Sustained AhR activity programs memory fate of early effector CD8+ T cells.

Identification of mechanisms that program early effector T cells to either terminal effector T (Teff) or memory T (Tm) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early Teff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8+ Teff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8+ T cells up-regulate HIF-1α to compete with AhR for HIF-1ß, leading to the loss of AhR activity in HIF-1αhigh short-lived effector cells, but sustained in HIF-1αlow memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8+ MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how Teff cells are regulated to differentiate into memory cells.

Advancing MicroRNA Detection: Enhanced Biotin-Streptavidin Dual-Mode Phase Imaging Surface Plasmon Resonance Aptasensor.

MicroRNAs (miRNAs) are novel tumor biomarkers owing to their important physiological functions in cell communication and the progression of multiple diseases. Due to the small molecular weight, short sequence length, and low concentration levels of miRNA, miRNA detection presents substantial challenges, requiring the advancement of more refined and sensitive techniques. There is an urgent demand for the development of a rapid, user-friendly, and sensitive miRNA analysis method. Here, we developed an enhanced biotin-streptavidin dual-mode phase imaging surface plasmon resonance (PI-SPR) aptasensor for sensitive and rapid detection of miRNA. Initially, we evaluated the linear sensing range for miRNA detection across two distinct sensing modalities and investigated the physical factors that influence the sensing signal in the aptamer-miRNA interaction within the PI-SPR aptasensor. Then, an enhanced biotin-streptavidin amplification strategy was introduced in the PI-SPR aptasensor, which effectively reduced the nonspecific adsorption by 20% and improved the limit of detection by 548 times. Furthermore, we have produced three types of tumor marker chips, which utilize the rapid sensing mode (less than 2 min) of PI-SPR aptasensor to achieve simultaneous detection of multiple miRNA markers in the serum from clinical cancer patients. This work not only developed a new approach to detect miRNA in different application scenarios but also provided a new reference for the application of the biotin-streptavidin amplification system in the detection of other small biomolecules.

The effects of pterygomaxillary disjunction in surgically assisted rapid maxillary expansion: A systematic review and meta-analysis.

OBJECTIVE: This study aims to assess the expansive effects of pterygomaxillary disjunction (PMD) in surgically assisted rapid maxillary expansion (SARME) surgery using a meta-analysis approach. MATERIALS AND METHODS: The study conducted a comprehensive literature search across five databases: PubMed, Scopus, Medline, Embase, and Cochrane, adhering to the PRISMA 2020 guidelines. Dental alterations were assessed using either cone-beam computed tomography (CBCT) or dental casts, while skeletal changes were exclusively measured from CBCT scans. We analysed the dentoskeletal changes between PMD +/- groups and conducted a within-group comparison. The primary focus of the results was on the mean differences observed in pre- and post-operative measurements. RESULTS: Dental expansion was larger in the PMD+ group but not statistically significant. Skeletal expansion showed a significantly larger expansion in the posterior region in the PMD+ group (P = .033). Without PMD, anterior palatal expansion was significantly larger (P = .03), and the buccal tipping of posterior teeth was also significantly larger (P = .011) to achieve acceptable dental expansion outcomes. CONCLUSIONS: Both PMD +/- groups of SARME surgery can achieve satisfactory dental expansion outcomes. However, bone expansion and tooth inclination are also important factors that influence orthodontic treatment and post-expansion stability. By reducing the bony resistance with PMD, larger posterior palatal expansion and more parallel bony expansion are observed. In contrast, without PMD, there is smaller palatal expansion and greater tooth inclination in the posterior region. This could potentially lead to compromised periodontal conditions following expansion.

Alpha-Lipoic Acid Inhibits Spontaneous Diabetes and Autoimmune Recurrence in Non-Obese Diabetic Mice by Enhancing Differentiation of Regulatory T Cells and Showed Potential for Use in Cell Therapies for the Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is caused by the destruction of ß cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective treatment for T1D. However, the survival of islet grafts is often disrupted by recurrent autoimmunity. Alpha-lipoic acid (ALA) has been reported to have immunomodulatory effects and, therefore, may have therapeutic potential in the treatment of T1D. In this study, we investigated the therapeutic potential of ALA in autoimmunity inhibition. We treated non-obese diabetic (NOD) mice with spontaneous diabetes and islet-transplantation mice with ALA. The onset of diabetes was decreased and survival of the islet grafts was extended. The populations of Th1 cells decreased, and regulatory T cells (Tregs) increased in ALA-treated mice. The in vitro Treg differentiation was significantly increased by treatment with ALA. The adoptive transfer of ALA-differentiated Tregs into NOD recipients improved the outcome of the islet grafts. Our results showed that in vivo ALA treatment suppressed spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Tregs. Our study also demonstrated the therapeutic potential of ALA in Treg-based cell therapies and islet transplantation used in the treatment of T1D.

