasis after radical prostatectomy and to improve its diagnosis and treatment. Methods: The clinical data of four patients with bladder metastasis after radical prostatectomy were retrospectively analyzed from January 2011 to December 2021. Three cases suffered from intermittent gross hematuria, and only one case was found to have an elevated prostate-specific antigen (PSA) value. Transurethral resection of bladder tumor was performed in four cases, in which one case also underwent resection of urethral mass. Three cases received endocrine therapy, one of which added intravesical instillation and radiation therapy. Another case received chemotherapy based on comprehensive treatment. Results: According to the pathological and immunohistochemical results, three cases were acinar adenocarcinoma of the prostate with Gleason score of 9, and all cases were PSA positive and negative for cytokeratin 7 (CK7) and GATA binding protein 3 (GATA-3). One case was small cell neuroendocrine carcinoma of the prostate and was positive for chromogranin A (CGA), synaptophysin (SYN), and cluster of differentiation 56 (CD56). During the follow-up period of 4 to 13 months, one case was lost to follow-up and three cases were alive. Conclusion: Bladder metastasis after radical prostatectomy is rare, and pathology combined with immunohistochemistry is the gold standard for its diagnosis. Pathological type determines its treatment. Systemic treatment is essential, and local treatment is the most palliative means. Early diagnosis and treatment is significant for better prognosis.

10.
Adv Sci (Weinh) ; 10(26): e2300834, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37428471

RESUMO

Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS-CoV-2 infection via upregulating angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans-activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzo[a]pyrene increases the susceptibility of lung epithelial cells to SARS-CoV-2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown or interferon-λ2/λ3 stimulation downregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzo[a]pyrene enhances SARS-CoV-2 infection by boosting NR4A2-induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS-CoV-2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.


Assuntos
COVID-19 , Idoso , Masculino , Humanos , Animais , Camundongos , COVID-19/metabolismo , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/metabolismo , Benzo(a)pireno/metabolismo , Pulmão/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo
11.
J Womens Health Dev ; 6(1): 31-35, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37168527

RESUMO

Objective: To evaluate the short-term efficacy of pelvic magnetic stimulation combined with pelvic muscle biofeedback on female Idiopathic Overactive Bladder (IOAB). Methods: 96 cases of IOAB females were randomly divided into control group (magnetic stimulation treatment n=48) and observation group (magnetic stimulation with biofeedback n=48). All the patients were dealt with the sacralneuromagnetic stimulation (once, qod), with 5 times in total. Then the patients in observation group were processed with biofeedback (10 times). Overactive Bladder Symptom Score (OABSS), Patients Perception Bladder Condition (PPBC) and Incontinence Quality of Life Scale (I-QOL) were evaluated as the indexes. Results: The effective rate of control group and observation group respectively were 89.58% and 93.75%. There were significant differences (P=0.67). The OABSS and PPBC of two groups were decreased, I-QOL were increased after treatment (P<0.05). Difference was statistically significant in OABSS three months after treatment between the two groups (P=0.00).The recurrence rate of three months after treatment of the two groups were 18.75% and 6.38% (P=0.04). Conclusions: Both magnetic stimulation alone and magnetic stimulation with biofeedback were effective and safe in female patients with IOAB. Magnetic stimulation with biofeedback may reduce the recurrence rate and continue to improve the symptoms in a certain extent.

12.
Med Sci Monit ; 29: e938758, 2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36869580

RESUMO

BACKGROUND Delayed graft function (DGF) caused by ischemia-reperfusion injury is a common pathophysiological process that should be monitored by specific biomarkers in addition to serum creatinine. Thus, this single-center retrospective study aimed to investigate the association between levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecular-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and interleukin-18 (IL-18) in DGF associated with acute kidney injury in kidney transplant recipients (KTRs) and estimated glomerular filtration rate (eGFR) at 3 years post-transplant. MATERIAL AND METHODS A total of 102 KTRs [14(13.7%) of DGF and 88(86.3%) of NON-DGF] were enrolled. DGF was defined as "dialysis is needed within 1 week after kidney transplantation". NGAL, KIM-1, L-FABP, and IL-18 were obtained from perfusate samples of donation-after-cardiac-death (DCD) kidneys, and measured by ELISA. RESULTS Compared to the NON-DGF group, KTRs in the DGF group had a statistically significant increase in levels of NGAL (P<0.001) and KIM-1 (P<0.001). Multiple logistic regression analyses showed that NGAL (OR=1.204, 95% CI 1.057-1.372, P=0.005) and KIM-1 (OR=1.248, CI=1.065-1.463, P=0.006) could be regarded as independent risk factors. The accuracy of NGAL and KIM-1 was 83.3% and 82.1%, respectively, calculated using the area under the receiver operating characteristic curve. Furthermore, the eGFR at 3 years post-transplant had a moderate negative correlation with NGAL (r=-0.208, P=0.036) and KIM-1 (r=-0.260, P=0.008). CONCLUSIONS Our results support those from previous studies showing that perfusate levels of NGAL and KIM-1 are associated with DGF in KTRs and also with reduced eGFR at 3 years post-transplant.


