PHA-665752's Antigrowth and Proapoptotic Effects on HSC-3 Human Oral Cancer Cells.

c-Met is a tyrosine-kinase receptor, and its aberrant activation plays critical roles in tumorigenesis, invasion, and metastatic spread in many human tumors. PHA-665752 (PHA) is an inhibitor of c-Met and has antitumor effects on many hematological malignancies and solid cancers. However, the activation and expression of c-Met and its role and the antitumor effect of PHA on human oral squamous cell carcinoma (OSCC) cells remain unclear. Here, we investigated the activation and expression of c-Met and the effects of PHA on the growth of a highly tumorigenic HSC-3 human OSCC cell line with high c-Met phosphorylation and expression. Of note, c-Met was highly expressed and phosphorylated on Y1234/1235 in HSC-3 cells, and PHA treatment significantly suppressed the growth and induced apoptosis of these cells. Moreover, PHA that inhibited the phosphorylation (activation) of c-Met further caused the reduced phosphorylation and expression levels of Src, protein kinase B (PKB), mammalian target of rapamycin (mTtor), and myeloid cell leukemia-1 (Mcl-1) in HSC-3 cells. In addition, the antiangiogenic property of PHA in HSC-3 cells was shown, as evidenced by the drug's suppressive effect on the expression of hypoxia-inducible factor-1α (HIF-1α), a critical tumor angiogenic transcription factor. Importantly, genetic ablation of c-Met caused the reduced growth of HSC-3 cells and decreased Src phosphorylation and HIF-1α expression. Together, these results demonstrate that c-Met is highly activated in HSC-3 human oral cancer cells, and PHA exhibits strong antigrowth, proapoptotic, and antiangiogenic effects on these cells, which are mediated through regulation of the phosphorylation and expression of multiple targets, including c-Met, Src, PKB, mTOR, Mcl-1, and HIF-1α.

Clinical molecular subtyping reveals intrinsic mesenchymal reprogramming in gastric cancer cells.

The mesenchymal cancer phenotype is known to be clinically related to treatment resistance and a poor prognosis. We identified gene signature-based molecular subtypes of gastric cancer (GC, n = 547) based on transcriptome data and validated their prognostic and predictive utility in multiple external cohorts. We subsequently examined their associations with tumor microenvironment (TME) features by employing cellular deconvolution methods and sequencing isolated GC populations. We further performed spatial transcriptomics analysis and immunohistochemistry, demonstrating the presence of GC cells in a partial epithelial-mesenchymal transition state. We performed network and pharmacogenomic database analyses to identify TGF-ß signaling as a driver pathway and, thus, a therapeutic target. We further validated its expression in tumor cells in preclinical models and a single-cell dataset. Finally, we demonstrated that inhibition of TGF-ß signaling negated mesenchymal/stem-like behavior and therapy resistance in GC cell lines and mouse xenograft models. In summary, we show that the mesenchymal GC phenotype could be driven by epithelial cancer cell-intrinsic TGF-ß signaling and propose therapeutic strategies based on targeting the tumor-intrinsic mesenchymal reprogramming of medically intractable GC.

Taxonomic Review of the Genus Caloptilia Hübner, 1825 (Lepidoptera: Gracillariidae) with Descriptions of Three New Species and Seven Newly Recorded Species from Korea.

In this study, 29 species of Caloptilia Hübner, 1825, belonging to the family Gracillariidae, were recognized in Korea. Among these, three species, i.e., C. purpureus sp. nov., C. koreana sp. nov., and C. xanthos sp. nov., are described as new to science. In addition, seven species of this genus are reported for the first time in Korea. All known species were enumerated, based on their available information. Adult specimens and genitalia of the new and newly recorded species were examined and described using all available information.

Recurrence of Uncomplicated Diverticulitis: A Meta-Analysis.

