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1.
Food Chem ; 402: 134518, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36303395

RESUMO

Ethyl vanillin is an important synthetic flavor that occupies a large market share in food additives. However, the shortcomings in terms of too fast aroma release rate and poor powder properties have severely limited its further application. In this work, the intrinsic mechanism of ethyl vanillin oiling-out process is revealed with the help of process analytical technologies. Further, a green and efficient spherical particles preparation technology is developed by constructing the oiling-out phase diagram of ethyl vanillin in the aqueous solution of sodium chloride. The ethyl vanillin spherical product has excellent powder properties with high bulk density (0.74 g/cm3), good sphericity (93.4 %), high flowability (29°), high yield (>95 %) and adjustable particle size distribution. More importantly, the spherical product exhibits 57.9 % lower aroma release rate at 323.15 K and 1400 % higher critical caking cycle compared to irregularly shaped powder, which confirms its sustained release and anti-caking function.


Assuntos
Benzaldeídos , Pós , Preparações de Ação Retardada , Solventes
2.
Artigo em Inglês | MEDLINE | ID: mdl-36220621

RESUMO

BACKGROUND: PDEs regulate cAMP levels which is critical for PKA activity-dependent activation of CREB-mediated transcription in learning and memory. Inhibitors of PDEs like PDE4 and Pde7 improve learning and memory in rodents. However, the role of PDE7 in cognition or learning and memory has not been reported yet. METHODS: Therefore, we aimed to explore the cognitive effects of a PDE7 subtype, PDE7a, using combined pharmacological and genetic approaches. RESULTS: PDE7a-nko mice showed deficient working memory, impaired novel object recognition, deficient spatial learning & memory, and contextual fear memory, contrary to enhanced cued fear memory, highlighting the potential opposite role of PDE7a in the hippocampal neurons. Further, pharmacological inhibition of PDE7 by AGF2.20 selectively strengthens cued fear memory in C57BL/6 J mice, decreasing its extinction but did not affect cognitive processes assessed in other behavioral tests. The further biochemical analysis detected deficient cAMP in neural cell culture with genetic excision of the PDE7a gene, as well as in the hippocampus of PDE7a-nko mice in vivo. Importantly, we found overexpression of PKA-R and the reduced level of pPKA-C in the hippocampus of PDE7a-nko mice, suggesting a novel mechanism of the cAMP regulation by PDE7a. Consequently, the decreased phosphorylation of CREB, CAMKII, eif2a, ERK, and AMPK, and reduced total level of NR2A have been found in the brain of PDE7a-nko animals. Notably, genetic excision of PDE7a in neurons was not able to change the expression of NR2B, BDNF, synapsin1, synaptophysin, or snap25. CONCLUSION: Altogether, our current findings demonstrated, for the first time, the role of PDE7a in cognitive processes. Future studies will untangle PDE7a-dependent neurobiological and molecular-cellular mechanisms related to cAMP-associated disorders.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Nucleotídeo Cíclico Fosfodiesterase do Tipo 7 , Memória de Curto Prazo , Aprendizagem Espacial , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Medo , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Sinaptofisina/metabolismo , Memória , Nucleotídeo Cíclico Fosfodiesterase do Tipo 7/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 7/metabolismo
3.
Carbohydr Polym ; 300: 120237, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36372504

RESUMO

The effects of dietary chitosan (0, 2, 4, 6, 8 and 10 g/kg) on the growth, health condition and disease resistance of golden pompano Trachinotus ovatus were evaluated. Dietary chitosan significantly enhanced weight gain, with the highest observed in fish fed the 6 g/kg chitosan diet. This chitosan level significantly promoted gut health by increasing villus length, lipase and protease activities and intestinal barrier-related genes expression. Meanwhile, dietary 6 g/kg chitosan improved the inflammatory response and anti-oxidative capacity of fish by regulating the expression of genes involved in NF-κB pathway and Nrf2 pathway, respectively. Furthermore, after challenge with Vibrio harveyi for 2 weeks, the survival rate increased significantly when dietary chitosan level was 6 g/kg. Overall, our results indicate that 6 g/kg chitosan is the optimal dose for enhancing growth, health and disease resistance of fish, but excessive chitosan (10 g/kg) weakens its beneficial effects.


