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1.
J Environ Manage ; 291: 112725, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33962290

RESUMO

Riboflavin is commercially produced primarily by bio-fermentation. Nonetheless, purification and separation are particularly complex and costly. Adsorption from the fermentation liquor is an alternative riboflavin separation technology during which a cost-efficient adsorbent is highly desired. In this study, a low-cost activated algal biomass-derived biochar (AABB) was applied as an adsorbent to efficiently adsorb riboflavin from an aqueous solution. The adsorption capacity of riboflavin on AABB increased with the increase in pyrolysis temperature and initial riboflavin concentration. The adsorption isotherms were well described by the Freundlich and Langmuir models. The AABB displayed excellent adsorption performance and its maximum adsorption capacity was 476.9 mg/g, which was 6.8, 6.8, and 5.2 times higher than that of laboratory-prepared activated rape straw biochar, activated broadbean shell biochar and commercial activated carbon, respectively, which was mainly ascribed to its larger specific surface area and abundant functional groups. The mass transfer model results showed that mass transfer resistance was dependent on both the film mass transfer and porous diffusion. Raman and Fourier transform-infrared spectra confirmed the presence of π-π interactions and hydrogen bonding between riboflavin and the AABB. The adsorption of riboflavin onto AABB was a spontaneous process, which was dominated by van der Waals forces. These results will be beneficial for developing effective riboflavin recovery technologies and simultaneously utilizing waste algal blooms.

2.
J Biol Chem ; : 100730, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33933448

RESUMO

Proper dendrite morphogenesis and synapse formation are essential for neuronal development and function. Dasm1, a member of the immunoglobulin superfamily, is known to promote dendrite outgrowth and excitatory synapse maturation in vitro. However, the in vivo function of Dasm1 in neuronal development and the underlying mechanisms are not well understood. To learn more, Dasm1 knockout mice were constructed and employed to confirm that Dasm1 regulates dendrite arborization and spine formation in vivo. We performed a yeast two-hybrid screen using Dasm1, revealing MRCKß as a putative partner; additional lines of evidence confirmed this interaction and identified cytoplasmic proline-rich region (823-947 aa) of Dasm1 and MRCKß self-activated kinase domain (CC1, 410-744 aa) as necessary and sufficient for binding. Using co-immunoprecipitation assay, auto-phosphorylation assay and BS3 cross-linking assay, we show that Dasm1 binding triggers a change in MRCKß's conformation and subsequent dimerization, resulting in auto-phosphorylation and activation. Activated MRCKß in turn phosphorylates a class 2 regulatory myosin light chain (MLC2), which leads to enhanced actin rearrangement, causing the dendrite outgrowth and spine formation observed before. Removal of Dasm1 in mice leads to behavioral abnormalities. Together, these results reveal a crucial molecular pathway mediating cell surface and intracellular signaling communication to regulate actin dynamics and neuronal development in the mammalian brain.

3.
Cancer Sci ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33931921

RESUMO

Bladder cancer (BLCA) remains the leading cause of cancer-related mortality among genitourinary malignancies worldwide. BLCA metastasis represents the primary reason for its poor prognosis. In this study, we report that decreased expression of partitioning defective 3 (Par3), a polarity protein (encoded by PARD3), is associated with tumor aggressive phenotypes and poor prognosis in BLCA patients. Consistently, ablation of Par3 promotes the metastasis and invasion of BLCA cells in vitro and in vivo. Further studies reveal that zinc finger protein Snail represses the expression of Par3 by binding to E2-box (CAGGTG) of PARD3 promoter-proximal. Inhibition of GSK-3ß promotes the expression and nuclear localization of Snail and then reduces the expression of Par3, resulting in the metastasis and invasion of BLCA cells. Moreover, we detected the interaction between Par3 (936-1356 aa) and ZO-1 (1372-1748 aa), which is involved in the maintenance of tight junction. Together, our results demonstrate that the GSK-3ß/Snail/Par3/ZO-1 axis regulates BLCA metastasis, and Snail is a major regulator for Par3 protein expression in BLCA.