Background and objective: This study aimed to investigate the estimated rate and risk of recurrence of uncomplicated diverticulitis (UCD) after the first episode through a meta-analysis. Methods: Eligible studies were searched and reviewed; 27 studies were included in this study. Subgroup analyses were performed, based on lesion location, medical treatment, follow-up period, and study location. Results: The estimated recurrence rate of UCD was 0.129 (95% confidence interval [CI] 0.102-0.162). The recurrence rates of the right-and left-sided colon were 0.092 (95% CI 27.063-0.133) and 0.153 (95% CI 0.104-0.218), respectively. The recurrence rate according to follow-up period was highest in the subgroup 1-2 years, compared with that of other subgroups. The recurrence rate of the Asian subgroup was significantly lower than that of the non-Asian subgroup (0.092, 95% CI 0.064-0.132 vs. 0.147, 95% CI 0.110-0.192; p = 0.043 in the meta-regression test). There were significant correlations between UCD recurrence and older age and higher body temperature. However, UCD recurrence was not significantly correlated with medications, such as antibiotics or anti-inflammatory drugs. Conclusions: In this study, detailed information on estimated recurrence rates of UCD was obtained. In addition, older age and higher body temperature may be risk factors for UCD recurrence after the first episode.

Global Nepticulidae, Opostegidae, and Tischeriidae (Lepidoptera): temporal dynamics of species descriptions and their authors.

This study identifies the number of named and described species of three monotrysian, plant-mining lepidopteran families worldwide: Nepticulidae and Opostegidae (Nepticuloidea), and Tischeriidae (Tischerioidea). At the end of 2021, we estimated that a total of 1000 Nepticulidae species, 197 Opostegidae species, and 170 Tischeriidae species have been described since the taxonomic practice of describing species began in the 18th century. We examine and discuss the history of descriptions and authorship of species worldwide for each of the three families. We found that the total (accumulative) number of species described increased with each time period delineated. About five new species were described per year on average, or about 22 new species were described per year in the 21st century. We recognize researchers with the most number of described species in these three taxa.

Harmonic scalpels compared with electrocautery in reconstructive flap harvesting: A meta-analysis.

BACKGROUND: Numerous studies have compared electrical devices used for flap surgery, but the results are inconsistent. This research was performed to evaluate the efficacy of two different types of electric devices: electrocautery and ultrasonic shears. METHODS: The PubMed, Embase, and Scopus databases were searched systematically. A total of 505 cases were included in this study, including 209 electrocautery and 296 harmonic scalpel cases. The following information was retrieved from the included studies: the first author of the article, publication year, flap type, flap harvest time, drain volume, bleeding volume and postoperative complications. Hematoma, infection, flap necrosis and wound dehiscence were considered postoperative complications. The Q statistic for heterogeneity and the I2 index were calculated. If I2 < 50%, we used a fixed-effects model; if I2 > 50%, we employed a random-effects model in our meta-analysis. RESULTS: A total of eight studies which met the inclusion criteria were included and reviewed systematically for a meta-analysis. The harmonic scalpel yielded a statistically significantly more favorable flap harvest time and drain volume than did electrocautery. The Harmonic scalpel led to a shorter flap harvest time by 26.29 min (95% CI = -39.38 to -13.2; p < .00001) and smaller drain volume by 58.76 ml (95% CI = -105.27 to -12.25; p = .01) on average. However, there were no significant differences in the bleeding volume or incidence rates of infection, flap necrosis and wound dehiscence. CONCLUSION: The Harmonic scalpel method yields better outcomes in terms of the flap harvest time and drain volume than does the conventional electrocautery method. Therefore, the Harmonic scalpel is a better option for cauterization and dissection in flap surgery.

Management of Chronic Idiopathic Pain in Patients With Dental Implant Without a Clear Pathological Lesion: A Retrospective Study.

