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1.
Zool Res ; 45(4): 937-950, 2024 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-39021082

RESUMO

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.


Assuntos
Proteínas Relacionadas à Autofagia , Autofagia , Células-Tronco Neurais , Animais , Células-Tronco Neurais/fisiologia , Células-Tronco Neurais/metabolismo , Camundongos , Autofagia/fisiologia , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos Knockout , Proteína Sequestossoma-1/metabolismo , Proteína Sequestossoma-1/genética , Regulação da Expressão Gênica , Proteínas de Neoplasias
2.
Toxics ; 12(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38922110

RESUMO

The main objective of our study is to explore the associations between combined exposure to urinary heavy metals and high remnant cholesterol (HRC), a known cardiovascular risk factor. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we conducted a cross-sectional analysis of 5690 participants, assessing urinary concentrations of ten heavy metals. Ten heavy metals in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Fasting residual cholesterol ≥0.8 mmol/L was defined as HRC (using blood samples). Statistical analyses included weighted multivariable logistic regression, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the associations of heavy metal exposure with HRC. Stratified analyses based on individual characteristics were also conducted. Multivariable logistic regression found that the four metals (OR Q4 vs. Q1: 1.33, 95% CI: 1.01-1.75 for barium (Ba); OR Q4 vs. Q1: 1.50, 95% CI: 1.16-1.94 for cadmium (Cd); OR Q4 vs. Q1: 1.52, 95% CI: 1.15-2.01 for mercury (Hg); OR Q4 vs. Q1: 1.35, 95% CI: 1.06-1.73 for lead (Pb)) were positively correlated with the elevated risk of HRC after adjusting for covariates. In addition, all three mixed models, including WQS (OR: 1.25; 95% CI: 1.07-1.46), qgcomp (OR: 1.17; 95% CI: 1.03-1.34), and BKMR, consistently showed a significant positive correlation between co-exposure to heavy metal mixtures and HRC, with Ba and Cd being the main contributors within the mixture. These associations were more pronounced in younger adults (20 to 59 years), males, and those with a higher body mass index status (≥25 kg/m2). Our findings reveal a significant relationship between exposure to the mixture of heavy metals and HRC among US adults, with Ba and Cd being the major contributors to the mixture's overall effect. Public health efforts aimed at reducing heavy metal exposure can help prevent HRC and, in turn, cardiovascular disease.

3.
J Leukoc Biol ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833591

RESUMO

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.

4.
Nat Commun ; 15(1): 3838, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714685

RESUMO

The powerful capability of reconfigurable intelligent surfaces (RISs) in tailoring electromagnetic waves and fields has put them under the spotlight in wireless communications. However, the current designs are criticized due to their poor frequency selectivity, which hinders their applications in real-world scenarios where the spectrum is becoming increasingly congested. Here we propose a filtering RIS to feature sharp frequency-selecting and 2-bit phase-shifting properties. It permits the signals in a narrow bandwidth to transmit but rejects the out-of-band ones; meanwhile, the phase of the transmitted signals can be digitally controlled, enabling flexible manipulations of signal propagations. A prototype is designed, fabricated, and measured, and its high quality factor and phase-shifting characteristics are validated by scattering parameters and beam-steering phenomena. Further, we conduct a wireless communication experiment to illustrate the intriguing functions of the RIS. The filtering behavior enables the RIS to perform wireless signal manipulations with anti-interference ability, thus showing big potential to advance the development of next-generation wireless communications.

