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1.
Nature ; 627(8004): 534-539, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448599

RESUMO

Numerous modern technologies are reliant on the low-phase noise and exquisite timing stability of microwave signals. Substantial progress has been made in the field of microwave photonics, whereby low-noise microwave signals are generated by the down-conversion of ultrastable optical references using a frequency comb1-3. Such systems, however, are constructed with bulk or fibre optics and are difficult to further reduce in size and power consumption. In this work we address this challenge by leveraging advances in integrated photonics to demonstrate low-noise microwave generation via two-point optical frequency division4,5. Narrow-linewidth self-injection-locked integrated lasers6,7 are stabilized to a miniature Fabry-Pérot cavity8, and the frequency gap between the lasers is divided with an efficient dark soliton frequency comb9. The stabilized output of the microcomb is photodetected to produce a microwave signal at 20 GHz with phase noise of -96 dBc Hz-1 at 100 Hz offset frequency that decreases to -135 dBc Hz-1 at 10 kHz offset-values that are unprecedented for an integrated photonic system. All photonic components can be heterogeneously integrated on a single chip, providing a significant advance for the application of photonics to high-precision navigation, communication and timing systems.

2.
Nature ; 620(7972): 78-85, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532812

RESUMO

Photonic integrated circuits are widely used in applications such as telecommunications and data-centre interconnects1-5. However, in optical systems such as microwave synthesizers6, optical gyroscopes7 and atomic clocks8, photonic integrated circuits are still considered inferior solutions despite their advantages in size, weight, power consumption and cost. Such high-precision and highly coherent applications favour ultralow-noise laser sources to be integrated with other photonic components in a compact and robustly aligned format-that is, on a single chip-for photonic integrated circuits to replace bulk optics and fibres. There are two major issues preventing the realization of such envisioned photonic integrated circuits: the high phase noise of semiconductor lasers and the difficulty of integrating optical isolators directly on-chip. Here we challenge this convention by leveraging three-dimensional integration that results in ultralow-noise lasers with isolator-free operation for silicon photonics. Through multiple monolithic and heterogeneous processing sequences, direct on-chip integration of III-V gain medium and ultralow-loss silicon nitride waveguides with optical loss around 0.5 decibels per metre are demonstrated. Consequently, the demonstrated photonic integrated circuit enters a regime that gives rise to ultralow-noise lasers and microwave synthesizers without the need for optical isolators, owing to the ultrahigh-quality-factor cavity. Such photonic integrated circuits also offer superior scalability for complex functionalities and volume production, as well as improved stability and reliability over time. The three-dimensional integration on ultralow-loss photonic integrated circuits thus marks a critical step towards complex systems and networks on silicon.

3.
Nature ; 582(7812): 365-369, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32555486

RESUMO

Optical frequency combs have a wide range of applications in science and technology1. An important development for miniature and integrated comb systems is the formation of dissipative Kerr solitons in coherently pumped high-quality-factor optical microresonators2-9. Such soliton microcombs10 have been applied to spectroscopy11-13, the search for exoplanets14,15, optical frequency synthesis16, time keeping17 and other areas10. In addition, the recent integration of microresonators with lasers has revealed the viability of fully chip-based soliton microcombs18,19. However, the operation of microcombs requires complex startup and feedback protocols that necessitate difficult-to-integrate optical and electrical components, and microcombs operating at rates that are compatible with electronic circuits-as is required in nearly all comb systems-have not yet been integrated with pump lasers because of their high power requirements. Here we experimentally demonstrate and theoretically describe a turnkey operation regime for soliton microcombs co-integrated with a pump laser. We show the appearance of an operating point at which solitons are immediately generated by turning the pump laser on, thereby eliminating the need for photonic and electronic control circuitry. These features are combined with high-quality-factor Si3N4 resonators to provide microcombs with repetition frequencies as low as 15 gigahertz that are fully integrated into an industry standard (butterfly) package, thereby offering compelling advantages for high-volume production.

4.
New Phytol ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509454

RESUMO

Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear. Here, through analysis of a suppressor for the OsEIN2 over-expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre-mRNA for efficient splicing and stabilization, allowing for subsequent DNG701-mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre-mRNA, leading to transgene silencing. SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000-grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele. Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.

