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1.
Front Oncol ; 14: 1288041, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962263

RESUMO

Background: Small Bowel Adenocarcinoma (SBA) is rare, occult and life-threatening malignancy in digestive system. Given low incidence and nonspecific symptoms, SBA is frequently detected in later stages. Double contrast enhanced ultrasound (DCEUS) is an innovative imaging technique applied to visualize the gastrointestinal tract, merging intravenous contrast-enhanced ultrasound with oral contrast-enhanced ultrasound. In this case, DCEUS was utilized and successfully detected an SBA of the jejunum. Case presentation: A Chinese woman, aged 64, sought consultation in the gastroenterology department at our hospital, reporting symptoms of abdominal pain. Three months before entering the hospital, she underwent gastroscopy and colonoscopy which suggested chronic gastritis, and she was treated with oral drugs. However, her symptoms were not relieved, and even worsened. To further investigate, DCEUS was performed. The oral contrast agent dilated the luminal space of the upper gastrointestinal tract, resolving the hindrance caused by gas in the gastrointestinal tract and creating an acoustic window for scanning. Through this acoustic window, oral agent contrast-enhanced ultrasound (OA-CEUS) revealed a localized thickening of jejunal intestinal wall measuring 4x3 cm. Following intravenous injection of ultrasound contrast agent, the jejunal lesion exhibited faster enhancement and heterogeneous hyper-enhancement. Finally, the patient underwent jejunal tumor resection. Pathological examination revealed a jejunal adenocarcinoma. Conclusion: The timely diagnosis of SBA can be challenging. DCEUS may have the potential to contribute to diagnosis and detailed evaluation of SBA, particularly in cases involving jejunum. Further researches are needed to fully explore the benefits of DCEUS in the standard diagnostic approach for small bowel diseases.

2.
World Neurosurg ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960308

RESUMO

OBJECTIVE: To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). METHODS: A randomized, single -blind,sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the Day 3 and Day 21 of treatment.The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs,latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score (LESS), spinal cord independence measure (SCIM) score and gait parameters (stride speed, stride frequency, stride length, ground reaction force). RESULTS: On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the lower extremity motor score and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS and SCIM between the two groups (p<0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (p<0.01), and the ground reaction force (GRF) was increased (p<0.05). There was no significant difference in the LESS of the lower limbs between the two groups (p > 0.05). CONCLUSIONS: ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

3.
Nat Commun ; 15(1): 5550, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956014

RESUMO

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood. Here, we use poly(A) inclusive RNA isoform sequencing (PAIso-seq) for profiling the transcriptome-wide poly(A) tails in both in vivo and in vitro matured mouse and human oocytes. Our results demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes. Moreover, the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes, contributing to reduced translation of these deadenylase machinery components and subsequently impaired global maternal mRNA deadenylation. Our findings highlight impaired maternal mRNA deadenylation as a distinct molecular defect in in vitro MII oocytes.


Assuntos
Oócitos , Poliadenilação , Oócitos/metabolismo , Animais , Humanos , Feminino , Camundongos , Poli A/metabolismo , Técnicas de Maturação in Vitro de Oócitos , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Transcriptoma , RNA Mensageiro Estocado/metabolismo , RNA Mensageiro Estocado/genética , Metáfase , Exorribonucleases , Proteínas Repressoras , Proteínas de Ciclo Celular
4.
J Pers Soc Psychol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976396

