Conjugated Poly(ionic liquid)-Based Nanoporous Membrane for Rapid Moisture Response.

Stimuli-responsive nanoporous materials represent a newly emerging category of functional materials, for which instant and significant response behavior is strongly demanded but still challenging. Herein, a new kind of conjugated poly(ionic liquid)s (PILs) synthesized via a simple one-pot spontaneous nucleophilic substitution and polymerization between 4,4'-vinylenedipyridine and propargyl bromide is reported. A nanoporous membrane actuator is further developed via ionic complexation between the current PIL and trimesic acid. The actuator carries a gradient density in the hydrophobicity content along the membrane cross-section, which results in a fast response to moisture.

A Novel Punch Technique for Facial Pigmented Melanocytic Nevus.

The punch tool is a swift and practical instrument in the facial pigmented melanocytic nevus. However, few studies have evaluated the efficacy of the method for facial pigmented nevus. The aim of this study was to evaluate the practicability and effectiveness of removing facial pigmented nevus by punch biopsy technique. This was an observational study of patients with facial pigmented nevus in the Hospital of Plastic Surgery, Weifang Medical University. The ages of patients ranged from 15 to 36 years (average, 25 y). The outcome evaluations included Vancouver Scar Scale (VSS) score, esthetic appearance, and patient satisfaction. Following standard procedures, preoperative surgical excision was performed with safety margins. Anatomopathologic analysis of the surgical specimen was used as the gold standard to evaluate the accuracy of diagnosis by punch biopsy. From January 2019 to January 2020, this punch technique was carried out on 96 patients (151 pigmented nevus) with 35 melanocytic nevus on the forehead, 39 on the cheek, 21 on the eyelid, and 45 on the nose, whereas 11 were on nasolabial folds. The diameters of pigmented nevus are 0.5 to 10 mm on the face. All patients were evaluated at a follow-up visit ranging from 6 to 20 months (average, 11±1.5 mo) and healed with no complication. The histopathological examinations of the skin lesions showed benign outcomes. The mean Vancouver Scar Scale were 1.1±0.4. Ideal cosmetic and functional outcomes were achieved in 94 patients (97.9%). All patients achieved complete satisfaction except 2 patients with partial satisfaction. No recurrences and complications were recorded. This study demonstrated that the punch technique is an effective method to remove facial pigmented melanocytic nevus with acceptable functional and esthetic outcomes without relapse.

Construction of Fusion Protein with Carbohydrate-Binding Module and Leaf-Branch Compost Cutinase to Enhance the Degradation Efficiency of Polyethylene Terephthalate.

Poly(ethylene terephthalate) (PET) is a manufactured plastic broadly available, whereas improper disposal of PET waste has become a serious burden on the environment. Leaf-branch compost cutinase (LCC) is one of the most powerful and promising PET hydrolases, and its mutant LCCICCG shows high catalytic activity and excellent thermal stability. However, low binding affinity with PET has been found to dramatically limit its further industrial application. Herein, TrCBM and CfCBM were rationally selected from the CAZy database to construct fusion proteins with LCCICCG, and mechanistic studies revealed that these two domains could bind with PET favorably via polar amino acids. The optimal temperatures of LCCICCG-TrCBM and CfCBM-LCCICCG were measured to be 70 and 80 °C, respectively. Moreover, these two fusion proteins exhibited favorable thermal stability, maintaining 53.1% and 48.8% of initial activity after the incubation at 90 °C for 300 min. Compared with LCCICCG, the binding affinity of LCCICCG-TrCBM and CfCBM-LCCICCG for PET has been improved by 1.4- and 1.3-fold, respectively, and meanwhile their degradation efficiency on PET films was enhanced by 3.7% and 24.2%. Overall, this study demonstrated that the strategy of constructing fusion proteins is practical and prospective to facilitate the enzymatic PET degradation ability.

[Developments in Research on Salivary Biomarkers in the Diagnosis of Systemic Diseases].

