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1.
Adv Mater ; : e2314175, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635920

RESUMO

Sorption-based atmospheric water harvesting (SAWH) is a promising technology to alleviate freshwater scarcity. Recently, hygroscopic salt-hydrogel composites (HSHCs) have emerged as attractive candidates with their high water uptake, versatile designability, and scale-up fabrication. However, achieving high-performance SAWH applications for HSHCs has been challenging because of their sluggish kinetics, attributed to their limited mass transport properties. Herein, a universal network engineering of hydrogels using a cryogelation method is presented, significantly improving the SAWH kinetics of HSHCs. As a result of the entangled mesh confinements formed during cryogelation, a stable macroporous topology is attained and maintained within the obtained entangled-mesh hydrogels (EMHs), leading to significantly enhanced mass transport properties compared to conventional dense hydrogels (CDHs). With it, corresponding hygroscopic EMHs (HEMHs) simultaneously exhibit faster moisture sorption and solar-driven water desorption. Consequently, a rapid-cycling HEMHs-based harvester delivers a practical freshwater production of 2.85 Lwater kgsorbents -1 day-1 via continuous eight sorption/desorption cycles, outperforming other state-of-the-art hydrogel-based sorbents. Significantly, the generalizability of this strategy has been validated by extending it to other hydrogels used in HSHCs. Overall, this work offers a new approach to efficiently address long-standing challenges of sluggish kinetics in current HSHCs, promoting them toward the next-generation SAWH applications. This article is protected by copyright. All rights reserved.

2.
Cancer Lett ; 585: 216647, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38301911

RESUMO

The Notch signaling pathway plays pivotal roles in cell proliferation, stemness and invasion of non-small cell lung cancer (NSCLC). The human Notch family consists of four receptors, namely Notch1, Notch2, Notch3, and Notch4. These receptors are transmembrane proteins that play crucial roles in various cellular processes. Notch1 mostly acts as a pro-carcinogenic factor in NSCLC but sometimes acts as a suppressor. Notch2 has been demonstrated to inhibit the growth and progression of NSCLC, whereas Notch3 facilitates these biological behaviors of NSCLC. The role of Notch4 in NSCLC has not been fully elucidated, but it is evident that Notch4 promotes tumor progression. At present, drugs targeting the Notch pathway are being explored for NSCLC therapy, a majority of which are already in the stage of preclinical research and clinical trials, with bright prospects in the clinical treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptor Notch1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores Notch/metabolismo , Receptor Notch2/metabolismo , Receptor Notch3 , Transdução de Sinais
3.
Cell Rep ; 43(2): 113703, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38265933

RESUMO

Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell differentiation, whose role in organogenesis remains elusive. Here, by combination of cleavage under targets and tagmentation (CUT&Tag), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing, we show a dramatic increase in the H3K36me3 level from the secondary transition phase and decipher the related transcriptional alteration. Using single-cell RNA sequencing, we define that pancreatic deletion of Setd2 results in abnormalities in both exocrine and endocrine lineages: hyperproliferative tip progenitor cells lead to abnormal differentiation; Ngn3+ endocrine progenitors decline due to the downregulation of Nkx2.2, leading to insufficient endocrine development. Thus, these data identify SETD2 as a crucial player in embryonic pancreas development, providing a clue to understanding the dysregulation of histone modifications in pancreatic disorders.


Assuntos
Cromatina , Pâncreas , Animais , Camundongos , Diferenciação Celular , Histona-Lisina N-Metiltransferase/genética , Organogênese/genética
4.
Diabetes ; 73(2): 237-249, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37963393

RESUMO

The important role of m6A RNA modification in ß-cell function has been established; however, how it regulates pancreatic development and endocrine differentiation remains unknown. Here, we generated transgenic mice lacking RNA methyltransferase-like 3 (Mettl3) specifically in Pdx1+ pancreatic progenitor cells and found the mice with the mutation developed hyperglycemia and hypoinsulinemia at age 2 weeks, along with an atrophic pancreas, reduced islet mass, and abnormal increase in ductal formation. At embryonic day 15.5, Mettl3 deletion had caused a significant loss of Ngn3+ endocrine progenitor cells, which was accompanied by increased Sox9+ ductal precursor cells. We identified histone deacetylase 1 (Hdac1) as the critical direct m6A target in bipotent progenitors, the degeneration of which caused abnormal activation of the Wnt/Notch signaling pathway and blocked endocrine differentiation. This transformation could be manipulated in embryonic pancreatic culture in vitro through regulation of the Mettl3-Hdac1-Wnt/Notch signaling axis. Our finding that Mettl3 determines endocrine lineage by modulating Hdac1 activity during the transition of bipotent progenitors might help in the development of targeted endocrine cell protocols for diabetes treatment.


