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BACKGROUND: It was estimated that approximately 25 percent of Taiwanese residents were ABO blood group A. Many subgroups of A, however, revealed ambiguous serologic typing results. This study aimed to delineate the molecular basis of the A3, Ax, and weak A phenotypes. STUDY DESIGN AND METHODS: Serologic analyses including adsorption and elution assay, serum transferases activity assay, and saliva test were performed to determine the unique phenotypes of these samples. DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism were performed to further investigate the relationships between the genetic characteristics and phenotypic features of these samples. RESULTS: Three single-nucleotide transitions (745C>T, 820G>A, and a novel 860C>T) were found in nine A3/A3B cases. In addition, the Ax and A3B subjects shared the same 860C>T mutation. This A(x) allele with 860C>T transition expressed A3B phenotype in A(x)/B101 heterozygote but Ax phenotype in A(x)/O01 heterozygote. This allelic enhancement was also observed in the weak A family with Aw05 allele, which was previously not found in Taiwan. CONCLUSION: This allelic enhancement phenomenon was prone to cause serologic discrepancy between parents and children. Genotyping could help us to resolve this problem. Thus, a novel mutation is reported among Taiwanese blood donors. [ABSTRACT FROM AUTHOR]

Coral reefs are among the most diverse and valuable ecosystems on the planet, providing numerous benefits to human societies, including fisheries, coastal protection, and biodiversity conservation. In order to effectively manage and conserve coral reefs, it is essential to understand the value of the ecosystem services they provide. The System of Environmental-Economic Accounting (SEEA) framework offers a comprehensive approach for accounting for ecosystem services, which can be useful for assessing the value of natural environments. While the validity of SEEA for many marine ecosystems is increasingly acknowledged, there remains a scarcity of studies that have investigated SEEA in the context of coral reef ecosystems. To bridge this gap, this study offers extensive examination and investigates the evolution of coral reef ecosystem service research under the SEEA framework in over nearly three decades, providing a rich dataset for understanding trends and gaps. The research findings reveal interdisciplinary methodological integration in coral reef ecosystem research, incorporating remote sensing, environmental science, ecology, environmental economics, ecological economics, computer science, and citizen science. Across different time periods, within the shared focus of coral reef health and sustainability, there has been a transition from concerns about the impacts of human activities to a concentration on climate change, supported by empirical evidence and case studies. These research results contribute to our better understanding of the value of coral reef ecosystems., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Both vestibular schwannoma (VS) and Meniere's disease (MD) patients underwent hydrops MRI to clarify the relationship between VS and endolymphatic hydrops (EH)., Methods: Eighty patients with VS or MD underwent an inner ear test battery followed by hydrops MRI, and were then divided into 3 groups. Group A comprised 58 MD patients (62 ears) with positive EH but negative VS. Group B included 18 VS patients (18 ears) with negative EH, while Group C consisted of 4 patients (4 ears) who had VS concomitant with EH. Another 14 MD patients who tested negative for EH on hydrops MRI were initially excluded from this cohort, but were later included for comparison., Results: The decreasing prevalence of EH at the cochlea, saccule and utricle in Group A was identified in 59 (95%), 42 (68%) and 40 (65%) ears, respectively, mimicking a declining sequence of abnormality rates running from audiometry (86%), cervical vestibular-evoked myogenic potential (cVEMP) test (55%) to the ocular (oVEMP) test (53%). However, such decreasing trend was not identified in Groups B and C. In Groups C and A combined, 4 (6%) of 62 EH patients had concomitant VS. Conversely, 4 (18%) of 22 VS patients in Groups C and B combined had concurrent EH., Conclusion: A very low (6%) rate of VS in EH patients indicates that VS in EH patients may be coincidental. In contrast, EH was identified in 18% prevalence of VS patients, mirroring the 22% prevalence of cochlear EH demonstrated in VS donors through histopathological studies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Effective and rapid heat transfer is critical to improving electronic components' performance and operational stability, particularly for highly integrated and miniaturized devices in complex scenarios. However, current thermal manipulation approaches, including the recent advancement in thermal metamaterials, cannot realize fast and unidirectional heat flow control. In addition, any defects in thermal conductive materials cause a significant decrease in thermal conductivity, severely degrading heat transfer performance. Here, the utilization of silicon-based valley photonic crystals (VPCs) is proposed and numerically demonstrated to facilitate ultrafast, unidirectional heat transfer through thermal radiation on a microscale. Utilizing the infrared wavelength region, the approach achieves a significant thermal rectification effect, ensuring continuous heat flow along designed paths with high transmission efficiency. Remarkably, the process is unaffected by temperature gradients due to the unidirectional property, maintaining transmission directionality. Furthermore, the VPCs' inherent robustness affords defect-immune heat transfer, overcoming the limitations of traditional conduction methods that inevitably cause device heating, performance degradation, and energy waste. The design is fully CMOS compatible, thus will find broad applications, particularly for integrated optoelectronic devices., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Key Points: We proposed a hierarchical framework including an unsupervised candidate image selection and a weakly supervised patch image detection based on multiple instance learning (MIL) to effectively estimate eosinophil quantities in tissue samples from whole slide images. MIL is an innovative approach that can help deal with the variability in cell distribution detection and enable automated eosinophil quantification from sinonasal histopathological images with a high degree of accuracy. The study lays the foundation for further research and development in the field of automated histopathological image analysis, and validation on more extensive and diverse datasets will contribute to real-world application., (© 2024 ARS‐AAOA, LLC.)

