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1.
Proc Natl Acad Sci U S A ; 120(40): e2304096120, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748052

RESUMO

Eight extant species of pangolins are currently recognized. Recent studies found that two mitochondrial haplotypes identified in confiscations in Hong Kong could not be assigned to any known pangolin species, implying the existence of a species. Here, we report that two additional mitochondrial haplotypes identified in independent confiscations from Yunnan align with the putative species haplotypes supporting the existence of this mysterious species/population. To verify the new species scenario we performed a comprehensive analysis of scale characteristics and 138 whole genomes representing all recognized pangolin species and the cryptic new species, 98 of which were generated here. Our morphometric results clearly attributed this cryptic species to Asian pangolins (Manis sp.) and the genomic data provide robust and compelling evidence that it is a pangolin species distinct from those recognized previously, which separated from the Philippine pangolin and Malayan pangolin over 5 Mya. Our study provides a solid genomic basis for its formal recognition as the ninth pangolin species or the fifth Asian one, supporting a new taxonomic classification of pangolins. The effects of glacial climate changes and recent anthropogenic activities driven by illegal trade are inferred to have caused its population decline with the genomic signatures showing low genetic diversity, a high level of inbreeding, and high genetic load. Our finding greatly expands current knowledge of pangolin diversity and evolution and has vital implications for conservation efforts to prevent the extinction of this enigmatic and endangered species from the wild.


Assuntos
Genômica , Pangolins , Animais , Efeitos Antropogênicos , Ásia , China , Pangolins/genética , Crescimento Demográfico
2.
Proc Natl Acad Sci U S A ; 120(11): e2214556120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36888664

RESUMO

Computationally designed protein nanoparticles have recently emerged as a promising platform for the development of new vaccines and biologics. For many applications, secretion of designed nanoparticles from eukaryotic cells would be advantageous, but in practice, they often secrete poorly. Here we show that designed hydrophobic interfaces that drive nanoparticle assembly are often predicted to form cryptic transmembrane domains, suggesting that interaction with the membrane insertion machinery could limit efficient secretion. We develop a general computational protocol, the Degreaser, to design away cryptic transmembrane domains without sacrificing protein stability. The retroactive application of the Degreaser to previously designed nanoparticle components and nanoparticles considerably improves secretion, and modular integration of the Degreaser into design pipelines results in new nanoparticles that secrete as robustly as naturally occurring protein assemblies. Both the Degreaser protocol and the nanoparticles we describe may be broadly useful in biotechnological applications.


Assuntos
Nanopartículas , Vacinas , Proteínas , Nanopartículas/química
3.
Acc Chem Res ; 57(17): 2572-2581, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39159428

RESUMO

ConspectusElectrides make up a fascinating group of materials with unique physical and chemical properties. In these materials, excess electrons do not behave like normal electrons in metals or form any chemical bonds with atoms. Instead, they "float" freely in the gaps within the material's structure, acting like negatively charged particles called anions (see the graph). Recently, there has been a surge of interest in van der Waals (vdW) electrides or electrenes in two dimensions. A typical example is layered lanthanum bromide (LaBr2), which can be taken as [La3+(Br1-)2]+•(e-). Each excess free electron is trapped within a hexagonal pore, forming dense dots of electron density. These anionic electrons are loosely bound, giving vdW electrides some unique properties such as ferromagnetism, superconductivity, topological features, and Dirac plasmons. The high density of the free electron makes electrides very promising for applications in thermionic emission, organic light-emitting diodes, and high-performance catalysts.In this Account, we first discuss the discovery of numerous vdW electrides through high-throughput computational screening of over 67,000 known inorganic crystals in Materials Project. A dozen of them have been newly discovered and have not been reported before. Importantly, they possess completely different structural prototypes and properties of anionic electrons compared to widely studied electrides such as Ca2N. Finding these new vdW electrides expands the variety of electrides that can be made in the experiment and opens up new possibilities for studying their unique properties and applications.Then, based on the screened vdW electrides, we delve into their various emerging properties. For example, we developed a new magnetic mechanism specific to atomic-orbital-free ferromagnetism in electrides. We uncover the dual localized and extended nature of the anionic electrons in such electrides and demonstrate the formation of the local moment by the localized feature and the ferromagnetic interaction by the direct overlapping of their extended states. We further show the effective tuning of the magnetic properties of vdW electrides by engineering their structural, electronic, and compositional properties. Besides, we show that the complex interaction between the multiple quantum orderings in vdW electrides leads to many interesting properties including valley polarization, charge density waves, a topological property, a superconducting property, and a thermoelectrical property.Moreover, we discuss strategies to leverage the unique intrinsic properties of vdW electrides for practical applications. We show that these properties make vdW electrides potential candidates for advanced applications such as spin-orbit torque memory devices, valleytronic devices, K-ion batteries, and thermoelectricity. Finally, we discuss the current challenges and future perspectives for research using these emerging materials.

