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1.
Neural Regen Res ; 18(2): 410-415, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900438

RESUMO

Modified constraint-induced movement therapy (mCIMT) has shown beneficial effects on motor function improvement after brain injury, but the exact mechanism remains unclear. In this study, amplitude of low frequency fluctuation (ALFF) metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control cortical impact (CCI) rat model simulating traumatic brain injury. At 3 days after control cortical impact model establishment, we found that the mean ALFF (mALFF) signals were decreased in the left motor cortex, somatosensory cortex, insula cortex and the right motor cortex, and were increased in the right corpus callosum. After 3 weeks of an 8-hour daily mCIMT treatment, the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively. The mALFF signal values of left corpus callosum, left somatosensory cortex, right medial prefrontal cortex, right motor cortex, left postero dorsal hippocampus, left motor cortex, right corpus callosum, and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group. Finally, we identified brain regions with significantly decreased mALFF values at 3 days postoperatively. Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions. Our findings suggest that functional cortical plasticity changes after brain injury, and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric cortical remodeling. mALFF values correlate with behavioral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

2.
Nat Commun ; 13(1): 4887, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068211

RESUMO

Wild yak (Bos mutus) and domestic yak (Bos grunniens) are adapted to high altitude environment and have ecological, economic, and cultural significances on the Qinghai-Tibetan Plateau (QTP). Currently, the genetic and cellular bases underlying adaptations of yak to extreme conditions remains elusive. In the present study, we assembled two chromosome-level genomes, one each for wild yak and domestic yak, and screened structural variants (SVs) through the long-read data of yak and taurine cattle. The results revealed that 6733 genes contained high-FST SVs. 127 genes carrying special type of SVs were differentially expressed in lungs of the taurine cattle and yak. We then constructed the first single-cell gene expression atlas of yak and taurine cattle lung tissues and identified a yak-specific endothelial cell subtype. By integrating SVs and single-cell transcriptome data, we revealed that the endothelial cells expressed the highest proportion of marker genes carrying high-FST SVs in taurine cattle lungs. Furthermore, we identified pathways which were related to the medial thickness and formation of elastic fibers in yak lungs. These findings provide new insights into the high-altitude adaptation of yak and have important implications for understanding the physiological and pathological responses of large mammals and humans to hypoxia.


Assuntos
Células Endoteliais , Genoma , Aclimatação/genética , Animais , Bovinos , Humanos , Mamíferos/genética , RNA , Transcriptoma/genética
3.
Front Aging Neurosci ; 14: 976164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072479

RESUMO

Background: Increased social distance is one of the manifestations of social impairment. Chronic low back pain (CLBP) is one of factors associated with increased social distance and social withdrawal. Exercise therapy is an effective means to social impairment. However, whether exercise could reduce social distance in patients with CLBP remains unknown. This study aimed to investigate the effect of exercise on social distance in middle-aged and elderly patients with CLBP. Methods: The longitudinal intervention recruited 29 middle-aged and elderly patients with CLBP from various communities in Yangpu District, Shanghai, China. The participants received exercise intervention for 8 weeks. The assessments were conducted before and after the intervention, including social distance, pain intensity, unpleasantness of pain, Roland-Morris Questionnaire (RMDQ), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Intention to treat analysis was performed. Results: After the 8-week exercise intervention, the social distance of patients with CLBP was shorter than that before intervention and showed significant difference (p < 0.05). The scores of pain intensity, unpleasantness of pain, RMDQ, SAS, and SDS also decreased and were significantly different between pre- and post-intervention (p < 0.05). In addition, the social distance, pain intensity, unpleasantness of pain, RMDQ, SAS, and SDS scores of the moderate CLBP group decreased more after the intervention compared with those of the mild CLBP group. Conclusion: The 8-week exercise intervention cannot only shorten the social distance in middle-aged and elderly patients with CLBP but also relieve pain, disability, and negative emotions.

