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1.
Nat Methods ; 21(4): 597-608, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38379073

RESUMO

Quantifying the number of progenitor cells that found an organ, tissue or cell population is of fundamental importance for understanding the development and homeostasis of a multicellular organism. Previous efforts rely on marker genes that are specifically expressed in progenitors. This strategy is, however, often hindered by the lack of ideal markers. Here we propose a general statistical method to quantify the progenitors of any tissues or cell populations in an organism, even in the absence of progenitor-specific markers, by exploring the cell phylogenetic tree that records the cell division history during development. The method, termed targeting coalescent analysis (TarCA), computes the probability that two randomly sampled cells of a tissue coalesce within the tissue-specific monophyletic clades. The inverse of this probability then serves as a measure of the progenitor number of the tissue. Both mathematic modeling and computer simulations demonstrated the high accuracy of TarCA, which was then validated using real data from nematode, fruit fly and mouse, all with related cell phylogenetic trees. We further showed that TarCA can be used to identify lineage-specific upregulated genes during embryogenesis, revealing incipient cell fate commitments in mouse embryos.


Assuntos
Desenvolvimento Embrionário , Células-Tronco , Animais , Camundongos , Filogenia , Diferenciação Celular/genética , Divisão Celular
2.
Nucleic Acids Res ; 51(10): 4774-4790, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-36929421

RESUMO

Normal erythropoiesis requires the precise regulation of gene expression patterns, and transcription cofactors play a vital role in this process. Deregulation of cofactors has emerged as a key mechanism contributing to erythroid disorders. Through gene expression profiling, we found HES6 as an abundant cofactor expressed at gene level during human erythropoiesis. HES6 physically interacted with GATA1 and influenced the interaction of GATA1 with FOG1. Knockdown of HES6 impaired human erythropoiesis by decreasing GATA1 expression. Chromatin immunoprecipitation and RNA sequencing revealed a rich set of HES6- and GATA1-co-regulated genes involved in erythroid-related pathways. We also discovered a positive feedback loop composed of HES6, GATA1 and STAT1 in the regulation of erythropoiesis. Notably, erythropoietin (EPO) stimulation led to up-regulation of these loop components. Increased expression levels of loop components were observed in CD34+ cells of polycythemia vera patients. Interference by either HES6 knockdown or inhibition of STAT1 activity suppressed proliferation of erythroid cells with the JAK2V617F mutation. We further explored the impact of HES6 on polycythemia vera phenotypes in mice. The identification of the HES6-GATA1 regulatory loop and its regulation by EPO provides novel insights into human erythropoiesis regulated by EPO/EPOR and a potential therapeutic target for the management of polycythemia vera.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Eritropoese , Fator de Transcrição GATA1 , Proteínas Repressoras , Animais , Humanos , Camundongos , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Eritroides/metabolismo , Fator de Transcrição GATA1/metabolismo , Perfilação da Expressão Gênica , Policitemia Vera/genética , Policitemia Vera/metabolismo , Proteínas Repressoras/metabolismo
3.
PLoS Genet ; 18(1): e1009993, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34986161

RESUMO

SEDS (Shape, Elongation, Division and Sporulation) proteins are widely conserved peptidoglycan (PG) glycosyltransferases that form complexes with class B penicillin-binding proteins (bPBPs, with transpeptidase activity) to synthesize PG during bacterial cell growth and division. Because of their crucial roles in bacterial morphogenesis, SEDS proteins are one of the most promising targets for the development of new antibiotics. However, how SEDS proteins recognize their substrate lipid II, the building block of the PG layer, and polymerize it into glycan strands is still not clear. In this study, we isolated and characterized dominant-negative alleles of FtsW, a SEDS protein critical for septal PG synthesis during bacterial cytokinesis. Interestingly, most of the dominant-negative FtsW mutations reside in extracellular loops that are highly conserved in the SEDS family. Moreover, these mutations are scattered around a central cavity in a modeled FtsW structure, which has been proposed to be the active site of SEDS proteins. Consistent with this, we found that these mutations blocked septal PG synthesis but did not affect FtsW localization to the division site, interaction with its partners nor its substrate lipid II. Taken together, these results suggest that the residues corresponding to the dominant-negative mutations likely constitute the active site of FtsW, which may aid in the design of FtsW inhibitors.