6.
World J Clin Cases ; 12(14): 2350-2358, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38765753

RESUMO

BACKGROUND: This study presents an evaluation of the computed tomography lymphangiography (CTL) features of lymphatic plastic bronchitis (PB) and primary chylothorax to improve the diagnostic accuracy for these two diseases. AIM: To improve the diagnosis of lymphatic PB or primary chylothorax, a retrospective analysis of the clinical features and CTL characteristics of 71 patients diagnosed with lymphatic PB or primary chylothorax was performed. METHODS: The clinical and CTL data of 71 patients (20 with lymphatic PB, 41 with primary chylothorax, and 10 with lymphatic PB with primary chylothorax) were collected retrospectively. CTL was performed in all patients. The clinical manifestations, CTL findings, and conventional chest CT findings of the three groups of patients were compared. The chi-square test or Fisher's exact test was used to compare the differences among the three groups. A difference was considered to be statistically significant when P < 0.05. RESULTS: (1) The percentages of abnormal contrast medium deposits on CTL in the three groups were as follows: Thoracic duct outlet in 14 (70.0%), 33 (80.5%) and 8 (80.0%) patients; peritracheal region in 18 (90.0%), 15 (36.6%) and 8 (80.0%) patients; pleura in 6 (30.0%), 33 (80.5%) and 9 (90.0%) patients; pericardium in 6 (30.0%), 6 (14.6%) and 4 (40.0%) patients; and hilum in 16 (80.0%), 11 (26.8%) and 7 (70.0%) patients; and (2) the abnormalities on conventional chest CT in the three groups were as follows: Ground-glass opacity in 19 (95.0%), 18 (43.9%) and 8 (80.0%) patients; atelectasis in 4 (20.0%), 26 (63.4%) and 7 (70.0%) patients; interlobular septal thickening in 12 (60.0%), 11 (26.8%) and 3 (30.0%) patients; bronchovascular bundle thickening in 14 (70.0%), 6 (14.6%) and 4 (40.0%) patients; localized mediastinal changes in 14 (70.0%), 14 (34.1%), and 7 (70.0%) patients; diffuse mediastinal changes in 6 (30.0%), 5 (12.2%), and 3 (30.0%) patients; cystic lesions in the axilla in 2 (10.0%), 6 (14.6%), and 2 (20.0%) patients; and cystic lesions in the chest wall in 0 (0%), 2 (4.9%), and 2 (4.9%) patients. CONCLUSION: CTL is well suited to clarify the characteristics of lymphatic PB and primary chylothorax. This method is an excellent tool for diagnosing these two diseases.

7.
Nano Lett ; 24(22): 6821-6827, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38787786

RESUMO

In the quasi-two-dimensional superconductor NbSe2, the superconducting transition temperature (Tc) is layer-dependent, decreasing by about 60% in the monolayer limit. However, for the extremely anisotropic copper-based high-Tc superconductor Bi2Sr2CaCu2O8+δ (Bi-2212), the Tc of the monolayer is almost identical with that of its bulk counterpart. To clarify the effect of dimensionality on superconductivity, here, we successfully fabricate ultrathin flakes of iron-based high-Tc superconductors CsCa2Fe4As4F2 and CaKFe4As4. It is found that the Tc of monolayer CsCa2Fe4As4F2 (after tuning to the optimal doping by ionic liquid gating) is about 20% lower than that of the bulk crystal, while the Tc of three-layer CaKFe4As4 decreases by 46%, showing a more pronounced dimensional effect than that of CsCa2Fe4As4F2. By carefully examining their anisotropy and the c-axis coherence length, we reveal the general trend and empirical law of the layer-dependent superconductivity in these quasi-two-dimensional superconductors.

8.
Mol Cell ; 84(10): 1917-1931.e15, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38723633

RESUMO

Many multi-spanning membrane proteins contain poorly hydrophobic transmembrane domains (pTMDs) protected from phospholipid in mature structure. Nascent pTMDs are difficult for translocon to recognize and insert. How pTMDs are discerned and packed into mature, muti-spanning configuration remains unclear. Here, we report that pTMD elicits a post-translational topogenesis pathway for its recognition and integration. Using six-spanning protein adenosine triphosphate-binding cassette transporter G2 (ABCG2) and cultured human cells as models, we show that ABCG2's pTMD2 can pass through translocon into the endoplasmic reticulum (ER) lumen, yielding an intermediate with inserted yet mis-oriented downstream TMDs. After translation, the intermediate recruits P5A-ATPase ATP13A1, which facilitates TMD re-orientation, allowing further folding and the integration of the remaining lumen-exposed pTMD2. Depleting ATP13A1 or disrupting pTMD-characteristic residues arrests intermediates with mis-oriented and exposed TMDs. Our results explain how a "difficult" pTMD is co-translationally skipped for insertion and post-translationally buried into the final correct structure at the late folding stage to avoid excessive lipid exposure.


