This study showed an interaction between oral bacteria, lifestyle factors and genetic polymorphisms on the risk of oral cancer. The results also provided biological support for the established ...association between poor oral hygiene and oral cancer risk.
Abstract
Poor oral hygiene may lead to overgrowth of pathogenic oral bacteria, which may induce chronic inflammation to promote the oncogenesis of oral squamous cell carcinoma (OSCC). This study investigated the association between oral bacterial profile and OSCC risk in a case-control study of 138 OSCC cases and 151 controls (88 cases and 90 controls for the discovery group and 50 cases and 61 controls for the validation group). Oral bacterial profiles were characterized by targeted sequencing of the 16S rRNA gene. Three species of periodontopathogenic bacteria, Prevotella tannerae, Fusobacterium nucleatum, and Prevotella intermedia, were associated with an increased OSCC risk. This association was modified by the genetic polymorphisms of TLR2 and TLR4. Use of alcohol, betel quids and cigarettes and poor oral hygiene were associated with a higher percentage of oral periodontopathogenic bacteria. The association between alcohol and periodontopathogenic bacteria was modified by the genetic polymorphism of ALDH2, with a stronger positive association observed among the ALDH2-deficient individuals. The percentage of periodontopathogenic bacteria was positively correlated with the level of salivary IL1β, an inflammatory cytokine. Overall, our results showed a positive association between periodontopathogenic bacteria and OSCC risk and this relationship may be influenced by lifestyle and genetic factors. Our results provided further biological support for the established association between poor oral hygiene and OSCC risk. This suggested that improving oral hygiene may reduce OSCC risk and should be part of a public health campaign to prevent the occurrence of OSCC.
Trastuzumab emtansine (T-DM1) is an antibody drug conjugate (ADC) that was recently approved for the treatment of HER-2-positive metastatic breast cancer. The drug sensitivity of ADCs depends mainly ...on the internalization efficiency of the drug. Caveolin-1 was shown to promote T-DM1 internalization and enhance drug sensitivity. Whether caveolin-1 can be overexpressed to improve T-DM1 efficacy is interesting and has the potential for clinical application. In this study, diabetes drug metformin was investigated in terms of induction of caveolin-1 expression for increased efficacy of subsequent T-DM1 application. BT-474 cells were pretreated with metformin, followed by combined therapy with metformin and T-DM1. The T-DM1 internalization and drug efficacy were determined, and the protein expressions for signal transduction were also monitored. Caveolin-1 shRNA was applied to suppress endogenous caveolin-1 expression, and the ability of metformin to promote T-DM1 efficacy was investigated. Result showed that in BT-474 cells pretreated with metformin, cellular caveolin-1 overexpression was induced, which then promoted drug efficacy by enhancing T-DM1 internalization. As cellular caveolin-1 was suppressed by shRNA, the effect of metformin-enhanced T-DM1 cytotoxicity was decreased. This study demonstrated that metformin can be applied prior to T-DM1 treatment to improve the clinical efficacy of T-DM1 by enhancing caveolin-1-mediated endocytosis.
2D ferroelectric material has emerged as an attractive building block for high‐density data storage nanodevices. Although monolayer van der Waals ferroelectrics have been theoretically predicted, a ...key experimental breakthrough for such calculations is still not realized. Here, hexagonally stacking α‐In2Se3 nanoflake, a rarely studied van der Waals polymorph, is reported to exhibit out‐of‐plane (OOP) and in‐plane (IP) ferroelectricity at room temperature. Ferroelectric multidomain states in a hexagonal α‐In2Se3 nanoflake with uniform thickness can survive to 6 nm. Most strikingly, the electric‐field‐induced polarization switching and hysteresis loop are, respectively, observed down to the bilayer and monolayer (≈1.2 nm) thicknesses, which designates it as the thinnest layered ferroelectric and verifies the corresponding theoretical calculation. In addition, two types of ferroelectric nanodevices employing the OOP and IP polarizations in 2H α‐In2Se3 are developed, which are applicable for nonvolatile memories and heterostructure‐based nanoelectronics/optoelectronics.
The thinnest layered ferroelectric is demonstrated for the first time at room temperature. The semiconducting hexagonal α‐In2Se3 nanoflakes exhibit out‐of‐plane and in‐plane ferroelectricity that are closely intercorrelated. The polarization switching and hysteresis loops can be realized in the thickness as thin as ≈2.3 nm (bilayer) and ≈1.2 nm (monolayer). Two types of ferroelectric switchable devices are proposed to show the potential application in nonvolatile memories.
