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BACKGROUND: Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. METHODS: Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs' gene and protein expression was conducted using human colon cancer cells. RESULTS: Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. CONCLUSION: This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.
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Background: High horseshoe-shaped anal fistula (HHAF) is a complex disease that manifests in the perianal region and typically requires surgical intervention for treatment. However, the current therapeutic approaches are limited by the high rates of postoperative recurrence and anal incontinence. To overcome the limitations of traditional surgical approaches, we introduce the bared external anal sphincter (BEAS) technique. Our study aims to compare the clinical efficacy of BEAS surgery with that of the modified Hanley procedure in a real-world setting. Materials and methods: This single-centre, prospective cohort study will be conducted in a tertiary hospital in China and aims to evaluate the short-term clinical efficacy and safety of BEAS surgery and modified Hanley surgery in HHAF patients from March 2024 to March 2026. Data from the prospective database of this tertiary referral hospital will be used to obtain insights into the clinical outcomes of these surgical treatments. The primary outcome of this study will be the wound healing rate within six months, while the secondary outcomes will include the time to return to work, the maximum visual analogue scale pain score (VAS-PS) within 1-5 days postsurgery, and the Cleveland Clinic Florida Incontinence Score (CCF-IS) and Quality of Life in Anal Fistula Questionnaire Score (QoLAF-QS) at 1, 3, and 6 months postsurgery. Moreover, logistic regression analysis will be used to explore the risk factors for anal fistula recurrence after the BEAS procedure. Discussion: This will be the first cohort study to evaluate the differences in therapeutic outcomes between patients who undergo BEAS surgery and patients who undergo surgery via the modified Hanley procedure. By conducting a detailed observation of the efficacy and treatment results of these two surgical methods, this study aims to reveal the differences the clinical effectiveness of these approaches and to provide evidence-based support for future randomized controlled trials (RCTs).
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Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.
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The quaternion cubature Kalman filter (QCKF) algorithm has emerged as a prominent nonlinear filter algorithm and has found extensive applications in the field of GNSS/SINS integrated attitude determination and positioning system (GNSS/SINS-IADPS) data processing for unmanned aerial vehicles (UAV). However, on one hand, the QCKF algorithm is predicated on the assumption that the random model of filter algorithm, which follows a white Gaussian noise distribution. The noise in actual GNSS/SINS-IADPS is not the white Gaussian noise but rather a ubiquitous non-Gaussian noise. On the other hand, the use of quaternions as state variables is bound by normalization constraints. When applied directly in nonlinear non-Gaussian system without considering normalization constraints, the QCKF algorithm may result in a mismatch phenomenon in the filtering random model, potentially resulting in a decline in estimation accuracy. To address this issue, we propose a novel Gaussian sum quaternion constrained cubature Kalman filter (GSQCCKF) algorithm. This algorithm refines the random model of the QCKF by approximating non-Gaussian noise with a Gaussian mixture model. Meanwhile, to account for quaternion normalization in attitude determination, a two-step projection method is employed to constrain the quaternion, which consequently enhances the filtering estimation accuracy. Simulation and experimental analyses demonstrate that the proposed GSQCCKF algorithm significantly improves accuracy and adaptability in GNSS/SINS-IADPS data processing under non-Gaussian noise conditions for Unmanned Aerial Vehicles (UAVs).
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Backgrounds: Numerous lines of evidence support the intricate interplay between Parkinson's disease (PD) and the PINK1-dependent mitophagy process. This study aimed to evaluate differences in plasma PINK1 levels among idiopathic PD, PD syndromes (PDs), and healthy controls. Methods: A total of 354 participants were included, consisting of 197 PD patients, 50 PDs patients, and 107 healthy controls were divided into two cohorts, namely the modeling cohort (cohort 1) and the validated cohort (cohort 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis was performed on PINK1 and α-synuclein oligomer (Asy-no). The utilization of the area under the curve (AUC) within the receiver-operating characteristic (ROC) curves served as a robust and comprehensive approach to evaluate and quantify the predictive efficacy of plasma biomarkers alone, as well as combined models, in distinguishing PD patients from controls. Results: PINK1 and Asy-no were elevated in the plasma of PD and PDs patients compared to healthy controls. The AUCs of PINK1 (0.771) and Asy-no (0.787) were supposed to be potentially eligible plasma biomarkers differentiating PD from controls but could not differentiate PD from PDs. Notably, the PINK + Asy-no + Clinical RBD model showed the highest performance in the modeling cohort and was comparable with the PINK1 + Clinical RBD in the validation cohort. Moreover, there is no significant correlation between PINK1 and UPDRS, MMSE, HAMD, HAMA, RBDQ-HK, and ADL scores. Conclusion: These findings suggest that elevated PINK1 in plasma holds the potential to serve as a non-invasive tool for distinguishing PD patients from controls. Moreover, the outcomes of our investigation lend support to the plausibility of implementing a feasible blood test in future clinical translation.
