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1.
Biomaterials ; 313: 122756, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39182327

RESUMEN

Currently, the treatment of bone defects in arthroplasty is a challenge in clinical practice. Nonetheless, commercially available orthopaedic scaffolds have shown limited therapeutic effects for large bone defects, especially for massiveand irregular defects. Additively manufactured porous tantalum, in particular, has emerged as a promising material for such scaffolds and is widely used in orthopaedics for its exceptional biocompatibility, osteoinduction, and mechanical properties. Porous tantalum has also exhibited unique advantages in personalised rapid manufacturing, which allows for the creation of customised scaffolds with complex geometric shapes for clinical applications at a low cost and high efficiency. However, studies on the effect of the pore structure of additively manufactured porous tantalum on bone regeneration have been rare. In this study, our group designed and fabricated a batch of precision porous tantalum scaffolds via laser powder bed fusion (LPBF) with pore sizes of 250 µm (Ta 250), 450 µm (Ta 450), 650 µm (Ta 650), and 850 µm (Ta 850). We then performed a series of in vitro experiments and observed that all four groups showed good biocompatibility. In particular, Ta 450 demonstrated the best osteogenic performance. Afterwards, our team used a rat bone defect model to determine the in vivo osteogenic effects. Based on micro-computed tomography and histology, we identified that Ta 450 exhibited the best bone ingrowth performance. Subsequently, sheep femur and hip defect models were used to further confirm the osteogenic effects of Ta 450 scaffolds. Finally, we verified the aforementioned in vitro and in vivo results via clinical application (seven patients waiting for revision total hip arthroplasty) of the Ta 450 scaffold. The clinical results confirmed that Ta 450 had satisfactory clinical outcomes up to the 12-month follow-up. In summary, our findings indicate that 450 µm is the suitable pore size for porous tantalum scaffolds. This study may provide a new therapeutic strategy for the treatment of massive, irreparable, and protracted bone defects in arthroplasty.

2.
BMC Musculoskelet Disord ; 25(1): 598, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075374

RESUMEN

BACKGROUND: Management of anterior cervical corpectomy and fusion (ACCF)-derived adjacent segment disease (ASD) represented a challenge facing the surgeons. METHODS: A 41-year man diagnosed as C3-4 level ASD derived from C5-level ACCF surgery 13 years ago was admitted to the hospital for numbness and pain in the right shoulder and upper limb. Percutaneous full-endoscopic anterior transcorporeal cervical discectomy (PEATCD) was performed, and pre- and postoperative clinical and imaging data were collected. RESULTS: The operation was completed within 70 min, and no clinical or radiological complication was reported. The visual analog scale (VAS) score decreased from preoperative 5 points to postoperative 1 point. Numbness was relieved postoperatively and disappeared completely at postoperative 3 months. Imaging data indicated sufficient spinal cord decompression, good channel repairing and cervical alignment. CONCLUSIONS: Channel-repairing PEATCD was successfully performed to treat ACCF-derived ASD, nevertheless, the long-term efficacy remained tracing and further clinical trials were needed to validate its efficacy.


Asunto(s)
Vértebras Cervicales , Fusión Vertebral , Humanos , Masculino , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Fusión Vertebral/métodos , Fusión Vertebral/efectos adversos , Adulto , Endoscopía/métodos , Discectomía Percutánea/métodos , Resultado del Tratamiento , Discectomía/métodos
3.
Ann Surg ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38881456

