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Oxygen evolution reaction is a pivotal anodic reaction for electrolysis, however, it remains the obstacle from its sluggish reaction kinetics originating from multiple electron transfer pathways at electrochemical interfaces. Especially, it remains a challenge to achieve stable operation at elevated current densities as electrodes suffer oxidative environment in corrosive conditions. Herein, we report that the conducting polymer polypyrrole electrodeposited Pr0.7Sr0.3CoO3 perovskite oxides for durable oxygen evolution electrodes. We found that the conducting polymer electrodeposited oxides exhibited a highly durable electrochemical oxygen evolution performance maintaining >99% of initial activities during the accelerated durability test. Meanwhile, bare metal oxides presented significant performance drops (<6% of initial activities) over the consecutive 20,000 accelerated durability test. High-resolution transmission electron microscope images identified the maintenance of high crystallinity of the heterostructure, suggesting that the electrodeposited pPy clusters can effectively delocalize highly polarized electrodes preventing material corrosion. The overall water electrolysis experiments further demonstrated that the heterostructure showed excellent stability at the high current density of 100 mA cm-2 over 700 hours. This marks the first report of the delocalized polarization benefiting from conducting polymers for durable oxygen evolution for perovskite oxides, suggesting great potential for scalable water electrolysis., (© 2024 Wiley‐VCH GmbH.)

Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology. MECP2 duplication syndrome (MDS or MRXSL in OMIM; OMIM#300260) is one such CNV disorder caused by duplications spanning methyl CpG-binding protein 2 (MECP2) and other genes on Xq28. Using an antisense oligonucleotide (ASO) to normalize MECP2 dosage is sufficient to rescue abnormal neurological phenotypes in mouse models overexpressing MECP2 alone, implicating the importance of increased MECP2 dosage within CNVs of Xq28. However, because MDS CNVs span MECP2 and additional genes, we generated human neurons from multiple MDS patient-derived induced pluripotent cells (iPSCs) to evaluate the benefit of using an ASO against MECP2 in a MDS human neuronal context. Importantly, we identified a signature of genes that is partially and qualitatively modulated upon ASO treatment, pinpointed genes sensitive to MeCP2 function, and altered in a model of Rett syndrome, a neurological disorder caused by loss of MeCP2 function. Furthermore, the signature contained genes that are aberrantly altered in unaffected control human neurons upon MeCP2 depletion, revealing gene expression programs qualitatively sensitive to MeCP2 levels in human neurons. Lastly, ASO treatment led to a partial rescue of abnormal neuronal morphology in MDS neurons. All together, these data demonstrate that ASOs targeting MECP2 benefit human MDS neurons. Moreover, our study establishes a paradigm by which to evaluate the contribution of individual genes within a CNV to pathogenesis and to assess their potential as a therapeutic target., (© The Author(s) 2024. Published by Oxford University Press.)

While tobacco smoking is a risk factor in the development of oral squamous cell carcinoma (OSCC), only a fraction of smokers develop the disease. Compelling evidence shows that microbial community composition is associated with carcinogenesis, suggesting that the microbiome may play a role in cancer development of smokers. We previously showed that black raspberry (BRB) protects against OSCC induced by the tobacco constituent dibenzo[def,p]chrysene (DBP) altering genetic and epigenetic markers in a manner consistent with its cancer preventive activity. In the present study, we conducted a mouse experiment to investigate the effects of BRB and DBP individually and in combination on the oral and gut microbiota. DBP-induced DNA damage in the mouse oral cavity which is an essential step for the development of OSCC in mice. 16S rRNA gene sequencing revealed that BRB significantly increased microbial diversity and shifted microbiome composition in the gut and oral cavity, whereas DBP had no significant effect. In both gut and oral microbiota, Akkermansia muciniphila was significantly reduced after BRB treatment; however, this was not consistent with pure culture in vitro assays suggesting that the impact of BRB on A. muciniphila may be mediated through indirect mechanisms including the host or other microbes. Indeed BRB, but not DBP, was found to modulate the growth kinetics of human gut microbes in vitro including lactic acid bacteria and Bacteroides spp. The results of the current study further emphasize the interplay of microbiome and environmental factors in the development and prevention of OSCC.

Purpose: Scalp cooling therapy (SCT) improves chemotherapy-induced alopecia (CIA), but there are few published data about its efficacy in an Asian-predominant population. We report our tertiary institution experience of SCT in patients with breast or gynaecological cancers undergoing chemotherapy., Methods: The Paxman scalp cooling system was employed for eligible women with breast or gynaecological cancers receiving anthracycline or taxane-based chemotherapy. Only patients with Grade (G) 0-1 alopecia by common terminology criteria for adverse events (CTCAE) version 4.0 were eligible initially, but patients with G2 alopecia were later included in the study. SCT was performed at each chemotherapy cycle, commencing 30 min prior to and continuing up to 90 min after completion of the drug infusion. Patients were assessed at the start and end of each session for hair preservation (defined as G0-2 alopecia) and comfort level of SCT (rated on a 5-point visual scale). The primary end point was success of hair preservation or hair regrowth after completion of all cycles of chemotherapy., Results: Eighty-three patients were enrolled over a period of 18 months from December 2017 to October 2019, with a total of 510 scalp cooling cycles performed. 94.0% (n = 78) of patients reported a comfort score of 3 and above, indicating that the procedure was comfortable, upon a 5-point visual scale. Patients receiving weekly paclitaxel had highest success in hair preservation at 76.7% (23/30 patients), with a lower rate of hair preservation observed for the 3 weekly paclitaxel regimen (50%, 2/4 patients). In contrast, only 1 patient (5.3%, 1/19 patients) who underwent chemotherapy with anthracycline and cyclophosphamide achieved hair preservation., Conclusion: SCT is well tolerated in an Asian-predominant population. Among women with breast or gynaecological cancers receiving taxane and/or anthracycline based chemotherapy, those who underwent SCT were about 50% more likely to achieve hair preservation or hair regrowth, as compared to historical controls., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage-induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in non-smokers; these results suggest the potential contribution of B[a]P in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC at late stages even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings we tested the hypothesis, in a Phase 0 clinical study, that BRB administration reduces DNA damage induced by B[a]P in buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected at four weeks after BRB cessation (washout period). B[a]P-induced DNA damage (BPDE-N2-dG) was evaluated by LC-MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (p = 0.01506) compared to baseline, 36.1% at the end of BRB administration (p = 0.00355), and 16.6% after BRB cessation (p = 0.007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Integrating structural colors and conductivity into aqueous inks has the potential to revolutionize wearable electronics, providing flexibility, sustainability, and artistic appeal to electronic components. This study aims to introduce bioinspired color engineering to conductive aqueous inks. Our self-assembly approach involves mixing poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with sulfonic acid-modified polystyrene (sPS) colloids to generate non-iridescent structural colors in the inks. This spontaneous structural coloration occurs because PEDOT:PSS and sPS colloids can self-assemble into core-shell structures and reversibly cluster into photonic aggregates of maximally random jammed packing within the aqueous environment, as demonstrated by small-angle X-ray scattering. Dissipative particle dynamics simulation confirms that the self-assembly aggregation of PEDOT:PSS chains and sPS colloids can be manipulated by the polymer-colloid interactions. Utilizing the finite-difference time-domain method, we demonstrate that the photonic aggregates of the core-shell colloids achieve close to maximum jammed packing, making them suitable for producing vivid structural colors. These versatile conductive inks offer adjustable color saturation and conductivity, with conductivity levels reaching 36 S cm -1 through the addition of polyethylene glycol oligomer, while enhanced water resistance and mechanical stability are achieved by doping with a cross-linker, poly(ethylene glycol) diglycidyl ether. With these unique features, the inks can create flexible, patterned circuits through processes like coating, writing, and dyeing on large areas, providing eco-friendly, visually appealing colors for customizable, stylish, comfortable, and wearable electronic devices.