Saliva, an important biological fluid secreted by oral glands, serves multiple functions. It performs cleaning and protective functions for oral tissues, safeguarding against biological, mechanical and chemical stimuli, while allowing for the sensory perception of taste and temperature. It is also responsible for the preliminary digestion of food. These functions and properties of saliva are attributed to the presence of electrolytes, buffers, proteins, glycoproteins, and lipids in saliva. Recent studies have found that saliva contains biomarkers that are closely connected with the pathophysiological status of the human body, suggesting that saliva makes an ideal biological fluid for drug monitoring and biomarker screening. Therefore, salivary biomarkers can be used as an instrument for physical monitoring and localization of the occurrence of diseases, thereby accomplishing early diagnosis of diseases and assessment of the overall health status of patients. However, the actual application of salivary biomarkers in the diagnosis and treatment of systemic diseases is still not widely available, and the establishment of evaluation criteria and the exploration of its mechanism are not sufficiently investigated. Herein, we reviewed the latest research findings on applying the salivary biomarkers in the diagnosis of systemic diseases.

HiVTac: A High-Speed Vision-Based Tactile Sensor for Precise and Real-Time Force Reconstruction with Fewer Markers.

Although they have been under development for years and are attracting a lot of attention, vision-based tactile sensors still have common defects-the use of such devices to infer the direction of external forces is poorly investigated, and the operating frequency is too low for them to be applied in practical scenarios. Moreover, discussion of the deformation of elastomers used in vision-based tactile sensors remains insufficient. This research focuses on analyzing the deformation of a thin elastic layer on a vision-based tactile sensor by establishing a simplified deformation model, which is cross-validated using the finite element method. Further, this model suggests a reduction in the number of markers required by a vision-based tactile sensor. In subsequent testing, a prototype HiVTac is fabricated, and it demonstrates superior accuracy to its vision-based tactile sensor counterparts in reconstructing an external force. The average error of inferring the direction of external force is 0.32∘, and the root mean squared error of inferring the magnitude of the external force is 0.0098 N. The prototype was capable of working at a sampling rate of 100 Hz and a processing frequency of 1.3 kHz, even on a general PC, allowing for real-time reconstructions of not only the direction but also the magnitude of an external force.

Sorafenib-Loaded PLGA-TPGS Nanosystems Enhance Hepatocellular Carcinoma Therapy Through Reversing P-Glycoprotein-Mediated Multidrug Resistance.

Multidrug resistance (MDR) is a key determinant for hepatocellular carcinoma chemotherapy failure. P-glycoprotein is one of the main causes of MDR by causing drug efflux in tumor cells. In order to solve this thorny problem, we prepared a sorafenib-loaded polylactic acid-glycolic acid (PLGA) - D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (SPTNs). SPTNs were successfully synthesized through an ultrasonic emulsion solvent evaporation method with a favourable encapsulation efficiency of 90.35%. SPTNs were almost spherical in shape with uniform particle size (215.70 ± 0.36 nm), narrow polydispersity index (0.27 ± 0.02) and negative surface charge (-26.01 ± 0.65 mV). In the cellular uptake assay, the intracellular coumarin-6 (C6) fluorescence of TPGS component-based PLGA nanoparticles (C6-PTNs) was 1.63-fold higher relative to that of PVA component-based PLGA nanoparticles (C6-PVNs). The half-maximal inhibitory concentration and apoptosis ratio of SPTNs against HepG2/MDR cells were 3.90 µM and 75.62%, respectively, which were notably higher than free SF and sorafenib-PLGA-PVA nanoparticles (SPVNs). The anti-drug efflux activities of SPTNs were assessed by the intracellular trafficking assay using verapamil as a P-gp inhibitor. SPTNs could effectively inhibit the drug efflux in tumor cells detected by flow cytometry, and suppressed relative MDR1 gene as well as P-glycoprotein expression in tumor cells. Attributed to the MDR reversion effect of SPTNs, the in vivo antitumor efficacy experiment showed that SPTNs significantly inhibited the tumor growth of HepG2/MDR xenograft-bearing nude mice, and obviously reduced the toxicity against liver and kidney compared with SF treatment. In summary, SPTNs, as highly efficient and safe antitumor nano delivery systems, showed promising potential for hepatocellular carcinoma therapy through reversing P-glycoprotein-mediated MDR. Graphical Abstract.

[Latest Research Findings on Health Management Based on Saliva Testing].