Assuntos
Quitosana , Doenças dos Peixes , Perciformes , Vibrioses , Animais , Resistência à Doença , Quitosana/farmacologia , Perciformes/fisiologia , Ração Animal/análise , Doenças dos Peixes/tratamento farmacológico , Suplementos Nutricionais , Dieta , Peixes , Nível de Saúde , Imunidade Inata
4.
J Colloid Interface Sci ; 629(Pt A): 173-181, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36081202

RESUMO

HYPOTHESIS: Colloids with rough topography demonstrate more complex interactions and tremendous potential in industrial applications. However, relevant studies suffer from a range of challenges, including cumbersome synthesis, complex characterization, and very limited functionalities. A comprehensive study of rough nanoparticles can not only broaden our understanding of rough colloids, but also help to avoid some of their detrimental impacts in real life (e.g., clogging and pumping failures in slurry processing). EXPERIMENTS: A facile route to precisely control the surface roughness of silica nanoparticles and a highly efficient method to characterize the surface roughness were developed respectively. The fabricated particles can be applied for the immobilization of metal nanostructures; their cytotoxic effects and the capability to be used as a drug-delivery vehicle were also evaluated. FINDINGS: Modifying the addition time of precursors (i.e., TEOS and MPTMS) can precisely control the surface roughness of silica nanoparticles. The developed characterization method based on TEM observations allows statistical analyses on a large number of particles, and therefore features very reasonable accuracy. These rough particles behave like microporous materials, where the loading strategy is closely related to their surface roughness. Medium rough particles are promising carriers of metal nanostructures, while the roughest ones are excellent candidate for doxorubicin delivery to cancer cells.


Assuntos
Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , Nanopartículas/química , Doxorrubicina/farmacologia , Coloides/química , Sistemas de Liberação de Medicamentos
5.
J Affect Disord ; 321: 242-252, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36349650

RESUMO

BACKGROUND: Diosgenin is a well-known steroid saponin possessing neuroprotective activities. However, it is unknown whether diosgenin could alleviate depression-like symptoms. METHODS: The antidepressant-like effect of diosgenin was investigated in mice induced by chronic restraint stress. The effects of diosgenin on behaviors, inflammation, neuroendocrine, neurotrophic function, and gut microbiota were evaluated. RESULTS: The results showed that diosgenin alleviated the depressive-like behaviors in mice. In addition, diosgenin was found to reduce serum concentrations of proinflammatory cytokines and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Besides, diosgenin could activate hippocampal brain-derived neurotrophic factor (BDNF)/TrkB/ERK/CREB signaling pathway and improve the expression of postsynaptic protein PSD95. Meanwhile, the neurogenesis which was inhibited by chronic restraint stress, was totally reversed by diosgenin. Moreover, diosgenin increased the abundance of phylum Firmicutes and the genus Lactobacillus in stressed mice. The results further showed that diosgenin caused a strong correlation between gut microbiota composition and inflammation, the HPA axis activity, or hippocampus neurotrophic function. LIMITATIONS: Only male mice were used for evaluation in the present study, which limits the understanding of effects of diosgenin on the both sexes. In addition, the results only indicate microbiota at the phylum or genus mediate the regulation of neuroinflammation, neuroendocrine, and neurotrophic function, but does not elucidate how microbiota modulate the systems via their primary or secondary metabolites. CONCLUSIONS: The present study shows that diosgenin exerts the antidepressant activity, which is associated with the enhancement of neurotrophic function and the inhibition of inflammatory and neuroendocrine activities via the regulation of gut microbiota.


Assuntos
Diosgenina , Microbioma Gastrointestinal , Masculino , Feminino , Camundongos , Animais , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Inflamação/tratamento farmacológico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico
6.
Bioact Mater ; 20: 339-354, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35784639

