Ventriculoperitoneal Shunt Alone for Spontaneous Cerebrospinal Fluid Rhinorrhea as a Presenting Symptom of Hemi-hydranencephaly.

A 27-year-old female patient presented with chronic spontaneous cerebrospinal fluid (CSF) rhinorrhea. She had deformity and weakness on the left side since childhood. Imaging examinations demonstrated hemi-hydranencephaly with a nearly complete absence of the right cerebral hemisphere, which was replaced with a membranous sac filled with CSF. She was accompanied with a frontal midline tumor containing lipids. After ventriculoperitoneal shunt, the CSF rhinorrhea completely ceased and no direct repair of the CSF fistula was necessary. The ventriculoperitoneal shunt procedure changes the CSF flow dynamics and releases the intracranial pressure, which may be a simple and effective procedure for CSF rhinorrhea in hemi-hydranencephaly.

Association of cigarette smoking with oral bacterial microbiota and cardiometabolic health in Chinese adults.

The interplay among cigarette smoking status, oral microbiota, and cardiometabolic health is poorly understood. We aimed to examine the association of cigarette smoking status with oral microbiota and to assess the association of the identified microbial features with cardiometabolic risk factors in a Chinese population. This study included 587 participants within the Central China Cohort, including 111 smokers and 476 non-smokers, and their oral microbiota was profiled by 16S rRNA sequencing. Both oral microbial alpha- and beta-diversity were distinct between smokers and non-smokers (p < 0.05). With adjustment for sociodemographics, alcohol and tea drinking, tooth brushing frequency, and body mass index, the relative abundance of nine genera and 26 pathways, including the genus Megasphaera and two pathways involved in inositol degradation which have potentially adverse effects on cardiometabolic health, was significantly different between two groups (FDR q < 0.20). Multiple microbial features related to cigarette smoking were found to partly mediate the associations of cigarette smoking with serum triglycerides and C-reactive protein levels (p-mediation < 0.05). In conclusion, cigarette smoking status may have impacts on the oral microbial features, which may partially mediate the associations of cigarette smoking and cardiometabolic health.

Association of the number of natural teeth with dietary diversity and nutritional status in older adults: A cross-sectional study in China.

AIM: To investigate the association of the number of natural teeth with overall dietary diversity and nutritional status in a nationally representative study among older adults in China. MATERIALS AND METHODS: A cross-sectional analysis was conducted among community-dwelling adults aged 65 years or older from the Chinese Longitudinal Healthy Longevity Study. According to the self-reported number of natural teeth, participants were categorized into ≥20, 10-19, 1-9 natural teeth, and edentulous. Dietary diversity score (DDS) was constructed based on intake frequencies of 10 food groups assessed by a simplified food frequency questionnaire. The geriatric nutritional risk index was used to measure the malnutrition status (i.e., normal, mild malnutrition, and moderate-to-severe malnutrition) among a subgroup of participants. Linear and multinomial logistic regression models were used to examine the corresponding associations. RESULTS: Among 54,796 study participants, the mean (SD) age was 87.86 (11.45) years, 82.7% had poor dentition (<20 natural teeth), and 27.3% wore dentures. After multivariable adjustment, participants with poor dentition had lower DDSs (ßedentulous  = -0.39, 95% confidence interval [CI], -0.48, -0.30; ß1-9 teeth  = -0.46, 95% CI, -0.55, -0.37; ß10-19 teeth  = -0.36, 95% CI, -0.46, -0.26) than those with 20 natural teeth or more. For individual food items, edentulous, 1-9 and 10-19 natural teeth were associated with lower odds of regular intake of fresh fruits, fresh vegetables, meat, fish and aquatic products, eggs, legumes, preserved vegetables, tea, and garlic, but higher odds of regular intake of sugar and sweets. Among participants with poor dentition, individuals without dentures had lower intake frequencies of most food groups than those wearing dentures. In addition, poor dentition was related to lower odds of normal nutritional status (odds ratio = 0.49, 95% CI, 0.27, 0.89). CONCLUSIONS: Older adults with poor dentition had significantly lower dietary diversity and worse nutritional status. Future studies are warranted to identify effective interventions to improve the dietary quality and nutrition status among partially and fully edentulous individuals, including those with Stage IV periodontitis.

Exploration of the underlying comorbidity mechanism in psoriasis and periodontitis: a bioinformatics analysis.