Assuntos
Adenina/análogos & derivados , Pâncreas , Via de Sinalização Wnt , Camundongos , Animais , Pâncreas/metabolismo , Camundongos Transgênicos , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo
5.
Graefes Arch Clin Exp Ophthalmol ; 262(3): 847-855, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37672101

RESUMO

OBJECTIVE: To study the effect of astigmatism correction, rotational stability, and related factors of two different haptic type toric intraocular lenses. METHODS: A prospective, randomized, controlled trial. Cataract patients with preoperative corneal astigmatism of > 1 D were randomly implanted with C-loop haptic toric IOL (AcrySof-toric IOL) (group A) or plate-haptic toric IOL (AT TORBI 709 M IOL) (group B). The residual astigmatism, intraocular lens rotation, and visual quality were determined and compared between the two groups at 3 months after surgery. RESULTS: Seventy-nine eyes were included in this study, including 40 eyes in the group A and 39 eyes in the group B. No significant difference in preoperative visual acuity, intraocular pressure, and ophthalmic biological parameters was found between the two groups. There was no significant difference in residual astigmatism between the two groups at 3 months after surgery (P > 0.05). The rotation degree in the group A was 3.85 ± 2.92°, the rotation degree in the group B was 2.33 ± 2.31°, and a significant difference in intraocular lens rotation was identified between the two groups (P < 0.05). Upon exploring the rotation-related factors of the two different haptic type toric intraocular lenses, the rotation after implanting C-loop haptic toric IOL was positively correlated with axial length (Pearson r = 0.522, P = 0.01) and corneal white-to-white distance (Pearson correlation analysis r = 0.356, P = 0.024). CONCLUSIONS: The two different haptic type toric intraocular lenses effectively corrected regular corneal astigmatism and provided a good rotational stability after surgery. But the stability of plate-haptic toric IOL was better than that of C-loop haptic toric IOL. The rotational stability of C-loop haptic toric IOL was often related to axial length and corneal white-to-white distance.


Assuntos
Astigmatismo , Doenças da Córnea , Lentes Intraoculares , Humanos , Astigmatismo/cirurgia , Tecnologia Háptica , Estudos Prospectivos , Córnea
6.
Materials (Basel) ; 16(15)2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37570174

RESUMO

The water retention curve (WRC) of a geosynthetic clay liner (GCL) is influenced by the presence of exchangeable cations in the leachate during changes in water content in a landfill construction. This research aims to investigate the impact of salinity on the WRC of GCL. To measure the WRC of GCL under different sodium chloride (NaCl) concentrations on the drying path, a chilled-mirror dew-point device capable of controlling the GCL's volume was employed. Additionally, the dry state microstructure of the GCL was examined using electron microscopy. The test outcomes indicate that GCL hydrated with higher salinity has greater suction at the same water content during drying. This influence can be attributed to changes in salinity and the precipitation of NaCl crystals within the bentonite when water evaporates, which in turn affects the bentonite's microstructure and leads to increased matric suction. By introducing the Fredlund and Xing model and parameter relationship, it is possible to predict the WRC of GCL under salinity effects after measuring the WRC under different salinity conditions on the drying path.