Association between socioeconomic status and severity of oral epithelial dysplasia using a Taiwanese Nationwide Oral Mucosal Screening Program: a retrospective analysis.

BACKGROUND: The study aimed to investigate the association between socioeconomic status and severity of oral epithelial dysplasia (OED) using current data from the Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). METHODS: This retrospective analysis was conducted in the Department of Oral and Maxillofacial Surgery at a general hospital in Taipei, Taiwan. A total of 134 participants were analysed from a previous study database of 150 patients. The inclusion criteria included age > 20 years and a history of either tobacco or betel nut use. Background information, including para-habits such as betel and tobacco use, was analysed using the Pearson chi-square (χ2) test; furthermore, the correlation of background information with OED severity was investigated using logistic regression (mild or moderate/severe). RESULTS: High school education level (P < 0.001), poor self-awareness (P = 0.002), current betel use (P < 0.001), and tobacco use (P = 0.003) were highly correlated with moderate- and severe OED (P < 0.05). The odds ratio (OR) of education status above senior high school was 0.03 (95% confidence interval [CI] 0.01-0.15, P < 0.001), while that of junior high school was 1. Current betel chewing (OR 6.57 [95% CI 1.17-37.0], P = 0.033) was significantly associated with OED severity compared with never or ex-use of betel. CONCLUSIONS: We found a strong correlation between the severity of OED and current betel use and low education status. The current study revealed that the socioeconomic status, poor self-awareness, and para-habit history of the patients with OED should be evaluated to identify high-risk individuals using TNOMSP.

Red nucleus IL-33 facilitates the early development of mononeuropathic pain in male rats by inducing TNF-α through activating ERK, p38 MAPK, and JAK2/STAT3.

BACKGROUND: Our recent studies have identified that the red nucleus (RN) dual-directionally modulates the development and maintenance of mononeuropathic pain through secreting proinflammatory and anti-inflammatory cytokines. Here, we further explored the action of red nucleus IL-33 in the early development of mononeuropathic pain. METHODS: In this study, male rats with spared nerve injury (SNI) were used as mononeuropathic pain model. Immunohistochemistry, Western blotting, and behavioral testing were used to assess the expressions, cellular distributions, and actions of red nucleus IL-33 and its related downstream signaling molecules. RESULTS: IL-33 and its receptor ST2 were constitutively expressed in the RN in naive rats. After SNI, both IL-33 and ST2 were upregulated significantly at 3 days and peaked at 1 week post-injury, especially in RN neurons, oligodendrocytes, and microglia. Blockade of red nucleus IL-33 with anti-IL-33 neutralizing antibody attenuated SNI-induced mononeuropathic pain, while intrarubral administration of exogenous IL-33 evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 generated an algesic effect in the early development of SNI-induced mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3, suppression of NF-κB, ERK, p38 MAPK, and JAK2/STAT3 with corresponding inhibitors markedly attenuated SNI-induced mononeuropathic pain or IL-33-evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 contributed to SNI-induced mononeuropathic pain by stimulating TNF-α expression, which could be abolished by administration of inhibitors against ERK, p38 MAPK, and JAK2/STAT3, but not NF-κB. CONCLUSIONS: These results suggest that red nucleus IL-33 facilitates the early development of mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3. IL-33 mediates algesic effect partly by inducing TNF-α through activating ERK, p38 MAPK and JAK2/STAT3.

CS1003, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer therapy.