BACKGROUND: Increasing evidence indicates that psoriasis (PSO) and periodontitis (PD) are likely to occur together, however, the underlying mechanism remains unclear. MATERIALS AND METHODS: The expression profiles of PSO (lesion vs non-lesion, GSE30999, GSE14905) and PD (affected vs unaffected gingival tissue, GSE16134, GSE10334) were downloaded from the GEO database. First, we investigated the common differentially expressed genes (DEGs) of PSO and PD. Then, GO and KEGG enrichment analysis, protein interaction network (PPI) construction, and hub gene identification analysis were carried out. Finally, GO and KEGG enrichment analysis, miRNA interaction analysis, and transcription factors (TFs) interaction analysis for hub genes were performed. RESULTS: Eighteen DEGs were identified for further analysis, including 15 up-regulated genes and 3 down-regulated genes. 9 hub genes were then identified via Cytohubba, including IL1B, CXCL1, CXCL8, MMP12, CCL18, SELL, CXCL13, FCGR3B, and SELE. Their functions are mainly enriched in two aspects: neutrophil chemotaxis and migration, chemokine activation and interaction. The enriched signaling pathways includes three categories: host defense, inflammation-related signaling pathways, and disease-related pathways. 9 common miRNAs based on experimental evidence and 10 common TFs were further identified in both PSO and PD. CONCLUSION: Our study revealed possible comorbidity mechanisms in PSO and PD from the perspective of bioinformatics tentatively. The data can present new insight for joint prevention and treatment of in PSO and PD, as well as provide data support for further prospective studies.

Comparison of three-dimensional maxillary growth across spheno-occipital synchondrosis maturation stages.

BACKGROUND: This study aimed to three-dimensionally compare the maxillary growth among the spheno-occipital synchondrosis (SOS) maturation stages in both genders. METHODS: This is a cross-sectional study of a retrospective type in which cone-beam computed tomography (CBCT) images of 500 patients aged 6 to 25 years (226 males and 274 females) were analyzed. The SOS was evaluated using the four-stage scoring system; completely open, partially fused, semi-fused, or completely fused. The SOS scoring and three-dimensional cephalometric measurements were analyzed by Invivo 6.0.3 software. Descriptive and analytical statistics were performed and a P-value < 0.05 was considered statistically significant. RESULTS: There was a statistically significant difference in maxillary measurements among SOS maturation stages in both genders (P < 0.05). The mean differences in the maxillary growth among the SOS maturation stages between SOS stages 2 and 3 were higher than those between stages 1and 2 and stages 3 and 4 for maxillary length and height in both genders. However, the mean difference in the maxillary width was higher between SOS stages 1 and 2 than those stages 2 and 3 and stages 3 and 4. On other hand, there may be lesser maxillary growth between SOS stages 3 and 4 for maxillary width, length (in males), and height. The growth curves showed high active growth of the maxilla as the SOS was still fusing (especially stage 2 and 3) than those of the fused (stage 4). Moreover, the acceleration of growth occurred earlier in females than males regarding chronological age but not for SOS maturation stages. CONCLUSIONS: The SOS maturation stages are valid and reliable maxillary skeletal maturation indicators for three-dimensional maxillary growth in both genders.

Efficient Atmospheric Transport of Microplastics over Asia and Adjacent Oceans.

We developed a regional atmospheric transport model for microplastics (MPs, 10 µm to 5 mm in size) over Asia and the adjacent Pacific and Indian oceans, accounting for MPs' size- and shape-dependent aerodynamics. The model was driven by tuned atmospheric emissions of MPs from the land and the ocean, and the simulations were evaluated against coastal (n = 19) and marine (n = 56) observations. Our tuned atmospheric emissions of MPs from Asia and the adjacent oceans were 310 Gg y-1 (1 Gg = 1 kton) and 60 Gg y-1, respectively. MP lines and fragments may be transported in the atmosphere >1000 km; MP pellets in our model mostly deposited near-source. We estimated that 1.4% of the MP mass emitted into the Asian atmosphere deposited into the oceans via atmospheric transport; the rest deposited over land. The resulting net atmospheric transported MP flux from Asia into the oceans was 3.9 Gg y-1, twice as large as a previous estimate for the riverine-transported MP flux from Asia into the oceans. The uncertainty of our simulated atmospheric MP budget was between factors of 3 and 7. Our work highlighted the impacts of the size and morphology on the aerodynamics of MPs and the importance of atmospheric transport in the source-to-sink relationship of global MP pollution.

