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1.
J Phys Chem A ; 128(28): 5473-5480, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38968435

RESUMO

Liquid-phase synthesis of atomically precise nanoclusters has experienced rapid development recently, where polar solvents are indispensable in such a process. However, the regulation effect of solvents on the structural and electronic properties of different metal clusters and cluster assembly materials is still not well understood. Herein, a comprehensive density functional theory calculation has been performed to explore the solvation effect on heteroatom-doped endohedral gold clusters that always have remarkable stabilities and tunable electronic structures. The solvation free energy of the M@Au12 clusters (M = Cr, Mo, W, Co, Rh, Ir, Cu, Ag, and Au) was found to be related to the charge distribution of the central doped-atom M and the outer Au12 cage. Moreover, the aqueous solvent was observed to be able to increase the adsorption capacity of M@Au12 to O2 following the activation of O2 through the charge transfer from M@Au12 to O2, in which the transferred electrons occupy the π antibonding orbital of O2. In addition, the water solvent can also improve the hydrogenation reaction of O2 to form OOH over M@Au12, where the activation energy barrier for this process is very low with the participation of the solvent. Considering the importance of solvents in the liquid-phase synthesis of atomically precise clusters, these findings highlighted here could provide valuable theoretical guidance in potential applications of functional gold nanoclusters, especially in the liquid-phase cluster catalysis.

2.
J Am Chem Soc ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39021150

RESUMO

The pursuit of robust, long-range magnetic ordering in two-dimensional (2D) materials holds immense promise for driving technological advances. However, achieving this goal remains a grand challenge due to enhanced quantum and thermal fluctuations as well as chemical instability in the 2D limit. While magnetic ordering has been realized in atomically thin flakes of transition metal chalcogenides and metal halides, these materials often suffer from air instability. In contrast, 2D carbon-based materials are stable enough, yet the challenge lies in creating a high density of local magnetic moments and controlling their long-range magnetic ordering. Here, we report a novel wafer-scale synthesis of an air-stable metallo-carbon nitride monolayer (MCN, denoted as MN4/CNx), featuring ultradense single magnetic atoms and exhibiting robust room-temperature ferromagnetism. Under low-pressure chemical vapor deposition conditions, thermal dehydrogenation and polymerization of metal phthalocyanine (MPc) on copper foil at elevated temperature generate a substantial number of nitrogen coordination sites for anchoring magnetic single atoms in monolayer MN4/CNx (where M = Fe, Co, and Ni). The incorporation of densely populating MN4 sites into monolayer MCN networks leads to robust ferromagnetism up to room temperature, enabling the observation of anomalous Hall effects with excellent chemical stability. Detailed electronic structure calculations indicate that the presence of high-density metal sites results in the emergence of spin-split d-bands near the Fermi level, causing a favorable long-range ferromagnetic exchange coupling through direct exchange interactions. Our work demonstrates a novel synthesis approach for wafer-scale MCN monolayers with robust room-temperature ferromagnetism and may shed light on practical electronic and spintronic applications.

3.
Bioorg Chem ; 151: 107619, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39024806

RESUMO

Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.

4.
Int J Ophthalmol ; 17(7): 1248-1254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39026914

RESUMO

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or flat anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P<0.001) with 2.9±1.6 medications (P=0.046) at 1d, and 17.4±6.7 mm Hg (P<0.001) with 1.3±1.7 medications (P<0.001) at 12mo. The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo, respectively. A total of 32 (94.1%) eyes achieved initial anatomical success. During follow-up, 2 (5.9%) eyes failed and 8 (23.5%) eyes relapsed, yielding a 12-month anatomical success rate of 64.3%. Complications including anterior synechia (8.82%), choroidal/ciliary detachment (5.88%) and hypopyon (2.94%) were observed within 1wk. CONCLUSION: LCP is simple, safe, and effective in reforming the anterior chamber in malignant glaucoma.

5.
Dalton Trans ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016624

RESUMO

Correction for 'A robust and porous titanium metal-organic framework for gas adsorption, CO2 capture and conversion' by Xuze Pan, et al., Dalton Trans., 2023, 52, 3896-3906, https://doi.org/10.1039/D2DT03158B.

