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1.
Bioresour Technol ; : 130716, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641301

RESUMO

Oleanolic acid and its derivatives are widely used in the pharmaceutical, agricultural, cosmetic and food industries. Previous studies have shown that oleanolic acid production levels in engineered cell factories are low, which is why oleanolic acid is still widely extracted from traditional medicinal plants. To construct a highly efficient oleanolic acid production strain, rate-limiting steps were regulated by inducible promoters and the expression of key genes in the oleanolic acid synthetic pathway was enhanced. Subsequently, precursor pool expansion, pathway refactoring and diploid construction were considered to harmonize cell growth and oleanolic acid production. The multi-strategy combination promoted oleanolic acid production of up to 4.07 g/L in a 100 L bioreactor, which was the highest level reported.

2.
Neural Regen Res ; 19(10): 2157-2174, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38488550

RESUMO

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

3.
Research (Wash D C) ; 7: 0328, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550778

RESUMO

Pixel-level structure segmentations have attracted considerable attention, playing a crucial role in autonomous driving within the metaverse and enhancing comprehension in light field-based machine vision. However, current light field modeling methods fail to integrate appearance and geometric structural information into a coherent semantic space, thereby limiting the capability of light field transmission for visual knowledge. In this paper, we propose a general light field modeling method for pixel-level structure segmentation, comprising a generative light field prompting encoder (LF-GPE) and a prompt-based masked light field pretraining (LF-PMP) network. Our LF-GPE, serving as a light field backbone, can extract both appearance and geometric structural cues simultaneously. It aligns these features into a unified visual space, facilitating semantic interaction. Meanwhile, our LF-PMP, during the pretraining phase, integrates a mixed light field and a multi-view light field reconstruction. It prioritizes considering the geometric structural properties of the light field, enabling the light field backbone to accumulate a wealth of prior knowledge. We evaluate our pretrained LF-GPE on two downstream tasks: light field salient object detection and semantic segmentation. Experimental results demonstrate that LF-GPE can effectively learn high-quality light field features and achieve highly competitive performance in pixel-level segmentation tasks.

4.
J Med Chem ; 67(6): 4583-4602, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38498304

RESUMO

Toll-like receptor (TLR) 2 is a transmembrane receptor that participates in the innate immune response by forming a heterodimer with TLR1 or TLR6. TLR2 agonists play an important role in tumor therapy. Herein, we synthesized a series of 3-(2H-chromen-3-yl)-5-aryl-1,2,4-oxadiazole derivatives and identified WYJ-2 as a potent small and selective molecule agonist of TLR2/1, with an EC50 of 18.57 ± 0.98 nM in human TLR2 and TLR1 transient-cotransfected HEK 293T cells. WYJ-2 promoted the formation of TLR2/1 heterodimers and activated the nuclear factor kappa B (NF-κB) signaling pathway. Moreover, our study indicated that WYJ-2 could induce pyroptosis in cancer cells, mediated by activating the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. WYJ-2 exhibited effective anti-non-small cell lung cancer (NSCLC) activity in vitro and in vivo. The discovery that activating TLR2/1 induces pyroptosis in cancer cells may highlight the prospects of TLR2/1 agonists in cancer treatment in the future.


Assuntos
Neoplasias Pulmonares , Receptor 2 Toll-Like , Humanos , Receptor 2 Toll-Like/metabolismo , Receptor 1 Toll-Like/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Transdução de Sinais , NF-kappa B/metabolismo
5.
Orthop Surg ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488263

RESUMO

OBJECTIVES: Bankart lesion is one of the most common lesions of the glenohumeral joint. Several double-row suture methods were reported for Bankart repair, which could provide more stability, yet more motion limitation and complications. Therefore, we introduced a new double-row Bankart repair technique, key point double-row suture which used one anchor in the medial line. The purpose of this article is to investigate the clinical outcomes of this new method and to compare it with single-row suture. METHODS: Seventy-eight patients receiving key point double-row suture or single-row suture from October 2010 to June 2014 were collected retrospectively. The basic information including gender, age, dominant arm, and number of episodes of instability was collected. Before surgery, the glenoid bone loss was measured from the CT scan. The visual analogue scale, American shoulder and elbow surgeons, the University of California at Los Angeles shoulder scale, and subjective shoulder value were valued before surgery and at the last follow-up. RESULTS: Forty-four patients (24 patients receiving single-row suture and 20 patients receiving key point double-row suture) were followed up successfully. The follow-up period was 9.2 ± 1.1 years (range, 7.8-11.4 years). At the last follow-up, no significant differences were detected for any of the clinical scores. The recurrence rate was 12.5% for the single-row group and 10% for the double-row group, respectively (p = 0.795) 14 patients (31.8%) in the single-row group and nine patients (26.5%) in the double-row group were tested for active range of motion. A statistically significant difference was found only for the internal rotation at 90° abduction (48.9° for single-row and 76.7° for key point double-row, p = 0.033). CONCLUSION: The key point double-row sutures for Bankart lesions could achieve similar long-term outcomes compared with single-row suture, and one medial anchor did not result in a limited range of motion. The low recurrence rate and previous biomechanical results also indicate the key point double-row suture is a reliable method.