Non-nociceptive, persistent idiopathic facial pain (PIFP) is a poorly localized, continuous dull pain that occurs even in the absence of apparent pathological lesions or clinical neurologic deficiency. This study aimed to investigate the disease characteristics of PIFP that developed after dental implant treatment. The clinical characteristics of pain as well as treatment method and outcomes were retrospectively analyzed in 20 patients diagnosed with PIFP. The patients developed pain either after implant fixation or prosthetic treatment. In most patients, the pain persisted not only around the implant region but also at a distant site from the related implant (13/20, 65%). Many patients desired removal of the implants to manage the pain although the pain was not considered to be related to the implant treatment. In 12 patients, the related implants were removed, but 67% (n = 8/12) of the patients still experienced chronic pain after implant removal. Medication helped decrease the pain in most patients (n = 17). Pregabalin and clonazepam showed relatively higher efficiency than other medications for controlling the pain. The results showed that although the onset of PIFP was related to dental implant treatment, implant removal could not be considered a reliable option for the management of PIFP. Although medication controls the pain at least partially, complete pain control with medication should not be expected. These results demonstrate that an accurate diagnosis of PIFP is important for the selection of appropriate treatment.

Anti-growth and pro-apoptotic effects of dasatinib on human oral cancer cells through multi-targeted mechanisms.

Dasatinib is an inhibitor of Src that has anti-tumour effects on many haematological and solid cancers. However, the anti-tumour effects of dasatinib on human oral cancers remain unclear. In this study, we investigated the effects of dasatinib on different types of human oral cancer cells: the non-tumorigenic YD-8 and YD-38 and the tumorigenic YD-10B and HSC-3 cells. Strikingly, dasatinib at 10 µM strongly suppressed the growth and induced apoptosis of YD-38 cells and inhibited the phosphorylation of Src, EGFR, STAT-3, STAT-5, PKB and ERK-1/2. In contrast, knockdown of Src blocked the phosphorylation of EGFR, STAT-5, PKB and ERK-1/2, but not STAT-3, in YD-38 cells. Dasatinib induced activation of the intrinsic caspase pathway, which was inhibited by z-VAD-fmk, a pan-caspase inhibitor. Dasatinib also decreased Mcl-1 expression and S6 phosphorylation while increased GRP78 expression and eIF-2α phosphorylation in YD-38 cells. In addition, to its direct effects on YD-38 cells, dasatinib also exhibited anti-angiogenic properties. Dasatinib-treated YD-38 or HUVEC showed reduced HIF-1α expression and stability. Dasatinib alone or conditioned media from dasatinib-treated YD-38 cells inhibited HUVEC tube formation on Matrigel without affecting HUVEC viability. Importantly, dasatinib's anti-growth, anti-angiogenic and pro-apoptotic effects were additionally seen in tumorigenic HSC-3 cells. Together, these results demonstrate that dasatinib has strong anti-growth, anti-angiogenic and pro-apoptotic effects on human oral cancer cells, which are mediated through the regulation of multiple targets, including Src, EGFR, STAT-3, STAT-5, PKB, ERK-1/2, S6, eIF-2α, GRP78, caspase-9/3, Mcl-1 and HIF-1α.

Anthropometric Changes in the Upper Lip Between the Standing Position in the Clinic and Supine Position on the Operative Table in Secondary Cleft Lip Nasal Deformities.

BACKGROUND: We evaluated changes in lip height and length by position in cleft lip nasal deformity patients who underwent treatment with Millard technique. METHODS: A retrospective review of the medical records and an anthropometric analysis of photographs were performed in 209 cases of cleft lip nasal deformity. In the photogrammetric analysis, the lip height and length were calculated with respect to the intercanthal width. To evaluate the change in the difference between the cleft- and noncleft-side measurements between the standing and supine positions, the difference between the cleft- and noncleft-side measurements (Δnc-c) was calculated. We identified which patients and surgical factors affected the difference between the cleft- and noncleft-side measurements between the standing and supine positions (Δst-sp). RESULTS: From a total of 120 cases, cases with missing medical charts and clinical photographs were excluded, and 89 cases were included in this study. The discrepancy between the cleft-side lip height and noncleft-side lip height was significantly different between the standing and supine positions (P = 0.007). According to the univariate regression analysis, Δst-sp (sbal-cphi) had a significant positive correlation with body mass index (P = 0.044). In the final multiple linear regression analysis, body mass index had a significant positive correlation with Δst-sp (sbal-cphi, P = 0.044). CONCLUSION: In our results, the difference in vertical lip height is easy to underestimate in the supine position during surgery. Therefore, surgeons should verify lip height with the patient in the sitting or standing position during the operation to avoid undercorrecting lips with short heights.