7.
Sci Rep ; 13(1): 11354, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443369

RESUMO

There are various internal fixation methods in treating lumbosacral spinal tuberculosis. The study compared the stability and stress distribution in surrounding tissues/implants, such as discs, endplates and screw-rod internal fixation system, etc. when applying three different lumbar internal fixation methods to treat lumbosacral spinal tuberculosis. A finite element model was constructed and validated. The spinal stability was restored using three methods: a titanium cage with lateral double screw-rod fixation (group 1), autologous bone with posterior double screw-rod fixation (group 2), and a titanium cage with posterior double screw-rod fixation (group 3). For comparison, group 4 represented the intact L3-S1 spine. Finally, a load was applied, and the ranges of motion and Von Mises stresses in the cortical endplates, screw-rod internal fixation system and cortical bone around the screws in the different groups were recorded and analyzed. All six ranges of motion (flexion, extension, left/right lateral bending, left/right rotation) of the surgical segment were substantially lower in groups 1 (0.53° ~ 1.41°), 2 (0.68° ~ 1.54°) and 3 (0.55° ~ 0.64°) than in group 4 (4.48° ~ 10.12°). The maximum stress in the screw-rod internal fixation system was clearly higher in group 2 than in groups 1 and 3 under flexion, left/right lateral bending, and left/right rotation. However, in extension, group 1 had the highest maximum stress in the screw-rod internal fixation system. Group 2 had the lowest peak stresses in the cortical endplates in all directions. The peak stresses in the cortical bone around the screws were higher in group 1 and group 2 than in group 3 in all directions. Thus, titanium cage with posterior double screw-rod fixation has more advantages in immediate reconstruction of lumbosacral spinal stability and prevention of screw loosening.


Assuntos
Fusão Vertebral , Tuberculose da Coluna Vertebral , Humanos , Análise de Elementos Finitos , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/cirurgia , Titânio , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Rotação , Fenômenos Biomecânicos , Fusão Vertebral/métodos , Amplitude de Movimento Articular
8.
Phys Rev Lett ; 130(25): 256701, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37418721

RESUMO

The interaction between acoustic wave and magnetization in ferromagnetic thin films has attracted great attention due to its interesting physics and potential applications. However, up to now, the magneto-acoustic interaction has mainly been studied on the basis of magnetostriction. In this Letter, we develop a phase field model of magneto-acoustic interaction based on the Einstein-de Haas effect, and predict the acoustic wave during the ultrafast core reversal of magnetic vortex in a ferromagnetic disk. Because of the Einstein-de Haas effect, the ultrafast change of magnetization at the vortex core leads to a large mechanical angular momentum, which induces a body couple at the vortex core and excites a high-frequency acoustic wave. Moreover, the displacement amplitude of the acoustic wave is highly dependent on the gyromagnetic ratio. The smaller the gyromagnetic ratio is, the larger the displacement amplitude is. The present work not only provides a new mechanism for dynamic magnetoelastic coupling but also sheds new insights on the magneto-acoustic interaction.


Assuntos
Acústica , Som , Física , Movimento (Física) , Aminas , Fenômenos Magnéticos
9.
IEEE Trans Pattern Anal Mach Intell ; 45(10): 11856-11868, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37192026

RESUMO

Pre-training on large-scale datasets has played an increasingly significant role in computer vision and natural language processing recently. However, as there exist numerous application scenarios that have distinctive demands such as certain latency constraints and specialized data distributions, it is prohibitively expensive to take advantage of large-scale pre-training for per-task requirements. we focus on two fundamental perception tasks (object detection and semantic segmentation) and present a complete and flexible system named GAIA-Universe(GAIA), which could automatically and efficiently give birth to customized solutions according to heterogeneous downstream needs through data union and super-net training. GAIA is capable of providing powerful pre-trained weights and searching models that conform to downstream demands such as hardware constraints, computation constraints, specified data domains, and telling relevant data for practitioners who have very few datapoints on their tasks. With GAIA, we achieve promising results on COCO, Objects365, Open Images, BDD100 k, and UODB which is a collection of datasets including KITTI, VOC, WiderFace, DOTA, Clipart, Comic, and more. Taking COCO as an example, GAIA is able to efficiently produce models covering a wide range of latency from 16 ms to 53 ms, and yields AP from 38.2 to 46.5 without whistles and bells. GAIA is released at https://github.com/GAIA-vision.