Background: It is crucial to identify factors that can predict the risk of mortality in patients newly diagnosed with interstitial lung disease (ILD). This study sought to develop and assess a composite scoring system for mortality prediction among ILD patients based on cardiovascular parameters, which were previously reported as predictors of survival., Methods: We prospectively enrolled patients with newly diagnosed ILD and monitored their survival status for 24 months. Surviving and deceased patients were compared regarding their baseline characteristics including clinical, pulmonary, and cardiovascular parameters. A system of composite scores was established based on significant cardiovascular parameters and the Gender-Age-Physiology (GAP) score. Receiver operating characteristic curves were generated to identify their optimal cut-off values. Univariate as well as multiple multivariate regression models were built to investigate the mortality prediction of different individual and combined parameters., Results: Ninety-six patients newly diagnosed with ILD underwent cardiovascular evaluation. In univariate analysis, three cardiovascular parameters were identified as significant predictors of mortality risk in ILD patients, either individually or as a combination of composite scores: tricuspid regurgitation velocity > 3.1 m/s; N-terminal pro-B-type natriuretic peptide level > 300 pg/ml and computed tomography pulmonary artery/ascending aorta diameter ratio > 0.9. In multivariate analysis, a composite score of those parameters [hazard ratio (HR) = 2.37 (confidence interval [CI]:1.06-5.33); p = 0.037; Score 1] and GAP score [HR = 1.62 (CI: 1.11-2.36); p = 0.012] were the most significant predictors for mortality among ILD patients. Combination of Score 1 and GAP score (Score 2) can increase the accuracy of survival predictions (area under the curve 0.83; p < 0.001)., Conclusions: A composite score based on cardiovascular parameters and the GAP score can be used to predict the risk of mortality of patients with ILD. Such a score achieved better diagnostic accuracy than the GAP score alone. Nevertheless, further larger-scale randomized controlled trials are required for evaluation of the newly proposed score and confirmation of our results., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cardiopulmonary exercise testing (CPET) is a unique diagnostic tool that assesses the functional capacity of the heart, lungs, and peripheral oxidative system in an integrated manner. However, the clinical utility of CPET for evaluating interstitial lung disease (ILD) remains uncertain. The objective of this study was to determine the predictive value of CPET for mortality in subjects with ILD., Methods: We prospectively enrolled subjects with ILD who underwent CPET at a tertiary medical center in Taiwan and followed up their survival status for 12 months. Mortality prediction was based on comparing CPET parameters between subjects who survived and those who died. We further analyzed CPET parameters that showed significant differences using receiver operating characteristic curves to identify their optimal cutoff values., Results: A total of 106 newly diagnosed subjects with ILD underwent CPET, and the 1-y mortality rate was 7.5%. Six CPET variables were found to be significant predictors of mortality: peak oxygen consumption, oxygen pulse, end-tidal partial pressure of carbon dioxide, heart rate recovery 1 min after CPET, minute ventilation to carbon dioxide output slope, and functional aerobic impairment. We calculated a summed score by adding the number of CPET variables that exceeded their cutoff values. Subjects with a summed score of 6 had a 1-y survival rate of only 25%, whereas subjects with scores of 0-5 had a survival rate of 98%., Conclusions: In conclusion, the summed score represents a useful tool for screening patients with ILD who can undergo a CPET to determine their prognosis., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Graphitic carbon exhibits distinctive characteristics that can be modulated by varying the number of carbon layers. Here, we developed a method to control the growth of graphitic carbon layers through pyrolysis of zeolitic imidazolate frameworks (ZIFs). The key is to pyrolyze hollow-structured ZIF-8 containing Co ions to simultaneously obtain an amorphous carbon source for graphitic carbons and Co metal nanoparticles for catalyzing graphitization of amorphous carbons. Owing to sparsely distributed Co ions within ZIF-8, Co nanoparticles are formed, which leads to localized graphitization. The graphitic carbon obtained contained two to five layers, unlike carbonized ZIF-67. The few-layered graphitic carbon was subjected to KOH activation and employed as a support for atomic-sized Co(OH) 2 owing to the short routes for Co nanoparticle egress and OH - ion movement. Our strategy does not involve any highly corrosive process for catalyst leaching and can even be used to produce atomic-sized Co(OH) 2 with few-layered graphitic carbons., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Objective: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS)., Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available., Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage. Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progression-free survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA , FGFR2 , and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0-16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%., Conclusion: Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted., Competing Interests: Natalie YL Ngoi reports honorarium and travel from AstraZeneca, and honorarium from Pfizer and Merck., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: Limited research has explored the long-term effect of reduced PM 2.5 exposure on cognitive function. This study aimed to investigate the effects of time-dependent PM 2.5 exposure and the interactions of PM 2.5 and aging on declines in Mini-Mental State Examination (MMSE) scores, in carriers and non-carriers of the APOE-ε4 allele., Methods: Participants aged over 60 were recruited for this cohort study, undergoing MMSE tests twice from the Taiwan Biobank Program from 2008 to 2020. Participants with dementia or baseline MMSE scores <24 were excluded. Annual PM 2.5 levels were estimated using a hybrid kriging/land use regression model with extreme gradient boosting, treated as a time-dependent variable. Generalized estimating equations were used to assess the impacts of repeated PM 2.5 on MMSE decline, further stratified by the presence of APOE-ε4 alleles., Results: After follow-up, 290 participants out of the overall 7,000 community residents