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1.
Genes Dev ; 37(21-24): 1041-1051, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38110249

RESUMO

We show here that mir-279/996 are absolutely essential for development and function of Johnston's organ (JO), the primary proprioceptive and auditory organ in Drosophila Their deletion results in highly aberrant cell fate determination, including loss of scolopale cells and ectopic neurons, and mutants are electrophysiologically deaf. In vivo activity sensors and mosaic analyses indicate that these seed-related miRNAs function autonomously to suppress neural fate in nonneuronal cells. Finally, genetic interactions pinpoint two neural targets (elav and insensible) that underlie miRNA mutant JO phenotypes. This work uncovers how critical post-transcriptional regulation of specific miRNA targets governs cell specification and function of the auditory system.


Assuntos
Proteínas de Drosophila , MicroRNAs , Animais , MicroRNAs/genética , Audição/genética , Drosophila/genética , Proteínas de Drosophila/genética , Órgãos dos Sentidos/fisiologia
2.
Nature ; 629(8012): 586-591, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720080

RESUMO

Light-emitting diodes (LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiencies (EQEs) of more than 25% with narrowband emission1,2, but these LEDs have limited operating lifetimes. We posit that poor long-range ordering in perovskite QD films-variations in dot size, surface ligand density and dot-to-dot stacking-inhibits carrier injection, resulting in inferior operating stability because of the large bias required to produce emission in these LEDs. Here we report a chemical treatment to improve the long-range order of perovskite QD films: the diffraction intensity from the repeating QD units increases three-fold compared with that of controls. We achieve this using a synergistic dual-ligand approach: an iodide-rich agent (aniline hydroiodide) for anion exchange and a chemically reactive agent (bromotrimethylsilane) that produces a strong acid that in situ dissolves smaller QDs to regulate size and more effectively removes less conductive ligands to enable compact, uniform and defect-free films. These films exhibit high conductivity (4 × 10-4 S m-1), which is 2.5-fold higher than that of the control, and represents the highest conductivity recorded so far among perovskite QDs. The high conductivity ensures efficient charge transportation, enabling red perovskite QD-LEDs that generate a luminance of 1,000 cd m-2 at a record-low voltage of 2.8 V. The EQE at this luminance is more than 20%. Furthermore, the stability of the operating device is 100 times better than previous red perovskite LEDs at EQEs of more than 20%.

3.
J Virol ; 98(1): e0131923, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38084961

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a serious global pig industry disease. Understanding the mechanism of viral replication and developing efficient antiviral strategies are necessary for combating with PRRS virus (PRRSV) infection. Recently, nanobody is considered to be a promising antiviral drug, especially for respiratory viruses. The present study evaluated two nanobodies against PRRSV nucleocapsid (N) protein (PRRSV-N-Nb1 and -Nb2) for their anti-PRRSV activity in vitro and in vivo. The results showed that intracellularly expressed PRRSV-N-Nb1 significantly inhibited PRRSV-2 replication in MARC-145 cells (approximately 100%). Then, the PRRSV-N-Nb1 fused with porcine IgG Fc (Nb1-pFc) as a delivering tag was produced and used to determine its effect on PRRSV-2 replication in porcine alveolar macrophages (PAMs) and pigs. The inhibition rate of Nb1-pFc against PRRSV-2 in PAMs could reach >90%, and it can also inhibit viral replication in vivo. Epitope mapping showed that the motif Serine 105 (S105) in PRRSV-2 N protein was the key amino acid binding to PRRSV-N-Nb1, which is also pivotal for the self-interaction of N protein via binding to Arginine 97. Moreover, viral particles were not successfully rescued when the S105 motif was mutated to Alanine (S105A). Attachment, entry, genome replication, release, docking model analysis, and blocking enzyme-linked immunosorbent assay (ELISA) indicated that the binding of PRRSV-N-Nb1 to N protein could block its self-binding, which prevents the viral replication of PRRSV. PRRSV-N-Nb1 may be a promising drug to counter PRRSV-2 infection. We also provided some new insights into the molecular basis of PRRSV N protein self-binding and assembly of viral particles.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) causes serious economic losses to the swine industry worldwide, and there are no highly effective strategies for prevention. Nanobodies are considered a promising novel approach for treating diseases because of their ease of production and low costing. Here, we showed that PRRSV-N-Nb1 against PRRSV-N protein significantly inhibited PRRSV-2 replication in vitro and in vivo. Furthermore, we demonstrated that the motif Serine 105 (S105) in PRRSV-N protein was the key amino acid to interact with PRRSV-N-Nb1 and bond to its motif R97, which is important for the self-binding of N protein. The PRRSV-N-Nb1 could block the self-interaction of N protein following viral assembly. These findings not only provide insights into the molecular basis of PRRSV N protein self-binding as a key factor for viral replication for the first time but also highlight a novel target for the development of anti-PRRSV replication drugs.