6.
Front Physiol ; 15: 1349253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505709

RESUMO

Introduction: Muscle and bone constitute the two main parts of the musculoskeletal system and generate an intricately coordinated motion system. The crosstalk between muscle and bone has been under investigation, leading to revolutionary perspectives in recent years. Method and results: In this review, the evolving concept of muscle-bone interaction from mechanical coupling, secretory crosstalk to stem cell exchange was explained in sequence. The theory of mechanical coupling stems from the observation that the development and maintenance of bone mass are largely dependent on muscle-derived mechanical loads, which was later proved by Wolff's law, Utah paradigm and Mechanostat hypothesis. Then bone and muscle are gradually recognized as endocrine organs, which can secrete various cytokines to modulate the tissue homeostasis and remodeling to each other. The latest view presented muscle-bone interaction in a more direct way: the resident mesenchymal stromal cell in the skeletal muscle, i.e., fibro-adipogenic progenitors (FAPs), could migrate to the bone injury site and contribute to bone regeneration. Emerging evidence even reveals the ectopic source of FAPs from tissue outside the musculoskeletal system, highlighting its dynamic property. Conclusion: FAPs have been established as the critical cell connecting muscle and bone, which provides a new modality to study inter-tissue communication. A comprehensive and integrated perspective of muscle and bone will facilitate in-depth research in the musculoskeletal system and promote novel therapeutic avenues in treating musculoskeletal disorders.

7.
J Craniofac Surg ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498013

RESUMO

This study aimed to introduce a surgery technique-Sommerlad-Furlow palatoplasty (SFP) and analyze the risk factors of velopharyngeal insufficiency (VPI) and palatal fistula after SFP. Cases after SFP under the age of 5 between 2011 and 2021 were reviewed, and the cases with complete follow-up information were included. Univariate and multivariate logistic regression were used to evaluate the effects of surgical age, surgery technique, surgeon's experience, and cleft type on velopharyngeal function and the occurrence of palatal fistula. SFP is a safe and effective procedure to increase the palatal length and reconstruct the levator veli palatini sling. The speech outcome after SFP was associated with cleft type and age at operation. Age = 1.285 years is the best cutoff value. The fistula occurrence was associated with cleft type only.

8.
Int J Hyg Environ Health ; 257: 114342, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401403

RESUMO

Growing evidences supported that arsenic exposure contributes to non-alcoholic fatty liver disease (NAFLD) risk, but findings were still inconsistent. Additionally, once absorbed, arsenic is methylated into monomethyl and dimethyl arsenicals. However, no studies investigated the association of arsenic metabolism with NAFLD. Our objectives were to evaluate the associations of arsenic exposure and arsenic metabolism with NAFLD prevalence. We conducted a case-control study with 1790 participants derived from Dongfeng-Tongji cohort and measured arsenic species (arsenite, arsenate, monomethylarsonate [MMA], dimethylarsinate [DMA], and arsenobetaine) in urine. Arsenic exposure (∑As) was defined as the sum of inorganic arsenic (iAs), MMA, and DMA. Arsenic metabolism was evaluated as the proportions of inorganic-related species (iAs%, MMA%, and DMA%) and methylation efficiency ratios (primary methylation index [PMI], secondary methylation index [SMI]). NAFLD was diagnosed by liver ultrasound. Logistic regression was used to evaluate the associations. The median of ∑As was 13.24 µg/g creatinine. The ∑As showed positive and nonlinear association with moderate/severe NAFLD (OR: per log-SD = 1.33, 95% CI: [1.03,1.71]; Pfor nonlinearity = 0.021). The iAs% (OR: per SD = 1.16, 95% CI: [1.03,1.30]) and SMI (OR: per log-SD = 1.16, 95% CI: [1.03,1.31]) showed positive while MMA% (OR: per SD = 0.80, 95% CI: [0.70,0.91]) and PMI (OR: per log-SD = 0.86, 95% CI: [0.77,0.96]) showed inverse associations with NAFLD. Moreover, the ORs (95% CI) of NAFLD for each 5% increase in iAs% was 1.36 (1.17,1.58) when MMA% decreased and 1.07 (1.01,1.13) when DMA% decreased; and for each 5% increase in MMA%, it was 0.74 (0.63,0.86) and 0.79 (0.69,0.91) when iAs% and DMA% decreased, respectively. The results suggest that inorganic arsenic exposure is positively associated with NAFLD risk and arsenic methylation efficiency plays a role in the NAFLD. The findings provide clues to explore potential interventions for the prevention of NAFLD. Prospective studies are needed to validate our findings.