4.
Nano Lett ; 24(1): 402-410, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38153842

RESUMO

The ability of drugs to cross the blood-brain barrier (BBB) is crucial for treating central nervous system (CNS) disorders. Inspired by natural viruses, here we report a glucose and polydopamine (GPDA) coating method for the construction of delivery platforms for efficient BBB crossing. Such platforms are composed of nanoparticles (NPs) as the inner core and surface functionalized with glucose-poly(ethylene glycol) (Glu-PEG) and polydopamine (PDA) coating. Glu-PEG provides selective targeting of the NPs to brain capillary endothelial cells (BCECs), while PDA enhances the transcytosis of the NPs. This strategy is applicable to gold NPs (AuNPs), silica, and polymeric NPs, which achieves as high as 1.87% of the injected dose/g of brain in healthy brain tissues. In addition, the GPDA coating manages to deliver NPs into the tumor tissue in the orthotopic glioblastoma model. Our study may provide a universal strategy for the construction of delivery platforms for efficient BBB crossing and brain drug delivery.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Células Endoteliais , Ouro/farmacologia , Encéfalo , Sistemas de Liberação de Medicamentos/métodos
5.
Nano Lett ; 24(1): 43-50, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37930062

RESUMO

The defect emission from h-BN at 1.55 eV is interesting as it enables optical readout of spins. It is necessary to identify the nature of the relevant point defects for its controlled introduction. However, it is challenging to engineer point defects in h-BN without changing the local atomic structure. Here, we controllably introduce boron vacancies in h-BN using an ultrahigh spatial resolution and low-energy He+ ion beam. By optimizing the He+ ion irradiation conditions, we control the quantity and location of defects spatially and along the depth of h-BN to achieve a robust photoluminescence emission at 1.55 eV from 10 K to room temperature. We show that as-generated defects activate an additional Raman mode at 1295 cm-1. Electron energy loss spectroscopy confirms introduction of boron vacancies without modification of the local h-BN crystal structure. Our results provide a deterministic strategy to create scalable boron vacancy emitters in h-BN for quantum photonics.

6.
Nano Lett ; 24(33): 10275-10283, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39106329

RESUMO

Defect engineering is widely used to impart the desired functionalities on materials. Despite the widespread application of atomic-resolution scanning transmission electron microscopy (STEM), traditional methods for defect analysis are highly sensitive to random noise and human bias. While deep learning (DL) presents a viable alternative, it requires extensive amounts of training data with labeled ground truth. Herein, employing cycle generative adversarial networks (CycleGAN) and U-Nets, we propose a method based on a single experimental STEM image to tackle high annotation costs and image noise for defect detection. Not only atomic defects but also oxygen dopants in monolayer MoS2 are visualized. The method can be readily extended to other two-dimensional systems, as the training is based on unit-cell-level images. Therefore, our results outline novel ways to train the model with minimal data sets, offering great opportunities to fully exploit the power of DL in the materials science community.

7.
J Cell Mol Med ; 28(2): e18069, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38051678

RESUMO

To evaluate the change of total antioxidant capacity (TAC) and ascorbic acid (AA) between femtosecond laser in situ keratomileusis (FS-LASIK) and laser-assisted lenticule extraction (LALEX). A prospective non-randomized study was conducted, and 33 and 75 eyes that had undergone FS-LASIK or LALEX surgeries were enrolled, respectively. The tear films near corneal incisions were collected, and the concentrations of TAC and AA were determined. The generalized linear mixed model was adopted to calculate the adjusted odds ratio (aOR) with 95% confidence interval (CI) of TAC and AA between the two groups. The AA reduction was significant 1 month after the LALEX and FS-LASIK procedures (both p < 0.05), and the decrement in AA level was significantly larger in the FS-LASIK group compared to the LALEX group (p = 0.0002). In the subgroup analysis, the LALEX group demonstrated a lower decrement in TAC level in the individuals with dry eye disease (DED) than the FS-LASIK group (p = 0.0424), and the LALEX group demonstrated a significantly lower AA decrement in the participants with high myopia (p = 0.0165) and DED (p = 0.0043). The LALEX surgery causes lesser AA decrement compared to FS-LASIK surgery especially for the patients with DED.