The programmed cell death protein 1 (PD-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. PD-1 antibodies can block the interaction of PD-1 with its ligands (PD-L1 and PD-L2), restore T cells activation, and elicit antitumor activity. In this paper, we reported a novel PD-1 monoclonal antibody (mAb) CS1003, which is a humanized IgG4 PD-1 mAb generated by conventional hybridoma technology, and currently being developed in multiple clinical trials as monotherapy or in combination with other anticancer agents. We showed that CS1003 bound to recombinant human, cynomolgus monkey, and mouse PD-1 with EC50 values of 0.1757, 0.2459, and 0.3664 nM, respectively. CS1003 blocked PD-1 interaction with its ligands, dose-dependently enhanced T cell proliferation and secretion of cytokines (IL-2 and IFN-γ) to the levels comparable to the reference antibody pembrolizumab. Intraperitoneal administration of CS1003 (0.1, 0.5, 2.5 mg/kg, once every 3 days) dose-dependently suppressed the growth of MC38-hPD-L1 colon cancer in hPD-1 knock-in mice. Pharmacokinetics (PK) study revealed a linear PK profile within the dose range of 2-18 mg/kg following single intravenous administration in cynomolgus monkey. These data provide a comprehensive preclinical characterization of CS1003 that supports its clinical development for cancer immunotherapy.

Myocardial tissue-specific Dnmt1 knockout in rats protects against pathological injury induced by Adriamycin.

Novel molecular mechanisms of the pathophysiology of heart failure (HF) are continuously being discovered, including epigenetic regulation. Among epigenetic marks, the role of DNA hypomethylation in shaping heart morphology and function in vivo and the pathogenesis of cardiomyopathy and/or HF, especially in adults, has not been clearly established. Here we show that the strong expression of DNA methyltransferase 1 (Dnmt1) is obviously downregulated in the WT adult rat heart with age. By contrast, the expression of Dnmt1 is upregulated suddenly in heart tissues from pressure overload-induced HF mice and adriamycin-induced cardiac injury and HF mice, consistent with the increased expression of Dnmt1 observed in familial hypertrophic cardiomyopathy (FHCM) patients. To further assess the role of Dnmt1, we generated myocardium-specific Dnmt1 knockout (Dnmt1 KO) rats using CRISPR-Cas9 technology. Echocardiographic and histopathological examinations demonstrated that Dnmt1 deficiency is associated with resistance to cardiac pathological changes and protection at the global and organization levels in response to pathological stress. Furthermore, Dnmt1 deficiency in the myocardium restricts the expressional reprogramming of genes and activates pathways involved in myocardial protection and anti-apoptosis in response to pathological stress. Transcriptome and genome-wide DNA methylation analyses revealed that these changes in regulation are linked to alterations in the methylation status of genes due to Dnmt1 knockout. The present study is the first to investigate in vivo the impact of genome-wide cardiac DNA methyltransferase deficiency on physiological development and the pathological processes of heart tissues in response to stress. The exploration of the role of epigenetics in the development, modification, and prevention of cardiomyopathy and HF is in a very preliminary stage but has an infinite future.

Pretreatment body mass index as a prognostic predictor in patients with oral squamous cell carcinoma.

OBJECTIVES: To evaluate whether low body mass index (BMI) is a potential adverse prognostic factor in patients with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: This cross-sectional study included 320 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The pretreatment BMI was measured as a common indicator of the pretreatment nutritional status to calculate the overall survival in Kaplan-Meier method. The adverse histopathological features of margin status, depth of invasion (DOI), lymphovascular invasion (LVSI), perineural invasion (PNI), and extranodal extension (ENE) were analyzed using the Cox regression model. RESULTS: Low BMI (underweight), DOI > 5 mm, and ENE were identified as detrimental prognostic factors. On multivariate Cox regression analysis, the low BMI group (odds ratio [OR] = 1.683; 95% confidence interval [95% CI] 1.116-2.539; P = 0.022), DOI > 5 mm (OR = 2.399; 95% CI 1.459-3.943; P = 0.001), and ENE (OR = 2.467; 95% CI 1.540-3.951; P = 0.000) yielded reduced survival rate. CONCLUSIONS: The lower BMI had an important and significant effect on the survival of patients with oral cancer and their surgical outcomes. In addition to the adverse histopathological features, a DOI > 5 mm and positive ENE were also identified as the most important prognostic factors. CLINICAL RELEVANCE: Underweight patients with low BMI, DOI of > 5 mm, and positive ENE should receive more intensive nutritional supplementation and postoperative adjuvant therapy.

Adoptive transfer of DMSO-induced regulatory T cells exhibits a similar preventive effect compared to an in vivo DMSO treatment for chemical-induced experimental encapsulating peritoneal sclerosis in mice.

Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). This disease leads to intestinal obstruction with or without peritonitis. The imbalance between the populations of Th17 and regulatory T (Treg) cells (higher Th17 cells and lower Treg cells) is part of the pathogenesis of EPS formation. We demonstrated that dimethyl sulfoxide (DMSO) effectively inhibited autoimmune diabetes recurrence in the islet transplantation of NOD mice via the induction of the differentiation of Treg cells. In this study, we investigated the therapeutic potential of DMSO in the inhibition of EPS formation by a mouse model. Under DMSO treatment, the thickening of the parietal and visceral peritoneum was significantly reduced. The populations of CD4, CD8, and IFN-γ-producing CD4 and CD8 T cells were decreased. The populations of IL-4-producing CD4 T lymphocytes, IL-10-producing CD4 T lymphocytes, CD4 CD69 T lymphocytes and Treg lymphocytes were increased. The expression levels of the cytokines IFN-γ, IL-17a, TNF-α and IL-23, in ascites, were significantly decreased following the DMSO treatment. Furthermore, the differentiation of Treg cells was induced by DMSO from naïve CD4 T cells in vitro, and these cells were adoptively transferred into the EPS mice and significantly prevented EPS formation, exhibiting a comparable effect to the in vivo DMSO treatment. We also demonstrated that the differentiation of Treg cells by DMSO occurred via the activation of STAT5 by its epigenetic effect, without altering the PI3K-AKT-mTOR or Raf-ERK pathways. Our results demonstrated, for the first time, that in vivo DMSO treatment suppresses EPS formation in a mouse model. Furthermore, the adoptive transfer of Treg cells that were differentiated from naïve CD4 T cells by an in vitro DMSO treatment exhibited a similar effect to the in vivo DMSO treatment for the prevention of EPS formation.

Ultralow-voltage electrothermal MEMS based fiber-optic scanning probe for forward-viewing endoscopic OCT.

We report an ultralow-voltage, electrothermal (ET) micro-electro-mechanical system (MEMS) based probe for forward-viewing endoscopic optical coherence tomography (OCT) imaging. The fully assembled probe has a diameter of 5.5 mm and a length of 55 mm, including the imaging optics and a 40 mm long fiber-optic cantilever attached on a micro-platform of the bimorph ET MEMS actuator. The ET MEMS actuator provides a sufficient mechanical actuation force as well as a large vertical displacement, achieving up to a 3 mm optical scanning range with only a 3 VACp-p drive voltage with a 1.5 VDC offset. The imaging probe was integrated with a swept-source OCT system of a 100 kHz A-scan rate, and its performance was successfully demonstrated with cross-sectional imaging of biological tissues ex vivo and in vivo at a speed up to 200 frames per second.

Tolerance of lamb and mouse oocytes to cryoprotectants during vitrification.

SummaryMouse and lamb oocytes were vitrified with, or exposed to, different cryoprotectants and evaluated for their effects on their survival and developmental competence after in vitro fertilization (IVF) and activation treatments. Control oocytes remained untreated, whilst the remainder were exposed to three different combinations of vitrification solutions [dimethyl sulfoxide (DMSO) + ethylene glycol (EG), EG only, or propanediol (PROH) + EG] and either vitrified or left unfrozen (exposed groups). Oocytes in the control and vitrified groups underwent IVF and developmental competence was assessed to the blastocyst stage. In lambs, survival rate in vitrified oocytes was significantly lower than for oocytes in the exposed groups (P <0.05). Blastocyst development was low in vitrified oocytes compared with controls (<6% vs 38.9%, P <0.01). Parthenogenetic activation was more prevalent in vitrified lamb oocytes compared with controls (P <0.05). No evidence of zona pellucida hardening or cortical granule exocytosis could account for reduced fertilization rates in vitrified lamb oocytes. Mouse oocytes demonstrated a completely different response to lamb oocytes, with survival and parthenogenetic activation rates unaffected by the vitrification process. Treatment of mouse oocytes with DMSO + EG yielded significantly higher survival and cleavage rates than treatment with PROH + EG (87.8% and 51.7% vs 32.7% and 16.7% respectively, P <0.01), however cleavage rate for vitrified oocytes remained lower than for the controls (51.7% vs 91.7%, P <0.01) as did mean blastocyst cell number (33 ± 3.1 vs 42 ± 1.5, P <0.05). From this study, it is clear that lamb and mouse show different tolerances to cryoprotectants commonly used in vitrification procedures, and careful selection and testing of species-compatible cryoprotectants is required when vitrifying oocytes to optimize survival and embryo development.

Mouth-opening device as a treatment modality in trismus patients with head and neck cancer and oral submucous fibrosis: a prospective study.