RESUMO

Recent advances in large language models are enabling the computational intelligent analysis of psychology in natural language. Here, the Fill-Mask Association Test (FMAT) is introduced as a novel and integrative method leveraging Masked Language Models to study and measure psychology from a propositional perspective at the societal level. The FMAT uses Bidirectional Encoder Representations from Transformers (BERT) models to compute semantic probabilities of option words filling in the masked blank of a designed query (i.e., a clozelike contextualized sentence). The current research presents 15 studies that establish the reliability and validity of the FMAT in predicting factual associations (Studies 1A-1C), measuring attitudes/biases (Studies 2A-2D), capturing social stereotypes (Studies 3A-3D), and retrospectively delineating lay perceptions of sociocultural changes over time (Studies 4A-4D). Empirically, the FMAT replicated seminal findings previously obtained with human participants (e.g., the Implicit Association Test) and other big-data text-analytic methods (e.g., word frequency analysis, the Word Embedding Association Test), demonstrating robustness across 12 BERT model variants and diverse training text corpora. Theoretically, the current findings substantiate the propositional (vs. associative) perspective on how semantic associations are represented in natural language. Methodologically, the FMAT allows for more fine-grained language-based psychological measurement, with an R package developed to streamline its workflow for use on broader research questions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

5.
NPJ Digit Med ; 7(1): 182, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971937

RESUMO

Computer-aided implant surgery has undergone continuous development in recent years. In this study, active and passive systems of dynamic navigation were divided into active dynamic navigation system group and passive dynamic navigation system group (ADG and PDG), respectively. Active, passive and semi-active implant robots were divided into active robot group, passive robot group and semi-active robot group (ARG, PRG and SRG), respectively. Each group placed two implants (FDI tooth positions 31 and 36) in a model 12 times. The accuracy of 216 implants in 108 models were analysed. The coronal deviations of ADG, PDG, ARG, PRG and SRG were 0.85 ± 0.17 mm, 1.05 ± 0.42 mm, 0.29 ± 0.15 mm, 0.40 ± 0.16 mm and 0.33 ± 0.14 mm, respectively. The apical deviations of the five groups were 1.11 ± 0.23 mm, 1.07 ± 0.38 mm, 0.29 ± 0.15 mm, 0.50 ± 0.19 mm and 0.36 ± 0.16 mm, respectively. The axial deviations of the five groups were 1.78 ± 0.73°, 1.99 ± 1.20°, 0.61 ± 0.25°, 1.04 ± 0.37° and 0.42 ± 0.18°, respectively. The coronal, apical and axial deviations of ADG were higher than those of ARG, PRG and SRG (all P < 0.001). Similarly, the coronal, apical and axial deviations of PDG were higher than those of ARG, PRG, and SRG (all P < 0.001). Dynamic and robotic computer-aided implant surgery may show good implant accuracy in vitro. However, the accuracy and stability of implant robots are higher than those of dynamic navigation systems.

6.
Plants (Basel) ; 13(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38931025

RESUMO

This study aimed to analyze the effects of salt stress on the growth physiology and plant-cell ultrastructure of Isatis indigotica Fort. (I. indigotica) to evaluate its adaptability under salt stress. The effects of different concentrations of salt (NaCl; 0, 25, and 300 mmol·L-1) on the agronomic traits, activities of related enzymes, ion balance, and mesophyll-cell ultrastructure of I. indigotica were studied in a controlled pot experiment. Results showed that compared with those of the control group, the aerial-part fresh weight, underground fresh weight, tiller number, root length, root diameter, plant height, and leaf area of salt-stressed I. indigotica increased at 25 mmol·L-1 and then decreased at 300 mmol·L-1. The changes in levels of superoxide dismutase, peroxidase, ascorbate peroxidase, and catalase showed a similar trend, with significant differences compared with control group. Salt stress altered the ion balance of I. indigotica, resulting in a significant increase in Na+ content and a significant decrease in K+ content. The contents of Ca2+ and Mg2+ changed to varying degrees. The analysis of the microstructure of the root showed that under salt treatment, the epidermal cells of the root significantly thickened and the diameter of the xylem decreased. The results of ultrastructural analysis of mesophylls showed that salt stress can cause cell-membrane contraction, cell-gap enlargement, disorder in the structures of chloroplasts and mitochondria, and an increase in the number of osmiophilic particles. These changes were aggravated by the increase in NaCl concentration. This study reveals the response of I. indigotica to salt stress and provides a basis for further study on the salt-tolerance mechanism of I. indigotica.

