Down-regulated TAB1 suppresses the replication of Coxsackievirus B5 via activating the NF-κB pathways through interaction with viral 3D polymerase.

Coxsackievirus Group B type 5 (CVB5), an important pathogen of hand-foot-mouth disease, is also associated with neurological complications and poses a public health threat to young infants. Among the CVB5 proteins, the nonstructural protein 3D, known as the Enteroviral RNA-dependent RNA polymerase, is mainly involved in viral genome replication and transcription. In this study, we performed immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify host proteins that interacted with CVB5 3D polymerase. A total of 116 differentially expressed proteins were obtained. Gene Ontology analysis identified that the proteins were involved in cell development and cell adhesion, distributed in the desmosome and envelope, and participated in GTPase binding. Kyoto Encyclopedia of Genes and Genomes analysis further revealed they participated in nerve diseases, such as Parkinson disease. Among them, 35 proteins were significantly differentially expressed and the cellular protein TGF-BATA-activated kinase1 binding protein 1 (TAB1) was found to be specifically interacting with the 3D polymerase. 3D polymerase facilitated the entry of TAB1 into the nucleus and down-regulated TAB1 expression via the lysosomal pathway. In addition, TAB1 inhibited CVB5 replication via inducing inflammatory factors and activated the NF-κB pathway through IκBα phosphorylation. Moreover, the 90-96aa domain of TAB1 was an important structure for the function. Collectively, our findings demonstrate the mechanism by which cellular TAB1 inhibits the CVB5 replication via activation of the host innate immune response, providing a novel insight into the virus-host innate immunity.

Efficacy, mechanism, and safety of melatonin-loaded on thermosensitive nanogels for rabbit VX2 tumor embolization: A novel design.

Transarterial chemoembolization (TACE) has been widely used for hepatocellular carcinoma. Reducing hypoxia in the tumor microenvironment after TACE remains a challenge as tumor progression is common in post-TACE patients due to the hypoxic tumor microenvironment. In this study, melatonin loaded on p(N-isopropyl-acrylamide-co-butyl methylacrylate) (PIB-M) was used for tumor embolism. Two types of human hepatoma cell lines were used to explore the mechanism by which melatonin prevents the growth and metastasis of cancer cells in vitro. A VX2 rabbit tumor model was used to evaluate the efficacy, mechanism, and safety of PIB-M in vivo. We found that under hypoxic condition, melatonin could inhibit tumor cell proliferation and migration by targeting hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) in vitro. In vivo, PIB-M inhibited tumor growth and metastasis in rabbit VX2 tumors by promoting apoptosis of tumor cells and targeting related angiogenic proteins and vascular permeability proteins. A high concentration of melatonin in the PIB-M group could be maintained in tumor tissue for 72 h after embolization. The liver and kidney functions were most damaged on the first day but recovered to normal on the seventh day after embolization in the PIB-M group. This novel method may open avenues for reduction of tumor growth and metastasis after TACE and is efficacy and safety, which may be used for treatment for other solid tumors and clinical translation.

A Joint Transcriptomic and Metabolomic Analysis Reveals the Regulation of Shading on Lignin Biosynthesis in Asparagus.

Asparagus belongs to the Liliaceae family and has important economic and pharmacological value. Lignin plays a crucial role in cell wall structural integrity, stem strength, water transport, mechanical support and plant resistance to pathogens. In this study, various biological methods were used to study the mechanism of shading on the asparagus lignin accumulation pathway. The physiological results showed that shading significantly reduced stem diameter and cell wall lignin content. Microstructure observation showed that shading reduced the number of vascular bundles and xylem area, resulting in decreased lignin content, and thus reducing the lignification of asparagus. Cinnamic acid, caffeic acid, ferulic acid and sinapyl alcohol are crucial intermediate metabolites in the process of lignin synthesis. Metabolomic profiling showed that shading significantly reduced the contents of cinnamic acid, caffeic acid, ferulic acid and sinapyl alcohol. Transcriptome profiling identified 37 differentially expressed genes related to lignin, including PAL, C4H, 4CL, CAD, CCR, POD, CCoAOMT, and F5H related enzyme activity regulation genes. The expression levels of POD, CCoAOMT, and CCR genes were significantly decreased under shading treatment, while the expression levels of CAD and F5H genes exhibited no significant difference with increased shading. The downregulation of POD, CCoAOMT genes and the decrease in CCR gene expression levels inhibited the activities of the corresponding enzymes under shading treatment, resulting in decreased downstream content of caffeic acid, ferulic acid, sinaperol, chlorogenic acid and coniferin. A significant decrease in upstream cinnamic acid content was observed with shading, which also led to decreased downstream metabolites and reduced asparagus lignin content. In this study, transcriptomic and metabolomic analysis revealed the key regulatory genes and metabolites of asparagus lignin under shading treatment. This study provides a reference for further understanding the mechanism of lignin biosynthesis and the interaction of related genes.