5.
Anesthesiology ; 140(6): 1134-1152, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38498811

RESUMO

BACKGROUND: Dexmedetomidine has repeatedly shown to improve anxiety, but the precise neural mechanisms underlying this effect remain incompletely understood. This study aims to explore the role of corticotropin-releasing hormone-producing hypothalamic paraventricular nucleus (CRHPVN) neurons in mediating the anxiolytic effects of dexmedetomidine. METHODS: A social defeat stress mouse model was used to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca2+ signal fiber photometry and ex vivo patch-clamp recordings were used to determine the excitability of CRHPVN neurons and investigate the specific mechanism involved. CRHPVN neuron modulation was achieved through chemogenetic activation or inhibition. RESULTS: Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRHPVN neuronal excitability. Chemogenetic activation of CRHPVN neurons decreased the time spent in the open arms of the elevated plus maze and in the central area of the open-field test. Conversely, chemogenetic inhibition of CRHPVN neurons had the opposite effect. Moreover, the suppressive impact of dexmedetomidine on CRHPVN neurons was attenuated by the α2-receptor antagonist yohimbine. CONCLUSIONS: The results indicate that the anxiety-like effects of dexmedetomidine are mediated via α2-adrenergic receptor-triggered inhibition of CRHPVN neuronal excitability in the hypothalamus.


Assuntos
Ansiedade , Dexmedetomidina , Neurônios , Núcleo Hipotalâmico Paraventricular , Estresse Psicológico , Animais , Masculino , Camundongos , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Hormônio Liberador da Corticotropina/metabolismo , Dexmedetomidina/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Estresse Psicológico/psicologia
6.
Br J Nutr ; : 1-30, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38826087

RESUMO

The epidemiological and burden characteristics of nutritional deficiencies (NDs) have been evolving, and it is crucial to identify geographical disparities and emerging trends. This study aimed to analyze the global, regional, and national trends in the burden of NDs over the past 30 years. Data were obtained from the Global Burden of Disease (GBD) 2019 database for the period 1990-2019. The study examined the incidence rates and disability-adjusted life years (DALYs) of NDs at various levels. Globally, the incidence rate of NDs decreased from 2226.2 per 100,000 in 2019 to 2096.3 per 100,000 in the same year, indicating a decline of 5.8%. The average annual percentage change (AAPC) was -0.21 (-0.31 to -0.11). Similarly, DALYs, prevalence, and mortality rates of NDs exhibited significant declines (AAPC = -3.21 [-3.45 to -2.96], AAPC = -0.53 [-0.55 to -0.51], and AAPC = -4.97 [-5.75 to -4.19], respectively). The incidence rate of NDs varied based on age group, gender, cause, and geographical area. Moreover, a negative association was observed between incidence and the sociodemographic index. At the regional level, the South Asia and Sub-Saharan Africa regions had the highest incidence rates of NDs. In conclusion, the global incidence rate of NDs showed a mixed pattern, while the DALY rate consistently declined. Additionally, prevalence and mortality rates of NDs decreased between 1990 and 2019.

7.
Surg Endosc ; 38(5): 2465-2474, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38456946

RESUMO

BACKGROUND: Bile duct leaks (BDLs) are serious complications that occurs after hepatobiliary surgery and trauma, leading to rapid clinical deterioration. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for BDLs, but it is not clear which patients will respond to this therapy and which patients will require additional surgical intervention. The aim of our study was to explore the predictors of successful ERCP for BDLs. METHODS: A retrospective analysis was conducted using data from six centers' databases. All consecutive patients who were clinically confirmed as BDLs were included in the study. Collected data were demographics, disease severity, and ERCP procedure characteristics. Univariate and multivariate analysis were used to select independent predictive factors that affect the outcome of ERCP for BDLs, and a nomogram was established. Calibration and ROC curves were used to evaluate the models. RESULTS: Four hundred and forty-eight consecutive patients were clinically confirmed as BDLs and 347 were excluded. In the 101 patients included patients, clinical success was achieved in 78 patients (77.2%). In logistic multivariable regression, two independent factors were negatively associated with the success of ERCP: SIRS (OR, 0.183; 95% CI 0.039-0.864; P = 0.032) and high-grade leak (OR 0.073; 95% CI 0.010-0.539; P = 0.010). Two independent factors were positively associated with the success of ERCP: leak-bridging drainage (OR 4.792; 95% CI 1.08-21.21; P = 0.039) and cystic duct leak (OR 6.193; 95% CI 1.03-37.17; P = 0.046). The prediction model with these four factors was evaluated using a receiver-operating characteristic (ROC) curve, which demonstrated an area under the curve of 0.9351. The calibration curve showed that the model had good predictive accuracy. CONCLUSION: Leak-bridging drainage and cystic duct leak are positive predictors for the success of ERCP, while SIRS and high-grade leak are negative predictors. This prediction model with nomogram has good predictive ability and practical clinical value, and may be helpful in clinical decision-making and prognostication.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Nomogramas , Humanos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Adulto , Doenças dos Ductos Biliares/cirurgia , Fístula Anastomótica/etiologia
8.
Proc Natl Acad Sci U S A ; 118(22)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34035175

