A Prediction Rule for the Dystonic Spread of Blepharospasm: A 4-Year Prospective Cohort Study.

OBJECTIVE: Blepharospasm (BSP), focal dystonia with the highest risk of spread, lacks clear understanding of early spreading risk factors and objective prognostic indicators. We aimed to identify these risk factors through clinical and electrophysiological assessments, and to establish a predictive model for dystonic spread in BSP. METHODS: We prospectively followed BSP patients for 4 years, collecting data on dystonic spread, and conducting electrophysiological evaluations. The blink reflex, masseter inhibitory reflex, and trigeminal somatosensory evoked potential were assessed. Univariable and multivariable Cox proportional hazard regression models were used to assess clinical characteristics associated with BSP dystonic spread. A predictive model was constructed using a nomogram, and performance of the model was evaluated using the area under the receiver operating characteristic curve. RESULTS: A total of 136 enrolled participants (mean age 56.34 years) completed a 4-year follow-up. Among them, 62 patients (45.6%) showed spread to other body regions. Multivariable Cox regression analysis showed that a high Hamilton Anxiety Scale score (hazard ratio 1.19, 95% confidence interval 1.13-1.25, p < 0.001), prolonged trigeminal somatosensory evoked potential mandibular branch P1-N2 peak interval (hazard ratio 1.11, 95% confidence interval 1.02-1.21, p = 0.017), and elevated trigeminal somatosensory evoked potential mandibular branch P1-N2 peak amplitude (hazard ratio 1.26, 95% confidence interval 1.12-1.41, p < 0.001) were independent risk factors for BSP dystonic spread within 4 years. Combining these factors, the predictive models demonstrated excellent discriminative ability, with the receiver operating characteristic curve score being 0.797, 0.790, 0.847, and 0.820 at 1, 2, 3 and 4 years after enrollment, respectively. INTERPRETATION: We established a predictive model with significant value for anticipating dystonic spread in BSP, offering crucial evidence. These findings contribute essential insights into the early clinical identification of the development and evolution of BSP diseases. ANN NEUROL 2024.

Mineralize It or Not: Comparative Proteomics and Elemental Analysis Reveal Ancestral Compositions of Iron Mineralized Molluscan Radulae.

The radula is a unique foraging organ to Mollusca, which is important for their evolution and taxonomic classification. Many radulae are mineralized with metals. Although the remarkable mechanical properties of mineralized radulae are well-studied, the formation of mineralization from nonmineralized radulae is poorly understood. Taking advantage of the recently sequenced octopus and chiton genomes, we were able to identify more species-specific radular proteins by proteomics. Comparing these proteomes with the known limpet radula proteome enabled us to gain insight into the molecular components of nonmineralized and mineralized radula, highlighting that iron mineralization in the chiton radula is possibly due to the evolution of ferritins and peroxiredoxins. Through an in vitro binding assay, ferritin is shown to be important to iron accumulation into the nonmineralized radula. Moreover, radular proteomes reflect their adaption to dietary habits to some extent. The octopus radula has many scaffold modification proteins to suit flexibility while the chiton radula has abundant sugar metabolism proteins (e.g., glycosyl hydrolases) to adapt to algae feeding. This study provides a foundation for the understanding of molluscan radula formation and evolution and may inspire the synthesis of iron nanomaterials.

Accelerated hazards model based on parametric families generalized with Bernstein polynomials.

A transformed Bernstein polynomial that is centered at standard parametric families, such as Weibull or log-logistic, is proposed for use in the accelerated hazards model. This class provides a convenient way towards creating a Bayesian nonparametric prior for smooth densities, blending the merits of parametric and nonparametric methods, that is amenable to standard estimation approaches. For example optimization methods in SAS or R can yield the posterior mode and asymptotic covariance matrix. This novel nonparametric prior is employed in the accelerated hazards model, which is further generalized to time-dependent covariates. The proposed approach fares considerably better than previous approaches in simulations; data on the effectiveness of biodegradable carmustine polymers on recurrent brain malignant gliomas is investigated.

Silver doped-silica nanoparticles reinforced poly (ethylene glycol) diacrylate/hyaluronic acid hydrogel dressings for synergistically accelerating bacterial-infected wound healing.