7.
BMC Complement Med Ther ; 24(1): 246, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915038

RESUMO

INTRODUCTION: The clinical symptoms of Lumbar Disc Herniation (LDH) can be effectively ameliorated through Lever Positioning Manipulation (LPM), which is closely linked to the brain's pain-regulating mechanisms. Magnetic Resonance Imaging (MRI) offers an objective and visual means to study how the brain orchestrates the characteristics of analgesic effects. From the perspective of multimodal MRI, we applied functional MRI (fMRI) and Magnetic Resonance Spectrum (MRS) techniques to comprehensively evaluate the characteristics of the effects of LPM on the brain region of LDH from the aspects of brain structure, brain function and brain metabolism. This multimodal MRI technique provides a biological basis for the clinical application of LPM in LDH. METHODS AND ANALYSIS: A total of 60 LDH patients and 30 healthy controls, matched by gender, age, and years of education, will be enrolled in this study. The LDH patients will be divided into two groups (Group 1, n = 30; Group 2, n = 30) using a random number table method. Group 1 will receive LPM treatment once every two days, for a total of 12 times over 4 weeks. Group 2 will receive sham LPM treatment during the same period as Group 1. All 30 healthy controls will be divided into Group 3. Multimodal MRI will be performed on Group 1 and Group 2 at three time points (TPs): before LPM (TP1), after one LPM session (TP2), and after a full course of LPM treatment. The healthy controls (Group 3) will not undergo LPM and will be subject to only a single multimodal MRI scan. Participants in both Group 1 and Group 2 will be required to complete clinical questionnaires. These assessments will focus on pain intensity and functional disorders, using the Visual Analog Scale (VAS) and the Japanese Orthopaedic Association (JOA) scoring systems, respectively. DISCUSSION: The purpose of this study is to investigate the multimodal brain response characteristics of LDH patients after treatment with LPM, with the goal of providing a biological basis for clinical applications. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/NCT05613179 , identifier: NCT05613179.


Assuntos
Encéfalo , Deslocamento do Disco Intervertebral , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Deslocamento do Disco Intervertebral/terapia , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Adulto , Masculino , Feminino , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Adulto Jovem , Degeneração do Disco Intervertebral
8.
Angew Chem Int Ed Engl ; : e202407064, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940290

RESUMO

The continuous electrolyte decomposition and uncontrolled dendrite growth caused by the unstable solid electrolyte interphase (SEI) have largely hindered the development of Li metal batteries. Here, we demonstrate that tuning the facet of current collector can regulate the composition of SEI and the subsequent Li deposition behavior using single-crystal Cu foils as an ideal platform. The theoretical and experimental studies reveal that the (100) facet of Cu possesses strong adsorption to anions, guiding more anions to participate preferentially in the inner Helmholtz plane and further promoting the formation of the stable inorganic-rich SEI. Consequently, the single-crystal Cu foils with a single [100] orientation (s-Cu(100)) achieve the dendrite-free Li deposition with enhanced Li plating/stripping reversibility. Moreover, the Li anode deposited on s-Cu(100) can stabilize the operation of an Ah-level pouch cell (350 Wh kg-1) with a low negative/positive capacity ratio (~2) and lean electrolyte (2.4 g Ah-1) for 150 cycles. Impressively, this strategy demonstrates universality in a series of electrolytes employed different anions. This work provides new insights into the correlation between the SEI and current collector, opening a universal avenue towards high-performance Li metal batteries.

