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1.
Dig Liver Dis ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734568

RESUMO

Intrahepatic Cholangiocarcinoma (iCCA) with FGFR alterations is relatively rare, and its identification is important in the era of targeted therapy. We collected a large series of FGFR-altered cases in the Chinese population and characterized their clinicopathological and genetic features. Among the 18 FGFR-altered cases out of 260 iCCAs, 10 were males and 8 were females, ranging in age from 35 to 74 years (mean, 57.3 years; median, 58 years). Pathologically, they include 9 cases of large duct (LD, 50 %) and small duct (SD, 50 %) types each. All of them (100 %, 18/18) showed microsatellite stable (MSS) and low tumor mutation burden (TMB). Genetically, FGFR alterations involved FGFR1 (20 %), FGFR2 (70 %), and FGFR3 (10 %), with FGFR2 rearrangement accounting for the most (11/18). The most frequently altered genes/biological processes were development/proliferation-related pathways (44 %), chromatin organization (20 %), and tumor suppressors (32 %). Our study further revealed the clinicopathological and genetic features of FGFR-altered iCCA and demonstrated that its occurrence may show regional or ethnic variability and is less common in the Chinese population. A significant number of LD-type iCCA cases also have FGFR alterations rather than the SD type.

2.
J Cancer ; 15(10): 2940-2947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706898

RESUMO

Background: Three subphenotypes were identified for unresectable hepatocellular carcinoma (uHCC) after frontline transarterial chemoembolization (TACE). This study aimed to develop an individual smHAP-Ⅱ nomogram for uHCC patients after TACE. Methods: Between January 2007 to December 2016, 1517 uHCC patients undergoing TACE were included from four hospitals in China (derivation cohort: 597 cases; validation cohort: 920 cases). Multivariable Cox proportion regression analysis was used to develop a nomogram, incorporating postoperative subphenotypes (Phenotype 1, 2, 3) and HAP score (Score 0 to 4). The model was validated by a 1000-time bootstrap resampling procedure. The performance of the model was compared with existing ones by Harrell's C-index and Area Under Curve (AUC). Results: Postoperative subphenotypes modified the HAP score (smHAP-Ⅱ nomogram) was developed and validated, with the Harrell's C-index of the nomogram was 0.679 (SD: 0.029) for the derivation cohort and 0.727(SD:0.029) for the external cohort. The area under curves of the nomogram for 1-, 3-, and 5-year OS were 0.750, 0.710, and 0.732 for the derivation cohort, respectively (0.789, 0.762, and 0.715 for the external cohort). In the calibration curves stratified by treatment after TACE, the lines for re-TACE and stop-TACE cross at 0.23, indicating that patients with a 3-year predicted survival >23% would not benefit from TACE. Conclusions: The addition of postoperative subphenotypes significantly improved the prognostic performance. The smHAP-Ⅱ nomogram can be used for accurate prognostication and selection of optimal candidates for TACE, with the value to guide sequential treatment strategy.

3.
Microbiol Spectr ; : e0361723, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624222

RESUMO

We conducted a comprehensive analysis of the total microbiome and transcriptionally active microbiome communities in the roots and root nodules of Prosopis cineraria, an important leguminous tree in arid regions of many Asian countries. Mature P. cineraria trees growing in the desert did not exhibit any detected root nodules. However, we observed root nodules on the roots of P. cineraria growing on a desert farm and on young plants growing in a growth chamber, when inoculated with rhizosphere soil, including with rhizosphere soil from near desert tree roots that had no nodules. Compared to nearby soil, non-nodulated roots were enriched with Actinobacteria (e.g., Actinophytocola sp.), whereas root nodules sampled from the desert farm and growth chamber had abundant Alphaproteobacteria (e.g., Ensifer sp.). These nodules yielded many microbes in addition to such nitrogen-fixing bacteria as Ensifer and Sinorhizobium species. Significant differences exist in the composition and abundance of microbial isolates between the nodule surface and the nodule endosphere. Shotgun metagenome analysis of nodule endospheres revealed that the root nodules comprised over 90% bacterial DNA, whereas metatranscriptome analysis showed that the plant produces vastly more transcripts than the microbes in these nodules. Control inoculations demonstrated that four out of six Rhizobium, Agrobacterium, or Ensifer isolates purified from P. cineraria nodules produced nodules in the roots of P. cineraria seedlings under greenhouse conditions. The best nodulation was achieved when seedlings were inoculated with a mixture of those bacterial strains. Though root nodulation could be achieved under water stress conditions, nodule number and nodule biomass increased with copious water availability. .IMPORTANCEMicrobial communities were investigated in roots and root nodules of Prosopis cineraria, a leguminous tree species in arid Asian regions that is responsible for exceptionally important contributions to soil fertility in these dramatically dry locations. Soil removed from regions near nodule-free roots on these mature plants contained an abundance of bacteria with the genetic ability to generate nodules and fix nitrogen but did not normally nodulate in their native rhizosphere environment, suggesting a very different co-evolved relationship than that observed for herbaceous legumes. The relative over-expression of the low-gene-density plant DNA compared to the bacterial DNA in the nodules was also unexpected, indicating a very powerful induction of host genetic contributions within the nodule. Finally, the water dependence of nodulation in inoculated seedlings suggested a possible link between early seedling growth (before a deep root system can be developed) and the early development of nitrogen-fixing capability.