Assuntos
Retículo Endoplasmático , Dobramento de Proteína , Humanos , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/química , ATPases Translocadoras de Prótons/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/química , Células HEK293 , Domínios Proteicos , Interações Hidrofóbicas e Hidrofílicas , Processamento de Proteína Pós-Traducional , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/química
10.
Int J Endocrinol ; 2024: 3950894, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571926

RESUMO

Objective: To explore associations of combined exposure to metabolic/inflammatory indicators with thyroid nodules. Methods: We reviewed personal data for health screenings from 2020 to 2021. A propensity score matching method was used to match 931 adults recently diagnosed with thyroid nodules in a 1 : 4 ratio based on age and gender. Conditional logistic regression and Bayesian kernel machine regression (BKMR) were used to explore the associations of single metabolic/inflammatory indicators and the mixture with thyroid nodules, respectively. Results: In the adjusted models, five indicators (ORQ4 vs. Q1: 1.30, 95% CI: 1.07-1.58 for fasting blood glucose; ORQ4 vs. Q1: 1.30, 95% CI: 1.08-1.57 for systolic blood pressure; ORQ4 vs. Q1: 1.26, 95% CI: 1.04-1.53 for diastolic blood pressure; ORQ4 vs. Q1: 1.23, 95% CI: 1.02-1.48 for white blood cell; ORQ4 vs. Q1: 1.28, 95% CI: 1.07-1.55 for neutrophil) were positively associated with the risk of thyroid nodules, while high-density lipoproteins (ORQ3 vs. Q1: 0.75, 95% CI: 0.61-0.91) were negatively associated with the risk of thyroid nodules. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the metabolic and inflammatory mixture exhibited a significant positive association with thyroid nodules in a dose-response pattern, with systolic blood pressure being the greatest contributor within the mixture (conditional posterior inclusion probability of 0.82). No interaction effects were found among the five indicators. These associations were more prominent in males, participants with higher age (≥40 years old), and individuals with abnormal body mass index status. Conclusions: Levels of the metabolic and inflammatory mixture have a linear dose-response relationship with the risk of developing thyroid nodules, with systolic blood pressure levels being the most important contributor.

11.
Chem Sci ; 15(14): 5192-5200, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38577355

RESUMO

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

12.
Adv Mater ; : e2400236, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563243

RESUMO

Skin-interfaced high-sensitive biosensing systems to detect electrophysiological and biochemical signals have shown great potential in personal health monitoring and disease management. However, the integration of 3D porous nanostructures for improved sensitivity and various functional composites for signal transduction/processing/transmission often relies on different materials and complex fabrication processes, leading to weak interfaces prone to failure upon fatigue or mechanical deformations. The integrated system also needs additional adhesive to strongly conform to the human skin, which can also cause irritation, alignment issues, and motion artifacts. This work introduces a skin-attachable, reprogrammable, multifunctional, adhesive device patch fabricated by simple and low-cost laser scribing of an adhesive composite with polyimide powders and amine-based ethoxylated polyethylenimine dispersed in the silicone elastomer. The obtained laser-induced graphene in the adhesive composite can be further selectively functionalized with conductive nanomaterials or enzymes for enhanced electrical conductivity or selective sensing of various sweat biomarkers. The possible combination of the sensors for real-time biofluid analysis and electrophysiological signal monitoring with RF energy harvesting and communication promises a standalone stretchable adhesive device platform based on the same material system and fabrication process.