RESUMO

Microlasers in near-degenerate supermodes lay the cornerstone for studies of non-Hermitian physics, novel light sources, and advanced sensors. Recent experiments of the stimulated scattering in supermode microcavities reported beating phenomena, interpreted as dual-mode lasing, which, however, contradicts their single-mode nature due to the clamped pump field. Here, we investigate the supermode Raman laser in a whispering-gallery microcavity and demonstrate experimentally its single-mode lasing behavior with a side-mode suppression ratio (SMSR) up to 37 dB, despite the emergence of near-degenerate supermodes by the backscattering between counterpropagating waves. Moreover, the beating signal is recognized as the transient interference during the switching process between the two supermode lasers. Self-injection is exploited to manipulate the lasing supermodes, where the SMSR is further improved by 15 dB and the laser linewidth is below 100 Hz.

9.
J Stroke Cerebrovasc Dis ; 33(2): 107554, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176227

RESUMO

BACKGROUND: The causal effect of C-reactive protein (CRP) on intracerebral hemorrhage (ICH) remains controversial. We discussed the causal association of CRP with ICH based on two-sample Mendelian randomization. METHODS: The data from two genome-wide association studies (GWAS) of European ancestry was extracted, including circulating CRP levels (204,402 individuals) and ICH (1,687 cases and 201,146 controls). The inverse variance weighted (IVW) method was primary tool to evaluate the causal relationship of circulating CRP levels on ICH risk. MR-Egger regression and MR-PRESSO global test were utilized to identify pleiotropy. Heterogeneity was discussed with Cochran's Q test. The leave-one-out analysis explored the reliability of the results. RESULTS: 54 SNPs were identified as instrumental variables (IVs) for circulating CRP levels, and these IVs had no significant horizontal pleiotropy, heterogeneity, or bias. MR analysis demonstrated a causal relationship between elevated circulating CRP levels and decreased risk of ICH (ORIVW = 0.828, 95% CI 0.692-0.992, P = 0.040). CONCLUSION: Elevated circulating CRP levels demonstrated a significant potentially protective causal relationship with risk of ICH.


Assuntos
Proteína C-Reativa , Análise da Randomização Mendeliana , Humanos , Proteína C-Reativa/genética , Estudo de Associação Genômica Ampla , Reprodutibilidade dos Testes , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/genética
10.
Inflammopharmacology ; 32(3): 1983-1998, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642223

RESUMO

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.


Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Xantonas , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Xantonas/farmacologia , Camundongos , Masculino , Colite/tratamento farmacológico , Colite/induzido quimicamente , Doenças Metabólicas/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças
11.
Inorg Chem ; 62(26): 10044-10048, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37338532

RESUMO

A unique heteropolyoxotantalate (hetero-POTa) cluster [P2O7Ta5O14]7- (P2Ta5) was first developed using pyrophosphate as a key to open the ultrastable skeleton of the classical Lindqvist-type [Ta6O19]8- precursor. The P2Ta5 cluster can serve as a general and flexible secondary building unit to create a family of brand-new multidimensional POTa architectures. This work not only promotes the limited structural diversity of hetero-POTa but also provides a practical strategy for new extended POTa architectures.

