Comparison between piezoelectric force microscopy images and current‐voltage data consecutively obtained using conductive atomic force microscopy below transition voltages for a highly oriented ...ferroelectric BiFeO3 nano‐island confirms that ferroelectric polarization reversal induces transitions of forward‐direction, and thus down‐ and up‐polarization is accompanied by positive‐ and negative‐forward diode‐like behavior, respectively.
Non-small cell lung cancer (NSCLC), which represents 80–85% of lung cancer cases, is one of the leading causes of human death worldwide. The majority of patients undergo an intensive and invasive ...treatment regimen, which may include radiotherapy, chemotherapy, targeted therapy, immunotherapy, or a combination of these, depending on disease stage and performance status. Despite advances in therapeutic regimens, the 5-year survival of NSCLC is approximately 20–30%, largely due to diagnosis at advanced stages. Conventional chemotherapy is still the standard treatment option for patients with NSCLC, especially those with advanced disease. However, the emergence of resistance to chemotherapeutic agents (chemoresistance) poses a significant obstacle to the management of patients with NSCLC. Therefore, to develop efficacious chemotherapeutic approaches for NSCLC, it is necessary to understand the mechanisms underlying chemoresistance. Several mechanisms are known to mediate chemoresistance. These include altered cellular targets for chemotherapy, decreased cellular drug concentrations, blockade of chemotherapy-induced cell cycle arrest and apoptosis, acquisition of epithelial–mesenchymal transition and cancer stem cell-like phenotypes, deregulated expression of microRNAs, epigenetic modulation, and the interaction with tumor microenvironments. In this review, we summarize the mechanisms underlying chemoresistance and tumor recurrence in NSCLC and discuss potential strategies to avoid or overcome chemoresistance.
Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common inflammatory skin ...disease; however, the association with vitamin D remains unclear.
We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D supplementation.
This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months.
Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the healthy controls. The level of 25(OH)D was inversely associated with the severity of acne, and there was a significant negative correlation with inflammatory lesions. In a subsequent trial, improvement in inflammatory lesions was noted after supplementation with vitamin D in 39 acne patients with 25(OH)D deficiency.
Limitations of the study include the small number of patients in the supplementation study and the natural fluctuation of acne.
Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels were inversely correlated with acne severity, especially in patients with inflammatory lesions.
CRISPR effectors, which comprise a CRISPR-Cas protein and a guide (g)RNA derived from the bacterial immune system, are widely used for target-specific genome editing. When the gRNA recognizes genomic ...loci with sequences that are similar to the target, deleterious mutations can occur. Off-target mutations with a frequency below 0.5% remain mostly undetected by current genome-wide off-target detection techniques. Here we report a method to effectively detect extremely small amounts of mutated DNA based on predicted off-target-specific amplification. In this study, we used various genome editors to induce intracellular genome mutations, and the CRISPR amplification method detected off-target mutations at a significantly higher rate (1.6~984 fold increase) than an existing targeted amplicon sequencing method. In the near future, CRISPR amplification in combination with genome-wide off-target detection methods will allow detection of genome editor-induced off-target mutations with high sensitivity and in a non-biased manner.
X-box binding protein 1 (XBP1) mRNA processing plays a crucial role in the unfolded protein response (UPR), which is activated in response to endoplasmic reticulum (ER) stress. Upon accumulation of ...the UPR-converted XBP1 mRNA splicing from an unspliced (u) XBP1 (inactive) isoform to the spliced (s) XBP1 (active) isoform, inositol-requiring enzyme 1 α (IRE1α) removes a 26-nucleotide intron from uXBP1 mRNA. Recent studies have reported the assessment of ER stress by examining the ratio of sXBP1 to uXBP1 mRNA (s/uXBP1 ratio) via densitometric analysis of PCR bands relative to increased levels of sXBP1 to uXBP1 using a housekeeping gene for normalization. However, this measurement is visualized by gel electrophoresis, making it very difficult to quantify differences between the two XBP1 bands and complicating data interpretation. Moreover, most commonly used housekeeping genes display an unacceptably high variable expression pattern of the s/uXBP1 ratio under different experimental conditions, such as various phases of development and different cell types, limiting their use as internal controls. For a more quantitative determination of XBP1 splicing activity, we measured the expression levels of total XBP1 (tXBP1: common region of s/uXBP1) and sXBP1 via real-time PCR using specific primer sets. We also designed universal real-time PCR primer sets capable of amplifying a portion of each u/s/tXBP1 mRNA that is highly conserved in eukaryotes, including humans, monkeys, cows, pigs, and mice. Therefore, we provide a more convenient and easily approachable quantitative real-time PCR method that can be used in various research fields to assess ER stress.