RESUMEN

OBJECTIVE: This study evaluated the efficacy of various local management strategies for diabetic foot ulcers (DFUs). BACKGROUND: Several surgical and non-surgical local interventional approaches are available for the treatment of DFUs. The comparative effectiveness of different treatments is unknown, and it remains unclear which approach is the optimal choice for DFUs treatment due to limited direct comparisons. METHODS: We did a systematic review and meta-analysis to select the optimal approach to DFUs local management. We searched Medline, Embase, Web of Science, and ClinicalTrials.gov from inception to September 1, 2023, to identify relevant randomized controlled trials (RCTs). We analysed data by pairwise meta-analyses with a random-effects model. A network meta-analysis using the surface under the cumulative ranking curve (SUCRA) was performed to evaluate the comparative efficacy of different interventional approaches in the early (within 12 wk) and late stages (over 12 wk). RESULTS: 141 RCTs involving 14076 patients and exploring 14 interventional strategies were eligible for inclusion. Most studies (102/141) had at least one risk-of-bias dimension. Good consistency was observed during the analysis. Local pairwise comparisons demonstrated obvious differences in the early-stage healing rate and early- and late-stage healing times, while no significant difference in the late-stage healing rate or adverse events were noted. SUCRAs identified the standard of care (SOC) + decellularized dressing (DD), off-loading (OL), and autogenous graft (AG) as the three most effective interventions within 12 weeks for both healing rate (97%, mean rank: 1.4; 90%, mean rank: 2.3; 80.8%, mean rank: 3.5, respectively) and healing time (96.7%, mean rank: 1.4; 83.0%, mean rank: 3.0; 76.8%, mean rank: 3.8, respectively). After 12 weeks, local drug therapy (LDT) (89.5%, mean rank: 2.4) and OL (82.4%, mean rank: 3.3) ranked the highest for healing rate, and OL (100.0%, mean rank: 1.0) for healing time. With respect to adverse events, moderate and high risks were detected in the SOC + DD (53.7%, mean rank: 7.0) and OL (24.4%, mean rank: 10.8) groups, respectively. CONCLUSION: The findings suggest that OL provided considerable benefits for DFU healing in both the early and late stages, but the high risk of adverse events warrants caution. SOC+DD may be the preferred option in the early stages, with an acceptable risk of adverse events.

4.
Nat Commun ; 15(1): 4113, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750029

RESUMEN

Stretchable phosphorescence materials potentially enable applications in diverse advanced fields in wearable electronics. However, achieving room-temperature phosphorescence materials simultaneously featuring long-lived emission and good stretchability is challenging because it is hard to balance the rigidity and flexibility in the same polymer. Here we present a multiphase engineering for obtaining stretchable phosphorescent materials by combining stiffness and softness simultaneously in well-designed block copolymers. Due to the microphase separation, copolymers demonstrate an intrinsic stretchability of 712%, maintaining an ultralong phosphorescence lifetime of up to 981.11 ms. This multiphase engineering is generally applicable to a series of binary and ternary initiator systems with color-tunable phosphorescence in the visible range. Moreover, these copolymers enable multi-level volumetric data encryption and stretchable afterglow display. This work provides a fundamental understanding of the nanostructures and material properties for designing stretchable materials and extends the potential of phosphorescence polymers.

5.
JACS Au ; 4(3): 1018-1030, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38559727

RESUMEN

The coarse-grained (CG) model serves as a powerful tool for the simulation of polymer systems; its reliability depends on the accurate representation of both structural and dynamical properties. However, strong correlations between structural and dynamical properties on different scales and also a strong memory effect, enforced by chain connectivity between monomers in polymer systems, render developing a chemically specific systematic CG model a formidable task. In this study, we report a systematic CG approach that combines the iterative Boltzmann inversion (IBI) method and the generalized Langevin equation (GLE) dynamics. Structural properties are ensured by using conservative CG potentials derived from the IBI method. To retrieve the correct dynamical properties in the system, we demonstrate that using a combination of a Rouse-type delta function and a time-dependent short-time kernel in the GLE simulation is practically efficient. The former can be used to adjust the long-time diffusion dynamics, and the latter can be reconstructed from an iterative procedure according to the velocity autocorrelation function (ACF) from all-atomistic (AA) simulations. Taking the polystyrene as an example, we show that not only structural properties of radial distribution function, intramolecular bond, and angle distributions can be reproduced but also dynamical properties of mean-square displacement, velocity ACF, and force ACF resulted from our CG model have quantitative agreement with the reference AA model. In addition, reasonable agreements are observed in other collective properties between our GLE-CG model and the AA simulations as well.