Assuntos
Arsênio , Arsenicais , Hepatopatia Gordurosa não Alcoólica , Humanos , Arsênio/análise , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos de Casos e Controles , Exposição Ambiental , Arsenicais/urina , Ácido Cacodílico/urina
9.
Natl Sci Rev ; 11(3): nwad314, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38312384

RESUMO

Flexible devices and functional systems with elaborated three-dimensional (3D) architectures can endow better mechanical/electrical performances, more design freedom, and unique functionalities, when compared to their two-dimensional (2D) counterparts. Such 3D flexible devices/systems are rapidly evolving in three primary directions, including the miniaturization, the increasingly merged physical/artificial intelligence and the enhanced adaptability and capabilities of heterogeneous integration. Intractable challenges exist in this emerging research area, such as relatively poor controllability in the locomotion of soft robotic systems, mismatch of bioelectronic interfaces, and signal coupling in multi-parameter sensing. By virtue of long-time-optimized materials, structures and processes, natural organisms provide rich sources of inspiration to address these challenges, enabling the design and manufacture of many bioinspired 3D flexible devices/systems. In this Review, we focus on bioinspired 3D flexible devices and functional systems, and summarize their representative design concepts, manufacturing methods, principles of structure-function relationship and broad-ranging applications. Discussions on existing challenges, potential solutions and future opportunities are also provided to usher in further research efforts toward realizing bioinspired 3D flexible devices/systems with precisely programmed shapes, enhanced mechanical/electrical performances, and high-level physical/artificial intelligence.

10.
Int J Legal Med ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38332350

RESUMO

Bone age assessment (BAA) is crucial in various fields, including legal proceedings, athletic competitions, and clinical medicine. However, the use of X-ray methods for age estimation without medical indication is subject to ethical debate, especially in forensic and athletic fields. The application of magnetic resonance imaging (MRI) with non-ionizing radiation can overcome this limitation in BAA. This study aimed to compare the application value of several MRI modalities of proximal humeral in BAA. A total of 468 patients with shoulder MRIs were retrospectively collected from a Chinese Han population aged 12-30 years (259 males and 209 females) for training and testing, including T1 weighted MRI (T1WI), T2 weighted MRI (T2WI), and Proton density weighted MRI (PDWI). Optimal regression models were established for age estimation, yielding mean absolute error (MAE) values below 2.0 years. The MAE values of T1WI were the lowest, with 1.700 years in males and 1.798 years in females. The area under the curve (AUC) and accuracy values of different MRI modalities of 16-year and 18-year thresholds were all around 0.9. For the 18-year threshold, T1WI outperformed T2WI and PDWI. In conclusion, the three MRI modalities of the proximal humerus can serve as reliable indicators for age assessment, while the T1WI performed better in age assessment and classification.