Being one of the most important exocrine fluids of the human body, saliva can reflect the health status of the body. Soliva collection has various advantages--it is simple, painless, fast, and safe, and soliva can be collected multiple times a day. Therefore, it has been gradually applied in the exploration for biomarkers for disease detection, providing a basis for the monitoring of the course of diseases, medication monitoring, and efficacy evaluation. We should implement health management based on saliva testing, collect the medical data of the healthy and diseased individuals and monitor their whole life cycle health, perform clinical cohort study, aggregate the data on platforms for big data on health and medicine, manage and provide guidance for the health status of populations, pinpoint the high-risk factors for pathogenesis, and provide effective intervention, early warning, and assessment of the vital signs of individuals, thereby reinforcing health management of the whole life cycle and safeguarding people's health in an all-round way. In addition, it drives the development of the health industry and bears strategic significance for the promotion of national economic development. It is becoming a hot research topic promising great potential and impressive applicational prospects. Herein, we reviewed new techniques for clinical saliva testing and health management based on saliva testing.

Pueraria flavones-loaded bile salt liposomes with improved intestinal absorption and oral bioavailability: in vitro and in vivo evaluation.

Pueraria flavone (PF), the main component of Pueraria lobata, is a traditional Chinese medicine used for the treatment of cardiovascular and cerebrovascular diseases; however, it exhibits low oral bioavailability because of its poor membrane permeability. In this study, PF-loaded sodium deoxycholate-decorated liposomes (SDC-Lips) were prepared using the reverse-phase evaporation method and optimised using the Box-Behnken design method. The morphology, particle size, zeta potential, and entrapment efficiency of these PF-loaded SDC-Lips were evaluated. The release behaviours of PF-loaded SDC-Lips in simulated gastric and intestinal fluids were consistent with the Weibull kinetic model. In situ intestinal perfusion studies showed that the absorption characteristics of free PF in rats were mainly passive diffusion and partly active transport, and the duodenum was the main absorption site. After encapsulated with SDC-Lips, the absorption of PF increased significantly. The in vivo pharmacokinetic parameters of area under the plasma concentration-time curve (AUC)(0 → 12 h) and AUC(0 → ∞) of PF-loaded SDC-Lips after intragastric administration were 1.34-fold and 1.543-fold, respectively. Overall, the PF-loaded SDC-Lips improved the oral absorption of PF by increasing its solubility and might be considered a promising formulation strategy for prolonging the biological activity time of PF.

Analysis of by high-throughput sequencing: Helicobacter pylori infection and salivary microbiome.

BACKGROUND: There have been reports of Helicobacter pylori (H. pylori) in the oral cavity and it has been suggested that the oral cavity may be a reservoir for H. pylori reflux from the stomach. High-throughput sequencing was used to assess the structure and composition of oral microbiota communities in individuals with or without confirmed H. pylori infection. METHODS: Saliva samples were obtained from 34 H. pylori infected and 24 H. pylori uninfected subjects. Bacterial genomic DNA was extracted and examined by sequencing by amplification of the 16S rDNA V3-V4 hypervariable regions followed by bioinformatics analysis. Saliva sampling was repeated from 22 of the 34 H. pylori infected subjects 2 months after H. pylori eradication. RESULTS: High-quality sequences (2,812,659) clustered into 95,812 operational taxonomic units (OTUs; 97% identity). H. pylori was detected in the oral cavity in infected (12/34), uninfected (11/24) and eradicated (15/22) subjects by technique of high-throughput sequencing, occupying 0.0139% of the total sequences. Alpha diversity of H. pylori infected subjects was similar to that of uninfected subjects (Shannon: 1417.58 vs. 1393.60, p > 0.05, ACE: 1491.22 vs. 1465.97, p > 0.05, Chao 1: 1417.58 vs. 1393.60, p > 0.05, t-test). Eradication treatment decreased salivary bacterial diversity (Shannon, p = 0.015, ACE, p = 0.003, Chao 1, p = 0.002, t-test). Beta diversity analysis based on unweighted UniFrac distances showed that the salivary microbial community structure differed between H. pylori infected and uninfected subjects (PERMANOVAR, pseudo-F: 1.49, p = 0.033), as well as before and after H. pylori eradication (PERMANOVAR, pseudo-F: 3.34, p = 0.001). Using LEfSe analysis, 16 differentially abundant genera were defined between infected and uninfected subjects, 12 of which had a further alteration after successful eradication. CONCLUSIONS: Our study using high-throughput sequencing showed that H. pylori was present commonly in the oral cavity with no clear relation to H. pylori infection of the stomach. Both H. pylori infection and eradication therapy caused alterations in community and structure of the oral microbiota. TRIAL REGISTRATION: clinicaltrials.gov, NCT03730766. Registered 2 Nov 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/ NCT03730766.