Elevating the working temperature delivers a simple and universal approach to enhance the energy storage performances of supercapacitors owing to the fundamental improvements in ion transportation kinetics. Among all heating methods, introducing green and sustainable photothermal heating on supercapacitors (SCs) is highly desired yet remains an open challenge, especially for developing an efficient and universal photothermal heating strategy that can be generally applied to arbitrary SC devices. Flash-enabled graphene (FG) absorbers are produced through a simple and facile flash reduction process, which can be coated on the surface of any SC devices to lift their working temperature via a photothermal effect, thus, improving their overall performance, including both power and energy densities. With the systematic temperature-dependent investigation and the in-depth numerical simulation of SC performances, an evident enhancement in capacitance up to 65% can be achieved in photothermally enhanced SC coin cell devices with FG photo-absorbers. This simple, practical, and universal enhancement strategy provides a novel insight into boosting SC performances without bringing complexity in electrode fabrication/optimization. Also, it sheds light on the highly efficient utilization of green and renewable photothermal energies for broad application scenarios, especially for energy storage devices., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H 2 S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H 2 S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism., (© 2024. The Author(s).)

Developing programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library. Leveraging the potency of the bacterial type IV secretion system-a contact-dependent DNA delivery nanomachine-we have established a positive feedback mechanism to selectively enrich for bacteria displaying nanobodies that target antigen-expressing cells. Our platform successfully identified functional CAMs capable of recognizing three distinct outer membrane proteins (TraN, OmpA, OmpC), demonstrating its efficacy in CAM discovery. This approach holds promise for engineering bacterial cell-cell adhesion, such as directing the antibacterial activity of programmed inhibitor cells toward target bacteria in mixed populations., (© 2024. The Author(s).)

Reaction of a rare and well-characterized Mn III -superoxo species, Mn(BDP Br P)(O 2 ⋅) (1, H 2 BDP Br P=2,6-bis((2-(S)-di(4-bromo)phenylhydroxylmethyl-1-pyrrolidinyl)methyl)pyridine), with 4-dimethylaminophenol at -80 °C proceeds via concerted proton electron transfer (CPET) to produce a Mn III -hydroperoxo complex, Mn(BDP Br P)(OOH) (2), alongside 4-dimethylaminophenoxy radical; whereas, upon treatment with 4-nitrophenol, complex 1 undergoes a proton transfer process to afford a Mn IV -hydroperoxo complex, [Mn(BDP Br P)(OOH)] + (3). Intriguingly, the reactions of 1 with 4-chlorophenol and 4-methoxyphenol follow two routes of CPET and sequential proton and electron transfer to furnish complex 2 in the end. UV-vis and EPR spectroscopic studies coupled with DFT calculations provided support for this wide mechanistic spectrum of activating various phenol O-H bonds by a single Mn III -superoxo complex, 1., (© 2024 Wiley-VCH GmbH.)

