Investigating a Machine Learning Approach to Predicting White Pixel Defects in Wafers-A Case Study of Wafer Fabrication Plant F.

CMOS image sensor (CIS) semiconductor products are integral to mobile phones and photographic devices, necessitating ongoing enhancements in efficiency and quality for superior photographic outcomes. The presence of white pixels serves as a crucial metric for assessing CIS product performance, primarily arising from metal impurity contamination during the wafer production process or from defects introduced by the grinding blade process. While immediately addressing metal impurity contamination during production presents challenges, refining the handling of defects attributed to grinding blade processing can notably mitigate white pixel issues in CIS products. This study zeroes in on silicon wafer manufacturers in Taiwan, analyzing white pixel defects reported by customers and leveraging machine learning to pinpoint and predict key factors leading to white pixel defects from grinding blade operations. Such pioneering practical studies are rare. The findings reveal that the classification and regression tree (CART) and random forest (RF) models deliver the most accurate predictions (95.18%) of white pixel defects caused by grinding blade operations in a default parameter setting. The analysis further elucidates critical factors like grinding load and torque, vital for the genesis of white pixel defects. The insights garnered from this study aim to arm operators with proactive measures to diminish the potential for customer complaints.

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.

Allyl Isothiocyanate Suppresses the Proliferation in Oral Squamous Cell Carcinoma via Mediating the KDM8/CCNA1 Axis.

The dysregulated expression of cyclin genes can lead to the uncontrolled proliferation of cancer cells. Histone demethylase Jumonji-C domain-containing protein 5 (KDM8, JMJD5) and cyclin A1 (CCNA1) are pivotal in cell cycle progression. A promising candidate for augmenting cancer treatment is Allyl isothiocyanate (AITC), a natural dietary chemotherapeutic and epigenetic modulator. This study aimed to investigate AITC's impact on the KDM8/CCNA1 axis to elucidate its role in oral squamous cell carcinoma (OSCC) tumorigenesis. The expression of KDM8 and CCNA1 was assessed using a tissue microarray (TMA) immunohistochemistry (IHC) assay. In vitro experiments with OSCC cell lines and in vivo experiments with patient-derived tumor xenograft (PDTX) and SAS subcutaneous xenograft tumor models were conducted to explore AITC's effects on their expression and cell proliferation. The results showed elevated KDM8 and CCNA1 levels in the OSCC patient samples. AITC exhibited inhibitory effects on OSCC tumor growth in vitro and in vivo. Additionally, AITC downregulated KDM8 and CCNA1 expression while inducing histone H3K36me2 expression in oral cancer cells. These findings underscore AITC's remarkable anticancer properties against oral cancer, highlighting its potential as a therapeutic option for oral cancer treatment by disrupting the cell cycle by targeting the KDM8/CCNA1 axis.

A Prospective Follow-up Study on Risk Factors to Predict the Progression of Unruptured Intracranial Aneurysms on Enhanced HR-MRI.

RATIONALE AND OBJECTIVES: To prospectively investigate the potential correlation between qualitative and quantitative assessment of aneurysm wall enhancement (AWE) on initial enhanced high-resolution magnetic resonance imaging (HR-MRI) and aneurysm progression during follow-up. MATERIALS AND METHODS: From June 2016 to January 2021, we prospectively recruited patients with unruptured intracranial aneurysms (UIAs) for enhanced HR-MRI examination. The patients' demographic and clinical data and aneurysm characteristics, including AWE features, were collected and analyzed. Follow-up images were compared to evaluate IA progression. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the risk factors associated with aneurysm progression. RESULTS: Seventy-seven patients with 95 UIAs met our research criteria, and the median follow-up time was 15.7 months. Progression was observed in 18 aneurysms; the remaining 77 remained stable. Progressive UIAs were larger in size, more frequently displayed obvious AWE and showed a higher enhancement ratio (ER) than nonprogressive UIAs. Multivariate Cox regression analysis showed that both ER (hazard ratio, 6.304, p < 0.001) and aneurysm size (hazard ratio, 1.343, p = 0.014) were independent risk factors for aneurysm progression. The combination of ER and aneurysm size had an area under the curve of 0.920 for the prediction of aneurysm progression, with a sensitivity of 88.9% and specificity of 87.0%. CONCLUSION: A higher ER value of the aneurysm wall and a larger aneurysm size on initial HR-MRI may predict an increased risk of aneurysm progression, which suggests that closer monitoring by imaging or preventive intervention may be required for the clinical management of these aneurysms.

