Recent progress and prospects of dimer and multimer acceptors for efficient and stable polymer solar cells.

High power conversion efficiency (PCE) and long-term stability are essential prerequisites for the commercialization of polymer solar cells (PSCs). Small-molecule acceptors (SMAs) are core materials that have led to recent, rapid increases in the PCEs of the PSCs. However, a critical limitation of the resulting PSCs is their poor long-term stability. Blend morphology degradation from rapid diffusion of SMAs with low glass transition temperatures (Tgs) is considered the main cause of the poor long-term stability of the PSCs. The recent emergence of oligomerized SMAs (OSMAs), composed of two or more repeating SMA units (i.e., dimerized and trimerized SMAs), has shown great promise in overcoming these challenges. This innovation in material design has enabled OSMA-based PSCs to reach impressive PCEs near 19% and exceptional long-term stability. In this review, we summarize the evolution of OSMAs, including their research background and recent progress in molecular design. In particular, we discuss the mechanisms for high PCE and stability of OSMA-based PSCs and suggest useful design guidelines for high-performance OSMAs. Furthermore, we reflect on the existing hurdles and future directions for OSMA materials towards achieving commercially viable PSCs with high PCEs and operational stabilities.

Genome-wide identification of R2R3-MYB transcription factor subfamily genes involved in salt stress in rice (Oryza sativa L.).

BACKGROUND: R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. RESULTS: In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. CONCLUSION: This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.

Effects of Degreasing Pretreatment on Immunohistochemistry and Molecular Analysis of Gastrointestinal and Breast Cancer Samples.

Lymph node status is a key factor in determining stage, treatment, and prognosis in cancers. Small lymph nodes in fat-rich gastrointestinal and breast cancer specimens are easily missed in conventional sampling methods. This study examined the effectiveness of the degreasing pretreatment with dimethyl sulfoxide (DMSO) in lymph node detection and its impact on the analysis of clinical treatment-related proteins and molecules. Thirty-three cases of gastrointestinal cancer specimens from radical gastrectomy and 63 cases of breast cancer specimens from modified radical mastectomy were included. After routine sampling of lymph nodes, the specimens were immersed in DMSO for 30 minutes for defatting. We assessed changes in the number of detected lymph nodes and pN staging in 33 gastrointestinal cancer specimens and 37 breast cancer specimens. In addition, we analyzed histologic characteristics, Masson trichrome special staining, and immunohistochemistry (gastrointestinal cancer: MMR, HER2, and PD-L1; breast cancer: ER, PR, AR, HER2, Ki-67, and PD-L1). Molecular status was evaluated for colorectal cancer (KRAS, NRAS, BRAF, and microsatellite instability) and breast cancer (HER2) in gastrointestinal cancer specimens and the remaining 26 breast cancer specimens. Compared with conventional sampling, DMSO pretreatment increased the detection rate of small lymph nodes (gastrointestinal cancer: P < .001; breast cancer: P < .001) and improved pN staging in 1 case each of gastric cancer, colon cancer, and rectal cancer (3/33; 9.1%). No significant difference in the morphology, special staining, protein, and molecular status of cancer tissue after DMSO treatment was found. Based on these results and our institutional experience, we recommend incorporating DMSO degreasing pretreatment into clinical pathologic sampling practices.

Novel self-expandable stent-based endobiliary radiofrequency ablation for unresectable malignant biliary obstruction.