RESUMO

Myocardial infarction (MI) leads to massive cardiomyocyte death and deposition of collagen fibers. This fibrous tissue disrupts electrical signaling in the myocardium, leading to cardiac systolic and diastolic dysfunction, as well as arrhythmias. Conductive hydrogels are a promising therapeutic strategy for MI. Here, we prepared a highly water-soluble conductive material (GP) by grafting polypyrrole (PPy) onto non-conductive gelatin. This component was added to the gel system formed by the Schiff base reaction between oxidized xanthan gum (OXG) and gelatin to construct an injectable conductive hydrogel. The prepared self-healing OGGP3 (3 wt% GP) hydrogel had good biocompatibility, elastic modulus, and electrical conductivity that matched the natural heart. The prepared biomaterials were injected into the rat myocardial scar tissue 2 days after MI. We found that the cardiac function of the rats treated with OGGP3 was improved, making it more difficult to induce arrhythmias. The electrical resistivity of myocardial fibrous tissue was reduced, and the conduction velocity of myocardial tissue was increased. Histological analysis showed reduced infarct size, increased left ventricular wall thickness, increased vessel density, and decreased inflammatory response in the infarcted area. Our findings clearly demonstrate that the OGGP3 hydrogel attenuates ventricular remodeling and inhibits infarct dilation, thus showing its potential for the treatment of MI.

7.
Ear Nose Throat J ; : 1455613221136360, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317416

RESUMO

OBJECTIVE: The purpose of this study was to analyze the difference of survival rates in paitents with oropharyngeal keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), basaloid squamous cell carcinoma (BSCC), and papillary squamous cell carcinoma (PSCC). MATERIALS AND METHODS: Patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2015 were collected from the SEER database. Cox proportional hazards models and Kaplan-Meier curves were used for survival analysis. Propensity score matching (PSM) was performed to adjust for the effect of confounding variables. Due to the small sample size of PSCC, this study did not perform PSM between it and other subtypes. RESULTS: The 5-year cancer-specific survival (CSS) rate of PSCC was higher than that of KSCC, NKSCC, and BSCC (0.627 vs. 0.812 vs. 0.789 vs. 0.875, P < 0.05); And the CSS rate of KSCC was lower than that of other subtypes both before and after PSM. In addition, the 5-year and 10-year CSS rates of BSCC were not different from NKSCC (P > 0.05), but not as good as NKSCC in the long term (P = 0.028). After PSM, the 5-year, 10-year, and long-term prognosis of BSCC were significantly worse than those of NKSCC (P < 0.001). CONCLUSION: The 5-year CSS of PSCC was better than the other three subtypes. The short-term prognosis of BSCC was not significantly different from NKSCC, but the long-term survival was lower than that of NKSCC, and the difference was more obvious after PSM. Meanwhile, the prognosis of KSCC was worst.

8.
Medicine (Baltimore) ; 101(43): e30783, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36316944

RESUMO

Laparoscopic surgery could be considered as an art of geometric algebra. However, very little is studied in the context of bariatric surgery. The current study aims to explore the possible influence concept of geometric algebra on the surgical process in the overweight and obese patients in the setting of laparoscopic sleeve gastrectomy (LSG). During the study period, clinical data of subjects who underwent LSG was retrospectively analyzed. Parameters examined include body mass index (BMI), umbilical-xiphoidal interval (U-X) and umbilical-fundus (U-F) interval. In this study, LSG was performed via central view approach (C) and left view approach (L). In both groups, the body surface projection points of viewing hole (V), main and accessory operating holes (O1 and O2) and surface display of fundus (F) were connected to form a geometric figure. The accessibility of the surgical instrument into the fundus, the need for elongated instruments and related intra- and post-operative parameters were noted. The overweight and obese subjects showed a significant increased U-X and U-F interval compared to the non-obese subjects. The length of both U-X and U-F interval were correlated with the BMI. The geometric figure is quite different between L and C approach with significant increase of area of quadrangle. Significant longer O1-F, O2-F and V-F interval was calculated in C approach of patients and thus the elongated instruments were frequently required. The integration of the concept geometric algebra with the proper selection of troca may provide a better surgical experience and smooth surgical process.