Various cutaneous wounds are easily infected with external bacteria, which might result in a chronic wound and ongoing consequences. However, the appropriate development of biomaterials for the controllable delivery of antibacterial silver (Ag) and the simultaneous enhancement of mechanical adhesiveness remains an urgent challenge. Herein, we proposed a double network (DN) hydrogel dressings based on a covalent network of polyethylene glycol diacrylate (PEGDA) and a coordination network between catechol-modified hyaluronic acid (C-HA) and Ag-doped mesoporous silica nanoparticle (AMSN) for promoting the bacterial-infected full-thickness skin wound regeneration. This distinctive dual cross-linked structure of PEGDA/C-HA-AMSN significantly improved physicochemical properties, including gelation time, mechanical performance, and tissue adhesion strength. Importantly, PEGDA/C-HA-AMSN served as a hydrogel dressing that can respond to the acidic environment of bacterial-infected wounds leading to the controllable and optimized delivery of Ag, enabling the durable antibacterial activity accompanied by favorable cytocompatibility and angiogenesis capability. Further in vivo studies validated the higher efficacy of hydrogel dressings in treating wound healing by the synergistic antibacterial, anti-inflammatory, and pro-vascular strategies, meaning the prominent potential of the prepared dressings for overcoming the concerns of wound theranostics.

Correlation Analysis of Pathological Features and Axillary Lymph Node Metastasis in Patients with Invasive Breast Cancer.

Objective: To investigate the risk factors of axillary lymph node metastasis in patients with invasive breast cancer. Methods: This study retrospectively included 122 cases of invasive breast cancer patients admitted to the First Medical Center of PLA General Hospital from January 2019 to September 2020. According to postoperative pathological results, axillary lymph node metastasis was divided into axillary lymph node metastasis (ALNM) group (n =40) and non-axillary lymph node metastasis (NALNM) group (n =82). General demographic information was collected and compared between the two groups. Collected pathological results included lymphovascular invasion (LVI) and the expression of estrogen receptor (ER), progestogen receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 detected by immunohistochemistry. Imaging parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) including apparent diffusion coefficient (ADC), early enhanced rate, and time-intensity curve (TIC) were also included into univariate analysis. The variables with differences between the two groups were compared by univariate analysis, and the related factors of axillary lymph node metastasis were analyzed by logistic regression model. Results: There was no significant difference in general demographic information between the two groups. No significant differences were found in the positive rates of HER-2, ER, PR, Ki-67, pathological types, and clavicular lymph node metastasis and skin chest wall invasion between the two groups (P > 0.05). The proportion of LVI in ALNM group was significantly higher than that in NALNM group (37.50% vs. 6.10%, P < 0.001). The proportion of breast cancer on the left side in the ALNM group was higher than that in the NALNM group, and the difference was statistically significant (70.00% vs. 47.56%, P = 0.019). There were no significant differences in the imaging parameters obtained by DCE-MRI between the two groups. Binary logistics regression analysis showed that LVI (OR =12.258, 95% CI =3.681-40.812, P < 0.001) and left breast cancer (OR =3.598, 95% CI =1.404-9.219, P = 0.008) were risk factors for axillary lymph node metastasis in patients with invasive breast cancer. Conclusion: The formation of vascular tumor thrombi in breast cancer tissue and left breast cancer are risk factors for axillary lymph node metastasis in invasive breast cancer and might be helpful for preoperative detailed assessment of the patient's condition.

Bismuth-Decorated Beta Zeolites Catalysts for Highly Selective Catalytic Oxidation of Cellulose to Biomass-Derived Glycolic Acid.