BACKGROUND AND AIMS: Endobiliary radiofrequency ablation (RFA) is an emerging endoscopic palliative adjunctive therapy used for the local treatment of unresectable malignant biliary obstruction (MBO). However, irregular ablation ranges caused by insufficient electrode-to-bile duct contact pose a significant obstacle. We investigated the feasibility of a self-expandable stent (SES)-based electrode with a customized RFA generator in the porcine liver and common bile duct (CBD). METHODS: An SES-RFA system with polarity switching was developed to perform endobiliary RFA. The ablation ranges of 20 ablation protocols were evaluated to validate the feasibility of the newly developed RFA system in the porcine liver. Nine of 20 ablation protocols were selected for evaluation in the porcine CBD with cholangiography, endoscopy, and histologic and immunohistochemical analysis. RESULTS: The SES-RFA system with polarity switching was successfully constructed and demonstrated high accuracy and reproducibility. The ablation area was clearly identified between the 2 SESs. The ablation ranges and degree of mucosal damage, including terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling-positive and heat shock protein 70-positive depositions, increased proportionally with ablation protocols in the porcine liver and CBD (all P < .05). Ablation length and depth linearly increased with ablation protocols from 8.74 ± .25 to 31.25 ± .67 mm and 1.61 ± .09 to 11.94 ± .44 mm, respectively. CONCLUSIONS: The SES-RFA system with polarity switching between electrodes provided an even circumferential area of ablation and enhanced ablation depth between the electrodes. This novel endobiliary RFA system is a promising modality for local ablation in patients with unresectable MBO.

Construction of Seven-Membered Oxacycles Using a Rh(I)-Catalyzed Cascade C-C Formation/Cleavage of Cyclobutenol Derivatives.

Herein, we describe the synthesis of substituted oxepane derivatives through the skeletal remodeling of 4-hydroxy-2-cyclobutenones, which are readily prepared from commercially available dialkyl squarates upon their reaction with acrylonitrile. Mechanistically, a Rh(I)-catalyzed C-C bond formation and cleavage cascade is proposed. Specifically, a fused [3.2.0] bicycle is proposed to form from dialkyl squarate-derived cyclobutenols via an unusual Rh(I)-catalyzed intermolecular oxa-Michael addition of a tertiary alcohol with acrylonitrile, followed by an intramolecular conjugate addition/migratory insertion. Subsequent C(sp3)-C(sp3) bond cleavage through a Rh-catalyzed ß-carbon elimination is then theorized to furnish the oxepane scaffold. Computational studies support the formation of an intermediate [3.2.0] bicycle but also point to an alternative pathway for the formation of the oxepane products involving a Rh(III) intermediate. Additional studies have shown the overall process to be stereoretentive. The functional groups that are introduced in this process can be leveraged to form fused or bridged ring systems.

Comparison of PET tracing and biodistribution between 64Cu-labeled micro-and nano-polystyrene in a murine inhalation model.

INTRODUCTION: Recent studies showed the presence of microplastic in human lungs. There remains an unmet need to identify the biodistribution of microplastic after inhalation. In this study, we traced the biodistribution of inhaled micro-sized polystyrene (mPS) and/or nano-sized PS (nPS) using 64Cu with PET in mice. METHODS: We used 0.2-0.3-µm sized mPS and 20-nm sized nPS throughout. 64Cu-DOTA-mPS, 64Cu-DOTA-nPS and/or 64CuCl2 were used to trace the distribution in the murine inhalation model. PET images were acquired using an INVEON PET scanner at 1, 12, 24, 48, and 72 h after intratracheal instillation, and the SUVmax for interesting organs were determined, biodistribution was then determined in terms of percentage injected dose/gram of tissue (%ID/g). Ex vivo tissue-radio thin-layer chromatography (Ex vivo-radioTLC) was used to demonstrate the existence of 64Cu-DOTA-PS in tissue. RESULTS: PET image demonstrated that the amount of 64Cu-DOTA-mPS retained within the lung was significantly higher than 64Cu-DOTA-nPS until 72 h; SUVmax values of 64Cu-DOTA-mPS in lungs was 11.7 ± 5.0, 48.3 ± 6.2, 65.5 ± 2.3, 42.2 ± 13.1, and 13.2 ± 2.3 at 1, 12, 24, 48, and 72 h respectively whereas it was 31.2 ± 3.1, 17.3 ± 5.9, 10.0 ± 3.4, 8.1 ± 2.4 and 8.9 ± 3.6 for 64Cu-DOTA-nPS at the corresponding timepoints. The biodistribution data supported the PET data with a similar pattern of clearance of the radioactivity from the lung. nPS cleared rapidly post instillation in comparison to mPS within the lungs. Higher accumulation of %ID/g for nPS (roughly 2 times) were observed compared to mPS in spleen, liver, intestine, thymus, kidney, brain, salivary gland, ovary, and urinary bladder. Ex vivo-radioTLC was used to demonstrate that the detected gamma rays originated from 64Cu-DOTA-mPS or nPS. CONCLUSION: PET image demonstrated the differences in accumulations of mPS and/or nPS between lungs and other interesting organs. The information provided may be used as the basis for future studies on the toxicity of mPS and/or nPS.