Assuntos
Bactérias/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Mutação , Substituição de Aminoácidos , Bactérias/genética , Proteínas de Bactérias/genética , Domínio Catalítico , Proteínas de Membrana/genética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Peptidoglicano/biossíntese , Conformação Proteica , Uridina Difosfato Ácido N-Acetilmurâmico/análogos & derivados , Uridina Difosfato Ácido N-Acetilmurâmico/metabolismo
4.
Nat Methods ; 18(12): 1506-1514, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34857936

RESUMO

Mapping the cell phylogeny of a complex multicellular organism relies on somatic mutations accumulated from zygote to adult. Available cell barcoding methods can record about three mutations per barcode, enabling only low-resolution mapping of the cell phylogeny of complex organisms. Here we developed SMALT, a substitution mutation-aided lineage-tracing system that outperforms the available cell barcoding methods in mapping cell phylogeny. We applied SMALT to Drosophila melanogaster and obtained on average more than 20 mutations on a three-kilobase-pair barcoding sequence in early-adult cells. Using the barcoding mutations, we obtained high-quality cell phylogenetic trees, each comprising several thousand internal nodes with 84-93% median bootstrap support. The obtained cell phylogenies enabled a population genetic analysis that estimates the longitudinal dynamics of the number of actively dividing parental cells (Np) in each organ through development. The Np dynamics revealed the trajectory of cell births and provided insight into the balance of symmetric and asymmetric cell division.


Assuntos
Biologia Computacional/métodos , Drosophila melanogaster/metabolismo , Microscopia/métodos , Mutação , Alelos , Animais , Animais Geneticamente Modificados , Divisão Celular , Linhagem da Célula , Replicação do DNA , Drosophila melanogaster/embriologia , Endonucleases/metabolismo , Funções Verossimilhança , Masculino , Mutagênese , Fenótipo , Filogenia , Saccharomyces cerevisiae/genética , Análise de Célula Única
5.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34789566

RESUMO

We report a molecular switching ensemble whose states may be regulated in synergistic fashion by both protonation and photoirradiation. This allows hierarchical control in both a kinetic and thermodynamic sense. These pseudorotaxane-based molecular devices exploit the so-called Texas-sized molecular box (cyclo[2]-(2,6-di(1H-imidazol-1-yl)pyridine)[2](1,4-dimethylenebenzene); 14+, studied as its tetrakis-PF6- salt) as the wheel component. Anions of azobenzene-4,4'-dicarboxylic acid (2H+•2) or 4,4'-stilbenedicarboxylic acid (2H+•3) serve as the threading rod elements. The various forms of 2 and 3 (neutral, monoprotonated, and diprotonated) interact differently with 14+, as do the photoinduced cis or trans forms of these classic photoactive guests. The net result is a multimodal molecular switch that can be regulated in synergistic fashion through protonation/deprotonation and photoirradiation. The degree of guest protonation is the dominating control factor, with light acting as a secondary regulatory stimulus. The present dual input strategy provides a complement to more traditional orthogonal stimulus-based approaches to molecular switching and allows for the creation of nonbinary stimulus-responsive functional materials.

6.
PLoS Genet ; 17(4): e1009366, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33857142

RESUMO

SEDS family peptidoglycan (PG) glycosyltransferases, RodA and FtsW, require their cognate transpeptidases PBP2 and FtsI (class B penicillin binding proteins) to synthesize PG along the cell cylinder and at the septum, respectively. The activities of these SEDS-bPBPs complexes are tightly regulated to ensure proper cell elongation and division. In Escherichia coli FtsN switches FtsA and FtsQLB to the active forms that synergize to stimulate FtsWI, but the exact mechanism is not well understood. Previously, we isolated an activation mutation in ftsW (M269I) that allows cell division with reduced FtsN function. To try to understand the basis for activation we isolated additional substitutions at this position and found that only the original substitution produced an active mutant whereas drastic changes resulted in an inactive mutant. In another approach we isolated suppressors of an inactive FtsL mutant and obtained FtsWE289G and FtsIK211I and found they bypassed FtsN. Epistatic analysis of these mutations and others confirmed that the FtsN-triggered activation signal goes from FtsQLB to FtsI to FtsW. Mapping these mutations, as well as others affecting the activity of FtsWI, on the RodA-PBP2 structure revealed they are located at the interaction interface between the extracellular loop 4 (ECL4) of FtsW and the pedestal domain of FtsI (PBP3). This supports a model in which the interaction between the ECL4 of SEDS proteins and the pedestal domain of their cognate bPBPs plays a critical role in the activation mechanism.


