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1.
World J Clin Cases ; 12(17): 3235-3242, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898830

RESUMO

BACKGROUND: This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion (UBE-LIF), utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment, and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw placement. The advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies, and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients, and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for reference. CASE SUMMARY: A 44-year-old patient presented to our hospital. Combining various clinical data, we diagnosed the patient with lumbar disc herniation with radiculopathy, lumbar spondylolisthesis, and lumbar spinal stenosis. We developed a surgical plan of "UBE decompression + UBE-LIF + orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation". The results were satisfactory. CONCLUSION: We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good results. Therefore, the technique is worthy of clinical promotion.

2.
Elife ; 122024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842277

RESUMO

Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic environment. However, it remains unclear how the brain encodes and uses rule information to guide behavior. Here, we made single-unit recordings while head-fixed mice performed a cross-modal sensory selection task where they switched between two rules: licking in response to tactile stimuli while rejecting visual stimuli, or vice versa. Along a cortical sensorimotor processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial (MM) and anterolateral (ALM) motor areas, single-neuron activity distinguished between the two rules both prior to and in response to the tactile stimulus. We hypothesized that neural populations in these areas would show rule-dependent preparatory states, which would shape the subsequent sensory processing and behavior. This hypothesis was supported for the motor cortical areas (MM and ALM) by findings that (1) the current task rule could be decoded from pre-stimulus population activity; (2) neural subspaces containing the population activity differed between the two rules; and (3) optogenetic disruption of pre-stimulus states impaired task performance. Our findings indicate that flexible action selection in response to sensory input can occur via configuration of preparatory states in the motor cortex.


Assuntos
Córtex Motor , Animais , Camundongos , Córtex Motor/fisiologia , Masculino , Córtex Somatossensorial/fisiologia , Neurônios/fisiologia , Feminino , Optogenética , Comportamento Animal/fisiologia
3.
Sensors (Basel) ; 24(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38931492

RESUMO

A staggered vane-shaped slot-line slow-wave structure (SV-SL SWS) for application in W-band traveling wave tubes (TWTs) is proposed in this article. In contrast to the conventional slot-line SWSs with dielectric substrates, the proposed SWS consists only of a thin metal sheet inscribed with periodic grooves and two half-metal enclosures, which means it can be easily manufactured and assembled and has the potential for mass production. This SWS not only solves the problem of the dielectric loading effect but also improves the heat dissipation capability of such structures. Meanwhile, the SWS design presented here covers a -15 dB S11 frequency range from 87.5 to 95 GHz. The 3-D simulation for a TWT based on the suggested SWS is also investigated. Under dual-electron injection conditions with a total voltage of 17.2 kV and a total current of 0.3 A, the maximum output power at 90 GHz is 200 W, with a 3 dB bandwidth up to 4 GHz. With a good potential for fabrication using microfabrication techniques, this structure can be a good candidate for millimeter-wave TWT applications.

4.
NPJ Precis Oncol ; 8(1): 133, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879686

RESUMO

Neurofibromatosis type 2 (NF2) is a tumor suppressor gene implicated in various tumors, including mesothelioma, schwannomas, and meningioma. As a member of the ezrin, radixin, and moesin (ERM) family of proteins, merlin, which is encoded by NF2, regulates diverse cellular events and signalling pathways, such as the Hippo, mTOR, RAS, and cGAS-STING pathways. However, the biological role of NF2 in tumorigenesis has not been fully elucidated. Furthermore, cross-cancer mutations may exert distinct biological effects on tumorigenesis and treatment response. In addition to the functional inactivation of NF2, the codeficiency of other genes, such as cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B), BRCA1-associated protein-1 (BAP1), and large tumor suppressor 2 (LATS2), results in unique tumor characteristics that should be considered in clinical treatment decisions. Notably, several recent studies have explored the metabolic and immunological features associated with NF2, offering potential insights into tumor biology and the development of innovative therapeutic strategies. In this review, we consolidate the current knowledge on NF2 and examine the potential connection between cancer metabolism and tumor immunity in merlin-deficient malignancies. This review may provide a deeper understanding of the biological roles of NF2 and guide possible therapeutic avenues.