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Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care. In this study, we explored the combination effect of CBD and dasatinib on A549 cells. CBD in combination with dasatinib could induce significant synergistic apoptosis in vitro (ZIP > 10) and in vivo. The combination of CBD and low-dose dasatinib exhibited antiproliferative and proapoptotic effects through up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2 in A549 cells. The xenograft mouse model suggested that the combination was more efficient and safer. In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.
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Cannabidiol , Neoplasias Pulmonares , Humanos , Animales , Ratones , Dasatinib/farmacología , Dasatinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Transducción de Señal , Línea Celular Tumoral , Apoptosis , Proliferación Celular , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
Background: Osteoporosis increases bone brittleness and the risk of fracture. Umbilical cord mesenchymal stem cell (UCMSC) treatment is effective, but how to improve the biological activity and clinical efficacy of UCMSCs has not been determined. METHODS: A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 106 cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κß ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10-6 mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, ß-catenin, RUNX2, IFN-γ and IL-17 in the bone tissue were measured via Western blotting. RESULTS: The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, ß-catenin, and runx2 was upregulated, and IFN-γ and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment. CONCLUSION: HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/ß-catenin pathway and inhibition of inflammation.
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Constructing wrinkles by utilizing strain-driven surface instability in film-substrate systems is a general method to prepare micronano structures, which have a wide range of applications in smart surfaces and devices such as flexible electronics, reversible wetting, friction, and optics. However, cracks generated during the preparation and use process significantly affect the uniformity of wrinkled surfaces and degrade the functional properties of the film devices. The realization of crack-free wrinkles with high stretchability in hard film systems is still a great challenge. Here, we report on a facile technique for controllable preparation of large-area, highly stretchable, crack-free wrinkled surfaces by ultraviolet ozone (UVO) treatment of Ecoflex. The thickness dependence of the wrinkles and the in situ wrinkling process during mechanical loading are investigated. The wrinkles including striped, labyrinth-like, herringbone, and transitional structures are controllable by changing strain mode (uniaxial or biaxial), loading history (simultaneous or sequential), strain anisotropy, and gradient loading. The wrinkled surfaces obtained using UVO-treated Ecoflex have tunable wetting and optical properties and can maintain excellent mechanical stability under large strains. This study provides a facile method for the preparation of large-area, crack-free wrinkles, which is simple, fast, low-cost, and robust. The resulting wrinkled surfaces remain stable under high stretching, which is beneficial for many practical applications, especially in the cases of large strains.
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OBJECTIVES: The ATN's different modalities (fluids and neuroimaging) for each of the Aß (A), tau (T), and neurodegeneration (N) elements are used for the biological diagnosis of Alzheimer's disease (AD). We aim to identify which ATN category achieves the highest potential for diagnosis and predictive accuracy of longitudinal cognitive decline. METHODS: Based on the availability of plasma ATN biomarkers (plasma-derived Aß42/40 , p-tau181, NFL, respectively), CSF ATN biomarkers (CSF-derived Aß42 /Aß40 , p-tau181, NFL), and neuroimaging ATN biomarkers (18F-florbetapir (FBP) amyloid-PET, 18F-flortaucipir (FTP) tau-PET, and fluorodeoxyglucose (FDG)-PET), a total of 2340 participants were selected from ADNI. RESULTS: Our data analysis indicates that the area under curves (AUCs) of