Assuntos
Ceratomileuse Assistida por Excimer Laser In Situ , Humanos , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Antioxidantes , Estudos Prospectivos , Lasers de Excimer/uso terapêutico , Córnea/cirurgia
8.
BMC Genomics ; 25(1): 510, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783193

RESUMO

Domesticated safflower (Carthamus tinctorius L.) is a widely cultivated edible oil crop. However, despite its economic importance, the genetic basis underlying key traits such as oil content, resistance to biotic and abiotic stresses, and flowering time remains poorly understood. Here, we present the genome assembly for C. tinctorius variety Jihong01, which was obtained by integrating Oxford Nanopore Technologies (ONT) and BGI-SEQ500 sequencing results. The assembled genome was 1,061.1 Mb, and consisted of 32,379 protein-coding genes, 97.71% of which were functionally annotated. Safflower had a recent whole genome duplication (WGD) event in evolution history and diverged from sunflower approximately 37.3 million years ago. Through comparative genomic analysis at five seed development stages, we unveiled the pivotal roles of fatty acid desaturase 2 (FAD2) and fatty acid desaturase 6 (FAD6) in linoleic acid (LA) biosynthesis. Similarly, the differential gene expression analysis further reinforced the significance of these genes in regulating LA accumulation. Moreover, our investigation of seed fatty acid composition at different seed developmental stages unveiled the crucial roles of FAD2 and FAD6 in LA biosynthesis. These findings offer important insights into enhancing breeding programs for the improvement of quality traits and provide reference resource for further research on the natural properties of safflower.


Assuntos
Carthamus tinctorius , Ácidos Graxos Dessaturases , Ácidos Graxos Insaturados , Genoma de Planta , Carthamus tinctorius/genética , Carthamus tinctorius/metabolismo , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Sementes/genética , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Genômica/métodos , Regulação da Expressão Gênica de Plantas , Anotação de Sequência Molecular
9.
Small ; : e2405358, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291888

RESUMO

The replacement of oxygen evolution reactions with organic molecule oxidation reactions to enable energy-efficient hydrogen production has been a subject of interest. However, further reducing reaction energy consumption and releasing hydrogen from organic molecules continue to pose significant challenges. Herein, a strategy is proposed to produce hydrogen and formic acid from formaldehyde using Ag/Co3O4 interface catalysts at the anode. The key to improving the performance of Ag-based catalysts for formaldehyde oxidation lies in the strong SMSI achieved through the well-designed "spontaneous redox reaction" between Ag and Co3O4 precursors. Nano-sized Ag particles are uniformly dispersed on Co3O4 nanosheets, and electron-deficient Agδ+ are formed by the SMSI between Ag and Co3O4. Ag/Co3O4 demonstrates exceptional formaldehyde oxidation activity at low potentials of 0.32 V versus RHE and 0.65 V versus RHE, achieving current densities of 10 and 100 mA cm-2, respectively. The electrolyzer "Ag/Co3O4||20% Pt/C" achieves over 195% hydrogen efficiency and over 98% formic acid selectivity, maintaining stable operation for 60 hours. This work not only presents a novel approach to precisely modulate Ag particle size and interface electronic structure via SMSI, but also provides a promising approach to efficient and energy-saving hydrogen production and the transformation of harmful formaldehyde.

10.
Small ; : e2402567, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39132749

RESUMO

The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

11.
J Med Virol ; 96(4): e29549, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38563352

RESUMO

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.