6.
Laryngoscope ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874287

RESUMO

BACKGROUND AND PURPOSE: The aims of our study are to evaluate the diagnostic performance and prognostic value of radiological lymph node (LN) characteristics in pN+ oral cavity squamous carcinoma (OSCC). MATERIALS AND METHODS: pN+ OSCC treated between 2012 and 2020 were included. Preoperative imaging was reviewed by a single radiologist blinded to pathologic findings for the following nodal features: imaging-positive LN (iN+), laterality and total number, and image-identified extranodal extension (iENE). The sensitivity of iN+ for pN+ was calculated. The diagnostic performance of other nodal features was evaluated in the iN+ subgroup. The association of radiologic nodal features with overall survival (OS) was evaluated. Inter-rater kappa for radiologic nodal features was assessed in 100 randomly selected cases. RESULTS: Of 406 pN+ OSCC, 288 were iN+. The sensitivity of iN+ for pN+ was 71% overall, and improved to 89% for pN+ LN >1.5 cm. Within iN+, sensitivity/specificity for LN size (>3 cm), total LN number (>4), and ENE were 0.44/0.95, 0.57/0.84, and 0.27/0.96, respectively. Sensitivity of iENE was higher in the subset, with major (>2 mm) versus minor (≤2 mm) pENE (43% vs. 13%, p = 0.001). Reduced OS was observed in iN+ versus iN- (p = 0.006), iENE+ versus iENE- (p = 0.004), LN size >3 versus ≤3 cm (p < 0.001), and higher LN number (p < 0.001). Inter-rater kappa for iN+, laterality, total LN number, and presence of iENE were 0.71, 0.57, 0.78, and 0.69, respectively. CONCLUSION: Our study shows that despite modest sensitivity of most radiological nodal features, the specificity of image-identified nodal features is high and their prognostic values are retained in pN+ OSCC. LEVEL OF EVIDENCE: Level 3 (retrospective review comparing cases and controls) Laryngoscope, 2024.

7.
Nanotechnology ; 35(36)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38861958

RESUMO

Solid electrolyte-gated transistors exhibit improved chemical stability and can fulfill the requirements of microelectronic packaging. Typically, metal oxide semiconductors are employed as channel materials. However, the extrinsic electron transport properties of these oxides, which are often prone to defects, pose limitations on the overall electrical performance. Achieving excellent repeatability and stability of transistors through the solution process remains a challenging task. In this study, we propose the utilization of a solution-based method to fabricate an In2O3/ZnO heterojunction structure, enabling the development of efficient multifunctional optoelectronic devices. The heterojunction's upper and lower interfaces induce energy band bending, resulting in the accumulation of a large number of electrons and a significant enhancement in transistor mobility. To mimic synaptic plasticity responses to electrical and optical stimuli, we utilize Li+-doped high-k ZrOxthin films as a solid electrolyte in the device. Notably, the heterojunction transistor-based convolutional neural network achieves a high accuracy rate of 93% in recognizing handwritten digits. Moreover, our research involves the simulation of a typical sensory neuron, specifically a nociceptor, within our synaptic transistor. This research offers a novel avenue for the advancement of cost-effective three-terminal thin-film transistors tailored for neuromorphic applications.

8.
Materials (Basel) ; 17(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38893861

RESUMO

The fretting wear behaviors of silicone rubber under dry friction and different lubrication conditions are studied experimentally. Water, engine oil, dimethyl silicone oil (DSO), and dimethyl silicone oil doped with graphene oxide (DSO/GO) are selected as lubricants. Under the liquid lubrication conditions, the silicone rubber samples are always immersed in the same volume of lubricant. The contact model of a 440C steel ball and silicone rubber sample is the sphere-on-flat contact. The reciprocating fretting wear experiments are carried out using the reciprocating friction wear tester. A scanning electron microscope and three-dimensional white-light interference profilometer are used to detect the surface wear morphology and obtain the wear volume, respectively. The influences of normal force, lubrication condition, and displacement amplitude on fretting wear behavior are discussed. The fretting wear performances of silicone rubber under different fretting states and lubrication conditions are compared. The results show that for a small normal force, silicone rubber has the best wear resistance under DSO/GO lubrication. While for a large normal force, silicone rubber has the best wear resistance under engine oil lubrication.