Prenatal to peripubertal exposure to Di(2-ethylhexyl) phthalate induced endometrial atrophy and fibrosis in female mice.

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.

Deep learning in negative small-bowel capsule endoscopy improves small-bowel lesion detection and diagnostic yield.

OBJECTIVES: Although several studies have shown the usefulness of artificial intelligence to identify abnormalities in small-bowel capsule endoscopy (SBCE) images, few studies have proven its actual clinical usefulness. Thus, the aim of this study was to examine whether meaningful findings could be obtained when negative SBCE videos were reanalyzed with a deep convolutional neural network (CNN) model. METHODS: Clinical data of patients who received SBCE for suspected small-bowel bleeding at two academic hospitals between February 2018 and July 2020 were retrospectively collected. All SBCE videos read as negative were reanalyzed with the CNN algorithm developed in our previous study. Meaningful findings such as angioectasias and ulcers were finally decided after reviewing CNN-selected images by two gastroenterologists. RESULTS: Among 202 SBCE videos, 103 (51.0%) were read as negative by humans. Meaningful findings were detected in 63 (61.2%) of these 103 videos after reanalyzing them with the CNN model. There were 79 red spots or angioectasias in 40 videos and 66 erosions or ulcers in 35 videos. After reanalysis, the diagnosis was changed for 10 (10.3%) patients who had initially negative SBCE results. During a mean follow-up of 16.5 months, rebleeding occurred in 19 (18.4%) patients. The rebleeding rate was 23.6% (13/55) for patients with meaningful findings and 16.1% (5/31) for patients without meaningful findings (P = 0.411). CONCLUSION: Our CNN algorithm detected meaningful findings in negative SBCE videos that were missed by humans. The use of deep CNN for SBCE image reading is expected to compensate for human error.

Calcium pyrophosphate crystal deposition with rotator cuff tear-A case report.

Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory arthritis induced by calcium pyrophosphate (CPP) crystals and clinically it is called pseudogout. It usually deposits in articular cartilage and in periarticular soft tissues. But no cases of pseudogout in the rotator cuff without cartilage deposition or destruction have been reported so far. We present a case of a 57-year-old woman who was diagnosed as pseudogout with rotator cuff tear.

Delivery Strategies of siRNA Therapeutics for Hair Loss Therapy.

Therapeutic needs for hair loss are intended to find small interfering ribonucleic acid (siRNA) therapeutics for breakthrough. Since naked siRNA is restricted to meet a druggable target in clinic,, delivery systems are indispensable to overcome intrinsic and pathophysiological barriers, enhancing targetability and persistency to ensure safety, efficacy, and effectiveness. Diverse carriers repurposed from small molecules to siRNA can be systematically or locally employed in hair loss therapy, followed by the adoption of new compositions associated with structural and environmental modification. The siRNA delivery systems have been extensively studied via conjugation or nanoparticle formulation to improve their fate in vitro and in vivo. In this review, we introduce clinically tunable siRNA delivery systems for hair loss based on design principles, after analyzing clinical trials in hair loss and currently approved siRNA therapeutics. We further discuss a strategic research framework for optimized siRNA delivery in hair loss from the scientific perspective of clinical translation.

Preoperative increased pronation angle of the first metatarsus associated with correction loss after hallux valgus surgery: A semi-weight-bearing computed tomography study.