Assuntos
Interleucina-18 , Transplante de Rim , Humanos , Lipocalina-2 , Estudos Retrospectivos , Função Retardada do Enxerto , Prognóstico , Biomarcadores , Proteínas de Ligação a Ácido Graxo , Rim , Fígado
13.
Materials (Basel) ; 16(3)2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36770153

RESUMO

Inorganic scintillators are of great significance in the fields of medical CT, high-energy physics and industrial nondestructive testing. In this work, we confirm that the Pb4Lu3F17: Re (Re = Tb, Eu, Sm, Dy, Ho) crystals are promising candidates for a new kind of scintillator. Detailed crystal structure information is obtained by the Rietveld refinement analysis. Upon X-ray irradiation, all these scintillators exhibited characteristic 4f-4f transitions. The Ce and Gd ions were verified to be useful for enhancing the scintillation intensity via introducing energy transfer processes. The integrated scintillation intensity of the Pb4Lu3F17: Tb/Ce is about 16.8% of the commercial CsI (Tl) single crystal. Our results manifested that Pb4Lu3F17: Re has potential application in X-ray detection and imaging.

14.
J Chemother ; 35(2): 104-116, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35285783

RESUMO

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Bancos de Tecidos
15.
Neuroimage Clin ; 36: 103267, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36510412

RESUMO

This study's aim was to investigate functional brain connectivity changes among patients with moyamoya disease (MMD) with limb paresthesia, using functional connectivity analysis based on resting-state functional magnetic resonance imaging (rs-fMRI). A total of 181 patients with MMD were enrolled, including 57 with left limb paresthesia (MLP group), 61 with right limb paresthesia (MRP group), and 63 without paresthesia (MWP group). Encephaloduroarteriosynangiosis (EDAS) was performed in 20 of the 57 patients with left limb paresthesia and 15 of the 61 patients with right limb paresthesia. Twenty-nine age- and sex-matched healthy controls (HC group) were recruited during the same period. All participants underwent rs-fMRI examination, and the patients treated with EDAS were re-examined 3-4 months after the surgery. After data preprocessing, we selected Brodmann area 3 on each side of the brain as the seed region to construct a functional connectivity network of the whole brain, and then we analyzed the differences in functional connectivity between the HC group, MWP group, MLP group, and MRP group. The functional connectivity of Brodmann area 3 (on either side) with the ipsilateral frontal (superior frontal gyrus, middle frontal gyrus, and inferior frontal gyrus) and parietal (supramarginal gyrus, angular gyrus, and superior parietal lobule) cortices was increased among patients with MMD. The functional connectivity enhancement in these brain regions was broader and greater in patients with contralateral limb paresthesia than in patients without paresthesia, and the regions with functional connectivity changes were roughly distributed symmetrically among the MLP group and the MRP group. There were no changes 3-4 months after EDAS in the increased functional connectivity between the frontal and parietal cortices and Brodmann area 3. Limb paresthesia in patients with MMD may be driven by abnormal functional connectivity in the frontal and parietal cortices. Functional changes in associated brain regions may be a target for evaluating the severity of MMD and its response to treatment.