9.
Genes (Basel) ; 15(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38927715

RESUMO

Peroxisome proliferator-activated receptor γ (PPARG) has various splicing variants and plays essential roles in the regulation of adipocyte differentiation and lipogenesis. However, little is known about the expression pattern and effect of the PPARG on milk fat synthesis in the buffalo mammary gland. In this study, we found that only PPARG-X17 and PPARG-X21 of the splicing variant were expressed in the buffalo mammary gland. Amino acid sequence characterization showed that the proteins encoded by PPARG-X17 and PPARG-X21 are endonuclear non-secreted hydrophilic proteins. Protein domain prediction found that only the PPARG-X21-encoded protein had PPAR ligand-binding domains (NR_LBD_PPAR), which may lead to functional differences between the two splices. RNA interference (RNAi) and the overexpression of PPARG-X17 and PPARG-X21 in buffalo mammary epithelial cells (BMECs) were performed. Results showed that the expression of fatty acid synthesis-related genes (ACACA, CD36, ACSL1, GPAT, AGPAT6, DGAT1) was significantly modified (p < 0.05) by the RNAi and overexpression of PPARG-X17 and PPARG-X21. All kinds of FAs detected in this study were significantly decreased (p < 0.05) after RNAi of PPARG-X17 or PPARG-X21. Overexpression of PPARG-X17 or PPARG-X21 significantly decreased (p < 0.05) the SFA content, while significantly increased (p < 0.05) the UFA, especially the MUFA in the BMECs. In conclusion, there are two PPARG splicing variants expressed in the BMECs that can regulate FA synthesis by altering the expression of diverse fatty acid synthesis-related genes. This study revealed the expression characteristics and functions of the PPARG gene in buffalo mammary glands and provided a reference for further understanding of fat synthesis in buffalo milk.


Assuntos
Búfalos , Glândulas Mamárias Animais , PPAR gama , Animais , Búfalos/genética , Búfalos/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Glândulas Mamárias Animais/metabolismo , Feminino , Células Epiteliais/metabolismo , Processamento Alternativo , Ácidos Graxos/metabolismo , Ácidos Graxos/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Leite/metabolismo
10.
J Am Chem Soc ; 146(25): 17003-17008, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38865191

RESUMO

We report here a new type of metal fluoride cluster that can be stabilized inside fullerene via in situ fluorine encapsulation followed by exohedral trifluoromethylation, giving rise to rare-earth metal fluoride clusterfullerenes (FCFs) M2F@C80(CF3) (M = Gd and Y). The molecular structure of Gd2F@C80(CF3) was unambiguously determined by single-crystal X-ray analysis to show a µ2-fluoride-bridged Gd-F-Gd cluster with short Gd-F bonds of 2.132(7) and 2.179(7) Å. The 19F NMR spectrum of the diamagnetic Y2F@C80(CF3) confirms the existence of the endohedral F atom, which exhibits a triplet with a large 19F-89Y coupling constant of 74 Hz and a high temperature sensitivity of the 19F chemical shift of 0.057 ppm/K. Theoretical studies reveal the ionic Y-F bonding nature arising from the highest electronegativity of the F element and an electronic configuration of [Y2F]5+@[C80]5- with an open-shell carbon cage, which thus necessitates the stabilization of FCFs by exohedral trifluoromethylation.