6.
Int J Surg ; 110(5): 3050-3059, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38446872

RESUMEN

BACKGROUND: Consensus on the various interventions for degenerative lumbar spondylolisthesis (DLS) remains unclear. MATERIALS AND METHODS: The authors searched PubMed, Embase, Cochrane Library, Web of Science, and major scientific websites until 01 November 2023, to screen eligible randomized controlled trials (RCTs) involving the treatment of DLS. The seven most common DLS interventions [nonsurgical (NS), decompression only (DO), decompression plus fusion without internal fixation (DF), decompression plus fusion with internal fixation (DFI), endoscopic decompression plus fusion (EDF), endoscopic decompression (ED), and circumferential fusion (360F)] were compared. The primary (pain and disability) and secondary (complications, reoperation rate, operation time, blood loss, length of hospital stay, and satisfaction) outcomes were analyzed. RESULTS: Data involving 3273 patients in 16 RCTs comparing the efficacy of different interventions for DLS were reported. In terms of improving patient pain and dysfunction, there was a significant difference between surgical and NS. EDF showed the greatest improvement in short-term and long-term dysfunction (probability, 7.1 and 21.0%). Moreover, EDF had a higher complication rate (probability 70.8%), lower reoperation rate (probability, 20.2%), and caused greater blood loss (probability, 82.5%) than other surgical interventions. Endoscopic surgery had the shortest hospitalization time (EDF: probability, 42.6%; ED: probability, 3.9%). DF and DFI had the highest satisfaction scores. CONCLUSIONS: Despite the high complication rate of EDF, its advantages include improvement in pain, lower reoperation rate, and shorter hospitalization duration. Therefore, EDF may be a good option for patients with DLS as a less invasive surgical approach.


Asunto(s)
Vértebras Lumbares , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Espondilolistesis , Humanos , Espondilolistesis/cirugía , Vértebras Lumbares/cirugía , Descompresión Quirúrgica/métodos , Fusión Vertebral/métodos , Fusión Vertebral/efectos adversos , Resultado del Tratamiento , Reoperación/estadística & datos numéricos
7.
Am J Hematol ; 99(4): 662-678, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38197307

RESUMEN

Chimeric antigen receptor (CAR) T-cell therapy, an innovative immunotherapeutic against relapsed/refractory B-cell lymphoma, faces challenges due to frequent viral infections. Despite this, a comprehensive review addressing risk assessment, surveillance, and treatment management is notably absent. This review elucidates immune response compromises during viral infections in CAR-T recipients, collates susceptibility risk factors, and deliberates on preventive strategies. In the post-pandemic era, marked by the Omicron variant, new and severe threats to CAR-T therapy emerge, necessitating exploration of preventive and treatment measures for COVID-19. Overall, the review provides recommendations for viral infection prophylaxis and management, enhancing CAR-T product safety and recipient survival.


Asunto(s)
Linfoma de Células B , Receptores Quiméricos de Antígenos , Virosis , Humanos , Receptores Quiméricos de Antígenos/uso terapéutico , Inmunoterapia Adoptiva/efectos adversos , Linfoma de Células B/terapia , Virosis/etiología , Antígenos CD19 , Tratamiento Basado en Trasplante de Células y Tejidos
8.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1017006

RESUMEN

Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.