Assuntos
Proteínas de Bactérias/ultraestrutura , Proteínas de Escherichia coli/ultraestrutura , Proteínas de Membrana/ultraestrutura , Complexos Multiproteicos/ultraestrutura , Proteínas de Ligação às Penicilinas/ultraestrutura , Peptidoglicano Glicosiltransferase/ultraestrutura , Conformação Proteica , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Modelos Moleculares , Complexos Multiproteicos/química , Complexos Multiproteicos/genética , Proteínas de Ligação às Penicilinas/química , Proteínas de Ligação às Penicilinas/genética , Peptidoglicano/química , Peptidoglicano/genética , Peptidoglicano/ultraestrutura , Peptidoglicano Glicosiltransferase/química , Peptidoglicano Glicosiltransferase/genética , Peptidil Transferases/química , Peptidil Transferases/genética , Peptidil Transferases/ultraestrutura
7.
J Dairy Sci ; 107(4): 1877-1886, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37923199

RESUMO

Xanthine oxidase (XO), a rate-limiting enzyme in uric acid production, is the pivotal therapeutic target for gout and hyperuricemia. In this study, 57 peptides from α-lactalbumin and ß-lactoglobulin were obtained via virtual enzymatic hydrolysis, and 10 XO inhibitory peptides were virtually screened using molecular docking. Then toxicity, allergenicity, solubility, and isoelectric point of the obtained 10 novel peptides were evaluated by in silico tools. The XO activity of these synthetic peptides was tested using an in vitro assay by high-performance liquid chromatography. Their inhibitory mechanism was further explored by molecular docking. The results showed that 4 peptides GL, PM, AL, and AM exhibited higher inhibitory activity, and their half maximal inhibitory concentration in vitro was 10.20 ± 0.89, 23.82 ± 0.94, 34.49 ± 0.89, and 40.45 ± 0.92 mM, respectively. The peptides fitted well with XO through hydrogen bond, hydrophobic interaction, and van der Waals forces, and amino acid residues Glu802, Leu873, Arg880, and Pro1076 played an important role in this process. Overall, this study indicated 4 novel peptides GL, PM, AL, and AM from whey protein exhibited XO inhibitory activity, and they might be useful and safe XO inhibitors for hyperuricemia prevention and treatment.


Assuntos
Supressores da Gota , Hiperuricemia , Animais , Supressores da Gota/farmacologia , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/veterinária , Xantina Oxidase/química , Xantina Oxidase/metabolismo , Proteínas do Soro do Leite , Simulação de Acoplamento Molecular , Inibidores Enzimáticos/química , Peptídeos/farmacologia
8.
Angew Chem Int Ed Engl ; 63(36): e202407805, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-38870085

RESUMO

New stimulus-responsive scaffolds are of interest as constituents of hierarchical supramolecular ensembles. 1,3,5-2,4,6-Functionalized, facially segregated benzene moieties have a time-honored role as building blocks for host molecules. However, their user as switchable motifs in the construction of multi-component supramolecular structures remains poorly explored. Here, we report a molecular cage 1, which consists of a bent anthracene dimer 3 paired with 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene 2. As the result of the pH-induced ababab↔bababa isomerization of the constituent-functionalized benzene units derived from 2, this cage can reversibly convert between an open state and a closed form, both in solution and in the solid state. Cage 1 was used to create stimuli-responsive hierarchical superstructures, namely Russian doll-like complexes with [K⊂18-crown-6⊂1]+ and [K⊂cryptand-222⊂1]+. The reversible assembly and disassembly of these superstructures could be induced by switching cage 1 from its open to closed form. The present study thus provides an unusual example where pH-triggered conformation motion within a cage-like scaffold is used to control the formation and disassociation of hierarchical ensembles.

