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1.
Integr Zool ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567525

RESUMO

Porcupines, members of the Hystricidae family, represent a unique group of herbivorous mammals. This study details the identification of a newly discovered mandible fragment of Hystrix primigenia, along with a right cheek tooth series from the middle Turolian Kemiklitepe-A fossil locality. While Hystrix fossils are found in numerous localities, the materials are often limited to a few dental fragments or isolated teeth, posing challenges to systematic investigations. The examination of this lower tooth series prompted a comprehensive review of all H. primigenia findings across Eurasia, shedding light on its adaptive characteristics over time and space. Our paleobiogeographical analysis indicates the absence of H. depereti in Late Miocene Türkiye, while the dispersal range of H. primigenia is broader than that of H. depereti in Eurasia. Additionally, the study delves into the discussion of H. primigenia and H. depereti findings in Eurasia, ultimately refining the categorization of Late Miocene Hystrix discoveries in Türkiye to two species: H. primigenia and H. kayae. Our review suggests the possibility of an additional H. kayae finding from Samos, Greece.

2.
J Integr Plant Biol ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639466

RESUMO

The mountains of Southwest China comprise a significant large mountain range and biodiversity hotspot imperiled by global climate change. The high species diversity in this mountain system has long been attributed to a complex set of factors, and recent large-scale macroevolutionary investigations have placed a broad timeline on plant diversification that stretches from 10 million years ago (Mya) to the present. Despite our increasing understanding of the temporal mode of speciation, finer-scale population-level investigations are lacking to better refine these temporal trends and illuminate the abiotic and biotic influences of cryptic speciation. This is largely due to the dearth of organismal sampling among closely related species and populations, spanning the incredible size and topological heterogeneity of this region. Our study dives into these evolutionary dynamics of speciation using genomic and eco-morphological data of Stellera chamaejasme L. We identified four previously unrecognized cryptic species having indistinct morphological traits and large metapopulation of evolving lineages, suggesting a more recent diversification (~2.67-0.90 Mya), largely influenced by Pleistocene glaciation and biotic factors. These factors likely influenced allopatric speciation and advocated cyclical warming-cooling episodes along elevational gradients during the Pleistocene. The study refines the evolutionary timeline to be much younger than previously implicated and raises the concern that projected future warming may influence the alpine species diversity, necessitating increased conservation efforts.

3.
Ecol Evol ; 14(4): e11225, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584774

RESUMO

A new species of Papaveraceae, Corydalis sunhangii, in the section Trachycarpae, is described and illustrated from Nyingchi City, Xizang, China. The new species has some resemblance to Corydalis kingdonis, but differs by radical leaves prominent, usually several, blade tripinnate (vs. insignificant, few, blade bi- to triternate); cauline leaf usually one, much smaller than radical leaves, usually situated in lower half of stem (vs. usually two, larger than radical leaves, concentrated in upper third of stem); racemes densely 13-35-flowered (vs. rather lax, 4-11-flowered); claw of lower petal shallowly saccate (vs. very prominently and deeply saccate); capsule oblong, with raised lines of dense papillae (vs. broadly obovoid, smooth). Phylogenetic analysis, based on 68 protein-coding plastid genes of 49 samples, shows that C. sunhangii is not closely related to any hitherto described species, which is consistent with our morphological analysis.

4.
Phys Rev Lett ; 132(10): 104001, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38518322

RESUMO

Phototaxis phenomenon is fundamental and critical for optical manipulation of micro-objects. Here, we report the size-dependent negative or positive phototaxis behaviors for microdroplets containing interfacial energy absorber flying in a laser. The critical diameters for such negative-to-positive turnover are studied through both experiments and simulation with different liquids and absorbers, which establishes the mechanism and reveals the role of both the liquid and the absorber inside the microdroplets. This study offers new insight for the manipulation of the phototaxis behavior of micro-objects, showing potential applications in optical trapping and transporting systems that involve light-microdroplet interactions.