12.
J Nanobiotechnology ; 21(1): 81, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36890521

RESUMO

Endometriosis is an estrogen-dependent chronic inflammatory disease. Hormonal and surgical treatments are the most commonly used clinical therapies, but they have many sides effects or are traumatic to the body. Therefore, specific drugs for endometriosis treatment are urgently needed to develop. In this study, we identified two features of endometriosis, namely the continuous recruitment of neutrophils into the ectopic lesions and the higher uptake of glucose by ectopic cells. For the above features, we designed a glucose oxidase-loaded bovine serum albumin nanoparticle (BSA-GOx-NPs) that is inexpensive and facilitates large-scale production. After injection, BSA-GOx-NPs were high specifically delivered to ectopic lesions in a neutrophil-dependent manner. Furthermore, BSA-GOx-NPs deplete glucose and induce apoptosis in the ectopic lesions. Whereupon BSA-GOx-NPs produced excellent anti-endometriosis effects when administrated in both acute and chronic inflammatory phases. These results reveal for the first time that the neutrophil hitchhiking strategy is effective in chronic inflammatory disease and provide a non-hormonal and easy-to-achieve approach for endometriosis treatment.


Assuntos
Nanopartículas , Neutrófilos , Portadores de Fármacos , Soroalbumina Bovina , Apoptose
13.
J Nanobiotechnology ; 21(1): 462, 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38041074

RESUMO

Chemotherapy can cause severe pain for patients, but there are currently no satisfactory methods of pain relief. Enhancing the efficacy of chemotherapy to reduce the side effects of high-dose chemotherapeutic drugs remains a major challenge. Moreover, the treatment of chemotherapy-induced peripheral neuropathic pain (CIPNP) is separate from chemotherapy in the clinical setting, causing inconvenience to cancer patients. In view of the many obstacles mentioned above, we developed a strategy to incorporate local anesthetic (LA) into a cisplatin-loaded PF127 hydrogel for painless potentiated chemotherapy. We found that multiple administrations of cisplatin-loaded PF127 hydrogels (PFC) evoked severe CIPNP, which correlated with increased pERK-positive neurons in the dorsal root ganglion (DRG). However, incorporating ropivacaine into the PFC relieved PFC-induced CIPNP for more than ten hours and decreased the number of pERK-positive neurons in the DRG. Moreover, incorporating ropivacaine into the PFC for chemotherapy is found to upregulate major histocompatibility complex class I (MHC-I) expression in tumor cells and promote the infiltration of cytotoxic T lymphocytes (CD8+ T cells) in tumors, thereby potentiating chemotherapy efficacy. This study proposes that LA can be used as an immunemodulator to enhance the effectiveness of chemotherapy, providing new ideas for painless cancer treatment.


Assuntos
Antineoplásicos , Neuralgia , Humanos , Ropivacaina/efeitos adversos , Cisplatino , Linfócitos T CD8-Positivos/metabolismo , Hidrogéis , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Antineoplásicos/efeitos adversos
14.
Eur Heart J ; 43(43): 4579-4595, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-35929617

RESUMO

AIMS: Exercise confers protection against cardiovascular ageing, but the mechanisms remain largely unknown. This study sought to investigate the role of fibronectin type-III domain-containing protein 5 (FNDC5)/irisin, an exercise-associated hormone, in vascular ageing. Moreover, the existence of FNDC5/irisin in circulating extracellular vesicles (EVs) and their biological functions was explored. METHODS AND RESULTS: FNDC5/irisin was reduced in natural ageing, senescence, and angiotensin II (Ang II)-treated conditions. The deletion of FNDC5 shortened lifespan in mice. Additionally, FNDC5 deficiency aggravated vascular stiffness, senescence, oxidative stress, inflammation, and endothelial dysfunction in 24-month-old naturally aged and Ang II-treated mice. Conversely, treatment of recombinant irisin alleviated Ang II-induced vascular stiffness and senescence in mice and vascular smooth muscle cells. FNDC5 was triggered by exercise, while FNDC5 knockout abrogated exercise-induced protection against Ang II-induced vascular stiffness and senescence. Intriguingly, FNDC5 was detected in human and mouse blood-derived EVs, and exercise-induced FNDC5/irisin-enriched EVs showed potent anti-stiffness and anti-senescence effects in vivo and in vitro. Adeno-associated virus-mediated rescue of FNDC5 specifically in muscle but not liver in FNDC5 knockout mice, promoted the release of FNDC5/irisin-enriched EVs into circulation in response to exercise, which ameliorated vascular stiffness, senescence, and inflammation. Mechanistically, irisin activated DnaJb3/Hsp40 chaperone system to stabilize SIRT6 protein in an Hsp70-dependent manner. Finally, plasma irisin concentrations were positively associated with exercise time but negatively associated with arterial stiffness in a proof-of-concept human study. CONCLUSION: FNDC5/irisin-enriched EVs contribute to exercise-induced protection against vascular ageing. These findings indicate that the exerkine FNDC5/irisin may be a potential target for ageing-related vascular comorbidities.