in the Biobank dataset demonstrated incidences of MMSE declines (<24), with an average MMSE score decline of 1.11 per year. Participants with ε4/ε4 alleles in the APOE gene had significantly 3.68-fold risks of MMSE decline. High levels of PM 2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. As annual levels of PM 2.5 decreased over time, the impact of PM 2.5 on MMSE decline also slowly diminished., Conclusion: Long-term PM 2.5 exposure may be associated with increased risk of MMSE decline, despite improvements in ambient PM 2.5 levels over time. Validation of these results necessitates a large-scale prospective cohort study with more concise cognitive screening tools., Competing Interests: DISCLOSURES This study was supported by grants from theMinistry of Science and Technology(MOST 108-2221-E-039-009-MY3) andTaichung Veterans General Hospital(TCVGH-1123601B). The funders did not participate in the study design, data collection and analysis, publication decision, or manuscript preparation. The authors report no conflicts with any product mentioned or concept discussed in this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Osteoarthritis (OA) is the most prevalent type of arthritis worldwide and a leading cause of years lost to pain and disability. Among the current pharmacological treatments for OA, symptomatic slow-acting drugs for OA (SYSADOA) induce pain relief and aim to improve joint function by relieving inflammation while causing fewer gastrointestinal and cardiovascular adverse events than non-steroidal anti-inflammatory drugs (NSAIDs). SKCPT is a herbal SYSADOA formulated from Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris powdered extracts. This preparation has been shown to induce cartilage protection and anti-inflammatory effects in preclinical studies and inhibit glycosaminoglycan degradation and catabolic gene expression in human OA chondrocytes and cartilage., Aim of the Study: We aimed to evaluate the non-inferiority of SKCPT to celecoxib and safety for treating knee OA., Materials and Methods: This multicenter, randomized, double-blind, phase III clinical trial enrolled adults with primary knee OA who were randomized (1:1) to SKCPT 300 mg twice daily or celecoxib 200 mg once daily for 12 weeks., Results: In total, 278 patients were assigned to treatment (SKCPT, 136; celecoxib, 142) for approximately 12 weeks. The primary endpoint was the mean change of Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) pain subscale scores from baseline to Day 84. The mean change (least squares [LS] mean ± standard error) from baseline to Day 84 was -23.74 ± 1.48 for SKCPT and -25.88 ± 1.44 for celecoxib. The two-sided 95% confidence interval of the difference (LS mean) between groups was [-1.94, 6.20], confirming that the upper limit was less than the non-inferiority margin of 10. Additionally, there were no significant differences in the secondary endpoints (mean changes of K-WOMAC pain, physical, stiffness subscale, and total score, and the frequency and number of doses of rescue medications) between groups at all time points. Differences between groups in adverse events and adverse drug reactions were not significant, and no serious adverse events occurred., Conclusions: SKCPT efficacy was non-inferior, and its safety profile was similar, to celecoxib. Building on previous results showing that SYSADOA reduce NSAID intake, the present results suggest that the SYSADOA SKCPT could effectively replace NSAIDs in knee OA treatment while avoiding long-term side effects., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Young Mo Kim received honoraria from SK Chemicals Co. Ltd. The remaining authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study presents the enzymatic synthesis of resveratrol-3,4'-O-α-diglucoside (RDG) using a hyperactive O-α-glycoligase (MalA-D416R/Q450S) and α-glucopyranosyl fluoride as the donor substrate. The transglycosylation rate for resveratrol by MalA-D416R/Q450S was maximized in 100 mM Tris-HCl (pH 9.5) containing 20 % DMSO at 45°C. Because the pK a of the 4'-OH group of resveratrol is lower than that of the 3-OH group, the 4'-OH group is more nucleophilic at the alkaline pH, leading to a preference for glycosylation at the 4'-OH site rather than the 3-OH site. This preference makes resveratrol 3-O-α-glucoside (R3G) as the more efficient acceptor than resveratrol 4'-O-α-glucoside (R4'G), resulting in negligible production of resveratrol 3-O-α-glucoside (R3G) due to its complete consumption in the second transglycosylation reaction when using a 2:1 ratio of donor to acceptor substrates. From a preparative scale reaction, R4'G and RDG were isolated with yields of 41.2 % and 43.3 %, respectively. The water solubility of RDG exceeded 1.67 M, which represents more than a 9,800-fold improvement compared to resveratrol. In a hydrolysis experiment using intestinal α-glycosidase from rat, the α-glucosides of resveratrol (R4'G and RDG) were completely deglycosylated to the aglycone., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Affect recall is key to psychological assessment and decision-making. However, self-concepts (self-beliefs) may bias retrospective affect reports such that they deviate from lived experiences. Does this experience-memory gap apply to solitude experiences? We hypothesized that individuals misremember how they feel overall and when in solitude, in line with self-concepts of introversion, self-determined/not-self-determined solitude motivations, and independent/interdependent self-construal. A pilot study comparing retrospective to daily affect reports captured over 2 weeks (N = 104 UK university students) provided preliminary evidence of introversion and not-self-determined solitude shaping affect recall., Methods: In the main pre-registered study, participants aged 18-49 in the UK (N = 160) and Hong Kong (N = 159) reported their momentary affective states and social situations 5 times per day over 7 days, then recalled how they felt over the week., Results and Discussion: Individuals higher in self-determined solitude were more prone to retrospectively overestimate their high- and low-arousal positive affect in solitude and showed less overestimation/more underestimation of negative affect in solitude. Higher not-self-determined solitude was associated with overestimating loneliness, and higher interdependent self-construal with overestimating loneliness and energy levels, in solitude. Comparisons based on residence/ethnicity suggest culture influences solitude-seeking and affective memory. Implications for well-being and affect measurement are discussed., (© 2024 The Author(s). Journal of Personality published by Wiley Periodicals LLC.)