13.
Sci Total Environ ; 927: 172175, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38575018

RESUMO

The use of plastic mulch films in agriculture leads to the inevitable accumulation of plastic debris in soils. Here, we explored the potential of earthworm gut-inhabiting bacterial strains (Mycobacterium vanbaalenii (MV), Rhodococcus jostii (RJ), Streptomyces fulvissimus (SF), Bacillus simplex (BS), and Sporosarcina globispora (SG) to degrade plastic films (⌀ = 15 mm) made from commonly used polymers: low-density polyethylene film (LDPE-f), polylactic acid (PLA-f), polybutylene adipate terephthalate film (PBAT-f), and a commercial biodegradable mulch film, Bionov-B® (composed of Mater-Bi, a feedstock with PBAT, PLA and other chemical compounds). A 180-day experiment was conducted at room temperature (x̄ =19.4 °C) for different strain-plastic combinations under a low carbon media (0.1× tryptic soy broth). Results showed that the tested strain-plastic combinations did not facilitate the degradation of LDPE-f (treated with RJ and SF), PBAT-f (treated with BS and SG), and Bionov-B (treated with BS, MV, and SG). However, incubating PLA-f with SF triggered a reduction in the molecular weights and an increase in crystallinity. Therefore, we used PLA-f as model plastic to study the influence of temperature ("room temperature" & "30 °C"), carbon source ("carbon-free" & "low carbon supply"), and strain interactions ("single strains" & "strain mixtures") on PLA degradation. SF and SF + RJ treatments significantly fostered PLA degradation under 30 °C in a low-carbon media. PLA-f did not show any degradation in carbon-free media treatments. The competition between different strains in the same system likely hindered the performance of PLA-degrading strains. A positive correlation between the final pH of culture media and PLA-f weight loss was observed, which might reflect the pH-dependent hydrolysis mechanism of PLA. Our results situate SF and its co-culture with RJ strains as possible accelerators of PLA degradation in temperatures below PLA glass transition temperature (Tg). Further studies are needed to test the bioremediation feasibility in soils.


Assuntos
Biodegradação Ambiental , Oligoquetos , Plásticos , Animais , Poluentes do Solo/metabolismo , Microbioma Gastrointestinal , Bactérias/metabolismo , Microbiologia do Solo , Poliésteres
14.
Adv Mater ; 36(26): e2402001, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38597787

RESUMO

Molecular semiconductor (MSC) is a promising candidate for spintronic applications benefiting from its long spin lifetime caused by light elemental-composition essence and thus weak spin-orbit coupling (SOC). According to current knowledge, the SOC effect, normally dominated by the elemental composition, is the main spin-relaxation causation in MSCs, and thus the molecular structure-induced SOC change is one of the most concerned issues. In theoretical study, molecular isomerism, a most prototype phenomenon, has long been considered to possess little difference on spin transport previously, since elemental compositions of isomers are totally the same. However, here in this study, quite different spin-transport performances are demonstrated in ITIC and its structural isomers BDTIC experimentally, for the first time, though the charge transport and molecular stacking of the two films are very similar. By further experiments of electron-paramagnetic resonance and density-functional-theory calculations, it is revealed that noncovalent-conformational locks (NCLs) formed in BDTIC can lead to enhancement of SOC and thus decrease the spin lifetime. Hence, this study suggests the influences from the structural-isomeric effect must be considered for developing highly efficient spin-transport MSCs, which also provides a reliable theoretical basis for solving the great challenge of quantificational measurement of NCLs in films in the future.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 164-168, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38436314

RESUMO

OBJECTIVES: To study the association of hypercoagulability with urinary protein and renal pathological damage in children with immunoglobulin A vasculitis with nephritis (IgAVN). METHODS: Based on the results of coagulation function, 349 children with IgAVN were divided into a hypercoagulability group consisting of 52 children and a non-hypercoagulability group consisting of 297 children. Urinary protein and renal pathological features were compared between the two groups, and the factors influencing the formation of hypercoagulability in children with IgAVN were analyzed. RESULTS: Compared with the non-hypercoagulability group, the hypercoagulability group had significantly higher levels of urinary erythrocyte count, 24-hour urinary protein, urinary protein/creatinine, urinary immunoglobulin G/creatinine, and urinary N-acetyl-ß-D-glucosaminidase (P<0.05). The hypercoagulability group also had a significantly higher proportion of children with a renal pathological grade of III-IV, diffuse mesangial proliferation, capillary endothelial cell proliferation, or >25% crescent formation (P<0.05). The multivariate logistic regression analysis showed that capillary endothelial cell proliferation and glomerular crescent formation >25% were associated with the formation of hypercoagulability in children with IgAVN (P<0.05). CONCLUSIONS: The renal injury in IgAVN children with hypercoagulability is more severe, with greater than 25% crescent formation and increased proliferation of glomerular endothelial cells being important contributing factors that exacerbate the hypercoagulable state in IgAVN.