4.
Am J Nucl Med Mol Imaging ; 12(4): 122-128, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072764

RESUMO

Primary pulmonary artery sarcoma (PAS) is a malignant neoplasm of the pulmonary vascular system originating from the intima, with clinical and imaging manifestations similar to those of pulmonary thromboembolism (PTE), and is often misdiagnosed. Spectral CT and PET/CT can clearly show the extent and metastasis of PAS and are valuable in visualizing adjacent structures such as lungs, bronchi, and mediastinum, providing a strong imaging basis for the diagnosis and differentiation of PAS, allowing treatment monitoring and follow-up.

5.
J Card Surg ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047383

RESUMO

OBJECTIVE: This study aimed to detect the predictors of vein graft disease (VGD) progression between 1 week and 1 year after surgery and to evaluate the impact of secondary prevention medications. METHODS: A total of 218 consecutive patients underwent surgical coronary revascularization were evaluated by coronary computed tomography angiography both at 1-week and 1-year follow-up. Logistic regression analyses were performed to investigate the predictors of VGD progression. A risk score (0-4) was set up to evaluate implementation result of secondary prevention measures according to 1-year follow-up result. Association between VGD progression and the risk score was assessed. RESULTS: VGD progression occurred in 11.3% of saphenous vein grafts (SVG) and 22.1% of patients. At the patient level, poor vein graft (odds ratio [OR] = 4.25), noncontrolled hyperlipidemia (OR = 3.01), and diabetes mellitus (DM) (OR = 2.96) were predictors, while diameter of SVG (mm, OR = 0.35) was protective factor. At the graft level, DM (OR = 3.52), noncontrolled hyperlipidemia (OR = 2.33), and peripheral artery disease (PAD) (OR = 2.20) were predictors, while number of SVGs (OR = 0.63), diameter of SVG (mm, OR = 0.39), and mean graft flow >25 ml/min (OR = 0.35) were protective factors. VGD progression was significantly associated with the risk score at both the patient (OR = 1.52) and the graft level (OR = 1.38). CONCLUSIONS: Poor vein graft, noncontrolled hyperlipidemia and DM were predictors of VGD progression between 1 week and 1 year after surgery at the patient level, while larger SVG diameter was a protective factor. DM, PAD and noncontrolled hyperlipidemia were predictors at the graft level, while a number of SVGs, larger SVG diameter, and mean graft flow >25 ml/min were protective factors. Implementation failure of secondary prevention medications was associated with VGD progression from as early as 1 year after surgery.

6.
J Inflamm Res ; 15: 5247-5263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120185

RESUMO

Objective: C/EBPß, a crucial transcription factor, regulates innate immunity and inflammatory responses. However, the role played by C/EBPß in alveolar macrophage (AM) inflammatory responses remains unknown. This study aimed to investigate the role and mechanism of C/EBPß in alveolar macrophages (AMs) from the transcriptional level and to search for natural compounds targeting C/EBPß. Methods: Rat AMs were infected with Lv-sh-C/EBPß and treated with LPS, and the expression levels of iNOS, TNF-α, IL-6, and IL-1ß were measured by RT-qPCR, Western blotting, and ELISA. Mechanistically, transcriptome sequencing (RNA-seq) revealed changes in gene expression patterns in AMs after LPS stimulation and C/EBPß knockdown. Functional enrichment analyses and rescue experiments identified and validated inflammation-associated cell signaling pathways regulated by C/EBPß. Furthermore, virtual screening was used to search for natural compounds that inhibit C/EBPß with the structure of helenalin as a reference. Results: Following stimulation with LPS, AMs exhibited an increased expression of C/EBPß. C/EBPß knockdown significantly decreased the expression levels of inflammatory mediators. A total of 374 differentially expressed genes (DEGs) were identified between LPS-stimulated C/EBPß knockdown and negative control cells. The NOD-like receptor signaling may be a key target for C/EBPß, according to functional enrichment analyses of the DEGs. Further experiments showed that the muramyl dipeptide (MDP, NOD2 agonist) reversed the downregulation of inflammatory mediators and the NF-κB pathway caused by the C/EBPß knockdown. The virtual screening revealed that N-caffeoyltryptophan, orilotimod, and petasiphenone have comparable pharmacological properties to helenalin (a known C/EBPß inhibitor) and demonstrate a great binding capacity to C/EBPß. Conclusion: Ablation of C/EBPß may attenuate LPS-induced inflammatory damage in AMs by inhibiting the NOD2 receptor signaling pathway. Three natural compounds, N-caffeoyltryptophan, orilotimod, and petasiphenone, may be potential C/EBPß inhibitors.