Assuntos
Proteínas do Nucleocapsídeo , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Anticorpos de Domínio Único , Animais , Aminoácidos , Linhagem Celular , Proteínas do Nucleocapsídeo/metabolismo , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Serina , Anticorpos de Domínio Único/farmacologia , Suínos , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos
4.
Proc Natl Acad Sci U S A ; 119(49): e2212630119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36442134

RESUMO

In the primary step of natural light harvesting, the solar photon energy is captured in a photoexcited electron-hole pair, or an exciton, in chlorophyll. Its conversion to chemical potential occurs in the special pair reaction center, which is reached by downhill ultrafast excited-state energy transport through a network of chromophores. Being inherently quantum, transport could in principle occur via a matter wave, with vast implications for efficiency. How long a matter wave remains coherent is determined by the intensity by which the exciton is disturbed by the noisy biological environment. The stronger this is, the stronger the electronic coupling between chromophores must be to overcome the fluctuations and phase shifts. The current consensus is that under physiological conditions, quantum coherence vanishes on the 10-fs time scale, rendering it irrelevant for the observed picosecond transfer. Yet, at low-enough temperature, quantum coherence should in principle be present. Here, we reveal the onset of longer-lived electronic coherence at extremely low temperatures of ∼20 K. Using two-dimensional electronic spectroscopy, we determine the exciton coherence times in the Fenna-Matthew-Olson complex over an extensive temperature range. At 20 K, coherence persists out to 200 fs (close to the antenna) and marginally up to 500 fs at the reaction center. It decays markedly faster with modest increases in temperature to become irrelevant above 150 K. At low temperature, the fragile electronic coherence can be separated from the robust vibrational coherence, using a rigorous theoretical analysis. We believe that by this generic principle, light harvesting becomes robust against otherwise fragile quantum effects.


Assuntos
Temperatura Baixa , Eletrônica , Temperatura , Fenômenos Físicos , Clorofila
5.
Nano Lett ; 24(9): 2765-2772, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38393855

RESUMO

Alloying lanthanide ions (Yb3+) into perovskite quantum dots (Yb3+:CsPb(Cl1-xBrx)3) is an effective method to achieve efficient near-infrared (NIR) luminescence (>950 nm). Increasing the Yb3+ alloying ratio in the perovskite matrix enhances the luminescence intensity of Yb3+ emission at 990 nm. However, high Yb3+ alloying (>15%) results in vacancy-induced inferior material stability. In this work, we developed a polarity-mediated antisolvent manipulation strategy to resolve the incompatibility between a high Yb3+ alloying ratio and inferior stability of Yb3+:CsPb(Cl1-xBrx)3. Precise control of solution polarity enables increased uniformity of the perovskite matrix with fewer trap densities. Employing this strategy, we obtain Yb3+:CsPb(Cl1-xBrx)3 with the highest Yb3+ alloying ratio of 30.2% and a 2-fold higher electroluminescence intensity at 990 nm. We lever the engineered Yb3+:CsPb(Cl1-xBrx)3 to fabricate NIR-LEDs, achieving a peak external quantum efficiency (EQE) of 8.5% at 990 nm: this represents the highest among perovskite NIR-LEDs with an emission wavelength above 950 nm.