Laser-induced graphene (LIG) is a promising material for various applications due to its unique properties and facile fabrication. However, the electrochemical performance of LIG is significantly lower than that of pure graphene, limiting its practical use. Theoretically, integrating other conductive materials with LIG can enhance its performance. In this study, we investigated the effects of incorporating gold nanoparticles (AuNPs) and titanium dioxide (TiO 2 ) into LIG on its electrochemical properties using ReaxFF molecular dynamics (MD) simulations and experimental validation. We found that both AuNPs and TiO 2 improved the work function and surface potential of LIG, resulting in a remarkable increase in output voltage by up to 970.5% and output power density by 630% compared to that of pristine LIG. We demonstrated the practical utility of these performance-enhanced LIG by developing motion monitoring devices, self-powered sensing systems, and robotic hand platforms. Our work provides new insights into the design and optimization of LIG-based devices for wearable electronics and smart robotics, contributing to the advancement of sustainable technologies.

Chlorin e6 is a well-known photosensitizer used in photodynamic diagnosis and therapy. A method for identifying and purifying a novel process-related impurity during the synthesis of chlorin e6 has been developed. Its structure was elucidated using NMR and HRMS. This new impurity is formed from chlorophyll b rather than chlorophyll a , which is the source of chlorin e6. The intermediates formed during chlorin e6 synthesis were monitored using HPLC-mass spectrometry. This new impurity was identified as rhodin g 7 7 1 -ethyl ester, the structure of which remains unknown to date. The cytotoxic effects of this novel compound in both dark and light conditions were studied against five cancer cell lines (HT29, MIA-PaCa-2, PANC-1, AsPC-1, and B16F10) and a normal cell line (RAW264.7) and compared to those of chlorin e6. Upon irradiation using a laser at 0.5 J/cm 2 , rhodin g 7 7 1 -ethyl ester demonstrated higher cytotoxicity (2-fold) compared to chlorin e6 in the majority of the cancer cell lines. Furthermore, this new compound exhibited higher dark cytotoxicity compared to chlorin e6. Studies on singlet oxygen generation, the accumulation in highly vascular liver tissue, and the production of reactive oxygen species in MIA-PaCa-2 cancer cells via rhodin g 7 7 1 -ethyl ester correspond to its higher cytotoxicity as a newly developed photosensitizer. Therefore, rhodin g 7 7 1 -ethyl ester could be employed as an alternative or complementary agent to chlorin e6 in the photodynamic therapy for treating cancer cells.

Obesity and its associated hepatic steatosis have become a global concern, posing numerous health hazards. Photodynamic therapy (PDT) is a unique approach that promotes anti-obesity by releasing intracellular fat. Chlorin e6 (Ce6)-PDT was tested for its anti-obesity properties in male ovariectomized (OVX) beagle dogs, as well as male C57BL/6 and Balb/c mice. The 12 OVX beagles were randomly assigned to one of four groups: high-fat diet (HFD) only, Ce6 only, Ce6 + 10 min of light-emitting diode light (LED) treatment, and Ce6 + 15 min of light treatment. We assessed several parameters, such as body weight, adipose tissue morphology, serum biochemistry, and body fat content analysis by computed tomography (CT) scan in HFD-fed beagle dogs. At the end of the study period, dogs that were treated for 35 days with Ce6 and exposed to LED irradiation (660 nm) either for 10 min (Ce6 + 10 min of light) or for 15 min (Ce6 + 15 min of light) had decreased body weight, including visceral and subcutaneous fats, lower aspartate transaminase (AST)/alanine transaminase (ALT) ratios, and a reduction in the area of individual adipocytes with a concomitant increase in the number of adipocytes. Furthermore, C57BL/6 male mice following an HFD diet were effectively treated by Ce6-PDT treatment through a reduction in weight gain and fat accumulation. Meanwhile, Ce6-PDT attenuated hepatocyte steatosis by decreasing the epididymal adipose tissue and balloon degeneration in hepatocytes in HFD-fed Balb/c mice. Taken together, our results support the idea that Ce6-PDT is a promising therapeutic strategy for the recovery of obesity and obesity-related hepatic steatosis.