9.
J Chem Phys ; 159(12)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-38127373

RESUMEN

How to fabricate perpendicularly oriented domains (PODs) of lamellar and cylinder phases in block copolymer thin films remains a major challenge. In this work, via a coarse-grained molecular dynamics simulation study, we report a solvent evaporation strategy starting from a mixed solution of A-b-B-type diblock copolymers (DBCs) and single-chain nanoparticles (SCNPs) with the same composition, which is capable of spontaneously generating PODs in drying DBC films induced by the interface segregation of SCNPs. The latter occurs at both the free surface and substrate and, consequently, neutralizes the interface selectivity of distinct blocks in DBCs, leading to spontaneous formation of PODs at both interfaces. The interface segregation of SCNPs is related to the weak solvophilicity of the internal cross-linker units. A mean-field theory calculation demonstrates that the increase in the chemical potential of SCNPs in the bulk region drives their interface segregation along with solvent evaporation. We believe that such a strategy can be useful in regulating the PODs of DBC films in practical applications.

10.
JMIR Public Health Surveill ; 9: e46385, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37934562

RESUMEN

BACKGROUND: Sleep is an important physiological behavior in humans that is associated with the occurrence and development of various diseases. However, the association of sleep duration with health-related outcomes, including obesity-related factors, musculoskeletal diseases, and mortality because of different causes, has not been systematically reported. OBJECTIVE: This study aims to systematically investigate the effect of sleep duration on health-related outcomes. METHODS: Overall, 54,664 participants with sleep information from 8 survey cycles of the National Health and Nutrition Examination Survey (2005-2020) were included in the analysis. Health-related outcomes comprised obesity-related outcomes (ie, BMI, obesity, waist circumference, and abdominal obesity), metabolism-related outcomes (ie, uric acid, hyperuricemia, and bone mineral density [BMD]), musculoskeletal diseases (ie, osteoarthritis [OA] and rheumatoid arthritis [RA]), and mortality because of different causes. The baseline information of participants including age, sex, race, educational level, marital status, total energy intake, physical activity, alcohol consumption, smoking, hypertension, and diabetes was also collected as covariates. Information about the metabolism index, disease status, and covariates was acquired from the laboratory, examination, and questionnaire data. Survival information, including survival status, duration, and cause of death, was obtained from the National Death Index records. Quantile regression models and Cox regression models were used for association analysis between sleep duration and health-related outcomes. In addition, the threshold effect analysis, along with smooth curve fitting method, was applied for the nonlinear association analysis. RESULTS: Participants were divided into 4 groups with different sleep durations. The 4 groups showed significant differences in terms of baseline data (P<.001). The quantile regression analysis indicated that participants with increased sleep duration showed decreased BMI (ß=-.176, 95% CI -.220 to -.133; P<.001), obesity (odds ratio [OR] 0.964, 95% CI 0.950-0.977; P<.001), waist circumference (ß=-.219, 95% CI -.320 to -.117; P<.001), abdominal obesity (OR 0.975, 95% CI 0.960-0.990; P<.001), OA (OR 0.965, 95% CI 0.942-0.990; P=.005), and RA (OR 0.940, 95% CI 0.912-0.968; P<.001). Participants with increased sleep duration also showed increased BMD (ß=.002, 95% CI .001-.003; P=.005), as compared with participants who slept <5.5 hours. A significant saturation effect of sleep duration on obesity, abdominal obesity, and hyperuricemia was detected through smooth curve fitting and threshold effect analysis (sleep duration>inflection point). In addition, a significant threshold effect of sleep duration on BMD (P<.001); OA (P<.001); RA (P<.001); and all-cause (P<.001), cardiovascular disease-cause (P<.001), cancer-cause (P=.005), and diabetes-cause mortality (P<.001) was found. The inflection point was between 6.5 hours and 9 hours. CONCLUSIONS: The double-edged sword effect of sleep duration on obesity-related outcomes, embolism-related diseases, musculoskeletal diseases, and mortality because of different causes was detected in this study. These findings provided epidemiological evidence that proper sleep duration may be an important factor in the prevention of multisystem diseases.