5.
Angew Chem Int Ed Engl ; : e202400761, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497902

RESUMO

Lithium batteries employing Li or silicon (Si) anodes hold promise for the next-generation energy storage systems. However, their cycling behavior encounters rapid capacity degradation due to the vulnerability of solid electrolyte interphases (SEIs). Though anion-derived SEIs mitigate this degradation, the unavoidable reduction of solvents introduces heterogeneity to SEIs, leading to fractures during cycling. Here, we elucidate how the reductive stability of solvents, dominated by the electrophilicity (EPT) and coordination ability (CDA), delineates the SEI formed on Li or Si anodes. Solvents exhibiting lower EPT and CDA demonstrate enhanced tolerance to reduction, resulting in inorganic-rich SEIs with homogeneity. Guided by these criteria, we synthesized three promising solvents tailored for Li or Si anodes. The decomposition of these solvents is dictated by their EPTs under similar solvation structures, imparting distinct characteristics to SEIs and impacting battery performance. The optimized electrolyte, 1 M lithium bis(fluorosulfonyl)imide (LiFSI) in N-Pyrrolidine-trifluoromethanesulfonamide (TFSPY), achieves 600 cycles of Si anodes with a capacity retention of 81 % (1910 mAh g-1). In anode-free Cu||LiNi0.5Co0.2Mn0.3O2 (NCM523) pouch cells, this electrolyte sustains over 100 cycles with an 82 % capacity retention. These findings illustrate that reducing solvent decomposition benefits SEI formation, offering valuable insights for the designing electrolytes in high-energy lithium batteries.

6.
ACS Nano ; 18(11): 7877-7889, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38450636

RESUMO

The octopus, as one of the most famous celebrities in bionics, has provided various inspirations for camouflage materials, soft-bodied robots, and flexible grabbers. The miniaturization of such structures will help the development of microrobots, microdelivery of drugs, and surface coating. With the lack of relevant effective preparation approaches, however, the generation of such octopus-like structures with a size of ∼1 µm or below is challenging. Here, we develop an approach based on laser-microdroplet interaction for generating an octopus-like structure with a size of ∼1 µm. The developed approach uses laser-microdroplet interaction to provide a large driving force of ∼107 Pa at a confined space (<1 µm), locally crumpling the precursor in the microdroplet. The locally crumpled particles possess both crumpled and uncrumpled structures that resemble an octopus's head and soft body. In the adhesion test, the octopus-like particles exhibit high adhesive properties in air, in water, and on a flexible substrate. In the electrochemical test, the octopus-like particles on flexible electrodes show good electrochemical and adhesive properties under hundreds of bending cycles. Benefiting from the combination of crumpled and uncrumpled morphologies, the created particles with octopus-like microstructure are demonstrated to possess comprehensive performance, exhibiting wide application potentials in the fields of microswimmers, surface coatings, and electrochemistry. Additionally, the method developed in this work has the advantages of concentrated energy in a confined space, displaying prospective potentials in micro- and nanoprocessing.

7.
Adv Healthc Mater ; : e2304674, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501303

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory disease with uncontrolled inflammation and demage to the intestinal barrier. Rhein, a bioactive compound in traditional Chinese medicine, has anti-inflammatory and intestinal repair effect. However, their clinical application is limited by their hydrophobicity and poor bioavailability. L-arginine, as a complement to NO, has synergistic and attenuating effects. In this paper, red/NIR-I fluorescent carbon dots based on rhein and doped with L-arginine (RA-CDs), which are synthesized by a hydrothermal process without any organic solvents, are reported. RA-CDs preserve a portion of the functional group of the active precursor, increase rhein solubility, and emit red/NIR-I light for biological imaging. In vitro experiments show that RA-CDs scavenge excessive reactive oxygen species (ROS), protect cells from oxidative stress, and enable the fluorescence imaging of inflamed colons. In a DSS-induced UC mouse model, both delayed and prophylactic treatment with RA-CDs via intraperitoneal and tail vein injections alleviate UC severity by reducing intestinal inflammation and restoring the intestinal barrier. This study highlights a novel strategy for treating and imaging UC with poorly soluble small-molecule drugs.

8.
J Control Release ; 368: 318-328, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428530

RESUMO

Dry eye disease (DED) is a common and frequent ocular surface disease worldwide, which can cause severe ocular surface discomfort and blurred vision. Inflammation and reactive oxygen species (ROS) play decisive roles in the development of DED. However, existing treatments usually focus on anti-inflammation while ignore the role of ROS in DED. Ever worse, the clinical preparations are easily cleared by nasolacrimal ducts, resulting in poor therapeutic effect. To circumvent these obstacles, here we designed a phenylboronic acid (PBA) modified liposome co-loading immunosuppressant cyclosporin A (CsA) and antioxidant crocin (Cro). The CsA/Cro PBA Lip achieved mucoadhesion through the formation of covalent bonds between PBA and the sialic acid residues on mucin, and consequently improved the retention of drugs on the ocular surface. By inhibiting ROS production and blocking NF-κB inflammatory pathway, CsA/Cro PBA Lip successfully promoted the healing of damaged corneal epithelium, eventually achieving the goal of relieving DED. CsA/Cro PBA Lip is proven a simple yet effective dual-drug delivery system, exhibiting superior antioxidant and anti-inflammatory effects both in vitro and in vivo. This approach holds great potential in the clinical treatment of DED and other related mucosal inflammations.