Background: NLRP2 belongs to the subcortical maternal complex (SCMC) of mammalian oocytes and preimplantation embryos. This multiprotein complex, encoded by maternal-effect genes, plays a pivotal role in the zygote-to-embryo transition, early embryogenesis, and epigenetic (re)programming. The maternal inactivation of genes encoding SCMC proteins has been linked to infertility and subfertility in mice and humans. However, the underlying molecular mechanisms for the diverse functions of the SCMC, particularly how this cytoplasmic structure influences DNA methylation, which is a nuclear process, are not fully understood., Results: We undertook joint transcriptome and DNA methylome profiling of pre-ovulatory germinal-vesicle oocytes from Nlrp2 -null, heterozygous (Het), and wild-type (WT) female mice. We identified numerous differentially expressed genes (DEGs) in Het and Nlrp2 -null when compared to WT oocytes. The genes for several crucial factors involved in oocyte transcriptome modulation and epigenetic reprogramming, such as DNMT1, UHRF1, KDM1B and ZFP57 were overexpressed in Het and Nlrp2 -null oocytes. Absence or reduction of Nlrp2 , did not alter the distinctive global DNA methylation landscape of oocytes, including the bimodal pattern of the oocyte methylome. Additionally, although the methylation profile of germline differentially methylated regions (gDMRs) of imprinted genes was preserved in oocytes of Het and Nlrp2 -null mice, we found altered methylation in oocytes of both genotypes at a small percentage of the oocyte-characteristic hyper- and hypomethylated domains. Through a tiling approach, we identified specific DNA methylation differences between the genotypes, with approximately 1.3% of examined tiles exhibiting differential methylation in Het and Nlrp2 -null compared to WT oocytes., Conclusions: Surprisingly, considering the well-known correlation between transcription and DNA methylation in developing oocytes, we observed no correlation between gene expression differences and gene-body DNA methylation differences in Nlrp2 -null versus WT oocytes or Het versus WT oocytes. We therefore conclude that post-transcriptional changes in the stability of transcripts rather than altered transcription is primarily responsible for transcriptome differences in Nlrp2 -null and Het oocytes., Competing Interests: Competing interests: The authors declare that they have no competing interests.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairments, and behavioral changes. The presence of abnormal beta-amyloid plaques and tau protein tangles in the brain is known to be associated with AD. However, current limitations of imaging technology hinder the direct detection of these substances. Consequently, researchers are exploring alternative approaches, such as indirect assessments involving monitoring brain signals, cognitive decline levels, and blood biomarkers. Recent studies have highlighted the potential of integrating genetic information into these approaches to enhance early detection and diagnosis, offering a more comprehensive understanding of AD pathology beyond the constraints of existing imaging methods. Our study utilized electroencephalography (EEG) signals, genotypes, and polygenic risk scores (PRSs) as features for machine learning models. We compared the performance of gradient boosting (XGB), random forest (RF), and support vector machine (SVM) to determine the optimal model. Statistical analysis revealed significant correlations between EEG signals and clinical manifestations, demonstrating the ability to distinguish the complexity of AD from other diseases by using genetic information. By integrating EEG with genetic data in an SVM model, we achieved exceptional classification performance, with an accuracy of 0.920 and an area under the curve of 0.916. This study presents a novel approach of utilizing real-time EEG data and genetic background information for multimodal machine learning. The experimental results validate the effectiveness of this concept, providing deeper insights into the actual condition of patients with AD and overcoming the limitations associated with single-oriented data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Soluble methane monooxygenase (sMMO) oxidizes a wide range of carbon feedstocks (C1 to C8) directly using intracellular NADH and is a useful means in developing green routes for industrial manufacturing of chemicals. However, the high-throughput biosynthesis of active recombinant sMMO and the ensuing catalytic oxidation have so far been unsuccessful due to the structural and functional complexity of sMMO, comprised of three functionally complementary components, which remains a major challenge for its industrial applications. Here we develop a catalytically active miniature of sMMO (mini-sMMO), with a turnover frequency of 0.32 s -1 , through an optimal reassembly of minimal and modified components of sMMO on catalytically inert and stable apoferritin scaffold. We characterise the molecular characteristics in detail through in silico and experimental analyses and verifications. Notably, in-situ methanol production in a high-cell-density culture of mini-sMMO-expressing recombinant Escherichia coli resulted in higher yield and productivity (~ 3.0 g/L and 0.11 g/L/h, respectively) compared to traditional methanotrophic production., (© 2024. The Author(s).)