Assuntos
Vesículas Extracelulares , Sirtuínas , Humanos , Camundongos , Animais , Idoso , Pré-Escolar , Fibronectinas/metabolismo , Fatores de Transcrição/metabolismo , Camundongos Knockout , Envelhecimento , Angiotensina II/farmacologia , Inflamação/metabolismo , Músculo Esquelético/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo
15.
J Acoust Soc Am ; 153(3): 1564, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37002084

RESUMO

Baleen whales produce a wide variety of frequency-modulated calls. Extraction of the time-frequency (TF) structures of these calls forms the basis for many applications, including abundance estimation and species recognition. Typical methods to extract the contours of whale calls from a spectrogram are based on the short-time Fourier transform and are, thus, restricted by a fixed TF resolution. Considering the low-frequency nature of baleen whale calls, this work represents the contours using a pseudo-Wigner-Ville distribution for a higher TF resolution at the cost of introducing cross terms. An adaptive threshold is proposed followed by a modified Gaussian mixture probability hypothesis density filter to extract the contours. Finally, the artificial contours, which are caused by the cross terms, can be removed in post-processing. Simulations were conducted to explore how the signal-to-noise ratio influences the performance of the proposed method. Then, in experiments based on real data, the contours of the calls of three kinds of baleen whales were extracted in a highly accurate manner (with mean deviations of 5.4 and 0.051 Hz from the ground-truth contours at sampling rates of 4000 and 100 Hz, respectively) with a recall of 75% and a precision of 78.5%.


Assuntos
Vocalização Animal , Baleias , Animais , Análise de Fourier , Fatores de Tempo
16.
Drug Dev Res ; 84(2): 296-311, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36644989

RESUMO

Small molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4-(4-aminophenyl)-6-phenylisoxazolo[3,4-b]pyridine-3-amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC50 = 123 nM) and FLT3-internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 µM. Besides, F15 exhibited potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell lines MOLM-13 (IC50 = 253 nM) and MV4-11 (IC50 = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/farmacologia , Aminas/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/farmacologia , Tirosina Quinase 3 Semelhante a fms/uso terapêutico , Apoptose , Proliferação de Células
17.
Arch Orthop Trauma Surg ; 143(1): 317-328, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34304280

RESUMO

INTRODUCTION: More than 19% of patients undergoing knee arthroscopies suffers from articular cartilage defects. The chondral or osteochondral lesion has negative impacts on the knee joints function and the life quality of patients. However, the treatment remains challenging as hyaline cartilage is not renewable. The purpose of this study was to systematically analyze the data of randomized controlled trials for comparing the postoperative outcomes between osteochondral autologous transplantation (OAT) and microfracture (MF) procedure. We hypothesized that the outcomes were better in OAT than MF procedure. MATERIALS AND METHODS: A systematic literature search of the EMBASE, Pubmed, and Cochrane Library databases was conducted based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The outcome measures include: the rate of excellent or good results, the rate of return to sports, the failure rate, osteoarthritis rate, International Cartilage Repair Society (ICRS) score, Lysholm Knee Score, and Tegner scale. The statistical analysis was completed using Review Manager (RevMan, version 5.3) software. RESULTS: The systematic search identified 7 studies with a total of 346 patients. The pooled result showed significant differences between the two groups in the rate of return to sports and failure. The following outcome scores showed significant improvement (pre- vs postoperatively): Lysholm score (p = 0.02), Tegner scale (p < 0.00001), and ICRS score (p < 0.00001). The differences were not significant in the excellent or good results and the rate of osteoarthritis. CONCLUSION: The patients in OAT group may return to play quicker, even return to pre-injury level of activity compared to the MF group. OAT is better than MF procedure in accordance with Lysholm score, Tegner score, ICRS score, and the rate of failure. However, few studies have reported long-term outcomes and there has no uniform criteria for safe return to sports. Further research is needed. LEVEL OF EVIDENCE: Level II, meta-analysis of randomized controlled trials.