11.
Sci Transl Med ; 16(734): eade7347, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38354227

RESUMO

Nonalcoholic fatty liver (NAFL) remains relatively benign, but high-risk to end-stage liver diseases become highly prevalent when it progresses into nonalcoholic steatohepatitis (NASH). Our current understanding of the development of NAFL to NASH remains insufficient. In this study, we revealed MAP kinase (MAPK) activation as the most notable molecular signature associated with NASH progression across multiple species. Furthermore, we identified suppressor of IKKε (SIKE) as a conserved and potent negative controller of MAPK activation. Hepatocyte-specific overexpression of Sike prevented NASH progression in diet- and toxin-induced mouse NASH models. Mechanistically, SIKE directly interacted with TGF-ß-activated kinase 1 (TAK1) and TAK1-binding protein 2 (TAB2) to interrupt their binding and subsequent TAK1-MAPK signaling activation. We found that indobufen markedly up-regulated SIKE expression and effectively improved NASH features in mice and macaques. These findings identify SIKE as a MAPK suppressor that prevents NASH progression and provide proof-of-concept evidence for targeting the SIKE-TAK1 axis as a potential NASH therapy.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transdução de Sinais/fisiologia , Hepatócitos/metabolismo , Perfilação da Expressão Gênica , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fígado/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
12.
Cell Prolif ; : e13610, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38356342

RESUMO

Orofacial muscle defect due to congenital anomalies, tumour ablation or traumatic accident that exceeds endogenous regeneration capacity may lead to sustained deficits in masticatory function and nutrition intake. Functional recovery has always been the goal of muscle tissue repair, but currently, there is no suitable model for quantitative analyses of either functional consequences or treatment efficacy of orofacial muscle defect. This study proposed a critical size volumetric muscle loss (VML) model in mouse masseter with impaired mastication on nutrition. Full-thickness VML defects in diameter of 1.0, 1.5, 2.0 and 3.0 mm were generated in the centre of the mouse masseter using a biopsy punch to determine the critical size for functional impairment. In the VML region, myogenesis was dampened but fibrogenesis was activated, as long with a reduction in the density of the neuromuscular junction and an increase in vascular density. Accordingly, persistent fibrosis was observed in the centre region of VML in all diameters. The 2.0 mm diameter was the critical threshold to masticatory function impairment after VML in the masseter. VML of 3.0 mm diameter led to a significant impact on nutrition intake and body weight gain. Autologous muscle graft effectively relieved the fibrosis and functional deficit after VML injury in the masseter. This model serves as a reliable tool in studying functional recovery strategies for orofacial muscle defects.

13.
Sci Total Environ ; 920: 170894, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38367736

RESUMO

Polypropylene microplastics (PP-MPs) are emerging environmental contaminants that have the potential to cause adverse effects on aquatic organisms. Reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) is a valuable tool for assessing the gene expression profiles under PP-MPs stress. To obtain an accurate gene expression profile of tissue inflammation and apoptosis that reflects the molecular mechanisms underlying the impact of PP-MPs on Chinese sturgeon, identifying reliable reference genes is crucial for RT-qPCR analysis. In this study, we constructed an experiment model of Chinese sturgeon exposed to PP-MPs, assessed the pathological injury, metabolic profile responses and oxidative stress in liver, evaluated the reliability of 8 reliable reference genes by 4 commonly used algorithms including GeNorm, NormFinder, BeatKeeper, Delta Ct, and then analyzed the performance of inflammatory response genes in liver, spleen and kidney with the best reference gene. HE staining revealed that the cytoplasm full small vacuoles and nucleus diameter increased were occurred in the liver cell of PP-MPs in treatment groups. Additionally, oxidative and biochemical parameters were significantly changes in the liver of treatment groups. For the reference genes in PP-MPs exposure experiments, this study screening the optimal reference genes including: EF1α and GAPDH for liver and spleen, and GAPDH and RPS18 for kidney. Besides, 2 inflammatory response genes (NLRP3, TNF-α) were chosen to assess the optimal reference genes using the least stable reference gene (TUB) as a control, verified the practicality of the select reference genes in different tissues. We also found that the low concentration of PP-MPs could induce the liver tissue damage and inflammatory response in Chinese sturgeon. Our study initially evaluated the impact of short-time exposure with PP-MPs in Chinese sturgeon and provided 3 sets of validated optimal reference genes in Chinese sturgeon exposure to PP-MPs.