CSF-A, neuroimaging-T, and neuroimaging-N were ranked the top three ATN candidates for accurate diagnosis of AD. Moreover, neuroimaging ATN biomarkers display the best predictive ability for longitudinal cognitive decline among the three categories. To note, neuroimaging-T correlates well with cognitive performances in a negative correlation manner. Meanwhile, participants in the "N" element positive group, especially the CSF-N positive group, experience the fastest cognitive decline compared with other groups defined by ATN biomarkers. In addition, the voxel-wise analysis showed that CSF-A related to tau accumulation and FDG-PET indexes more strongly in subjects with MCI stage. According to our analysis of the data, the best three ATN candidates for a precise diagnosis of AD are CSF-A, neuroimaging-T, and neuroimaging-N. CONCLUSIONS: Collectively, our findings suggest that plasma, CSF, and neuroimaging biomarkers differ considerably within the ATN framework; the most accurate target biomarkers for diagnosing AD were the CSF-A, neuroimaging-T, and neuroimaging-N within each ATN modality. Moreover, neuroimaging-T and CSF-N both show excellent ability in the prediction of cognitive decline in two different dimensions.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neuroimagen , Disfunción Cognitiva/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Biomarcadores , Proteínas tau , Péptidos beta-AmiloidesRESUMEN
Immunosuppressant reduction (ISR) is a common treatment for kidney transplant recipients experiencing infections, but its impacts on kidney transplant outcomes remains unclear. This retrospective single-center study included 300 patients who underwent kidney transplantation between January 2017 and April 2020. The post-transplant timeline was divided into four distinct phases: ≤1 month, 2-6 months, 7-12 months, and >12 months. Patients were categorized based on the presence of clinically relevant infections and whether they received ISR. Significant differences were observed in the spectrum of clinically relevant infections across the post-transplant phases. During the ≤1 month phase, primary infections were associated surgical operation, such as urinary tract infections involving Enterococcus spp. and Candida spp. Cytomegalovirus and BK polyomavirus (BKPyV) infections increased during the 2-6 months and 7-12 months periods. Approximately one-third of patients experienced ISR due to infection, with BKPyV infections being the primary causes. Recipients who experienced their first ISR due to infection between 2-6 months and 7-12 months had worse graft survival comparing with patients without any infections. ISR due to infections between 2 and 6 months was associated with a higher risk of rejection. Tailored ISR strategies should be developed according to temporal dynamics of immunosuppressive intensity to prevent rejection.
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Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Trasplante de Riñón/efectos adversos , Inmunosupresores/uso terapéutico , Estudios Retrospectivos , Receptores de TrasplantesRESUMEN
Phosphatidylglycerol (PG) is a mitochondrial phospholipid required for mitochondrial cristae structure and cardiolipin synthesis. PG must be remodeled to its mature form at the endoplasmic reticulum (ER) after mitochondrial biosynthesis to achieve its biological functions. Defective PG remodeling causes MEGDEL (non-alcohol fatty liver disease and 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like) syndrome through poorly defined mechanisms. Here, we identify LPGAT1, an acyltransferase that catalyzes PG remodeling, as a candidate gene for MEGDEL syndrome. We show that PG remodeling by LPGAT1 at the ER is closely coordinated with mitochondrial transport through interaction with the prohibitin/TIMM14 mitochondrial import motor. Accordingly, ablation of LPGAT1 or TIMM14 not only causes aberrant fatty acyl compositions but also ER retention of newly remodeled PG, leading to profound loss in mitochondrial crista structure and respiration. Consequently, genetic deletion of the LPGAT1 in mice leads to cardinal features of MEGDEL syndrome, including 3-methylglutaconic aciduria, deafness, dilated cardiomyopathy, and premature death, which are highly reminiscent of those caused by TIMM14 mutations in humans.