Isolation and characterization of cells derived from human epithelial rests of Malassez.

The epithelial rests of Malassez (ERMs) might represent a valuable source of oral epithelial cells with stem cell properties. The purpose of this study was to isolate and characterize cells derived from human ERM, and compare them with cells derived from matched normal oral mucosa (NOM). Matched tissue specimens of the periodontal ligament of extracted tooth and NOM were collected. Cells were isolated in culture, then characterized by immunohistochemistry and flow cytometry for expression of pancytokeratin, ESA, PDGFRB, CD31 and CD44. 3D organotypic cultures were constructed by growing epithelial cells on top of fibroblast-populated collagen gels. Both ERM and NOM-isolated cells expressed the markers of epithelial lineage (ESA and pancytokeratin), and to some extent PDGFR, an indicator of a more mesenchymal phenotype, but not the endothelial cell marker CD31. Cells with epithelial morphology were isolated from periodontium of cervical, middle and apical parts of the root, but contained a significantly lower percentage of ESA and pancytokeratin-positive cells than when isolating cells from NOM (p < 0.001). ERM cells expressed a significantly higher percentage of the stem cell-related molecule CD44 (cervical 92.93 ± 0.25%, middle 93.8 ± 0.26%, apical 94.36 ± 0.41%) than cells isolated from NOM (27.8 ± 1.47%, p < 0.001). When grown in 3D organotypic cultures and in collagen gels, ERM cells formed a less differentiated epithelium than NOM cells, but expressing pancytokeratin and vimentin. In conclusion, epithelial cells could be isolated from human periodontium and grown in culture; their in vitro characterization indicates that they have a less differentiated phenotype compared with cells derived from normal oral epithelium.

Prevalence of dentin hypersensitivity among the residents of Xi'an city, China.

OBJECTIVE: To investigate the prevalence and intra-oral distribution of dentine hypersensitivity (DH) and to evaluate the related risk factors. MATERIAL AND METHODS: A total of 1320 subjects, aged between 20 and 69 years old, were selected from six communities in the urban areas of Xi'an, China. The data were collected by conducting individual interviews using a standard questionnaire; then, the clinical examination was performed for patients who reported about the discomforts they felt in their teeth when subjected to chemical, mechanical and thermal stimuli. Dentine hypersensitivity (DH) was diagnosed by a subject short, sharp pain in response to a blast of cold air from a triple syringe. RESULTS: While replying to the questionnaire, 445 subjects reported about signs of discomfort in the teeth. DH was diagnosed in 336 persons by clinic examination. Thus, the overall prevalence of DH was 33.7% in the questionnaire and 25.5% in the intraoral test. The prevalence of DH was higher in females (33.8%) than in males (22.2%). Furthermore, we found that the prevalence of DH was highest in the age group of 50-59 years (39.3%). The most common initiation factors were acid (37.7%) followed by cold stimuli (35.8%). In general, most subjects with sensitive teeth had a higher educational background. CONCLUSIONS: The prevalence of DH was 25.5% in the population of Xi'an City in China. More emphasis should give to middle-aged and old females while planning oral health intervention campaigns. In addition, premolars and cervical surfaces should be examined for the prevention of DH.

A Comparison between splenic fossa and subhepatic fossa auxiliary partial heterotopic liver transplantation in a porcine model.