Assuntos
Microplásticos , Plásticos , Animais , Polipropilenos/toxicidade , Reprodutibilidade dos Testes , Peixes , Reação em Cadeia da Polimerase em Tempo Real
14.
Plants (Basel) ; 13(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38337976

RESUMO

Although hydrogen gas (H2)-treated soil improves crop biomass, this approach appears difficult for field application due to the flammability of H2 gas. In this report, we investigated whether and how H2 applied in hydrogen nanobubble water (HNW) improves the yield and quality of cherry tomato (Lycopersicon esculentum var. cerasiforme) with and without fertilizers. Two-year-long field trials showed that compared to corresponding controls, HNW without and with fertilizers improved the cherry tomato yield per plant by 39.7% and 26.5% in 2021 (Shanghai), respectively, and by 39.4% and 28.2% in 2023 (Nanjing), respectively. Compared to surface water (SW), HNW increased the soil available nitrogen (N), phosphorus (P), and potassium (K) consumption regardless of fertilizer application, which may be attributed to the increased NPK transport-related genes in roots (LeAMT2, LePT2, LePT5, and SlHKT1,1). Furthermore, HNW-irrigated cherry tomatoes displayed a higher sugar-acid ratio (8.6%) and lycopene content (22.3%) than SW-irrigated plants without fertilizers. Importantly, the beneficial effects of HNW without fertilizers on the yield per plant (9.1%), sugar-acid ratio (31.1%), and volatiles (20.0%) and lycopene contents (54.3%) were stronger than those achieved using fertilizers alone. In short, this study clearly indicated that HNW-supplied H2 not only exhibited a fertilization effect on enhancing the tomato yield, but also improved the fruit's quality with a lower carbon footprint.

15.
J Clin Invest ; 134(5)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206764

RESUMO

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Inteligência Artificial , Dieta Hiperlipídica/efeitos adversos , Ácido Graxo Sintases/genética , Hepatopatia Gordurosa não Alcoólica/genética
16.
J Lipid Res ; 65(3): 100513, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38295985

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific Food and Drug Administration-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding molecular modulator in NAFLD, however, are still elusive. KDM1A, commonly known as lysine-specific histone demethylase 1, has been reported to increase glucose uptake in hepatocellular carcinoma. In addition, a recent study suggests that inhibition of KDM1A reduces lipid accumulation in primary brown adipocytes. We here investigated the role of KDM1A, one of the most important histone demethylases, in NAFLD. In this study, we observed a significant upregulation of KDM1A in NAFLD mice, monkeys, and humans compared to the control group. Based on these results, we further found that the KDM1A can exacerbate lipid accumulation and inflammation in hepatocytes and mice. Mechanistically, KDM1A exerted its effects by elevating chromatin accessibility, subsequently promoting the development of NAFLD. Furthermore, the mutation of KDM1A blunted its capability to promote the development of NAFLD. In summary, our study discovered that KDM1A exacerbates hepatic steatosis and inflammation in NAFLD via increasing chromatin accessibility, further indicating the importance of harnessing chromatin remodeling and epigenetic alteration in combating NAFLD. KDM1A might be considered as a potential therapeutic target in this regard.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Cromatina/genética , Histona Desmetilases/genética , Inflamação/genética , Lipídeos
17.
Nat Neurosci ; 27(2): 272-285, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38172439

RESUMO

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACCGlu) projecting to the VTA indirectly inhibit dopaminergic neurons (VTADA) by activating local GABAergic interneurons (VTAGABA), and this effect is reinforced after nerve injury. VTADA neurons in turn project to the ACC and synapse to the initial ACCGlu neurons to convey feedback information from emotional changes. Thus, an ACCGlu-VTAGABA-VTADA-ACCGlu positive-feedback loop mediates the progression to and maintenance of persistent pain and comorbid anxiodepressive-like behavior. Disruption of this feedback loop relieves hyperalgesia and anxiodepressive-like behavior in a mouse model of neuropathic pain, both acutely and in the long term.


Assuntos
Neuralgia , Área Tegmentar Ventral , Camundongos , Animais , Giro do Cíngulo , Hiperalgesia , Retroalimentação , Neurônios Dopaminérgicos/fisiologia , Ácido gama-Aminobutírico
18.
Microsc Res Tech ; 87(5): 922-932, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38173320