Factors Associated with Attitudes toward Aging among Taiwanese Middle-Aged and Older Adults: Based on Population-Representative National Data.

In middle-aged and older adults, attitude toward aging (ATA) exerts significant influences on their current and future health. For health promotion to be successful, participants' ATA requires health care providers' attention. Knowing the factors associated with ATA can facilitate future studies to investigate effective interventions. The aim of this study was to identify the factors associated with ATA in middle-aged and older adults. This cross-sectional study analyzed data of a nationally representative sample of adults aged 58 years and older collected in a population-based longitudinal study: the Taiwan Longitudinal Study on Aging (TLSA). To identify the factors associated with ATA, we investigated demographic factors (age, gender, education, marital and cohabitation status, and financial satisfaction status) and health-related factors (number of co-morbidities, depression, physical function dependency) with bivariate analysis and multiple regression analysis. To identify the activities beneficial to ATA over and above demographic and health-related factors, various activities (exercise, volunteer service, and leisure activities) were each examined individually by multiple regression analysis. The factors detrimental to ATA were advanced age, a higher number of co-morbidities, living alone, depression, and dependence on physical function. Those beneficial to ATA were higher education, financial satisfaction, physical exercise, volunteer service, and six leisure activities.

Prevalence, complete genome, and metabolic potentials of a phylogenetically novel cyanobacterial symbiont in the coral-killing sponge, Terpios hoshinota.

Terpios hoshinota is an aggressive, space-competing sponge that kills various stony corals. Outbreaks of this species have led to intense damage to coral reefs in many locations. Here, the first large-scale 16S rRNA gene survey across three oceans revealed that bacteria related to the taxa Prochloron, Endozoicomonas, SAR116, Ruegeria, and unclassified Proteobacteria were prevalent in T. hoshinota. A Prochloron-related bacterium was the most dominant and prevalent cyanobacterium in T. hoshinota. The complete genome of this uncultivated cyanobacterium and pigment analysis demonstrated that it has phycobiliproteins and lacks chlorophyll b, which is inconsistent with the definition of Prochloron. Furthermore, the cyanobacterium was phylogenetically distinct from Prochloron, strongly suggesting that it should be a sister taxon to Prochloron. Therefore, we proposed this symbiotic cyanobacterium as a novel species under the new genus Candidatus Paraprochloron terpiosi. Comparative genomic analyses revealed that 'Paraprochloron' and Prochloron exhibit distinct genomic features and DNA replication machinery. We also characterized the metabolic potentials of 'Paraprochloron terpiosi' in carbon and nitrogen cycling and propose a model for interactions between it and T. hoshinota. This study builds a foundation for the study of the T. hoshinota microbiome and paves the way for better understanding of ecosystems involving this coral-killing sponge.

Comparison of the accuracy of diagnoses of oral potentially malignant disorders with dysplasia by a general dental clinician and a specialist using the Taiwanese Nationwide Oral Mucosal Screening Program.