6.
Cardiovasc Diabetol ; 23(1): 252, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010053

RESUMO

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) were initially recommended as oral anti-diabetic drugs to treat type 2 diabetes (T2D), by inhibiting SGLT2 in proximal tubule and reduce renal reabsorption of sodium and glucose. While many clinical trials demonstrated the tremendous potential of SGLT2i for cardiovascular diseases. 2022 AHA/ACC/HFSA guideline first emphasized that SGLT2i were the only drug class that can cover the entire management of heart failure (HF) from prevention to treatment. Subsequently, the antiarrhythmic properties of SGLT2i have also attracted attention. Although there are currently no prospective studies specifically on the anti-arrhythmic effects of SGLT2i. We provide clues from clinical and fundamental researches to identify its antiarrhythmic effects, reviewing the evidences and mechanism for the SGLT2i antiarrhythmic effects and establishing a novel paradigm involving intracellular sodium, metabolism and autophagy to investigate the potential mechanisms of SGLT2i in mitigating arrhythmias.


Assuntos
Antiarrítmicos , Arritmias Cardíacas , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Humanos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Antiarrítmicos/uso terapêutico , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/prevenção & controle , Arritmias Cardíacas/metabolismo , Resultado do Tratamento , Frequência Cardíaca/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/metabolismo , Potenciais de Ação/efeitos dos fármacos , Sódio/metabolismo
7.
Appl Opt ; 63(6): A7-A15, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38437352

RESUMO

Accurate and efficient counting of shrimp larvae is crucial for monitoring reproduction patterns, assessing growth rates, and evaluating the performance of aquaculture. Traditional methods via density estimation are ineffective in the case of high density. In addition, the image contains bright spots utilizing the point light source or the line light source. Therefore, in this paper an automated shrimp counting platform based on optics and image processing is designed to complete the task of counting shrimp larvae. First, an area light source ensures a uniformly illuminated environment, which helps to obtain shrimp images with high resolution. Then, a counting algorithm based on improved k-means and a side window filter (SWF) is designed to achieve an accurate number of shrimp in the lamp house. Specifically, the SWF technique is introduced to preserve the body contour of shrimp larvae, and eliminate noise, such as water impurities and eyes of shrimp larvae. Finally, shrimp larvae are divided into two groups, independent and interdependent, and counted separately. Experimental results show that the designed optical counting system is excellent in terms of visual effect and objective evaluation.


Assuntos
Algoritmos , Aquicultura , Animais , Olho , Processamento de Imagem Assistida por Computador , Larva
8.
Chem Biodivers ; : e202400963, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778509

RESUMO

The Sterculia genus is comprised of approximately 300 species, which have been widely used as traditional medicines to treat inflammation, snake bites, gastrointestinal diseases, skin diseases, microbial infections and many other diseases. To gain a comprehensive understanding of the therapeutic potential of Sterculia plants, an extensive literature search was conducted in CNKI, Bing, Wanfang Database, Springer Database, Elsevier Database, Google Scholar, Baidu Scholar, PubMed, and other similar websites from January 1971 to March 2024. The research indicated that Sterculia species predominantly contain flavonoids, terpenoids, phenylpropanoids, fatty acids, alkaloids and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, antioxidant, antibacterial and other biological activities have been reported. Nevertheless, there isn't much scholarly research on the therapeutic material basis of the genus Sterculia. This review reports the ethnobotany, phytochemicals, and biological activities of the plants in the Sterculia genus as herbal remedies.

9.
Mikrochim Acta ; 191(7): 387, 2024 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869719

RESUMO

A novel construction strategy is introduced for an ultrasensitive dynamic light scattering (DLS) immunosensor targeting alpha fetoprotein (AFP). This approach relies on a self-assembled heptamer fusion protein (A1-C4bpα), incorporating the dual functions of multivalent recognition and crosslinking aggregation amplification due to the presence of seven AFP-specific A1 nanobodies on the A1-C4bpα heptamer. Leveraging antibody-functionalized magnetic nanoparticles for target AFP capture and DLS signal output, the proposed heptamer-assisted DLS immunosensor offers high sensitivity, strong specificity, and ease of operation. Under the optimized conditions, the designed DLS immunosensor demonstrates excellent linear detection of AFP in the concentration range 0.06 ng mL-1 to 512 ng mL-1, with a detection limit of 15 pg mL-1. The selectivity, accuracy, precision, practicability, and reliability of this newly developed method were further validated through an assay of AFP levels in spiked and actual human serum samples. This work introduces a novel approach for constructing ultrasensitive DLS immunosensors, easily extendable to the sensitive determination of other targets via simply replacing the nanobody sequence, holding great promise in various applications, particularly in disease diagnosis.