The use of autogenous tooth bone graft powder in the treatment of osseous defects after impacted mandibular third molar extraction: a prospective split-mouth clinical pilot study.

BACKGROUND: Impaction of mandibular third molars (M3) is one of the most common diseases. Extraction of M3 usually exacerbates osseous defects at the distal aspect of the adjacent second molar (M2). BonMaker® ATB has been cited as a novel autogenous bone grafting material. The aim of this pilot study was to introduce a novel method for repairing the distal osseous defects of M2 after the surgical removal of M3 with autogenous tooth graft powder (ATGP). METHOD: A total of five patients were enrolled in this prospective split-mouth clinical pilot study. Four impacted wisdom teeth were extracted bilaterally from each patient with proximal alveolar bone loss ≥ 5 mm of M3. The ATGP was prepared chairside from two extracted one side third molars and randomly implanted in one of the M3 extraction sockets, and the other side was treated with a blank and considered the control site. Patients were followed up at 6 months. RESULTS: The five patients included three males and two females. Their ages ranged from 25 to 30 years, with a median of 27 years. Primary wound healing without complications was achieved in all the patients. There was a greater tendency for swelling of the cheeks and trismus to occur at the experimental site on the third postoperative day. Compared with the control site, the experimental site exhibited progressive bone filling and ossification in the sixth postoperative month. Moreover, the probing pocket depth of the experimental site was lower than that of the control site. CONCLUSION: The results of this study demonstrate that ATGP effectively and economically repairs distal osseous defects of M2. Further study is required to validate the effectiveness with a larger study population.

Comparison of spheno-occipital synchondrosis maturation stages with three-dimensional assessment of mandibular growth.

BACKGROUND: This study aimed to compare spheno-occipital synchondrosis (SOS) maturation stages with a three-dimensional assessment of mandibular growth. METHODS: This is a cross-sectional study of a retrospective type, in which cone-beam computed tomography (CBCT) images of 500 patients aged 6 to 25 years (226 males and 274 females) were analyzed. The SOS was evaluated using the four-stage scoring system; completely open, partially fused, semi-fused, or completely fused. The SOS scoring and three-dimensional cephalometric measurements were analyzed by Invivo 6.0.3 software. Descriptive and analytical statistics were performed, and a P-value < 0.05 was considered statistically significant. RESULTS: There was a statistically significant difference in mandibular measurements among SOS maturation stages in both sexes (P < 0.05). The skeletal growth increments of mandibular variables across the SOS stages had higher mean differences between SOS stages 2 and 3 than those between stages 1 and 2 and stages 3 and 4 in both sexes. The mandibular growth curves increased with chronological age (earlier in females) and SOS maturation stages (mostly in stages 1, 2, and 3 than stage 4). CONCLUSIONS: The SOS maturation stages are valid and reliable mandibular skeletal indicators as evaluated with three-dimensional cephalometric mandibular measurements. The findings of growth increments and constructed growth curves of mandibular growth might be helpful in diagnosis and treatment planning.

Evaluation of Spheno-occipital Synchondrosis Fusion in Chinese Population Using CBCT: A Cross-sectional Study.

AIM: This study sought to assess the fusion of spheno-occipital synchondrosis (SOS) in Chinese population using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This is a cross-sectional study in which data were randomly collected based on the pre-existing institutional records. Following selection criteria, the CBCT images of 500 patients aged 6-25 years (226 males and 274 females) were analyzed. Three-dimensional virtual models were oriented at a standardized position, then adjusted to the median sagittal plane (MSP) view. A four-stage scoring system was used; completely open, partially fused, semi-fused, or completely fused. The student's t-test, one-way ANOVA, Pearson correlation, and linear regression analysis were used and the significant level was set at ≤0.05. RESULTS: The mean age of closure of stages 1, 2, 3, and 4 were 7.44, 9.62, 12.94, and 19.03 years in females, and 8.79, 11.13, 14.82, and 20.18 years in males, respectively. There was significantly strong positive correlation between spheno-occipital fusion and age (female: r = 0.853, male: r = 0.879; p <0.001), with 1.47 ± 0.33 years earlier fusion in females. All inter- and intra-stages mean ages were statistically significant in both genders. The transition age model demonstrated a mean age (in years) between stages 1-2 (10.1), stages 2-3 (12.79), and stage 3-4 (17.93) for males, and stages 1-2 (8.96), stages 2-3 (11.45), and stage 3-4 (16.69) for females. CONCLUSIONS: The present findings of SOS stages of fusion in both genders could guide age estimation and assessment of normal skeletal growth patterns and active skeletal growth period in the Chinese population. CLINICAL SIGNIFICANCE: There is still controversy about the time to closure of the SOS because of population and assessment technique variations. This study could be used as a reference for the specific examined population during planning for dentofacial orthopedic and/or orthognathic surgery and dental implant prosthesis for both genders. Moreover, these finding may be useful for medical purposes.