Deconvolution of diffuse gastric cancer and the suppression of CD34 on the BALB/c nude mice model.

BACKGROUND: Gastric cancer is a considerable burden for worldwide patients. And diffuse gastric cancer is the most insidious subgroup with poor survival. The phenotypic characterization of the diffuse gastric cancer cell line can be useful for gastric cancer researchers. In this article, we aimed to characterize the diffuse gastric cancer cells with MRI and transcriptomic data. We hypothesized that gene expression pattern is associated with the phenotype of the cells and that the heterogeneous enhancement pattern and the high tumorigenicity of SNU484 can be modulated by the perturbation of the highly expressed gene. METHODS: We evaluated the 9.4 T magnetic resonance imaging and transcriptomic data of the orthotopic mice models from diffuse gastric cancer cells such as SNU484, Hs746T, SNU668, and KATO III. We included MKN74 as an intestinal cancer control cell. After comprehensive analysis integrating MRI and transcriptomic data, we selected CD34 and validated the effect by shRNA in the BALB/c nude mice models. RESULTS: SNU484, SNU668, Hs746T, and MKN74 formed orthotopic tumors by the 5 weeks after cell injection. The diffuse phenotype was found in the SNU484 and Hs746T. SNU484 was the only tumor showing the heterogeneous enhancement pattern on T2 images with a high level of CD34 expression. Knockdown of CD34 decreased the round-void shape in the H&E staining (P = 0.028), the heterogeneous T2 enhancement, and orthotopic tumorigenicity (100% vs 66.7%). The RNAseq showed that the suppressed CD34 is associated with the downregulated gene-sets of the extracellular matrix remodeling. CONCLUSION: Suppression of CD34 in the human-originated gastric cancer cell suggests that it is important for the round-void histologic shape, heterogeneous enhancement pattern on MRI, and the growth of gastric cancer cell line.

The Impact of Extramural Venous Invasion in Colorectal Cancer: A Detailed Analysis Based on Tumor Location and Evaluation Methods.

This study aimed to elucidate the prognostic implications of extramural venous invasion (EMVI) in colorectal cancer (CRC) through a meta-analysis. Eighteen eligible studies were included in this meta-analysis. Data on the prevalence of EMVI and the correlation between EMVI and survival were collected from these studies. In addition, a subgroup analysis was conducted based on tumor location and evaluation methods. The estimated prevalence of EMVI was 28.3% (95% confidence interval [CI] = 23.1% to 34.0%) in patients with CRC. The estimated prevalence of EMVI in patients with colon cancer and rectal cancer was 23.0% (95% CI = 17.6% to 29.6%) and 35.7% (95% CI = 22.3% to 51.6%), respectively. Based on the evaluation method, the estimated prevalence of EMVI were 28.3% (95% CI = 23.2% to 34.1%) and 27.3% (95% CI = 8.4% to 60.6%) in pathologic and radiologic examinations, respectively. The correlation of EMVI with worse overall and disease-free survival rates was significant (hazard ratio = 1.773, 95% CI = 1.483-2.120, and hazard ratio = 2.059, 95% CI = 1.683-2.520, respectively). However, in the subgroup analysis with radiologic examination, there was no significant difference in survival rates between patients with and without EMVI. Our study showed that EMVI was frequently detected in 28.3% of patients with CRC and was correlated to worse survival. The detection of EMVI can be useful for predicting the prognosis of patients with CRC.

A new species of Ceratosticha Meyrick, 1935 (Lepidoptera: Psychidae) from Korea.

Ceratosticha lineata Roh Byun, sp. n., is described from Korea. Adults, genitalia, and larvae of the species are described, and DNA barcodes are provided.

Prognostic Implication of Metastatic Lymph Node Ratio in Colorectal Cancers: Comparison Depending on Tumor Location.