Structural and kinetic characterization of Porphyromonas gingivalis glutaminyl cyclase.

Porphyromonas gingivalis is a bacterial species known to be involved in the pathogenesis of chronic periodontitis, that more recently has been as well associated with Alzheimer's disease. P. gingivalis expresses a glutaminyl cyclase (PgQC) whose human ortholog is known to participate in the beta amyloid peptide metabolism. We have elucidated the crystal structure of PgQC at 1.95 Å resolution in unbound and in inhibitor-complexed forms. The structural characterization of PgQC confirmed that PgQC displays a mammalian fold rather than a bacterial fold. Our biochemical characterization indicates that PgQC uses a mammalian-like catalytic mechanism enabled by the residues Asp149, Glu182, Asp183, Asp218, Asp267 and His299. In addition, we could observe that a non-conserved Trp193 may drive differences in the binding affinity of ligands which might be useful for drug development. With a screening of a small molecule library, we have identified a benzimidazole derivative rendering PgQC inhibition in the low micromolar range that might be amenable for further medicinal chemistry development.

Determination of the cleavage site of enterovirus 71 VP0 and the effect of this cleavage on viral infectivity and assembly.

Hand, foot, and mouth disease (HFMD) is a major public health concern, especially among infants and young children. The primary pathogen of HFMD is enterovirus 71 (EV71), whose capsid assembly mechanism including capsid protein processing has been widely studied. However, some of its mechanisms remain unclear, such as the VP0 cleavage. This study aimed to identify the cleavage site of the EV71 VP0 capsid protein and to elucidate the effects of EV71 VP0 cleavage on viral infectivity and assembly. A mass spectrometry analysis indicated that the cleavage site of EV71 VP0 is located between residues Lys69 and Ser70. To analyze the importance of either residue to cleavage, we designed single mutations of Lys69, Ser70 and double mutations respectively and implemented these genomes to encapsulation. The results indicated that Ser70 is more important for VP0 cleavage and EV71 infectivity. In addition, exogenous expression of EV71 protease 2A and 3C was used to verify whether they play roles in VP0 cleavage. Analyses also showed that none of them participate in this process. This study provides novel insights into the mechanisms of EV71 capsid maturation, which may be a potential target to improve the productivity and immunogenicity of EV71 vaccines.

Micromechanics of cellularized biopolymer networks.

Collagen gels are widely used in experiments on cell mechanics because they mimic the extracellular matrix in physiological conditions. Collagen gels are often characterized by their bulk rheology; however, variations in the collagen fiber microstructure and cell adhesion forces cause the mechanical properties to be inhomogeneous at the cellular scale. We study the mechanics of type I collagen on the scale of tens to hundreds of microns by using holographic optical tweezers to apply pN forces to microparticles embedded in the collagen fiber network. We find that in response to optical forces, particle displacements are inhomogeneous, anisotropic, and asymmetric. Gels prepared at 21 °C and 37 °C show qualitative difference in their micromechanical characteristics. We also demonstrate that contracting cells remodel the micromechanics of their surrounding extracellular matrix in a strain- and distance-dependent manner. To further understand the micromechanics of cellularized extracellular matrix, we have constructed a computational model which reproduces the main experiment findings.