10.
Graefes Arch Clin Exp Ophthalmol ; 261(9): 2557-2565, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37004517

RESUMO

OBJECTIVE: This study aimed to evaluate the visual performance and rotational stability of the multifocal toric intraocular lens in myopes. METHODS: This prospective, observational study included patients with an axial length of ≥24.5 mm and regular corneal astigmatism of >1 diopter who underwent phacoemulsification cataract surgery and implantation of a multifocal toric intraocular lens (AT LISA toric 909M). The visual acuity, defocus curves, residual astigmatism, rotational stability, higher-order aberrations (HOAs), modulation transfer function (MTF), spectacle dependence and patient satisfaction were evaluated 3 months after surgery. RESULTS: Forty-three eyes from 30 patients were enrolled in this study. Postoperatively, uncorrected distance and near visual acuities (logMAR) were 0.09 ± 0.08 (standard deviation, SD) and 0.14 ± 0.08, respectively. The defocus curve analysis provided a bimodal curve showing two peaks of maximum vision at 0.0 D and at -3.0 D defocus level. The multifocal toric intraocular lens showed excellent rotational stability; the mean rotation was 4.02 ± 2.49 (SD) degrees at 3 months postoperatively. Refractive predictability was excellent with a mean spherical equivalent of 0.19 ± 0.37 (SD) diopters (D) and a mean refractive cylinder of -0.34 ± 0.39 (SD) D. CONCLUSIONS: The diffractive multifocal toric intraocular lens, AT LISA toric 909M, provided effective distance and near visual acuities in myopic eyes. It was a predictable and effective device with good rotational stability for the correction of preexisting astigmatism during cataract surgery. In this study, more than 80% of patients achieved spectacle independence.


Assuntos
Astigmatismo , Catarata , Lentes Intraoculares , Facoemulsificação , Humanos , Implante de Lente Intraocular , Astigmatismo/complicações , Astigmatismo/cirurgia , Estudos Prospectivos , Refração Ocular , Catarata/complicações
11.
iScience ; 25(11): 105300, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36304103

RESUMO

Testosterone is essential to human growth and development as well as immune regulation. Zika virus (ZIKV), an emerging arbovirus associated with neurological complications including neuroinflammation, can also cause testicular damage and decrease testosterone secretion. However, whether the dysregulation of testosterone plays a role in the process of neuroinflammation during ZIKV pathogenesis is still unclear. In this study, we found that ZIKV infection caused testicular damage and decreased testosterone secretion in male mice, and testosterone supplementation after ZIKV infection reduced their mortality and attenuated the pathological symptoms. Further investigation revealed that testosterone treatment after ZIKV infection alleviated inflammation and nerve injury in the mouse brain. Additionally, reduced CD8+ T cell infiltration and interferon-gamma production were observed in brains of testosterone-treated mice. Overall, our results demonstrated that testosterone plays a protective role in ZIKV-infected mice, and thus it can be developed as a potential therapeutic drug against ZIKV infection.

12.
Ophthalmic Res ; 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36223730

RESUMO

PURPOSE: To analyze the incidence and outcomes of repositioning surgery to correct misalignment of several toric intraocular lenses (IOLs) after cataract surgery. METHODS: In this retrospective study, patients who underwent repositioning surgery to correct misalignment of toric IOLs following cataract surgery between January 2019 and December 2021 were enrolled. The medical data on patients' age, gender, preoperative axial length, corneal astigmatism, the axis of astigmatism, IOL models, IOL axis, uncorrected distance visual acuity, residual refraction, and postoperative outcomes were analyzed. RESULTS: Among the 1135 eyes implanted with toric IOLs at Qingdao Eye Hospital, 23 (2.026%, 23/1135) underwent repositioning surgery. Univariate analysis revealed that the incidence of repositioning surgery was significantly lower with AcrySof (0.636%, 5/786) than with ZEISS (2.959%, 5/169) and TECNIS (7.222%, 13/180) IOL platforms; The incidence of repositioning surgery with monofocal toric IOLs (1.169%, 11/941) was significantly lower than multifocal toric IOLs (6.186%, 12/194) (P<0.001); Additionally, a significant difference in age was also observed (P=0.002). Multivariate logistic regression analysis showed that IOL platform (P=0.004) and younger age (P=0.006) were independent risk factors for repositioning surgery. CONCLUSION: The incidence of repositioning surgery of toric IOLs after cataract surgery was 2.026%. It was linked to the IOL platform, multifocal toric IOLs, and younger age.