7.
Pain Med ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36066447

RESUMO

BACKGROUND: The majority of existing clinical studies used active transcranial direct current stimulation (tDCS) over the superficial areas of pain neuromatrix to regulate pain, with conflicting results. Nevertheless, few studies have investigated the effect of tDCS on pain thresholds by focusing on targets in deep parts of the pain neuromatrix. METHODS: This study applied single session of high-definition tDCS (HD-tDCS) targeting the anterior cingulate cortex (ACC) with a parallel and sham-controlled design, to compare the antinociceptive effects in healthy individuals through assessing changes in pain thresholds. Sixty-six (mean age, 20.5 ± 2.4) female individuals were randomly allocated into the anodal, cathodal, or sham HD-tDCS groups. The primary outcome of the study was pain thresholds (pressure pain threshold, heat pain threshold, and cold pain threshold), which were evaluated before and after stimulation by the quantitative sensory tests. RESULTS: Only cathodal HD-tDCS targeting the ACC significantly increased heat pain threshold (p < 0.05) and pressure pain threshold (p < 0.01) in healthy individuals compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain threshold. Furthermore, no statistically significant difference was found in pain thresholds between anodal vs. sham HD-tDCS (p > 0.38). Independent of HD-tDCS protocols, the positive and negative affective schedule scores were decreased immediately after stimulation compared with baseline. CONCLUSIONS: The present study has found that cathodal HD-tDCS targeting the ACC provided a strong antinociceptive effect (increase in pain threshold), demonstrating a positive biological effect of HD-tDCS. CLINICAL TRIALS REGISTRATION: An RCT was carried out at Shanghai University of Sport, China, from December 2021 to March 2022. Trial registration: ChiCTR2100053531. Registered 24 November 2021, http://www.chictr.org.cn/index.aspx.

8.
ACS Omega ; 7(34): 29543-29570, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36061652

RESUMO

The application of hydraulic fracturing stimulation technology to improve the productivity of unconventional oil and gas reservoirs is a well-established practice. With the increasing exploration and development of unconventional oil and gas resources, the associated geological conditions and physical properties are gradually becoming more and more complex. Therefore, it is necessary to develop technologies that can improve the development benefits to meet these challenges. In recent years, improving the effect of hydraulic fracturing stimulation in unconventional oil and gas reservoirs through the use of nanomaterials and technologies has attracted increasing attention. In this paper, we review the current status and research progress of the application of nanomaterials and technologies in various aspects of hydraulic fracturing in unconventional oil and gas reservoirs, expound the mechanism and advantages of these nanomaterials and technologies in detail, and provide future research directions. The reviewed literature indicates that nanomaterials and technologies show exciting potential applications in the hydraulic fracturing of unconventional reservoirs; for example, the sand-carrying and rheological properties of fracturing fluids can be significantly enhanced through the addition of nanomaterials. The use of nanomaterials to modify proppants can improve their compressive strength, thus meeting the needs of different reservoir conditions. The fracturing flowback fluid treatment efficiency and purification effect can be improved through the use of nanophotocatalysis and nanomembrane technologies, while degradable fracturing completion tools developed based on nanomaterials can effectively improve the efficiency of fracturing operations. Nanorobots and magnetic nanoparticles can be used to more efficiently monitor hydraulic fracturing and to accurately map the hydraulic fracture morphology. However, due to the complex preparation process and high cost of nanomaterials, more work is needed to fully investigate the application mechanisms of nanomaterials and technologies, as well as to evaluate the economic feasibility of these exciting technologies. The main research objective of this review is to comprehensively summarize the application and research progress of nanomaterials and technologies in various aspects of hydraulic fracturing in unconventional oil and gas reservoirs, analyze the existing problems and challenges, and propose some targeted forward-looking recommendations, which may be helpful for future research and applications.