Clinical and genetic spectra of Charcot-Marie-Tooth disease in Chinese Han patients.

Charcot-Marie-Tooth disease (CMT) is a common hereditary motor and sensory neuropathy. Epidemiological data for Chinese CMT patients are few. This study aimed to analyze the electrophysiological and genetic characteristics of Chinese Han patients. A total of 106 unrelated patients with the clinical diagnosis of CMT were included. Clinical examination, nerve conduction studies (NCS), next-generation sequencing (NGS), and bioinformatic analyses were performed. Genetic testing was performed for 82 patients; 27 (33%) patients carried known CMT-associated gene mutations. PMP22 duplication was detected in 10 (12%) patients and GJB1 mutations in 9 (11%) patients. The mutation rate was higher in patients with a positive family history than in the sporadic cases (50% vs. 27%, p < 0.05). Six novel CMT-associated gene mutations including BSCL2 (c.461C>T), LITAF (c.32C>G), MFN2 (c.497C>T), GARS (c.794C>T), NEFL (c.280C>T), and MPZ (c.440T>C) were discovered. All except the LITAF (c.32C>G) mutation were identified as "disease causing" via bioinformatic analyses. In this Chinese Han population, the frequency of PMP22 gene duplication in those with CMT1 was slightly (50% vs. 70%-80%) less than in Western/Caucasian populations. The novel CMT-associated gene mutations broaden the mutation diversity of CMT1. NGS should be considered for genetic analyses in CMT patients.

Active targeting docetaxel-PLA nanoparticles eradicate circulating lung cancer stem-like cells and inhibit liver metastasis.

Lung cancer is the major cause of cancer related lethality worldwide, and metastasis to distant organs is the pivotal cause of death for the vast majority of lung cancer patients. Accumulated evidence indicates that lung cancer stem-like cells (CSLCs) play important roles in metastagenesis, and these circulating CSLCs may be important targets to inhibit the subsequent metastasis. The present study was aimed at establishing CSLC-targeting polylactic acid (PLA) encapsulated docetaxel nanoparticles for antimetastatic therapy. Cyclic binding peptides were screened on CSLCs in vitro and the peptide CVKTPAQSC exhibiting high specific binding ability to pulmonary adenocarcinoma tissue was subsequently conjugated to the nanoparticles loaded with docetaxel (NDTX). Antimetastatic effect of CSLC-targeting nanoparticles loaded with docetaxel (TNDTX) was evaluated in a nude mouse model of liver metastasis. Results showed that, in the absence of targeting peptide, NDTX hardly exhibited any antimetastatic effect. However, TNDTX treatment significantly decreased the metastatic tumor area in the nude mouse liver. Histopathological and serological results also confirmed the antimetastatic efficacy of TNDTX. To our knowledge, this is the first report on establishing a CSLC-based strategy for lung cancer metastatic treatment, and we hope this will offer a potential therapeutic approach for management of metastatic lung cancer.

Spatial-temporal dynamics of collective chemosensing.

Although the process of chemosensing by individual cells is intrisically stochastic, multicellular organisms exhibit highly regulated responses to external stimulations. Two key elements to understand the deterministic features of chemosensing are intercellular communications and the role of pacemaker cells. To characterize the collective behavior induced by these two factors, we study the spatial-temporal calcium dynamics of fibroblast cells in response to ATP stimulation. We find that closely packed cell colonies exhibit faster, more synchronized, and highly correlated responses compared to isolated cells. In addition, we demonstrate for chemosensing the existence of pacemaker cells and how the presence of gap junctions impact the first step of the collective response. By further comparing these results with the calcium dynamics of cells embedded in thin hydrogel films, where intercellular communication is only possible via diffusing molecules, we conclude that gap junctions are required for synchronized and highly correlated responses among cells in high density colonies. In addition, in high density cell colonies, both communication channels lead to calcium oscillations following the stimulation by external ATP. While the calcium oscillations associated with cells directly exposed to external flows were transient, the oscillations of hydrogel trapped cells can persist with a fundamental frequency and higher harmonics. Our observations and measurements highlight the crucial role of intercellular signaling for generating regulated spatial and temporal dynamics in cell colonies and tissues.