Four-in-One Stimulus-Responsive Long-Lived Luminescent Systems Based on Pyrene-Doped Amorphous Polymers.

Materials exhibiting ultralong luminescent lifetime show promising applications in the fields of information encryption, sensing, and bioimaging. Herein, we present a low-cost and general strategy to achieve stimulus-responsive ultralong organic phosphorescence (UOP) based on pyrene chromophores doped into polymer matrices. The UOP of the resulted systems presents radiation-, concentration-, time-, and excitation-dependent characteristics. The UOP color can be turned from blue to red by changing the excitation wavelength or the concentration of chromophores. Experimental results prove that these characteristics are attributed to the consumption of triplet oxygen and the different aggregation states of chromophores in the polymer matrices. Finally, we demonstrate that these systems could be applied for multilevel information encryption. This work would promote further development of multi-responsive long-lived luminescent materials.

The exploration of neuraminidase inhibitory activity on Fallopia denticulata, an ethnic herb in China.

This study was designed to explore the bioactive ingredients in the extracts of Fallopia denticulata (C.C. Huang) Holub, a medicinal plant grown in China, which exhibits the best neuraminidase (NA) inhibition activity. Three fractions of ethyl acetate, ethanol, and water were tested on NA inhibition assay, and the best one was conducted by ultra-performance liquid chromatography-time-of-flight mass spectrometry in the negative and positive modes to analyze the metabolic components. The results revealed the identification of the following 21 compounds: 3 organic acids, 11 flavonoids, 1 coumarin, and 6 others, such as ß-daucosterol, gallic acid, and syringic acid, of which 12 compounds were discovered for the first time in F. denticulata. In addition, we used the molecular docking technique to support the anti-NA activity of each compound in the best extract. The results confirmed that the two better bioactive compounds were (-)-epicatechin gallate and (+)-catechin. Therefore, F. denticulata could be used as a potential material for new anti-influenza drugs.

A study on facial features of children with Williams syndrome in China based on three-dimensional anthropometric measurement technology.

To describe special facial features of children with Williams syndrome in China by using method of three-dimensional craniofacial anthropometry. Using three-dimensional stereo photogrammetric device, 14 craniofacial anthropometric measurements were performed and five indices were calculated in 52 children with Williams syndrome and 208 age and sex matched controls of Han Chinese ethnicity. Except intercanthal width, mouth breadth, morphological face height, nasal height-breadth index, nasal breadth-depth index, morphological ear index, the Williams syndrome group under 3 years old were smaller than the control group in the other 12 variables. Compared with the control group, the Williams syndrome group aged 3-5 years old had smaller biocular breadth, nasal length, nasorostral angle, bitragal breadth, ear width, morphological ear index and face depth. The Williams syndrome group aged above 6 years old had smaller biocular breadth, nasal breadth, bitragal breadth, ear width, ear length and face depth than the control group. The craniofacial variability index of the Williams syndrome group was greater than the control group. Greater variation was found among children with Williams syndrome than normal in China, specifically at eye, nose, ear and face shape, which demonstrate the usefulness of three-dimensional stereo photogrammetric analysis in supporting accurate diagnose of the patient with Williams syndrome.

The Effects of a Toothpaste Containing the Active Ingredients of Galla chinensis and Sodium Fluoride on Dentin Hypersensitivity and Sealing of Dentinal Tubules: An In Vitro Study and an Eight-Week Clinical Study in 98 Patients.