9.
ACS Omega ; 7(34): 29959-29966, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36061740

RESUMO

The anode is considered to be a key factor to improve the single-chamber bioelectrochemical system's efficiency to degrade oily sludge in sediment while generating electricity. There are few studies on the effect of the anode structure on the performance of oily sludge MFCs systematically. In this paper, an oily sludge bioelectrical system was constructed using carbon felt and carbon plate as anode materials, adjusting the anode material arrangement as transverse and longitudinal, and using different anode materials from single to sextuple anodes. The results of this study showed that the rate of degradation of oily sludge was greater with carbon felt (17.04%) than with the carbon plate (13.11%), with transverse (23.61%) than with the longitudinal (19.82%) arrangement of anodes, and with sextuple anodes (33.72%) than with a single anode (25.26%) in the sediment microbial fuel cells (SMFCs). A similar trend was observed when the voltage, power density, and electromotive force (EMF) of SMFCs were estimated between the carbon felt and carbon plate, transverse and longitudinal arrangements, single and sextuple anodes. It is concluded that the proper adjustment of anode arrangements, using carbon felt as an anode material, and increasing the number of anodes to six may accelerate the rate of degradation of oily sludge in oily sludge sediment microbial fuel cells (SMFCs). Furthermore, the electricity generation performance was also improved.

10.
J Clin Lipidol ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-36064883

RESUMO

BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. OBJECTIVE: We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. METHODS: An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. RESULTS: GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. CONCLUSIONS: The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP.

11.
Opt Lett ; 47(17): 4419-4422, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048668

RESUMO

In this Letter, a compact cyclic mode converter (CMC) based on a mechanical fiber grating is proposed and fabricated to eliminate differential mode group delay and mode-dependent loss in the mode division multiplexing (MDM) transmission system. The proposed CMC can realize cyclical interchange of any input mode among the LP01/LP11a/LP11b modes, which requires only one mechanical grating. The mode conversion is evaluated by observing the mode field patterns of the fiber output. The experimental results prove that the introduction of CMC does not significantly degrade the transmission performance of the photonic lanterns back-to-back system. The insertion loss and the average cross talk of the whole system are lower than 5 dB and -11.3 dB, respectively. The proposed CMC provides a new method for reducing link damage in the MDM transmission system.

12.
Front Pharmacol ; 13: 964037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091834

RESUMO

Background: The coronavirus disease of 2019 (COVID-19) is a severe public health issue that has infected millions of people. The effective prevention and control of COVID-19 has resulted in a considerable increase in the number of cured cases. However, little research has been done on a complete metabonomic examination of metabolic alterations in COVID-19 patients following treatment. The current project pursues rigorously to characterize the variation of serum metabolites between healthy controls and COVID-19 patients with nucleic acid turning negative via untargeted metabolomics. Methods: The metabolic difference between 20 COVID-19 patients (CT ≥ 35) and 20 healthy controls were investigated utilizing untargeted metabolomics analysis employing High-resolution UHPLC-MS/MS. COVID-19 patients' fundamental clinical indicators, as well as health controls, were also collected. Results: Out of the 714 metabolites identified, 203 still significantly differed between COVID-19 patients and healthy controls, including multiple amino acids, fatty acids, and glycerophospholipids. The clinical indexes including monocytes, lymphocytes, albumin concentration, total bilirubin and direct bilirubin have also differed between our two groups of participators. Conclusion: Our results clearly showed that in COVID-19 patients with nucleic acid turning negative, their metabolism was still dysregulated in amino acid metabolism and lipid metabolism, which could be the mechanism of long-COVID and calls for specific post-treatment care to help COVID-19 patients recover.