Assuntos
Difusão Dinâmica da Luz , Limite de Detecção , alfa-Fetoproteínas , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia , Humanos , Imunoensaio/métodos , Anticorpos Imobilizados/imunologia , Técnicas Biossensoriais/métodos , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/imunologia , Nanopartículas de Magnetita/química
10.
Int Wound J ; 21(1): e14614, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38272824

RESUMO

We conducted this study aimed to explore the effect of operating room nursing intervention on wound infection in patients undergoing ovarian cysts surgery. A computer system was used to search PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure databases, from database inception to October 2023, for randomised controlled trials (RCTs) on the application of operating room nursing intervention to ovarian cyst surgery. Literature that met the requirements was independently screened by two researchers, and data were extracted and assessed for literature quality. RevMan 5.4 software was applied for data analysis. Fifteen RCTs involving 1187 patients were finally included. The analyses revealed that, compared with routine nursing, the implementation of operating room nursing intervention had a significant advantage in reducing the incidence of wound infections (1.17% vs. 5.44%, odds ratio [OR]: 0.30, 95% confidence interval [CI]: 0.15-0.58, p = 0.0004) and postoperative complications (6.34% vs. 25.17%, OR: 0.20, 95%CI: 0.13-0.29, p < 0.00001), as well as being able to shorten the operative time (standardised mean difference [SMD]: -3.93, 95%CI: -5.67 to -2.20, p < 0.00001), hospital length of stay (SMD: -2.54, 95%CI: -3.19 to -1.89, p < 0.00001) and gastrointestinal recovery time (SMD: -1.61, 95%CI: -2.24 to -0.98, p < 0.00001) in patients undergoing ovarian cysts surgery. This study confirmed by meta-analysis that the operating room nursing intervention can significantly reduce the incidence of wound infection and complications, shorten the operative time, gastrointestinal recovery time, and hospital length of stay after ovarian cyst surgery.


Assuntos
Enfermagem de Centro Cirúrgico , Cistos Ovarianos , Infecção dos Ferimentos , Feminino , Humanos , Complicações Pós-Operatórias/prevenção & controle , Enfermagem Perioperatória , Cistos Ovarianos/cirurgia
11.
Angew Chem Int Ed Engl ; 63(7): e202313900, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38158383

RESUMO

N1 -methyladenosine (m1 A) is a prevalent post-transcriptional RNA modification, and the distribution and dynamics of the modification play key epitranscriptomic roles in cell development. At present, the human AlkB Fe(II)/α-ketoglutarate-dependent dioxygenase family member ALKBH3 is the only known mRNA m1 A demethylase, but its catalytic mechanism remains unclear. Here, we present the structures of ALKBH3-oligo crosslinked complexes obtained with the assistance of a synthetic antibody crystallization chaperone. Structural and biochemical results showed that ALKBH3 utilized two ß-hairpins (ß4-loop-ß5 and ß'-loop-ß'') and the α2 helix to facilitate single-stranded substrate binding. Moreover, a bubble-like region around Asp194 and a key residue inside the active pocket (Thr133) enabled specific recognition and demethylation of m1 A- and 3-methylcytidine (m3 C)-modified substrates. Mutation of Thr133 to the corresponding residue in the AlkB Fe(II)/α-ketoglutarate-dependent dioxygenase family members FTO or ALKBH5 converted ALKBH3 substrate selectivity from m1 A to N6 -methyladenosine (m6 A), as did Asp194 deletion. Our findings provide a molecular basis for understanding the mechanisms of substrate recognition and m1 A demethylation by ALKBH3. This study is expected to aid structure-guided design of chemical probes for further functional studies and therapeutic applications.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , RNA , Humanos , RNA/química , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , RNA Mensageiro/metabolismo , Desmetilação , Compostos Ferrosos , Homólogo AlkB 3 da Dioxigenase Dependente de alfa-Cetoglutarato/metabolismo
12.
Semin Cancer Biol ; 83: 261-268, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33785448