Catalytic conversion of cellulose to liquid fuel and highly valuable platform chemicals remains a critical and challenging process. Here, bismuth-decorated ß zeolite catalysts (Bi/ß) were exploited for highly efficient hydrolysis and selective oxidation of cellulose to biomass-derived glycolic acid in an O2 atmosphere, which exhibited an exceptionally catalytic activity and high selectivity as well as excellent reusability. It was interestingly found that as high as 75.6% yield of glycolic acid over 2.3 wt% Bi/ß was achieved from cellulose at 180 °C for 16 h, which was superior to previously reported catalysts. Experimental results combined with characterization revealed that the synergetic effect between oxidation active sites from Bi species and surface acidity on H-ß together with appropriate total surface acidity significantly facilitated the chemoselectivity towards the production of glycolic acid in the direct, one-pot conversion of cellulose. This study will shed light on rationally designing Bi-based heterogeneous catalysts for sustainably generating glycolic acid from renewable biomass resources in the future.

Aberrant Neuregulin 1/ErbB Signaling in Charcot-Marie-Tooth Type 4D Disease.

Charcot-Marie-Tooth type 4D (CMT4D) is an autosomal recessive demyelinating form of CMT characterized by progressive motor and sensory neuropathy. N-myc downstream regulated gene 1 (NDRG1) is the causative gene for CMT4D. Although more CMT4D cases have been reported, the comprehensive molecular mechanism underlying CMT4D remains elusive. Here, we generated a novel knockout mouse model in which the fourth and fifth exons of the Ndrg1 gene were removed. Ndrg1-deficient mice develop early progressive demyelinating neuropathy and limb muscle weakness. The expression pattern of myelination-related transcriptional factors, including SOX10, OCT6, and EGR2, was abnormal in Ndrg1-deficient mice. We further investigated the activation of the ErbB2/3 receptor tyrosine kinases in Ndrg1-deficient sciatic nerves, as these proteins play essential roles in Schwann cell myelination. In the absence of NDRG1, although the total ErbB2/3 receptors expressed by Schwann cells were significantly increased, levels of the phosphorylated forms of ErbB2/3 and their downstream signaling cascades were decreased. This change was not associated with the level of the neuregulin 1 ligand, which was increased in Ndrg1-deficient mice. In addition, the integrin ß4 receptor, which interacts with ErbB2/3 and positively regulates neuregulin 1/ErbB signaling, was significantly reduced in the Ndrg1-deficient nerve. In conclusion, our data suggest that the demyelinating phenotype of CMT4D disease is at least in part a consequence of molecular defects in neuregulin 1/ErbB signaling.

Association between radiation dose to organs at risk and acute patient reported outcome during radiation treatment for head and neck cancers.

BACKGROUND: Associations between patient-reported outcomes and dose to organs at risk (OARs) may promote management and guide future investigations. METHODS: We retrospectively evaluated PROs and OAR dose in head and neck (H&N) cancer. RESULTS: In 169 patients, we identified weak associations between: "Difficulty swallowing/chewing" and increased mean RT dose to the oral cavity, larynx, pharyngeal constrictor muscles (PCM) and contralateral parotid; "choking/coughing" and larynx mean dose; "problems with mucus in mouth and throat" and oral cavity, contralateral parotid mean dose and parotid V30, contralateral submandibular gland and PCM mean dose; "difficulty with voice/speech" and oral cavity, contralateral parotid, contralateral submandibular gland and larynx mean dose; and "dry mouth" and ipsilateral submandibular gland, oral cavity and PCM mean dose. CONCLUSION: We identified weak associations between PRO and dose to OARs-these data can guide on treatment management, patient counseling, and serve as a baseline for future investigations.

Plastic responses of fine root morphology and architecture traits to nitrogen addition in ectomycorrhizal and arbuscular mycorrhizal tree species in an evergreen broadleaved forest.

We measured the morphology traits (specific root length, specific root surface area, root tissue density, average root diameter) and architecture traits (root fork, root fork ratio, increase rate of root length, root tip density, root fork density) of fine roots in two mycorrhiza tree species, Castanopsis faberi (ectomycorrhizal) and Schima superba (arbuscular mycorrhizal), in an evergreen broadleaved forest in the middle subtropical zone. Root bags method was used in an in situ nitrogen deposition experiment. The aim of this study was to reveal the differences in the plastic responses of fine root morphology and architecture traits to nitrogen deposition between the different mycorrhizal trees. The plastic responses of specific root length, specific root surface area and root fork to nitrogen addition decreased from the first-order root to the fourth-order root, while root tissue density showed an opposite pattern. Such a result indicated a trade-off between nutrient acquisition and resource maintenance of different fine root orders. Different mycorrhizal tree species adopted diffe-rent adaptation strategies to the variations of soil nitrogen availability. C. faberi adopted an opportuni-stic strategy, which relied on fine root to improve nutrient absorption efficiency, enhanced the capacity of space expansion and in-situ nutrient absorption to focus on rapid nutrient absorption strategy. S. superba did not change fine root morphological traits through the trade-off between nutrient absorption efficiency and root construction cost, but relied more on the complementarity between mycorrhizal fungi and fine root architecture traits for nutrient acquisition. The differences in the cost of maintaining and constructing fine root C between different mycorrhizal trees led to fine root adopting the most suitable nutrient capture strategy.