Diets high in gelatinized starch and high in gelatinized starch supplemented with salt-induced metabolic disorders and changes in gut microbiota have scarcely been studied. In this study, mice on ...wheat starch diets (WD) exhibited significantly higher body weight, white adipose tissue (WAT), and gut permeability compared to those on normal diet (ND). However, gelatinized wheat starch diet (GWD) and NaCl-supplemented gelatinized wheat starch diet (SGW) mice did not increase body and WAT weights or dyslipidemia, and maintained consistent colon pH at ND levels. WD mice showed higher levels of
,
, and
and lower levels of
compared to ND mice. However, GWD and SGW mice showed a significantly different gut microbial composition, such as a lower proportion of
and
, and higher proportion of
and
compared to WD mice. High starch diet-induced dysbiosis caused increase of lipid accumulation and inflammation-related proteins' expression, thereby leading to non-alcoholic fatty liver disease. However, GWD and SGW showed lower levels than that, and it might be due to the difference in the gut microbial composition compared to WD. Taken together, diets high in gelatinized starch and high in gelatinized starch supplemented with salt induced mild metabolic disorders compared to native starch.
Polydimethylsiloxane (PDMS) has been widely used in fabricating microfluidic devices for prototyping and proof-of-concept experiments. Due to several material limitations, PDMS has not been widely ...adopted for commercial applications that require large-scale production. This paper describes a novel injection-molded plastic array 3D culture (IMPACT) platform that incorporates a microfluidic design to integrate patterned 3D cell cultures within a single 96-well (diameter = 9 mm) plate. Cell containing gels can be sequentially patterned by capillary-guided flow along the corner and narrow gaps designed within the 96-well form factor. Compared to PDMS-based hydrophobic burst valve designs, this work utilizes hydrophilic liquid guides to obtain rapid and reproducible patterned gels for co-cultures. When a liquid droplet (i.e. cell containing fibrin or collagen gel) is placed on a corner, spontaneous patterning is achieved within 1 second. Optimal dimensionless parameters required for successful capillary loading have been determined. To demonstrate the utility of the platform for 3D co-culture, angiogenesis experiments were performed by patterning HUVEC (human umbilical endothelial cells) and LF (lung fibroblasts) embedded in 3D fibrin gels. The angiogenic sprouts (with open lumen tip cells expressing junctional proteins) are comparable to those observed in PDMS based devices. The IMPACT device has the potential to provide a robust high-throughput experimental platform for vascularized microphysiological systems.
We present the origin of the observed differentiation of lactose and lactulose achieved by complexation with sodiated l -arginine (ArgNa + ). We find that the infrared multiphoton dissociation ...(IRMPD) bands in 3600–3650 and >3650 cm −1 regimes for gas phase lactose and lactulose, respectively, vanish when forming host–guest complexes with ArgNa + . We interpret these differences in the IRMPD spectra by scrutinizing the interactions between the functional groups (guanidium, –CO 2 − Na + ) in ArgNa + and –OHs in lactose/lactulose. Our calculated structures and infrared spectra of lactose/ArgNa + and lactulose/ArgNa + host–guest pairs indicate that the functional groups interact with the low- and high-frequency –OH stretch modes of lactose and lactulose, respectively, in the 3600–3720 cm −1 window.
...the authors used limited numbers of IVs (three single nucleotide polymorphisms (SNP) with top significance and seven SNPs on functionally relevant genes).1 Genetic instruments tend to have weak ...power due to the limited availability of population-specific information on genetic associations.3 Bias from weak instruments can result in misleading estimates of causal effects. If the variants in total explain a larger proportion of the variance in the exposure, this will lead to more precise estimates of causal effects, thus increasing the power for MR analysis.3 Therefore, the approach of using multiple genetic variants in different gene regions is suitable for an MR study. Including more instruments, where each instrument explains an extra variation in the phenotype, should provide more information on the causal estimate. ...I believe that the findings of this MR study should be interpreted by taking the aforementioned methodological concerns into consideration.
Although a number of different methods have been used to quantify soil bacteria, identifying the optimal method(s) for soil bacterial abundance is still in question. No single method exists for ...undertaking an absolute microbial count using culture-dependent methods (CDMs) or even culture-independent methods (CIMs). This study investigated soil storage and pretreatment methods for optimal bacterial counts. Appropriate storage temperature (4°C) and optimal pretreatment methods (sonication time for 3 min and centrifugation at 1400 g) were necessary to preserve bacterial cell viability and eliminate interference from soil particles. To better estimate soil bacterial numbers under various cellular state and respiration, this study also evaluated three CDMs (i.e., colony forming unit, spotting, and most probable number (MPN) and three CIMs (i.e., flow cytometry (FCM), epifluorescence microscopy (EM) count, and DNA quantitation). Each counting method was tested using 72 soil samples collected from a local arable farm site at three different depths (i.e., 10-20, 90-100, and 180-190 cm). Among all CDMs, MPN was found to be rapid, simple, and reliable. However, the number of bacteria quantified by MPN was 1-2 orders lower than that quantified by CIMs, likely due to the inability of MPN to count anaerobic bacteria. The DNA quantitation method appeared to overestimate soil bacterial numbers, which may be attributed to DNA from dead bacteria and free DNA in the soil matrix. FCM was found to be ineffective in counting soil bacteria as it was difficult to separate the bacterial cells from the soil particles. Dyes used in FCM stained the bacterial DNA and clay particles. The EM count was deemed a highly effective method as it provided information on soil mineral particles, live bacteria, and dead bacteria; however, it was a time-consuming and labor-intensive process. Combining both types of methods was considered the best approach to acquire better information on the characteristics of indigenous soil microorganisms (aerobic versus anaerobic, live versus dead).
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