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1.
Adv Sci (Weinh) ; : e2402917, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38962930

RESUMO

The confinement of waves in open systems represents a fundamental phenomenon extensively explored across various branches of wave physics. Recently, significant attention is directed toward bound states in the continuum (BIC), a class of modes that are trapped but do not decay in an otherwise unbounded continuum. Here, the theoretical investigation and experimental demonstration of the existence of quasi-bound states in the continuum (QBIC) for ultrasonic waves are achieved by leveraging an elastic Fabry-Pérot metasurface resonator. Several intriguing properties of the ultrasound quasi-bound states in the continuum that are robust to parameter scanning are unveiled, and experimental evidence of a remarkable Q-factor of 350 at ≈1 MHz frequency, far exceeding the state-of-the-art using a fully acoustic underwater system is presented. The findings contribute novel insights into the understanding of BIC for acoustic waves, offering a new paradigm for the design of efficient, ultra-high Q-factor ultrasound devices.

2.
Sci Rep ; 14(1): 15150, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956232

RESUMO

Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1-14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Gastrectomia , Oxaliplatina , Ácido Oxônico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Masculino , Feminino , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Tegafur/uso terapêutico , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Gastrectomia/métodos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Ácido Oxônico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Quimioterapia Adjuvante/métodos , Paclitaxel Ligado a Albumina/administração & dosagem , Paclitaxel Ligado a Albumina/uso terapêutico , Adulto , Intervalo Livre de Doença , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Albuminas/administração & dosagem
3.
Sci Rep ; 14(1): 15128, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956254

RESUMO

Mohr-Coulomb (MC) strength criterion has been widely used in many classical analytical expressions and numerical modeling due to its simple physical calculation, but the MC criterion is not suitable for describing the failure envelope of rock masses. In order to directly apply MC parameters to analytical expressions or numerical modeling in rock slope stability analysis, scholars established a criterion for converting Hoek-Brown (HB) parameters to equivalent MC parameters. However, the consistency of HB parameters and equivalent MC parameters in calculating critical acceleration of slope needs to be further explored and confirmed. Therefore, HB parameters are converted into equivalent MC parameters by considering the influence of slope angle (1# case and 2# case when slope angle is not considered and slope angle is considered respectively). Then, the lower-bound of finite element limit analysis is used for numerical modeling, and the results of calculating critical acceleration using HB parameters and equivalent MC parameters are compared, and the influence of related parameters on the calculation of critical acceleration is studied. Finally, the influence of different critical accelerations on the calculation of slope permanent displacement is further analyzed through numerical cases and engineering examples. The results show that: (1) In the 1# case, the critical acceleration obtained by the equivalent MC parameters are significantly larger than that obtained by the 2 #case and the HB parameters, and this difference becomes more obvious with the increase of slope angle. The critical acceleration obtained by the 2# case is very close to the HB parameters; (2) In the 1# case, slope height is inversely proportional to ΔAc (HB(Ac) - 1#(Ac)), and with the increase of slope height, ΔAc decreases, while in the 2# case, the difference of ΔAc (HB(Ac) - 2#(Ac)) is not significant; (3) In the 1# case, the sensitivity of the HB parameters to ΔAc is D > GSI > mi > σci, but in the 2# case, there is no sensitivity-related regularity; (4) The application of HB parameters and equivalent MC parameters in slope permanent displacement is studied through numerical cases and engineering examples, and the limitations of equivalent MC parameters in rock slope stability evaluation are revealed.