BACKGROUND: The proportion of the number of involved lymph nodes (LNs) to the number of examined LNs-defined as metastatic LN ratio (mLNR)-has been considered as a prognostic parameter. This study aims to elucidate the prognostic implication of the mLNR in colorectal cancer (CRC) according to the tumor location. METHODS: We evaluated the correlation between prognoses and the involved and examined LNs as well as mLNR according to the tumor location in 266 surgically resected human CRCs. Besides, to evaluate the optimal cutoff for high and low mLNRs, we investigated the correlation between mLNR and survival according to the various cutoffs. RESULTS: LN metastasis was found in 146 cases (54.9%), and colon and rectal cancers were found in 116 (79.5%) and 30 (20.5%) of the cases, respectively. The mean mLNRs were significantly higher in rectal cancer than in colon cancer (0.38 ± 0.28 vs. 0.21 ± 0.24, P = 0.003). Besides this, the number of involved LNs in rectal cancer was significantly high compared to colon cancer (11.83 ± 10.92 vs. 6.37 ± 7.78, P = 0.014). However, there was no significant difference in the examined LNs between the rectal and colon cancers (31.90 ± 12.28 vs. 36.60 ± 18.11, P = 0.181). In colon cancer, a high mLNR was significantly correlated with worse survival for all cutoffs (0.1, 0.2, 0.3, and 0.4). However, rectal cancer only showed a significant correlation between high mLNR and worse survival in the subgroup with a cutoff of 0.2. CONCLUSIONS: Our results showed that high mLNR was significantly correlated with worse survival. The number of involved LNs and mLNRs were significantly higher in rectal cancer than in colon cancer. The cutoff of 0.2 can be useful for the differentiation of prognostic groups, regardless of tumor location.

Risk of Ischemic Stroke After a Facial Bone Fracture in Elderly Patients.

BACKGROUND: Ischemic stroke is a major disease in our aging society, and the incidence of facial bone fractures among the elderly has increased. However, there have been few studies evaluating stroke after facial bone fractures. The purpose of this study was to investigate the frequency and risk of stroke after facial bone fractures. METHODS: This study included patients 65 years or older with a diagnosis of facial bone fracture (study group) and patients who had previously undergone plastic surgery procedures such as mass excisions or cosmetic surgery (control group) from 2006 to 2015. We evaluated the incidence of new-onset ischemic stroke and its associated risk factors during a 1-year follow-up period. Patients were excluded if they had a history of stroke or if they were lost to follow-up during the course of the study period. RESULTS: There were no demographic differences between the 2 groups except in age. According to the hazard ratio, the study group had a significantly higher risk of ischemic stroke than did the control group during the follow-up period. There was an identified interaction between the sexes. Only the women in our study group had an increased risk of ischemic stroke that was statistically significant. After adjusting for the risk factors, the increased stroke risk in patients in the study group persisted at about the same level as in the unadjusted analysis. Regarding the stroke-free survival rates, the curve also showed that the study group had a significantly lower 1-year stroke-free survival rate. CONCLUSIONS: Facial bone fractures are associated with increased risk of stroke at 1-year follow-up among elderly patients, particularly women.

Instrumental development of a quasi-relativistic ultrashort electron beam source for electron diffractions and spectroscopies.

A stable femtosecond electron beam system has been configured for time-resolved pump-probe experiments. The ultrafast electron diffraction (UED) system is designed with a sub-MeV photoelectron beam source pulsed by a femtosecond UV laser and nondispersive beamline components, including a bunch compressor-a pulsed S-band klystron is installed and fully commissioned with 5.5 MW peak power in a 2.5 µs pulse length. A single-cell RF photo-gun is designed to produce 1.6-16 pC electron bunches in a photoemission mode with 150 fs pulse duration at 0.5-1 MeV. The measured RF system jitters are within 1% in magnitude and 0.2° in phase, which would induce 3.4 keV and 0.25 keV of ΔE, corresponding to 80 fs and 5 fs of Δt, respectively. Our particle-in-cell simulations indicate that the designed bunch compressor reduces the time-of-arrival jitter by about an order of magnitude. The transport and focusing optics of the designed beamline with the bunch compressor enables an energy spread within 10-4 and a bunch length (electron probe) within <500 fs. In this paper, the design analysis and instrumental test results are presented along with the development of the quasi-relativistic UED system.