Assuntos
Infecções por Papillomavirus , Gravidez , Feminino , Humanos , Recém-Nascido , Adulto , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Pesquisa , Taiwan/epidemiologia , Fatores de Risco
12.
Opt Lett ; 49(20): 5913-5916, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39404570

RESUMO

High Al content (60%) p-AlGaN with different NH3 flow rates was grown using metal-organic chemical vapor deposition (MOCVD), and changes in its photoelectric properties were studied using the Hall effect tester (Hall) and cathodoluminescence (CL) spectrometer. The results show that the film resistivity increases from 3.8â€…Ω·cm to 46.5â€…Ω·cm with increasing NH3 flow rate. The impurity peak intensity of p-AlGaN grown under high NH3 flow conditions is particularly high, indicating numerous point defects. The results of high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) show a large number of Ga interstitial atoms (Gai) at the interface. As Gai acts as a donor, this may be the main reason for the increase in resistivity. And under high NH3 flow conditions, a lattice distortion and a high density of dislocation occur between p-AlGaN and p-GaN, which can lead to enhanced carrier scattering and decreased mobility. Additional validation via LED growth experiments indicates that the luminescence intensity of samples with low ammonia concentration increased by more than 13000 times.

13.
Diabetes Obes Metab ; 26(11): 5222-5232, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39171569

RESUMO

AIM: We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). MATERIALS AND METHODS: In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. RESULTS: After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. CONCLUSIONS: In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Obesidade , Humanos , Feminino , Masculino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Obesidade/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Resultado do Tratamento , Pontuação de Propensão , Estudos de Coortes , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon
14.
Vet Res ; 55(1): 132, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375803

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine viral infectious diseases worldwide. Vaccination is a key strategy for the control and prevention of PRRS. At present, the NADC30-like PRRSV strain has become the predominant epidemic strain in China, superseding the HP-PRRSV strain. The existing commercial vaccines offer substantial protection against HP-PRRSV, but their efficacy against NADC30-like PRRSV is limited. The development of a novel vaccine that can provide valuable cross-protection against both NADC30-like PRRSV and HP-PRRSV is highly important. In this study, an infectious clone of a commercial MLV vaccine strain, GD (HP-PRRSV), was first generated (named rGD). A recombinant chimeric PRRSV strain, rGD-SX-5U2, was subsequently constructed by using rGD as a backbone and embedding several dominant immune genes, including the NSP2, ORF5, ORF6, and ORF7 genes, from an NADC30-like PRRSV isolate. In vitro experiments demonstrated that chimeric PRRSV rGD-SX-5U2 exhibited high tropism for MARC-145 cells, which is of paramount importance in the production of PRRSV vaccines. Moreover, subsequent in vivo inoculation and challenge experiments demonstrated that rGD-SX-5U2 confers cross-protection against both HP-PRRSV and NADC30-like PRRSV, including an improvement in ADG levels and a reduction in viremia and lung tissue lesions. In conclusion, our research demonstrated that the chimeric PRRSV strain rGD-SX-5U2 is a novel approach that can provide broad-spectrum protection against both HP-PRRSV and NADC30-like PRRSV. This may be a significant improvement over previous MLV vaccinations.


Assuntos
Proteção Cruzada , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Vacinas Virais , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Animais , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Síndrome Respiratória e Reprodutiva Suína/virologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Suínos , Vacinas Virais/imunologia , China
15.
Physiol Plant ; 176(5): e14548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39318054

RESUMO

Reactive oxygen species (ROS) have been extensively suggested to stimulate ethylene production. However, the molecular mechanism by which ROS stimulate ethylene production remains largely unclear. Here, transcriptome profiling was used to verify if ROS could stimulate ethylene production via direct formation of ethylene from ROS. Trichloroisocyanuric acid (TCICA) can stimulate seed germination in rice. When transcriptome profiling was performed to determine the molecular responsiveness of rice seeds to TCICA, TCICA was initially proven to be a ROS-generating reagent. A total of 300 genes potentially responsive to TCICA treatment were significantly annotated to cysteine, and the expression of these genes was significantly upregulated. Nonetheless, the levels of cystine did not exhibit significant changes upon TCICA exposure. Cystine was then proven to be a substrate that reacted with TCICA to form ethylene under FeSO4 conditions. Moreover, 7 of 22 genes responsive to TCICA were common with the hydrogen peroxide (H2O2)-responsive genes. Ethylene was then proven to be produced from cysteine or cystine by reacting with H2O2 under FeSO4 condition, and the hydroxyl radical (OH-) was proposed to be the free radical species responsible for ethylene formation under FeSO4 condition. These results provide the first line of evidence that ethylene can be produced from ROS in a non-enzymatic manner, thereby unveiling one new molecular mechanism by which ROS stimulate ethylene production and offering novel insights into the crosstalk between ethylene and ROS.