13.
J Clin Endocrinol Metab ; 107(12): 3231-3241, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36125175

RESUMO

CONTEXT: Diabetes is an age-related disease; however, the mechanism underlying senescent beta cell failure is still unknown. OBJECTIVE: The present study was designed to investigate whether and how the differentiated state was altered in senescent human beta cells by excluding the effects of impaired glucose tolerance. METHODS: We calculated the percentage of hormone-negative/chromogranin A-positive endocrine cells and evaluated the expressions of forkhead box O1 (FoxO1) and Urocortin 3 (UCN3) in islets from 31 nondiabetic individuals, divided into young (<40 years), middle-aged (40-60 years) and elderly (>60 years) groups. We also assessed adaptive unfolded protein response markers glucose-regulated protein 94 (GRP94), and spliced X-box binding protein 1 (XBP1s) in senescent beta cells and their possible contributions to maintaining beta cell identity and differentiation state. RESULTS: We found an almost 2-fold increase in the proportion of dedifferentiated cells in elderly and middle-aged groups compared with the young group (3.1 ± 1.0% and 3.0 ± 0.9% vs 1.7 ± 0.5%, P < .001). This was accompanied by inactivation of FoxO1 and loss of UCN3 expression in senescent human beta cells. In addition, we demonstrated that the expression levels of adaptive unfolded protein response (UPR) components GRP94 and XBP1s declined with age. In vitro data showed knockdown GRP94 in Min6-triggered cells to dedifferentiate and acquire progenitor features, while restored GRP94 levels in H2O2-induced senescent Min6 cells rescued beta cell identity. CONCLUSION: Our finding highlights that the failure to establish proper adaptive UPR in senescent human beta cells shifts their differentiated states, possibly representing a crucial step in the pathogenesis of age-related beta cell failure.


Assuntos
Desdiferenciação Celular , Células Secretoras de Insulina , Pessoa de Meia-Idade , Humanos , Idoso , Peróxido de Hidrogênio/metabolismo , Células Secretoras de Insulina/metabolismo , Resposta a Proteínas não Dobradas , Glucose/metabolismo , Envelhecimento
14.
Ophthalmic Res ; 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35970172

RESUMO

OBJECTIVE: The objective of this study was to determine the toxic effect and clinical characteristics of 1 mg/ml cefuroxime sodium on retinas after phacoemulsification in vitrectomized eyes. METHODS: Cataract patients with vitrectomized eyes were studied retrospectively. Phacoemulsification combined with intraocular lens implantation was performed uneventfully. Best Corrected Visual Acuity(BCVA), intraocular pressure(IOP), fundus photography, macular central thickness, and angiography were collected and analyzed. They were studied in patients with macular edema to evaluate macular toxicity. RESULTS: 92 cases (92 eyes) were enrolled, including 44 eyes of males and 48 eyes of females with an average age of 55.35 ± 12.32 years. Univariate analysis showed that the intraoperative use of balanced salt solution (BSS) containing 1 mg/ml cefuroxime sodium compound electrolyte and macular involvement in primary vitrectomy were important risk factors for macular edema on the first day after cataract surgery (P < 0.05). In addition, the characteristics of this kind of macular edema were studied; the thickness of macular fovea was significantly high at 1-day follow-up (P < 0.05), but there was no difference between pre-operation and 1-week post-operation (P > 0.05). CONCLUSION: Low-concentration cefuroxime sodium can cause acute macular edema in vitrectomized eyes, which can heal within one week after surgery.

15.
Mol Metab ; 64: 101559, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35940555

RESUMO

OBJECTIVE: The mechanistic target of rapamycin complex 1 (mTORC1) is a key molecule that links nutrients, hormones, and growth factors to cell growth/function. Our previous studies have shown that mTORC1 is required for ß-cell functional maturation and identity maintenance; however, the underlying mechanism is not fully understood. This work aimed to understand the underlying epigenetic mechanisms of mTORC1 in regulating ß-cell functional maturation. METHODS: We performed Microarray, MeDIP-seq and ATAC-seq analysis to explore the abnormal epigenetic regulation in 8-week-old immature ßRapKO islets. Moreover, DNMT3A was overexpressed in ßRapKO islets by lentivirus, and the transcriptome changes and GSIS function were analyzed. RESULTS: We identified two major epigenetic silencing mechanisms, DNMT3A-dependent DNA methylation and PRC2-dependent H3K27me3 modification, which are responsible for functional immaturity of Raptor-deficient ß-cell. Overexpression of DNMT3A partially reversed the immature transcriptome pattern and restored the impaired GSIS in Raptor-deficient ß-cells. Moreover, we found that Raptor directly regulated PRC2/EED and H3K27me3 expression levels, as well as a group of immature genes marked with H3K27me3. Combined with ATAC-seq, MeDIP-seq and ChIP-seq, we identified ß-cell immature genes with either DNA methylation and/or H3K27me3 modification. CONCLUSION: The present study advances our understanding of the nutrient sensor mTORC1, by integrating environmental nutrient supply and epigenetic modification, i.e., DNMT3A-mediated DNA methylation and PRC2-mediated histone methylation in regulating ß-cell identity and functional maturation, and therefore may impact the disease risk of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Epigênese Genética , Metilação de DNA/genética , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética/genética , Histonas/genética , Histonas/metabolismo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo
16.
J Endocrinol ; 255(1): 1-9, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35695299