Screening for oral potentially malignant disorders (OPMDs) with dysplasia in high-risk groups is suggested in countries with a high prevalence of the disorders. This study aimed to compare the accuracy of diagnoses of OPMDs with dysplasia made by a primary examiner (general dental clinician) and a specialist (oral and maxillofacial surgeon) using the current Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). A total of 134 high-risk participants were enrolled for oral mucosal screening via the TNOMSP. A primary examiner and a specialist examined each participant. Mucosal biopsies were obtained and subjected to histopathological analysis. The OPMD most frequently diagnosed by the primary examiner was thin homogeneous leukoplakia (48/134; 35.8%), and in 39/134 participants (29.1%) the diagnosis was uncertain, but abnormalities were suggested. The OPMDs most frequently diagnosed by the specialist were erythroleukoplakia (23/134; 17.2%) and thin homogeneous leukoplakia (21/134; 15.7%), and 51/134 participants (38.1%) were diagnosed with other diseases. Via histopathology, 70/134 participants (52.3%) were diagnosed with dysplasia, and 58/134 (43.3%) were diagnosed with benign conditions. The specialist's diagnoses exhibited a higher specificity, positive predictive value, and accuracy than the primary examiners. A specialist using the current TNOMSP for high-risk participants diagnosed OPMDs with dysplasia more accurately than a primary examiner. Early diagnosis of high-risk OPMDs is crucial in countries with a high prevalence of the disorders. Proficient examination via the current TNOMSP by trained clinician is effective for the management of OPMDs with dysplasia.

Triptolide suppresses oral cancer cell PD-L1 expression in the interferon-γ-modulated microenvironment in vitro, in vivo, and in clinical patients.

Biological and prognostic roles of programmed death ligand 1 (PD-L1) remain unclear in oral squamous cell carcinoma (OSCC). Moreover, the pivotal role of tumor microenvironmental interferon-gamma (IFN-γ) in host responses to malignant cells, oral cancer growth, and PD-L1 expression has not been adequately studied. Thus, PD-L1 expression in 130 OSCC samples was analyzed using immunohistochemistry, which was found significantly overexpressed at the tumor site (P < .01). We further analyzed the effects of IFN-γ on OSCC cell proliferation using enzyme-linked immunosorbent assays and found that IFN-γ drives PD-L1 expression in OSCC cells in a dose-dependent manner. Triptolide (TPL), a bioactive compound isolated from Tripterygium wilfordii, exhibits anti-inflammatory and antitumor activities. To investigate whether the antitumor effect of TPL involves the suppression of PD-L1 expression, we treated OSCC cells in vitro and a patient-derived tumor xenograft (PDTX) model with TPL. TPL suppressed PD-L1 expression in the PDTX model, inhibiting tumor growth, and in OSCC cells in an IFN-γ-modulated microenvironment. We concluded that TPL inhibits tumor growth in oral cancer and downregulates PD-L1 expression in oral cancer cells in vitro. Our results provide evidence for the clinical development of PD-L1-targeted therapy for OSCC.

Downregulation of Jumonji-C domain-containing protein 5 inhibits proliferation by silibinin in the oral cancer PDTX model.

Dysregulation of histone demethylase Jumonji-C domain-containing protein 5 (JMJD5) has been identified as a great effect on tumorigenesis. Silibinin is a commonly used anti-hepatotoxic drug and exhibits anticancer effect in various cancers. However, the antitumor mechanism between silibinin and JMJD5 in oral squamous cell carcinoma (OSCC) remains unclear. In this study, the clinical significance of JMJD5 on OSCC patients was assessed through tissue microarray. Furthermore, mice bearing patient-derived tumor xenografts (PDTXs) and tongue cancer cell lines were treated with silibinin and evaluated for tumor growth and JMJD5 expression. High expression of JMJD5 in oral cancer was significantly associated with tumor size (P = 0.0241), cervical node metastasis (P = 0.0001) and clinical stage (P = 0.0002), was associated with worse survival rate compared with that of the total cohort (P = 0.0002). Collectively the data indicate that JMJD5 expression may be suitable for detection of unfavorable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. In addition, silibinin inhibits cancer growth in vitro and in PDTX models. Furthermore, metastasis-associated protein 1 (MTA1) could regulate the expression for JMJD5 and had a positive correlation with JMJD5. Moreover, silibinin could downregulate JMJD5 and MTA1 in oral cancer. Present study thus identifies that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression. In addition, silibinin is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating JMJD5 in OSCC, through a mechanism likely involving MTA1/JMJD5 axis.

Noise-like pulse generation around 1.3-µm based on cascaded Raman scattering.