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes., Competing Interests: Competing interests statement:The authors declare no competing interest.

Hexanucleotide repeat expansion in C9ORF72 ( C9 ) is the most prevalent mutation among amyotrophic lateral sclerosis (ALS) patients. The patients carry over ~30 to hundreds or thousands of repeats translated to dipeptide repeats (DPRs) where poly-glycine-arginine (GR) and poly-proline-arginine (PR) are most toxic. The structure-function relationship is still unknown. Here, we examined the minimal neurotoxic repeat number of poly-GR and found that extension of the repeat number led to a loose helical structure disrupting plasma and nuclear membrane. Poly-GR/PR bound to nucleotides and interfered with transcription. We screened and identified a sulfated disaccharide that bound to poly-GR/PR and rescued poly-GR/PR-induced toxicity in neuroblastoma and C9-ALS -iPSC-derived motor neurons. The compound rescued the shortened life span and defective locomotion in poly-GR/PR expressing Drosophila model and improved motor behavior in poly-GR-injected mouse model. Overall, our results reveal structural and toxicity mechanisms for poly-GR/PR and facilitate therapeutic development for C9 -ALS.

Introduction: Focused assessment with sonography for trauma helps detect abdominal free fluid. Prehospital ultrasound scanning is also important because the early diagnosis of hemoperitoneum may reduce the time to definitive treatment in the hospital. This study investigated whether prehospital ultrasound scanning can help detect abdominal free fluid., Materials and Methods: In this systematic review, relevant databases were searched for studies investigating prehospital ultrasound examinations for abdominal free fluid in trauma patients. The prehospital ultrasound results were compared with computed tomography, surgery, or hospital ultrasound examination data. The pooled sensitivity and specificity values were analyzed using forest plots. The overall predictive power was calculated by the summary receiver operating characteristic curve. The quality of the included studies was assessed using the quality assessment of diagnostic accuracy studies tool. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was performed to assess the certainty of evidence., Result: This meta-analysis comprised six studies that included 1356 patients. The pooled sensitivity and specificity values were 0.596 (95% confidence interval [CI] = 0.345-0.822) and 0.970 (95% CI = 0.953-0.983), respectively. The pooled area under the summary receiver operating characteristic curve was 0.998. The quality assessment tool showed favorable results. In the GRADE analysis, the quality of evidence was very low for sensitivity and high for specificity when prehospital ultrasound was used for hemoperitoneum diagnosis., Conclusion: The specificity of abdominal free fluid detection using prehospital ultrasound examinations in trauma patients was very high., (© 2023. The Author(s).)