OBJECTIVES: This study investigated the clinical effectiveness of intervention with an open-mouth exercise device designed to facilitate maximal interincisal opening (MIO) and improve quality of life in patients with head and neck (H&N) cancer and oral submucous fibrosis (OSF). MATERIALS AND METHODS: Sixty patients with H&N cancer, OSF, and trismus (MIO < 35 mm) participated in the functional rehabilitation program. An open-mouth exercise device intervention group and conventional group, each consisting of 20 patients, underwent a 12-week training and exercising program and follow-up. For the control group, an additional 20 patients were randomly selected to match the demographic characteristics of the aforementioned two groups. RESULTS: The patients' MIO improvements in the aforementioned three groups were 14.0, 10.5, and 1.3 mm, respectively. CONCLUSION: Results of this study confirm the significant improvement in average mouth-opening range. In addition, according to patient feedback, significant improvements in health-related quality of life and reductions in trismus symptoms occurred in the open-mouth exercise device group. CLINICAL RELEVANCE: This newly designed open-mouth exercise device can facilitate trismus patients with H&N cancer and OSF and improve mouth-opening range and quality of life.

Comparison of the hospitalization period after microvascular reconstruction flap in trismus patients: free anterolateral thigh flap versus free forearm flap.

OBJECTIVES: The primary strategy for treating oral squamous cell carcinoma (OSCC) is therapeutic resection, with the trismus resection defect reconstructed via free flap. The most popular free flaps include the radial forearm free flap (RFFF) and anterolateral thigh free flap (ALT). This study investigated the relationships between the hospitalization period and a variety of surgical outcomes, as well as maximum inter-incisor distance (IID), in trismus patients who chewed betel nuts. MATERIALS AND METHODS: Forty-nine primary OSCC patients who chewed betel nuts and underwent surgical resection and reconstruction between 2010 and 2016 were enrolled in this retrospective study. The data were from a single center in Taiwan. The outcome variable after flap recovery surgery was the duration of postoperative hospitalization. Other factors that were analyzed comprised correlations between hospitalization and a variety of factors, including postoperative inter-incisor distances (IIDs), operative time, gender, and WBC count, upon stratification into two reconstruction groups. RESULTS: The mean postoperative hospitalization duration in the ALT group was 22.9 ± 7.2 days, which was significantly shorter than that in the RFFF group (27.8 ± 7.0 days; p = 0.019). Two-week postoperative IID (ALT group: 16.1 ± 0.8 mm; RFFF group: 7.0 ± 0.6 mm) was inversely related to the duration of hospitalization (p = 0.022, r = - 0.372). CONCLUSIONS: The ALT flap is more effective than the RFFF flap to reduce the length of hospitalization in trismus patients. CLINICAL RELEVANCE: The ALT flap should be considered as a first-line technique in OSCC reconstruction in trismus patient reconstruction.

Comparative evaluation of autofluorescence imaging and histopathological investigation for oral potentially malignant disorders in Taiwan.

OBJECTIVES: Autofluorescence imaging is gaining popularity as an adjunctive test for oral potentially malignant disorders (OPMD). This study evaluated the efficacy of autofluorescence imaging based on the current standard oral mucosal disorder checklist in Taiwan. MATERIALS AND METHODS: In total, 126 patients suspected to have mucosal disorders at the Division of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei, Taiwan, were enrolled. Following a conventional oral examination by using the oral mucosal disorder checklist and an autofluorescence imaging examination, all participants underwent histopathological examination to access epithelial dysplasia. RESULTS: Among 126 patients, 68 patients were diagnosis as having an OPMD and 63 having epithelial dysplasia. Autofluorescence imaging exhibited a sensitivity, specificity, positivity predictive value (PPV), negative predictive value (NPV), and accuracy of 77.94%, 35.42%, 63.10%, 53.13%, and 60.34%, respectively, for OPMD and of 88.89%, 43.86%, 63.64%, 78.13%, and 67.50%, respectively, for epithelial dysplasia. After the exclusion of 48 non-OPMD cases according to the checklist, the sensitivity, specificity, PPV, NPV, and accuracy of autofluorescence imaging became 87.50%, 72.73%, 94.23%, 53.33%, and 85.07%, respectively, for epithelial dysplasia. CONCLUSION: The efficacy of epithelial dysplasia identification and OPMD risk assessment can be increased after the exclusion of the non-OPMD cases through autofluorescence imaging. CLINICAL RELEVANCE: Autofluorescence imaging is a useful adjunct that can assist specialists in assessing OPMD patients prone to dysplasia without compromising patient care.