4.
Anim Biotechnol ; 35(1): 2337760, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38656923

RESUMO

Although the knee joint (KNJ) and temporomandibular joint (TMJ) all belong to the synovial joint, there are many differences in developmental origin, joint structure and articular cartilage type. Studies of joint development in embryos have been performed, mainly using poultry and rodents. However, KNJ and TMJ in poultry and rodents differ from those in humans in several ways. Very little work has been done on the embryonic development of KNJ and TMJ in large mammals. Several studies have shown that pigs are ideal animals for embryonic development research. Embryonic day 30 (E30), E35, E45, E55, E75, E90, Postnatal day 0 (P0) and Postnatal day 30 (P30) embryos/fetuses from the pigs were used for this study. The results showed that KNJ develops earlier than TMJ. Only one mesenchymal condensate of KNJ is formed on E30, while two mesenchymal condensates of TMJ are present on E35. All structures of KNJ and TMJ were formed on E45. The growth plate of KNJ begins to develop on E45 and becomes more pronounced from E55 to P30. From E75 to E90, more and more vascular-rich cartilage canals form in the cartilage regions of both joints. The cartilaginous canal of the TMJ divides the condyle into sections along the longitudinal axis of the condyle. This arrangement of cartilaginous canal was not found in the KNJ. The chondrification of KNJ precedes that of TMJ. Ossification of the knee condyle occurs gradually from the middle to the periphery, while that of the TMJ occurs gradually from the base of the mandibular condyle. In the KNJ, the ossification of the articular condyle is evident from P0 to P30, and the growth plate is completely formed on P30. In the TMJ, the cartilage layer of condyle becomes thinner from P0 to P30. There is no growth plate formation in TMJ during its entire development. There is no growth plate formation in the TMJ throughout its development. The condyle may be the developmental center of the TMJ. The chondrocytes and hypertrophic chondrocytes of the growth plate are densely arranged. The condylar chondrocytes of TMJ are scattered, while the hypertrophic chondrocytes are arranged. Embryonic development of KNJ and TMJ in pigs is an important bridge for translating the results of rodent studies to medical applications.


Assuntos
Articulação do Joelho , Articulação Temporomandibular , Animais , Suínos/embriologia , Articulação Temporomandibular/embriologia , Articulação Temporomandibular/crescimento & desenvolvimento , Articulação do Joelho/embriologia , Articulação do Joelho/crescimento & desenvolvimento , Cartilagem Articular/embriologia , Cartilagem Articular/crescimento & desenvolvimento , Feminino , Desenvolvimento Embrionário/fisiologia , Embrião de Mamíferos
5.
Mayo Clin Proc ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38661595