Introduction: Molecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven trials of targeted therapy matched to tumour molecular profiles, with improved outcomes reported using such an approach. Here, we review NGS results and treatment outcomes for a cohort of Asian MBC patients in the phase I unit of a tertiary centre., Methods: Patients with MBC referred to a phase I unit underwent NGS via Ion AmpliSeq Cancer Hotspot v2 (ACH v2, 2014-2017) prior to institutional change to FoundationOne CDx (FM1; 2017-2022). Patients were counselled on findings and enrolled on matched therapeutic trials, where available. Outcomes for all subsequent treatment events were recorded to data cut-off on January 31, 2022., Results: A total of 215 patients were enrolled with successful NGS in 158 patients. The PI3K/AKT/PTEN pathway was the most altered with one or more of the pathway member genes PIK3/AKT/PTEN affected in 62% (98/158) patients and 43% of tumours harbouring a PIK3CA alteration. Tumour mutational burden (TMB) was reported in 96/109 FM1 sequenced patients, with a mean TMB of 5.04 mt/Mb and 13% (12/96) with TMB ≥ 10 mt/Mb. Treatment outcomes were evaluable in 105/158 patients, with a pooled total of 216 treatment events recorded. Matched treatment was administered in 47/216 (22%) events and associated with prolonged median progression-free survival (PFS) of 21.0 weeks [95% confidence interval (CI) 11.7, 26.0 weeks] versus 12.1 weeks (95% CI 10.0, 15.4 weeks) in unmatched, with hazard ratio (HR) for progression or death of 0.63 (95% CI 0.41, 0.97; p = 0.034). In the subgroup of PIK3/AKT/PTEN -altered MBC, the HR for progression or death was 0.57 (95% CI 0.35, 0.92; p = 0.02), favouring matched treatment. Per-patient overall survival (OS) analysis (n = 105) showed improved survival for patients receiving matched treatment versus unmatched, with median OS (mOS) of 30.1 versus 11.8 months, HR = 0.45 (95% CI 0.24, 0.84; p = 0.013). Objective response rate (ORR) in the overall population was similar in matched and unmatched treatment events (23.7% versus 17.2%, odds ratio of response 1.14 95% CI 0.50, 2.62; p = 0.75)., Conclusions: Broad-panel NGS in MBC is feasible, allowing therapeutic matching, which was associated with improvements in PFS and OS., Competing Interests: RW reported serving on the advisory board of Pfizer and Novartis and receiving honoraria from Pfizer, AstraZeneca, Novartis, and Merck MSD and travel funding from Merck MSD outside the submitted work. NN reported honoraria from Merck, MSD, AstraZeneca, and ASGO; research funding from Cyclacel and iOnctura; and travel funding from AstraZeneca and JSGO. SO reported honoraria and consulting with Astra Zeneca, Pfizer, Novartis, Eli Lilly, and Roche. AW reported advisory board membership and/or speaker activity with honoraria with AstraZeneca, Novartis, Eisai, DKSH, Pfizer, and Roache and research funding from Otsuka Pharmaceuticals. VH reported consultancy/advisory activity with DKSH, AstraZeneca, Novartis, MSD, and Pfizer. RS reported serving on the advisory board of Bristol Myers Squibb, Merck, Eisai, Bayer, Taiho, Novartis, MSD, DKSH, and GSK; receiving honoraria from MSD, Eli Lilly, Bristol Myers Squibb, Roche, Taiho, AstraZeneca, Ipsen, and DKSH; and receiving grants from Roche, AstraZeneca, Taiho, Eisai, DKSH, Paxman Coolers, Natera, and MSD outside the submitted work. RAS reported honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche/Genentech, Takeda, Yuhan, Amgen, Bayer, Merck, Merck Serono, and Puma Biotechnology; consulting or advisory role with AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Pfizer, Roche/Genentech, Taiho Pharmaceutical, Yuhan, Takeda, Amgen, Lilly, Merck, Janssen, Puma Biotechnology, Merck Serono, Bayer, and Thermo Fisher Scientific; and research funding from AstraZeneca and Boehringer Ingelheim. WY reported consulting or advisory role with AbbVie/Genentech, Amgen, Bristol Myers Squibb, Ipsen, Novartis, and AstraZeneca; speakers’ bureau with Lilly, Sanofi/Aventis, Taiho Pharmaceutical, Eisai, Bayer, and MSD Oncology; and travel and accommodation expenses from Pfizer. SCL reports honoraria and consulting activity with AstraZeneca, Pfizer, Novartis, Eli Lilly, Roche, ACT Genomics, and Eisai and research funding from Taihi, Eisai, Pfizer, and ACT Genomics. JL reported advisory activity with AstraZeneca, Novartis, Roche, DKSH, Pfizer, and MSD; receiving honoraria from AstraZeneca, Novartis, Roche, DKSH, MSD, Eisai, and Pierre Fabre; receiving research funding from CTI BioPharma, Daiichi Sankyo, and Synthon Pharmaceuticals; and receiving travel grant from AstraZeneca and MSD outside the submitted work. DT is an employee of the National University Health System Singapore and reports personal fees for advisory board membership from AstraZeneca, Bayer, BioNTech Boehringer Ingelheim, Eisai, Genmab, GSK, MSD, PMV Pharma, and Roche; personal fees as an invited speaker from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, and Takeda; ownership of stocks/shares of Asian Microbiome Library AMiLi; institutional research grants from AstraZeneca, Bayer, Karyopharm Therapeutics, and Roche; institutional funding as coordinating PI from AstraZeneca, MSD, Eisai, Roche, and Bergen Bio; institutional funding as local PI from Roche, BioNTech, PMV Pharma, GSK, Sutro Pharma, Bayer, Byondis B.V., and Zeria Pharmaceutical Co., Ltd.; a previous non-renumerated role as Chair of the Asia Pacific Gynecologic Oncology Trials Group APGOT; a previous non-renumerated role as the Society President of the Gynecologic Cancer Group Singapore; non-renumerated membership of the Board of Directors of the GCIG; research funding from the National Medical Research Council NMRC Clinician Scientist Award Senior Investigator Grant CSASI21jun-0003, the Pangestu Family Foundation Gynaecological Cancer Research Fund; and product samples from AstraZeneca, Eisai, and MSD non-financial interest for research trials. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Walsh, Ong, Cheo, Low, Jayagopal, Lee, Ngoi, Ow, Wong, Lim, Lim, Heong, Sundar, Soo, Chee, Yong, Goh, Lee, Tan and Lim.)

The question of whether spatial attention can modulate initial afferent activity in area V1, as measured by the earliest visual event-related potential (ERP) component "C1", is still the subject of debate. Because attention always enhances behavioral performance, previous research has focused on finding evidence of attention-related enhancements in visual neural responses. However, recent psychophysical studies revealed a complex picture of attention's influence on visual perception: attention amplifies the perceived contrast of low-contrast stimuli while dampening the perceived contrast of high-contrast stimuli. This evidence suggests that attention may not invariably augment visual neural responses but could instead exert inhibitory effects under certain circumstances. Whether this bi-directional modulation of attention also manifests in C1 and whether the modulation of C1 underpins the attentional influence on contrast perception remain unknown. To address these questions, we conducted two experiments (N = 67 in total) by employing a combination of behavioral and ERP methodologies. Our results did not unveil a uniform attentional enhancement or attenuation effect of C1 across all subjects. However, an intriguing correlation between the attentional effects of C1 and contrast appearance for high-contrast stimuli did emerge, revealing an association between attentional modulation of C1 and the attentional modulation of contrast appearance. This finding offers new insights into the relationship between attention, perceptual experience, and early visual neural processing, suggesting that the attentional effect on subjective visual perception could be mediated by the attentional modulation of the earliest visual cortical response., (© 2023 Society for Psychophysiological Research.)

In the context of rapid urbanization, metropolitan areas are facing the risk of supply-demand mismatches among ecosystem services. Investigating the patterns, relationships, and driving factors of multiple supply-demand risks is of great significance to support the efficient management of regional ecological risks. We quantified the single/comprehensive supply-demand risk rates of six ecosystem services in Wuhan Metropolitan Area at the township scale in 2000, 2010, and 2020. By applying the self-organizing feature map network and optimal parameter geo-detector, we identified supply-demand risks bundles of ecosystem services and influencing factors of comprehensive risks. The results showed significant spatial variations in the supply-demand risks of typical ecosystem services from 2000 to 2020. The supply-demand risk associated with grain production, water yield, carbon sequestration, and green space recreation increased, while soil conservation and water purification risks decreased. The comprehensive ecosystem services supply-demand risk increased from 0.41 to 0.45, indicating a 'core area increase and periphery decrease' trend. Throughout the study period, the area exhibited bundles of comprehensive extremely high-risk bundles (B 1 ), comprehensive high-risk bundles (B 2 ), water purification high-risk bundles (B 3 ), and grain production-soil conservation risk bundles (B 4 ). The transition of risk types from B 3 to B 2 and from B 2 to B 1 suggested an increase in the combination and intensity of supply-demand risk. Vegetation cover, nighttime light index, and population density were the main driving factors for spatial variations in comprehensive supply-demand risk. Ecologi-cal risk assessment based on ecosystem services supply-demand bundles could provide an effective and reliable way to regulate multiple regional risk issues.