Assuntos
Vasculite por IgA , Nefrite , Trombofilia , Criança , Humanos , Creatinina , Células Endoteliais , Rim , Vasculite por IgA/complicações , Trombofilia/etiologia , Imunoglobulina A
16.
Huan Jing Ke Xue ; 45(3): 1349-1360, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471851

RESUMO

Pollution variation, source characteristics, and meteorological effects of water-soluble inorganic ions (WSIIs) in PM2.5 were analyzed in Xinxiang city, Henan Province. PM2.5 samples and their chemical components were monitored online by using URG-9000 in four seasons:winter (January, 2022), spring (April, 2022), summer (July, 2022), and fall (October, 2022). The results showed that the TWSIIs had the same seasonal fluctuations as PM2.5. The average seasonal concentrations of WSIIs ranged from 19.62-72.15 µg·m-3, accounting for more than 60% of PM2.5, demonstrating that WSIIs were the major components of PM2.5. The annual concentration value of NO3-/SO42- was 2.11, which showed an increasing trend, suggesting predominantly mobile sources for secondary inorganic aerosols (SNA). Further, the molar concentration value [NH4+]/[NO3-] was 1.95, demonstrating that agriculture emissions were the dominant contributors to atmospheric nitrogen. Furthermore, the backward trajectory analysis showed that the concentrations of Ca2+ and Mg2+ were higher when the northeasterly wind prevailed and the wind speed was high. High values of SOR and NOR were correlated with low temperatures and high relative humidity (T < 8℃, RH > 60%), demonstrating that more gaseous precursors were converted into sulfate and nitrate. At high temperatures (T > 24℃), there was no apparent high NOR value like that for SOR, mainly due to the decomposition of NH4NO3 at high temperatures. Finally, backward trajectories associated with the PMF-resolved results were used to explore the regional transport characteristics. The results illustrated that dust sources in the study areas were mainly influenced by air trajectories originating from the northwest regions, whereas secondary sulfate, secondary nitrate, and biomass sources contributed more to WSIIs when wind speed and altitude air masses were low in the area surrounding the observation site.

17.
Adv Sci (Weinh) ; 11(19): e2306850, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38477543

RESUMO

Micro-Doppler effect is a vital feature of a target that reflects its oscillatory motions apart from bulk motion and provides an important evidence for target recognition with radars. However, establishing the micro-Doppler database poses a great challenge, since plenty of experiments are required to get the micro-Doppler signatures of different targets for the purpose of analyses and interpretations with radars, which are dramatically limited by high cost and time-consuming. Aiming to overcome these limits, a low-cost and powerful simulation platform of the micro-Doppler effects is proposed based on time-domain digital coding metasurface (TDCM). Owing to the outstanding capabilities of TDCM in generating and manipulating nonlinear harmonics during wave-matter interactions, it enables to supply rich and high-precision electromagnetic signals with multiple micro-Doppler frequencies to describe the micro-motions of different objects, which are especially favored for the training of artificial intelligence algorithms in automatic target recognition and benefit a host of applications like imaging and biosensing.

18.
Int Immunopharmacol ; 129: 111559, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38330794

RESUMO

Antibiotic-resistant Serratia marcescens (Sm) is known to cause bloodstream infections, pneumonia, etc. The nod-like receptor family, pyrin domain-containing 3 (NLRP3), has been implicated in various lung infections. Yet, its role in Sm-induced pneumonia was not well understood. In our study, we discovered that deletion of Nlrp3 in mice significantly improved Sm-induced survival rates, reduced bacterial loads in the lungs, bronchoalveolar lavage fluid (BALF), and bloodstream, and mitigated the severity of acute lung injury (ALI) compared to wild-type (WT) mice. Mechanistically, we observed that 24 h post-Sm infection, NLRP3 inflammasome activation occurred, leading to gasdermin D NH2-terminal (GSDMD-NT)-induced pyroptosis in macrophages and IL-1ß secretion. The NLRP3 or NLRP3 inflammasome influenced the expression PD-L1 and PD-1, as well as the count of PD-L1 or PD-1-expressing macrophages, alveolar macrophages, interstitial macrophages, PD-L1-expressing neutrophils, and the count of macrophage receptors with collagenous structure (MARCO)-expressing macrophages, particularly MARCO+ alveolar macrophages. The frequency of MARCO+ alveolar macrophages, PD-1 expression, particularly PD-1+ interstitial macrophages were negatively or positively correlated with the Sm load, respectively. Additionally, IL-1ß levels in BALF correlated with three features of acute lung injury: histologic score, protein concentration and neutrophil count in BALF. Consequently, our findings suggest that Nlrp3 deletion offers protection agaisnt acute Sm pneumonia in mice by inhibiting inflammasome activation and reducing Sm infection-induced PD-L1/PD-1 or MARCO expression, particularly in macrophages. This highlights potential therapeutic targets for Sm and other gram-negative bacteria-induced acute pneumonia.