9.
Mol Plant Pathol ; 25(6): e13483, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38829344

RESUMO

As a universal second messenger, cytosolic calcium (Ca2+) functions in multifaceted intracellular processes, including growth, development and responses to biotic/abiotic stresses in plant. The plant-specific Ca2+ sensors, calmodulin and calmodulin-like (CML) proteins, function as members of the second-messenger system to transfer Ca2+ signal into downstream responses. However, the functions of CMLs in the responses of cotton (Gossypium spp.) after Verticillium dahliae infection, which causes the serious vascular disease Verticillium wilt, remain elusive. Here, we discovered that the expression level of GbCML45 was promoted after V. dahliae infection in roots of cotton, suggesting its potential role in Verticillium wilt resistance. We found that knockdown of GbCML45 in cotton plants decreased resistance while overexpression of GbCML45 in Arabidopsis thaliana plants enhanced resistance to V. dahliae infection. Furthermore, there was physiological interaction between GbCML45 and its close homologue GbCML50 by using yeast two-hybrid and bimolecular fluorescence assays, and both proteins enhanced cotton resistance to V. dahliae infection in a Ca2+-dependent way in a knockdown study. Detailed investigations indicated that several defence-related pathways, including salicylic acid, ethylene, reactive oxygen species and nitric oxide signalling pathways, as well as accumulations of lignin and callose, are responsible for GbCML45- and GbCML50-modulated V. dahliae resistance in cotton. These results collectively indicated that GbCML45 and GbCML50 act as positive regulators to improve cotton Verticillium wilt resistance, providing potential targets for exploitation of improved Verticillium wilt-tolerant cotton cultivars by genetic engineering and molecular breeding.


Assuntos
Cálcio , Resistência à Doença , Gossypium , Doenças das Plantas , Proteínas de Plantas , Gossypium/microbiologia , Gossypium/genética , Gossypium/metabolismo , Gossypium/imunologia , Resistência à Doença/genética , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Cálcio/metabolismo , Regulação da Expressão Gênica de Plantas , Calmodulina/metabolismo , Calmodulina/genética , Arabidopsis/microbiologia , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/metabolismo , Ascomicetos/fisiologia , Ascomicetos/patogenicidade , Plantas Geneticamente Modificadas , Verticillium/fisiologia , Verticillium/patogenicidade
10.
Ann Hematol ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842567

RESUMO

Diffuse large B-cell lymphoma (DLBCL) represents the most common tumor in non-Hodgkin's lymphoma. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor highly expressed in healthy tissues but downregulated in many cancers. Although cell proliferation-related metabolism rewiring has been well characterized, less is known about the mechanism of metabolic changes with DLBCL. Herein, we investigated the expressions of NDRG2, MYC and Myc-interacting zinc finger protein 1 (MIZ-1) in seven human lymphoma (mostly DLBCLs) cell lines. NDRG2 expression was inversely correlated with the expressions of MYC and MIZ-1. Further, we explored the regulatory mechanism and biological functions underlying the lymphomagenesis involving NDRG2, MYC and MIZ-1. MYC and MIZ-1 promoted DLBCL cell proliferation, while NDRG2 induced apoptosis in LY8 cells. Moreover, NDRG2 methylation was reversed by the 5-Aza-2'-deoxycytidine (5-Aza-CDR) treatment, triggering the downregulation of MYC and inhibiting DLBCL cell survival. MYC interacts with NDRG2 to regulate energy metabolism associated with mTOR. Remarkably, supporting the biological significance, the converse correlation between NDRG2 and MYC was observed in human DLBCL tumor tissues (R = -0.557). Bioinformatics analysis further validated the association among NDRG2, MYC, MIZ-1, mTOR, and related metabolism genes. Additionally, NDRG2 (P = 0.001) and MYC (P < 0.001) were identified as promising prognostic biomarkers in DLBCL patients through survival analysis. Together, our data demonstrate that the MYC/MIZ-1 complex interplays with NDRG2 to influence the proliferation and apoptosis of DLBCL cells and show the characterizations of NDRG2, MYC and MIZ-1 for metabolism features and prediction prognosis in DLBCL.