9.
Angew Chem Int Ed Engl ; 63(41): e202409713, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39031452

RESUMO

The introduction of precise pore defects into nanocarbon structures results in the emergence of distinct physicochemical characteristics. However, there is a lack of research on non-planar chiral nanographene involving precise pore defects. Herein, we have developed two analogues to the π-extended pentadecabenzo[9]helicene (EP9H) containing embedded pore defects. Each molecules, namely extended dodecabenzo[7]helicene (ED7H; 1) or extended nonabenzo[5]helicene (EN5H; 2), exhibits dual-state emission. Significantly, the value of |glum| of 1 is exceptionally high at 1.41×10-2 in solution and BCPL as 254 M-1 cm-1. In PMMA film, |glum| of 1 is 8.56×10-3, and in powder film, it is 5.00×10-3. This study demonstrates that nanocarbon molecules with pore defects exhibit dual-state emission properties while maintaining quite good chiral luminescence properties. It was distinguished from the aggregation-caused quenching (ACQ) effect corresponding to the nanocarbon without embedded defect. Incorporating pore defects into chiral nanocarbon molecules also simplifies the synthesis process and enhances the solubility of the resulting product. These findings suggest that the introduction of pore defects can be a viable approach to improve nanocarbon molecules.

10.
J Am Chem Soc ; 145(25): 14010-14018, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37327391

RESUMO

Controllable solid-state transformations can provide a basis for novel functional materials. Herein, we report a series of solid-state systems that can be readily transformed between amorphous, co-crystalline, and mixed crystalline states via grinding or exposure to solvent vapors. The present solid materials were constructed using an all-hydrocarbon macrocycle, cyclo[8](1,3-(4,6-dimethyl)benzene) (D4d-CDMB-8) (host), and neutral aggregation-caused quenching dyes (guests), including 9,10-dibromoanthracene (1), 1,8-naphtholactam (2), diisobutyl perylene-3,9-dicarboxylate (3), 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (4), 4,7-di(2-thienyl)-benzo[2,1,3]thiadiazole (5), and 4-imino-3-(pyridin-2-yl)-4H-quinolizine-1-carbonitrile (6). Seven co-crystals and six amorphous materials were obtained via host-guest complexation. Most of these materials displayed turn-on fluorescence emission (up to 20-fold enhancement relative to the corresponding solid-state guests). The interconversion between amorphous, co-crystalline states, and crystalline mixtures could be induced by exposure to solvent vapors or by subjecting to grinding. The transformations could be monitored readily by means of single-crystal and powder X-ray diffraction analyses, as well as solid-state fluorescent emission spectroscopy. The externally induced structural interconversions resulted in time-dependent fluorescence changes. This allowed sets of privileged number array codes to be generated.

11.
Sensors (Basel) ; 23(9)2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37177445

RESUMO

At present, SLAM is widely used in all kinds of dynamic scenes. It is difficult to distinguish dynamic targets in scenes using traditional visual SLAM. In the matching process, dynamic points are incorrectly added to the pose calculation with the camera, resulting in low precision and poor robustness in the pose estimation. This paper proposes a new dynamic scene visual SLAM algorithm based on adaptive threshold homogenized feature extraction and YOLOv5 object detection, named AHY-SLAM. This new method adds three new modules based on ORB-SLAM2: a keyframe selection module, a threshold calculation module, and an object detection module. The optical flow method is used to screen keyframes for each frame input in AHY-SLAM. An adaptive threshold is used to extract feature points for keyframes, and dynamic points are eliminated with YOLOv5. Compared with ORB-SLAM2, AHY-SLAM has significantly improved pose estimation accuracy over multiple dynamic scene sequences in the TUM open dataset, and the absolute pose estimation accuracy can be increased by up to 97%. Compared with other dynamic scene SLAM algorithms, the speed of AHY-SLAM is also significantly improved under a guarantee of acceptable accuracy.

12.
Molecules ; 28(16)2023 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-37630294

RESUMO

In the past half-century, macrocycles with different structures and functions, have played a critical role in supramolecular chemistry. Two macrocyclic moieties can be linked to form bismacrocycle molecules. Compared with monomacrocycle, the unique structures of bismacrocycles led to their specific recognition and assembly properties, also a wide range of applications, including molecular recognition, supramolecular self-assembly, advanced optical material construction, etc. In this review, we focus on the structure of bismacrocycle and their applications. Our goal is to summarize and outline the possible future development directions of bismacrocycle research.