Assuntos
Síndromes do Olho Seco , Lipossomos , Humanos , Lipossomos/uso terapêutico , Antioxidantes/uso terapêutico , Espécies Reativas de Oxigênio , Soluções Oftálmicas , Síndromes do Olho Seco/tratamento farmacológico , Inflamação/tratamento farmacológico , Ciclosporina
9.
PeerJ ; 12: e16822, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313009

RESUMO

As a member of Aceratheriinae, the genus Plesiaceratherium in Europe is widely distributed and highly diverse. However, only one species of Plesiaceratherium (i.e., P. gracile) exists in China with a discontinuous distribution range. Recently, we have discovered new materials of Plesiaceratherium in the lower layers of the Zhang'enbao Formation exposed in Miaoerling in Tongxin County, China. The new materials are well-preserved and can be separated from other Plesiaceratherium species by the following combination of features: the long and generally flat skull, with closed frontoparietal crests; the deep nasal notch at the level of P4; the high supraorbital margin, with its anterior margin at the level of the M1/M2 boundary; the medium-sized upper I1, with an oval abraded surface; the semi-molarized upper premolars with the protocone and hypocone joined by a lingual bridge; the strong constrictions of protocone on the upper molars; the absent buccal cingulum on upper cheek teeth; the cheek teeth are covered by cement on the buccal walls; the convex base of mandibular corpus; the inclined backward ramus; and the mandibular foramen above the teeth neck. Based on the combination of characteristics and phylogenetic analysis, we herein establish the new species as Plesiaceratherium tongxinense sp. nov. living in the late Early Miocene. Phylogenetic analysis reveals that P. tongxinense is in the basal position of the genus Plesiaceratherium, providing more detailed morphological characteristics of the plesiaceratheres.


Assuntos
Fósseis , Perissodáctilos , Animais , Filogenia , Osso Frontal/anatomia & histologia , China
10.
Nature ; 627(8002): 101-107, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418886

RESUMO

Li-ion batteries (LIBs) for electric vehicles and aviation demand high energy density, fast charging and a wide operating temperature range, which are virtually impossible because they require electrolytes to simultaneously have high ionic conductivity, low solvation energy and low melting point and form an anion-derived inorganic interphase1-5. Here we report guidelines for designing such electrolytes by using small-sized solvents with low solvation energy. The tiny solvent in the secondary solvation sheath pulls out the Li+ in the primary solvation sheath to form a fast ion-conduction ligand channel to enhance Li+ transport, while the small-sized solvent with low solvation energy also allows the anion to enter the first Li+ solvation shell to form an inorganic-rich interphase. The electrolyte-design concept is demonstrated by using fluoroacetonitrile (FAN) solvent. The electrolyte of 1.3 M lithium bis(fluorosulfonyl)imide (LiFSI) in FAN exhibits ultrahigh ionic conductivity of 40.3 mS cm-1 at 25 °C and 11.9 mS cm-1 even at -70 °C, thus enabling 4.5-V graphite||LiNi0.8Mn0.1Co0.1O2 pouch cells (1.2 Ah, 2.85 mAh cm-2) to achieve high reversibility (0.62 Ah) when the cells are charged and discharged even at -65 °C. The electrolyte with small-sized solvents enables LIBs to simultaneously achieve high energy density, fast charging and a wide operating temperature range, which is unattainable for the current electrolyte design but is highly desired for extreme LIBs. This mechanism is generalizable and can be expanded to other metal-ion battery electrolytes.

11.
Nanomicro Lett ; 16(1): 123, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372847

RESUMO

Conformable and wireless charging energy storage devices play important roles in enabling the fast development of wearable, non-contact soft electronics. However, current wireless charging power sources are still restricted by limited flexural angles and fragile connection of components, resulting in the failure expression of performance and constraining their further applications in health monitoring wearables and moveable artificial limbs. Herein, we present an ultracompatible skin-like integrated wireless charging micro-supercapacitor, which building blocks (including electrolyte, electrode and substrate) are all evaporated by liquid precursor. Owing to the infiltration and permeation of the liquid, each part of the integrated device attached firmly with each other, forming a compact and all-in-one configuration. In addition, benefitting from the controllable volume of electrode solution precursor, the electrode thickness is easily regulated varying from 11.7 to 112.5 µm. This prepared thin IWC-MSC skin can fit well with curving human body, and could be wireless charged to store electricity into high capacitive micro-supercapacitors (11.39 F cm-3) of the integrated device. We believe this work will shed light on the construction of skin-attachable electronics and irregular sensing microrobots.