4.
J Biol Chem ; : 107551, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002671

RESUMO

Isoforms of microtubule associated protein 2 (MAP2) differ from their homologue Tau in the sequence and interactions of the N-terminal region. Binding of the N-terminal region of MAP2c (N-MAP2c) to the dimerization/docking domains of the regulatory subunit RIIα of cAMP-dependent protein kinase (RIIDD2) and to the Src-homology domain 2 of growth factor receptor-bound protein 2 (Grb2) have been described long time ago. However, the structural features of the complexes remained unknown due to the disordered nature of MAP2. Here we provide structural description of the complexes. We have solved solution structure of N-MAP2c in complex with RIIDD2, confirming formation of an amphiphilic α-helix of MAP2c upon binding, defining orientation of the α-helix in the complex and showing that its binding register differs from previous predictions. Using chemical shift mapping, we characterized the binding interface of SH2-Grb2 and rat MAP2c phosphorylated by the tyrosine kinase Fyn in their complex, and proposed a model explaining differences between SH2-Grb2 complexes with rat MAP2c and phosphopeptides with a Grb2-specific sequence. The results provide the structural basis of a potential role of MAP2 in regulating cAMP-dependent phosphorylation cascade via interactions with RIIDD2 and Ras signaling pathway via interactions with SH2-Grb2.

5.
Neural Netw ; 179: 106486, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38986185

RESUMO

Reservoir computing approximation and generalization bounds are proved for a new concept class of input/output systems that extends the so-called generalized Barron functionals to a dynamic context. This new class is characterized by the readouts with a certain integral representation built on infinite-dimensional state-space systems. It is shown that this class is very rich and possesses useful features and universal approximation properties. The reservoir architectures used for the approximation and estimation of elements in the new class are randomly generated echo state networks with either linear or ReLU activation functions. Their readouts are built using randomly generated neural networks in which only the output layer is trained (extreme learning machines or random feature neural networks). The results in the paper yield a recurrent neural network-based learning algorithm with provable convergence guarantees that do not suffer from the curse of dimensionality when learning input/output systems in the class of generalized Barron functionals and measuring the error in a mean-squared sense.

6.
Food Chem ; 459: 140345, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38986204

RESUMO

Considering the high abundance of bound polyphenols (BP) in whole grain dietary fiber (DF), this study utilized multi-omics approach to evaluate the impact of BP of defatted rice bran insoluble DF (RIDF) in modulating obesity. Mice on high-fat diet were gavage-administered RIDF, BP-removed or formulated RIDF. The results indicated that DF significantly reduced serum total cholesterol, triglycerides, high-density and low-density lipoprotein cholesterol levels. Moreover, hepatic lipid accumulation and damage induced by high-fat diet were significantly ameliorated with DF intervention. The presence of BP increased the abundance of beneficial bacteria g_Akkermansia and g_Butyricicocus, as well as the expression of butyric acid/propionic acid. Furthermore, the expression of hepatic lipids and lipid-like molecules was significantly decreased under the combined intervention of BP and DF, and this was accompanied by alterations in genes related to lipid, sterol, and cholesterol metabolic biological processes. These findings suggest that BP contribute to the anti-obesity effects of DF.

7.
Methods Mol Biol ; 2821: 179-193, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38997489

RESUMO

Characterization of peptide antibodies through identification of their target epitopes is of utmost importance, as information about epitopes provide important knowledge, among others, for discovery and development of new therapeutics, vaccines, and diagnostics.This chapter describes a strategy for mapping of continuous peptide antibody epitopes using resin-bound and soluble peptides. The approach combines three different types of peptide sets for full characterization of peptide antibodies; (i) overlapping peptides, used to locate antigenic regions; (ii) truncated peptides, used to identify the minimal peptide length required for antibody binding; and (iii) substituted peptides, used to identify the key residues important for antibody binding and to determine the specific contribution of key residues. For initial screening, resin-bound peptides are used for epitope estimation, while soluble peptides subsequently are used for final epitope characterization and identification of critical hot spot residues. The combination of resin-bound peptides and soluble peptides for epitope mapping provides a time-saving and straightforward approach for characterization of antibodies recognizing continuous epitopes, which applies to peptide antibodies and occasionally antibodies directed to larger proteins as well.