11.
J Ethnopharmacol ; 333: 118488, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38925319

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, in addition to hypertension, hyperglycemia, and hyperlipidemia, the prevalence of hyperuricemia (HUA) has increased considerably. Being the fourth major health risk factor, HUA can affect the kidneys and cardiovascular system. Chrysanthemi Indici Flos is a flavonoid-containing traditional Chinese patent medicine that exhibits a uric acid (UA)-lowering effect. However, the mechanisms underlying Chrysanthemi Indici Flos-enriched flavonoid part (CYM.E) mediated alleviation of HUA remain unelucidated. AIM OF THE STUDY: This study aimed to elucidate the efficacy of CYM.E in preventing and treating HUA and its specific effects on UA-related transport proteins, to explore possible mechanism. METHODS: The buddleoside content in CYM.E was determined through high-performance liquid chromatography. HUA was induced in mice models using adenine and potassium oxonate. Subsequently, mice were administered 10 mg/kg allopurinol, and 30, 60, and 90 mg/kg CYM.E to evaluate the effects of CYM.E on the of HUA mice model. Herein, plasma uric acid (UA), creatinine (CR), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) contents, along with serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. Additionally, xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were determined. The histomorphologies of the liver and kidney tissues were examined through hematoxylin and eosin staining. The messenger RNA (mRNA) expression of facilitated glucose transporter 9 (GLUT9), organic anion transporter (OAT)1, OAT3, and adenosine triphosphate binding cassette subfamily G2 (ABCG2) in the kidney was assessed by real-time quantitative polymerase chain reaction. Furthermore, the expression of urate transporter 1 (URAT1), GLUT9, OAT1, and OAT3 in the kidney, OAT4, and ABCG2 proteins was determined by immunohistochemistry and western blotting. RESULTS: The buddleoside content in CYM.E was approximately 32.77%. CYM.E improved body weight and autonomous activity in HUA mice. Additionally, it reduced plasma UA, BUN, and CR levels and serum ALT and AST activities, thus improving hepatic and renal functions, which further reduced the plasma UA content. CYM.E reduced histopathological damage to the kidneys. Furthermore, it lowered plasma TC, TG, and LDL-c levels, thereby improving lipid metabolism disorder. CYM.E administration inhibited hepatic XOD and ADA activities and reduced the mRNA expression of renal GLUT9. CYM.E inhibited the protein expression of renal URAT1, GLUT9, and OAT4, and increased the mRNA and protein expression of renal OAT1, OAT3, and ABCG2. Altogether, these results show that CYM.E could inhibit the production and promote reabsorption of UA and its excretion.


Assuntos
Modelos Animais de Doenças , Flavonoides , Hiperuricemia , Transportadores de Ânions Orgânicos , Ácido Úrico , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/induzido quimicamente , Ácido Úrico/sangue , Masculino , Flavonoides/farmacologia , Flavonoides/análise , Camundongos , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Flores/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Alopurinol/farmacologia , Camundongos Endogâmicos ICR
12.
Proc Natl Acad Sci U S A ; 121(27): e2312337121, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38923987

RESUMO

Sodium-ion batteries (SIBs) as one of the promising alternatives to lithium-ion batteries have achieved remarkable progress in the past. However, the all-climate performance is still very challenging for SIBs. Herein, 15-Crown-5 (15-C-5) is screened as an electrolyte additive from a number of ether molecules theoretically. The good sodiophilicity, high molecule rigidity, and bulky size enable it to reshape the solvation sheath and promote the anion engagement in the solvated structures by molecule crowding. This change also enhances Na-ion transfer, inhibits side reactions, and leads to a thin and robust solid-electrolyte interphase. Furthermore, the electrochemical stability and operating temperature windows of the electrolyte are extended. These profits improve the electrochemical performance of SIBs in all climates, much better than the case without 15-C-5. This improvement is also adopted to µ-Sn, µ-Bi, hard carbon, and MoS2. This work opens a door to prioritize the potential molecules in theory for advanced electrolytes.

13.
J Am Chem Soc ; 146(29): 19998-20008, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38865282

RESUMO

As the dimensionality of materials generally affects their characteristics, thin films composed of low-dimensional nanomaterials, such as nanowires (NWs) or nanoplates, are of great importance in modern engineering. Among various bottom-up film fabrication strategies, interfacial assembly of nanoscale building blocks holds great promise in constructing large-scale aligned thin films, leading to emergent or enhanced collective properties compared to individual building blocks. As for 1D nanostructures, the interfacial self-assembly causes the morphology orientation, effectively achieving anisotropic electrical, thermal, and optical conduction. However, issues such as defects between each nanoscale building block, crystal orientation, and homogeneity constrain the application of ordered films. The precise control of transdimensional synthesis and the formation mechanism from 1D to 2D are rarely reported. To meet this gap, we introduce an interfacial-assembly-induced interfacial synthesis strategy and successfully synthesize quasi-2D nanofilms via the oriented attachment of 1D NWs on the liquid interface. Theoretical sampling and simulation show that NWs on the liquid interface maintain their lowest interaction energy for the ordered crystal plane (110) orientation and then rearrange and attach to the quasi-2D nanofilm. This quasi-2D nanofilm shows enhanced electric conductivity and unique optical properties compared with its corresponding 1D geometry materials. Uncovering these growth pathways of the 1D-to-2D transition provides opportunities for future material design and synthesis at the interface.