To test the alternative possible locations for the placement of a liver graft and the relevant surgical technique issues, we developed a porcine model of auxiliary partial heterotopic liver transplantation (APHLT) and evaluated the difference between 2 styles of liver transplantation, either subhepatic fossa or splenic fossa APHLT, by comparing survival and biochemical indexes. Thirty-eight miniature pigs were randomly divided into 2 groups. A left hemihepatic graft without the middle hepatic vein (HV) was procured from the living donor. In group A (n = 9), an 8 mm diameter polytetrafluoroethylene (PTFE) graft approximately 2.5 cm long was connected to the left HV while another PTFE graft of the same size was connected to the left portal vein (PV). The liver graft was implanted in the right subhepatic fossa following splenectomy and right nephrectomy. In group B (n = 10), a PTFE graft of the same size was connected to the left HV while the liver graft was implanted in the splenic fossa following splenectomy and left nephrectomy. Survival rate and complications were observed at 2 weeks after transplantation. Data were collected from 5 animals in group A and 6 animals in group B that survived longer than 2 weeks. The liver function and renal function of the recipients returned to normal at 1 week after surgery in both groups. Eighty-eight percent (14/16) of the PTFE grafts remained patent at 2 weeks after surgery, but 44% of the PTFE grafts (7/16) developed mural thrombus. No significant differences in the survival rate and biochemistry were found between the 2 groups. In conclusion, the splenic fossa APHLT can achieve beneficial outcomes similar to the subhepatic fossa APHLT in miniature pigs, although it also has a high morbidity rate due to hepatic artery thrombosis, PV thrombosis, and PTEF graft mural thrombus formation. Liver Transplantation 22 812-821 2016 AASLD.

The effect of carbon nanotubes and titanium dioxide incorporated in PDMS on biofilm community composition and subsequent mussel plantigrade settlement.

This study investigated the effect of carbon nanotubes (CNTs) and titanium dioxide (TiO2) incorporated in PDMS on biofilm formation and plantigrade settlement of Mytilus coruscus. TiO2 increased bacterial density, and CNTs also increased bacterial density but reduced diatom density in biofilms after 28 days. Further analysis was conducted between bacterial communities on glass, PDMS, CNTs (0.5 wt%) and TiO2 (7.5 wt%). ANOSIM analysis revealed significant differences (R > 0.9) between seven, 14, 21 and 28 day-old bacterial communities. MiSeq sequencing showed that CNTs and TiO2 impacted the composition of 28 day-old bacterial communities by increasing the abundance of Proteobacteria and decreasing the abundance of Bacteroidetes. The maximum decreased settlement rate in 28 day-old biofilms on CNTs and TiO2 was > 50% in comparison to those on glass and PDMS. Thus, CNTs and TiO2 incorporated in PDMS altered the biomass and community composition of biofilms, and subsequently decreased mussel settlement.

Efficacy of dexmedetomidine on postoperative shivering: a meta-analysis of clinical trials.

PURPOSE: Shivering is a frequent complication in the postoperative period. The aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on postoperative shivering. METHODS: Two researchers independently searched PubMed, EMBASE and the Cochrane Central Register of Controlled Trials for controlled clinical trials. The meta-analysis was performed by Review Manager. RESULTS: Thirty-nine trials with 2,478 patients were included in this meta-analysis. Dexmedetomidine reduced postoperative shivering compared with placebo (risk ratio [RR] = 0.26; 95% confidence interval [CI]: 0.20 to 0.34), with a minimum effective dose of 0.5 µg·kg(-1) (RR = 0.36; 95% CI: 0.21 to 0.60). The anti-shivering effect can be achieved both intravenously and epidurally when administered within two hours prior to the end of surgery. The efficacy of dexmedetomidine was similar to widely used anti-shivering agents, such as fentanyl, meperidine, tramadol, clonidine and so on; however, dexmedetomidine may increase the incidence of sedation, hypotension, bradycardia and dry mouth. CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows superiority over placebo, but not over other anti-shivering agents. Therefore, considering its high price and potential adverse events, dexmedetomidine may not be appropriate solely for the purpose of the prevention of postoperative shivering.

Ribonuclease A-polymer conjugates via in situ growth for cancer treatment.

Efficient delivery of therapeutic proteins is a critical aspect for protein-based cancer treatment. Herein, an in situ growth approach was employed to prepare ribonuclease A (RNase A)-polymer conjugates by incorporating a cationic polymer, poly(N,N'-dimethylamino-2-ethyl methacrylate) (P(DMAEMA)), and a hydrophobic polymer, poly(N-isopropylacrylamide) (P(NIPAM)), through atom transfer radical polymerization (ATRP). The synthesized RNase A-polymer conjugates (namely R-P(D-b-N)) could preserve the integrity of RNase A and exhibit a unique combination of cationic and hydrophobic properties, leading to enhanced intracellular delivery efficiency. The successful delivery of RNase A by R-P(D-b-N) conjugates effectively triggered the cell apoptosis through the mitochondria-dependent signaling pathway to achieve the anti-proliferative response. Additionally, the conjugates could inhibit cell migration and thus possess the potential for the suppression of tumor metastasis. Overall, our findings highlight that the introduction of cationic and hydrophobic moieties via ATRP provides a versatile platform for the intracellular delivery of therapeutic proteins, offering a new avenue for treating diverse diseases.