Novel mutation in the periaxin gene causal to Charcot-Marie-Tooth disease type 4F.

Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy. Mutations in the periaxin gene (PRX) can cause CMT type 4F, an autosomal recessive neuropathy, which is clinically characterized by slowly progressive distal muscle atrophy and weakness, with pes cavus deformity of the foot, and the absence of deep tendon reflexes. To date, dozens of reports of PRX mutations have been published worldwide, but none have been reported in Chinese patients. Here, we describe a 14-year-old Chinese boy with neuropathy characterized by slowly progressive limb weakness and atrophy, as well as sensory ataxia, whose cerebrospinal protein levels were 1627 mg/L. Genetic analysis identified a novel homozygous mutation, c.1174C>T (p.R392X), in exon 6 of PRX, which is the first case of its kind recorded in China.

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Nitrogen deposition will affect the morphology of fine roots and its absorption of nutrien-ts, resulting in changes nutrient cycling in terrestrial ecosystems. In order to understand the effects of nitrogen deposition on fine root morphological traits of Castanopsis fabri and C. carlesii, two ectomycorrhizas tree species, we carried out in situ experiment using the root bags method in an evergreen broadleaved forest in the subtropical zone. The results showed that the plastic responses of specific root length and specific root surface area of low-order roots (first to third order) to nitrogen addition was higher than that of high-order roots (fourth order). The plastic responses of root tissue density to nitrogen addition increased from the first-order to the fourth-order, while the average root diameter of each order had no significant plastic responses to nitrogen addition. There was a certain synergistic change between the plastic response of specific root length and specific surface area in the low order fine root and the plastic response of tissue density in the high order fine root. The specific root length, specific root surface area and root tissue density of the two species showed opposite plastic responses to nitrogen addition, indicating that different ectomycorrhizal tree species had different nutrient foraging strategies. C. fabri adopted rapid absorption strategy by increasing specific root length, specific root surface area, and proliferation rate of fine root length, while C. carlesii adopted a relatively conservative resource absorption strategy by increasing tissue density of fine roots.

[Effects of hypergravity exposure after 30 days of simulated weightlessness on chemokine CCL20 and its receptor CCR6 in gingival tissue of rhesus macaque].

PURPOSE: To study the effect of hypergravity exposure after 30 days of simulated weightlessness on the expression of chemokine CCL20 and its receptor CCR6 in gingival tissue of rhesus macaque. METHODS: Twenty-three male rhesus monkeys were randomly divided into 4 groups, namely control group (A,n=3), weightlessness group (B,n=3), hypergravity group (C,n=3) and hypergravity exposure after 30 days of simulated weightlessness group (D, n=14). Group D was further divided into 4 subgroups according to the values of overload as: +11 Gx /270 s group (D1, n=3), +13 Gx /230 s group (D2,n=4), +15 Gx/200 s group (D3,n=4) and +13 Gx /230 s with 9 days of recovery group (D4, n=3). Histopathological changes of gingival tissues were observed by hematoxylin-eosin staining and the expressions of CCL20 and CCR6 were detected by immunohistochemistry (IHC) and quantitative real-time PCR (Q-PCR). SPSS 17.0 software package was used for statistical analysis. RESULTS: Histological observation showed that no significant histopathological change was found in the gingival tissues in all experimental groups. However, there were more infiltrated lymphocytes and neutrophils in the experimental groups. Normal gingival epithelial cells were hardly stained by anti-CCL20 but weakly stained by anti-CCR6. In the experimental groups, CCL20 could be detected in the basal layer of the gingival epithelial tissue, and CCR6 could be detected in the spinous layer and the basal layer of the gingival epithelium. The CCL20 and CCR6 expression in the gingival tissues of each experimental group were significantly higher than those of the control group, not only at the protein level but at the mRNA level (P<0.05) except the CCL20 expression in the weightlessness group. CONCLUSIONS: Hypergravity exposure after 30 days of simulated weightlessness will not lead to significant pathological changes in gingival tissues, but can induce the expression of chemokine CCL20 and its receptor CCR6 in gingival tissue.