Cementless bilateral synchronous total hip arthroplasty in ankylosing spondylitis with hip ankylosis.

PURPOSE: This study was a retrospective analysis of early and mid-term clinical effects and perioperative management of cementless bilateral synchronous total hip arthroplasty (THA) in patients with ankylosing spondylitis (AS) with bilateral hip ankylosis. METHODS: Fifteen AS patients (30 hips) with bilateral hip ankylosis were managed with cementless bilateral synchronous THA. Surgical outcome was evaluated using the visual analogue scale (VAS), the range of motion and the Harris score. RESULTS: The mean follow-up period was 29.3 months. At the last follow-up visit, the VAS score decreased from 7.53 ± 0.99 before the operation to 2.40 ± 0.91. The Harris score increased from 24.8 ± 7.42 before the operation to 83.8 ± 4.61. The total range of motion increased from 78.73 ± 14.53 before the operation to 209.73 ± 16.19 after the operation. After the operation, there was one case of early hip dislocation, one case of femoral nerve stretch injury and one case of superficial incision infection. There were no cases of deep venous thrombosis. X-ray examinations did not show prosthetic loosening or displacement. CONCLUSION: AS patients with bilateral hip ankylosis can be treated with cementless bilateral synchronous THA, which could greatly improve hip joint function without significant complications. The clinical effects proved to be satisfactory.

Nanoplastics aggravated TDCIPP-induced transgenerational developmental neurotoxicity in zebrafish depending on the involvement of the dopamine signaling pathway.

Plastics pose a hazard to the environment. Although plastics have toxicity, microplastics (MPs) and nanoplastics (NPs) are capable of interacting with the rest pollutants in the environment, so they serve as the carriers and interact with organic pollutants to modulate their toxicity, thus resulting in unpredictable ecological risks. PS-NPs and TDCIPP were used expose from 2 h post-fertilization (hpf) to 150 days post-fertilization (dpf) to determine the bioaccumulation of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and its potential effects on neurodevelopment in F1 zebrafish (Danio rerio) offspring under the action of polystyrene nano plastics (PS-NPs). The exposure groups were assigned to TDCIPP (0, 0.4, 2 or 10 µg/L) alone group and the PS-NPs (100 µg/L) and TDCIPP co-exposed group. F1 embryos were collected and grown in clean water to 5 dpf post-fertilization. PS-NPs facilitated the bioaccumulation of TDCIPP in the gut, gill, head，gonad and liver of zebrafish in a sex-dependent manner and promoted the transfer of TDCIPP to their offspring, thus contributing to PS-NPs aggravated the inhibition of offspring development and neurobehavior of TDCIPP-induced. In comparison with TDCIPP exposure alone, the combination could notably down-regulate the levels of the dopamine neurotransmitter, whereas the levels of serotonin or acetylcholine were not notably different. This result was achieved probably because PS-NPs interfered with the TDCIPP neurotoxic response of zebrafish F1 offspring not through the serotonin or acetylcholine neurotransmitter pathway. The increased transfer of TDCIPP to the offspring under the action of PS-NPs increased TDCIPP-induced transgenerational developmental neurotoxicity, which was proven by a further up-regulation/down-regulation the key gene and protein expression related to dopamine synthesis, transport, and metabolism in F1 larvae, in contrast to TDCIPP exposure alone. The above findings suggested that dopaminergic signaling involvement could be conducive to the transgenerational neurodevelopmental toxicity of F1 larval upon parental early co-exposure to PS-NPs and TDCIPP.

Enhanced neuroprotective effects of resveratrol delivered by nanoparticles on hydrogen peroxide-induced oxidative stress in rat cortical cell culture.