5.
Adv Sci (Weinh) ; : e2400623, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898767

RESUMO

Solar-driven interfacial evaporation is an emerging desalination technology that can potentially relieve the freshwater scarcity issue. To obtain high and continuous evaporation rates for all-weather, chemically engineered structural materials have been widely explored for simultaneous photothermal and electrothermal conversion. However, many previously reported fabrication processes involve poor integration and considerable energy loss. Herein, a scalable photo-electro-thermal textile is proposed to enable high efficiency, long-term salt rejection, and solar-driven desalination. Specifically, the photo-electro-thermal yarns with a core (commercial electric wire)-shell (polypyrrole-decorated Tencel) structure realize the integration of electrothermal and photothermal conversion. The wrapping eccentricity of 1.53 mm and pitch of 3 T cm-1 for the electric wire are rationally regulated to achieve a high surface temperature of over 52 °C at a 3 V DC input. As a result, exceptional and stable evaporation rates of 5.57 kg m-2 h-1 (pure water) and 4.89 kg m-2 h-1 (3.5 wt.% brine) under 1 kW m-2·radiation with a 3 V input voltage are realized. Practical application shows that the textiles can achieve high water collection of over 46 kg m-2 d-1 over the whole day of operation. The constructed photo-electro-thermal textile-based evaporator provides an effective method for commercial and scalable photo-electro-thermal conversion to achieve high-performance and salt-resistant solar-driven desalination.

6.
Environ Pollut ; 351: 124059, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703979

RESUMO

The hazards of man-made chiral compounds are of great public concern, with reports of worrying stereoselective compounds and an urgent need to assess their transport. This study evaluated the transport of 2-arylpropionic acid derivatives enantiomers (2-APA) in porous media under a variety of solution chemistry conditions via column packing assays. The results revealed the introduction of Malic acid (MA) enantiomers enhanced the mobility of 2-APA enantiomers, but the enhancement effect was different for different 2-APA enantiomers. Batch sorption experiments confirmed that the MA enantiomers occupied the sorption site of the quartz sand, thus reducing the deposition of the 2-APA enantiomer. Homo- or heterochirality between 2-APA and MA dominates the transport of 2-APA enantiomers, with homochirality between them triggering stronger retention and vice versa. Further evaluating the effect of solution chemistry conditions on the transport of 2-APA enantiomers, increased ionic strength attenuated the mobility of 2-APA enantiomers, whereas introduced coexisting cations enhanced the retention of 2-APA enantiomers in the column. The redundancy analyses corroborated these solution chemistry conditions were negatively correlated with the transport of 2-APA enantiomers. The coupling of pH and these conditions reveals electrostatic forces dominate the transport behavior and stereoselective interactions of 2-APA enantiomers. Distinguishing the transport of enantiomeric pair helps to understand the difference in stereoselectivity of enantiomers and promises to remove the more hazardous one.


Assuntos
Propionatos , Estereoisomerismo , Propionatos/química , Porosidade , Adsorção , Malatos/química , Concentração de Íons de Hidrogênio
7.
J Transl Med ; 22(1): 518, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816750

RESUMO

BACKGROUND: Dysbiosis of the gut microbiota is pivotal in Crohn's disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown. METHODS: CD patients were divided into an HBOT group (n = 10) and a control group (n = 10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16 S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed. RESULTS: HBOT significantly reduced the level of C-reactive protein (CRP) (80.79 ± 42.05 mg/L vs. 33.32 ± 18.31 mg/L, P = 0.004) and the Crohn's Disease Activity Index (CDAI) (274.87 ± 65.54 vs. 221.54 ± 41.89, P = 0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P = 0.089) and remission (20%vs.50%, P = 0.160) at week 4. CONCLUSIONS: HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605 .


Assuntos
Doença de Crohn , Disbiose , Microbioma Gastrointestinal , Oxigenoterapia Hiperbárica , Inflamação , Doença de Crohn/terapia , Doença de Crohn/microbiologia , Humanos , Disbiose/terapia , Disbiose/microbiologia , Animais , Feminino , Masculino , Inflamação/terapia , Adulto , Intestinos/microbiologia , Pessoa de Meia-Idade , Transplante de Microbiota Fecal , Camundongos , Camundongos Endogâmicos C57BL , Adulto Jovem
8.
JTO Clin Res Rep ; 5(5): 100672, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715965