Asunto(s)
Diabetes Mellitus , Hiperuricemia , Enfermedades Musculoesqueléticas , Osteoartritis , Humanos , Encuestas Nutricionales , Obesidad Abdominal , Sueño , Obesidad
11.
Biomed Pharmacother ; 168: 115632, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37806094

RESUMEN

Spinal Cord Injury (SCI) is a devastating neurological disorder comprising primary mechanical injury and secondary inflammatory response-mediated injury for which an effective treatment is still unavailable. It is well known that secondary inflammatory responses are a significant cause of difficulties in neurological recovery. An immune imbalance between M1/M2 macrophages at the sites of injury is involved in developing and progressing the secondary inflammatory response. Recently, Mesenchymal Stem Cells (MSCs) have shown significant therapeutic potential in tissue engineering and regenerative medicine due to their potential multidirectional differentiation and immunomodulatory properties. Accumulating evidence shows that MSCs can regulate the balance of M1/M2 macrophage polarization, suppress downstream inflammatory responses, facilitate tissue repair and regeneration, and improve the prognosis of SCI. This article briefly overviews the impact of macrophages and MSCs on SCI and repair. It discusses the mechanisms by which MSCs regulate macrophage plasticity, including paracrine action, release of exosomes and apoptotic bodies, and metabolic reprogramming. Additionally, the article summarizes the relevant signaling pathways of MSCs that regulate macrophage polarization.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal , Humanos , Macrófagos/metabolismo , Células Madre Mesenquimatosas/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Diferenciación Celular , Exosomas/metabolismo , Médula Espinal/metabolismo
12.
ACS Macro Lett ; 12(8): 1052-1057, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37449975

RESUMEN

We investigate the molecular origin of mechanical reinforcement in a polymer nanocomposite (PNC) under a glass state via molecular dynamics simulations. The strength of the PNC system is found to be reinforced mainly via reduced plastic deformations of the nanoparticle neighborhood (NN). Such a reinforcement effect is found to decay with an increase in the strain rate. The Arrhenius-Eyring relation is used to analyze its origin. The amplitude of the reinforcement is found to be determined by the difference between the energy barrier (ΔE) for the activation of NN and the work (W) done by the applied stress to conquer that barrier. A larger strain rate is found to result in a larger W and, hence, a weaker reinforcement effect. Such a strain-rate dependence is verified in the experimental tensile tests of a poly(vinyl alcohol)/SiO2 composite system. These results not only provide a new understanding of the molecular origin of the reinforcement effect in the PNC system, but also pave the way for a better design of the PNC material properties.

13.
Front Immunol ; 14: 1098683, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37404817

RESUMEN

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease and closely associated with both genetic and environmental factors. Volatile organic chemicals (VOC), a common environment pollutant, was associated with some autoimmune diseases, while whether VOC exposure or which VOC leads to RA is yet clarified. Methods: A cross-sectional study using data from the 6 survey cycles (2005-2006, 2011-2012, 2013-2014, 2015-2016, 2017-2018, 2017-2020) of NHANES program was performed. The RA or non-arthritis status of participant was identified through a questionnaire survey. The quantile logistic regression method was used for correlation analysis between VOC metabolites (VOCs) in urine and RA. The covariates included age, gender, race, educational level, marital status, total energy intake, physical activity, smoking, hypertension, diabetes, urine creatinine, albumin and marihuana use. Results: A total of 9536 participants (aged 20 to 85) with 15 VOCs, comprising 618 RA and 8918 non-arthritis participants, was finally included for analysis. Participants in the RA group showed higher VOCs in urine than that in the non-arthritis group. A positive association between 2 VOCs (AMCC: Q4: OR=2.173, 95%CI: 1.021, 4.627. 3HPMA: Q2: OR=2.286, 95%CI: 1.207 - 4.330; Q4: OR=2.663, 95%CI: 1.288 -5.508.) and RA was detected in the model 3, which was independent of all the covariates. The relative parent compounds of the two VOCs included N,N-Dimethylformamide and acrolein. Discussion: These findings suggested that the VOC exposure significantly associated with RA, providing newly epidemiological evidence for the establishment that environmental pollutants associated with RA. And also, more prospective studies and related experimental studies are needed to further validate the conclusions of this study.