13.
Dev Comp Immunol ; 137: 104526, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36058385

RESUMO

The G protein-coupled receptor 84 (GPR84) is a putative medium-chain fatty acids (MCFAs) receptor involved in immune regulation and other metabolic processes. Most available studies focused on the GPR84 characterization from mammals, neglecting vital information that could be obtained from other levels of life, such as amphibians, necessary for an apt evolutionary understanding of the orphan GPR84. Hence, this study molecularly characterized and functionally explored the GPR84 from the Chinese Giant Salamander (Andrias davidianus). Therefore, we report that the Chinese Giant Salamander (CGS), one of the world's largest amphibians, expresses a GPR84 protein having 376 amino acids, with about 70% homologous to other amphibians and around 50% to human GPR84. Investigating the relative localized expression of gpr84 mRNA in CGS using quantitative PCR revealed the highest expression in the kidney and liver. Furthermore, four medium-chain fatty acids (MCFAs) at micromolar levels activated CGS-GPR84 transfected and expressed in HEK293 cells. In HEK293 cells, four different concentrations of MCFAs inhibited forskolin-induced cAMP accumulation and resulted in a dose-dependent increase in extracellular signal-regulated kinases 1 and 2 (ERK1/2). Interestingly, MCFAs activation of GPR84 concomitantly led to the upregulation of inflammatory mediators such as Nuclear Factor Kappa B (NF-κB) and IL-6. Conclusively, this study successfully elucidated the intriguing molecular and functional properties of CGS GPR84, particularly as an immune modulator, and has positioned the findings within the existing body of knowledge for a better overall understanding of GPR84, especially in amphibians.


Assuntos
Interleucina-6 , NF-kappa B , Aminoácidos , Animais , China , Colforsina/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ácidos Graxos/metabolismo , Células HEK293 , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Mamíferos/genética , NF-kappa B/metabolismo , RNA Mensageiro/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Urodelos
14.
Cell Metab ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36103895

RESUMO

The tumor microenvironment (TME) is a unique niche governed by constant crosstalk within and across all intratumoral cellular compartments. In particular, intratumoral high potassium (K+) has shown immune-suppressive potency on T cells. However, as a pan-cancer characteristic associated with local necrosis, the impact of this ionic disturbance on innate immunity is unknown. Here, we reveal that intratumoral high K+ suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). We identify the inwardly rectifying K+ channel Kir2.1 as a central modulator of TAM functional polarization in high K+ TME, and its conditional depletion repolarizes TAMs toward an anti-tumor state, sequentially boosting local anti-tumor immunity. Kir2.1 deficiency disturbs the electrochemically dependent glutamine uptake, engendering TAM metabolic reprogramming from oxidative phosphorylation toward glycolysis. Kir2.1 blockade attenuates both murine tumor- and patient-derived xenograft growth. Collectively, our findings reveal Kir2.1 as a determinant and potential therapeutic target for regaining the anti-tumor capacity of TAMs within ionic-imbalanced TME.

15.
Genet Med ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36107168

RESUMO

PURPOSE: This study aimed to investigate the spectrum and characteristics of segmental aneuploidies (SAs) of <10 megabase (Mb) length in human preimplantation blastocysts. METHODS: Preimplantation genetic testing for aneuploidy was performed in 15,411 blastocysts from 5171 patients using a validated 1 Mb resolution platform. The characteristics and spectrum of SAs, including the incidence, sizes, type, inheritance pattern, clinical significance, and embryo distribution, were studied. RESULTS: In total, 6.4% of the 15,411 blastocysts carried SAs of >10 Mb, 4.9% of embryos had SAs ranging between 1 to 10 Mb, and 84.3% of 1 to 10 Mb SAs were <5 Mb in size. Inheritance pattern analysis indicated that approximately 63.8% of 1 to 10 Mb SAs were inherited and were predominantly 1 to 3 Mb in size. Furthermore, 18.4% of inherited SAs and 51.9% de novo 1 to 10 Mb SAs were pathogenic or likely pathogenic (P/LP). Different from whole-chromosome aneuploidies, reanalysis indicated that 50% of the de novo 1 to 10 Mb SAs and 70% of the >10 Mb SAs arose from mitotic errors. CONCLUSION: Based on the established platform, 1 to 10 Mb SAs are common in blastocysts and include a subset of P/LP SAs. Inheritance pattern analysis and clinical interpretation based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines contributed to determine the P/LP SAs.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36063202