RESUMO

OBJECTIVE: To evaluate the association of 5 major cause-specific non-cardiovascular disease (CVD) and non-cancer deaths with cardiorespiratory fitness (CRF). METHODS: Patients were 36,645 men (43.3±9.3 years) free of known CVD and cancer at baseline who completed a maximal treadmill graded exercise test during a preventive examination at the Cooper Clinic (Dallas, Texas) between 1971 and 2003. CRF was quantified as maximal treadmill exercise test duration and grouped as low (referent), moderate, and high. Cause-specific non-CVD non-cancer deaths were (1) diabetes or kidney disease, (2) chronic respiratory disease, (3) acute respiratory and infectious disease, (4) injuries, and (5) other non-CVD non-cancer deaths. RESULTS: A total of 694 non-CVD non-cancer deaths occurred during an average of 17 years of follow-up. After adjustment for covariates, hazard ratios (95% confidence intervals) for moderate and high CRF, respectively, were 0.57 (0.47 to 0.69) and 0.43 (0.34 to 0.54) for overall non-CVD non-cancer deaths (P<.0001); 0.39 (0.28 to 0.54) and 0.17 (0.10 to 0.28) for diabetes or kidney disease (P<.001); 0.36 (0.22 to 0.59) and 0.09 (0.04 to 0.20) for chronic respiratory diseases (P<.001 for all); 0.74 (0.47 to 1.16) and 0.34 (0.19 to 0.61) for acute respiratory and infectious diseases (P<.01 for both); and 0.48 (0.35 to 0.66) and 0.38 (0.26 to 0.55) for any other non-CVD non-cancer deaths (P<.0001 for both). CONCLUSION: Higher levels of CRF were significantly associated with lower risk of mortality from the 5 major non-CVD non-cancer causes. These results suggest that improvement in CRF may reduce non-CVD non-cancer deaths, which account for a significant proportion of adult mortality.

6.
Emerg Microbes Infect ; 13(1): 2332660, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38678636

RESUMO

Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Surtos de Doenças , Imunização Secundária , SARS-CoV-2 , Humanos , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Estudos Retrospectivos , Masculino , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Adulto , Feminino , Pessoa de Meia-Idade , Surtos de Doenças/prevenção & controle , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Idoso , Adulto Jovem , Eficácia de Vacinas
7.
Adv Mater ; : e2400333, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652082

RESUMO

Wireless and wearable sensors attract considerable interest in personalized healthcare by providing a unique approach for remote, noncontact, and continuous monitoring of various health-related signals without interference with daily life. Recent advances in wireless technologies and wearable sensors have promoted practical applications due to their significantly improved characteristics, such as reduction in size and thickness, enhancement in flexibility and stretchability, and improved conformability to the human body. Currently, most researches focus on active materials and structural designs for wearable sensors, with just a few exceptions reflecting on the technologies for wireless data transmission. This review provides a comprehensive overview of the state-of-the-art wireless technologies and related studies on empowering wearable sensors. The emerging functional nanomaterials utilized for designing unique wireless modules are highlighted, which include metals, carbons, and MXenes. Additionally, the review outlines the system-level integration of wireless modules with flexible sensors, spanning from novel design strategies for enhanced conformability to efficient transmitting data wirelessly. Furthermore, the review introduces representative applications for remote and noninvasive monitoring of physiological signals through on-skin and implantable wireless flexible sensing systems. Finally, the challenges, perspectives, and unprecedented opportunities for wireless and wearable sensors are discussed.

8.
Sci Total Environ ; 926: 171834, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38521258

RESUMO

The co-occurrence of microplastics (MPs) with potentially toxic metals in the environment stresses the need to address their physicochemical interactions and the potential ecological and human health implications. Here, we investigated the reaction of aqueous U with agricultural soil and high-density polyethylene (HDPE) through the integration of batch experiments, microscopy, and spectroscopy. The aqueous initial concentration of U (100 µM) decreased between 98.6 and 99.2 % at pH 5 and between 86.2 and 98.9 % at pH 7.5 following the first half hour of reaction with 10 g of soil. In similar experimental conditions but with added HDPE, aqueous U decreased between 98.6 and 99.7 % at pH 5 and between 76.1 and 95.2 % at pH 7.5, suggesting that HDPE modified the accumulation of U in soil as a function of pH. Uranium-bearing precipitates on the cracked surface of HDPE were identified by SEM/EDS after two weeks of agitation in water at both pH 5 and 7.5. Accumulation of U on the near-surface region of reacted HDPE was confirmed by XPS. Our findings suggest that the precipitation of U was facilitated by the weathering of the surface of HDPE. These results provide insights about surface-mediated reactions of aqueous metals with MPs, contributing relevant information about the mobility of metals and MPs at co-contaminated agricultural sites.