Assuntos
Anticorpos , Mapeamento de Epitopos , Epitopos , Peptídeos , Mapeamento de Epitopos/métodos , Peptídeos/imunologia , Peptídeos/química , Epitopos/imunologia , Epitopos/química , Anticorpos/imunologia , Anticorpos/química , Solubilidade , Humanos
8.
Acta Biomater ; 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39043290

RESUMO

Extracellular vesicles (EV) are a heterogeneous group of lipid particles excreted by cells. They play an important role in regeneration, development, inflammation, and cancer progression, together with the extracellular matrix (ECM), which they constantly interact with. In this review, we discuss direct and indirect interactions of EVs and the ECM and their impact on different physiological processes. The ECM affects the secretion of EVs, and the properties of the ECM and EVs modulate EVs' diffusion and adhesion. On the other hand, EVs can affect the ECM both directly through enzymes and indirectly through the modulation of the ECM synthesis and remodeling by cells. This review emphasizes recently discovered types of EVs bound to the ECM and isolated by enzymatic digestion, including matrix-bound nanovesicles (MBV) and tissue-derived EV (TiEV). In addition to the experimental studies, computer models of the EV-ECM-cell interactions, from all-atom models to quantitative pharmacology models aiming to improve our understanding of the interaction mechanisms, are also considered. STATEMENT OF SIGNIFICANCE: Application of extracellular vesicles in tissue engineering is an actively developing area. Vesicles not only affect cells themselves but also interact with the matrix and change it. The matrix also influences both cells and vesicles. In this review, different possible types of interactions between vesicles, matrix, and cells are discussed. Furthermore, the united EV-ECM system and its regulation through the cellular activity are presented.

9.
Nano Lett ; 24(29): 9027-9033, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38984823

RESUMO

We study, both theoretically and experimentally, strong interaction between a quasi-bound state in the continuum (QBIC) supported by a resonant metasurface with an epsilon-near-zero (ENZ) guided mode excited in an ultrathin ITO layer. We observe and quantify the strong coupling regime of the QBIC-ENZ interaction in the hybrid metasurface manifested through the mode splitting over 200 meV. We also measure experimentally the resonant nonlinear response enhanced near the ENZ frequency and observe the effective nonlinear refractive index up to ∼4 × 10-13 m2/W in the ITO-integrated dielectric nanoresonators, which provides a promising platform for low-power nonlinear photonic devices.

10.
Nano Lett ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041646

RESUMO

Chiral nanostructures allow engineering of chiroptical responses; however, their design usually relies on empirical approaches and extensive numerical simulations. It remains unclear if a general strategy exists to enhance and maximize the intrinsic chirality of subwavelength photonic structures. Here, we suggest a microscopic theory and uncover the origin of strong chiral responses of resonant nanostructures. We reveal that the reactive helicity density is critically important for achieving maximum chirality at resonances. We demonstrate our general concept on the examples of planar photonic crystal slabs and metasurfaces, where out-of-plane mirror symmetry is broken by a bilayer design. Our findings provide a general recipe for designing photonic structures with maximum chirality, paving the way toward many applications, including chiral sensing, chiral emitters and detectors, and chiral quantum optics.

11.
Sci Total Environ ; 947: 174467, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969122

RESUMO

Although industrial activities are significant contributors to atmospheric releases of particulate matter (PM) and associated toxic substances that lead to adverse human health effects, a knowledge gap exists concerning the human health risk resulting from such activities owing to lack of evaluation of industrial emissions. Here, we comprehensively characterized and quantified PM from 118 full-scale industrial plants. The dominant (97.9 %) PM showed diameters of <2.5 µm; 79.0 % had diameters below 1 µm. Annual atmospheric releases of Fe and heavy metals (As, Cd, Cr, Cu, Ni, Pb, Zn) contained in fine PM from these global industrial activities are estimated to be 51,161 t and 69,591 t, respectively. Emissions of heavy metals from these industries cause increased cancer risk, estimated to range from 1461 % to 50,752 %. Five crystalline compounds (ZnO, PbSO4, Mn3O4, Fe3O4, Fe2O3) that can indicate specific industrial sources are identified. Global annual emissions of these toxic compounds in fine PM from the industrial sources are estimated to be 78,635 t. The Global South displayed higher emissions than the Global North. These results are significant for recognizing regional health risks of industrial emissions.