4.
Neuroscience ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33895340

RESUMO

In adult mammals, axon regeneration is limited within the lesion site after injury to the optic nerve. Changes in the microenvironment of lesion sites play an important role in retinal ganglion cells (RGCs) axon regeneration along with other intrinsic factors. In this study, the effect of the lesion site on the microenvironment and axon growth was evaluated using a refined optic nerve crush (ONC) injury model, in which the injury range was extended compared to classical injury. The number of regenerated axons labeled anterogradely with cholera toxin B fragment (CTB) was significantly increased in the long-range crush injury (LI) group compared to the ONC group at distances of 500, 1000 and 1500 µm from the initial site of the injury. These data confirmed that RGC axons can regenerate inside the lesion site. Immunofluorescence and proteomic analysis showed that the microenvironment at the lesion site was highly heterogeneous. The levels of myelin-associated inhibitors, chondroitin-sulfate proteoglycans (CSPGs) and other axon growth inhibitors decreased inside the lesion site compared to the posterior segment of the optic nerve lesion site. The expression of multiple lysosome-related enzymes, metabolic inhibitors including cholesterol esterase, cathepsin B, D, Z and arylsulfatase B (ARSB) were significantly increased inside the lesion site for the LI group compared to the normal optic nerves. Our results suggest that the model of long range optic nerve injury is more useful towards understanding the lesion microenvironment and the endogenous regeneration of RGCs. Also, we showed that myelin and neurocan (a CSPG) are differently expressed in the optic nerve between the interior and posterior lesion sites and may explain why axons cannot reach the brain through the lesion site.

5.
J Dig Dis ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871932

RESUMO

OBJECTIVE: We performed a meta-analysis to systematically summarize previous studies on the accuracy of AI in the detection of esophageal cancer and neoplasms in endoscopic images, so as to provide scientific evidence for the effectiveness of AI-assisted diagnostic models. METHODS: We searched the databases of PubMed, Embase and Cochrane for studies on AI-assisted esophageal cancer and neoplasms in endoscopic images. We used a bivariate mixed-effects binary regression model to calculate the pooled diagnostic efficacy of AI. Subgroup analyses and meta-regression were performed to explore the sources of heterogeneity. We also compared the effectiveness of AI with that of endoscopists. RESULT: A total of 16 studies were included in our meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and AUC were 0.94 (95%CI: 0.92-0.96), 0.85 (95%CI: 0.73-0.92), 6.397 (95%CI: 3.380-12.106), 0.065 (95%CI: 0.041-0.102), 98.881 (95%CI: 39.446-247.865) and 0.97 (95%CI: 0.95-0.98), respectively. AI-based models showed a better performance than endoscopists in terms of the pooled sensitivity (0.94; 95%CI: 0.84-0.98 vs. 0.82; 95%CI: 0.77-0.86, p < 0.01). CONCLUSION: The use of AI was shown to achieve a high accuracy in the detection of early esophageal cancer. However, most of the studies were based on retrospective review of selected images, further validation in prospective trials is expected.

6.
J Int Med Res ; 49(4): 300060521999766, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33909981

RESUMO

OBJECTIVE: To evaluate the effect of a new negative-pressure drainage system in thoracoscopic lung cancer surgery; thereby, providing a new option for postoperative drainage. METHODS: We retrospectively analyzed data for 200 patients who underwent thoracoscopic surgery between May 2018 and October 2019. According to the thoracic drainage method, the patients were divided into the thoracic tube group and the new system group. The epidemiological and clinicopathological data were compared before operation, and the clinical effect of thoracic drainage was compared after operation. RESULTS: There was no significant difference in epidemiological and clinicopathological data between the two groups. There was also no significant difference in drain removal time, hospital stay, and complication rates between the two groups. However, the incidences of pleural effusion and poor incision healing in the new system group were lower than in the thoracic tube group. Visual analog scale (VAS) scores in the new system group were lower than those in the thoracic tube group at each postoperative interval; therefore, the new system group required less analgesia. CONCLUSION: The new system was not inferior to thoracic tubes regarding the drainage effect after thoracoscopic lung cancer surgery. Hence, the system is an alternative to traditional thoracic tubes.