Assuntos
Cirurgia Bariátrica , Laparoscopia , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Sobrepeso , Gastrectomia , Índice de Massa Corporal , Obesidade/cirurgia , Resultado do Tratamento
9.
J Pain Res ; 15: 3381-3397, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36317163

RESUMO

Purpose: In this study, we aimed to systematically determine the trend, research hotspots, and directions of the future development of acupuncture for neuropathic pain (NP) by bibliometric analysis. Methods: Based on the relevant literature on acupuncture for NP in the databases of Web of Science from January 2002 to December 2021, Citespace software and VOSviewer were used to determine the use of acupuncture for the treatment of NP. The annual publications, countries, authors, research institutions, keywords, co-cited references, and journals were analyzed to explore the research hotspot and development trends in this field. Results: A total of 1462 records of acupuncture for NP from 2002 to 2021 were obtained. Chingliang Hsieh (20) is the most effective author and Han JS (585 co-citations) is the most influential author. The most productive institutions and countries are Kyung Hee UNIV (88) and China, respectively (480). UNIV Maryland of the USA has the highest centrality (0.12). Evidence-based complementary and alternative medicine (89) is the most prolific journal, and Pain is the most influential journal (4200 co-citations). Ji-sheng Han (2003) is the most frequently cited article (158 co-citations). Electroacupuncture, bee-venom acupuncture, and percutaneous electrical stimulation are the most commonly studied acupuncture types. The analgesic mechanism of acupuncture and acupuncture-neuroimaging was a research hotspot over the years. The clinical evidence of acupuncture for NP should be further studied in the future. Conclusion: The study using bibliometric analysis methods to investigate the publications on acupuncture for NP so as to provide potential research directions in the future.

10.
Front Bioeng Biotechnol ; 10: 1039777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329703

RESUMO

Peripheral nerve injury is a clinically common injury that causes sensory dysfunction and locomotor system degeneration, which seriously affects the quality of the patients' daily life. Long gapped defects in large nerve are difficult to repair via surgery and limited donor source of autologous nerve greatly challenges the successful nerve repair by transplantation. Significantly, remarkable progress has been made in repairing the peripheral nerve injury using artificial nerve grafts and a variety of products for peripheral nerve repair have emerged been approved globally in recent years. The raw materials of these commercial products includes natural/synthetic polymers, extracellular matrix. Despite a lot of effort, the desirable functional recovery still remains great challenges in long gapped nerve defects. Thus this review discusses the recent development of tissue engineering products for peripheral nerve repair and the design of bionic grafts improving the local microenvironment for accelerating nerve regeneration against locomotor disorder, which may provide potential strategies for the repair of long gaps or thick nerve defects by multifunctional biomaterials.

11.
J Dig Dis ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36326787

RESUMO

BACKGROUND AND OBJECTIVE: Systemic inflammatory responses are common in patients with chronic severe hepatitis (CSH) and increase their risk of mortality. Knowledge regarding the impact of the systemic inflammatory response on short-term outcomes in noncirrhotic CSH patients is limited. PATIENTS AND METHODS: We collected data from two prospective, multicenter cohorts from the CATCH-LIFE non-cirrhotic cohort. Cox regression was used to explore the association between systemic inflammation markers and 90-day liver transplant (LT)-free mortality. Generalized additive model (GAM) was used to illustrate the quantitative curve relationship between the neutrophil-to-lymphocyte ratio (NLR) and 90-day LT-free mortality. Kaplan-Meier methods were used to estimate the 90-year LT-free survival rates. RESULTS: The prevalence of CSH in the CATCH-LIFE study was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively. Noninfected patients accounted for 75% of CSH patients, and the NLR was independently associated with 90-day LT-free mortality. Quantitative analysis of the association between the NLR and 90-day LT-free mortality showed that an NLR of 2.9 may represent the starting point for disease deterioration in CSH patients without infection. CONCLUSIONS: This study identified the NLR as an independent risk factor for 90-day LT-free mortality in noncirrhotic CLD patients. The NLR can better indicate the systemic inflammatory response in noninfected CSH patients. An NLR of 2.9 may be the cutoff for disease aggravation onset in CSH patients without infection.