Asunto(s)
Artritis Reumatoide , Contaminantes Ambientales , Compuestos Orgánicos Volátiles , Humanos , Estudios Transversales , Encuestas Nutricionales , Estudios Prospectivos , Artritis Reumatoide/epidemiología , Contaminantes Ambientales/efectos adversos
14.
PLoS Comput Biol ; 19(6): e1011218, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37289843

RESUMEN

Synthetic lethality (SL) occurs when mutations in two genes together lead to cell or organism death, while a single mutation in either gene does not have a significant impact. This concept can also be extended to three or more genes for SL. Computational and experimental methods have been developed to predict and verify SL gene pairs, especially for yeast and Escherichia coli. However, there is currently a lack of a specialized platform to collect microbial SL gene pairs. Therefore, we designed a synthetic interaction database for microbial genetics that collects 13,313 SL and 2,994 Synthetic Rescue (SR) gene pairs that are reported in the literature, as well as 86,981 putative SL pairs got through homologous transfer method in 281 bacterial genomes. Our database website provides multiple functions such as search, browse, visualization, and Blast. Based on the SL interaction data in the S. cerevisiae, we review the issue of duplications' essentiality and observed that the duplicated genes and singletons have a similar ratio of being essential when we consider both individual and SL. The Microbial Synthetic Lethal and Rescue Database (Mslar) is expected to be a useful reference resource for researchers interested in the SL and SR genes of microorganisms. Mslar is open freely to everyone and available on the web at http://guolab.whu.edu.cn/Mslar/.


Asunto(s)
Neoplasias , Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/genética , Mutaciones Letales Sintéticas , Mutación , Genoma Bacteriano/genética , Bases de Datos Genéticas , Neoplasias/genética
15.
ACS Nano ; 17(11): 10958-10964, 2023 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-37252750

RESUMEN

As the initially discovered allotrope of boron, amorphous elementary boron (AE-B) has been reported for more than two centuries. Several possible structures of AE-B have been proposed during the past decades. Due to its noncrystalline nature, however, the structure of AE-B has not yet been determined. We notice that AE-B can be dissolved in organic solvents, although the solubility is very low. After surface adsorption from solution, the individual or the self-assembled structure of AE-B molecules can be characterized at the single-molecule or nanoscopic level, which may be helpful to reveal the molecular structure of AE-B. Atomic force microscopy (AFM) imaging shows that AE-B is a chain-like molecule with a thickness (or height) of 0.17 ± 0.01 nm, which agrees well with the diameter of a B atom, demonstrating that the structure of an AE-B molecule contains only one layer of B atoms. Results from high-resolution transmission electron microscopy (HRTEM) indicate that AE-B molecules can be self-assembled into a nanosheet with parallel lines. The width of each line is 0.27 nm, and the periodical length along the chain axial direction is 0.32 ± 0.01 nm. These results indicate that AE-B is composed of a ladder-like inorganic polymer with B4 as the structural unit. This conclusion is supported by the single-chain elasticity obtained by single-molecule AFM and quantum mechanical calculations. We expect that this fundamental study is not only an ending of the two-century-old scientific mystery but also the beginning of the research and applications of AE-B (ladder B) as a polymeric material. The research strategy may be also used to study other amorphous inorganic materials.