9.
ACS Appl Mater Interfaces ; 16(14): 17442-17452, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38551195

RESUMO

Engineering targeted and reliable charge transfer pathways in multiphase photocatalysts remains a challenge. Herein, we conceptualize the Cd@CdS-ZnO/reduced graphene oxide (rGO)/ZnS heterostructures coupled with reliable carrier migration channels and visible-light response antennas by building rGO-integrated electrochemical nanoreactors and an ion-exchange process. In this ternary catalyst, the Cd clusters and rGO perform as charge relays to boost carrier transport via the Z-scheme route and accelerate photogenerated carriers to react with surface-adsorbed substances. Meanwhile, thanks to CdS, the heterostructures have photocatalytic properties under visible light illumination and can also inhibit self-corrosion by shielding Cd clusters to avoid disrupting charge transfer channels. Therefore, the special heterostructure demonstrates fascinating photocatalytic hydrogen production activity without the intervention of cocatalysts. This work provides a feasible protocol for improving the interfaces between metals and semiconductors to achieve efficient photocatalytic hydrogen generation.

10.
J Ethnopharmacol ; 327: 118016, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38462027

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis pilosula (C. pilosula), also called "Dangshen" in Chinese, is derived from the roots of Codonopsis pilosula (Franch.) Nannf. (C. pilosula), Codonopsis pilosula var. Modesta (Nannf.) L.D.Shen (C. pilosula var. modesta) or Codonopsis pilosula subsp. Tangshen (Oliv.) D.Y.Hong (C. pilosula subsp. tangshen), is a well-known traditional Chinese medicine. It has been regularly used for anti-aging, strengthening the spleen and tonifying the lungs, regulating blood sugar, lowering blood pressure, strengthening the body's immune system, etc. However, the mechanism, by which, C. pilosula exerts its therapeutic effects on brain aging remains unclear. AIM OF THE STUDY: This study aimed to investigate the underlying mechanisms of the protective effects of C. pilosula water extract (CPWE) on the hippocampal tissue of D-galactose-induced aging mice. MATERIALS AND METHODS: In this research, plant taxonomy has been confirmed in the "The Plant List" database (www.theplantlist.org). First, an aging mouse model was established through the intraperitoneal injections of D-galactose solution, and low-, medium-, and high-dose CPWE were administered to mice by gavage for 42 days. Then, the learning and memory abilities of the mice were examined using the Morris water maze tests and step-down test. Hematoxylin and eosin staining was performed to visualize histopathological damage in the hippocampus. A transmission electron microscope was used to observe the ultrastructure of hippocampal neurons. Immunohistochemical staining was performed to examine the expression of glial fibrillary acidic protein (GFAP), the marker protein of astrocyte activation, and autophagy-related proteins, including microtubule-associated protein light chain 3 (LC3) and sequestosome 1 (SQSTM1)/p62, in the hippocampal tissues of mice. Moreover, targeted metabolomic analysis was performed to assess the changes in polar metabolites and short-chain fatty acids in the hippocampus. RESULTS: First, CPWE alleviated cognitive impairment and ameliorated hippocampal tissue damage in aging mice. Furthermore, CPWE markedly alleviated mitochondrial damage, restored the number of autophagosomes, and activated autophagy in the hippocampal tissue of aging mice by increasing the expression of LC3 protein and reducing the expression of p62 protein. Meanwhile, the expression levels of the brain injury marker protein GFAP decreased. Moreover, quantitative targeted metabolomic analysis revealed that CPWE intervention reversed the abnormal levels of L-asparagine, L-glutamic acid, L-glutamine, serotonin hydrochloride, succinic acid, and acetic acid in the hippocampal tissue of aging mice. CPWE also significantly regulated pathways associated with D-glutamine and D-glutamate metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartate, and glutamate metabolisms, and aminoacyl-tRNA biosynthesis. CONCLUSIONS: CPWE could improve cognitive and pathological conditions induced by D-galactose in aging mice by activating autophagy and regulating metabolism, thereby slowing down brain aging.


Assuntos
Codonopsis , Camundongos , Animais , Codonopsis/química , Galactose , Encéfalo , Envelhecimento , Autofagia
11.
J Cancer ; 15(7): 2066-2073, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434985