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Sordera , Pérdida Auditiva Sensorineural , Errores Innatos del Metabolismo , Humanos , Animales , Ratones , Fosfatidilgliceroles , Pérdida Auditiva Sensorineural/genética , Errores Innatos del Metabolismo/genética , Sordera/genética , CardiolipinasRESUMEN
BACKGROUND: Patients with gastrointestinal tumors often suffer from poor nutritional status during treatment. Surgery is the main treatment for these patients, but the long postoperative recovery period is often accompanied by digestive and absorption dysfunction, leading to further deterioration of the nutritional status. Early enteral nutrition support is hypothesized to be helpful in improving this situation, but the exact effects have yet to be studied in depth. AIM: To observe the effect of early enteral nutritional support on postoperative recovery in patients with surgically treated gastrointestinal tract tumors, with the expectation that by improving the nutritional status of patients, the recovery process would be accelerated and the incidence of complications would be reduced, thus improving the quality of life. METHODS: A retrospective analysis of 121 patients with gastrointestinal tract tumors treated in our hospital from January 2020 to January 2023 was performed. Fifty-three of these patients received complete parenteral nutrition support as the control group for this study. The other 68 patients received early enteral nutritional support as the observation group of this study. The clinical indicators comparing the two groups included time to fever, time to recovery of postoperative bowel function, time to postoperative exhaustion, and length of hospital stay. The changes in immune function and nutritional indexes in the two groups were compared. Furthermore, we utilized the SF-36 scale to compare the changes in the quality of life between the two groups of patients. Finally, the occurrence of postoperative complications between the two patient groups was also compared. RESULTS: The postoperative fever time, postoperative bowel function recovery time, postoperative exhaustion time, and hospitalization time were all higher in the control group than in the observation group (P < 0.05). The levels of CD3+, CD4+, immunoglobulin (Ig) A, IgM, and IgG in the observation group were significantly higher than those in the control group at 1 d and 7 d postoperatively, while CD8+ was lower than in the control group (P < 0.05). Total protein, albumin, prealbumin, and transferrin levels were significantly higher in the observation group than in the control group at 7 d postoperatively (P < 0.05). The SF-36 scores of patients in the observation group were significantly higher than those in the control group (P < 0.0001). The overall incidence of adverse reactions after the intervention was significantly lower in the control group than in the observation group (P = 0.021). CONCLUSION: We found that patients with gastrointestinal tumors are nutritionally vulnerable, and early enteral nutrition support programs can improve the nutritional status of patients and speed up postoperative recovery. This program can not only improve the immune function of the patient and protect the intestinal function, but it can also help to improve the quality of life of the patient. However, this program will increase the incidence of complications in patients. Caution should be taken when adopting early enteral nutrition support measures for patients with gastric cancer. The patient's condition and physical condition should be comprehensively evaluated and closely monitored to prevent possible complications.
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BACKGROUND: Despite extensive work to identify diagnostic plasma markers for Parkinson's disease (PD), there are still no accepted and validated surrogate biomarkers. Mitophagy-associated proteins (MAPs), including PTEN-induced putative kinase 1 (PINK1), Parkin, phosphoglycerate mutase 5 (PGAM5), BCL2 interacting protein 3 (BNIP3), and phosphorylated-TBK1 (p-TBK1), are, to our best knowledge, not well studied as a panel of biomarkers of neurodegeneration in PD. METHODS: The study population comprised 116 age-matched controls (HC), 179 PD patients, alongside and 90 PD syndromes (PDs) divided between two cohorts: (i) the modeling cohort (cohort 1), including 150 PD, 97 HC, and 80 PDs; and (ii) the validated cohort (cohort 2), including 29 PD, 19 HC, and 10 PDs. RESULTS: MAPs are elevated in the plasma of PD patients. PINK1, Parkin, and PGAM5 displayed the top three measurable increase trends in amplitude compared to BNIP3 and p-TBK1. Moreover, the area under the curve (AUC) values of PINK1, PGAM5, and Parkin were ranked the top three MAP candidates in diagnosis accuracy for PD from HC, but the MAPs make it hard to differentiate PD from PDs. In addition, there are higher plasma PINK1-Parkin levels and prominent diagnostic accuracy in A-synuclein (+) subjects than in A-synuclein (-) subjects. CONCLUSIONS: These results uncover that plasma MAPs (PINK1, Parkin, and PGAM5) may be potentially useful diagnostic biomarkers for PD diagnosis. Studies on larger cohorts would be required to test whether elevated plasma MAP levels are related to PD risk or prognosis.
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Triple-negative breast cancer (TNBC) is an aggressive molecular subtype that due to lack of druggable targets is treated with chemotherapy as standard of care. However, TNBC is prone to chemoresistance and associates with poor survival. The aim of this study was to explore the molecular mechanisms of chemoresistance in TNBC. Firstly, we found that the mRNA expression of Notch1 and CD73 in cisplatin-treated patient material associated with poor clinical outcome. Further, both were upregulated at the protein level in cisplatin-resistant TNBC cell lines. Overexpression of Notch1 intracellular domain (termed N1ICD) increased expression of CD73, whereas knockdown of Notch1 decreased CD73 expression. Using chromatin immunoprecipitation and Dual-Luciferase assay it was identified that N1ICD directly bound the CD73 promoter and activated transcription. Taken together, these findings suggest CD73 as a direct downstream target of Notch1, providing an additional layer to the mechanisms underlying Notch1-mediated cisplatin resistance in TNBC.