16.
J Pharmacol Exp Ther ; 386(1): 70-79, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37230799

RESUMEN

Portal hypertension (PT) commonly occurs in cirrhosis. Nitric oxide (NO) imbalance contributes to PT via reduced soluble guanylyl cyclase (sGC) activation and cGMP production, resulting in vasoconstriction, endothelial cell dysfunction, and fibrosis. We assessed the effects of BI 685509, an NO-independent sGC activator, on fibrosis and extrahepatic complications in a thioacetamide (TAA)-induced cirrhosis and PT model. Male Sprague-Dawley rats received TAA twice-weekly for 15 weeks (300-150 mg/kg i.p.). BI 685509 was administered daily for the last 12 weeks (0.3, 1, and 3 mg/kg p.o.; n = 8-11 per group) or the final week only (Acute, 3 mg/kg p.o.; n = 6). Rats were anesthetized to measure portal venous pressure. Pharmacokinetics and hepatic cGMP (target engagement) were measured by mass spectrometry. Hepatic Sirius Red morphometry (SRM) and alpha-smooth muscle actin (αSMA) were measured by immunohistochemistry; portosystemic shunting was measured using colored microspheres. BI 685509 dose-dependently increased hepatic cGMP at 1 and 3 mg/kg (3.92 ± 0.34 and 5.14 ± 0.44 versus 2.50 ± 0.19 nM in TAA alone; P < 0.05). TAA increased hepatic SRM, αSMA, PT, and portosystemic shunting. Compared with TAA, 3 mg/kg BI 685509 reduced SRM by 38%, αSMA area by 55%, portal venous pressure by 26%, and portosystemic shunting by 10% (P < 0.05). Acute BI 685509 reduced SRM and PT by 45% and 21%, respectively (P < 0.05). BI 685509 improved hepatic and extrahepatic cirrhosis pathophysiology in TAA-induced cirrhosis. These data support the clinical investigation of BI 685509 for PT in patients with cirrhosis. SIGNIFICANCE STATEMENT: BI 685509 is an NO-independent sGC activator that was tested in a preclinical rat model of TAA-induced nodular, liver fibrosis, portal hypertension, and portal systemic shunting. BI 685509 reduced liver fibrosis, portal hypertension, and portal-systemic shunting in a dose-dependent manner, supporting its clinical assessment to treat portal hypertension in patients with cirrhosis.


Asunto(s)
Hipertensión Portal , Cirrosis Hepática Experimental , Ratas , Masculino , Animales , Guanilil Ciclasa Soluble/farmacología , Tioacetamida/efectos adversos , Ratas Sprague-Dawley , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/tratamiento farmacológico , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Hígado , GMP Cíclico
17.
Opt Express ; 31(4): 6514-6528, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36823905

RESUMEN

Light detection and ranging (lidar) is widely accepted as an indispensable sensor for autonomous vehicles. There are two fundamental challenges in a lidar system: optical beam steering technique and ranging method. Optical phased array (OPA) is considered as one of the most promising beam steering schemes due to its solid state, compact size, and high reliability. As for ranging method, time-of-flight and frequency-modulate continuous-wave (FMCW) are commonly utilized in numerous research. However, they are impractical to commercial OPA lidar due to either requiring excessive optical power or the poor stability, high complexity, and high insertion loss of the FMCW source. As a result, the development of OPA lidars is significantly hindered by the lack of a feasible ranging method. In this paper, we present a phase-modulated continuous-wave (PhMCW) ranging method with excellent ranging accuracy and precision. Ranging error as low as 0.1 cm and precision on the order of 3.5 cm are achieved. In addition, theoretical and experimental study on simultaneous velocity measurement is carried out and velocity error as low as 0.15 cm/s is obtained. Finally, we develop a proof-of-concept OPA-PhMCW lidar and obtain a point cloud with excellent fidelity. Our work paves a novel approach to solid-state, cost-effective and high-performance OPA lidars.