RESUMO

Introduction: Malignant pleural mesothelioma (MPM) is a rare and universally lethal malignancy with limited treatment options. Immunotherapy with immune checkpoint inhibitors (ICIs) has recently been approved for unresectable MPM, but response to ICIs is heterogeneous, and reliable biomarkers for prospective selection of appropriate subpopulations likely to benefit from ICIs remain elusive. Methods: We performed multiscale integrative analyses of published primary tumor data set from The Cancer Genome Atlas (TCGA) and the French cohort E-MTAB-1719 to unravel the tumor immune microenvironment of MPM deficient in BAP1, one of the most frequently mutated tumor suppressor genes (TSGs) in the disease. The molecular profiling results were validated in independent cohorts of patients with MPM using immunohistochemistry and multiplex immunohistochemistry. Results: We revealed that BAP1 deficiency enriches immune-associated pathways in MPM, leading to increased mRNA signatures of interferon alfa/gamma response, activating dendritic cells, immune checkpoint receptors, and T-cell inflammation. This finding was confirmed in independent patient cohorts, where MPM tumors with low BAP1 levels are associated with an inflammatory tumor immune microenvironment characterized by increased exhausted precursor T-cells and macrophages but decreased myeloid-derived suppressor cells (MDSCs). In addition, BAP1low MPM cells are in close proximity to T cells and therefore can potentially be targeted with ICIs. Finally, we revealed that BAP1-proficient MPM is associated with a hyperactive mitogen-activated protein kinase (MAPK) pathway and may benefit from treatment with MEK inhibitors (MEKis). Conclusion: Our results suggest that BAP1 plays an immunomodulatory role in MPM and that BAP1-deficient MPM may benefit from immunotherapy, which merits further clinical investigation.

9.
ACS Sens ; 9(5): 2575-2584, 2024 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-38695880

RESUMO

Although electronic textiles that can detect external stimuli show great promise for fire rescue, existing firefighting clothing is still scarce for simultaneously integrating reliable early fire warning and real-time motion sensing, hardly providing intelligent personal protection under complex high-temperature conditions. Herein, we introduce an "all-in-one" hierarchically sandwiched fabric (HSF) sensor with a simultaneous temperature and pressure stimulus response for developing intelligent personal protection. A cross-arranged structure design has been proposed to tackle the serious mutual interference challenge during multimode sensing using two separate sets of core-sheath composite yarns and arrayed graphene-coated aerogels. The functional design of the HSF sensor not only possesses wide-range temperature sensing from 25 to 400 °C without pressure disturbance but also enables highly sensitive pressure response with good thermal adaptability (up to 400 °C) and wide pressure detection range (up to 120 kPa). As a proof of concept, we integrate large-scalable HSF sensors onto conventional firefighting clothing for passive/active fire warning and also detecting spatial pressure and temperature distribution when a firefighter is exposed to high-temperature flames, which may provide a useful design strategy for the application of intelligent firefighting protective clothing.


Assuntos
Pressão , Temperatura , Têxteis , Têxteis/análise , Humanos , Incêndios , Bombeiros , Roupa de Proteção , Grafite/química , Dispositivos Eletrônicos Vestíveis
10.
Adv Mater ; 36(29): e2400502, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38651254

RESUMO

Chemotherapy of glioblastoma (GBM) has not yielded success due to inefficient blood-brain barrier (BBB) penetration and poor glioma tissue accumulation. Aerobic glycolysis, as the main mode of energy supply for GBM, safeguards the rapid growth of GBM while affecting the efficacy of radiotherapy and chemotherapy. Therefore, to effectively inhibit aerobic glycolysis, increase drug delivery efficiency and sensitivity, a novel temozolomide (TMZ) nanocapsule (ApoE-MT/siPKM2 NC) is successfully designed and prepared for the combined delivery of pyruvate kinase M2 siRNA (siPKM2) and TMZ. This drug delivery platform uses siPKM2 as the inner core and methacrylate-TMZ (MT) as the shell component to achieve inhibition of glioma energy metabolism while enhancing the killing effect of TMZ. By modifying apolipoprotein E (ApoE), dual targeting of the BBB and GBM is achieved in a "two birds with one stone" style. The glutathione (GSH) responsive crosslinker containing disulfide bonds ensures "directional blasting" cleavage of the nanocapsules to release MT and siPKM2 in the high GSH environment of glioma cells. In addition, in vivo experiments verify that ApoE-MT/siPKM2 NC has good targeting ability and prolongs the survival of tumor-bearing nude mice. In summary, this drug delivery system provides a new strategy for metabolic therapy sensitization chemotherapy.