RESUMO

Thyroid cancer is not among the top cancers in terms of diagnosis or mortality but it still ranks fifth among the cancers diagnosed in women. Infact, women are more likely to be diagnosed with thyroid cancer than the males. The burden of thyroid cancer has dramatically increased in last two decades in China and, in the United States, it is the most diagnosed cancer in young adults under the age of twenty-nine. All these factors make it worthwhile to fully understand the pathogenesis of thyroid cancer. Towards this end, microRNAs (miRNAs) have constantly emerged as the non-coding RNAs of interest in various thyroid cancer subtypes on which there have been numerous investigations over the last decade and half. This comprehensive review takes a look at the current knowledge on the topic with cataloging of miRNAs known so far, particularly related to their utility as epigenetic signatures of thyroid cancer progression and metastasis. Such information could be of immense use for the eventual development of miRNAs as therapeutic targets or even therapeutic agents for thyroid cancer therapy.


Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Epigênese Genética , Epigenômica , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
13.
Mol Cell ; 57(1): 165-78, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-25544562

RESUMO

Although endogenous siRNAs (endo-siRNAs) have been described in many species, still little is known about their endogenous utility. Here, we show that Drosophila hairpin RNAs (hpRNAs) generate an endo-siRNA class with predominant expression in testes. Although hpRNAs are universally recently evolved, we identify highly complementary protein-coding targets for all hpRNAs. Importantly, we find broad evidence for evolutionary divergences that preferentially maintain compensatory pairing between hpRNAs and targets, serving as first evidence for adaptive selection for siRNA-mediated target regulation in metazoans. We demonstrate organismal impact of hpRNA activity, since knockout of hpRNA1 derepresses its target ATP synthase-ß in testes and compromises spermatogenesis and male fertility. Moreover, we reveal surprising male-specific impact of RNAi factors on germ cell development and fertility, consistent with testis-directed function of the hpRNA pathway. Finally, the collected hpRNA loci chronicle an evolutionary timeline that reflects their origins from prospective target genes, mirroring a strategy described for plant miRNAs.


Assuntos
Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos/genética , RNA Interferente Pequeno/genética , Espermatogênese/genética , Testículo/metabolismo , Adaptação Fisiológica/genética , Animais , Sequência de Bases , Evolução Biológica , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Fertilidade/genética , Humanos , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/metabolismo , Masculino , ATPases Mitocondriais Próton-Translocadoras/antagonistas & inibidores , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Subunidades Proteicas/antagonistas & inibidores , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Espermatozoides/crescimento & desenvolvimento , Espermatozoides/metabolismo , Testículo/crescimento & desenvolvimento
14.
Phytother Res ; 37(7): 2745-2758, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36794391

RESUMO

Dracocephalum Moldavica L. is a traditional herb for improving pharynx and relieving cough. However, the effect on pulmonary fibrosis is not clear. In this study, we explored the impact and molecular mechanism of total flavonoid extract from Dracocephalum moldavica L. (TFDM) on bleomycin-induced pulmonary fibrosis mouse model. Lung function testing, lung inflammation and fibrosis, and the related factors were detected by the lung function analysis system, HE and Masson staining, ELISA, respectively. The expression of proteins was studied through Western Blot, immunohistochemistry, and immunofluorescence while the expression of genes was analyzed by RT-PCR. The results showed that TFDM significantly improved lung function in mice, reduced the content of inflammatory factors, thereby reducing the inflammation. It was found that expression of collagen type I, fibronectin, and α-smooth muscle actin was significantly decreased by TFDM. The results further showed that TFDM interferes with hedgehog signaling pathway by decreasing the expression of Shh, Ptch1, and SMO proteins and thereby inhibiting the generation of downstream target gene Gli1 and thus improving pulmonary fibrosis. Conclusively, these findings suggest that TFDM improve pulmonary fibrosis by reducing inflammation and inhibition of the hedgehog signaling pathway.