13.
Anal Chem ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36367403

RESUMO

Fast and on-site detection is important for an effective antigene-doping strategy. However, the current gene doping (GD) evaluation methods require sophisticated instruments and laborious procedures, limiting their field applications. This study proposes a CRISPR/Cas12a-based detection platform (termed CasGDP) combining CRISPR/Cas12a and multiplexed Recombinase Polymerase Amplification (RPA) for rapid evaluation of GD. CasGDP showed high specificity for identifying the putative target genes such as EPO, IGF-1, and GH-1. By using fluorescence as the readout, the method achieved a limit-of-detection of 0.1 nM and 1 aM for unamplified and amplified target plasmids, respectively. Additionally, an in vitro GD cell model was successfully established with the human EPO gene (hEPO). The results indicated that the hEPO gene transfection promoted the hEPO protein expression. Furthermore, trace amounts of EPO transgene spiked in human serum were efficiently measured by CasGDP with fluorescence- and lateral flow device (LFD)-based readouts in 40 min. Finally, we designed a multiplexed microfluidic device and realized simultaneous detection of the three transgenes via LFD embedded in the device. To our knowledge, this is the first work that combines the CRISPR-based system and multiplexed RPA for GD detection. We anticipate CasGDP to be widely used as a rapid, sensitive, and robust tool for GD evaluation.

15.
J Synchrotron Radiat ; 29(Pt 6): 1429-1435, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36345751

RESUMO

Brownian motion of Cowpea mosaic virus (CPMV) in water was measured using small-angle X-ray photon correlation spectroscopy (SA-XPCS) at 19.2 µs time resolution. It was found that the decorrelation time τ(Q) = 1/DQ2 up to Q = 0.091 nm-1. The hydrodynamic radius RH determined from XPCS using Stokes-Einstein diffusion D = kT/(6πηRH) is 43% larger than the geometric radius R0 determined from SAXS in the 0.007 M K3PO4 buffer solution, whereas it is 80% larger for CPMV in 0.5 M NaCl and 104% larger in 0.5 M (NH4)2SO4, a possible effect of aggregation as well as slight variation of the structures of the capsid resulting from the salt-protein interactions.


Assuntos
Comovirus , Comovirus/química , Espalhamento a Baixo Ângulo , Difração de Raios X , Capsídeo
16.
Front Public Health ; 10: 1038017, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353282

RESUMO

COVID-19, referred to as new coronary pneumonia, is an acute infectious disease caused by a new type of coronavirus SARS-CoV-2. To evaluate the effect of integrated Chinese medicine and Western medicine in patients with COVID-19 from overseas. Data were collected from 178 COVID-19 patients overseas at First Affiliated Hospital of Xiamen University from April 1, 2021 to July 31, 2021. These patients received therapy of integrated Chinese medicine and western medicine. Demographic data and clinical characteristics were extracted and analyzed. In addition, the prescription which induced less length of PCR positive days and hospitalization days than the median value was obtained. The top 4 frequently used Chinese medicine and virus-related genes were analyzed by network pharmacology and bioinformatics analysis. According to the chest computed tomography (CT) measurement, abnormal lung findings were observed in 145 subjects. The median length of positive PCR/hospitalization days was 7/7 days for asymptomatic subjects, 14/24 days for mild subjects, 10/15 days for moderate subjects, and 14/20 days for severe subjects. The most frequently used Chinese medicine were Scutellaria baicalensis (Huangqin), Glycyrrhiza uralensis (Gancao), Bupleurum chinense (Chaihu), and Pinellia ternata (Banxia). The putative active ingredients were baicalin, stigmasterol, sigmoidin-B, cubebin, and troxerutin. ACE, SARS-CoV-2 3CL, SARS-CoV-2 Spike, SARS-CoV-2 ORF7a, and caspase-6 showed good binding properties to active ingredients. In conclusion, the clinical results showed that integrated Chinese medicine and Western medicine are effective in treating COVID-19 patients from overseas. Based on the clinical outcomes, the putative ingredients from Chinese medicine and the potential targets of SARS-CoV-2 were provided, which could provide a reference for the clinical application of Chinese medicine in treating COVID-19 worldwide.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Medicina Tradicional Chinesa , Hospitalização
17.
Clin Exp Med ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385419