Assuntos
Glioblastoma , Glicólise , Nanocápsulas , Temozolomida , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Animais , Temozolomida/farmacologia , Temozolomida/química , Nanocápsulas/química , Camundongos , Linhagem Celular Tumoral , Glicólise/efeitos dos fármacos , Humanos , Camundongos Nus , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , RNA Interferente Pequeno/metabolismo , Barreira Hematoencefálica/metabolismo , Glutationa/metabolismo , Glutationa/química
11.
bioRxiv ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38562797

RESUMO

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in biosynthesis of taurine from cysteine as well as the downstream derivatization of taurine into secondary taurine metabolites4,5. One such taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise7, nutritional taurine supplementation8, and alcohol consumption6,9. While taurine N-acetyltransferase activity has been previously detected in mammalian cells6,7, the molecular identity of this enzyme, and the physiologic relevance of N-acetyltaurine, have remained unknown. Here we show that the orphan body mass index-associated enzyme PTER (phosphotriesterase-related)10 is the principal mammalian taurine N-acetyltransferase/hydrolase. In vitro, recombinant PTER catalyzes bidirectional taurine N-acetylation with free acetate as well as the reverse N-acetyltaurine hydrolysis reaction. Genetic ablation of PTER in mice results in complete loss of tissue taurine N-acetyltransferase/hydrolysis activities and systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO mice exhibit lower body weight, reduced adiposity, and improved glucose homeostasis. These phenotypes are recapitulated by administration of N-acetyltaurine to wild-type mice. Lastly, the anorexigenic and anti-obesity effects of N-acetyltaurine require functional GFRAL receptors. Together, these data uncover enzymatic control of a previously enigmatic pathway of secondary taurine metabolism linked to energy balance.

12.
World J Diabetes ; 15(3): 530-551, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38591077

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is one of the serious complications of diabetes mellitus, and the existing treatments cannot meet the needs of today's patients. Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application. However, the specific mechanism by which it works is still unclear. Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair (NRDP) for the treatment of DKD will provide a new way of thinking for the research and development of new drugs. AIM: To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking, and then verify the initial findings by in vitro experiments. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredient targets of NRDP. Targets for DKD were obtained based on the Genecards, OMIM, and TTD databases. The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram, and Cytoscape 3.9.0 was used to build a "drug-component-target-disease" network. The String database was used to construct protein interaction networks. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology analysis were performed based on the DAVID database. After selecting the targets and the active ingredients, Autodock software was used to perform molecular docking. In experimental validation using renal tubular epithelial cells (TCMK-1), we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability, with glucose solution used to mimic a hyperglycemic environment. Flow cytometry was used to detect the cell cycle progression and apoptosis. Western blot was used to detect the protein expression of STAT3, p-STAT3, BAX, BCL-2, Caspase9, and Caspase3. RESULTS: A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP. Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products (AGEs)-receptor for AGEs (RAGE) signaling as the core pathway. Molecular docking showed good binding between each active ingredient and its core targets. In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells, blocked cell cycle progression in the G0/G1 phase, and reduced apoptosis in a concentration-dependent manner. Based on the results of Western blot analysis, NRDP differentially downregulated p-STAT3, BAX, Caspase3, and Caspase9 protein levels (P < 0.01 or P < 0.05). In addition, BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced, while BCL-2 and STAT3 protein expression was upregulated (P < 0.01). CONCLUSION: NRDP may upregulate BCL-2 and STAT3 protein expression, and downregulate BAX, Caspase3, and Caspase9 protein expression, thus activating the AGE-RAGE signaling pathway, inhibiting the vitality of TCMK-1 cells, reducing their apoptosis. and arresting them in the G0/G1 phase to protect them from damage by high glucose.

13.
Cell Rep ; 43(4): 113991, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38573855

RESUMO

The brain receives constant tactile input, but only a subset guides ongoing behavior. Actions associated with tactile stimuli thus endow them with behavioral relevance. It remains unclear how the relevance of tactile stimuli affects processing in the somatosensory (S1) cortex. We developed a cross-modal selection task in which head-fixed mice switched between responding to tactile stimuli in the presence of visual distractors or to visual stimuli in the presence of tactile distractors using licking movements to the left or right side in different blocks of trials. S1 spiking encoded tactile stimuli, licking actions, and direction of licking in response to tactile but not visual stimuli. Bidirectional optogenetic manipulations showed that sensory-motor activity in S1 guided behavior when touch but not vision was relevant. Our results show that S1 activity and its impact on behavior depend on the actions associated with a tactile stimulus.