18.
Chemosphere ; 315: 137738, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36608892

RESUMEN

BACKGROUND: Increasing evidence have been provided that the exposure to environment pollutants was associated obesity, while whether the exposure to volatile organic chemicals (VOC) was associated with obesity or abdominal obesity is yet to be clarified. METHOD: A cross-sectional study using data from the 6 survey cycles (2005-2006, 2011-2018, 2017-2020) of NHANES program was performed. Obesity and abdominal obesity were identified as a BMI >30 and a waist circumference >102 cm for men or >88 cm for women respectively. The quantile logistic regression method was used to analyze the association between VOC metabolites (VOCs) in urine and obesity, and the quantile regression method was used for the association analysis between VOCs in urine and BMI, as well as waist circumference. RESULTS: A total of 17 524 participants (4965 obesity, 7317 abdominal obesity) were included, and participants in the obesity or abdominal obesity groups showed higher VOCs in urine than that in the control group. The CEMA was identified as the risk factor for obesity and abdominal obesity in all the 4 models, and its detected OR for obesity in the Q2 to Q4 of model 3 was 1.169 (Q2, p < 0.05), 1.306 (Q3, p < 0.001) and 1.217 (Q4, p < 0.01) respectively. And its OR for abdominal obesity in the Q2 to Q4 of model 3 was 1.222 (Q2, p < 0.01), 1.448 (Q3, p < 0.001) and 1.208 (Q4, p < 0.05) respectively. A significantly positive association between CEMA and BMI, as well as waist circumference, was also detected. CONCLUSION: In this study, we found that the exposure to VOC (Acrolein, Acrylamide, Acrylonitrile, 1,3-Butadiene, Crotonaldehyde, Cyanide, N,N-Dimethylformamide, Ethylbenzene, styrene, Propylene oxide, Toluene and Xylene) was significantly associated with obesity or abdominal obesity. And also, more prospective studies and related experimental researches should be carried out to further demonstrate the conclusion of this study.


Asunto(s)
Compuestos Orgánicos Volátiles , Masculino , Humanos , Femenino , Compuestos Orgánicos Volátiles/metabolismo , Estudios Transversales , Obesidad Abdominal/epidemiología , Encuestas Nutricionales , Estudios Prospectivos , Obesidad/epidemiología
19.
Mater Today Bio ; 18: 100523, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36590980

RESUMEN

Intervertebral disc degeneration (IDD)-induced low back pain significantly influences the quality of life, placing a burden on public health systems worldwide. Currently available therapeutic strategies, such as conservative or operative treatment, cannot effectively restore intervertebral disc (IVD) function. Decellularized matrix (DCM) is a tissue-engineered biomaterial fabricated using physical, chemical, and enzymatic technologies to eliminate cells and antigens. By contrast, the extracellular matrix (ECM), including collagen and glycosaminoglycans, which are well retained, have been extensively studied in IVD regeneration. DCM inherits the native architecture and specific-differentiation induction ability of IVD and has demonstrated effectiveness in IVD regeneration in vitro and in vivo. Moreover, significant improvements have been achieved in the preparation process, mechanistic insights, and application of DCM for IDD repair. Herein, we comprehensively summarize and provide an overview of the roles and applications of DCM for IDD repair based on the existing evidence to shed a novel light on the clinical treatment of IDD.

20.
Front Pharmacol ; 14: 1122104, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36713841

RESUMEN

Neurodegenerative diseases (NDs) are disorders characterized by degenerative degeneration of neurons and loss of their function. NDs have a complicated pathophysiology, of which neuroinflammation and neuronal death are significant factors. The inflammatory process known as pyroptosis ("fiery death") is caused by a family of pore-forming proteins called Gasdermins (GSDMs), which appears downstream from the activation of the inflammasome. Clear evidence of enhanced pyroptosis-related proteins activity in common NDs has coincided with abnormal aggregation of pathological proteins (such as Aß, tau, α-synuclein et al.), making pyroptosis an attractive direction for the recent study of NDs. The purpose of this review is to provide an overview of the molecular mechanisms driving pyroptosis, the mechanistic links between pyroptosis and NDs, and emerging therapeutic strategies in Traditional Chinese Medicine (TCM) to inhibit pyroptosis for the treatment of NDs.

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