12.
Nanomicro Lett ; 16(1): 119, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363512

RESUMO

Due to the constraints imposed by physical effects and performance degradation, silicon-based chip technology is facing certain limitations in sustaining the advancement of Moore's law. Two-dimensional (2D) materials have emerged as highly promising candidates for the post-Moore era, offering significant potential in domains such as integrated circuits and next-generation computing. Here, in this review, the progress of 2D semiconductors in process engineering and various electronic applications are summarized. A careful introduction of material synthesis, transistor engineering focused on device configuration, dielectric engineering, contact engineering, and material integration are given first. Then 2D transistors for certain electronic applications including digital and analog circuits, heterogeneous integration chips, and sensing circuits are discussed. Moreover, several promising applications (artificial intelligence chips and quantum chips) based on specific mechanism devices are introduced. Finally, the challenges for 2D materials encountered in achieving circuit-level or system-level applications are analyzed, and potential development pathways or roadmaps are further speculated and outlooked.

13.
Nano Lett ; 24(7): 2157-2164, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38319745

RESUMO

Carbon support is essential for electrocatalysis, but limitations remain, as carbon corrosion can lead to electrocatalyst degradation and affect the long-term durability of electrocatalysts. Here, we studied the corrosion dynamics of carbon nanotubes (CNTs) and Vulcan carbon (VC) together with platinum (Pt) nanoparticles in real time by liquid cell (LC) transmission electron microscopy (TEM). The results showed that CNTs with a high degree of graphitization exhibited higher corrosion resistance compared to VC. Furthermore, we observed that the main degradation path of Pt nanoparticles in Pt/CNTs was ripening, while in Pt/VC, it was aggregation and coalescence, which was dominated by the interactions between Pt nanoparticles and different hybridization of carbon supports. Finally, we performed an ex situ CV stability test to confirm the conclusions obtained from in situ experiments. This work provides deep insights into the corrosion mechanism of carbon-supported electrocatalysts to optimize the design of electrocatalysts with a higher durability.

14.
Anal Chim Acta ; 1294: 342309, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38336411

RESUMO

BACKGROUND: Glycopeptide antibiotics (GPAs) represented by vancomycin (VAN) are clinically used as a first-line treatment for serious infections caused by Gram-positive pathogens. The use and dosing methods of GPAs are rigorously managed for safety considerations, which calls for fast and accurate quantification approaches. RESULT: A new sort of fluorescent probes for GPAs has been proposed, each of which was integrated by a fluorescein-based reporter and a GPAs' recognition peptide D-alanyl-D-alanine (D-Ala-D-Ala). These probes work as dynamic molecular switches, which mainly exist as non-fluorescent spirolactam forms in the absence of GPAs. GPAs binding with the dipeptide regulates the dynamic balance between fluorescence OFF lactam form and fluorescence ON ring-opened form, rendering these probes capable of GPAs detecting. The most promising one P1 exhibits excellent sensitivity and selectivity towards GPAs detection. SIGNIFICANCE: Different to previous developments, P1 consists of a single fluorophore without the need of a fluorescence-quenching group or a secondary dye, which is the smallest fluorescent probe for GPAs up to now. P1 realizes direct VAN quantification from complex biological samples including real serums, dispensing with additional drug extraction. More interestingly, both P1 and P6 can distinguish GPAs with different peptide backbones, which has not been achieved previously.


Assuntos
Antibacterianos , Glicopeptídeos , Fluorescência , Antibacterianos/química , Glicopeptídeos/química , Vancomicina/química , Alanina
15.
Cell Rep ; 43(3): 113833, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38416642

RESUMO

Influenza A virus (IAV) represents a constant public health threat. The single-stranded, segmented RNA genome of IAV is replicated in host cell nuclei as a series of 8 ribonucleoprotein complexes (vRNPs) with RNA structures known to exert essential function to support viral replication. Here, we investigate RNA secondary structures and RNA interactions networks of the IAV genome and construct an in vivo structure model for each of the 8 IAV genome segments. Our analyses reveal an overall in vivo and in virio resemblance of the IAV genome conformation but also wide disparities among long-range and intersegment interactions. Moreover, we identify a long-range RNA interaction that exerts an essential role in genome packaging. Disrupting this structure displays reduced infectivity, attenuating virus pathogenicity in mice. Our findings characterize the in vivo RNA structural landscape of the IAV genome and reveal viral RNA structures that can be targeted to develop antiviral interventions.