7.
J Chem Inf Model ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33905247

RESUMO

Understanding mechanisms of protein folding and binding is crucial to designing their molecular function. Molecular dynamics (MD) simulations and Markov state model (MSM) approaches provide a powerful way to understand complex conformational change that occurs over long time scales. Such dynamics are important for the design of therapeutic peptidomimetic ligands, whose affinity and binding mechanism are dictated by a combination of folding and binding. To examine the role of preorganization in peptide binding to protein targets, we performed massively parallel explicit-solvent MD simulations of cyclic ß-hairpin ligands designed to mimic the p53 transactivation domain and competitively bind mouse double minute 2 homologue (MDM2). Disrupting the MDM2-p53 interaction is a therapeutic strategy to prevent degradation of the p53 tumor suppressor in cancer cells. MSM analysis of over 3 ms of aggregate trajectory data enabled us to build a detailed mechanistic model of coupled folding and binding of four cyclic peptides which we compare to experimental binding affinities and rates. The results show a striking relationship between the relative preorganization of each ligand in solution and its affinity for MDM2. Specifically, changes in peptide conformational populations predicted by the MSMs suggest that entropy loss upon binding is the main factor influencing affinity. The MSMs also enable detailed examination of non-native interactions which lead to misfolded states and comparison of structural ensembles with experimental NMR measurements. In contrast to an MSM study of p53 transactivation domain (TAD) binding to MDM2, MSMs of cyclic ß-hairpin binding show a conformational selection mechanism. Finally, we make progress toward predicting accurate off rates of cyclic peptides using multiensemble Markov models (MEMMs) constructed from unbiased and biased simulated trajectories.

8.
Transl Psychiatry ; 11(1): 172, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731679

RESUMO

Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.

9.
Acta Pharmacol Sin ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772141

RESUMO

Nano drug-delivery systems (DDS) may significantly improve efficiency and reduce toxicity of loaded drugs, but a few nano-DDS are highly successful in clinical use. Unprotected nanoparticles in blood flow are often quickly cleared, which could limit their circulation time and drug delivery efficiency. Elongating their blood circulation time may improve their delivery efficiency or grant them new therapeutic possibilities. Erythrocytes are abundant endogenous cells in blood and are continuously renewed, with a long life span of 100-120 days. Hence, loading nanoparticles on the surface of erythrocytes to protect the nanoparticles could be highly effective for enhancing their in vivo circulation time. One of the key questions here is how to properly attach nanoparticles on erythrocytes for different purposes and different types of nanoparticles to achieve ideal results. In this review, we describe various methods to attach nanoparticles and drugs to the erythrocyte surface, and discuss the key factors that influence the stability and circulation properties of the erythrocytes-based delivery system in vivo. These data show that using erythrocytes as a host for nanoparticles possesses great potential for further development.

10.
J Steroid Biochem Mol Biol ; 210: 105859, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33677016

RESUMO

Androgens are essential for prostate cancer development. However, steroidogenesis has mainly been investigated in a limited number of prostate cancer cell lines, leading to varied conclusions and elusive clinical significance. Here, we established an ex vivo research platform with fresh biopsy samples transiently cultured with tritium- labelled androgens to trace steroidogenesis in prostate tissues and investigate its potential clinical application. DHEA was confirmed as the major precursor for androgen synthesis in the prostate. Significant amounts of oxidized DHEA and 5α-androstanedione were generated from DHEA in prostate biopsy samples. Prostatic steroidogenesis was independent of other clinical factors. Furthermore, prostatic steroidogenesis was suppressed after androgen deprivation therapy but increased upon treatment resistance, indicating that prostatic steroidogenesis was affected by clinical treatments. Overall, we provide an accessible research platform to characterize steroidogenesis in prostate tissue and indicate the correlation between prostatic steroidogenesis and disease progression.