14.
Mar Pollut Bull ; 205: 116546, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38870575

RESUMO

Paralytic shellfish toxins (PSTs) can pose a serious threat to human health. Among them, saxitoxin (STX) is one of the most potent natural neurotoxins. Here, the copepod Tigriopus japonicus, was exposed to environmentally relevant concentrations (2.5 and 25 µg/L) STX for 48 h. Although no lethal effects were observed at both concentrations, the transcriptome was significantly altered, and displayed a concentration-dependent response. STX exposure decreased the copepod's metabolism and compromised immune defense and detoxification. Additionally, STX disturbed signal transduction, which might affect other cellular processes. STX exposure could inhibit the copepod's chitin metabolism, disrupting its molting process. Also, the processes related to damage repair and protection were up-regulated to fight against high concentration exposure. Collectively, this study has provided an early warning of PSTs for coastal ecosystem not only because of their potent toxicity effect but also their bioaccumulation that can transfer up the food chain after ingestion by copepods.


Assuntos
Copépodes , Saxitoxina , Transcriptoma , Poluentes Químicos da Água , Copépodes/efeitos dos fármacos , Animais , Saxitoxina/toxicidade , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
15.
Nano Lett ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38843402

RESUMO

High-entropy alloys (HEAs) have garnered considerable attention as promising nanocatalysts for effectively utilizing Pt in catalysis toward oxygen reduction reactions due to their unique properties. Nonetheless, there is a relative dearth of attention regarding the structural evolution of HEAs in response to electrochemical conditions. In this work, we propose a thermal reduction method to synthesize high entropy nanoparticles by leveraging the confinement effect and abundant nitrogen-anchored sites provided by pyrolyzed metal-organic frameworks (MOFs). Notably, the prepared catalysts exhibit enhanced activity accompanied by structural reconstruction during electrochemical activation, approaching 1 order of magnitude higher mass activity compared to Pt/C in oxygen reduction. Atomic-scale structural characterization reveals that abundant defects and single atoms are formed during the activation process, contributing to a significant boost in the catalytic performance for oxygen reduction reactions. This study provides deep insights into surface reconstruction engineering during electrochemical operations, with practical implications for fuel cell applications.

16.
Eur Geriatr Med ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842653

RESUMO

PURPOSE: Numerous epidemiological studies have suggested a possible association between dysphagia and the risk of decline in Activities of daily living (ADL) among older adults. This systematic review and meta-analysis aimed to elucidate the relationship between dysphagia and ADL in older adults. METHODS: PubMed, Web of Science, Cochrane Library, Embase, Ebsco, MEDLINE, Wiley, CINAHL, and Ovid databases were comprehensively examined for relevant studies published up to October 31, 2022. Quantitative studies published in English were included to explore the relationship between dysphagia and ADL in people aged 65 years and older. The NIH Quality Assessment Tool was used to assess the study quality. R software was used to draw forest plots and I2 was employed to indicate study heterogeneity. Sensitivity analysis was performed using the one-by-one exclusion method. Publication bias was measured using funnel plots and Egger's test. RESULTS: A total of 3,498 studies were retrieved from the database, 22 of which were eventually included in the systematic evaluation, and 14 of which were subjected to meta-analysis. Data from nine studies were categorical variables, and meta-analysis results showed that swallowing disorders in older adults were associated with a lower ability to perform ADL (OR = 3.39, 95% CI: 2.55-4.50, p < 0.001), with moderate heterogeneity (I2 = 62%, p = 0.006). Data from seven studies were continuous variables, resulting in a negative association between the prevalence of dysphagia and ADLs in older adults (SMD = -0.80, 95% CI: -1.08 to -0.51, p < 0.001), with high heterogeneity (I2 = 94%, p < 0.001). Sensitivity analysis showed robust results, funnel plots and Egger's test indicated no publication bias. CONCLUSION: Dysphagia is significantly associated with the capacity to perform ADL. Prevention and screening of dysphagia in older patients dependent on others for daily care are needed. Further long-term studies are needed in the future to prove causality.