Assuntos
Flavonoides , Fibrose Pulmonar , Camundongos , Animais , Flavonoides/farmacologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Proteínas Hedgehog/metabolismo , Inflamação , Bleomicina
15.
Genes Dev ; 29(1): 48-62, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25561495

RESUMO

Recently, the BEN (BANP, E5R, and NAC1) domain was recognized as a new class of conserved DNA-binding domain. The fly genome encodes three proteins that bear only a single BEN domain ("BEN-solo" factors); namely, Insensitive (Insv), Bsg25A (Elba1), and CG9883 (Elba2). Insv homodimers preferentially bind CCAATTGG palindromes throughout the genome to mediate transcriptional repression, whereas Bsg25A and Elba2 heterotrimerize with their obligate adaptor, Elba3 (i.e., the ELBA complex), to recognize a CCAATAAG motif in the Fab-7 insulator. While these data suggest distinct DNA-binding properties of BEN-solo proteins, we performed reporter assays that indicate that both Bsg25A and Elba2 can individually recognize Insv consensus sites efficiently. We confirmed this by solving the structure of Bsg25A complexed to the Insv site, which showed that key aspects of the BEN:DNA recognition strategy are similar between these proteins. We next show that both Insv and ELBA proteins are competent to mediate transcriptional repression via Insv consensus sequences but that the ELBA complex appears to be selective for the ELBA site. Reciprocally, genome-wide analysis reveals that Insv exhibits significant cobinding to class I insulator elements, indicating that it may also contribute to insulator function. Indeed, we observed abundant Insv binding within the Hox complexes with substantial overlaps with class I insulators, many of which bear Insv consensus sites. Moreover, Insv coimmunoprecipitates with the class I insulator factor CP190. Finally, we observed that Insv harbors exclusive activity among fly BEN-solo factors with respect to regulation of Notch-mediated cell fate choices in the peripheral nervous system. This in vivo activity is recapitulated by BEND6, a mammalian BEN-solo factor that conserves the Notch corepressor function of Insv but not its capacity to bind Insv consensus sites. Altogether, our data define an array of common and distinct biochemical and functional properties of this new family of transcription factors.


Assuntos
Proteínas de Drosophila/genética , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Blastoderma/metabolismo , Proteínas Correpressoras/química , Proteínas Correpressoras/metabolismo , Cristalografia , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Modelos Moleculares , Ligação Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Alinhamento de Sequência , Transdução de Sinais , Fatores de Transcrição/química
16.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36768238

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is caused by the PRRS virus (PRRSV), which has brought huge economic losses to the pork industry worldwide since its first discovery in the late 1980s in North America. To date, there are no effective commercial vaccines or therapeutic drugs available for controlling the spread of PRRSV. Due to their unique advantages of high affinity and high specificity, nanobodies (Nbs) have received increasing attention in the process of disease diagnosis and treatment. Trans-activator transcription (TAT) can serve as a vector to carry specific proteins into cells by passing through cell membranes. In our previous study, a specific Nb against the PRRSV nucleocapsid (N) protein was screened using phage display technology. For this study, we developed a novel recombinant protein constituting a TAT-conjugated Nb, which we call TAT-Nb1. The target cell entry efficiency of TAT-Nb1 and its effect on PRRSV infection and replication were then investigated. Our results indicate that TAT delivered Nb1 into Marc-145 cells and porcine alveolar macrophages (PAMs) in a dose- and time-dependent manner. Furthermore, TAT-Nb1 dose-dependently suppressed PRRSV infection and replication, where this antiviral effect was independent of PRRSV strain. Co-immunoprecipitation results revealed that Nb1 efficiently interacted with the N protein of PRRSV. Taken together, the presented results suggest that TAT-Nb1 can effectively suppress PRRSV replication, and it may be considered as a new anti-PRRSV candidate drug.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Suínos , Antivirais/farmacologia , Antivirais/metabolismo , Linhagem Celular , Replicação Viral , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Proteínas do Nucleocapsídeo , Macrófagos Alveolares/metabolismo
17.
Sheng Li Xue Bao ; 75(2): 231-240, 2023 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-37089097

RESUMO

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.