11.
Biomed Pharmacother ; 138: 111468, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33740526

RESUMO

For women of reproductive age, polycystic ovary syndrome (PCOS) is not a rare heterogeneous endocrine disorder and metabolic dysfunction. Menstrual problems, hyperandrogenism, polycystic ovary (PCO) and infertility often affect these women, and they are also prone to metabolic syndrome (MS) and insulin resistance (IR). As an isoquinoline alkaloid, Berberine (BBR) is the main effective component of Coptis. BBR, as a multi-target, multi-path plant extract, can interfere with the development of PCOS and relate to pathological process from many aspects, with less adverse reactions. It is mentioned in this review that BBR can alleviate IR, reduce the level of serum androgen, regulate lipid metabolism and moderate chronic inflammation. BBR is often used in combination with metformin, compound cyproterone (CPA) and other drugs, in order to achieve better therapeutic effect on PCOS.

12.
Ann N Y Acad Sci ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33786847

RESUMO

Raoultella ornithinolytica is a poorly understood opportunistic pathogen, and the underlying mechanisms of its multidrug resistance and pathogenicity have not yet been comprehensively investigated. The multidrug-resistant (MDR) strain WM1 was isolated from the blood of a male patient in Tianjin, China, in 2018. Here, we describe the complete genome and provide a genomic analysis of R. ornithinolytica WM1. The isolate was resistant to all tested antimicrobials except amikacin, tobramycin, and tigecycline. Two plasmids, pWM1-1 (IncHI5) and pWM1-2 (IncR), carried multidrug-resistance regions. A large antimicrobial resistance island region resided on pWM1-1 and exhibited mosaic structures resulting from the acquisition of complex integrations of variable regions, including genes conferring resistance to multiple classes of antimicrobials. Moreover, WM1 possessed virulence-related elements that encode several virulence factors, including type I fimbriae, Escherichia coli common pilus, type II and VI secretion systems, yersiniabactin, enterobactin, and surface polysaccharide, indicating pathogenic potential. Furthermore, the core genome phylogeny and pan-genome analyses revealed extensive genetic diversity. Our analysis indicates the need for stringent infection control, antimicrobial stewardship, periodic resistance monitoring, and rational medication to address potential threats posed by MDR R. ornithinolytica strains.

13.
Biosci Rep ; 41(3)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33687056

RESUMO

BACKGROUND: Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The identification of effective markers for early diagnosis and prognosis is important for reducing mortality and ensuring that therapy for HNSCC is effective. Proteasome 26S subunit, non-ATPase 7 (PSMD7) is an ATP-independent component of the 19S regulatory subunit. The prognostic value of PSMD7 and the association with immune infiltration in HNSCC remains unclear. METHODS: The Sangerbox, Oncomine, UALCAN and Human Protein Atlas (HPA) databases were used to examine PSMD7 expression profiles in HNSCC. The CVCDAP was used to analysis the association of PSMD7 with the prognosis of patients with HNSCC. The mechanism was investigated with gene set enrichment analysis (GSEA). The association between expression of PSMD7 and immune infiltration in HNSCC was investigated using the Tumor Immune Estimation Resource (TIMER), TISIDB database and CIBERSORT algorithm. RESULTS: PSMD7 expression was significantly up-regulated in HNSCC compared with relative normal tissues. In addition, up-regulated PSMD7 expression was associated with various clinicopathological parameters. High expression of PSMD7 suggested inferior survival of HNSCC patients. GSEA and CERES score indicated that PSMD7 was closely correlated with tumor-related signaling pathways and cell survival. Functional analyses revealed that PSMD7 was positively correlated with various infiltration levels. Moreover, PSMD7 influenced the prognosis of HNSCC patients partially via immune infiltration. CONCLUSION: Our findings suggest that PSMD7 is associated poor prognosis in patients with HNSCC and plays an important role in tumor-related immune infiltration.