RESUMO

The introduction of immune checkpoint inhibitors (ICIs) has reshaped the therapy of hepatocellular carcinoma (HCC). ICIs are a novel therapy with frequent adverse events (AEs), including treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). However, no comprehensive overview of the toxicity spectrum of ICIs in HCC patients has been provided. Electronic databases were searched to identify eligible studies. A meta-analysis of the incidence rate of AEs in HCC patients treated with ICIs was performed. Lastly, the prognostic value of irAEs in HCC patients treated with ICIs was verified. Forty-seven studies with 6472 participations met the inclusion criteria. The pooled all-grade trAEs incidence rate was 83.4% (95% confidence interval [95% CI] 77.0-89.1%), ≥ grade 3 trAEs incidence rate was 33.0% (95% CI 26.9-39.5%), all-grade irAEs incidence rate was 34% (95% CI 22-47%), and ≥ grade 3 irAEs incidence rate was 9% (95% CI 5-14%). Aspartate aminotransferase (AST) increase (38%, 95% CI 35-40%) is the most common trAEs. Fatigue (14%, 95% CI 7-23%) is the most common irAEs. The pooled results also showed that 18.8% (95% CI 13.2-25.2%) of patients required systemic steroid therapy due to AEs, while 6.6% (95% CI 4.6-9.0%) of patients withdrew from treatment due to AEs. Additionally, patients experiencing irAEs may have a better progression-free survival (PFS) (multivariate analysis: hazard ratio [HR] = 0.41, 95% CI 0.27-0.61, I2 = 36.3%) but not overall survival (OS) (multivariate analysis: HR = 0.54, 95% CI 0.22-1.36, I2 = 83.2%) than those with no irAEs. Our study presents a systemic assessment of the AEs profile in HCC patients receiving ICIs, providing important reference for clinicians on toxicity profile. Besides, patients with irAEs may have a better PFS. More large-scale and prospective studies are needed to confirm our conclusions.

18.
Light Sci Appl ; 11(1): 323, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36357364

RESUMO

Flat lenses, including metalens and diffractive lens, have attracted increasing attention due to their ability to miniaturize the imaging devices. However, realizing a large scale achromatic flat lens with high performance still remains a big challenge. Here, we developed a new framework in designing achromatic multi-level diffractive lenses by light coherence optimization, which enables the implementation of large-scale flat lenses under non-ideal conditions. As results, a series achromatic polymer lenses with diameter from 1 to 10 mm are successfully designed and fabricated. The subsequent optical characterizations substantially validate our theoretical framework and show relatively good performance of the centimeter-scale achromatic multi-level diffractive lenses with a super broad bandwidth in optical wavelengths (400-1100 nm). After comparing with conventional refractive lens, this achromatic lens shows significant advantages in white-light imaging performance, implying a new strategy in developing practical planar optical devices.

19.
Cell Metab ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36351432

RESUMO

A hostile microenvironment in tumor tissues disrupts endoplasmic reticulum homeostasis and induces the unfolded protein response (UPR). A chronic UPR in both cancer cells and tumor-infiltrating leukocytes could facilitate the evasion of immune surveillance. However, how the UPR in cancer cells cripples the anti-tumor immune response is unclear. Here, we demonstrate that, in cancer cells, the UPR component X-box binding protein 1 (XBP1) favors the synthesis and secretion of cholesterol, which activates myeloid-derived suppressor cells (MDSCs) and causes immunosuppression. Cholesterol is delivered in the form of small extracellular vesicles and internalized by MDSCs through macropinocytosis. Genetic or pharmacological depletion of XBP1 or reducing the tumor cholesterol content remarkably decreases MDSC abundance and triggers robust anti-tumor responses. Thus, our data unravel the cell-non-autonomous role of XBP1/cholesterol signaling in the regulation of tumor growth and suggest its inhibition as a useful strategy for improving the efficacy of cancer immunotherapy.

20.
Glia ; 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36336959

RESUMO

ADGRG1 (also called GPR56) plays critical roles in brain development and wiring, including cortical lamination, central nervous system (CNS) myelination, and developmental synaptic refinement. However, the underlying mechanism(s) in mediating such diverse functions is not fully understood. Here, we investigate the function of one specific alternative splicing isoform, the GPR56 splice variant 4 (S4), to test the hypothesis that alternative splicing variants of GPR56 in part support its different functions. We created a new transgenic mouse line, Gpr56∆S4 , using CRISPR/Cas9, in which GPR56 S4 was deleted. Detailed phenotype analyses show that Gpr56∆S4 mice manifest no deficits in cortical architecture and CNS myelination compared to controls. Excitingly, they present significantly increased synapse densities, decreased synapse engulfment by microglia, and impaired eye-segregation. Taken together, our findings support that the GPR56 S4 variant is dispensable for cortical development and CNS myelination but is essential for microglia-mediated synaptic pruning.

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