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Lasiodiplodia theobromae is the main pathogen of mango stem-end rot disease, causing mango fruit decay and major economic loss. QoI resistance has been found in field populations of L. theobromae. The characterization and resistance mechanism of pyraclostrobin-resistant L. theobromae was investigated by using a combination of bioassays and biochemical and molecular methods. The pyraclostrobin resistance among the L. theobromae population samples from Hainan was 93.41%. The resistant isolates were stable after successive subculturing for 10 times on PDA. Cross-resistance was observed only between the Qols pyraclostrobin and azoxystrobin. The alternative oxidase (AOX) inhibitor SHAM notably decreased the EC50 values of pyraclostrobin for all tested L. theobromae isolates. Induction of AOX by pyraclostrobin was observed in mycelia cells of L. theobromae. After treatment with pyraclostrobin, the final ATP and AOX contents of all sensitive isolates were significantly lower than those of resistant isolates. The relevant mutation and high expression of the cytochrome b gene were not detected in resistant isolates. However, there were 4 mutations in the AOX gene, which were only observed in highly resistant isolates. Pretreatment with pyraclostrobin resulted in a significant upregulation of AOX gene expression, and the average expression level of the highly resistant isolates was 33-fold that of the control group. These results suggested that the AOX pathway is responsible for resistance to pyraclostrobin, and that the AOX-related resistance mechanism is common in field populations of L. theobromae in Hainan mango orchards.
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Ascomicetos , Mangifera , Ascomicetos/genética , MicelioRESUMEN
Background: We aimed to examine whether plasma-derived phosphoglycerate mutase 5 (PGAM5) can be a biomarker for Parkinson's disease (PD) diagnosis as well as its association with the severity of motor/non-motor manifestations of PD. Methods: We enrolled 124 patients with PD (PD group) and 50 healthy controls (HC group). We measured plasma PGAM5 levels using a quantitative sandwich enzyme immunoassay. Patients with PD underwent baseline evaluations using the Unified Parkinson's Disease Rating Scale (UPDRS), while participants in both groups were evaluated using scales for non-motor manifestations. Receiver operating characteristic curves were used to evaluate the predictive utility of plasma PAMG5 alone and combined with other factors. Results: Plasma PAMG5 levels were significantly higher in the PD group; the area under the curve (AUC) of plasma PGAM5 levels alone was 0.76. The AUC values for elderly participants and patients without hypertension were 0.78 and that for was 0.79. Notably, plasma PGAM5 levels combined with plasma oligomeric α-synuclein (α-syn) and the score of the REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK) showed AUC values of 0.80 and 0.82. Multivariable logistic analysis revealed that plasma PAMG5 levels were independently associated with PD (odds ratio,1.875 [95% confidence interval 1.206-2.916], p = 0.005) but not the severity of motor/non-motor manifestations of PD. Conclusion: Plasma PGAM5 is an independent biomarker for PD, especially among elderly patients (age > 60 years) and patients without hypertension. The predictive utility of PGAM5 was improved when combined with plasma oligomeric α-syn or the RBDQ-HK score.
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Trace natural products usually possess great biological activity, but the identification of the absolute configuration of monosaccharides in trace natural glycosides is still a challenge. The methods available are not suitable to distinguish enantiomers of monosaccharides in trace natural products when the amount of natural products is less than 1.0 mg. Therefore, this study explored an ultra-performance liquid chromatography with diode array detector coupled to quadrupole/time-of-flight mass spectrometry (UPLC-DAD-Q-TOF/MS) combined with modified one-pot monosaccharide derivatized protocol to distinguish enantiomers of monosaccharides in trace natural products. The experimental parameters were optimized to achieve multiple objectives, and detailed approaches were proposed to improve the sensitivity and resolution of the protonated ion and adduct ion of the monosaccharide derivatives. The retention time of the extracted ion chromatogram and the relative abundance ratio of the characteristic fragment ions were considered for the characterization of the absolute configuration of monosaccharides to distinguish the enantiomers of the monosaccharides of natural products. This strategy was successfully applied to distinguishing 8 pairs of aldose enantiomers, and was verified using trace D-lactose and trace narirutin, which are reference substances commercially available. Moreover, the absolute configuration of the monosaccharide of one trace new compound isolated from the seeds of Moringa oleifera Lam. was successfully identified using this procedure.