14.
Sci Total Environ ; 772: 144897, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33770894

RESUMO

Extremely high levels of atmospheric sulfate aerosols have still frequently occurred in China especially in winter haze periods and often been underestimated by models due to some missing formation mechanisms. Here we investigated the heterogeneous reaction dynamics of SO2 oxidation by the abundantly co-existing O3 and NO2 in the urban atmosphere of China by using a laboratory smog chamber simulation technique. Our results showed that with an increase of NH3 concentrations from 0.05 ppm to 1.5 ppm, SO2 oxidation by O3 can be greatly promoted and lead to an exponential increase of diameter growth factor (GF) of particles in the chamber from 1.29 to 1.98 for NaCl seeds and from 1.20 to 1.60 for (NH4)2SO4 seeds, along with an increasing uptake coefficient (γ) of SO2 from 4.47 × 10-5 to 1.52 × 10-4 on NaCl seeds and from 2.32 × 10-5 to 5.74 × 10-5 on (NH4)2SO4 seeds, respectively. The heterogeneous production of sulfate from oxidation of SO2 under NH3-rich conditions by O3 and NO2 mixture in the chamber was 2.0-3.5 times the sum of sulfate from SO2 oxidations by O3 and NO2, suggesting a strongly synergetic effect of the mixed oxidants on the heterogeneous oxidation of SO2, which can cause rapid formation of (NH4)2SO4 and NH4NO3 and is responsible for the explosive growth of PM2.5 in the winter haze period of China. Our chamber results further showed that such synergetic process is only efficient under NH3-rich conditions, clearly indicating that the combined controls on O3, NOx and NH3 are necessary for further mitigating the PM2.5 pollution in China.

15.
Zhongguo Zhen Jiu ; 41(2): 177-82, 2021 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-33788466

RESUMO

OBJECTIVE: To observe the effect of acupoint thread-embedding at "Zusanli" (ST 36) and "Fenglong" (ST 40) on the macrophage polarization of epididymis adipose tissue in obese mice, and to explore the action mechanism of acupoint thread-embedding on weight control. METHODS: Among 30 male C57BL/6 mice, 10 mice were randomly selected and fed with normal diet, and the remaining 20 mice were fed with high-fat diet to establish the obesity model. Sixteen mice with successful obesity model were randomly divided into a model group and an acupoint thread-embedding group, 8 mice in each group. Eight mice were selected from mice which were fed with normal diet as the normal group. On the next day of successful modeling, acupoint thread-embedding was performed at "Zusanli" (ST 36) and "Fenglong" (ST 40) in the acupoint thread-embedding group, once every 10 days for 4 times. The body weight was recorded at 0, 8, 16, 24, 32, 40 days into intervention; the level of glucose metabolism was compared after intervention; the level of lipid metabolism and weight of epididymal adipose tissue were compared at the end of the intervention; the mRNA expression of M1 and M2 macrophage-related cytokines interleukin-10 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were detected by real-time PCR; the mRNA and protein expression of M1 macrophage labeled inducible nitric oxide synthase (iNOS) and M2 macrophage labeled arginase-1 (Arg-1) were detected by real-time PCR and Western blot. RESULTS: Compared with the normal group, the body weight at 0, 8, 16, 24, 32, 40 days into intervention in the model group was increased (P<0.05); the results of glucose tolerance test at 0, 30, 60, 120 min and insulin tolerance test at 0, 30, 60, 90, 120 min in the model group were higher than those in the normal group (P<0.05); the levels of total cholesterol and triacylglycerol in the model group were significantly higher than those in the normal group (P<0.001, P<0.01); the weight of epididymal adipose tissue in the model group was significantly higher than that in the normal group (P<0.001); the mRNA expression of IL-6, MCP-1, TNF-α and iNOS was increased (P<0.05, P<0.01, P<0.001), that of IL-10, Arg-1 was decreased (P<0.01), the protein expression of iNOS was up-regulated (P<0.01), and that of Arg-1 was down-regulated (P<0.001). Compared with the model group, the body weight at 16, 24, 32, 40 days into treatment in the acupoint thread-embedding group was reduced (P<0.05); the results of glucose tolerance test at 30, 60, 120 min and insulin tolerance test at 30, 60 min in the acupoint thread-embedding group were lower than those in the model group (P<0.05); the levels of total cholesterol and triacylglycerol in the acupoint thread-embedding group were significantly lower than those in the model group (P<0.01, P<0.05); the weight of epididymal adipose tissue in the acupoint thread-embedding group was significantly lower than that in the model group (P<0.01); the mRNA expression of IL-6, MCP-1, TNF-α and iNOS was reduced (P<0.05), that of IL-10, Arg-1 was increased (P<0.05), the protein expression of iNOS was down-regulated (P<0.05), and that of Arg-1 was up-regulated (P<0.01). CONCLUSION: Acupoint thread-embedding at "Zusanli" (ST 36) and "Fenglong" (ST 40) may play a role in weight control by regulating the polarization of macrophages.