Assuntos
Córtex Somatossensorial , Animais , Camundongos , Córtex Somatossensorial/fisiologia , Masculino , Tato/fisiologia , Camundongos Endogâmicos C57BL , Optogenética , Percepção do Tato/fisiologia , Comportamento Animal , Feminino
14.
J Exp Med ; 221(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38597954

RESUMO

Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture. Infected alveolar macrophages (AMs) showed none of these extreme responses. Spike-dependent viral entry into AMs used ACE2 and Sialoadhesin/CD169, whereas IM entry used DC-SIGN/CD209. These results identify activated IMs as a prominent site of viral takeover, the focus of inflammation and fibrosis, and suggest targeting CD209 to prevent early pathology in COVID-19 pneumonia. This approach can be generalized to any human lung infection and to evaluate therapeutics.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Macrófagos , Inflamação , RNA Viral , Pulmão
15.
Mol Pharm ; 21(6): 2865-2877, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38666508

RESUMO

Imaging strategies for the specific detection and therapeutic monitoring of myocarditis are still lacking. Stimulator of interferon genes (STING) is a signal transduction molecule involved in an innate immune response. Here, we evaluated the feasibility of the recently developed STING-targeted radiotracer [18F]FBTA for positron emission tomography (PET) imaging to detect myocardial inflammation and monitor treatment in myocarditis mice. [18F]FBTA-PET imaging was performed in myocarditis mice and normal mice to verify the specificity of [18F]FBTA for the diagnosis of myocarditis. We also performed PET imaging in mice with myocarditis treated to verify the ability of [18F]FBTA in therapeutic monitoring. The expression of STING and inflammatory cell types was confirmed by flow cytometry and immunohistochemistry. [18F]FDG-PET imaging of myocarditis was used as a contrast. [18F]FBTA-PET imaging showed that the average radioactive uptake was significantly higher in the hearts of the myocarditis group than in the control group. STING was highly overexpressed in cardiac inflammatory cells, including macrophages, dendritic cells (DCs), and T cells. However, there was no significant difference in cardiac radiotracer uptake of [18F]FDG between the myocarditis group and the control group. Moreover, cardiac uptake of [18F]FBTA was significantly reduced in cyclosporin A-treated myocarditis mice and myocardial STING expression was also significantly reduced after the treatment. Overall, we showed that a STING-targeted PET tracer [18F]FBTA can be used to monitor changes in the inflammatory microenvironment in myocarditis. Besides, [18F]FBTA-PET is also suitable for real-time monitoring of myocarditis treatment, representing a promising diagnostic and therapeutic monitoring approach for myocarditis.


Assuntos
Proteínas de Membrana , Miocardite , Tomografia por Emissão de Pósitrons , Miocardite/diagnóstico por imagem , Miocardite/tratamento farmacológico , Miocardite/metabolismo , Animais , Camundongos , Tomografia por Emissão de Pósitrons/métodos , Proteínas de Membrana/metabolismo , Masculino , Compostos Radiofarmacêuticos , Fluordesoxiglucose F18 , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Miocárdio/metabolismo , Miocárdio/patologia , Células Dendríticas/metabolismo , Ciclosporina
16.
Mol Biomed ; 5(1): 11, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556586

RESUMO

Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m6A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan-Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m6A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m6A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Transportador 1 de Aminoácidos Neutros Grandes , RNA Circular , Neoplasias Gástricas , Animais , Feminino , Humanos , Masculino , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Linhagem Celular Tumoral , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Camundongos Nus , Prognóstico , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Metilação de RNA , RNA Circular/genética , RNA Circular/metabolismo
17.
Abdom Radiol (NY) ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451265

RESUMO

PURPOSE: To identify whether placental volume, T2 dark band volume, and cervical length measured by MRI correlate with massive hemorrhage (MH) in patients with placenta accreta spectrum (PAS) disorders. METHODS: A total of 163 pregnant women with PAS underwent preoperative MRI examination were divided into MH group and non-MH group. The placental volume, T2 dark band volume, and cervical length of PAS patients were measured and evaluated their ability to identify MH in patients with PAS. RESULTS: Patients with MH had a significantly larger placental volume, larger T2 dark band volume, and shorter cervical length than patients without MH (all P < 0.001). Multivariable logistic regression showed that placental volume (> 890 cm3), T2 dark band volume (> 35 cm3), and cervical length (< 30 mm) were significant independent risk factor in identification of MH. In all PAS patients, a positive linear correlation was found between placental volume and amount of blood loss (r = 0.527), and between T2 dark band volume and amount of blood loss (r = 0.642), and a negative linear correlation was found between cervical length and amount of blood loss (r = - 0.597). When combined with the three MRI indicators, the sensitivity and specificity in identifying cases at high risk for MH were 91.638% and 94.051%, respectively, with area under the curve (AUC) of 0.923. CONCLUSION: The placental volume, T2 dark band volume, and cervical length might be used to predict MH in patients with PAS.