Based on cascaded Raman scattering, near-infrared (NIR) noise-like pulses (NLPs) were successfully demonstrated using a Yb-doped fiber amplifier system. Through a nonlinear fiber amplifier using a germanium-zirconia-silica Yb3+-doped single mode fiber as a gain fiber, the fourth-order Stokes wave (4th-SW) can be excited to extend the emission peak of approximately 1.2-µm and a 3-dB bandwidth of approximately 130 nm. To further shift the wavelength more efficiently toward 1.3 µm, filtered NLPs with an emission peak at 1075 nm were adopted as seeded pulses to excite the fifth-order Stokes wave (5th-SW) because of the better conversion efficiency of stimulated Raman scattering without gain competition with Yb-doped fiber. The generated NIR NLPs were shown to be an excellent light source for the photoluminescence emission from three photon absorption of perovskite to illustrate the red shift of the emission peak owing to the reabsorption effect.

Molecular heterogeneity unravelled by single-cell transcriptomics in patients with essential thrombocythaemia.

Significant phenotypic heterogeneity exists in patients with all subtypes of myeloproliferative neoplasms (MPN), including essential thrombocythaemia (ET). Single-cell RNA sequencing (scRNA-Seq) holds the promise of unravelling the biology of MPN at an unprecedented level of resolution. Herein we employed this approach to dissect the transcriptomes in the CD34+ cells from the peripheral blood of seven previously untreated ET patients and one healthy adult. The mutational profiles in these patients were as follows: JAK2 V617F in two, CALR in three (one type I and two type II) and triple-negative (TN) in two. Our results reveal substantial heterogeneity within this enrolled cohort of patients. Activation of JAK/STAT signalling was recognized in discrepant progenitor lineages among different samples. Significantly disparate molecular profiling was identified in the comparison between ET patients and the control, between patients with different driver mutations (JAK2 V617F and CALR exon 9 indel), and even between patients harbouring the same driver. Intra-individual clonal diversity was also found in the CD34+ progenitor population of a patient, possibly indicating the presence of multiple clones in this case. Estimation of subpopulation size based on cellular immunophenotyping suggested differentiation bias in all analysed samples. Furthermore, combining the transcriptomic information with data from targeted sequencing enabled us to unravel key somatic mutations that are molecularly relevant. To conclude, we demonstrated that scRNA-Seq extended our knowledge of clonal diversity and inter-individual heterogeneity in patients with ET. The obtained information could potentially leapfrog our efforts in the elucidation of the pathogenesis of the disease.

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.

A histopathological evaluation and potential prognostic implications of oral squamous cell carcinoma with adverse features.

OBJECTIVES: This study aimed to evaluate the adverse clinicopathologic features of oral squamous cell carcinoma (OSCC), including margin status, depth of invasion, lymphovascular invasion, perineural invasion, and extranodal extension that significantly affect survival outcomes. MATERIALS AND METHODS: This retrospective cross-sectional study included 341 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The Kaplan-Meier method was used to estimate survival outcomes. A multivariable Cox regression model was used to evaluate the associations of various clinicopathologic features with 5-year overall survival (OS) outcomes in patients with pN0 and pN+ tumors. RESULTS: Overall, the patients had 5-year OS and progression-free survival rates of 60.0 and 47.9%, respectively. In the pN0 group, the multivariate analysis identified a positive margin (odds ratio [OR] = 16.3, 95% confidence interval [95% CI]: 3.7-72.3; P = 0.001), depth of invasion >5 mm (OR = 2.1, 95% CI: 1.2-3.7; P = 0.012), presence of lymphovascular space invasion (OR = 5.4, 95% CI: 1.3-22.0; P = 0.018), and presence of perineural invasion (OR = 4.3, 95% CI: 1.7-11.1; P = 0.002) as independent and significant prognosticators of OS. In the pN+ group, only the presence of extranodal extension independently predicted OS (OR = 1.7, 95% CI: 1.1-2.7; P = 0.0026). CONCLUSIONS: When determining survival prognosis for patients with a pN0 status, we recommended including all adverse features. In contrast, extranodal extension was the most important prognostic factor for patients with a pN+ status.

ENVirT: inference of ecological characteristics of viruses from metagenomic data.