Objectives: Due to the rarity of olfactory neuroblastoma (ONB), there is ongoing debate about optimal treatment strategies, especially for early-stage or locally advanced cases. Therefore, our study aimed to explore experiences from multiple centers to identify factors that influence the oncological outcomes of ONB., Methods: We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and a Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy., Results: In our cohort, the 5-year overall survival (OS) rate was 78.6%, and the 5-year disease-free survival (DFS) rate was 62.4%. The Cox proportional hazards model revealed that the modified Kadish (mKadish) stage and Dulguerov T status were significantly associated with DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though the result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status., Conclusion: Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Similarly, induction chemotherapy also did not show a survival benefit, even after stage matching.

Introduction: Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation., Methods: Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype 1 receptors (AT1R) in the NTS of rats were assessed., Results: Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation., Discussion: In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Wang, Sun, Wang, Tan and Wang.)

Augmented reality (AR) applications require displays with an extended color gamut to facilitate the presentation of increasingly immersive content. The waveguide (WG) display technology, which is typical AR demonstration method, is a critical constraint on the color gamut of AR systems because of the intrinsic properties of the holographic optical elements (HOEs) used in this technology. To overcome this limitation, we introduce a method of spatially modulated diffractive optics that can expand the color gamut of HOE-based WG displays. This approach involves spatial modulation using sub-pixelized HOEs, which enables the diffraction of red, green, and blue rays along identical directions. The proposed structure considers both the characteristics of the HOE and the wavelength sensitivity of the observer to optimize the color gamut. Consequently, an expanded color gamut was achieved. The results of the theoretical and experimental analyses substantiate the effectiveness and practicality of this method in enhancing the color gamut of HOE-based WG displays. Thus, the proposed method can facilitate the implementation of more immersive AR displays., (© 2024. The Author(s).)

Our study aimed to explore the impact and mechanism of Euonymus alatus leaf extract on age-dependent oxidative stress, neuroinflammation, and progressive memory impairments in aged mice. Twenty-four-month-old mice received EA-L3 (300 mg/kg/day) or the reference drug, donepezil (DPZ, 5 mg/kg/day), for 6 weeks, and learning and memory functions were detected using the Passive Avoidance Test (PAT). As expected, cognitive function deficits were detected in aged mice compared with young mice, and these deficits were significantly mitigated by dietary treatments with EA-L3. In parallel, it upregulated the brain-derived neurotrophic factor (BDNF) and subsequently activated the extracellular-signal-regulated kinase (ERK)/cAMP response element-binding (CREB) signaling in the mouse hippocampus and scopolamine-induced B35 and SH-SY5Y neuroblastoma cells. EA-L3 showed strong anti-inflammatory effects with decreased NF-κBp65, cyclooxygenase 2 (COX-2), and tumor necrosis factor alpha (TNF-α), increased interleukin (IL)-10, and doublecortin (DCX) protein expression in the hippocampus of aged mice. Similar results were also confirmed in LPS-induced BV-2 microglia and neuroblastoma cells upon treatment with EA-L3 extract. In addition, EA-L3 notably dose-dependently decreased ROS in BV2 cells after exposure to LPS. Taken together, EA-L3 might be used as a dietary supplement to alleviate oxidative stress, the deterioration of hippocampal-based memory tasks, and neuroinflammation in elderly people.

Cigarette smoke is a rich source of free radicals that can promote oxidative stress and carcinogenesis, including head and neck squamous cell carcinoma (HNSCC) development; importantly, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-iso-prostaglandin F2α (8-isoprostane) are biomarkers of oxidative stress. Several mechanisms, including the antioxidant properties of black raspberry (BRB), account for their chemopreventive effects. In the present clinical trial, we tested the hypothesis that BRB administration reduces biomarkers levels of oxidative stress in buccal cells and urine of smokers. One week after enrolling 21 smokers, baseline buccal cells and urine samples were collected before the administration of BRB lozenges for 8 weeks (5/day, 1 gm BRB/lozenge). Buccal cells and urine samples were collected at the middle and the end of BRB administration. The last samples were collected after the BRB cessation (washout period). We analyzed levels of 8-oxodG and 8-isoprostane (LC/MS-MS), urinary cotinine (ELISA), and creatinine (spectrophotometry). BRB significantly reduced the levels of 8-oxodG by 17.08% (P = 0.00079) in buccal cells and 12.44% (P = 0.034) in urine at the middle of BRB administration as compared with baseline; the corresponding values at the end of BRB administration were 16.46% (P = 0.026) in buccal cells and 25.72% (P = 0.202) in urine. BRB had no significant effect on the levels of urinary 8-isoprostane. BRB's capacity to inhibit 8-oxodG formation of smokers' buccal cells and urine is clearly evident and the reduction in 8-oxodG suggests that antioxidant abilities are central to BRB's HNSCC chemopreventive properties., Prevention Relevance: Cigarette smoke contains highly active components namely free radicals that can promote oxidative stress and oral cancer. We found that black raspberry (BRB) inhibited the formation of oxidative stress markers in the oral cavity and urine of smokers suggesting the antioxidant abilities of BRB in preventing oral cancer., (©2024 American Association for Cancer Research.)

By utilizing bicontinuous and nanoporous ordered nanonetworks, such as double gyroid (DG) and double diamond (DD), metamaterials with exceptional optical and mechanical properties can be fabricated through the templating synthesis of functional materials. However, the volume fraction range of DG in block copolymers is significantly narrow, making it unable to vary its porosity and surface-to-volume ratio. Here, the theoretically limited structural volume of the DG phase in coil-coil copolymers is overcome by enlarging the conformational asymmetry through the association of mesogens, providing fast access to achieving flexible structured materials of ultra-high porosities. The new materials design, dual-extractable nanocomposite, is created by incorporating a photodegradable block with a solvent-extractable mesogen (m) into an accepting block, resulting in a new hollow gyroid (HG) with the largely increased surface-to-volume ratio and porosity of 77 vol%. The lightweight HG exhibits a low refractive index of 1.11 and a very high specific reduced modulus, almost two times that of the typical negative gyroid (porosity≈53%) and three times that of the positive gyroid (porosity≈24%). This novel concept can significantly extend the DG phase window of block copolymers and the corresponding surface-to-volume ratio, being applicable for nanotemplate-synthesized nanomaterials with a great gain of mechanical, catalytic, and optoelectronic properties., (© 2023 Wiley‐VCH GmbH.)