RESUMO

Background: There are few effective prediction models for intermediate-stage hepatocellular carcinoma (IM-HCC) patients treated with transarterial chemoembolization (TACE) to predict overall survival (OS) is available. The learning survival neural network (DeepSurv) was developed to showed a better performance than cox proportional hazards model in prediction of OS. This study aimed to develop a deep learning-based prediction model to predict individual OS. Methods: This multicenter, retrospective, cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007, to December 31, 2016. Patients were divided into a training set(n=1075) and a test set(n=269) at a ratio of 8:2 to develop a deep learning-based algorithm (deepHAP IV). The deepHAP IV model was externally validated on an independent cohort(n=414) from the other three centers. The concordance index, the area under the receiver operator characteristic curves, and the calibration curve were used to assess the performance of the models. Results: The deepHAP IV model had a c-index of 0.74, whereas AUROC for predicting survival outcomes of 1-, 3-, and 5-year reached 0.80, 0.76, and 0.74 in the training set. Calibration graphs showed good consistency between the actual and predicted OS in the training set and the validation cohort. Compared to the other five Cox proportional-hazards models, the model this study conducted had a better performance. Patients were finally classified into three groups by X-tile plots with predicted 3-year OS rate (low: ≤ 0.11; middle: > 0.11 and ≤ 0.35; high: >0.35). Conclusion: The deepHAP IV model can effectively predict the OS of patients with IM-HCC, showing a better performance than previous Cox proportional hazards models.

12.
Appl Opt ; 63(5): 1292-1305, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38437309

RESUMO

Existing optical information hiding algorithms for multiple images require generating hidden keys for embedded images, resulting in the transmission of numerous keys. This challenge undermines the usage of these algorithms in low-quality networks. To address this issue and enhance transmission efficiency, we present a multi-image optical information hiding algorithm based on Fourier transformation principles, which is employed to generate hidden frequency maps and carrier frequency maps. Specific low-frequency information zones are extracted within these hidden frequency maps. A chaotic system integrates a phase mask, modulated with the low-frequency regions, positioned in the carrier frequency map's high-frequency sector. The final stego image is obtained by subjecting the carrier frequency map to inverse Fourier transformation. Experimental analysis shows that concealing three images takes only 0.0089 s, with extraction requiring 0.0658 s. Post-extraction PSNR values for hidden images exceed 32 dB. Robustness and anti-attack experiments were done to prove the security of this algorithm. The compared experiments between the proposed method and other state-of-the-art algorithms affirm the algorithm's attributes of simplicity, ease of implementation, robust security, and high efficiency. Importantly, the restoration process eliminates the necessity of transmitting hidden keys, reducing network burdens and enhancing both concealment and extraction efficiencies significantly.

13.
Adv Mater ; 36(19): e2313638, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38328994

RESUMO

The introduction of rotational freedom by twist angles in twisted bilayer (TB) transition metal dichalcogenides (TMDCs) can tailor the inherent properties of the TMDCs, which provides a promising platform to investigate the exotic physical properties. However, direct synthesis of high-quality TB-TMDCs with full twist angles is significantly challenging due to the substantial energy barriers during crystal growth. Here, a modified chemical vapor deposition strategy is proposed to synthesize TB-WS2 with a wide twist angle range from 0° to 120°. Utilizing a tilted SiO2/Si substrate, a gas flow disturbance is generated in the furnace tube to create a heterogeneous concentration gradient of the metal precursor, which provides an extra driving force for the growth of TB-WS2. The Raman and photoluminescence results confirm a weak interlayer coupling of the TB-WS2. High-quality periodic Moiré patterns are observed in the scanning transmission electron microscopy images. Moreover, owing to the strong correlation between the nonlinear optical response and the twisted crystal structure, tunable second harmonic generation behaviors are realized in the TB-WS2. This approach opens up a new avenue for the direct growth of high-crystalline-quality and pristine TB-TMDCs and their potential applications in nonlinear optical devices.

14.
J Phys Condens Matter ; 36(22)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38382124

RESUMO

The quantum anomalous Hall (QAH) insulator is a vital material for the investigation of emerging topological quantum effects, but its extremely low working temperature limits experiments. Apart from the temperature challenge, effective regulation of the topological state of QAH insulators is another crucial concern. Here, by first-principles calculations, we find a family of stable two-dimensional materials TlTiX (X = Si, Ge) are large-gap QAH insulators. Their extremely robust ferromagnetic (FM) ground states are determined by both the direct- and super-exchange FM coupling. In the absence of spin-orbit coupling (SOC), there exist a spin-polarized crossing point located at eachKandK' points, respectively. The SOC effect results in the spontaneous breaking ofC2symmetry and introduces a mass term, giving rise to a QAH state with sizable band gap. The tiny magnetocrystalline anisotropic energy (MAE) implies that an external magnetic field can be easily used to align magnetization deviating fromzdirection to thex-yplane, thereby leading to a transformation of the electronic state from the QAH state to the Weyl half semimetals state, which indicate monolayers TlTiX (X = Si, Ge) exhibit a giant magneto topological band effect. Finally, we examined the impact of stress on the band gap and MAE, which underlies the reasons for the giant magneto topological band effect attributed to the crystal field. These findings present novel prospects for the realization of large-gap QAH states with the characteristic of easily modifiable topological states.