Assuntos
Hemorragia Encefálica Traumática , Encéfalo , AVC Isquêmico , Neurogênese , Adulto , Animais , Humanos , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Mamíferos/fisiologia , Neurogênese/fisiologia , Hemorragia Encefálica Traumática/fisiopatologia , Hemorragia Encefálica Traumática/terapia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/terapia , Recuperação de Função Fisiológica , Medula Espinal/fisiologia , Medula Espinal/fisiopatologia
18.
Minim Invasive Ther Allied Technol ; 32(4): 153-162, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37051809

RESUMO

BACKGROUND: Robotic camera holders can overcome the shortcomings of human assistants, such as shaking and accidental rotation in endoscopic surgery. Robotic camera holder is not affected by the operation time and surgical position and reduces the size of the team. However, there is still controversy over the practicality of robotic camera holders. MATERIAL AND METHODS: We searched PubMed, Web of Science, Embase, Cochrane Library PubMed, Embase, Cochrane Library and Web of Science. The last database search was performed on 30 April 2022. Two reviewers independently reviewed the studies. RESULTS: A total of eight studies (n = 698, 354 controls and 344 robotic camera holders) were included in our analysis. The results showed that the robotic camera holder significantly outperformed human assistants on the frequency of lens cleaning (SMD, -0.48; 95% CI, -0.90 to -0.05) and inappropriate movements (MD, -3.57; 95% CI, -4.93 to -2.21). There was no difference in total operation time (MD, 6.99; 95% CI, -2.47 to 16.72), preparation time (MD, 2.43; 95% CI, -0.32 to 5.18) or blood loss (MD, 34.47; 95% CI, -8.05 to 76.98) between the robotic camera holder and human assistant. However, the robotic camera holder was significantly slower in the core operation (MD, 5.06; 95% CI, 1.18 to 8.94), and surgeons had mixed reviews of robotic systems. CONCLUSIONS: The robotic camera holder provided the surgeon with a highly stable environment. Although the robotic camera holder will not increase the total time, it still needs to improve the core operation time. There is much room for improvement in robotic camera holders. Further development of devices with intuitive control systems and a greater range of motion will be required to accommodate more complex surgeries.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgiões , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/métodos , Robótica/métodos , Duração da Cirurgia
19.
Angew Chem Int Ed Engl ; 62(5): e202212707, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36383643

RESUMO

Exploring new noncovalent bonding motifs with reversibly tunable binding affinity is of fundamental importance in manipulating the properties and functions of supramolecular self-assembly systems and materials. Herein, for the first time, we demonstrate a unique visible-light-switchable telluro-triazole/triazolium-based chalcogen bonding (ChB) system in which the Te moieties are connected by azobenzene cores. The binding strengths between these azo-derived ChB receptors and the halide anions (Cl- , Br- ) could be reversibly regulated upon irradiation by visible light of different wavelengths. The cis-bidentate ChB receptors exhibit enhanced halide anion binding ability compared to the trans-monodentate receptors. In particular, the telluro-triazolium-based ChB receptor can achieve both high and significantly photoswitchable binding affinities for halide anions, which enable it to serve as an efficient photocontrolled organocatalyst for ChB-assisted halide abstraction in a Friedel-Crafts alkylation benchmark reaction.

20.
Angew Chem Int Ed Engl ; 62(46): e202311089, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37770413

RESUMO

Resurfacing perovskite nanocrystals (NCs) with tight-binding and conductive ligands to resolve the dynamic ligands-surface interaction is the fundamental issue for their applications in perovskite light-emitting diodes (PeLEDs). Although various types of surface ligands have been proposed, these ligands either exhibit weak Lewis acid/base interactions or need high polar solvents for dissolution and passivation, resulting in a compromise in the efficiency and stability of PeLEDs. Herein, we report a chemically reactive agent (Iodotrimethylsilane, TMIS) to address the trade-off among conductivity, solubility and passivation using all-inorganic CsPbI3 NCs. The liquid TMIS ensures good solubility in non-polar solvents and reacts with oleate ligands and produces in situ HI for surface etching and passivation, enabling strong-binding ligands on the NCs surface. We report, as a result, red PeLEDs with an external quantum efficiency (EQE) of ≈23 %, which is 11.2-fold higher than the control, and is among the highest CsPbI3 PeLEDs. We further demonstrate the universality of this ligand strategy in the pure bromide system (CsPbBr3 ), and report EQE of ≈20 % at 640, 652, and 664 nm. This represents the first demonstration of a chemically reactive ligand strategy that applies to different systems and works effectively in red PeLEDs spanning emission from pure-red to deep-red.

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