Assuntos
Vírus da Influenza A , Influenza Humana , Animais , Camundongos , Humanos , Replicação Viral , Genoma , RNA Viral/genética , Vírus da Influenza A/genética , Interações Hospedeiro-Patógeno , Genoma Viral , Influenza Humana/genética
16.
J Surg Res ; 296: 182-188, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38277955

RESUMO

INTRODUCTION: Anastomotic leakage post-esophagectomy remains a significant challenge. Despite the use of both mechanical and manual anastomosis, leakage rates remain high. This study evaluated the effectiveness of the manual layered insertion anastomosis technique in addressing this issue. METHODS: A retrospective analysis was conducted on patients who underwent this technique from September 2020 to December 2021. The process involved thoracoscopic release of the esophagus, mediastinal lymph node dissection, laparoscopic stomach release, and its transformation into a tube. The latter was then guided to the neck for anastomosis. The posterior anastomotic wall was reshaped in the neck first for optimal insertion, followed by layered suturing with the gastric conduit. The anterior wall was subsequently sutured and repositioned into the chest. RESULTS: The study included 56 patients (51 men, five women, mean age 65.4 y), with nine having undergone neoadjuvant therapy. All received minimally invasive esophagectomy. Average intraoperative blood loss was 79.8 mL, operation time averaged 331 min, and feeding resumed after an average of 6.3 d. No anastomotic leakages were reported, with reduced incidences of anastomotic stenosis and gastric acid reflux compared to previous studies. CONCLUSIONS: The manual layered insertion anastomosis technique may reduce anastomotic leakage and associated complications, improving the efficacy of esophagectomy, which may improve postoperative results and patient quality of life, suggesting the method's potential suitability for wider clinical application.


Assuntos
Fístula Anastomótica , Neoplasias Esofágicas , Masculino , Humanos , Feminino , Idoso , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Fístula Anastomótica/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/complicações , Estudos Retrospectivos , Qualidade de Vida , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia
17.
Adv Sci (Weinh) ; 11(12): e2307020, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38239054

RESUMO

Control of convection plays an important role in heat transfer regulation, bio/chemical sensing, phase separation, etc. Current convection controlling systems generally depend on engineered energy sources to drive and manipulate the convection, which brings additional energy consumption into the system. Here the use of human hand as a natural and sustainable infrared (IR) radiation source for the manipulation of liquid convection is demonstrated. The fluid can sense the change of the relative position or the shape of the hand with the formation of different convection patterns. Besides the generation of static complex patterns, dynamic manipulation of convections can also be realized via moving of hand or finger. The use of such sustainable convections to control the movement of a floating "boat" is further achieved. The use of human hands as the natural energy sources provides a promising approach for the manipulation of liquid convection without the need of extra external energy, which may be further utilized for low-cost and intelligent bio/chemical sensing and separation.


Assuntos
Convecção , Temperatura Alta , Humanos , Raios Infravermelhos
18.
Nucleic Acids Res ; 52(D1): D798-D807, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37889020

RESUMO

Influenza viruses undergo frequent genomic mutations, leading to potential cross-species transmission, phenotypic changes, and challenges in diagnostic reagents and vaccines. Accurately evaluating and predicting the risk of such variations remain significant challenges. To address this, we developed the VarEPS-Influ database, an influenza virus variations risk evaluation system (VarEPS-Influ). This database employs a 'multi-dimensional evaluation of mutations' strategy, utilizing various tools to assess the physical and chemical properties, primary, secondary, and tertiary structures, receptor affinity, antibody binding capacity, antigen epitopes, and other aspects of the variation's impact. Additionally, we consider space-time distribution, host species distribution, pedigree analysis, and frequency of mutations to provide a comprehensive risk evaluation of mutations and viruses. The VarEPS-Influ database evaluates both observed variations and virtual variations (variations that have not yet occurred), thereby addressing the time-lag issue in risk predictions. Our current one-stop evaluation system for influenza virus genomic variation integrates 1065290 sequences from 224 927 Influenza A, B and C isolates retrieved from public resources. Researchers can freely access the data at https://nmdc.cn/influvar/.