13.
Angew Chem Int Ed Engl ; 62(15): e202300840, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36792540

RESUMO

A novel chiral nanographene (i.e. EP9H) with a pentadecabenzo[9]helicene core fragment has been synthesized and fully characterized. Single-crystal X-ray diffraction unambiguously confirms the helical structure. The fluorescence emission of EP9H is located in the near infrared region (λem =684 nm) with a medium quantum yield (0.10) for helicene derivatives. Cyclic voltammetry reveals its seven quasi-reversible redox states from -2 to +5. Furthermore, enantiopure EP9H displays distinct CD signals in a broad spectral range from 300 to 700 nm. Notably, compared to the reported small organic molecules, EP9H displays an outstanding |glum | value of 4.50×10-2 and BCPL as 304 M-1 cm-1 .

14.
Angew Chem Int Ed Engl ; 62(47): e202312599, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37821726

RESUMO

Cephalotaxus diterpenoids are attractive natural products with intriguing molecular frameworks and promising biological features. As a structurally unusual member, (-)-cephalotanin B possesses an extraordinarily congested heptacyclic skeleton, three lactone units, and nine consecutive stereocenters. Herein, we report an enantioselective total synthesis of (-)-cephalotanin B based on a divergent asymmetric Michael addition reaction, a novel Pauson-Khand/deacyloxylation process discovered in the development of a second-generation stereoselective Pauson-Khand reaction protocol, and an epoxide-opening/elimination/dual-lactonization cascade to construct the challenging propeller-shaped A-B-C ring system as key transformations.

15.
Int J Obes (Lond) ; 46(4): 793-801, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35091670

RESUMO

BACKGROUND: Obesity during pregnancy and lactation not only increases the incidence of metabolic disorders and gestational diabetes in mothers, but also programs adiposity and related metabolic diseases in offspring. The aim of this study was to investigate the effects of milk polar lipids on gut microbiota and glucose metabolism in high-fat diet (HFD)-fed rat dams. METHODS: Sprague Dawley (SD) female rats were fed a HFD for 8 weeks to induce obesity, followed by HFD with or without oral administration of polar lipids-enriched milk fat globule membrane (MFGM-PL) at 400 mg/kg BW during pregnancy and lactation. At the end of lactation, fresh fecal samples of dams were collected, the gut microbiota was assessed, and the insulin-signaling protein expression in peripheral tissues (adipose tissue, liver and skeletal muscle) were measured. RESULTS: MFGM-PL supplementation attenuated body weight gain, ameliorated serum lipid profiles and improved insulin sensitivity in obese dams at the end of lactation. 16 S rDNA sequencing revealed that MFGM-PL increased the community richness and diversity of gut microbiota. The composition of gut microbiota was also changed after MFGM-PL supplementation as shown by an increase in the ratio of Bacteroidetes/Firmicutes and the relative abundance of Akkermansia, as well as a decrease in the relative abundance of Ruminococcaceae. The functional prediction of microbial communities by PICRUSt analysis showed that there were 7 KEGG pathways related to carbohydrate metabolism changed after MFGM-PL supplementation to HFD dams, including glycolysis/gluconeogenesis and insulin signaling pathway. Furthermore, MFGM-PL improved insulin signaling in the peripheral tissues including liver, adipose tissue and skeletal muscle. CONCLUSIONS: MFGM-PL supplementation during pregnancy and lactation improves the glucose metabolism disorders in HFD-induced obese dams, which may be linked to the regulation of gut microbiota induced by MFGM-PL.