RESUMO

PURPOSE: Pancreatic cancer is a malignant tumor with a high degree of malignancy, strong heterogeneity, and high lethality. Trop2 is a transmembrane glycoprotein associated with the occurrence, development, and poor prognosis of pancreatic cancer. This study aims to develop 64Cu/177Lu-labeled anti-Trop2 monoclonal antibody (hIMB1636) for positron emission tomography (PET) imaging and radioimmunotherapy (RIT) application in pancreatic cancer tumor models. METHODS: The binding kinetics of hIMB1636 to Trop2 antigen was measured by Biolayer interferometry (BLI). Western blotting was used to screen the Trop2 expression of pancreatic cancer cell lines. Flow cytometry and cell immunofluorescence were used to evaluate the binding ability of hIMB1636 and Trop2 on the cell surface. hIMB1636 were conjugated with p-SCN-Bn-NOTA (NOTA) and DOTA-NHS-ester (DOTA) for 64Cu and 177Lu radiolabeling respectively. ImmunoPET imaging and RIT studies were performed using 64Cu-NOTA-hIMB1636 and 177Lu-DOTA-hIMB1636 in subcutaneous pancreatic cancer tumor models. RESULTS: hIMB1636 had a strong binding affinity to Trop2 according to the results of BLI. The T3M-4 cell line showed the strongest expression of Trop2 and specific binding ability of hIMB1636 according to the results of Western blotting, flow cytometry, and cell immunofluorescence. The radiochemical purity of 64Cu-NOTA-hIMB1636 and 177Lu-DOTA-hIMB1636 exceeded 95%. PET imaging showed gradually an accumulation of 64Cu-NOTA-hIMB1636 in T3M-4 tumor models. The maximum tumor uptake was 8.95 ± 1.07%ID/g (n = 4) at 48 h post injection (p.i.), which had significant differences with T3M-4-blocked and PaTu8988-negative groups (P < 0.001). The high-177Lu-hIMB1636 group demonstrated the strongest tumor suppression with standardized tumor volume about 94.24 ± 14.62% (n = 5) at 14 days p.i., significantly smaller than other groups (P < 0.05). Ex vivo biodistribution and histological staining verified the in vivo PET imaging and RIT results. CONCLUSIONS: This study demonstrated that 64Cu/177Lu-labeled hIMB1636 could noninvasively evaluate the expression level of Trop2 and inhibit the Trop2-overexpressed tumor growth in pancreatic cancer tumor models. Further clinical evaluation and translation of Trop2-targeted drug may be of great help in the stratification and management of pancreatic cancer patients.

17.
Chemosphere ; 308(Pt 1): 136262, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36055587

RESUMO

In this research, a comprehensive study was carried out on the removal of carbon tetrachloride (CT) in the anaerobic co-metabolism (ACM) reactor. The experiments showed that when the hydraulic retention time (HRT) was 36 h, pH was 7, and influent CT was 2.5mg/L, the average removal efficiency reached 82.45 ± 2.56% in the glucose co-metabolism substrate reactor, exhibiting a dramatic excellent difference in reaction performance from the other two reactors (p < 0.05) and a favorable tolerance on the CT shock loading. The content of extracellular polymeric substances (EPS) and volatile fatty acids (VFA) demonstrated that glucose could supply more energy to protect the microorganisms, which was the appropriate external energy source. Moreover, microbial community structure and biostatistics analysis demonstrated that Pseudomonas was the most important dechlorination bacteria in ACM reactors, which might via dehalogenation process mediate the transformation of CT. The succession of methanogenic bacteria further demonstrated that CT degradation using co-digestion require to destroy hydrogenotrophic methane generation pathway and the external energy substances could make up the lack of hydrogen in the treatment of CT. The change of intermediate products hinted that anaerobic dechlorination process of CT in an ACM reactor was a sequential dechlorination process, and major transformation products measured were CF. Overall, this study has improved our understanding of the roles of CT degradation process in ACM reactors.