3D monitoring of the microphase separations inside the intraocular lens.

Glistenings often occur after implanting the intraocular lens (IOL) due to the formation of numerous microvacuoles (MVs) and may lead to deterioration of vision quality. Previous studies showed the formation of MVs was associated with the hydrophobicity of IOL materials. Yet, the mechanism remains an open question due to the complexity of IOL polymer networks. In this study, two commercialized IOLs with similar hydrophobicity are found distinct in the formation of MVs. The 3D growth kinetics of MVs during cooling processes are captured for the first time by digital holographic microscopy (DHM) and the components of MVs are measured by DHM and Raman spectroscopy. The results reveal that the growth of MVs stems from the microphase separation of water and surrounding IOL polymers. A polymer swelling model is thus proposed to describe the microphase separation process which is found dependent on the elasticity of IOL polymer networks. The total volume of MVs is determined by the IOL hydrophobicity, while the elastic force of IOL polymer networks determines the number density and size of MVs. This study demonstrates an approach for characterizing the phase separation of crosslinked polymeric materials in biosystems and sheds lights on the refinement of IOL materials. STATEMENT OF SIGNIFICANCE: Glistenings due to the formation of numerous microvacuoles (MVs) in intraocular lens (IOL) can occur after IOL implantation, which may induce poor quality of vision. However, the underlying mechanism of MVs formation is still an open question. This study establishes an in-situ 3D imaging platform to monitor growth kinetics of the MVs in IOLs, which allows to uncover the mechanism of glistenings formation resulting from the microphase separation. The findings imply the material hydrophobicity influences the total volume of MVs, while the local elasticity of IOL polymer networks determines the number density and the size of MVs. This study offers a new approach for characterizing phase separation in crosslinking biosystems and sheds lights on the refinement of IOL materials.

Cryo-Shocked Platelet Coupled with ROS-Responsive Nanomedicine for Targeted Treatment of Thromboembolic Disease.

Thrombolysis with tissue plasminogen activator (tPA) provides the most common therapy for ischemic stroke onset within the past 4.5 h. However, enhanced neutrophil infiltration and secondary blood-brain barrier injury caused by tPA administration have limited its therapeutic application, and tPA treatment is often accompanied by hemorrhagic transformation. To overcome the limitations of thrombolysis by tPA, maximize the therapeutic efficacy, and improve the safety, herein, we report a cryo-shocked platelet-based cell-hitchhiking drug delivery system, which consists of cryo-shocked platelet (CsPLT) and reactive oxygen species (ROS)-responsive liposomes loaded with thrombolytic tPA and anti-inflammation drug aspirin (ASA). CsPLT and liposomes were facilely conjugated via host-guest interactions. Under the guidance of CsPLT, it selectively accumulated in the thrombus site and quickly released the therapeutic payloads in response to the high ROS. tPA subsequently exhibited localized thrombolytic activity to suppress the expansion of thrombus, while ASA assisted in the inactivation of reactive astrogliosis, microglial/macrophage, and obstruction of neutrophil infiltration. This cryo-shocked platelet-hitchhiking tPA/ASA delivery system not only improves the thrombus-targeting efficiency of the two drugs for highly localized thrombolytic effects and anti-inflammation actions and platelets inactivation but also provides insights to the development of targeted drug delivery systems for thromboembolic disease treatment.

Analysis of Tongue Muscle Strain During Speech From Multimodal Magnetic Resonance Imaging.