BACKGROUND: The effect of preoperative first metatarsal pronation on postoperative prognosis of hallux valgus (HV) surgery is under investigation. Utilizing semi-weight-bearing computed tomography, the preoperative pronation angle was assessed to quantify its impact on postoperative prognosis. METHODS: In a retrospective analysis of 31 feet, those with re-increased hallux valgus angle postoperatively were classified as the non-maintained group, and the remainder as the maintained group. Preoperative pronation angles were compared to establish a threshold. Subsequently, feet were re-classified into high or low-pronation categories. The relative risk of non-maintenance in high-pronation category was calculated. RESULTS: The non-maintained group exhibited a significantly higher preoperative pronation angle (p = 0.021), with a 28.4º threshold. The high-pronation category had a relative risk of 2.34 for non-maintenance. CONCLUSIONS: Increased preoperative first metatarsal pronation angle is associated with correction loss after HV surgery. Utilizing sWBCT to measure the pronation angle provides valuable insights into postoperative prognosis. LEVEL OF EVIDENCE: III.

Intranasal administration of nucleus-deliverable GATA3-TMD alleviates the symptoms of allergic asthma.

Although the T helper 2 (Th2) subset is a critical player in the humoral immune response to extracellular parasites and suppression of Th1-mediated inflammation, Th2 cells have been implicated in allergic inflammatory diseases such as asthma, allergic rhinitis, and atopic dermatitis. GATA binding protein 3 (GATA3) is a primary transcription factor that mediates Th2 differentiation and secretion of Th2 cytokines, including IL-4, IL-5, and IL-13. Here, a nucleus-deliverable form of GATA3-transcription modulation domain (TMD) (ndG3-TMD) was generated using Hph-1 human protein transduction domain (PTD) to modulate the transcriptional function of endogenous GATA3 without genetic manipulation. ndG3-TMD was shown to be efficiently delivered into the cell nucleus quickly without affecting cell viability or intracellular signaling events for T cell activation. ndG3-TMD exhibited a specific inhibitory function for the endogenous GATA3-mediated transcription, such as Th2 cell differentiation and Th2-type cytokine production. Intranasal administration of ndG3-TMD significantly alleviated airway hyperresponsiveness, infiltration of immune cells, and serum IgE level in an OVA-induced mouse model of asthma. Also, Th2 cytokine secretion by the splenocytes isolated from the ndG3-TMD-treated mice substantially decreased. Our results suggest that ndG3-TMD can be a new therapeutic reagent to suppress Th2-mediated allergic diseases through intranasal delivery.

The OsNAC24-OsNAP protein complex activates OsGBSSI and OsSBEI expression to fine-tune starch biosynthesis in rice endosperm.

Starch accounts for up to 90% of the dry weight of rice endosperm and is a key determinant of grain quality. Although starch biosynthesis enzymes have been comprehensively studied, transcriptional regulation of starch-synthesis enzyme-coding genes (SECGs) is largely unknown. In this study, we explored the role of a NAC transcription factor, OsNAC24, in regulating starch biosynthesis in rice. OsNAC24 is highly expressed in developing endosperm. The endosperm of osnac24 mutants is normal in appearance as is starch granule morphology, while total starch content, amylose content, chain length distribution of amylopectin and the physicochemical properties of the starch are changed. In addition, the expression of several SECGs was altered in osnac24 mutant plants. OsNAC24 is a transcriptional activator that targets the promoters of six SECGs; OsGBSSI, OsSBEI, OsAGPS2, OsSSI, OsSSIIIa and OsSSIVb. Since both the mRNA and protein abundances of OsGBSSI and OsSBEI were decreased in the mutants, OsNAC24 functions to regulate starch synthesis mainly through OsGBSSI and OsSBEI. Furthermore, OsNAC24 binds to the newly identified motifs TTGACAA, AGAAGA and ACAAGA as well as the core NAC-binding motif CACG. Another NAC family member, OsNAP, interacts with OsNAC24 and coactivates target gene expression. Loss-of-function of OsNAP led to altered expression in all tested SECGs and reduced the starch content. These results demonstrate that the OsNAC24-OsNAP complex plays key roles in fine-tuning starch synthesis in rice endosperm and further suggest that manipulating the OsNAC24-OsNAP complex regulatory network could be a potential strategy for breeding rice cultivars with improved cooking and eating quality.