18.
Sci Total Environ ; : 158795, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36115405

RESUMO

Simultaneous removal of ammonium and nitrate was achieved in a methane-fed moving bed biofilm reactor (MBBR). In the reactor, methanotrophic microorganisms oxidized methane under hypoxic conditions likely to methanol, hence providing an electron donor to denitrifiers to reduce nitrate to nitrite that then allowed anaerobic ammonium oxidizing bacteria (Anammox) to remove excess ammonium as N2. The ammonium and nitrate removal rates reached 72.09 ±â€¯5.81 mgNH4+-N/L/d and 62.61 ±â€¯4.17 mgNO3--N/L/d when the MBBR was operated in continuous mode. Nitrate removal by the methane-fed mixed consortia was confirmed in a batch test revealing a CH4/NO3- molar removal ratio of 1.15. The functional populations were unveiled by FISH analysis and 16S rRNA gene sequencing, which showed that the biofilm was dominated by Anammox bacteria (Candidatus Kuenenia) and diverse taxa associated with the capacity for denitrification: aerobic methanotrophs (Methylobacter, Methylomonas, and unclassified Methylococcaceae), methylotrophic denitrifiers (Opitutaceae and Methylophilaceae), and other heterotrophic denitrifiers (Ignavibacteriaceae, Anaerolineaceae, Comamonadaceae, Rhodocyclaceae and Thauera). Neither DAMO archaea nor DAMO bacteria were found in the sequencing analysis, indicating that more unknown community members possess the metabolic capacity of methanotrophic denitrification.

19.
Pharmaceutics ; 14(8)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36015354

RESUMO

Parkinson's disease (PD) is a serious neurodegenerative disease wherein the progressive destruction of dopaminergic neurons results in a series of related movement disorders. Effective oral delivery of anti-Parkinson's drugs is challenging owing to the blood-brain barrier (BBB) and the limited plasma exposure. However, polymeric nanoparticles possess great potential to enhance oral bioavailability, thus improving drug accumulation within the brain. In this work, biodegradable poly(ethylene glycol)-b-poly(trimethylene carbonate) (PEG-PTMC) nanoparticles (PPNPs) were developed to deliver Ginkgolide B (GB) as a potent treatment for PD, aiming to enhance its accumulation within both the blood and the brain. The resultant GB-PPNPs were able to facilitate sustained GB release for 48 h and to protect against 1-methyl-4-phenylpyridine (MPP+)-induced neuronal cytotoxicity without causing any toxic damage. Subsequent pharmacokinetic studies revealed that GB-PPNPs accumulated at significantly higher concentrations in the plasma and brain relative to free GB. Oral GB-PPNP treatment was also linked to desirable outcomes in an animal model of PD, as evidenced by improvements in locomotor activity, levels of dopamine and its metabolites, and tyrosine hydroxylase activity. Together, these data suggest that PPNPs may represent promising tools for the effective remediation of PD and other central nervous system disorders.

20.
Front Big Data ; 5: 931206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35993029

RESUMO

Human personality traits are key drivers behind our decision making, influencing our lives on a daily basis. Inference of personality traits, such as the Myers-Briggs personality type, as well as an understanding of dependencies between personality traits and user behavior on various social media platforms, is of crucial importance to modern research and industry applications such as recommender systems. The emergence of diverse and cross-purpose social media avenues makes it possible to perform user personality profiling automatically and efficiently based on data represented across multiple data modalities. However, research efforts on personality profiling from multi-source multi-modal social media data are relatively sparse; the impact of different social network data on profiling performance and of personality traits on applications such as recommender systems is yet to be evaluated. Furthermore, large-scale datasets are also lacking in the research community. To fill these gaps, in this work we develop a novel multi-view fusion framework PERS that infers Myers-Briggs personality type indicators. We evaluate the results not just across data modalities but also across different social networks, and also evaluate the impact of inferred personality traits on recommender systems. Our experimental results demonstrate that PERS is able to learn from multi-view data for personality profiling by efficiently leveraging highly varied data from diverse social multimedia sources. Furthermore, we demonstrate that inferred personality traits can be beneficial to other industry applications. Among other results, we show that people tend to reveal multiple facets of their personality in different social media avenues. We also release a social multimedia dataset in order to facilitate further research on this direction.

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