11.
J Hazard Mater ; 476: 134981, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908187

RESUMO

High-resolution identification of chromium (Cr) species, especially various organic-Cr complexes, in a convenient and economically-feasible manner is the prerequisite for achieving the advanced treatment of chromium wastewater. To this end, a colorimetric nano-Au sensor array was developed by taking advantage of the UV-spectra shift of gold nanoparticles (Au NPs) upon interaction with Cr species; specifically, four molecular modifiers [i.e., iminodiacetic acid (IDA), tripolyphosphate (TPP), cetyltrimethylammonium bromide (CTAB), and 1,5-diphenylcarbazide (DPC)] were intentionally employed for assembling nano-Au array receptors, which showed respective responses toward different Cr species through the formation of coordination, hydrophobic interaction, electrostatic attraction, and redox reaction, respectively; the "fingerprint" differences of the unique optical properties were then integrated for semi-quantitatively recognizing Cr species by pattern recognition techniques. Eleven ubiquitous Cr species [i.e., Cr(III), Cr(VI), and various Cr(III)-organic complexes] served as the model samples, which could be sensitively identified, no matter in individual or mixture mode, by the developed nano-Au sensor array on the basis of the colorimetric responses resulted from diverse nano-Au-aggregation behaviors, with excellent anti-interference ability in the simulated or actual water scenario. Attractively, the nano-Au sensor array can achieve very sensitive detection limit of the quantitative analyses of Cr species in a prompt in-situ manner, which usually requires a two-step process of separation and detection for the conventional analytical methods. Such a convenient strategy of Cr species discrimination conduces to rationally designing specific protocols for the advanced treatment of chromium wastewater.

12.
Sci Adv ; 10(25): eadp0575, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38896626

RESUMO

Dirac fermion in topological materials exhibits intriguing nonlinear optical responses. However, their direct correlation with the linearly dispersed band remains elusive experimentally. Here, we take topological semimetal ZrSiS as a paradigm, unveiling three unique nonlinear optical signatures of Dirac fermion. These signatures include strong quadrupolar response, quantum interference effect, and exponential divergent four-wave mixing (FWM), all of which are described by the prominent third-order nonlinear optical susceptibility. Resonantly enhanced by linear bands, quadrupolar second harmonic generation in centrosymmetric bulk overwhelms the electric-dipole contribution at the surface with inherent inversion symmetry breaking. Furthermore, owing to the interference between multiple resonant transition pathways within linear bands, difference-frequency FWM is several orders of magnitude stronger than sum-frequency FWM and third harmonic generation. The difference-frequency FWM further displays an inverse-square divergence toward degenerate excitation, whose scaling law perfectly matches with the long-sought behavior of Dirac fermion. These signatures lay the solid foundation toward the practical applications of topological materials in nonlinear optoelectronics and photonics.

13.
BMC Biotechnol ; 24(1): 40, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849776

RESUMO

BACKGROUND: This study compared the differences of microvesicles (MVs) and microvesicles-delivering Smad7 (Smad7-MVs) on macrophage M1 polarization and fibroblast differentiation in a model of Peyronie's disease (PD). METHODS: Overexpression of Smad7 in rat BMSCs was obtained by pCMV5-Smad7 transfection. MVs were collected from rat BMSCs using ultracentrifugation. In cells, 100 µg/mL of MVs or Smad7-MVs were used to treat the 100 ng/mL of lipopolysaccharide (LPS)-induced RAW264.7 cells or 10 ng/mL of recombinant transforming growth factor-ß1 (TGF-ß1)-induced fibroblasts. The pro-inflammatory cytokines and markers of M1 macrophages were measured in RAW264.7 cells, and the migration and markers of fibroblast differentiation were measured in fibroblasts. In rats, 50 µg of MVs or Smad7-MVs were used to treat the TGF-ß1-induced animals. The pathology of tunica albuginea (TA), the markers of M1 macrophages and fibroblast differentiation in the TA were measured. RESULTS: The MVs or Smad7-MVs treatment suppressed the LPS-induced macrophage M1 polarization and TGF-ß1-induced fibroblast differentiation. Moreover, the Smad7-MVs treatment decreased the fibroblast differentiation compared with the MVs treatment. In the TGF-ß1-induced TA of rats, MVs or Smad7-MVs treatment ameliorated the TA fibrosis by suppressing the macrophage M1 polarization and fibroblast differentiation. There was no significance on the M1-polarized macrophages between the MVs treatment and the Smad7-MVs treatment. Meanwhile, the Smad7-MVs treatment had an edge in terms of suppressing the fibroblast differentiation in the TGF-ß1-induced PD model compared with the MVs treatment. CONCLUSIONS: This study demonstrated that Smad7-MVs treatment had advantages over MVs treatment in suppressing of fibroblast differentiation in a model of PD.