BACKGROUND This study aimed to evaluate the desensitizing effect of toothpaste containing the active ingredients of an extract of Galla chinensis, both in vitro and in patients with dentin hypersensitivity. MATERIAL AND METHODS Ninety-eight patients with dentin hypersensitivity were divided into two study groups and given toothpaste containing either the active ingredients of Galla chinensis extract and sodium fluoride, or a control toothpaste containing only sodium fluoride. Assessments included the tactile stimulation test and the Schiff cold air sensitivity scale, which were conducted at the baseline examination and after 4 and 8 weeks of dental brushing. Twenty-five intact human premolars from 24 patients with dentin hypersensitivity were prepared and randomly divided into four groups, the untreated baseline group, the study group, the positive control group, and the control group. After brushing with different toothpaste for 7 days, the effects on dentinal tubule sealing in each group was determined by scanning electron microscopy (SEM), and the degree of dentinal tubule plugging and diameter of the open dentinal tubules were calculated. RESULTS Toothpaste containing the active ingredients of Galla chinensis and sodium fluoride significantly reduced the degree of dentin hypersensitivity when compared with toothpaste containing sodium fluoride alone after 4 weeks and 8 weeks of use. Toothpaste containing the active ingredients of Galla chinensis significantly reduced the number and diameter of the open dentinal tubules. CONCLUSIONS Toothpaste that contained the active ingredients of Galla chinensis and sodium fluoride reduced the symptoms of dentin hypersensitivity by sealing the dentinal tubules.

Photothermal and fluorescent dual-mode assay based on the formation of polydopamine nanoparticles for accurate determination of organophosphate pesticides.

A photothermal and fluorescent dual-mode assay for sensitive organophosphate pesticides (Ops) determination is reported based on alkaline phosphatase (ALP)-inhibition-induced formation of polydopamine (PDA) nanoparticles. In the presence of ALP, ascorbic acid 2-phosphate (AAP) can be catalyzed to produce ascorbic acid (AA). AA can reduce MnO2 nanosheets, further inhibiting the oxidation of dopamine (DA). Ops as an inhibitor for ALP activity prevents the formation of AA and the reduction of MnO2 nanosheets. Eventually, the formation of PDA nanoparticles is promoted. The inhibitory effect of Ops on ALP activity causes obvious changes of photothermal signals and fluorescence signal at 495 nm. The detection limit (LOD) of dimethoate is 0.1 µM. The method displays excellent sensing capability for the dimethoate assay in real water with good recoveries of 99.4-107.6%. Graphical abstract A photothermal and fluorescent dual-mode biosensor for sensitive Ops detection was reported based on alkaline phosphatase (ALP)-inhibition-induced formation of polydopamine (PDA) nanoparticles. The dual-mode method significantly improved the accuracy and reliability of the results.

Surface plasmon resonance assay for exosomes based on aptamer recognition and polydopamine-functionalized gold nanoparticles for signal amplification.

A novel surface plasmon resonance (SPR) strategy is introduced for the specific determination of exosomes based on aptamer recognition and polydopamine-functionalized gold nanoparticle (Au@PDA NP)-assisted signal amplification. Exosomes derived from hepatic carcinoma SMMC-7721 were selected as the model target. SMMC-7721 exosomes can be specifically captured by the aptamer ZY-sls that was complementary to the DNA tetrahedron probes (DTPs), and then the CD63 aptamer-linked Au@PDA NPs recognized SMMC-7721 exosomes for signal amplification. The DTPs were modified on a Au film for preventing Au deposition on the surface during the introduction of HAuCl4, and PDA coated on the AuNPs was used to reduce HAuCl4 in situ without any reductant assistance. It results in a further enhanced SPR signal. The assay can clearly distinguish SMMC-7721 exosomes from others (HepG2 exosomes, Bel-7404 exosomes, L02 exosomes, MCF-7 exosomes, and SW480 exosomes, respectively). SMMC-7721 exosomes are specifically determined as low as 5.6 × 105 particles mL-1. The method has successfully achieved specific determination of SMMC-7721 exosomes even in 50% of human serum without any pretreatment. Graphical abstract A novel surface plasmon resonance (SPR) strategy was introduced for the specific determination of exosomes based on aptamer recognition and polydopamine functionalized gold nanoparticles (Au@PDA NPs). The SPR signal was improved using the Au@PDA NPs assisted amplification.

Point-of-Care Assay of Alkaline Phosphatase Enzymatic Activity Using a Thermometer or Temperature Discoloration Sticker as Readout.