It is critically important to characterize the band alignment in semiconductor heterojunctions (HJs) because it controls the electronic and optical properties. However, the well‐known Anderson's ...model usually fails to predict the band alignment in bulk HJ systems due to the presence of charge transfer at the interfacial bonding. Atomically thin 2D transition metal dichalcogenide materials have attracted much attention recently since the ultrathin HJs and devices can be easily built and they are promising for future electronics. The vertical HJs based on 2D materials can be constructed via van der Waals stacking regardless of the lattice mismatch between two materials. Despite the defect‐free characteristics of the junction interface, experimental evidence is still lacking on whether the simple Anderson rule can predict the band alignment of HJs. Here, the validity of Anderson's model is verified for the 2D heterojunction systems and the success of Anderson's model is attributed to the absence of dangling bonds (i.e., interface dipoles) at the van der Waal interface. The results from the work set a foundation allowing the use of powerful Anderson's rule to determine the band alignments of 2D HJs, which is beneficial to future electronic, photonic, and optoelectronic devices.
The band alignment of stacked 2D material heterojunctions is experimentally proven to follow the Anderson's model. Based on this discovery it is demonstrated that electron affinity and band gap values are sufficient to construct the band alignment of stacked 2D heterojunctions.
Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently ...needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies.
Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association ...between alcohol or cigarette use and HNC risk. The current case‐control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio OR = 2.07; 95% confidence interval CI, 1.53‐2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04‐1.85) (heterogeneity‐P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2‐deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.
Monolayer molybdenum disulfide (MoS2) has become a promising building block in optoelectronics for its high photosensitivity. However, sulfur vacancies and other defects significantly affect the ...electrical and optoelectronic properties of monolayer MoS2 devices. Here, highly crystalline molybdenum diselenide (MoSe2) monolayers have been successfully synthesized by the chemical vapor deposition (CVD) method. Low-temperature photoluminescence comparison for MoS2 and MoSe2 monolayers reveals that the MoSe2 monolayer shows a much weaker bound exciton peak; hence, the phototransistor based on MoSe2 presents a much faster response time (<25 ms) than the corresponding 30 s for the CVD MoS2 monolayer at room temperature in ambient conditions. The images obtained from transmission electron microscopy indicate that the MoSe exhibits fewer defects than MoS2. This work provides the fundamental understanding for the differences in optoelectronic behaviors between MoSe2 and MoS2 and is useful for guiding future designs in 2D material-based optoelectronic devices.
Computing-in-memory (CIM) based on embedded nonvolatile memory is a promising candidate for energy-efficient multiply-and-accumulate (MAC) operations in artificial intelligence (AI) edge devices. ...However, circuit design for NVM-based CIM (nvCIM) imposes a number of challenges, including an arealatency-energy tradeoff for multibit MAC operations, patterndependent degradation in signal margin, and small read margin. To overcome these challenges, this article proposes the following: 1) a serial-input non-weighted product (SINWP) structure; 2) a down-scaling weighted current translator (DSWCT) and positive-negative current-subtractor (PN-ISUB); 3) a currentaware bitline clamper (CABLC) scheme; and 4) a triple-margin small-offset current-mode sense amplifier (TMCSA). A 55-nm 1-Mb ReRAM-CIM macro was fabricated to demonstrate the MAC operation of 2-b-input, 3-b-weight with 4-b-out. This nvCIM macro achieved T MAC = 14.6 ns at 4-b-out with peak energy efficiency of 53.17 TOPS/W.
Sarcopenia, a gradual loss of muscle mass and function, has been associated with poor health outcomes. Its correlation with another age-related degenerative process, impaired cognition, remains ...uncertain. This meta-analysis aimed to determine whether there is an association between sarcopenia and cognitive impairment.
PubMed and Scopus were searched for observational studies that investigated the association between sarcopenia and cognitive dysfunction. Participants' demographics and measurements, definition of sarcopenia, and tools for evaluating cognitive function were retrieved. The correlations between sarcopenia and cognitive impairment were expressed as crude and adjusted odds ratios with 95% confidence intervals (CIs).
Seven cross-sectional studies comprising 5994 participants were included. The crude and adjusted odds ratios were 2.926 (95% CI, 2.297-3.728) and 2.246 (95% CI, 1.210-4.168), respectively. The subgroup analysis showed that different target populations and sex specificity did not significantly modify the association, whereas the tools for evaluating cognitive function and modalities for measuring body composition did.
Sarcopenia was independently associated with cognitive impairment. Future cohort studies are warranted to clarify the causal correlation. The inclusion of relevant biomarkers and functional measurements is also recommended to elucidate the underlying biological mechanism.
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