Nasal Deviation in Patients With Asymmetric Mandibular Prognathism.

PURPOSE: This study was aimed to evaluate the nasal deviation in patients with asymmetric mandibular prognathism. MATERIALS AND METHODS: Thirty-five patients with skeletal class III malocclusion were included in the study. Significant mandibular asymmetry of >4 mm menton deviation in three-dimensional (3D) reformatted cone beam computed tomography images was defined as asymmetry group (n = 20). Patients without mandibular asymmetry served as control group (n = 15). The mandibular asymmetry was evaluated pre- and postoperatively. RESULTS: Nasal tip was significantly shifted to the deviated side of the mandible (short side) in the asymmetry group, as compared to the control group (1.5 ±â€Š0.9 degree, P < 0.01). Alar base angle (ABA) was significantly narrower in nondeviated side (long side) than in the deviated side in asymmetry group. However, control group showed no bilateral difference in ABA. Correction of deviated mandibular prognathism by isolated mandibular surgery resulted in change in the ABA but not the columella base position or nasal asymmetry. ABA on nondeviated side significantly decreased in proportion to the amount of transverse menton movement by surgery (r = -0.560, P < 0.01). CONCLUSION: Our results showed that mandibular chin deviation was accompanied by nasal deviation. Isolated mandibular surgery can potentially influence the alar base position on the contralateral side of deviation but not the nasal tip asymmetry. Therefore, clinicians should inform patients preoperatively of the fundamental limitation of mandibular surgery in cases with preexisting nasal asymmetry.

Understanding dual precipitation strengthening in ultra-high strength low carbon steel containing nano-sized copper precipitates and carbides.

Low carbon ferritic steel alloyed with Ti, Mo and Cu was hot rolled and interrupt cooled to produce nano-sized precipitates of copper and (Ti,Mo)C carbides. The steel had a tensile strength of 840 MPa, an increase in yield strength of 380 MPa over that of the plain carbon steel and reasonable ductility. Transmission electron microscopy and small angle neutron scattering were used to characterize size and volume fraction of the precipitates in the steels designed to form only copper precipitates and only (Ti,Mo)C carbides. The individual and combined precipitation strengthening contributions was calculated using the size and volume fraction of precipitates and compared with the measured values.

Erratum to: Understanding dual precipitation strengthening in ultra-high strength low carbon steel containing nano-sized copper precipitates and carbides.

[This corrects the article DOI: 10.1186/s40580-017-0110-5.].

Minimum hyaluronic acid (HA) modified magnetic nanocrystals with less facilitated cancer migration and drug resistance for targeting CD44 abundant cancer cells by MR imaging.

We report minimal amount of hyaluronic acid (HA) conjugated magnetic nanocrystals (mHMs) for targeted imaging of CD44 abundant breast cancer cells via MRI. These mHMs lead to less induced cancer migration and drug resistance, which is distinct from conventional approaches using nanoplatforms (imaging or therapeutic systems) that are completely covered with HA. To synthesize mHMs, magnetic nanocrystals (MNCs), as MRI contrast agents, were encapsulated mostly with polysorbate 80 (P80, non-reactive to HA) and partially with aminated P80 (reactive to HA). This system enabled conjugation of an immensely diminished amount of HA onto MNCs. While these nanoparticles maintained good CD44 targeted imaging efficacy, they also showed no cytotoxicity and colloidal stability. We varied the HA ratios on an equal amount of MNCs and identified that when more HA was attached on nanoparticles, there was more facilitated cancer migration and drug resistant potentials. We chose the lowest amount of HA conjugated mHMs (mHM1) and demonstrated that mHM1 selectively diagnosed tumor regions in vivo. We believe that the technique described herein can be applied to various applications using HA to detect CD44 abundant cancer cell lines and offer a basis to understand the interaction between the cellular response and surface modification of nanoparticles.