Background: Diagnostic dilemma between clinical Meniere's disease and radiological endolymphatic hydrops (EH) has emerged since the introduction of hydrops magnetic resonance imaging (MRI). The aim of this study is to explore the potential application of hydrops MRI on diagnosing the EH., Methods: This review was developed from peer-reviewed articles published in those journals listed on journal of citation reports. The MEDLINE database of the US National Library of Medicine, Scopus, and Google Scholar were used to collect articles based on the guidelines (PRISMA 2020 statement) for reporting reviews., Results: Initially, 470 articles were retrieved from 1983 to 2023, and 80 relevant articles were ultimately selected. The sensitivity (69%-92%) and specificity (78%-96%) values varied from each laboratory for detecting EH via hydrops MRI, probably due to candidate selection and the grading system employed., Conclusion: The application of hydrops MRI allows (1) differentiation between EH and sudden sensorineural hearing loss; (2) determination of the affected side of EH; and (3) confirmation of the diagnosis of EH concomitant with other disorders. Notably, not all differentials for EH can be visualized on MR images. One of the existing gaps to be filled is that updated hydrops MRI fails to identify distortion, that is, rupture, collapse, fistula, or fibrosis of the inner ear compartments, akin to what histopathological evidence can demonstrate. Hence, enhanced ultrahigh resolution of hydrops MRI is required for demonstrating fine structures of the inner ear compartments in the future., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The concept of early administration of P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) is widely accepted, but whether prehospital administration results in greater coronary reperfusion remains unclear. Our study aims to analyze the benefit and safety of prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor administration., Method: Three databases (PubMed, EMBASE, and Cochrane Library) were searched from database inception to June 2023. We included all types of studies except for conference publications, abstract presentations, reviews, and case reports. The primary outcomes were pre-PCI TIMI flow grade 2-3 (TIMI = Thrombolysis in Myocardial Infarction) and major bleeding. The secondary outcomes included post-PCI TIMI flow grade 2-3, major adverse cardiac events (MACE), recurrent myocardial infarction (MI), and short-term (30-day) mortality., Result: Eight individual studies with a total of 10823 patients were included in our meta-analysis. Compared with in-hospital P2Y12 inhibitor, prehospital P2Y12 inhibitor were associated with significantly higher rates of pre-PCI TIMI flow grade 2-3 (OR 1.32, 95% CI: 1.09-1.61, p  = 0.005) and post-PCI TIMI flow grade 2-3 (OR 1.43, 95% CI: 1.04-1.97, p  = 0.03), and a significantly lower risk of recurrent MI (OR 0.69, 95% CI: 0.49-0.96, p  = 0.03). There were no significant difference in the risk of major bleeding (OR 1.00, 95% CI: 0.75-1.32, p  = 0.98), MACE (OR 0.94, 95% CI: 0.70-1.25, p  = 0.65), or short-term mortality (OR 0.87, 95% CI: 0.50-1.51, p  = 0.61)., Conclusion: Prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor is associated with a significantly higher rate of pre-PCI and post-PCI TIMI flow grade 2-3, a reduced risk of recurrent MI, and no increase in major bleeding in STEMI patients undergoing primary PCI.

A common mRNA modification is 5-methylcytosine (m 5 C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m 5 C and impaired SRSF2 m 5 C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m 5 C recognition and the impact of the prevalent leukemia-associated mutation SRSF2 P95H . We show that SRSF2 binding and m 5 C colocalize within transcripts. Furthermore, knocking down the m 5 C writer NSUN2 decreases mRNA m 5 C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2 P95H mutation impairs the ability of the protein to read m 5 C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m 5 C hypomethylation and, combined with SRSF2 P95H , predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver., Competing Interests: Declaration of interests F.F. is a co-founder of Epics Therapeutics (Gosselies, Belgium)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The metallic-blue body coloration is a distinct characteristic found in seven species of the cosmopolitan genus Pimpla Fabricius, 1804. In this study, we focus on two externally similar species, namely P. cyanator Morley, 1914 in India and P. alishanensis (Kusigemati, 1984) in Taiwan, along with the Indian P. indra Cameron, 1899, which are the only three species in the Oriental region exhibiting this trait. By examining the type series of these two taxa and acquiring additional materials from Taiwan, we discovered female morphological variations that resemble the form of the holotype of P. cyanator. Consequently, we propose that P. alishanensis should be synonymized with P. cyanator (syn. nov.). Furthermore, we provide a redescription of P. cyanator based on morphological characters and molecular COI sequences. We also discuss its revised distribution, the diagnostic features distinguishing P. cyanator from other metallic-blue Pimpla species worldwide, the factors influencing the color change in specimens, and some potential misidentifications that have occurred in the past.