Assuntos
Diferenciação Celular , Micropartículas Derivadas de Células , Modelos Animais de Doenças , Fibroblastos , Macrófagos , Induração Peniana , Proteína Smad7 , Fator de Crescimento Transformador beta1 , Animais , Induração Peniana/metabolismo , Induração Peniana/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Ratos , Masculino , Proteína Smad7/metabolismo , Proteína Smad7/genética , Camundongos , Micropartículas Derivadas de Células/metabolismo , Células RAW 264.7 , Fator de Crescimento Transformador beta1/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Ratos Sprague-Dawley , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia
14.
Nat Commun ; 15(1): 3987, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734698

RESUMO

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.


Assuntos
Barreira Hematoencefálica , Encéfalo , Circulação Cerebrovascular , Nanopartículas , Alcaloides de Vinca , Animais , Alcaloides de Vinca/farmacologia , Alcaloides de Vinca/farmacocinética , Alcaloides de Vinca/administração & dosagem , Alcaloides de Vinca/química , Nanopartículas/química , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Camundongos , Circulação Cerebrovascular/efeitos dos fármacos , Masculino , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Humanos , Fármacos Neuroprotetores/farmacocinética , Fármacos Neuroprotetores/farmacologia , Camundongos Endogâmicos C57BL , Distribuição Tecidual , Sistemas de Liberação de Medicamentos , Camundongos Transgênicos
15.
Front Immunol ; 15: 1354992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736891

RESUMO

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application.


Assuntos
Biomarcadores Tumorais , Receptores de Hialuronatos , Leucemia , Células-Tronco Neoplásicas , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/imunologia , Receptores de Hialuronatos/metabolismo , Leucemia/metabolismo , Leucemia/terapia , Leucemia/imunologia , Biomarcadores Tumorais/metabolismo , Animais , Transdução de Sinais , Terapia de Alvo Molecular
16.
Proc Natl Acad Sci U S A ; 121(20): e2322625121, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38709915

RESUMO

Soft robots often draw inspiration from nature to navigate different environments. Although the inching motion and crawling motion of caterpillars have been widely studied in the design of soft robots, the steering motion with local bending control remains challenging. To address this challenge, we explore modular origami units which constitute building blocks for mimicking the segmented caterpillar body. Based on this concept, we report a modular soft Kresling origami crawling robot enabled by electrothermal actuation. A compact and lightweight Kresling structure is designed, fabricated, and characterized with integrated thermal bimorph actuators consisting of liquid crystal elastomer and polyimide layers. With the modular design and reprogrammable actuation, a multiunit caterpillar-inspired soft robot composed of both active units and passive units is developed for bidirectional locomotion and steering locomotion with precise curvature control. We demonstrate the modular design of the Kresling origami robot with an active robotic module picking up cargo and assembling with another robotic module to achieve a steering function. The concept of modular soft robots can provide insight into future soft robots that can grow, repair, and enhance functionality.

17.
Plant Divers ; 46(3): 421-424, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798722

RESUMO

•Four newly recorded species of Podostemaceae from southern China were identified by molecular and morphological evidence.•17 plastomes of Podostemaceae were newly sequenced and two novel polymorphic barcodes (ccsA and ndhA) detected.•Our findings reveal greater species richness (15 species from five genera) of Podostemaceae in China and supply molecular resources for research on taxonomy and phylogenomics of this enigmatic aquatic family.