Assuntos
Imageamento por Ressonância Magnética , Doença de Moyamoya , Humanos , Imageamento por Ressonância Magnética/métodos , Doença de Moyamoya/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos
16.
Respir Res ; 23(1): 316, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36403040

RESUMO

BACKGROUND: Eosinophilic asthma is a common subtype of severe asthma with high morbidity and mortality. The cytokine IL-5 has been shown to be a key driver of the development and progression of disease. Although approved monoclonal antibodies (mAbs) targeting IL-5/IL-5R have shown good safety and efficacy, some patients have inadequate responses and frequent dosing results in medication nonadherence. RESULTS: We constructed a novel trivalent bispecific nanobody (Nb) consisting of 3 VHHs that bind to 2 different epitopes of IL-5 and 1 epitope of albumin derived from immunized phage display libraries. This trivalent IL-5-HSA Nb exhibited similar IL-5/IL-5R blocking activities to mepolizumab (Nucala), an approved targeting IL-5 mAb. Surprisingly, this trivalent Nb was 58 times more active than mepolizumab in inhibiting TF-1-cell proliferation. In primate studies, the trivalent IL-5-HSA Nb showed excellent pharmacokinetic properties, and peripheral blood eosinophil levels remained significantly suppressed for two months after a single dose. In addition, the trivalent IL-5-HSA Nb could be produced on a large scale in a P. pastoris X-33 yeast system with high purity and good thermal stability. CONCLUSIONS: These findings suggest that the trivalent bispecific IL-5-HSA Nb has the potential to be a next-generation therapeutic agent targeting IL-5 for the treatment of severe eosinophilic asthma.


Assuntos
Asma , Eosinofilia Pulmonar , Animais , Interleucina-5/metabolismo , Interleucina-5/uso terapêutico , Eosinofilia Pulmonar/tratamento farmacológico , Eosinofilia Pulmonar/metabolismo , Asma/metabolismo , Eosinófilos/metabolismo , Anticorpos Monoclonais/uso terapêutico
17.
Front Neurosci ; 16: 1029388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389234

RESUMO

Purpose: To investigate the structural and network topological changes in the white matter (WM) in MMD patients with limb paresthesia by performing diffusion kurtosis imaging (DKI). Materials and methods: A total of 151 MMD patients, including 46 with left-limb paresthesia (MLP), 52 with right-limb paresthesia (MRP), and 53 without paresthesia (MWP), and 28 healthy controls (HCs) underwent whole-brain DKI, while the surgical patients were reexamined 3-4 months after revascularization. The data were preprocessed to calculate the fractional anisotropy (FA) and mean kurtosis (MK) values. Voxel-wise statistics for FA and MK images were obtained by using tract-based spatial statistics (TBSS). Next, the whole-brain network was constructed, and global and local network parameters were analyzed using graph theory. All parameters were compared among the HC, MWP, MLP, and MRP groups, and changes in the MMD patients before and after revascularization were also compared. Results: The TBSS analysis revealed significant reductions in FA and MK in extensive WM regions in the three patient groups. In comparison with the MWP group, the MLP group showed reductions in FA and MK in both right and left WM, mainly in the right WM, while the MRP group mainly showed a reduction in FA in the left WM region and demonstrated no significant change in MK. The graph theoretical analysis showed decreased global network efficiency, increased characteristic path length, and increased sigma in the MWP, MRP, and MLP groups in comparison with the HC group. Among local network parameters, the nodal efficiency decreased in the bilateral MFG and IFGtriang, while the degree decreased in the MFG.L and bilateral IFGtriang. Patients with right-limb paresthesia showed the lowest nodal efficiency and degree in MFG.L and IFGtriang.L, while those with left-limb paresthesia showed the lowest nodal efficiency in MFG.R and IFGtriang.R and the lowest degree in IFGtriang.R. Conclusion: A DKI-based whole-brain structural and network analysis can be used to detect changes in WM damage and network topological changes in MMD patients with limb paresthesia. FA is more sensitive than MK in detecting WM injury, while MFG and IFGtriang are the key nodes related to the development of acroparesthesia.

18.
Front Microbiol ; 13: 1015913, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338084

RESUMO

Natural pigments are playing important roles in our daily lives. They not only make products colorful but also provide various health benefits for humans. In addition, Pycnoporus genus, listed as food- and cosmetic-grade microorganism, is one of the promising organisms for developing natural pigments. In this study, a new fungal strain with high efficiency in producing intense orange pigments was isolated and identified as Pycnoporus sanguineus SYBC-L7. Different agro-industrial wastes were applied to evaluate the growth and pigment production of strain SYBC-L7. SYBC-L7 can grow rapidly and effectively produce pigments using wood chips as substrate in solid-state fermentation (SSF). Culture conditions were also optimized for value-added pigments production and the optimum production conditions were glucose as carbon source, ammonium tartrate as nitrogen source, initial pH 6.0, and relative humidity of 65%. Pigment components, cinnabarinic acid, tramesanguin, and 2-amino-9-formylphenoxazone-1-carbonic acid were confirmed by liquid chromatography-mass spectrometry. Meanwhile, an agar plate diffusion assay was performed to evaluate the antimicrobial activity of the pigment. These pigments showed more significant inhibition of Gram-positive than Gram-negative bacteria. The results showed that Pycnoporus sanguineus SYBC-L7 was able to cost-effectively produce intense natural orange pigments with antibacterial activity in SSF, which is the basis of their large-scale production and application.