12.
Anal Bioanal Chem ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028344

RESUMO

Free iron in human serum or non-transferrin-bound iron (NTBI) can generate free radicals and lead to oxidative damage. Moreover, it is highly toxic to various tissues and a vital biomarker related to the iron-loading status of thalassemia and Alzheimer's patients. In NTBI in healthy individuals, NTBI levels are typically less than 1 µM; current NTBI analysis usually requires advanced instrumentation and many-step sample pretreatment. To address this issue, we employed our invented BODIPY derivative, BODIPY-PH, as a fluorescence probe and trapped it onto the microcentrifuge tube lid using tapioca starch. The fluorescence intensity of BODIPY-PH increased with increasing NTBI concentration (turn-on). The developed portable reaction chamber facilitates rapid analysis (∼5 min) using small sample volumes (10 µL sample in a total volume of 600 µL). Under optimum conditions, using the sample-developed portable fluorescence device and fluorescence spectrometer, we achieved impressive limits of detection (LOD) of 0.003 and 0.0015 µM, respectively. Furthermore, the developed sensors show relatively high selectivity toward Fe3+ over other metal ions and biomolecules (i.e., Fe2+, Cr3+, Cu2+, and glucose). The sensor performance in serum samples of thalassemia patients exhibited no significant difference compared to the labeled value (obtained from standard methods). Overall, the developed fluorescence sensor is suitable for determining NTBI and offers high sensitivity, high selectivity, and a short incubation time (5 min). Moreover, the method requires a limited number of reagents, is simple to use, and uses low-cost equipment to determine NTBI in human serum samples.

13.
ACS Nano ; 18(29): 18880-18888, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38991129

RESUMO

Emitting light toward on-demand directions is important for various optoelectronic applications, such as optical communication, displaying, and ranging. However, almost all existing directional emitters are assemblies of passive optical antennae and external light sources, which are usually bulky and fragile and show unendurable loss of light power. Here we theoretically propose and experimentally demonstrate a conceptual design of a directional emitter, by using a single surface-emitting laser source itself to achieve dynamically controlled beam steering. The laser is built on photonic crystals that operate near the band edges in the continuum. By shrinking laser sizes to tens-of-wavelength, the optical modes quantize in three-dimensional momentum space, and each of them directionally radiates toward the far-field. Further utilizing the luminescence spectrum shifting effect under current injection, we consecutively select a sequence of modes into lasing action and show the laser maintaining single-mode operation with line widths at a minimum of 1.8 MHz and an emitting power of ∼10 milliwatts, and we demonstrate fast beam steering across a range of 3.2° × 4° on a time scale of 500 ns. Our work proposes a method for on-chip active beam steering for the development of automotive, industrial, and robotic applications.

14.
Bioresour Technol ; : 131136, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033827

RESUMO

The effects of three typical N-acyl-homoserine lactones (AHLs) on the tolerance of biological nitrogen removal (BNR) system to chronic exposure of zinc oxide nanoparticles (NPs) were investigated. C4-HSL successfully delayed the crash time of nitrogen removal performances in the NP-stressed system, while C6-HSL and C10-HSL maintained total nitrogen removal efficiencies throughout the 90-day NP exposure. All three AHLs increased NPs' contents captured in extracellular polymeric substances, alleviating membrane damage and preserving floc structure. The activities of tricarboxylic acid cycle-related enzymes and the relative abundances of BNR-related functional genes and genera were significantly enhanced. Besides, C6-HSL and C10-HSL augmented antioxidant enzyme activities and the abundances of functional genes and metabolites related to antioxidation, flagellar assembly, and chemotaxis, which synergistically reduced the reactive oxygen species' excessive accumulation. The tested AHLs effectively enhanced BNR systems' tolerance to chronic NP exposure, providing inspiration for quorum sensing applications in emerging contaminant removal.