Alkaline phosphatase (ALP) is a significant biomarker in clinical diagnostics, and the abnormal level of ALP enzyme in serum is closely related to various diseases such as bone or liver cancer, bone metastases, and extrahepatic biliary obstruction. Herein a simple and portable photothermal biosensor was developed for sensitive detection of ALP enzyme based on the formation of polydopamine (PDA) nanoparticles using a thermometer or temperature discoloration sticker as readout. A MnO2 nanosheet was first prepared using a novel one-pot strategy which was operationally simple and not overly time-consuming. Then dopamine (DA) was quickly polymerized into PDA nanoparticles in the presence of the MnO2 nanosheet. When the model analyte ALP was present, the substrate 2-phospho-l-ascorbic acid trisodium salt (AAP) was catalytically hydrolyzed into l-ascorbic acid (AA), resulting in the inhibition of the formation of the PDA nanoparticles owing to the fact that the MnO2 nanosheet was reduced to Mn2+ by the generated AA. Thus, a portable biosensor based on the photothermal properties of PDA nanoparticles for ALP enzyme detection was established with a detection limit as low as 0.1 U/L (thermometer) and 1 U/L (temperature discoloration sticker). In addition, it also showed excellent sensing performance for the ALP assay in human serum. Such a simple, label-free, cost-effective, and sensitive assay could exhibit real potential application for ALP detection and early diagnosis, especially in developing countries or remote regions.

Genome-wide DNA-methylation profiles in human bone marrow mesenchymal stem cells on titanium surfaces.

The characteristics of titanium (Ti) have been shown to influence dental implant fixation. Treatment of surfaces using the sandblasted, large-grit, acid-etched (SLA) method is widely used to provide effective osseointegration. However, the DNA methylation-associated mechanism by which SLA surface treatment affects osseointegration of human bone marrow mesenchymal stem cells (hBMSCs) remains elusive. Genome-wide methylation profiling of hBMSCs on SLA-treated and machined smooth Ti was performed using Illumina Infinium Methylation EPIC BeadChip at day 7 of osteogenic induction. In total, 2,846 CpG sites were differentially methylated in the SLA group compared with the machined group. Of these sites, 1,651 (covering 1,066 genes) were significantly hypermethylated and 1,195 (covering 775 genes) were significantly hypomethylated. Thirty significant enrichment pathways were observed, with Wnt signaling being the most significant. mRNA expression was identified by microarray and combined with DNA-methylation profiles. Thirty-seven genes displayed negative association between mRNA expression and DNA-methylation level, with the osteogenesis-related genes insulin-like growth factor 2 (IGF2) and carboxypeptidase X, M14 Family Member 2 (CPXM2) showing significant up-regulation and down-regulation, respectively. In summary, our results demonstrate differences between SLA-treated and machined surfaces in their effects on genome-wide DNA methylation and enrichment of osteogenic pathways in hBMSCs. We provide novel insights into genes and pathways affected by SLA treatment in hBMSCs at the molecular level.

Processive Degradation of Crystalline Cellulose by a Multimodular Endoglucanase via a Wirewalking Mode.

Processive hydrolysis of crystalline cellulose by cellulases is a critical step for lignocellulose deconstruction. The classic Trichoderma reesei exoglucanase TrCel7A, which has a closed active-site tunnel, starts each processive run by threading the tunnel with a cellulose chain. Loop regions are necessary for tunnel conformation, resulting in weak thermostability of fungal exoglucanases. However, endoglucanase CcCel9A, from the thermophilic bacterium Clostridium cellulosi, comprises a glycoside hydrolase (GH) family 9 module with an open cleft and five carbohydrate-binding modules (CBMs) and hydrolyzes crystalline cellulose processively. How CcCel9A and other similar GH9 enzymes bind to the smooth surface of crystalline cellulose to achieve processivity is still unknown. Our results demonstrate that the C-terminal CBM3b and three CBMX2s enhance productive adsorption to cellulose, while the CBM3c adjacent to the GH9 is tightly bound to 11 glucosyl units, thereby extending the catalytic cleft to 17 subsites, which facilitates decrystallization by forming a supramodular binding surface. In the open cleft, the strong interaction forces between substrate-binding subsites and glucosyl rings enable cleavage of the hydrogen bonds and extraction of a single cellulose chain. In addition, subsite -4 is capable of drawing the chain to its favored location. Cellotetraose is released from the open cleft as the initial product to achieve high processivity, which is further hydrolyzed to cellotriose, cellobiose and glucose by the catalytic cleft of the endoglucanase. On this basis, we propose a wirewalking mode for processive degradation of crystalline cellulose by an endoglucanase, which provides insights for rational design of industrial cellulases.