Pinning-Depinning Mechanisms of the Contact Line during Evaporation of Microdroplets on Rough Surfaces: A Lattice Boltzmann Simulation.

In this study, pinning and depinning of the contact line during droplet evaporation on the rough surfaces with randomly distributed structures is theoretically analyzed and numerically investigated. A fast Fourier transformation (FFT) method is used to generate the rough surfaces, whose skewness ( Sk), kurtosis ( K), and root-mean-square ( Rq) are obtained from real surfaces. A thermal multiphase LB model is proposed to simulate the isothermal pinning and depinning processes. The evaporation processes are recorded with the variations in contact angle, contact radius, and drop shape. It is found that the drops sitting on rough surfaces show different behavior from those on smoother surfaces. The former shows a pinned contact line during almost the whole lifetime. By contrast, the latter experiences a stick-slip-jump behavior until the drop disappears. At mesoscopic scale, the pinning of the contact line is actually a slow motion rather than a complete immobilization at the sharp edges. The dynamic equilibrium is achieved by the self-adjustment of the contact line according to each edge.

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

OBJECTIVES: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. MATERIAL AND METHODS: We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. RESULTS: Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). CONCLUSIONS: Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. CLINICAL RELEVANCE: LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Broadband rotary joint for high-speed ultrahigh-resolution endoscopic OCT imaging at 800 nm.

We report the development of a broadband rotary joint for high-speed ultrahigh-resolution endoscopic optical coherence tomography (OCT) imaging in the 800 nm spectral range. This rotary joint features a pair of achromatic doublets in order to achieve broadband operation for a 3 dB bandwidth over 150 nm. The measured one-way throughput of the rotary joint is greater than 80%, while the fluctuation of the double-pass coupling efficiency during 360 deg rotation is less than ±5% at a near video-rate speed of 20 revolutions/s (rps). The rotary joint is used in conjunction with a diffractive-optics-based endoscope and 800 nm spectral domain OCT system and achieved an ultrahigh axial resolution of ∼2.4 µm in air. The imaging performance is demonstrated by 3D circumferential imaging of a mouse colon in vivo.

Lattice Boltzmann Simulation of Droplets Impacting on Superhydrophobic Surfaces with Randomly Distributed Rough Structures.

Superhydrophobic surfaces have attracted much attention in environmental control because of their excellent water-repellent properties. A successful design of superhydrophobic surfaces requires a correct understanding of the influences of surface roughness on water-repellent behaviors. Here, a new approach, a mesoscale lattice Boltzmann simulation approach, is proposed and used to model the dynamic behavior of droplets impacting on surfaces with randomly distributed rough microstructures. The fast Fourier transformation method is used to generate non-Gaussian randomly distributed rough surfaces, with the skewness and kurtosis obtained from real surfaces. Then, droplets impacting on the rough surfaces are modeled. It is found that the shape of droplet spreading is obviously affected by the distributions of surface asperity. Decreasing the skewness and keeping the kurtosis around 3 is an effective method to enhance the ability of droplet rebound. The new approach gives more detailed insights into the design of superhydrophobic surfaces.

IFN-λ1 in CHO cells: its expression and biological activity.

BACKGROUND: Many studies have investigated the characteristics and biological activities of type III interferon (IFN), finding that it has similar features to type I IFN but also unique actions because it is recognized by a different receptor. RESULTS: A full-length recombinant human IFN-λ1 (rhIFN-λ1) cDNA was cloned into the pDF expression vector and stably expressed in Flp-In-CHO cells. After four purification steps (ammonium sulfate precipitation, SP Sepharose chromatography, Blue Sepharose 6 fast flow affinity chromatography and molecular sieve chromatography), the rhIFN-λ1 had a purity of about 90% and was found to have the predicted biological activities. The anti-viral activity of rhIFN-λ1 was determined as 106 IU/mg using the vesicular stomatitis virus (WISH-VSV) assay system. The anti-proliferation activity of rhIFN-λ1 was measured using the MTS method and the growth inhibition ratio was 57% higher than that for recombinant human IFN-α2b (rhIFN-α2b) when the rhIFN-λ1 concentration was 1000 IU/ml. rhIFN-λ1 had lower natural killer cell cytotoxicity than rhIFN-α2b. CONCLUSION: The Flp-In-CHO system is suitable for stably expressing rhIFN-λ1 that possesses the predicted anti-viral, anti-proliferation and natural killer cell cytotoxicity-promoting activities.