Association between regular physical activity and lower incidence of colorectal cancer in patients with diabetes mellitus: a nationwide cohort study.

AIM: The aim of this work was to investigate the association between changes in physical activity (PA) status and the development of colorectal cancer (CRC) in patients with diabetes. METHOD: This nationwide population study included 1 439 152 patients with diabetes who underwent a health screening provided by the Korean National Health Insurance Service between January 2009 and December 2012 and a follow-up screening after 2 years. Based on changes in PA status, participants were categorized into four groups: remained inactive, remained active, active-to-inactive and inactive-to-active. RESULTS: During the median follow-up period of 5.2 years, 38 244 new cases of CRC were diagnosed. Compared with the remained inactive group, among the three other groups, the remained active group had the lowest risk of CRC [adjusted hazard ratio (aHR) 0.93; 95% CI 0.90-0.96], followed by the inactive-to-active group (aHR 0.97; 95% CI 0.94-1.00) and active-to-inactive group (aHR 0.99; 95% CI 0.96-1.02), after adjusting for confounding variables (p = 0.0007). This reduction in cancer incidence in the remained active group was observed for both rectal cancer (aHR 0.87, 95% CI 0.79-0.95) and colon cancer (aHR 0.93, 95% CI 0.90-0.97), irrespective of sex. In terms of the intensity and amount of PA, moderate intensity PA was the most effective, and a positive correlation was found between the amount of PA and the reduction in CRC incidence. CONCLUSION: Regular PA was independently associated with a decreased risk of CRC in patients with diabetes. The intensity and amount of physical activity both play a role in reducing the risk.

Performance of Balloon-Assisted Enteroscopy for Non-ERCP Indications in Patients with Surgically Altered Gastrointestinal Anatomy.

BACKGROUND AND AIMS: Surgically altered gastrointestinal (GI) tract anatomy hinders deep enteroscopy. While enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) in patients with altered GI anatomy has been heavily investigated, the role of non-ERCP balloon-assisted enteroscopy (BAE) has yet to be fully elucidated.Please check and confirm the author names and initials are correct. Also, kindly confirm the details in the metadata are correct.I have checked all you asked and have no correction.  Thank you. METHODS: A multicenter retrospective study of non-ERCP BAEs in patients with surgically altered GI tract anatomy at two tertiary academic hospitals was performed from January 2006 to December 2020. Altered GI tract anatomy was defined by surgical reconstruction affecting the length, angle, or overall trajectory of the endoscope during the intended approach. The main outcome measurements included technical success rate, diagnostic and therapeutic yields, and complication rate.Please check the edit made in the title of the article and correct if necessary.No more correction. Thank you. RESULTS: A total of 68 patients with surgically altered GI tract anatomy underwent 56 antegrade and 24 retrograde non-ERCP BAE procedures. The technical success rate was 86.2% in both, including 83.9% via antegrade approach and 91.7% via retrograde approach. Antegrade approach in Roux-en-Y anatomy was associated with the lowest success rate of 77.8%, whereas retrograde approach in patients with colon resection resulted in the highest rate of 100%. The diagnostic and therapeutic yields of non-ERCP BAE were 79.4% and 82.9%, respectively. The diagnostic yields varied according to the procedural indications. The major complication was luminal perforation in one case (1.3%). CONCLUSIONS: Non-ERCP BAE is effective and safe via both antegrade and retrograde approaches with a high technical success rate and diagnostic and therapeutic yields in patients with surgically altered GI tract anatomy.

Examining the factors associated with inpatients' perception of overtreatment in Korea: a cross-sectional study.