Assuntos
Lesão Pulmonar Aguda , Pneumonia , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Serratia marcescens/genética , Serratia marcescens/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Pneumonia/metabolismo , Macrófagos/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Knockout
19.
ACS Biomater Sci Eng ; 10(3): 1722-1733, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38373308

RESUMO

Respiratory signals are critical clinical diagnostic criteria for respiratory diseases and health conditions, and respiratory sensors play a crucial role in achieving the desired respiratory monitoring effect. High sensitivity to a single factor can improve the reliability of respiratory monitoring, and maintaining the hygiene of the sensors is also important for daily health monitoring. Herein, we propose a flexible Au-modified anatase titanium dioxide resistive respiratory sensor, which can be mechanically compliantly attached to curved surfaces for respiratory monitoring in different modalities (i.e., respiratory intensity, frequency, and rate). The uniform and preferentially oriented anatase titanium dioxide films gained by the polymer-assisted deposition technique can be fabricated on flexible substrates through a liquid-assisted transferring process. The Au modification can enhance surface plasmon resonance to facilitate the photocatalytic activity of titanium dioxide, and the optimized distribution of Au on the surface of titanium dioxide film made the sensor have an excellent antibacterial effect. The uniquely designed encapsulation can effectively control the contact between the surface of titanium dioxide films and electrodes, allowing the flexible sensor to exhibit fast response time (0.71 s) and recovery time (1.06 s) to respiratory as well as insensitivity or low sensitivity to other factors (i.e., gas composition, humidity, temperature, stress, and strain). This work provided an effective strategy for flexible wearable respiratory sensors and has great potential in daily respiratory monitoring for health management and pandemic control.


Assuntos
Antibacterianos , Titânio , Reprodutibilidade dos Testes , Titânio/farmacologia , Titânio/química , Antibacterianos/farmacologia , Antibacterianos/química
20.
J Pharm Pharmacol ; 76(6): 681-690, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38422325

RESUMO

OBJECTIVES: Schisandrin B (Sch B) has been shown to possess anti-inflammatory and antioxidant properties, however, its antirheumatoid arthritis properties and potential mechanism remain unexplored. This study evaluated the potential of Sch B in adjuvant-induced arthritic (AIA) rats. METHODS: AIA was induced by injecting 0.1 ml of CFA into the paw of rats and the animals were administered with Sch B (50 mg/kg) for 28 days. The effects of Sch B were evaluated using arthritis severity, serum levels of oxido-inflammatory, and metabolic index parameters. KEY FINDINGS: Sch B eased arthritic symptoms by significantly reducing paw swelling and arthritic score and increased body weight gain. Moreover, Sch B alleviated the levels of oxido-inflammatory markers including interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, nuclear factor kappa B, transforming growth factor ß1, inducible nitric oxide synthase and malonaldehyde, as well as increased the levels of superoxide dismutase, glutathione, and Nrf2. Sch B also remarkably restored the altered levels of triglyceride, aspartate aminotransferase, lactic acid, pyruvate, phosphoenolpyruvate carboxylase, glucose, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor. In addition, Sch B markedly alleviated p65 expression in the treated AIA rats. CONCLUSION: This study suggests that Sch B alleviated AIA by reducing oxidative stress, inflammation, and angiogenesis.


Assuntos
Anti-Inflamatórios , Artrite Experimental , Ciclo-Octanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Mediadores da Inflamação , Lignanas , Estresse Oxidativo , Compostos Policíclicos , Fator A de Crescimento do Endotélio Vascular , Animais , Ciclo-Octanos/farmacologia , Ciclo-Octanos/uso terapêutico , Lignanas/farmacologia , Lignanas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Compostos Policíclicos/farmacologia , Compostos Policíclicos/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos , Anti-Inflamatórios/farmacologia , Masculino , Mediadores da Inflamação/metabolismo , Antioxidantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ratos Sprague-Dawley , Inflamação/tratamento farmacológico , Inflamação/metabolismo
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