15.
Consort Psychiatr ; 5(1): 44-47, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39021750

RESUMO

The Dhat syndrome is a culture-bound syndrome associated with anxiety and somatic and mood symptoms related to semen loss. It sometimes occurs in women, in whom it comes with vaginal discharge. Only a single case has been reported whereby Dhat delusion was associated with schizophrenia. In this case report, we dwell on two individuals suffering from a somatic-type delusional disorder with Dhat-like symptoms who had initially presented classical symptoms of the Dhat syndrome. Further studies are needed to explore the intersections of Dhat syndrome and psychoses, as well as the risk factors involved in mutual predisposition.

16.
Crit Rev Food Sci Nutr ; : 1-17, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38965668

RESUMO

Most studies on the beneficial effects of polyphenols on human health have focused on polyphenols extracted using aqueous organic solvents, ignoring the fact that a portion of polyphenols form complexes with polysaccharides. Polysaccharides and polyphenols are interrelated, and their interactions affect the physicochemical property, quality, and nutritional value of foods. In this review, the distribution of bound polyphenols in major food sources is summarized. The effect of food processing on the interaction between polyphenols and cell wall polysaccharides (CWP) is discussed in detail. We also focus on the digestion, absorption, and metabolic behavior of polysaccharide-polyphenol complexes. Different food processing techniques affect the interaction between CWP and polyphenols by altering their structure, solubility, and strength of interactions. The interaction influences the free concentration and extractability of polyphenols in food and modulates their bioaccessibility in the gastrointestinal tract, leading to their major release in the colon. Metabolism of polyphenols by gut microbes significantly enhances the bioavailability of polyphenols. The metabolic pathway and product formation rate of polyphenols and the fermentation characteristics of polysaccharides are affected by the interaction. Furthermore, the interaction exhibits synergistic or antagonistic effects on the stability, solubility, antioxidant and functional activities of polyphenols. In summary, understanding the interactions between polysaccharides and polyphenols and their changes in food processing is of great significance for a comprehensive understanding of the health benefits of polyphenols and the optimization of food processing technology.

17.
Nanophotonics ; 13(16): 2937-2949, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39006137

RESUMO

Thanks to their giant, yet tunable, Q-factor resonances, all-dielectric metasurfaces supporting the quasi-bound states in the continuum (q-BIC) resonances are well-suited to provide a promising platform for quantum-coherent light-matter interactions. Yet, the strong coupling regime, characterized by the hybrid light-matter states - polaritons, has not yet been fully explored in the mid-infrared regime. This paper investigates the parameter space of vibrational strong coupling (VSC) between material and metasurface cavities supporting q-BIC resonances in the mid-infrared spectral range. We outline the effects of transition dipole strength, damping rate, and the number of molecules coupled to a single cavity, as well as the cavity damping rates, to understand their respective impacts on VSC. By tuning the Q-factor of the metasurface and material parameters, a new transition light-matter coupling zone is introduced, bridging the gap between weak and strong coupling, where polaritons form but their linewidths prohibit their spectral identification. The study further identifies the effects of cavity linewidth on polariton peak separability in strongly coupled systems, highlighting that the cavities with smaller nonradiative losses and narrower linewidths facilitate better polariton separability. Moreover, we found that matching cavity and material loss, satisfying the critical strong coupling condition, enhances the coupling strength between cavity and material. Overall, these findings can guide the design of photonic cavities suited for VSC experiments, contributing to the burgeoning fields of polaritonic chemistry, light-mediated modulation of chemical reactivity, and highly sensitive molecular spectroscopy.