Assuntos
Pontos de Acupuntura , Epididimo , Tecido Adiposo , Animais , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos
16.
BMC Musculoskelet Disord ; 22(1): 283, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731057

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) program is an evidence-based improvement over non-ERAS traditional care. The aim of the present study was to analyze the safety, feasibility, and efficacy of an ERAS program in patients over 70 years undergoing lumbar arthrodesis by comparison with non-ERAS traditional care. METHODS: During January 2018 to December 2018, patients enrolled received non-ERAS traditional care, while the ERAS program was implemented from January to December 2019. Demographic characteristics, comorbidities, surgical data and postoperative recovery parameters were collected from all patients. Postoperative pain scores were evaluated by visual analog scales (VAS). The clinical outcomes were length of stay (LOS), postoperative complications and postoperative pain scores. Compliance results were also collected. RESULT: A total of 127 patients were enrolled, including 67 patients in the non-ERAS traditional care group and 60 patients in the ERAS group. The demographic characteristics and comorbidities of the two groups showed no significant differences. The LOS of patients treated with ERAS program (13.6 ± 4.0 days) was significantly less than that of patients treated with non-ERAS traditional care (15.6 ± 3.9 days) (p = 0.034). Complication rate was 8.3% in the ERAS group versus 20.9% in the non-ERAS traditional care group (p = 0.048). VAS (back) in the ERAS group was significantly lower on postoperative day (POD) 1 and POD2. Postoperative recovery parameters were improved in the ERAS group. The overall compliance with the ERAS program was 94%. CONCLUSIONS: Based on our results, ERAS program is safer and more effective for elderly patients over 70 undergoing lumbar arthrodesis than non-ERAS traditional care.

17.
J Biol Chem ; : 100568, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33753169

RESUMO

The enzyme NUDT15 efficiently hydrolyses the active metabolites of thiopurine drugs, which are routinely used for treating cancer and inflammatory diseases. Loss-of-function variants in NUDT15 are strongly associated with thiopurine intolerance, such as leukopenia, and pre-emptive NUDT15 genotyping has been clinically implemented to personalize thiopurine dosing. However, understanding the molecular consequences of these variants has been difficult, as no structural information was available for NUDT15 proteins encoded by clinically actionable pharmacogenetic variants due to their inherent instability. Recently, the small molecule NUDT15 inhibitor TH1760 has been shown to sensitize cells to thiopurines, through enhanced accumulation of 6-thio-guanine in DNA. Building upon this, we herein report the development of the potent and specific NUDT15 inhibitor, TH7755. TH7755 demonstrates a greatly improved cellular target engagement and 6-thioguanine potentiation compared to TH1760, while showing no cytotoxicity on its own. This potent inhibitor also stabilized NUDT15, enabling analysis by X-ray crystallography. We have determined high-resolution structures of the clinically relevant NUDT15 variants Arg139Cys, Arg139His, Val18Ile and V18_V19insGlyVal. These structures provide clear insights into the structural basis for the thiopurine intolerance phenotype observed in patients carrying these pharmacogenetic variants. These findings will aid in predicting the effects of new NUDT15 sequence variations yet to be discovered in the clinic.

18.
Biomed Pharmacother ; 137: 111271, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33561643

RESUMO

Cigarette smoking-related lung injury is one of the most common and fatal etiologies of many respiratory diseases, for which no effective interventions are available. Astragaloside Ⅳ (ASⅣ) is an active component extracted from Astragalus membranaceus. It is prescribed as a treatment for upper respiratory tract infections. Here, we report the potential anti-inflammatory effects and mechanisms of ASⅣ on cigarette smoking extract- (CSE)-exposed RAW264.7 cells. Murine macrophages were exposed to CSE, followed by administration of ASⅣ at 25-100 µg/mL for 24 h. ASⅣ significantly rescued CSE-induced cell death by inhibition of release pro-inflammatory cytokines. We measured autophagy as an intracellular scavenger by analyzing autophagic flux using tandem mRFP-GFP-LC3 fluorescence microscopy. Following administration with ASⅣ in CSE-exposed RAW264.7 cells, there was a notable increase in autophagosomes and a range of autophagic vacuoles were generated, as seen with transmission electron microscopy. Loss of autophagy following transfection siRNA aggravated inflammatory injury and release of inflammatory cytokines. Mechanistically, ASⅣ-triggered autophagy is mediated by the TLR4/NF-κB signaling pathway to reduce inflammation. Taken together, our findings suggest that ASⅣ acts stimulates autophagy, and that ASⅣ induces autophagy by inhibiting the TLR4/NF-κB signaling pathway, contributing to alleviation of inflammation.