PURPOSE: Muscle groups within the tongue in healthy and diseased populations show different behaviors during speech. Visualizing and quantifying strain patterns of these muscle groups during tongue motion can provide insights into tongue motor control and adaptive behaviors of a patient. METHOD: We present a pipeline to estimate the strain along the muscle fiber directions in the deforming tongue during speech production. A deep convolutional network estimates the crossing muscle fiber directions in the tongue using diffusion-weighted magnetic resonance imaging (MRI) data acquired at rest. A phase-based registration algorithm is used to estimate motion of the tongue muscles from tagged MRI acquired during speech. After transforming both muscle fiber directions and motion fields into a common atlas space, strain tensors are computed and projected onto the muscle fiber directions, forming so-called strains in the line of actions (SLAs) throughout the tongue. SLAs are then averaged over individual muscles that have been manually labeled in the atlas space using high-resolution T2-weighted MRI. Data were acquired, and this pipeline was run on a cohort of eight healthy controls and two glossectomy patients. RESULTS: The crossing muscle fibers reconstructed by the deep network show orthogonal patterns. The strain analysis results demonstrate consistency of muscle behaviors among some healthy controls during speech production. The patients show irregular muscle patterns, and their tongue muscles tend to show more extension than the healthy controls. CONCLUSIONS: The study showed visual evidence of correlation between two muscle groups during speech production. Patients tend to have different strain patterns compared to the controls. Analysis of variations in muscle strains can potentially help develop treatment strategies in oral diseases. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21957011.

PEG and ABA trigger methyl jasmonate accumulation to induce the MEP pathway and increase tanshinone production in Salvia miltiorrhiza hairy roots.

Tanshinones, a group of active ingredients in Salvia miltiorrhiza, are derived from at least two biosynthetic pathways, which are the mevalonate (MVA) pathway in the cytosol and the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway in the plastids. Abscisic acid (ABA) and methyl jasmonate (MJ) are two well-known plant hormones induced by water stress. In this study, effects of polyethylene glycol (PEG), ABA and MJ on tanshinone production in S. miltiorrhiza hairy roots were investigated, and the role of MJ in PEG- and ABA-induced tanshinone production was further elucidated. The results showed that tanshinone production was significantly enhanced by treatments with PEG, ABA and MJ. The mRNA levels of 3-hydroxy-3-methylglutaryl co-enzyme A reductase (HMGR), 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) and 1-deoxy-d-xylulose 5-phosphate synthase (DXS), as well as the enzyme activities of HMGR and DXS were stimulated by all three treatments. PEG and ABA triggered MJ accumulation. Effects of PEG and ABA on tanshinone production were completely abolished by the ABA biosynthesis inhibitor [tungstate (TUN)] and the MJ biosynthesis inhibitor [ibuprofen (IBU)], while effects of MJ were almost unaffected by TUN. In addition, MJ-induced tanshinone production was completely abolished by the MEP pathway inhibitor [fosmidomycin (FOS)], but was just partially arrested by the MVA pathway inhibitor [mevinolin (MEV)]. In conclusion, a signal transduction model was proposed that exogenous applications of PEG and ABA triggered endogenous MJ accumulation by activating ABA signaling pathway to stimulate tanshinone production, while exogenous MJ could directly induce tanshinone production mainly via the MEP pathway in S. miltiorrhiza hairy roots.

Clinicopathologic features and molecular analysis of enterovirus 71 infection: report of an autopsy case from the epidemic of hand, foot and mouth disease in China.

A 15-month boy with fatal hand, foot, and mouth disease (HFMD) exhibited atypical symptoms and progressed rapidly to death. An autopsy was performed the next day and tissue sections were stained for histopathological examination. His intestinal samples were tested for enterovirus 71 (EV71), and the whole-genome sequence of EV71 was analyzed. An autopsy revealed that the central nervous system, lungs, and gut displayed severe meningitis and brainstem encephalitis, remarkable pulmonary congestion, edema, moderate inflammatory infiltration, and hemorrhage as well as intestinal mucosal congestion, epithelial necrosis, thinning intestinal wall, and submucosal lymphoid follicular hyperplasia. The heart showed myocardial interstitial congestion, myocardial edema, and some inflammatory infiltrates. There were no significant alterations in the architecture of other organs. EV71 antigen and apoptotic cells were detected in brain, lung and intestine by immunohistochemical staining and TUNEL (TdT-mediated dUTP nick-end labeling) respectively. Intestinal contents and intestinal autopsy samples of this case were positive for EV71, and the EV71 strain was classified as subgenogroup C4. In China, the severe forms of HFMD were mostly caused by EV71 subgenogroup C4 infection. Severe intestinal damages may relate to EV71 subgenogroup C4 infection. Thus, children with severe EV71 HFMD may have serious pathological changes in their central nervous system, lungs, and gut. Physicians should pay special attention to infants with atypical symptoms, particularly in EV71 epidemic areas for early diagnosis and treatment.