Assuntos
Bases de Dados Genéticas , Influenza Humana , Orthomyxoviridae , Humanos , Anticorpos/genética , Epitopos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Mutação , Orthomyxoviridae/genética , Variação Genética , Genoma Viral , Medição de Risco
19.
J Virol ; 98(1): e0116623, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38054704

RESUMO

Both influenza A virus genome transcription (vRNA→mRNA) and replication (vRNA→cRNA→vRNA), catalyzed by the influenza RNA polymerase (FluPol), are dynamically regulated across the virus life cycle. It has been reported that the last amino acid I121 of the viral NS2 protein plays a critical role in promoting viral genome replication in influenza mini-replicon systems. Here, we performed a 20 natural amino acid substitution screening at residue NS2-I121 in the context of virus infection. We found that the hydrophobicity of the residue 121 is essential for virus survival. Interestingly, through serial passage of the rescued mutant viruses, we further identified adaptive mutations PA-K19E and PB1-S713N on FluPol which could effectively compensate for the replication-promoting defect caused by NS2-I121 mutation in the both mini-replicon and virus infection systems. Structural analysis of different functional states of FluPol indicates that PA-K19E and PB1-S713N could stabilize the replicase conformation of FluPol. By using a cell-based NanoBiT complementary reporter assay, we further demonstrate that both wild-type NS2 and PA-K19E/PB1-S713N could enhance FluPol dimerization, which is necessary for genome replication. These results reveal the critical role NS2 plays in promoting viral genome replication by coordinating with FluPol.IMPORTANCEThe intrinsic mechanisms of influenza RNA polymerase (FluPol) in catalyzing viral genome transcription and replication have been largely resolved. However, the mechanisms of how transcription and replication are dynamically regulated remain elusive. We recently reported that the last amino acid of the viral NS2 protein plays a critical role in promoting viral genome replication in an influenza mini-replicon system. Here, we conducted a 20 amino acid substitution screening at the last residue 121 in virus rescue and serial passage. Our results demonstrate that the replication-promoting function of NS2 is important for virus survival and efficient multiplication. We further show evidence that NS2 and NS2-I121 adaptive mutations PA-K19E/PB1-S713N regulate virus genome replication by promoting FluPol dimerization. This work highlights the coordination between NS2 and FluPol in fulfilling efficient genome replication. It further advances our understanding of the regulation of viral RNA synthesis for influenza A virus.


Assuntos
Vírus da Influenza A , Proteínas não Estruturais Virais , Humanos , Substituição de Aminoácidos , Aminoácidos/genética , RNA Polimerases Dirigidas por DNA/genética , Vírus da Influenza A/genética , Influenza Humana/genética , Proteínas Virais/genética , Replicação Viral , Proteínas não Estruturais Virais/metabolismo
20.
Autism Res ; 17(1): 148-161, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37987229

RESUMO

Improving the quality of family life (FQoL) is one of the ultimate goals for autism spectrum disorder (ASD) intervention, and parenting self-efficacy and social support are critical for the well-being of families. However, longitudinal studies focusing on FQoL and its predictors for families of children with ASD are scarce. This study aims to describe the characteristics of FQoL among parents of children newly diagnosed with ASD at two waves (newly diagnosed and diagnosed after one year) and to explore the predictors of FQoL at two waves. It was conducted at a tertiary hospital in Guangzhou, China. A total of 156 parents and their children were included in Wave 1, followed up with 110 in Wave 2 after 1 year. The overall satisfaction of FQoL improved (t = -2.128, p < 0.05), while satisfaction with physical/material well-being decreased (t = 5.972, p < 0.01). Additionally, the overall importance rating of FQoL improved but did not have statistical significance (p > 0.05). Parents with higher parenting self-efficacy (ß = 0.716, P < 0.01), and more subjective social support (ß = 1.127, p < 0.001) reported higher satisfaction with FQoL, and those with better social support utilization (ß = 1.066, p < 0.05) reported higher importance for FQoL. FQoL needs to be improved in the early stage of ASD diagnosis, and parental self-efficacy and social support can serve as the intervention targets.


Assuntos
Transtorno do Espectro Autista , Qualidade de Vida , Criança , Humanos , Poder Familiar , Seguimentos , Transtorno do Espectro Autista/diagnóstico , Autoeficácia , Pais , Apoio Social
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