RESUMO

Graves' disease (GD) is characterized by dysregulation of the immune system with aberrant immune cell function. However, there have been few previous studies on the role of monocytes in the pathology of GD. The object of this study was to investigate whether and how monocytes participate in GD pathology. CD14+ monocytes were isolated from untreated initial GD patients and healthy controls. Then, RNA-seq was performed to investigate changes in global mRNA expression in monocytes and found that type I interferon (IFN) signalling was among the top upregulated signalling pathways in GD monocytes. Type I IFN-induced sialic acid-binding immunoglobulin-like lectin1 (SIGLEC1) expression was significantly upregulated in untreated GD patients and correlated with thyroid parameters. Patient serum SIGLEC1 concentrations were reduced after anti-thyroid drug treatment. Inhibiting SIGLEC1 expression could inhibit proinflammatory cytokine (IL-1ß, IL-6, IL-8, IL-10 and M-CSF) expression in monocytes. In conclusion, our study suggested that type I IFN-mediated monocyte activation could have a deleterious effect on the pathogenesis of GD. These observations indicated that the inhibition of type I IFN-activated monocytes/macrophages could have a therapeutic effect on GD remission.


Assuntos
Doença de Graves , Interferon Tipo I , Lectinas , Proteínas de Membrana , Monócitos , Doença de Graves/genética , Doença de Graves/imunologia , Humanos , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Lectinas/genética , Lectinas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Monócitos/imunologia , Transdução de Sinais
17.
Int J Biol Markers ; 37(2): 134-139, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35345938

RESUMO

BACKGROUND: The monitoring of anti-p53 auto-antibodies in the peripheral blood has been used in cancer management; however, their clinical significance alone is limited. This pilot study aimed to describe the prevalence of elevated anti-p53 in newly diagnosed or recurrent upper gastrointestinal cancer or colorectal cancer in Chinese subjects. It also evaluated whether the addition of anti-p53 to a set of established tumor markers would allow for the detection of additional cancer cases than when using these markers alone. METHODS: A total of 573 subjects, including 187 healthy individuals, 169 patients with upper gastrointestinal cancer and 217 patients with colorectal cancer were included in this observational, prospective study. All subjects were required to provide up to 10 mL of blood. The following biomarkers were measured: anti-p53, carcinoembryonic antigen, cancer antigen (CA)19-9, and CA72-4. RESULTS: At the cutoff of 0.02 µg/mL, the sensitivity of anti-p53 in early-stage upper gastrointestinal cancer and colorectal cancer was 8.16% and 26.4%, and in late-stage disease was 7.81 and 28.0%, respectively. The specificity of anti-p53 in the healthy cohort at this cutoff was 98.4%. By adding anti-p53 to other tumor markers, the sensitivities were increased by 8.88%-9.47% in upper gastrointestinal cancer, and by 18.06%-25.00% in colorectal cancer; specificities decreased by 1%-2%. CONCLUSION: The addition of anti-p53 to established tumor markers may improve their diagnostic value for patients with colorectal cancer.