BACKGROUND: Estimating the parameters that describe the ecology of viruses,particularly those that are novel, can be made possible using metagenomic approaches. However, the best-performing existing methods require databases to first estimate an average genome length of a viral community before being able to estimate other parameters, such as viral richness. Although this approach has been widely used, it can adversely skew results since the majority of viruses are yet to be catalogued in databases. RESULTS: In this paper, we present ENVirT, a method for estimating the richness of novel viral mixtures, and for the first time we also show that it is possible to simultaneously estimate the average genome length without a priori information. This is shown to be a significant improvement over database-dependent methods, since we can now robustly analyze samples that may include novel viral types under-represented in current databases. We demonstrate that the viral richness estimates produced by ENVirT are several orders of magnitude higher in accuracy than the estimates produced by existing methods named PHACCS and CatchAll when benchmarked against simulated data. We repeated the analysis of 20 metavirome samples using ENVirT, which produced results in close agreement with complementary in virto analyses. CONCLUSIONS: These insights were previously not captured by existing computational methods. As such, ENVirT is shown to be an essential tool for enhancing our understanding of novel viral populations.

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.

Anti-oral cancer effects of triptolide by downregulation of DcR3 in vitro, in vivo, and in preclinical patient-derived tumor xenograft model.

BACKGROUND: Aberrant expression of decoy receptor 3 (DcR3) is considered to be a diagnostic and therapeutic target for human cancers. The aim of this study was to assess DcR3 as a target of the anticancer effects of triptolide (TPL) in preclinical patient-derived tumor xenograft (PDTX) models of oral squamous cell carcinoma (OSCC). METHODS: The expression of DcR3 was evaluated through immunohistochemistry, and correlations were examined using clinical variables. The effects of TPL on the expression of DcR3 and cell proliferation were investigated in OSCC cell lines and in PDTX models. RESULTS: DcR3 overexpression was associated with overall survival and tumor size. TPL significantly decreased tumor growth. Moreover, TPL inhibited the expression of metastasis-associated protein 1 (MTA1), a transcription factor for DcR3 in vivo, in vitro, and in PDTX models. CONCLUSION: TPL appeared to exert anticancer effects by repressing DcR3 and MTA1 in vitro, in vivo, and in PDTX models.

Microbial Functional Responses to Cholesterol Catabolism in Denitrifying Sludge.

The 2,3-seco pathway, the pathway for anaerobic cholesterol degradation, has been established in the denitrifying betaproteobacterium Sterolibacterium denitrificans. However, knowledge of how microorganisms respond to cholesterol at the community level is elusive. Here, we applied mesocosm incubation and 16S rRNA sequencing to reveal that, in denitrifying sludge communities, three betaproteobacterial operational taxonomic units (OTUs) with low (94% to 95%) 16S rRNA sequence similarity to Stl. denitrificans are cholesterol degraders and members of the rare biosphere. Metatranscriptomic and metabolite analyses show that these degraders adopt the 2,3-seco pathway to sequentially catalyze the side chain and sterane of cholesterol and that two molybdoenzymes-steroid C25 dehydrogenase and 1-testosterone dehydrogenase/hydratase-are crucial for these bioprocesses, respectively. The metatranscriptome further suggests that these betaproteobacterial degraders display chemotaxis and motility toward cholesterol and that FadL-like transporters may be the key components for substrate uptake. Also, these betaproteobacteria are capable of transporting micronutrients and synthesizing cofactors essential for cellular metabolism and cholesterol degradation; however, the required cobalamin is possibly provided by cobalamin-de novo-synthesizing gamma-, delta-, and betaproteobacteria via the salvage pathway. Overall, our results indicate that the ability to degrade cholesterol in sludge communities is reserved for certain rare biosphere members and that C25 dehydrogenase can serve as a biomarker for sterol degradation in anoxic environments. IMPORTANCE Steroids are ubiquitous and abundant natural compounds that display recalcitrance. Biodegradation via sludge communities in wastewater treatment plants is the primary removal process for steroids. To date, compared to studies for aerobic steroid degradation, the knowledge of anaerobic degradation of steroids has been based on only a few model organisms. Due to the increase of anthropogenic impacts, steroid inputs may affect microbial diversity and functioning in ecosystems. Here, we first investigated microbial functional responses to cholesterol, the most abundant steroid in sludge, at the community level. Our metagenomic and metatranscriptomic analyses revealed that the capacities for cholesterol approach, uptake, and degradation are unique traits of certain low-abundance betaproteobacteria, indicating the importance of the rare biosphere in bioremediation. Apparent expression of genes involved in cofactor de novo synthesis and salvage pathways suggests that these micronutrients play important roles for cholesterol degradation in sludge communities.