15.
Electrophoresis ; 45(9-10): 877-884, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38196015

RESUMO

Macrohaplotype combines multiple types of phased DNA variants, increasing forensic discrimination power. High-quality long-sequencing reads, for example, PacBio HiFi reads, provide data to detect macrohaplotypes in multiploidy and DNA mixtures. However, the bioinformatics tools for detecting macrohaplotypes are lacking. In this study, we developed a bioinformatics software, MacroHapCaller, in which targeted loci (i.e., short TRs [STRs], single nucleotide polymorphisms, and insertion and deletions) are genotyped and combined with novel algorithms to call macrohaplotypes from long reads. MacroHapCaller uses physical phasing (i.e., read-backed phasing) to identify macrohaplotypes, and thus it can detect multi-allelic macrohaplotypes for a given sample. MacroHapCaller was validated with data generated from our designed targeted PacBio HiFi sequencing pipeline, which sequenced ∼8-kb amplicon regions harboring 20 core forensic STR loci in human benchmark samples HG002 and HG003. MacroHapCaller also was validated in whole-genome long-read sequencing data. Robust and accurate genotyping and phased macrohaplotypes were obtained with MacroHapCaller compared with the known ground truth. MacroHapCaller achieved a higher or consistent genotyping accuracy and faster speed than existing tools HipSTR and DeepVar. MacroHapCaller enables efficient macrohaplotype analysis from high-throughput sequencing data and supports applications using discriminating macrohaplotypes.


Assuntos
Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Poliploidia , Análise de Sequência de DNA , Software , Humanos , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Algoritmos , Biologia Computacional/métodos , DNA/genética , DNA/análise , Repetições de Microssatélites/genética , Genética Forense/métodos , Técnicas de Genotipagem/métodos
16.
Nat Commun ; 15(1): 562, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233382

RESUMO

Twisted bilayer (TB) transition metal dichalcogenides (TMDCs) beyond TB-graphene are considered an ideal platform for investigating condensed matter physics, due to the moiré superlattices-related peculiar band structures and distinct electronic properties. The growth of large-area and high-quality TB-TMDCs with wide twist angles would be significant for exploring twist angle-dependent physics and applications, but remains challenging to implement. Here, we propose a reconfiguring nucleation chemical vapor deposition (CVD) strategy for directly synthesizing TB-MoS2 with twist angles from 0° to 120°. The twist angles-dependent Moiré periodicity can be clearly observed, and the interlayer coupling shows a strong relationship to the twist angles. Moreover, the yield of TB-MoS2 in bilayer MoS2 and density of TB-MoS2 are significantly improved to 17.2% and 28.9 pieces/mm2 by tailoring gas flow rate and molar ratio of NaCl to MoO3. The proposed reconfiguring nucleation approach opens an avenue for the precise growth of TB-TMDCs for both fundamental research and practical applications.

17.
Small ; : e2310753, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279635

RESUMO

The fabrication of periodic macroporous (PM) in Nb2 O5 via morphological control is crucial for improving the photocatalytic hydrogen evolution efficiency. In this study, Nb2 O5 with PM is synthesized using a straightforward colloidal crystal templating approach. This material features an open, interconnected macroporous architecture with nanoscale walls, high crystallinity, and substantial porosity. Extensive characterization reveals that this hierarchically structured Nb2 O5 possesses abundant surface active sites and is capable of capturing light effectively, facilitating rapid mass transfer and diffusion of reactants and markedly suppressing the recombination of photoexcited charge carriers. Macroporous Nb2 O5 exhibits superior water-splitting hydrogen evolution performance compared with its bulk and commercial counterparts, achieving a hydrogen production rate of 405 µmol g-1 h-1 , surpassing that of bulk Nb2 O5 (B-Nb2 O5 ) and commercial Nb2 O5 (C-Nb2 O5 ) by factors of 5 and 33, respectively. This study proposes an innovative strategy for the design of hierarchically structured PM, thereby significantly advancing the hydrogen evolution potential of Nb2 O5 .