18.
Bioresour Technol ; : 131130, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032533

RESUMO

During remediation of black-odorous sediment, the pathways of phosphorus immobilization require clarification alongside the oxidation of sulfide and ferrous. This study separated the oxidation stages of sulfide and ferrous through controlled sodium nitrate dosing ratios and methods, and analyzed the changes in phosphorus species and immobilization effects throughout these processes. Results showed that iron-bound phosphorus was the primary contributor to the phosphorus immobilization capacity of the sediment, with the increase ranging from 15 % to 56 % and affected the transformation between phosphorus sources or sinks across varying oxidation states. Additionally, the increase in abundance of phosphorus uptake and transport genes and of denitrifying phosphorus accumulation genes in sediment after ferrous oxidation (1 %-18 % and 87 %-164 %, respectively) indicated the potential for biological phosphorus immobilization. These results demonstrated that higher degrees of sediment oxidation correlate with stronger phosphorus immobilization capacities, providing theoretical bases for phosphorus immobilization during the restoration of black-odorous water bodies.

19.
J Integr Plant Biol ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888228

RESUMO

Callose, a ß-1,3-glucan plant cell wall polymer, regulates symplasmic channel size at plasmodesmata (PD) and plays a crucial role in a variety of plant processes. However, elucidating the molecular mechanism of PD callose homeostasis is limited. We screened and identified an Arabidopsis mutant plant with excessive callose deposition at PD and found that the mutated gene was α1-COP, a member of the coat protein I (COPI) coatomer complex. We report that loss of function of α1-COP elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme PdBG2. This process is linked to the functions of ERH1, an inositol phosphoryl ceramide synthase, and glucosylceramide synthase through physical interactions with the α1-COP protein. Additionally, the loss of function of α1-COP alters the subcellular localization of ERH1 and GCS proteins, resulting in a reduction of GlcCers and GlcHCers molecules, which are key sphingolipid (SL) species for lipid raft formation. Our findings suggest that α1-COP protein, together with SL modifiers controlling lipid raft compositions, regulates the subcellular localization of GPI-anchored PDBG2 proteins, and hence the callose turnover at PD and symplasmic movement of biomolecules. Our findings provide the first key clue to link the COPI-mediated intracellular trafficking pathway to the callose-mediated intercellular signaling pathway through PD.

20.
Cancer Epidemiol ; : 102599, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871555

RESUMO

BACKGROUND: Canine and human osteosarcoma are similar in clinical presentation and tumor genomics. Giant breed dogs experience elevated osteosarcoma incidence, and taller stature remains a consistent risk factor for human osteosarcoma. Whether evolutionarily conserved genes contribute to both human and canine osteosarcoma predisposition merits evaluation. METHODS: A multi-center sample of childhood osteosarcoma patients and controls underwent genome-wide genotyping and imputation. Ancestry-adjusted SNP associations were calculated within each dataset using logistic regression, then meta-analyzed across the three datasets, totaling 1091 patients and 3026 controls. Ten regions previously associated with canine osteosarcoma risk were mapped to the human genome, spanning ∼6 Mb. We prioritized association testing of 5985 human SNPs mapping to candidate osteosarcoma risk regions detected in Irish wolfhounds, the largest dog breed studied. Secondary analyses explored 6289 additional human SNPs mapping to candidate osteosarcoma risk regions identified in Rottweilers and greyhounds. RESULTS: Fourteen SNPs were associated with human osteosarcoma risk after adjustment for multiple comparisons, all within a 42 kb region of human Chromosome 7p12.1. The lead variant was rs17454681 (OR=1.25, 95 %CI: 1.12-1.39; P=4.1×10-5), and independent risk variants were not observed in conditional analyses. While the associated region spanned 2.1 Mb and contained eight genes in Irish wolfhounds, associations were localized to a 50-fold smaller region of the human genome and strongly implicate GRB10 (growth factor receptor-bound protein 10) in canine and human osteosarcoma predisposition. PheWAS analysis in UK Biobank data identified noteworthy associations of the rs17454681 risk allele with varied measures of height and pubertal timing. CONCLUSIONS: Our comparative oncology analysis identified a novel human osteosarcoma risk allele near GRB10, a growth inhibitor that suppresses activated receptor tyrosine kinases including IGF1R, PDGFRB, and EGFR. Epidemiologists may benefit from leveraging cross-species comparisons to identify haplotypes in highly susceptible but genetically homogenous populations of domesticated animals, then fine-mapping these associations in diverse human populations.

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