Comprehensive Insights Into Composition, Metabolic Potentials, and Interactions Among Archaeal, Bacterial, and Viral Assemblages in Meromictic Lake Shunet in Siberia.

Microorganisms are critical to maintaining stratified biogeochemical characteristics in meromictic lakes; however, their community composition and potential roles in nutrient cycling are not thoroughly described. Both metagenomics and metaviromics were used to determine the composition and capacity of archaea, bacteria, and viruses along the water column in the landlocked meromictic Lake Shunet in Siberia. Deep sequencing of 265 Gb and high-quality assembly revealed a near-complete genome corresponding to Nonlabens sp. sh3vir. in a viral sample and 38 bacterial bins (0.2-5.3 Mb each). The mixolimnion (3.0 m) had the most diverse archaeal, bacterial, and viral communities, followed by the monimolimnion (5.5 m) and chemocline (5.0 m). The bacterial and archaeal communities were dominated by Thiocapsa and Methanococcoides, respectively, whereas the viral community was dominated by Siphoviridae. The archaeal and bacterial assemblages and the associated energy metabolism were significantly related to the various depths, in accordance with the stratification of physicochemical parameters. Reconstructed elemental nutrient cycles of the three layers were interconnected, including co-occurrence of denitrification and nitrogen fixation in each layer and involved unique processes due to specific biogeochemical properties at the respective depths. According to the gene annotation, several pre-dominant yet unknown and uncultured bacteria also play potentially important roles in nutrient cycling. Reciprocal BLAST analysis revealed that the viruses were specific to the host archaea and bacteria in the mixolimnion. This study provides insights into the bacterial, archaeal, and viral assemblages and the corresponding capacity potentials in Lake Shunet, one of the three meromictic lakes in central Asia. Lake Shunet was determined to harbor specific and diverse viral, bacterial, and archaeal communities that intimately interacted, revealing patterns shaped by indigenous physicochemical parameters.

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.

Danshen extract circumvents drug resistance and represses cell growth in human oral cancer cells.

BACKGROUND: Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This study investigated the antiproliferative effects of a Danshen extract on human oral cancer SAS, SCC25, OEC-M1, and KB drug-resistant cell lines and elucidated the possible underlying mechanism. METHODS: We investigated the anticancer potential of the Danshen extract in human oral cancer cell lines and an in vivo oral cancer xenograft mouse model. The expression of apoptosis-related molecules was evaluated through Western blotting, and the concentration of in vivo apoptotic markers was measured using immunohistochemical staining. The antitumor effects of 5-fluorouracil and the Danshen extract were compared. RESULTS: Cell proliferation assays revealed that the Danshen extract strongly inhibited oral cancer cell proliferation. Cell morphology studies revealed that the Danshen extract inhibited the growth of SAS, SCC25, and OEC-M1 cells by inducing apoptosis. The Flow cytometric analysis indicated that the Danshen extract induced cell cycle G0/G1 arrest. Immunoblotting analysis for the expression of active caspase-3 and X-linked inhibitor of apoptosis protein indicated that Danshen extract-induced apoptosis in human oral cancer SAS cells was mediated through the caspase pathway. Moreover, the Danshen extract significantly inhibited growth in the SAS xenograft mouse model. Furthermore, the Danshen extract circumvented drug resistance in KB drug-resistant oral cancer cells. CONCLUSION: The study results suggest that the Danshen extract could be a potential anticancer agent in oral cancer treatment.