BACKGROUND: Patients' perception of receiving overtreatment can cause distrust in medical services. Unlike outpatients, inpatients are highly likely to receive many medical services without fully understanding their medical situation. This information asymmetry could prompt inpatients to perceive treatment as excessive. This study tested the hypothesis that there are systematic patterns in inpatients' perceptions of overtreatment. METHODS: We examined determinant factors of inpatients' perception of overtreatment in a cross-sectional design that used data from the 2017 Korean Health Panel (KHP), a nationally representative survey. For sensitivity analysis, the concept of overtreatment was analyzed by dividing it into a broad meaning (any overtreatment) and a narrow meaning (strict overtreatment). We performed chi-square for descriptive statistics, and multivariate logistic regression with sampling weights employing Andersen's behavioral model. RESULTS: There were 1,742 inpatients from the KHP data set that were included in the analysis. Among them, 347 (19.9%) reported any overtreatment and 77 (4.42%) reported strict overtreatment. Furthermore, we found that the inpatient's perception of overtreatment was associated with gender, marital status, income level, chronic disease, subjective health status, health recovery, and general tertiary hospital. CONCLUSION: Medical institutions should understand factors that contribute to inpatients' perception of overtreatment to mitigate patients' complaints due to information asymmetry. Moreover, based on the result of this study, government agencies, such as the Health Insurance Review and Assessment Service, should create policy-based controls and evaluate overtreatment behavior of the medical providers and intervene in the miscommunication between patients and providers.

Occurrence, time trends, and human exposure of siloxanes and synthetic musk compounds in indoor dust from Korean homes.

Siloxanes and synthetic musk compounds (SMCs) have been widely used as additives in household and personal care products. Humans are easily exposed to siloxanes and SMCs originating from these products through ingestion and dermal absorption of indoor dust. In the present study, indoor dust samples were analyzed for 19 siloxanes (cyclic and linear) and 12 SMCs (polycyclic, macrocyclic, and nitro musks) to assess their occurrence, time trends over time, source, and health risks. A total of 18 siloxanes and 10 SMCs were detected in all indoor dust samples obtained from 2011⎯2021, indicating widespread and long-term contamination. Higher detection frequencies and concentrations were associated with siloxanes and SMCs with higher use and strong resistance against degradation processes. Indoor dust samples were dominated by linear siloxanes (L11-L13), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran (HHCB), musk ketone (MK), and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN). The frequent use of household and personal care products is likely an important source of siloxane and SMC contamination in indoor environments. The concentrations of siloxanes and SMCs in indoor dust increased from 2011 to 2021, particularly, those of linear siloxanes, reflecting the impact of regulatory actions addressing cyclic siloxanes. The profiles of siloxanes remained stable throughout the study period, whereas those of SMCs shifted from nitro to polycyclic musks. The estimated daily intakes (EDIs) of siloxanes and SMCs arising from ingestion were greater than from dermal absorption of indoor dust. The EDIs of siloxanes and SMCs associated with indoor dust indicated that children are exposed to these pollutants.

Functional significance of serine 13 in the active site of glutathione S-transferase F3 from Oryza sativa.