In this study, we passively analyzed the near-field characteristics of thermally excited evanescent waves, which are radiation waves generated by the local dynamics of materials, including electron motions and lattice vibrations. The thermally excited evanescent waves on aluminium nitride (AlN) and gallium nitride (GaN) were measured using passive spectroscopic scattering-type scanning near-field optical microscopy (s-SNOM) in the wavelength ranges of 10.5-12.2 μm and 14.0-15.0 μm, which include the surface phonon-polariton (SPhP) wavelength of the studied dielectrics. We determined the unique decay characteristics of AlN and GaN, indicating a ten-fold increase in the probe area contributing to the scattering of waves near the SPhP wavelength compared to that in other wavelength ranges. The extended probe area correlated with the polariton decay lengths, indicating that the non-enhanced polaritons around K ~ ω/c were dominant in the scattered waves near the SPhP wavelength. In addition to the conventional passive detection mechanisms for metals, the proposed detection scheme will be a versatile passive detection model in the near future., (© 2023. Springer Nature Limited.)

The complex and heterogeneous nature of the lignin macromolecule has presented a lasting barrier to its utilization. To achieve high lignin yield, the technical lignin extraction process usually severely modifies and condenses the native structure of lignin, which is a critical drawback for its utilization in conversion processes. In addition, there is no method capable of separating lignin from plant biomass with controlled structural properties. Here, we developed an N-heterocycle-based deep eutectic solvent formed between lactic acid and pyrazole (La-Py DES) with a binary hydrogen bonding functionality resulting in a high affinity toward lignin. Up to 93.7% of lignin was extracted from wheat straw biomass at varying conditions from 90 °C to 145 °C. Through careful selection of treatment conditions as well as lactic acid to pyrazole ratios, lignin with controlled levels of ether linkage content, hydroxyl group content, and average molecular weight can be generated. Under mild extraction conditions (90 °C to 120 °C), light-colored native-like lignin can be produced with up to 80% yield, whereas ether linkage-free lignin with low polydispersity can be obtained at 145 °C. Overall, this study offers a new strategy for native lignin extraction and generating lignin with controlled structural properties.

Background: Risk factors associated with a suboptimal response to Gonadotropin-releasing hormone (GnRH) agonists include a high or low body mass index (BMI), prolonged use of oral contraceptive pills, and low luteinizing hormone (LH) levels on either the start or trigger days of controlled ovarian stimulation (COS). However, this approach may increase the need for a dual trigger and may also result in a higher incidence of ovarian hyperstimulation syndrome (OHSS) in hyper-responders. We aimed to investigate whether the maximum LH level during stimulation can serve as a predictive factor for achieving an optimal oocyte yield using the GnRH agonist trigger alone., Methods: We retrospectively reviewed all antagonist protocols or progestin-primed ovarian stimulation (PPOS) protocols triggered with GnRH agonist only between May 2012 and December 2022. Subjects were divided into three groups, depending on basal LH level and LH maximum level. The freeze-all strategy was implemented in all cycles: Group 1, consistently low LH levels throughout COS; Group 2, low basal LH level with high LH max level during COS; Group 3, consistently high LH levels throughout COS. The primary outcome was the oocyte yield rate. The secondary outcome includes the number of collected oocytes, suboptimal response to GnRH agonist trigger, oocyte maturity rate, fertilized rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. The pregnancy outcomes were calculated for the first FET cycle., Results: Following confounder adjustment, multivariable regression analysis showed that Group 1 (cycles with consistently low LH levels throughout COS) remains an independent predictor of suboptimal response (OR: 6.99; 95% CI 1.035-47.274). Group 1 (b = -12.72; 95% CI -20.9 to -4.55) and BMI (b = -0.25; 95% CI -0.5 to -0.004) were negatively associated with oocyte yield rate. Patients with low basal LH but high LH max levels had similar clinical outcomes compared to those with high LH max levels through COS., Conclusions: The maximum LH level during COS may serve as an indicator of LH reserve and could be a more reliable predictor of achieving an optimal oocyte yield when compared to relying solely on the basal LH level. In the case of hyper-responders where trigger agents (agonist-only or dual trigger) are being considered, we propose a novel strategy that incorporates the maximum LH level, rather than just the basal or trigger-day LH level, as a reference for assessing LH reserve. This approach aims to minimize the risk of obtaining suboptimal oocyte yield and improve overall treatment outcomes., 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 © 2023 Lee, Lin, Hsieh, Kao, Huang, Chao, Chen, Yang and Chen.)