Resveratrol (RES) has recently been reported as a potential antioxidant in treatment of ischemia/reperfusion injury through attenuating oxidative stress and apoptosis. However, application of RES is limited for its insolubility and short half-time. Latest evidence raises the possibility of developing nanoparticle-based delivery systems with improved solubility, stability and cytotoxicity of lipophilic drug. Here, we reported first a simple way to produce RES-loaded nanoparticles (RES-NPs) based on poly(N-vinylpyrrolidone)-b-poly(ε-caprolactone) polymer and further evaluated the protective effect of RES-NPs on hydrogen peroxide-induced oxidative stress and apoptosis in rat cortical cell culture. The controlled release pattern of RES-loaded nanoparticles was characterized by in vitro release experiments. Cytotoxicity tests proved cytocompatibility of these nanoparticles with neurons. Shown by coumarin-6 loaded nanoparticles, the uptake of nanoparticles by neurons was considered through endocytosis, which could lead to higher uptake efficiency at lower concentration. Thereby, the hypothesis is raised that RES-NPs could demonstrate enhanced neuroprotection compared to an equivalent dose of free RES at lower concentration, especially. It was further supported by enhanced reduction of LDH release, elimination of ROS and MDA, and attenuation of apoptosis signal (ratio of Bax/Bcl-2, activation of caspase-3). RES-NPs could be a potential treatment needing intensive research for ischemia/reperfusion related disorder including stroke.

Microbial keystone taxa drive succession of plant residue chemistry.

Managing above-ground plant carbon inputs can pave the way toward carbon neutrality and mitigating climate change. Chemical complexity of plant residues largely controls carbon sequestration. There exist conflicting opinions on whether residue chemistry diverges or converges after long-term decomposition. Moreover, whether and how microbial communities regulate residue chemistry remains unclear. This study investigated the decomposition processes and residue composition dynamics of maize straw and wheat straw and related microbiomes over a period of 9 years in three climate zones. Residue chemistry exhibited a divergent-convergent trajectory during decomposition, that is, the residue composition diverged during the 0.5-3 year period under the combined effect of straw type and climate and then converged to an array of common compounds during the 3-9 year period. Chemical divergence during the first 2-3 years was primarily driven by the changes in extracellular enzyme activity influenced by keystone taxa-guided bacterial networks, and the keystone taxa belonged to Alphaproteobacteria, particularly Rhizobiales. After 9 years, microbial assimilation became dominant, leading to chemical convergence, and fungi, particularly Chaetomium, were the main contributors to microbial assimilation. Overall, this study demonstrated that keystone taxa regulate the divergent-convergent trajectory in residue chemistry.

Tumor-Associated Macrophages Regulating a Polymer Nanoplatform for Synergistic Treatment of Breast Tumors.

Tumor-associated macrophages (TAMs) play a critical role in tumor progression and metastasis. Modulation of TAM polarization is one of the most effective strategies to change the immunosuppressive tumor microenvironment (TME). In this study, organic polymer nanoparticles (CPHT) were prepared using hyaluronic acid (HA)-conjugated disulfide-bonded polyethylene imide (PEIS) as a carrier through a self-assembly strategy. These nanoparticles were modified by transferrin (Tf) and loaded with chlorin e6 (Ce6). The results showed that CPHT had good dispersion with a particle size of about 30 nm. CPHT gradually disintegrated under the exposure with a high concentration of glutathione (GSH) in tumor cells, proving the possibility for the controlled release of Ce6 and photodynamic therapy. An in vitro test showed that the uptake of CPHT in tumor cells was mediated by both HA and Tf, indicating the active tumor-targeting capacity of CPHT. CPHT significantly downregulated the ratio of CD206/CD86 and triggered the upregulation of immune factors such as TNF-α and iNOS, suggesting the repolarization of TAMs. We also found that CPHT effectively induced ferroptosis in tumor cells through lipid peroxide accumulation, GSH depletion, and downregulation of lipid peroxidase (GPX4) expression. Animal experiments confirmed that CPHT not only effectively inhibited the growth of tumors in situ but also significantly decelerated the growth of the distal tumor. Elevated levels of CD86 and IFN-γ and decreased expression of CD206 were observed at the tumor sites post CPHT treatment. These results confirmed the value of CPHT as a multifunctional nanoplatform that can tune the TME and provide new hope for tumor treatment.

Skin-adhesive lignin-grafted-polyacrylamide/hydroxypropyl cellulose hydrogel sensor for real-time cervical spine bending monitoring in human-machine Interface.