17.
J Med Chem ; 67(13): 11182-11196, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38906533

RESUMO

Analogues of hormonal vitamin D, 1,25-dihydroxyvitamin D (1,25D), signal through the nuclear vitamin D receptor (VDR). They have potential in combination therapies with other anticancer agents such as histone deacetylase inhibitors (HDACi's). Here, we characterize the ZG series of hybrid compounds that combine HDACi within the backbone of a VDR agonist. All display improved solubility, with ZG-126 being the most robustly bifunctional molecule in multiple cell lines. ZG-126 is well tolerated and strongly induces VDR target gene expression in vivo at therapeutic doses. Its antitumor efficacy is superior to 1,25D and the HDACi SAHA, separately or together, in mouse models of melanoma and triple-negative breast cancer (TNBC). Notably, ZG-126 treatment reduces metastases almost 4-fold in an aggressive TNBC model. ZG-126 also reduces total macrophage infiltration and the proportion of immunosuppressive M2-polarized macrophages in TNBC tumors by 2-fold. ZG-126 thus represents a bifunctional and efficacious anticancer agent with improved physicochemical properties.


Assuntos
Antineoplásicos , Inibidores de Histona Desacetilases , Receptores de Calcitriol , Animais , Feminino , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/uso terapêutico , Camundongos Endogâmicos C57BL , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/metabolismo , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
18.
Sensors (Basel) ; 24(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732965

RESUMO

Although the rapid expansion of urban rail transit offers convenience to citizens, the issue of subway vibration cannot be overlooked. This study investigates the spatial distribution characteristics of vibration in the Fayuan Temple historic and cultural reserve. It involves using a V001 magnetoelectric acceleration sensor capable of monitoring low amplitudes with a sensitivity of 0.298 V/(m/s2), a measuring range of up to 20 m/s2, and a frequency range span from 0.5 to 100 Hz for in situ testing, analyzing the law of vibration propagation in this area, evaluating the impact on buildings, and determining the vibration reduction scheme. The reserve is divided into three zones based on the vertical vibration level measured during the in situ test as follows: severely excessive, generally excessive, and non-excessive vibration. Furthermore, the research develops a dynamic coupling model of vehicle-track-tunnel-stratum-structure to verify the damping effect of the wire spring floating plate track and periodic pile row. It compares the characteristics of three vibration reduction schemes, namely, internal vibration reduction reconstruction, periodic pile row, and anti-vibration reinforcement or reconstruction of buildings, proposing a comprehensive solution. Considering the construction conditions, difficulty, cost, and other factors, a periodic pile row is recommended as the primary treatment measure. If necessary, anti-vibration reinforcement or reconstruction of buildings can serve as supplemental measures.

19.
Neural Netw ; 176: 106331, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38701599

RESUMO

Adversarial attack reveals a potential imperfection in deep models that they are susceptible to being tricked by imperceptible perturbations added to images. Recent deep multi-object trackers combine the functionalities of detection and association, rendering attacks on either the detector or the association component an effective means of deception. Existing attacks focus on increasing the frequency of ID switching, which greatly damages tracking stability, but is not enough to make the tracker completely ineffective. To fully explore the potential of adversarial attacks, we propose Blind-Blur Attack (BBA), a novel attack method based on spatio-temporal motion information to fool multi-object trackers. Specifically, a simple but efficient perturbation generator is trained with the blind-blur loss, simultaneously making the target invisible to the tracker and letting the background be regarded as moving targets. We take TraDeS as our main research tracker, and verify our attack method on other excellent algorithms (i.e., CenterTrack, FairMOT, and ByteTrack) on MOT-Challenge benchmark datasets (i.e., MOT16, MOT17, and MOT20). BBA attack reduced the MOTA of TraDeS and ByteTrack from 69.1 and 80.3 to -238.1 and -357.0, respectively, indicating that it is an efficient method with a high degrees of transferability.


Assuntos
Algoritmos , Redes Neurais de Computação , Humanos , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Segurança Computacional
20.
Signal Transduct Target Ther ; 9(1): 141, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811527

RESUMO

The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+ T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.


Assuntos
Anticorpos Antivirais , Linfócitos T CD8-Positivos , COVID-19 , Células T de Memória , Reinfecção , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/imunologia , COVID-19/patologia , SARS-CoV-2/imunologia , Masculino , Feminino , Reinfecção/imunologia , Pessoa de Meia-Idade , Linfócitos T CD8-Positivos/imunologia , Adulto , Anticorpos Antivirais/imunologia , Células T de Memória/imunologia , Idoso , Linfócitos T CD4-Positivos/imunologia , Memória Imunológica
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