Discontinuous Versus In-Continuity Neck Dissection in Squamous Cell Carcinoma of the Tongue and Floor of the Mouth: Comparing the Rates of Locoregional Recurrence.

PURPOSE: To date, consensus has not been reached on which treatment modality, that is, in-continuity neck dissection or discontinuous neck dissection, is more appropriate for managing patients with squamous cell carcinoma (SCC) of the tongue and floor of the mouth. This study aimed to perform a meta-analysis to compare discontinuous neck dissection with in-continuity neck dissection as a treatment modality for SCC of the tongue and floor of the mouth. MATERIALS AND METHODS: The PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched for articles that compared discontinuous neck dissection with in-continuity neck dissection in SCC of the tongue and floor of the mouth until March 1, 2017. The predictor variable was whether discontinuous neck dissection or in-continuity neck dissection was performed in each group. The primary outcome variable was the incidence of locoregional recurrence. Two authors individually extracted the data and assessed the study quality. The meta-analysis was performed using Stata (version 13.0; StataCorp, College Station, TX). RESULTS: We included 8 studies with 796 patients in our meta-analysis. The results showed that in-continuity neck dissection had a statistically significantly lower incidence of locoregional recurrence than discontinuous neck dissection (random-effects model: relative risk, 0.459; 95% confidence interval, 0.240 to 0.877; P = .019). Because significant heterogeneity among studies (I2 = 74.5%, P < .001) was found in the heterogeneity evaluation, a separate analysis was performed. However, the results still showed that in-continuity neck dissection had a statistically significantly lower rate of locoregional recurrence than discontinuous neck dissection in patients with T2 and T3 SCC of the tongue and floor of the mouth (fixed-effects model: relative risk, 0.281; 95% confidence interval, 0.183 to 0.433; P < .001). CONCLUSIONS: Compared with discontinuous neck dissection, in-continuity neck dissection can significantly reduce the rate of locoregional recurrence in patients with SCC of the tongue and floor of the mouth.

Growth suppressive effect of pegylated arginase in malignant pleural mesothelioma xenografts.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a difficult-to-treat global disease. Pegylated arginase (BCT-100) has recently shown anti-tumor effects in hepatocellular carcinoma, acute myeloid leukemia and melanoma. This study aims to investigate the effects of PEG-BCT-100 in MPM. METHODS: A panel of 5 mesothelioma cell lines (H28, 211H, H226, H2052 and H2452) was used to study the in vitro effects of BCT-100 by crystal violet staining. The in vivo effects of BCT-100 were studied using 211H and H226 nude mice xenografts. Protein expression (argininosuccinate synthetase, ornithine transcarbamylase, cleaved PARP, cleaved caspase 3, cyclins (A2, D3, E1 and H), CDK4 and Ki67) and arginine concentration were evaluated by Western blot and ELISA respectively. Cellular localization of BCT-100 was detected by immunohistochemistry and immunoflorescence. TUNEL assay was used to identify cellular apoptotic events. RESULTS: Argininosuccinate synthetase was expressed in H28, H226, and H2452 cells as well as 211H and H266 xenografts. Ornithine transcarbamylase was undetectable in all cell lines and xenograft models. BCT-100 reduced in vitro cell viability (IC50 values at 13-24 mU/ml, 72 h) across different cell lines and suppressed tumor growth in both 211H and H226 xenograft models. BCT-100 (60 mg/kg) significantly suppressed tumor growth (p < 0.01) with prolonged median survival (p < 0.01) in both xenograft models. Combining BCT-100 with pemetrexed or cisplatin conferred no additional benefits over single agents. Serum and intratumoral arginine levels were effectively decreased by BCT-100, associated with cytosolic accumulation of BCT-100 within tumor cells. Apoptosis (PARP cleavage in 211H xenografts; Bcl-2 downregulation, and cleavage of PARP and caspase 3 in H226 xenografts; positive TUNEL staining in both) and G1 arrest (downregulation of cyclin A2, D3, E1 and CDK4 in 211H xenografts; suppression of cyclin A2, E1, H and CDK4 in H226 xenografts) were evident with BCT-100 treatment. Furthermore, proliferative factor Ki67 was downregulated in BCT-100 treatments arms. CONCLUSIONS: BCT-100 suppressed tumor growth with prolonged median survival partially mediated by intratumoral arginine depletion resulting in apoptosis and G1 arrest in mesothelioma xenograft models. The findings provide scientific evidence to support further clinical development of BCT-100 in treatment of MPM.