Developing a straightforward method to produce conductive hydrogels with excellent mechanical properties, self-adhesion, and biocompatibility remains a significant challenge. While current approaches aim to enhance mechanical performance, they often require additional steps or external forces for fixation, leading to increased production time and limited practicality. A novel lignin-grafted polyacrylamide/hydroxypropyl cellulose hydrogel (L-g-PAM/HPC hydrogel) with a semi-interpenetrating polymer network structure had been developed in this research that boasted exceptional adhesion to the skin (∼68 kPa) and stretchability properties (∼1637 %) compared to PAM-based hydrogels. By incorporating conductive additives such as silver nanowires and carbon nanocages to construct a bridge-like structure within the hydrogel matrix, the resulting AgC@L-g-PAM/HPC hydrogel exhibited impressive electrical conductivity, surpassing that of other PAM-based hydrogels relying on MXene, with a maximum value of 0.76 S/m. Furthermore, the AgC@L-g-PAM/HPC hydrogel retained its efficient electrical signal transmission capability even under mechanical stress. These make it an ideal flexible strain sensor capable of detecting various human motions. In this study, a smart real-time monitoring system was successfully developed for tracking cervical spine bending, serving as an extension for monitoring human activities.

Optimization of a lattice structure inspired by glass sponge.

The biomimetic design of engineering structures is based on biological structures with excellent mechanical properties, which are the result of billions of years of evolution. However, current biomimetic structures, such as ordered lattice materials, are still inferior to many biomaterials in terms of structural complexity and mechanical properties. For example, the structure ofEuplectella aspergillum, a type of deep-sea glass sponge, is an eye-catching source of inspiration for biomimetic design, many researches have introduced similar architecture in cellular solids. However, guided by scientific theory, how to surpass the mechanical properties ofE. aspergillumremains an unsolved problem. We proposed the lattice structure which firstly surpass theE. aspergillummechanically. The lattice structure of the skeleton ofE. aspergillumconsists of vertically, horizontally, and diagonally oriented struts, which provide superior strength and flexural resistance compared with the conventional square lattice structure. Herein, the structure ofE. aspergillumwas investigated in detail, and by using the theory of elasticity, a lattice structure inspired by the biomimetic structure was proposed. The mechanical properties of the sponge-inspired lattice structure surpassed the sponge structure under a variety of loading conditions, and the excellent performance of this configuration was verified experimentally. The proposed lattice structure can greatly improve the mechanical properties of engineering structures, and it improves strength without much redundancy of material. This study achieved the first surpassing of the mechanical properties of an existing sponge-mimicking design. This design can be applied to lattice structures, truss systems, and metamaterial cells.

Electron-acceptor density adjustments for preparation conjugated polymers with NIR-II absorption and brighter NIR-II fluorescence and 1064 nm active photothermal/gas therapy.

Designing conjugated polymers (CPs) with both efficient second near-infrared wavelength (NIR-II) fluorescence and NIR-II photothermal therapy performance remains a huge challenge, as the introduction of excessively strong electron donor and acceptor units significantly increase non-radiative decay. Herein, we describe an "electron acceptor density adjustment" strategy to address this problem, since a lower electron acceptor density in the conjugated polymer backbone can enhance the radiative rate constant and improve NIR-II fluorescence brightness. We used quaterthiophene (4T) with four repeated thiophene chain units and bithiophene (2 TC) modified with long alkyl side chains to reduce the electron acceptor density in the conjugated polymer backbone. The resultant 1064 nm absorption polymer, TTQ-2TC-4T displayed approximately 7.30-folds enhancement in NIR-II emission intensity compared to that of undoped TTQ-1T at the same mass concentration in toluene solution. Furthermore nanoparticles (TTQ-MnCO NPs) based on TTQ-2TC-4T and CO donors (Mn2(CO)10) were developed to realize NIR-II FI-guided 1064 nm laser-triggered NIR-II PTT/Gas synergistic therapy. The TTQ-MnCO NPs nanoparticles exhibited high photothermal conversion efficiency (η) of 44.43% at 1064 nm and high specific NIR-II fluorescence imaging of the cerebral vasculature of live mice. The in vivo results demonstrate that TTQ-MnCO NPs nanoparticles have excellent PTT/Gas synergistic therapeutic effects in MCF-7 tumor-bearing mice under 1064 nm laser irradiation. This study provides a new approach for optimizing both NIR-II fluorescence and NIR-II photothermal performance of NIR-II absorption conjugated polymers.