Assuntos
Microbioma Gastrointestinal , Resistência à Insulina , Animais , Dieta Hiperlipídica , Feminino , Microbioma Gastrointestinal/fisiologia , Glicolipídeos/farmacologia , Glicoproteínas , Insulina , Gotículas Lipídicas , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley
16.
FASEB J ; 35(4): e21454, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33749945

RESUMO

Milk contains about 4% fat globules with its surface covered by polar lipids. Despite the abundant consumption of dairy products, the biological effects of dietary milk polar lipids on metabolic health have only been sparsely examined. Maternal obesity results in neurodevelopmental disorders and cognitive impairment in offspring. Considering the importance of maternal nutrition, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to dams during pregnancy and lactation on neurodevelopment and its long-term programming effects on offspring cognition were examined. Female Sprague-Dawley rats consumed 8-week control diet (CON) or high-fat diet (HFD) to induce obesity before mating. Then, female rats were fed CON or HFD with or without the supplementation of 400 mg/kg body weight MFGM-PL during pregnancy and lactation. The offspring were fed 11-week HFD after weaning. MFGM-PL supplementation to obese dams suppressed body weight gain and hyperinsulinemia in both dams and offspring. Offspring born to obese dams displayed delayed neurological reflexes development, impaired neurogenesis before weaning, and cognitive impairment in adulthood, which were recovered by maternal MFGM-PL supplementation. Insulin resistance and aberrant brain-derived neurotrophic factor signaling were induced in the hippocampus of neonatal and adult offspring due to maternal and progeny HFD, but recovered by maternal MFGM-PL administration. This study demonstrates that maternal MFGM-PL supplementation can promote neurodevelopment and exert long-term effects against HFD-induced cognitive impairment in offspring via alleviating hippocampal insulin resistance. Hence, MFGM-PL is a promising ingredient for exerting beneficial programming effects on the brain health of offspring.


Assuntos
Sistema Nervoso Central/crescimento & desenvolvimento , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Lipídeos/farmacologia , Leite/química , Obesidade , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Lipídeos/administração & dosagem , Masculino , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ratos , Ratos Sprague-Dawley , Receptor trkB/genética , Receptor trkB/metabolismo
17.
J Fish Dis ; 45(6): 761-769, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35322884

RESUMO

Enterocytozoon hepatopenaei (EHP) and Vibrio parahaemolyticus acute hepatopancreatic necrosis disease (VPAHPND) are two of the diseases that have frequently infected farmed shrimp in recent years, causing great economic losses to the shrimp industry worldwide. In this study, we established a sensitive and accurate duplex droplet digital PCR (ddPCR) method that can simultaneously detect and quantify the two pathogens simultaneously. The results showed that the ddPCR methods could detect EHP and VPAHPND specifically. The sensitivity levels of ddPCR for EHP and VPAHPND were 2.3 copies/µl and 4.6 copies/µl, respectively, which were 10-fold higher than the sensitivity of the qPCR assay and showed good reproducibility. Twenty-six suspected diseased shrimp samples were used for practical determination. For EHP, the detection rates of ddPCR and qPCR were 53.84% and 42.31%, respectively; for VPAHPND, the detection rates of ddPCR and qPCR were both 23.08%. The results indicated that the ddPCR method shows superiority for detection in samples with low viral loads, which will facilitate monitoring of the source and transmission of EHP and VPAHPND and will help control shrimp epidemic disease.


Assuntos
Enterocytozoon , Doenças dos Peixes , Penaeidae , Vibrio parahaemolyticus , Animais , Enterocytozoon/genética , Necrose , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Vibrio parahaemolyticus/genética
18.
Acta Neurochir (Wien) ; 164(8): 2263-2269, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35665860

RESUMO

OBJECTIVE: To explore the therapeutic effect of combined selective peripheral neurotomy (cSPN) on the spasm of the lower limbs after spinal cord injury. METHODS: A prospective intervention (before-after trial) with an observational design was conducted in 14 spinal cord injury patients with severe lower limbs spasticity by cSPN. Given the severe spasm of hip adductor, triceps surae, and hamstring muscles in these patients, a total of 26 obturator nerve branches, 26 tibia nerve branches, and 4 sciatic nerve branches partial neurotomy were performed. The modified Ashworth scale, composite spasticity scale, surface electromyography, gait analysis, functional ambulation category, spinal cord independence measure, and modified spinal cord injury-spasticity evaluation tool were used before and after surgery. RESULTS: Compared with preoperative, the spasm of the hip adductor, triceps surae, and hamstrings of the lower limbs in the postoperative patients decreased significantly. The abnormal gait of knee flexion and varus in the standing stage were significantly reduced. The grading of walking ability and activities of daily living were significantly improved. CONCLUSIONS: Combined selective peripheral neurotomy can significantly reduce the spasm of lower limbs post spinal cord injury, improve abnormal gait, and improve motor function and activities of daily living. TRIAL REGISTRATION: ChiCTR1800019003 (2018-10-20).