Assuntos
Etilenos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Oryza , Espécies Reativas de Oxigênio , Sementes , Espécies Reativas de Oxigênio/metabolismo , Oryza/genética , Oryza/metabolismo , Oryza/efeitos dos fármacos , Sementes/efeitos dos fármacos , Sementes/genética , Sementes/metabolismo , Etilenos/metabolismo , Etilenos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Germinação/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Triazinas/farmacologia
16.
Macromol Rapid Commun ; : e2400698, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39470628

RESUMO

Fluorosilicone rubber is essential for sealing in extreme temperatures and non-polar environments due to its exceptional adaptability. However, achieving a high yield of fluorosilicone polymers with medium and high fluorine content remains a challenge. Herein, a facile gradient strategy is developed that involves modifying the method of cyclic monomer addition based on the rate of ring-opening polymerization (ROP), to improve yield and adjust fluorine content precisely. The polymerization process is designed and tailored based on the reaction rates of anionic ring-opening polymerization (AROP) and cationic ring-opening polymerization (CROP) via an efficient gradient strategy. The effects of the polymerization process on the viscosity and yield of vinyl fluorosilicone polymers and hydrofluorosilicone polymers are investigated and optimized. Notably, the as-prepared vinyl-terminated fluoromethylsilane with 60% fluorine content (FMS-Vi-60F) has a high yield (86.6%) and high viscosity (150 000 mPa·s) in a short reaction time, which is superior to previous methods. Clearly, the gradient ring-opening method developed in this work provides a facile and efficient synthesis for fabricating fluorosilicone polymers with a high yield and tunable fluorine content.

17.
Bioorg Chem ; 142: 106925, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37890213

RESUMO

Thirty new tricyclicmatrinic derivatives were successively synthesized and evaluated for their inhibitory activity on the accumulation of triglycerides (TG) in AML12 cells, using 12 N-m-trifluoromethylbenzenesulfonyl matrine (1) as the hit compound. Among the analogues, compound 7n possessing 11-trimethylbutylamine quaternary exerted the highest in vitro TG-lowering potency, as well as a good safety profile. 7n significantly attenuated the hepatic injury and steatosis, and ameliorated dyslipidemia and dysglycemia in the mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet. Primary mechanism study revealed that upregulation of peroxisome proliferator-activated receptors α (PPARα)-carnitine palmitoyltransferase 1A (CPT1A) pathway mediated the efficacy of 7n. Our study provides powerful information for developing this kind of compound into a new class of anti-NAFLD candidates, and compound 7n is worthy of further investigation as an ideal lead compound.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Matrinas , Triglicerídeos/metabolismo , Fígado/metabolismo , PPAR alfa/metabolismo , Camundongos Endogâmicos C57BL
18.
Dev Med Child Neurol ; 66(8): 1062-1073, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38263613

RESUMO

AIM: To determine the significant risk factors of cerebral palsy (CP) in Taiwanese children and the associations between infant-related and parent-related factors. METHOD: Data from 1 459 093 infants and their parents in Taiwan's national databases collected between 2009 and 2016 were used. The cohort with CP included children diagnosed with CP between birth and age 3 years; a total of 3254 children with CP were included in the final analysis. Hierarchical logistic regression models were used to estimate the odds ratio for the risk factors of CP. RESULTS: The hierarchical logistic regression models indicated that significant risk factors associated with CP are suburban location, low income, maternal and paternal diabetes mellitus, paternal substance abuse, paternal seizure disorder, male sex, birth by Cesarean section, singleton birth, low birthweight, being born extremely and very preterm, intraventricular hemorrhage, and periventricular leukomalacia, as well as tube feeding, ventilator use, and dopamine administration within 6 months of age. INTERPRETATION: In addition to common maternal and infant risk factors, we identified significant paternal risk factors associated with CP, including diabetes mellitus, seizure disorder, and substance abuse. The combination of maternal, paternal, and infant risk factors in CP holds great promise for early identification and intervention.