A Study on Voice Measures in Patients With Alzheimer's Disease.

OBJECTIVE: As Alzheimer's disease (AD) might provoke certain nerve disorders, patients with AD can acquire sensorimotor adaptation problems, and thus the acoustic characteristics of the speech they produce may differ from those of healthy subjects. This study aimed to (1) extract acoustic characteristics (relating to articulatory gestures) potentially useful for detecting AD and (2) examine whether these characteristics could help identify AD patients. METHODS: A total of 50 individuals participated in the study, including the AD group (17 cases), the Neurologically Healthy (NH) group (13 cases), the Mild Cognitive Impairment (MCI) group (11 cases), and the Vascular Cognitive Impairment (VCI) group (9 cases). Voice samples involving three vowels (/i/, /a/, and /u/) and six consonants (/p/, /pÊ°/, /t/, /tÊ°/, /k/, and /kÊ°/) were collected using a digital recorder (TASCAM DR40X). Microphone-to-mouth distance was maintained at 30 cm. Acoustic measures included F0, jitter, shimmer, HNR, F1, F2, F3, and VOT. RESULTS: One-way ANOVA tests were carried out to compare the acoustic measures among the four groups. F3 of vowel /u/, F2 bandwidth of vowel /a/, VOT of consonant /t/, and male participants' F0 of three vowels (/a/, /i/, and /u/) were found significantly different, while no significant differences were found in the other measures. CONCLUSION: Some acoustic characteristics can indeed help detect AD patients.

Screening for SH3TC2 variants in Charcot-Marie-Tooth disease in a cohort of Chinese patients.

Mutations in the SH3TC2 gene cause Charcot-Marie-Tooth disease type 4C (CMT4C), characterized by inherited demyelinating peripheral neuropathy. CMT4C is a common form of CMT4/autosomal recessive (AR) CMT1. This study examined the SH3TC2 variants, investigated genotype-phenotype correlations and explored the frequency of CMT4C in Chinese patients. A total of 206 unrelated patients of Chinese Han descent clinically diagnosed with CMT were recruited. All patients underwent detailed history-taking, neurological examination, laboratory workups, and electrophysiological studies. Genetic analysis was performed via high-throughput target sequencing (NGS). Three patients, one male and two females, were found to carry five SH3TC2 mutations: patient 1 (c.3154C > T, p.R1054X; c.929G > A, p.G310E); Patient 2 (c.2872_2872del, p.S958fs; c.3710C > T, p.A1237V) and Patient 3 (c.2782C > T, p.Q928X; c.929G > A, p.G310E). The c.2872_2872del, c.3710C > T and c.2782C > T variants were not reported before. CMT4C caused by SH3TC2 mutation is a very common type of CMT4/AR CMT1. Three novel mutations, c.2872_2872del, c.3710C > T and c.2782C > T, were found in this study. Combination of clinical phenotype, nerve conduction studies, genetic analysis and bioinformatics analysis are of vital importance in patients suspected as CMT.

The crystal structure of MreC provides insights into polymer formation.

MreC is a scaffold protein required for cell shape determination through interactions with proteins related to cell wall synthesis. Here, we determined the crystal structure of the major periplasmic part of MreC from Escherichia coli at 2.1 Å resolution. The periplasmic part of MreC contains a coiled-coil domain and two six-stranded barrel domains. The coiled-coil domain is essential for dimer formation, and the two monomers are prone to relative motion that is related to the small interface of ß-barrel domains. In addition, MreC forms an antiparallel filament-like structure along the coiled-coil direction, which is different from the helical array structure in Pseudomonas aeruginosa. Our structure deepens our understanding of polymer formation of MreC.