18.
J Ophthalmol ; 2024: 3181569, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812725

RESUMO

Purpose: The reference range for the preoperative anterior chamber angle width for ICL surgery is unclear. Our objective was to assess the clinical effect and the range of anterior chamber angle width of posterior-chamber implantable collamer lens V4c (ICL V4c) implantation in patients with anterior chamber depth (ACD) < 2.8 mm. Methods: Patients who underwent ICL V4c implantation with shallow ACD were included in this retrospective study. The patients' uncorrected and corrected distance visual acuity, angle of trabecular-iris (TIA), angle-opening distance (AOD500), trabecular-iris space area (TISA500), corneal endothelial cell density, vault, retinal nerve fiber layer thickness, intraocular pressure, visual field, and complications were analyzed. Results: Forty-one patients (68 eyes) completed at least 12 months of follow-up (median follow-up, 30 months). The effectiveness and safety indices were 1.09 ± 0.13 and 1.04 ± 0.21, respectively. The preoperative TIA values on the nasal and temporal sides were 39.78 ± 7.68 degree (range, 25.8-65.1 degree) and 41.54 ± 8.03 degree (range, 28.5-63.00 degree). Forty-seven eyes had uncorrected distance visual acuity ≥1.0, and 55 had corrected distance visual acuity ≥1.0 at the last follow-up visit. The TIA, AOD500, and TISA500 on the nasal and temporal sides were significantly reduced compared to those before surgery (all P < 0.01); no eye had an angle closure or elevated intraocular pressure. The ICL V4c vault was 290.88 ± 153.36 µm (range, 60.0-880.0 µm). No severe complications occurred in any patient. Conclusions: In patients with myopia with shallow ACD (2.55-2.79 mm), a preoperative TIA >25.8° is safe and effective for a relatively long time after surgery; however, an extended long-term close follow-up is needed.

19.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731831

RESUMO

Small secreted peptides (SSPs) play important roles in regulating plants' growth and development in response to external stimulus, but the genes and functions of SSPs in many species are still unknown. Therefore, it is particularly significant to characterize and annotate SSP genes in plant genomes. As a widely used stock of pears, Pyrus betulifolia has strong resistance to biotic and abiotic stresses. In this study, we analyzed the SSPs genes in the genome of P. betulifolia according to their characteristics and homology. A total of 1195 SSP genes were identified, and most of them are signaling molecules. Among these, we identified a new SSP, subtilase peptide 3 (SUBPEP3), which derived from the PA region of preSUBPEP3, increasing the expression level under salt stress. Both adding synthetic peptide SUBPEP3 to the culture medium of pears and the overexpression of SUBPEP3 in tobacco can improve the salt tolerance of plants. In summary, we annotated the SSP genes in the P. betulifolia genome and identified a small secreted peptide SUBPEP3 that regulates the salt tolerance of P. betulifolia, which provides an important theoretical basis for further revealing the function of SSPs.


Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Pyrus , Tolerância ao Sal , Pyrus/genética , Pyrus/metabolismo , Tolerância ao Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Salino/genética , Nicotiana/genética , Nicotiana/metabolismo , Sequência de Aminoácidos , Peptídeos/metabolismo , Peptídeos/genética , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/genética
20.
Eur J Med Chem ; 272: 116477, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38733884

RESUMO

The cellular-mesenchymal epithelial transition factor (c-Met) is a receptor tyrosine kinase (RTK) located on the 7q31 locus encoding the Met proto-oncogene and plays a critical role in regulating cell proliferation, metastasis, differentiation, and apoptosis through various signaling pathways. However, its aberrant activation and overexpression have been implicated in many human cancers. Therefore, c-Met is a promising target for cancer treatment. However, the anticancer effect of selective single-targeted drugs is limited due to the complexity of the signaling system and the involvement of different proteins and enzymes. After inhibiting one pathway, signal molecules can be transmitted through other pathways, resulting in poor efficacy of single-targeted drug therapy. Dual inhibitors that simultaneously block c-Met and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, We introduced c-Met kinase and the synergism between c-Met and other anti-tumor targets, then dual-target inhibitors based on c-Met for the treatment of cancers were summarized and their design concepts and structure-activity relationships (SARs) were discussed elaborately, providing a valuable insight for the further development of novel c-Met-based dual inhibitors.


Assuntos
Antineoplásicos , Neoplasias , Inibidores de Proteínas Quinases , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-met , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Relação Estrutura-Atividade , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Animais
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