Plant glutathione S-transferase (GST, EC 2.5.1.18) is an enzyme that detoxifies various electrophilic compounds including herbicides and organic pollutants by catalyzing the formation of conjugates with reduced glutathione (GSH). Although the structure and function of the GST subunits in rice, an important food in Asia, are not well understood, they are crucial for herbicide development. To investigate the role of active site residues in rice Phi-class GSTF3 (OsGSTF3), evolutionarily conserved serine residues were replaced with alanine using site-directed mutagenesis to obtain the mutants S13A, S38A, S69A, and S169A. These four mutants were expressed in Escherichia coli and purified to electrophoretic homogeneity using immobilized GSH affinity chromatography. Mutation of Ser13 to Ala resulted in substantial reductions in specific activities and kcat/Km values for the GSH-[1-chloro-2,4-dinitrobenzene (CDNB)] conjugation reaction. In contrast, mutations of Ser38, Ser69, and Ser169 to Ala had little effect on the activities and kinetic parameters. Additionally, the mutation of Ser13 to Ala significantly affected the KmGSH and I50 values of S-hexylglutathione and S-(2,4-dinitrophenyl)glutathione, which compete with GSH and the product of GSH-CDNB conjugation, respectively. A pH-log (kcat/KmCDNB) plot was used to estimate the pKa value of GSH in the enzyme-GSH complex of the wild-type enzyme, which was approximately 6.9. However, the pKa value of GSH in the enzyme-GSH complex of the S13A mutant was approximately 8.7, which was about 1.8 pK units higher than that of the wild-type enzyme. OsGSTF3 was also crystallized for crystallographic study, and the structure analyses revealed that Ser13 is located in the active site and that its side chain is in close proximity to the thiol group of glutathione bound in the enzyme. Based on these substitution effects on kinetic parameters, the dependence of kinetic parameters on the pH and 3-dimensional structure, it was suggested that Ser13 in rice OsGSTF3 is the residue responsible for catalytic activity by lowering the pKa of GSH in the enzyme-GSH complex and enhancing the nucleophilicity of the GSH thiol in the active site.

Pharmacokinetics and Tissue Distribution of Bee Venom-Derived Phospholipase A2 Using a Sandwich ELISA after Subcutaneous Injection of New Composition Bee Venom in Rats.

Bee venom is a traditional drug used to treat the nervous system, musculoskeletal system, and autoimmune diseases. A previous study found that bee venom and one of its components, phospholipase A2, can protect the brain by suppressing neuroinflammation and can also be used to treat Alzheimer's disease. Thus, new composition bee venom (NCBV), which has an increased phospholipase A2 content of up to 76.2%, was developed as a treatment agent for Alzheimer's disease by INISTst (Republic of Korea). The aim of this study was to characterize the pharmacokinetic profiles of phospholipase A2 contained in NCBV in rats. Single subcutaneous administration of NCBV at doses ranging from 0.2 mg/kg to 5 mg/kg was conducted, and pharmacokinetic parameters of bee venom-derived phospholipase A2 (bvPLA2) increased in a dose-dependent manner. Additionally, no accumulation was observed following multiple dosings (0.5 mg/kg/week), and other constituents of NCBV did not affect the pharmacokinetic profile of bvPLA2. After subcutaneous injection of NCBV, the tissue-to-plasma ratios of bvPLA2 for the tested nine tissues were all <1.0, indicating a limited distribution of the bvPLA2 within the tissues. The findings of this study may help understand the pharmacokinetic characteristics of bvPLA2 and provide useful information for the clinical application of NCBV.

CHRAC1 promotes human lung cancer growth through regulating YAP transcriptional activity.

ATP-dependent chromatin remodeling complexes regulate chromatin structure and play important roles in gene expression, differentiation, development and cancer progression. Dysregulation in the subunits of the complexes often has been found in different cancers, but how they influence cancer initiation and progression is not fully understood. Here, we show that Chromatin Accessibility Complex Subunit 1 (CHRAC1), the accessory subunit of chromatin remodeling complex, is highly expressed in lung cancer tissues, which correlates with poor prognosis in lung cancer patients. CHRAC1 overexpression promotes lung cancer cell proliferation and migration in vitro and tumor growth in genetically engineered KrasG12D.LSL lung adenocarcinoma mouse model. Consistent with this, CHRAC1 silencing inhibits cell proliferation and migration in lung cancer cells and suppresses tumor growth in xenograft mouse model. Further, CHRAC1 binds to the transcription coactivator Yes-associated protein (YAP), enhances the transcription of downstream target oncogenes in Hippo pathway and thus promotes the tumor growth. Together, our study defines a critical role of CHRAC1 in promoting YAP transcriptional activity and lung cancer tumorigenesis, which makes it a potential target for lung cancer.