Design and in vitro evaluation of a novel poly(methacrylic acid)/metronidazole antibacterial nanogel as an oral dosage form.

To overcome the undesirable side-effects of metronidazole (MTZ), ethylene glycol dimethacrylate is used as the cross-linker, and a series of poly(methacrylic acid) (PMAA) nanogels were prepared to load the MTZ. We investigated the morphology, size, in vitro release property in the simulated gastrointestinal medium, long-term antibacterial performance against Bacteroides fragilis, cytotoxicity, stability and activity of this novel MTZ/PMAA nanogel. The results indicate that the MTZ/PMAA nanogel sustained the release of MTZ in long-term antibacterial activity in the simulated gastrointestinal medium. This MTZ/PMAA nanogel exhibits less cytotoxicity than MTZ alone, suggesting that MTZ/PMAA nanogel is a more useful dosage form than MTZ for mild-to-moderate Clostridium difficile infections. The novel aspects of this study include the synthesis of a nanogel and the three-phase study of the release profile, which might be useful for other researchers in this field.

Citric acid-based hydroxyapatite composite scaffolds enhance calvarial regeneration.

Citric acid-based polymer/hydroxyapatite composites (CABP-HAs) are a novel class of biomimetic composites that have recently attracted significant attention in tissue engineering. The objective of this study was to compare the efficacy of using two different CABP-HAs, poly (1,8-octanediol citrate)-click-HA (POC-Click-HA) and crosslinked urethane-doped polyester-HA (CUPE-HA) as an alternative to autologous tissue grafts in the repair of skeletal defects. CABP-HA disc-shaped scaffolds (65 wt.-% HA with 70% porosity) were used as bare implants without the addition of growth factors or cells to renovate 4 mm diameter rat calvarial defects (n = 72, n = 18 per group). Defects were either left empty (negative control group), or treated with CUPE-HA scaffolds, POC-Click-HA scaffolds, or autologous bone grafts (AB group). Radiological and histological data showed a significant enhancement of osteogenesis in defects treated with CUPE-HA scaffolds when compared to POC-Click-HA scaffolds. Both, POC-Click-HA and CUPE-HA scaffolds, resulted in enhanced bone mineral density, trabecular thickness, and angiogenesis when compared to the control groups at 1, 3, and 6 months post-trauma. These results show the potential of CABP-HA bare implants as biocompatible, osteogenic, and off-shelf-available options in the repair of orthopedic defects.

The effect of nanowire length and diameter on the properties of transparent, conducting nanowire films.

This article describes how the dimensions of nanowires affect the transmittance and sheet resistance of a random nanowire network. Silver nanowires with independently controlled lengths and diameters were synthesized with a gram-scale polyol synthesis by controlling the reaction temperature and time. Characterization of films composed of nanowires of different lengths but the same diameter enabled the quantification of the effect of length on the conductance and transmittance of silver nanowire films. Finite-difference time-domain calculations were used to determine the effect of nanowire diameter, overlap, and hole size on the transmittance of a nanowire network. For individual nanowires with diameters greater than 50 nm, increasing diameter increases the electrical conductance to optical extinction ratio, but the opposite is true for nanowires with diameters less than this size. Calculations and experimental data show that for a random network of nanowires, decreasing nanowire diameter increases the number density of nanowires at a given transmittance, leading to improved connectivity and conductivity at high transmittance (>90%). This information will facilitate the design of transparent, conducting nanowire films for flexible displays, organic light emitting diodes and thin-film solar cells.