Assuntos
Paralisia Cerebral , Humanos , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/etiologia , Taiwan/epidemiologia , Fatores de Risco , Masculino , Feminino , Lactente , Recém-Nascido , Pré-Escolar
19.
Nutr Metab Cardiovasc Dis ; 34(7): 1631-1638, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38653673

RESUMO

BACKGROUND AND AIMS: It has been reported that maresin 1 (MaR1) is able to protect against the development of atherogenesis in cellular and animal models. This study was performed to investigate whether plasma MaR1 is associated with the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level. METHODS AND RESULTS: The study included 2822 non-ASCVD participants from a community-based cohort who were followed for about 8 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for ASCVD events according to baseline MaR1 quartiles were calculated using the Cox proportional hazards model. During follow-up, a total of 290 new ASCVD cases were identified. The restricted cubic spline analysis indicated a linear dose-response association between plasma MaR1 and incident ASCVD. In addition, the adjusted-HR (95% CI) for ASCVD events associated with one standard deviation increase in MaR1 was 0.79 (0.68-0.91). Moreover, the adjusted-HRs (95% CIs) for ASCVD events associated with the second, third and fourth quartiles versus the first quartile of plasma MaR1 were 1.00, 1.04 (0.76, 1.42), 0.88 (0.64, 1.22) and 0.58 (0.41, 0.84), respectively. Mediation analyses showed that the association between MaR1 and incident ASCVD was partially mediated by small dense low-density lipoprotein cholesterol, with a mediation proportion of 9.23%. Further, the net reclassification improvement and integrated discrimination improvement of ASCVD risk were significantly improved when MaR1 was added to basic model established by conventional risk factors (all p < 0.01). CONCLUSIONS: Elevated plasma MaR1 concentrations are associated with a lower risk of ASCVD development.


Assuntos
Aterosclerose , Biomarcadores , Ácidos Docosa-Hexaenoicos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aterosclerose/epidemiologia , Aterosclerose/sangue , Aterosclerose/diagnóstico , Biomarcadores/sangue , China/epidemiologia , Ácidos Docosa-Hexaenoicos/sangue , População do Leste Asiático , Incidência , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo
20.
Int J Med Sci ; 21(7): 1329-1336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818477

RESUMO

Purpose: The purpose of this study was to compare the differences in myopic control effects between orthokeratology (OK) contact lenses and defocus incorporated multiple segments (DIMS) spectacle lenses. Methods: A retrospective cohort study was conducted that included patients who had received OK lens, DIMS spectacle lens or single-vision spectacle treatments. A total of 54 eyes from 27 individuals, 38 eyes from 19 individuals and 42 eyes from 21 individuals were enrolled into the OK lens, DIMS and control groups, respectively. The primary outcomes were the changes in the spherical equivalent refraction (SER) and axial length (AXL) among the groups. A repeated-measure ANCOVA was adopted to calculate the SER progression and AXL elongation of the OK lens group compared with the DIMS group. Results: The difference in the SER progression was clinically non-significant in the OK lens group compared with the DIMS and control groups (P = 0.001). The total AXL elongation results were similar between the OK lens and DIMS groups, but these were lower than in the control group (P = 0.005). The repeated-measure ANCOVA revealed that the SER progression difference during the study interval was clinically non-significant in the OK lens group when compared with the DIMS group (P = 0.028). The AXL elongation results between the OK lens and DIMS populations did not illustrate a significant difference (P = 0.607). In a subgroup analysis of moderate astigmatism, better AXL control was observed in the DIMS subgroup compared with the OK lens subgroup (P = 0.016). Conclusions: The OK lens demonstrated a clinically non-significant effect on the SER and AXL controls compared with the DIMS spectacle lens.


Assuntos
Óculos , Miopia , Procedimentos Ortoceratológicos , Refração Ocular , Humanos , Miopia/terapia , Miopia/fisiopatologia , Masculino , Feminino , Procedimentos Ortoceratológicos/métodos , Estudos Retrospectivos , Refração Ocular/fisiologia , Adulto , Lentes de Contato , Adulto Jovem , Adolescente , Acuidade Visual , Resultado do Tratamento
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