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Productos Biológicos , Glicósidos , Glicósidos/química , Lactosa , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Monosacáridos/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Introduction: To explore the combined diagnostic value of plasma Lewy body-associated proteins (p-Asyn at ser129, total α-syn, and oligomeric α-syn) for the diagnosis of PD versus healthy controls (HCs) and other PD syndromes (PDs), as well as clinical characteristics prediction. Methods: This study included 145 participants: 79 patients with PD, 24 patients with PDs, and 42 HCs. A panel of plasma levels of p-Asyn, total α-syn, and oligomeric α-syn was measured by enzyme-linked immunosorbent assay (ELISA). The primary outcome was the discriminative accuracy of the combined three plasma biomarkers for PD. Results: The mean age was 65.43 (SD, 7.467) in the control group, 64.49 (SD, 8.224) in participants with PD, and 69.25 (SD, 7.952) in PDs. The plasma Lewy body-associated protein levels were significantly higher in patients with PD than in age-matched HCs, However, there was no difference in patients with PD and PDs. Of note, a combination of plasma p-Asyn, total α-syn, and oligomeric α-syn was a better biomarker for discriminating PD from HCs, with an AUC of 0.8552 (p < 0.0001, 95%CI, 0.7635-0.9409), which was significantly higher than plasma p-Asyn (ΔAUC, 0.1797), total α-syn (ΔAUC, 0.0891) and oligomeric α-syn (ΔAUC, 0.1592) alone. Meanwhile, Lewy body-associated proteins had no connections between different motor stages and dementia performances. Conclusion: Our results suggested that plasma Lewy body-associated proteins, may serve as a non-invasive biomarker to aid the diagnosis of PD from HCs. In addition, increased plasma Lewy body-associated proteins were not associated with the progression of motor and non-motor symptoms.
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Collagen peptides are a potential treatment for osteoporosis due to their antiosteoporosis activity. In this study, we prepared immobilized protease with eggshell membrane as carrier, and then hydrolyzed collagen to obtain collagen peptide. The antiosteoporosis of collagen peptides was confirmed by hBMSC osteogenic differentiation and bone mineralization improvement results. Surprisingly, antiosteoporosis of collagen peptides was related to the molecular weight of collagen peptides. This was derived from the osteoblast marker gene expressions, and mineral elements in P1 treatment were higher than those in P3 treatment. Consequently, these results confirmed that antiosteoporosis of low molecular weight collagen peptides is higher than that of higher molecular weight collagen peptides. Furthermore, the antiosteoporosis activity of P1 was due to its peptide sequences with known antiosteoporosis activity in P1. PRACTICAL APPLICATION: Using eggshell membrane as carrier to prepare immobilized protease was meaningful for solving the problem of resource waste. In addition, the results showed that collagen peptides possessed antiosteoporosis, and the effect of low molecular weight collagen peptides was better. This study provides a theoretical basis for developing high antiosteoporosis collagen peptides able to treat osteoporosis.
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Osteogénesis , Osteoporosis , Animales , Colágeno/química , Cáscara de Huevo , Endopeptidasas , Osteoporosis/tratamiento farmacológico , Péptido Hidrolasas , Péptidos/química , Péptidos/farmacologíaRESUMEN
By exploring the China International Fair for Investment and Trade's development process, this study analyzes its absolute advantages in future development, gradually lost comparative advantages, and potential crises. Through the data envelopment analysis model, the study analyzes its resource allocation efficiency based on two cooperation modes: traditional "Offline" investment mode and "Online + Offline" investment mode. Then we use vector autoregressive model to comprehensively investigate the impact and causality of the two input factors on output. We find that its comprehensive allocation efficiency presents a "U" shape that reflects the characteristics of its three stages: the first stage, 2001-2005; the second stage, 2006-2012; and the third stage, 2013-2020. The main factors affecting resource allocation efficiency are then deduced from the results: exhibition scale utilization, booth design innovation, project strength of participating enterprises, and the signing rate of overseas customers. The number of industrial and commercial groups (X4) and participating countries and regions (X6) have an important impact on the output indicators: signed contract projects (Y1). The empirical results verify that the "Online + Offline" investment mode is an effective and suitable mechanism to solve the problem of cooperation and investment constrained by the COVID-19 pandemic. Based on the results of empirical analysis, this study posits the path and countermeasures of realizing the transformation to "cloud" exhibition in the post-pandemic era. Especially, we should focus on building new mechanisms of business environment that will promote the active participation of national, regional, and international industrial and commercial groups. The purpose is to continuously strengthen the foundation of cooperative trust and innovate a new trust model of online cooperative trading.