18.
J Hazard Mater ; 468: 133824, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38377915

RESUMO

The study examined the transport behavior of the 2-aryl propionic acid (2-APA) chiral pharmaceutical enantiomers by means of a laboratory-scale saturated quartz sand column experiment. Four typical of 2-APA and their enantiomers were selected for the study under different types of chiral organic acids (COAs)-mediated effects. Differences in the transport of the 2-APA enantiomeric pairs have been identified in response to various pH, types of COAs, and enantiomeric structures of COAs. Redundancy analysis identified the factors responsible for the largest differences in transport of 2-APA enantiomeric pairs, while spectroscopic characterization and density function theory (DFT) studies elucidated the underlying mechanisms contributing to the differences in transport of enantiomeric pairs. Obvious correlations among homochirality or heterochirality between COAs and 2-APA enantiomeric pairs were observed for changes in the mobility of 2-APA. The results indicate widespread COAs significantly affect the transport behavior of chiral man-made chemicals, suggesting more attention is needed to fill the gap in the perception of the transport behavior of chiral compounds.

19.
Proc Natl Acad Sci U S A ; 121(7): e2316960121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38319964

RESUMO

The Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection from orthoebolavirus zairense (EBOV)-one of three orthoebolavirus species that have caused previous outbreaks. Ebola virus glycoprotein GP mediates viral infection and serves as the primary target of neutralizing antibodies. Here, we describe a universal Ebola virus vaccine approach using a structure-guided design of candidates with hyperglycosylation that aims to direct antibody responses away from variable regions and toward conserved epitopes of GP. We first determined the hyperglycosylation landscape on Ebola virus GP and used that to generate hyperglycosylated GP variants with two to four additional glycosylation sites to mask the highly variable glycan cap region. We then created vaccine candidates by displaying wild-type or hyperglycosylated GP variants on ferritin nanoparticles (Fer). Immunization with these antigens elicited potent neutralizing antisera against EBOV in mice. Importantly, we observed consistent cross-neutralizing activity against Bundibugyo virus and Sudan virus from hyperglycosylated GP-Fer with two or three additional glycans. In comparison, elicitation of cross-neutralizing antisera was rare in mice immunized with wild-type GP-Fer. These results demonstrate a potential strategy to develop universal Ebola virus vaccines that confer cross-protective immunity against existing and emerging filovirus species.


Assuntos
Vacinas contra Ebola , Ebolavirus , Doença pelo Vírus Ebola , Vacinas Virais , Humanos , Animais , Camundongos , Anticorpos Antivirais , Anticorpos Neutralizantes , Soros Imunes
20.
Small ; : e2309514, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38415913

RESUMO

Sustainable, durable, and diverse photochromic smart textiles based on bacterial cellulose (BC) have emerged as attractive candidates in UV-sensing applications due to the green and easy functionalization of BC. However, existing BC-based photochromic textiles lack photochromic efficiency and combining fastness. In this study, a green strategy for in situ fermentation is developed to achieve the directional distribution of functional particles and remarkable photochromism in photochromic bacterial cellulose (PBC). The unique functional design obtained by regulating the photochromic dye distribution in 3D nanonetworks of PBCs during in situ growth affords a more uniform distribution and high fastness. Benefiting from the uniform distribution of photochromic dyes and adequate utilization of the 3D network structure, more surface area is provided to receive and utilize the photon energy from the UV rays, making the photochromic process more effective. The as-prepared PBCs exhibited rapid (within 1 min) and stable (30 cycles) discoloration and multicolor selectivity. Their simple preparation process and exceptional wearability, e.g., their flexibility, lightweight, and air permeability, make them suitable for various applications, including tunable color switching systems, photopatterning, and daily sunlight UV monitoring. This study provides empirical value for the biofabrication of photochromic textiles and wearable flexible UV sensors.

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