Assuntos
Neoplasias Colorretais , Neoplasias Gastrointestinais , Anticorpos , Biomarcadores Tumorais , Antígeno CA-19-9 , Antígeno Carcinoembrionário , China/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Gastrointestinais/epidemiologia , Humanos , Projetos Piloto , Prevalência , Estudos Prospectivos
18.
J Clin Invest ; 131(24)2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34907913

RESUMO

Type 2 diabetes (T2D) is associated with defective insulin secretion and reduced ß cell mass. Available treatments provide a temporary reprieve, but secondary failure rates are high, making insulin supplementation necessary. Reversibility of ß cell failure is a key translational question. Here, we reverse engineered and interrogated pancreatic islet-specific regulatory networks to discover T2D-specific subpopulations characterized by metabolic inflexibility and endocrine progenitor/stem cell features. Single-cell gain- and loss-of-function and glucose-induced Ca2+ flux analyses of top candidate master regulatory (MR) proteins in islet cells validated transcription factor BACH2 and associated epigenetic effectors as key drivers of T2D cell states. BACH2 knockout in T2D islets reversed cellular features of the disease, restoring a nondiabetic phenotype. BACH2-immunoreactive islet cells increased approximately 4-fold in diabetic patients, confirming the algorithmic prediction of clinically relevant subpopulations. Treatment with a BACH inhibitor lowered glycemia and increased plasma insulin levels in diabetic mice, and restored insulin secretion in diabetic mice and human islets. The findings suggest that T2D-specific populations of failing ß cells can be reversed and indicate pathways for pharmacological intervention, including via BACH2 inhibition.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/antagonistas & inibidores , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Sinalização do Cálcio , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética , Células Secretoras de Insulina/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Células HEK293 , Humanos
19.
J Environ Sci (China) ; 108: 145-151, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34465428

RESUMO

This study investigated a combined low-thermal and CaO2 pretreatment to enhance the volatile fatty acid (VFA) production from waste activated sludge (WAS). The fermentative product was added to a sequencing batch reactor (SBR) as an external carbon source to enhance nitrogen removal. The results showed that the combined pretreatment improved WAS solubilization, releasing more biodegradable substrates, such as proteins and polysaccharides, from TB-EPS to LB-EPS and S-EPS. The maximum VFA production of 3529 ± 188 mg COD/L was obtained in the combined pretreatment (0.2 g CaO2/g VS + 70 °C for 60 min), which was 2.1 and 1.4-fold of that obtained from the sole low-thermal pretreatment and the control test, respectively. Consequently, when the fermentative liquid was added as an external denitrification carbon source, the effluent total nitrogen decreased to Class A of the discharge standard for pollutants in rural wastewater treatment plants in most areas of China.


Assuntos
Nitrogênio , Esgotos , Reatores Biológicos , Desnitrificação , Ácidos Graxos Voláteis , Fermentação , Peróxidos
20.
Ther Clin Risk Manag ; 17: 917-926, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511918

RESUMO

PURPOSE: This study compared the clinical outcomes after cataract surgery with implantation of refractive rotationally asymmetric bifocal intraocular lens (IOL) (LS-313 MF30) and apodized diffractive bifocal IOL (ReSTOR SN6AD1). METHODS: This was a prospective, non-randomized, controlled study, where patients diagnosed with age-related cataracts were selected for phacoemulsification combined with bilateral IOL implantation. Based on the type of IOL voluntarily implanted, the patients were divided into two groups, ie, refractive and diffractive groups. In total, 30 cases (60 eyes) were in a refractive group, while 30 cases (60 eyes) were in diffractive group. Three months after surgery, we examined the uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), defocus curve, objective visual quality, and subjective questionnaire. RESULTS: Three months after surgery, the UIVA of the refractive group (0.18 ± 0.08) logMAR was better than that of the diffractive group (0.29 ± 0.16) logMAR (P < 0.05). No significant difference in UDVA and UNVA was noted between the two groups. For a 4mm pupil diameter, the intraocular and total eye aberration, higher-order aberration (HOA), coma, spherical aberration, and trefoil in the refractive group were significantly higher than those in diffractive group (P < 0.05). The intraocular modulation transfer function (MTF), intraocular strehl ratio (SR), total eye MTF, and total eye SR in the refractive group were lower than those in diffractive group (P < 0.05). No significant difference in glare incidence, spectacle independence rate, and patient satisfaction was observed between the two groups (P > 0.05). The halos incidence in the refractive group was lower than the diffractive group (P < 0.05). CONCLUSION: Both bifocal IOLs obtained satisfactory UDVA and UNVA, with higher patient satisfaction. Unlike the apodized diffractive bifocal IOL, the refractive rotationally asymmetric bifocal IOL yielded slightly better UIVA, lower halos incidence, whereas the apodized diffractive bifocal IOL showed a better objective visual quality.

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