Assuntos
Espasticidade Muscular , Traumatismos da Medula Espinal , Atividades Cotidianas , Humanos , Extremidade Inferior/cirurgia , Espasticidade Muscular/etiologia , Espasticidade Muscular/cirurgia , Estudos Prospectivos , Nervo Isquiático/cirurgia , Espasmo , Traumatismos da Medula Espinal/cirurgia
19.
Molecules ; 27(15)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35897960

RESUMO

Although ginseng leaf is a good source of health-beneficial phytochemicals, such as polyphenols and ginsenosides, few studies have focused on the variation in compounds and bioactivities during leaf thermal processing. The efficiency of far-infrared irradiation (FIR) between 160 °C and 200 °C on the deglycosylation of bioactive compounds in ginseng leaves was analyzed. FIR treatment significantly increased the total polyphenol content (TPC) and kaempferol production from panasenoside conversion. The highest content or conversion ratio was observed at 180 °C (FIR-180). Major ginsenoside contents gradually decreased as the FIR temperature increased, while minor ginsenoside contents significantly increased. FIR exhibited high efficiency to produce dehydrated minor ginsenosides, of which F4, Rg6, Rh4, Rk3, Rk1, and Rg5 increased to their highest levels at FIR-190, by 278-, 149-, 176-, 275-, 64-, and 81-fold, respectively. Moreover, significantly increased antioxidant activities were also observed in FIR-treated leaves, particularly FIR-180, mainly due to the breakage of phenolic polymers to release antioxidants. These results suggest that FIR treatment is a rapid and efficient processing method for producing various health-beneficial bioactive compounds from ginseng leaves. After 30 min of treatment without leaf burning, FIR-190 was the optimum temperature for producing minor ginsenosides, whereas FIR-180 was the optimum temperature for producing polyphenols and kaempferol. In addition, the results suggested that the antioxidant benefits of ginseng leaves are mainly due to polyphenols rather than ginsenosides.


Assuntos
Panax , Folhas de Planta , Temperatura , Antioxidantes , Ginsenosídeos , Raios Infravermelhos , Quempferóis , Panax/química , Panax/efeitos da radiação , Folhas de Planta/química , Folhas de Planta/efeitos da radiação , Polifenóis
20.
J Am Chem Soc ; 143(5): 2315-2324, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33356188

RESUMO

Described here is a three-component self-assembly system that displays emergent behavior that differs from that of its constituents. The system comprises an all-hydrocarbon octaaryl macrocycle cyclo[8](1,3-(4,6-dimethyl)benzene (D4d-CDMB-8), corannulene (Cora), and I2. No appreciable interaction is seen between any pair of these three-components, either in cyclohexane or under various crystallization conditions. On the other hand, when all three-components are mixed in cyclohexane and allowed to undergo crystallization, a supramolecular iodine-containing capsule, ((D4d-CDMB-8)3⊃(Cora)2)⊃I2, is obtained. This all-hydrocarbon capsule consists of three D4d-CDMB-8 and two Cora subunits and contains a centrally bound I2 molecule as inferred from single-crystal and powder X-ray diffraction studies as well as solid-state 13C NMR and Raman spectroscopy. These analyses were complemented by solution-phase 1H NMR and UV-vis spectroscopic studies. No evidence of I2 escape from the capsule is seen, even at high temperatures (e.g., up to 418 K). The bound I2 is likewise protected from reaction with alkali or standard reductants in aqueous solution (e.g., saturated NaOH(aq) or aqueous Na2S2O3). It was also found that a mixed powder containing D4d-CDMB-8 and Cora in a 3:2 molar ratio could capture saturated I2 vapor or iodine from aqueous sources (e.g., 1.0 mM I2 in NaCl (35 wt %) or I2 + NaI(aq) (1.0 mM each)). The present system displays structural and functional features that go beyond what would be expected on the basis of a simple sum-of-the-components analysis. As such, it illustrates a new approach to creating self-assembled ensembles with emergent features.

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