RESUMO

Bruchidius coreanus is a serious pest on Gleditsia sinensis Lam during seed storage, causing significant losses to their yield in southwest China. To gain insight into their behavioral mechanisms, the external morphology, ultrastructure, and distribution of sensilla on antennae, maxillary palps, and labial palps of both male and female B. coreanus were observed using a scanning electron microscope. The results revealed that both male and female adults had serrated antennae comprising a scape, a pedicel, and nine flagellomeres (F1-F9). There were eight types and seven subtypes of antenna sensilla observed in both sexes, including Böhm sensilla (BS), two subtypes of sensilla chaetica (SC1 and SC2), two subtypes of sensilla trichodea (ST1 and ST2), three subtypes of sensilla basiconica (SB1, SB2, and SB3), sensilla auricillica (SA), sensilla styloconicum (SS), capitate pegs (CP), and sensilla cavity (SCa). The average length of BS and ST (ST1 and ST2) showed significant differences between males and females. Furthermore, the number of SC (SC1 and SC2), ST1, and SCa differed significantly between the sexes. Four types of sensilla were found on the maxillary palps and labial palps, with the length of ST on these palps significantly differing between males and females. Additionally, SS on male labial palps was significantly longer than in females. The number of SC significantly differed between the male and female maxillary palps and labial palps, while ST and SS showed significant differences in the maxillary palps. These findings will contribute to further electrophysiological recording and behavioral research. RESEARCH HIGHLIGHTS: The external morphology and distribution of various sensilla on the antennae, maxillary palps, and labial palps of Bruchidius coreanus were described. Eight types and seven subtypes of antenna sensilla were observed on the antennae, while four types of sensilla were observed on the maxillary palps and labial palps. The capitate pegs were found exclusively on the antennae of female B. coreanus.


Assuntos
Besouros , Sensilas , Feminino , Masculino , Animais , Sensilas/ultraestrutura , Microscopia Eletrônica de Varredura , Besouros/anatomia & histologia , Proteína 1 Semelhante a Receptor de Interleucina-1 , China , Antenas de Artrópodes/ultraestrutura
19.
Clin Appl Thromb Hemost ; 30: 10760296231223192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38166411

RESUMO

To investigate the predictive role of the neutrophil-platelet ratio (NPR) before intravenous thrombolysis (IVT) on hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS). AIS patients treated with IVT without endovascular therapy between June 2019 and February 2023 were included. Patients were divided into high NPR (>35) and low NPR (≤35) groups according to the optimal threshold NPR value for identifying high-risk patients before IVT. The baseline data and the incidence of HT and symptomatic intracranial hemorrhage (sICH) were compared between the two groups. The predictive role of the NPR and other related factors on HT after IVT was analyzed by multivariate logistic regression. A total of 247 patients were included, with an average age of 67.5 ± 12.4 years. Post-thrombolytic HT was observed in 18.6% of the patients, and post-thrombolytic sICH was observed in 1.2% of the patients. There were 69 patients in the high NPR group and 178 patients in the low NPR group. The incidence of HT in the high NPR group was significantly higher than that in the low NPR group (30.4% vs 16.3%, P < .05). The incidence of sICH was significantly higher in the high NPR group than in the low NPR group (14.5% vs 1.7%, P < .001). Multivariate logistic regression analysis showed that NPR > 35 was positively correlated with HT (odds ratio (OR) = 3.236, 95% confidence interval (CI): 1.481-7.068, P = .003) and sICH (OR = 13.644, 95% CI: 2.392-77.833, P = .003). A high NPR (>35) before IVT may be a predictor of HT in AIS patients. This finding may help clinicians make clinical decisions before IVT in AIS patients.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Pessoa de Meia-Idade , Idoso , Acidente Vascular Cerebral/etiologia , Ativador de Plasminogênio Tecidual/efeitos adversos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , Neutrófilos , Isquemia Encefálica/etiologia , Terapia Trombolítica/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Resultado do Tratamento
20.
Sci Rep ; 14(1): 1433, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228843

RESUMO

The ventilation work is an important step to be completed before the start of the positive pressure explosion-proof robot. The existing explosion-proof technology uses constant pressure inflation, which will cause explosive gas to accumulate in the corner area of the cavity for a long time. In order to solve this problem, a ventilation method with periodic pulse intake is proposed. Based on the finite element method, the cleaning and ventilation process of the positive pressure explosion-proof robot is simulated and analyzed. The concentration of explosive gas in the robot cavity with time under constant pressure intake and pulse intake with different periods and amplitudes is compared. The simulation results show that the pulse intake is beneficial to the ventilation of the corner position. The period and amplitude of the pulse intake has an effect on the ventilation efficiency, when the period is the same, the greater the amplitude of the pulse intake, the higher the ventilation efficiency; when the amplitude is the same, the smaller the period of the pulse intake, the higher the ventilation efficiency. After experimental verification, the validity of the simulation results is proved. This study helps to improve the ventilation efficiency of positive-pressure explosion-proof robots and provides guidance for practical applications.

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