19.
Phys Med Biol ; 66(6): 065008, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33535199

RESUMO

Automated segmentation of the esophagus is critical in image-guided/adaptive radiotherapy of lung cancer to minimize radiation-induced toxicities such as acute esophagitis. We have developed a semantic physics-based data augmentation method for segmenting the esophagus in both planning CT (pCT) and cone beam CT (CBCT) using 3D convolutional neural networks. One hundred and ninety-one cases with their pCTs and CBCTs from four independent datasets were used to train a modified 3D U-Net architecture and a multi-objective loss function specifically designed for soft-tissue organs such as the esophagus. Scatter artifacts and noises were extracted from week-1 CBCTs using a power-law adaptive histogram equalization method and induced to the corresponding pCT were reconstructed using CBCT reconstruction parameters. Moreover, we leveraged physics-based artifact induction in pCTs to drive the esophagus segmentation in real weekly CBCTs. Segmentations were evaluated using the geometric Dice coefficient and Hausdorff distance as well as dosimetrically using mean esophagus dose and D 5cc. Due to the physics-based data augmentation, our model trained just on the synthetic CBCTs was robust and generalizable enough to also produce state-of-the-art results on the pCTs and CBCTs, achieving Dice overlaps of 0.81 and 0.74, respectively. It is concluded that our physics-based data augmentation spans the realistic noise/artifact spectrum across patient CBCT/pCT data and can generalize well across modalities, eventually improving the accuracy of treatment setup and response analysis.

20.
Environ Pollut ; 275: 116485, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33556732

RESUMO

Magnetic biochars were prepared by chemical co-precipitation of Fe3+/Fe2+ onto rice straw (M-RSB) and sewage sludge (M-SSB), followed by pyrolysis treatment, which was also used to prepare the corresponding nonmagnetic biochars (RSB and SSB). The comparison of adsorption characteristics between magnetic and nonmagnetic biochars was investigated as a function of pH, contact time, and initial Cd2+ concentration. The adsorption of nonmagnetic biochars was better described by pseudo-second-order kinetic model, and the adsorption of RSB and SSB was better described by Langmuir and Freundlich models, respectively. Magnetization of the biochars did not change the applicability of their respective adsorption models, but reduced their adsorption capabilities. The maximum capacities were 42.48 and 4.64 mg/g for M-RSB and M-SSB, respectively, underperforming their nonmagnetic counterparts of 58.65 and 7.22 mg/g for RSB and SSB. Such a reduction was fundamentally caused by the decreases in the importance of cation-exchange and Cπ-coordination after magnetization, but the Fe-oxides contributed to the precipitation-dependent adsorption capacity for Cd2+ on magnetic biochars. The qualitative and quantitative characterization of adsorption mechanisms were further analyzed, in which the contribution proportions of cation-exchange after magnetization were reduced by 31.9% and 12.1% for M-RSB and M-SSB, respectively, whereas that of Cπ-coordination were reduced by 3.4% and 31.1% for M-RSB and M-SSB, respectively. These reductions suggest that for adsorbing Cd2+ the choice of conventional biochar was more relevant than whether the biochar was magnetized. However, magnetic biochars are easily separated from treated solutions, depending largely on initial pH. Their easy of separation suggests that magnetic biochars hold promise as more sustainable alternatives for the remediation of moderately Cd-contaminated environments, such as surface water and agriculture soil, and that magnetic biochars should be studied further.


Assuntos
Cádmio , Carvão Vegetal , Adsorção , Fenômenos Magnéticos , Água
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