Genistein is one of isoflavones, showing various biological functions for human health. MalA-D416A, termed O-α-glycoligase, is an acid/base catalytic residue-deficient mutant of a α-glucosidase from Sulfolobus solfataricus, synthesizing genistein 7-O-α-glucoside using α-glucosyl fluoride as the donor substrate. Through mutagenesis toward MalA-D416A, an O-α-glycoligase variant with two mutations (D416R and Q450S) was identified as a biocatalyst with a 58.8-fold enhanced catalytic efficiency for genistein compared to the parent enzyme. The use of a 2:1 ratio of α-glucosyl fluoride and genistein at pH 9 facilitated the synthesis of genistein 7,4'-O-α-diglucoside by MalA-D416R/Q450S. The α-diglucoside exhibited 2,459-fold improved water solubility compared to genistein itself as well as facile deglycosylation by the intestinal α-glucosidase from rat, suggesting the potential of the α-diglucoside for improved bioavailability in human intestine. Through molecular docking analyses the modulation of the active site conformation by these mutations was expected for proper binding of both genistein and the monoglucoside., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm 2 area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities.

Nasal endoscopy is routinely performed to distinguish the pathological types of masses. There is a lack of studies on deep learning algorithms for discriminating a wide range of endoscopic nasal cavity mass lesions. Therefore, we aimed to develop an endoscopic-examination-based deep learning model to detect and classify nasal cavity mass lesions, including nasal polyps (NPs), benign tumors, and malignant tumors. The clinical feasibility of the model was evaluated by comparing the results to those of manual assessment. Biopsy-confirmed nasal endoscopic images were obtained from 17 hospitals in South Korea. Here, 400 images were used for the test set. The training and validation datasets consisted of 149,043 normal nasal cavity, 311,043 NP, 9,271 benign tumor, and 5,323 malignant tumor lesion images. The proposed Xception architecture achieved an overall accuracy of 0.792 with the following class accuracies on the test set: normal = 0.978 ± 0.016, NP = 0.790 ± 0.016, benign = 0.708 ± 0.100, and malignant = 0.698 ± 0.116. With an average area under the receiver operating characteristic curve (AUC) of 0.947, the AUC values and F1 score were highest in the order of normal, NP, malignant tumor, and benign tumor classes. The classification performances of the proposed model were comparable with those of manual assessment in the normal and NP classes. The proposed model outperformed manual assessment in the benign and malignant tumor classes (sensitivities of 0.708 ± 0.100 vs. 0.549 ± 0.172, 0.698 ± 0.116 vs. 0.518 ± 0.153, respectively). In urgent (malignant) versus nonurgent binary predictions, the deep learning model achieved superior diagnostic accuracy. The developed model based on endoscopic images achieved satisfactory performance in classifying four classes of nasal cavity mass lesions, namely normal, NP, benign tumor, and malignant tumor. The developed model can therefore be used to screen nasal cavity lesions accurately and rapidly., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kwon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study represents a visual detection for total biogenic monoamines with naked eye as a simple and rapid semi-quantitative method for biogenic amine monitoring. The equivalent reaction of H 2 O 2 with ascorbic acid resulted in color development by an amine oxidase-peroxidase coupling reaction in the samples containing the biogenic monoamines higher than the subjected ascorbic acid by 10 μM. Upon employing the commercial doenjang extracts as a model food, an additional heating step was requested, and the expected ranges for the biogenic monoamines from 360 to 480 μM covered the real contents of the samples (360.2-407.3 μM). Therefore, this visual detection method makes it possible to decide with naked eye whether the sample contains the biogenic monoamines higher than the ascorbic acid supplemented as much as a control level on manufacturing sites without instrumental analysis., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The purpose was to compare the clinical and radiographic outcomes between preoperative mild and severe varus deformity after total knee arthroplasty (TKA) with medial stabilizing technique (MST). Methods: We retrospectively analyzed 158 knees of 125 female patients with a 2-year follow-up who underwent mechanically aligned TKA with MST between April 2018 and February 2021. Patients were divided into two groups; the severe varus group was defined as one with preoperative hip-knee ankle (HKA) angle ≥ 15° and the mild varus group with HKA angle < 15°. Pre- and post-operative clinical outcomes (Western Ontario and McMaster University Osteoarthritis Index, Knee Society Knee Score) and radiographic outcomes (medial proximal tibial angle (MPTA), HKA angle, lateral distal femoral angle (LDFA), joint line distance, and femoral component rotation angle) were compared between the groups. Results: Among the 158 knees analyzed, 131 and 27 were allocated to the mild and severe varus groups, respectively. Preoperative data showed that the MPTA (84.7° ± 2.8° vs. 80.7° ± 3.2°, p < 0.001) was significantly less in the severe varus group. In postoperative data, clinical outcomes were not different between the groups. Joint line distance (18.4 mm ± 2.8 mm vs. 18.6 mm ± 2.7 mm, p = 0.676) was also not significantly different. Femoral component rotation angle (-1.7° ± 1.0° vs. -1.0° ± 1.3°, p = 0.018) was more externally rotated in the severe varus group. Conclusions: Severe varus group showed comparable clinical and radiographic outcomes to that of mild varus group after mechanically aligned TKA with MST.

Tobacco smoking and human papillomavirus infection are established etiological agents in the development of head and neck squamous cell carcinoma (HNSCC). The incidence and mortality of HNSCC are higher in men than women. To provide biochemical basis for sex differences, we tested the hypothesis that carcinogen treatment using dibenzo[ def,p ]chrysene, which is an environmental pollutant and tobacco smoke constituent, in the absence or presence of the mouse papillomavirus infection results in significantly higher levels of DNA damage in the oral cavity in male than in female mice. However, the results of the present investigation do not support our hypothesis since we found that females were more susceptible to carcinogen-induced covalent DNA damage than males independent of the viral infection. Since DNA damage represents only a single-step in the carcinogenesis process, additional factors may contribute to sex differences in humans., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)