19.
Foods ; 11(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36360109

RESUMO

OBJECTIVE: Walnuts have rich nutritional value and are favored by the majority of consumers. As walnuts are shelled nuts, they are prone to suffer from defects such as mildew during storage. The fullness and mildew of the fruit impose effects on the quality of the walnuts. Therefore, it is of great economic significance to carry out a study on the rapid, non-destructive detection of walnut quality. METHODS: Terahertz spectroscopy, with wavelengths between infrared and electromagnetic waves, has unique detection advantages. In this paper, the rapid and nondestructive detection of walnut mildew and fullness based on terahertz spectroscopy is carried out using the emerging terahertz transmission spectroscopy imaging technology. First, the normal walnuts and mildewed walnuts are identified and analyzed. At the same time, the image processing is carried out on the physical samples with different kernel sizes to calculate the fullness of the walnut kernels. The THz image of the walnuts is collected to extract the spectral information in different regions of interest. Four kinds of time domain signals in different regions of interest are extracted, and three qualitative discrimination models are established, including the support vector machine (SVM), random forest (RF), and k-nearest neighbor (KNN) algorithms. In addition, in order to realize the visual expression of walnut fullness, the terahertz images of the walnut are segmented with a binarization threshold, and the walnut fullness is calculated by the proportion of the shell and kernel pixels. RESULTS: In the frequency domain signal, the amplitude intensity from high to low is the mildew sample, walnut kernel, and walnut shell, and the distinction between walnut kernel, shell samples, and mildew samples is high. The overall identification accuracy of the aforementioned three models is 90.83%, 97.38%, and 97.87%, respectively. Among them, KNN has the best qualitative discrimination effect. In a single category, the recognition accuracy of the model for the walnut kernel, walnut shell, mildew sample, and reference group (background) reaches 94%, 100%, 97.43%, and 100%, respectively. The terahertz transmission images of the five categories of walnut samples with different kernel sizes are processed to visualize the detection of kernel fullness inside walnuts, and the errors are less than 5% compared to the actual fullness of walnuts. CONCLUSION: This study illustrates that terahertz spectroscopy detection can achieve the detection of walnut mildew, and terahertz imaging technology can realize the visual expression and fullness calculation of walnut kernels. Terahertz spectroscopy and imaging provides a non-destructive detection method for walnut quality, which can provide a reference for the quality detection of other dried nuts with shells, thus having significant practical value.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36361114

RESUMO

Rural areas are vulnerable to natural disasters and tend to suffer severe losses. An EF4 tornado occurred in Funing on 23 June 2016, killing 99 people, injuring at least 846 people, and destroying more than 2000 houses. Using a multinomial logistic regression model, this study explored the influencing factors between housing damage and variables of building conditions, tornado intensity, and village environmental factors. The results show that 2-story houses and masonry houses were more likely to be slightly damaged or be in a dangerous state. Furthermore, the building area was positively related to houses in two categories: slight damage (SD) and dangerous and requiring immediate repair (DR), indicating that the larger or taller the house, the more severe the damage. In terms of tornado intensity, houses classified as SD were more likely to be hit by EF4 tornados than by EF3 tornados, and houses were damaged more by EF1 or EF2 tornados. This finding demonstrates that the level of housing damage was not strongly correlated with the tornado intensity. Slightly damaged houses exhibited the highest correlation with environmental factors. The proportion of slightly damaged houses was positively correlated with the water area in the village, unlike the proportion of houses in the DR and unable to be repaired (UR) categories. Moreover, the larger the water area of a village, the less housing damage it suffered. These findings provide new insights into minimizing housing damage in wind disasters to improve disaster prevention planning in rural areas.


Assuntos
Desastres , Tornados , Humanos , Habitação , China/epidemiologia , Água
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