Vertical gradient band-gap heterostructures of two-dimensional (2D) layered perovskites have attracted considerable research interest due to their superior optoelectronic properties and demonstrated potential for use in optical devices. However, its fabrication has been challenging. In this investigation, 2D Ruddlesden-Popper mixed halide perovskite single crystals with a vertical gradient band gap were synthesized by using a solid-state halide diffusion process. X-ray diffraction (XRD) and scanning electron microscopy (SEM) measurements after diffusion confirm that the crystalline and morphology remain intact. The transmittance and photoluminescence (PL) spectra show the formation of a vertical gradient band gap that is ascribed to gradient halide distribution through halide intermixing. The mixed halide crystal exhibits high stability with completely suppressed phase segregation in the time-dependent PL measurement. The time-resolved photoluminescence (TRPL) spectra prove that the mixed halide sample has an enhanced carrier transport due to the Förster resonance energy transfer (FRET) effect. Besides, the halide diffusion behavior is found to be different from the previously proposed "layer-by-layer" diffusion model in exfoliated crystals. The gradient band-gap structure is critical for various applications in which vertical carrier transport is demanded.

Inflammation is strongly associated with pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy. Dysregulated RNA splicing factors have been widely reported in tumorigenesis, but their involvement in pancreatitis and PDAC is not well understood. Here, we report that the splicing factor SRSF1 is highly expressed in pancreatitis, PDAC precursor lesions, and tumors. Increased SRSF1 is sufficient to induce pancreatitis and accelerate KRASG12D-mediated PDAC. Mechanistically, SRSF1 activates MAPK signaling-partly by upregulating interleukin 1 receptor type 1 (IL1R1) through alternative-splicing-regulated mRNA stability. Additionally, SRSF1 protein is destabilized through a negative feedback mechanism in phenotypically normal epithelial cells expressing KRASG12D in mouse pancreas and in pancreas organoids acutely expressing KRASG12D, buffering MAPK signaling and maintaining pancreas cell homeostasis. This negative feedback regulation of SRSF1 is overcome by hyperactive MYC, facilitating PDAC tumorigenesis. Our findings implicate SRSF1 in the etiology of pancreatitis and PDAC, and point to SRSF1-misregulated alternative splicing as a potential therapeutic target., Significance: We describe the regulation of splicing factor SRSF1 expression in the context of pancreas cell identity, plasticity, and inflammation. SRSF1 protein downregulation is involved in a negative feedback cellular response to KRASG12D expression, contributing to pancreas cell homeostasis. Conversely, upregulated SRSF1 promotes pancreatitis and accelerates KRASG12D-mediated tumorigenesis through enhanced IL1 and MAPK signaling. This article is highlighted in the In This Issue feature, p. 1501., (©2023 American Association for Cancer Research.)

Three germ layer formation on micropatterns are extremely useful for quantitative analysis of hiPSC (human induced pluripotent stem cells) pluripotency. Spatial patterns of stem cells differentiated on the micropatterns will be formed from about 24 hours after differentiation induction and usually quantitated near 48 hours. To delineate the germ layer formation process, temporal changes in spatial patterning of germ layers should be analyzed by noninvasive microscopy. This study proposed a series of image processing methods combined with a U-net automatic segmentation to segment differentiated hiPSCs captured by bright-field microscopy. High segmentation accuracy (83.3%) for the test bright-field images compared with their concurrent Hoechst images (85%) was achieved. Tempo-spatial patterning and formation process of germ layers on the micropatterns can be visualized and quantified by segmenting time-lapse bright-field microscopy images using our method.