Assuntos
Cartilagem Articular , Fraturas de Estresse , Traumatismos do Joelho , Osteoartrite , Humanos , Cartilagem Articular/cirurgia , Cartilagem Articular/lesões , Traumatismos do Joelho/cirurgia , Articulação do Joelho/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante Autólogo/métodos , Resultado do Tratamento
18.
Mol Genet Genomics ; 297(2): 485-494, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35146538

RESUMO

Eucommia ulmoides (E. ulmoides) is a deciduous perennial tree belonging to the order Garryales, and is known as "living fossil" plant, along with ginkgo (Ginkgo biloba), metaspaca (Metasequoia glyptostroboides) and dove tree (Davidia involucrata Baill). However, the genetic diversity and population structure of E. ulmoides are still  ambiguous nowdays. In this study, we re-sequenced the genomes of 12 E. ulmoides accessions from different major climatic geography regions in China to elucidate the genetic diversity, population structure and evolutionary pattern. By integration of phylogenetic analysis, principal component analysis and population structure analysis based on a number of high-quality SNPs, a total of 12 E. ulmoides accessions were clustered into four different groups. This result is consistent with their geographical location except for group samples from Shanghai and Hunan province. E. ulmoides accessions from Hunan province exhibited a closer genetic relationship with E. ulmoides accessions from Shanghai in China compared with other regions, which is also supported by the result of population structure analyses. Genetic diversity analysis further revealed that E. ulmoides samples in Shanghai and Hunan province were with higher genetic diversity than those in other regions in this study. In addition, we treated the E. ulmoides materials from Shanghai and Hunan province as group A, and the other materials from other places as group B, and then analyzed the evolutionary pattern of E. ulmoides. The result showed the significant differentiation (Fst = 0.1545) between group A and group B. Some candidate highly divergent genome regions were identified in group A by selective sweep analyses, and the function analysis of candidate genes in these regions showed that biological regulation processes could be correlated with the Eu-rubber biosynthesis. Notably, nine genes were identified from selective sweep regions. They were involved in the Eu-rubber biosynthesis and expressed in rubber containing tissues. The genetic diversity research and evolution model of E. ulmoides were preliminarily explored in this study, which laid the foundation for the protection of germplasm resources and the development and utilization of multipurpose germplasm resources in the future.


Assuntos
Eucommiaceae , China , Eucommiaceae/genética , Variação Genética/genética , Filogenia
19.
Small ; 18(15): e2106511, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35043579

RESUMO

The precision, minimal invasiveness, and integration of diagnosis and treatment are critical factors for tumor treatment at the present. Although nanomedicine has shown the potential in tumor precision treatment, nanocarriers with high efficiency, excellent targeting, controlled release, and good biocompatibility still need to be further explored. Hollow mesoporous manganese oxides nanomaterials (HM-MONs), as an efficient drug delivery carrier, have attracted substantial attention in applications of tumor diagnosis and therapy due to their unique properties, such as tumor microenvironment stimuli-responsiveness, prominent catalytic activity, excellent biodegradation, and outstanding magnetic resonance imaging ability. The HM-MONs can not only enhance the therapeutic efficiency but also realize multimodal diagnosis of tumors. Consequently, it is necessary to introduce applications based on HM-MONs in cancer diagnosis and therapy. In this review, the representative progress of HM-MONs in synthesis is discussed. Then, several promising applications in drug delivery, bio-imaging, and bio-detection are highlighted. Finally, the challenges and perspectives of the anticancer applications are summarized, which is expected to provide meaningful guidance on further research.


Assuntos
Nanopartículas , Neoplasias , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Humanos , Manganês , Compostos de Manganês , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Óxidos , Microambiente Tumoral
20.
Phys Rev Lett ; 128(7): 073901, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35244428

RESUMO

Kerr soliton microcombs in microresonators have been a prominent miniaturized coherent light source. Here, for the first time, we demonstrate the existence of Kerr solitons in an optomechanical microresonator, for which a nonlinear model is built by incorporating a single mechanical mode and multiple optical modes. Interestingly, an exotic vibrational Kerr soliton state is found, which is modulated by a self-sustained mechanical oscillation. Besides, the soliton provides extra mechanical gain through the optical spring effect, and results in phonon lasing with a red-detuned pump. Various nonlinear dynamics is also observed, including limit cycle, higher periodicity, and transient chaos. This work provides a guidance for not only exploring many-body nonlinear interactions, but also promoting precision measurements by featuring superiority of both frequency combs and optomechanics.

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