18.
J Hepatocell Carcinoma ; 11: 219-228, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38293613

RESUMO

Background: Previous studies have shown that the alpha-fetoprotein (AFP) response has been a key tumour marker in hepatocellular carcinoma (HCC), but its definition remains controversial. Recently, a new study has explored and defined the AFP serological response and used it to explain the subclass of intermediate-stage hepatocellular carcinoma (IM-HCC) with "sharp-falling" AFP change after transarterial chemoembolization (TACE). It may be a new and simple tool for assessing the prognosis of patients. This study aims to explore a simplified AFP trajectory and its impact on overall survival (OS) and disease-free survival (DFS) for IM-HCC after hepatectomy. Patients and Methods: Between January 2007 and May 2012, data from the Sun Yat-sen University Cancer Center was examined in this longitudinal, retrospective cohort study. A generalized additive model was applied to distinguish potential AFP dynamic trajectories. The Kaplan-Meier method was applied to analyze OS and DFS, and multivariate Cox models were used to calculate adjusted hazard ratios (aHRs) and 95% CIs for overall survival. Results: 144 patients who had IM-HCC with at least three AFP repeat measurements were included in the study. Three similar trajectories are displayed using the generalized additive model: low-stable (35.4%; n = 51), high-rising (36.1%; n = 52), and sharp-falling (28.5%; n = 41). Compared with the low-stable class, the aHRs for death were 2.84 (1.50, 5.41) and 0.59 (0.25, 1.40) for the high-rising and sharp-falling classes, adjusted by age and log AFP. Simplified AFP trajectory had higher relative importance than sex, intrahepatic tumor number, Child-Pugh class, and baseline AFP. Conclusion: The simplified AFP trajectory is a promising biomarker for IM-HCC patients undergoing hepatectomy. In the future, it should be verified by a larger population containing various stages of HCC.

19.
J Control Release ; 367: 184-196, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242212

RESUMO

The microneedle (MN) delivery system presents an attractive administration route for patients with Alzheimer's disease (AD). However, the passive drug delivery mode and low drug loading of MNs often result in unsatisfactory therapeutic efficiency. To address these dilemmas, we developed dual engine-drive bionic MNs for robust AD treatment. Specifically, free rivastigmine (RVT) and RVT particles were co-loaded within the MNs to construct the valve and chambers of the guava, respectively, which can serve as an active engine to promote drug permeation by generating capillary force. K2CO3 and citric acid were introduced as a pneumatic engine into the MNs to promote the permeation of free RVT into deeper skin layers for early intervention in AD. Further, the RVT particles served as a drug depot to provide continuous drug release for prolonged AD treatment. Compared with free RVT-loaded MNs, the dual engine-driven bionic MNs showed an increase in drug loading, cumulative transdermal permeability, and normalized bioavailability of approximately 40%, 22%, and 49%, respectively. Pharmacodynamic studies further confirmed that the dual engine-driven bionic MNs were most effective in restoring memory and recognition functions in mice with short-term memory dysfunction. Therefore, the dual engine-driven bionic MNs hold great promise for highly efficient AD treatment.


Assuntos
Doença de Alzheimer , Biônica , Humanos , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Pele , Administração Cutânea , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos , Agulhas
20.
Lab Chip ; 24(4): 933-945, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38273814

RESUMO

Three-dimensional rotation of cells is imperative in a variety of applications such as biology, medicine, and chemistry. We report for the first time a versatile approach for executing controllable 3D rotation of cells or particles at a bipolar electrode (BPE) array using a rotating electric field. The versatility of this method is demonstrated by 3D rotating various cells including yeast cells and K562 cells and the cells can be rotated to a desired orientation and immobilized for further operations. Our results demonstrate how electrorotation torque, induced charge electroosmosis (ICEO) flow and dielectrophoresis can be exerted on certain cells for modulating the rotation axis, speed, and direction. ICEO-based out-of-plane rotation is capable of rotating various cells in a vertical plane regardless of their shape and size. It can realize cell orientation by rotating cells toward a specific angle and enable cell rotation by steadily rotating multiple cells at a controllable speed. The rotation spectrum for in-plane rotation is further used to extract the cellular dielectric properties. This work offers a flexible method for controllable, contactless and precise rotation of different cells or particles, offering a rapid, high-throughput, and nondestructive rotation method for cell analysis and drug discovery.


Assuntos
Eletricidade , Eletro-Osmose , Condutividade Elétrica , Rotação , Eletrodos
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