Organic light-emitting field-effect transistors (OLEFETs) with bilayer structures have been widely studied due to their potential to integrate high-mobility organic transistors and efficient organic light-emitting diodes. However, these devices face a major challenge of imbalance charge transport, leading to a severe efficiency roll-off at high brightness. Here, we propose a solution to this challenge by introducing a transparent organic/inorganic hybrid contact with specially designed electronic structures. Our design aims to steadily accumulate the electrons injected into the emissive polymer, allowing the light-emitting interface to effectively capture more holes even when the hole current increases. Our numerical simulations show that the capture efficiency of these steady electrons will dominate charge recombination and lead to a sustained external quantum efficiency of 0.23% over 3 orders of magnitude of brightness (4 to 7700 cd/m 2 ) and current density (1.2 to 2700 mA/cm 2 ) from -4 to -100 V. The same enhancement is retained even after increasing the external quantum efficiency (EQE) to 0.51%. The high and tunable brightness with stable efficiency offered by hybrid-contact OLEFETs makes them ideal light-emitting devices for various applications. These devices have the potential to revolutionize the field of organic electronics by overcoming the fundamental challenge of imbalance charge transport.

Purpose: This study adopted the cervical and ocular vestibular-evoked myogenic potential (cVEMP and oVEMP) tests in Meniere's disease (MD) patients to correlate them with vestibular endolymphatic hydrops (EH) on MR images., Methods: A total of 25 patients with unilateral definite MD identified by positive cochlear hydrops on MR images were enrolled. All patients underwent audiometry, cVEMP test and oVEMP test, followed by MR imaging for confirmation., Results: A significantly declining sequence of abnormality rates in MD patients was identified from the audiometry (92%), cVEMP test (52%) to the oVEMP test (40%), which was consistent with a significantly decreasing order of prevalence of EH on MR images running from the cochlea (100%), saccule (56%) to the utricle (52%). The cVEMP test for detecting the saccular hydrops revealed a sensitivity of 62%, while the oVEMP test for assessing the utricular hydrops showed a sensitivity of 70%. However, correlating VEMP results with vestibular hydrops did not show any significant relationship. In addition, mean hearing level (MHL) at four frequencies (500, 1000, 2000, and 3000 Hz) of Grade I cochlear hydrops (51 ± 19 dB) did not significantly differ from Grade II cochlear hydrops (53 ± 19 dB)., Conclusion: Limitations of the updated MR imaging for visualizing the hydrops comprised: (1) failure to correlate vestibular hydrops with VEMP results, and (2) failure to correlate grade of cochlear hydrops with MHL. The reason is probably because updated MR imaging fails to identify distorted contour of the cochlea/utricle/saccule. Further advanced technique using ultrahigh resolution of fine structures in the inner ear compartments is essential to promote a wider use of MR imaging., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pancreatic ductal adenocarcinoma (PDA) is characterized by aggressive local invasion and metastatic spread, leading to high lethality. Although driver gene mutations during PDA progression are conserved, no specific mutation is correlated with the dissemination of metastases 1-3 . Here we analysed RNA splicing data of a large cohort of primary and metastatic PDA tumours to identify differentially spliced events that correlate with PDA progression. De novo motif analysis of these events detected enrichment of motifs with high similarity to the RBFOX2 motif. Overexpression of RBFOX2 in a patient-derived xenograft (PDX) metastatic PDA cell line drastically reduced the metastatic potential of these cells in vitro and in vivo, whereas depletion of RBFOX2 in primary pancreatic tumour cell lines increased the metastatic potential of these cells. These findings support the role of RBFOX2 as a potent metastatic suppressor in PDA. RNA-sequencing and splicing analysis of RBFOX2 target genes revealed enrichment of genes in the RHO GTPase pathways, suggesting a role of RBFOX2 splicing activity in cytoskeletal organization and focal adhesion formation. Modulation of RBFOX2-regulated splicing events, such as via myosin phosphatase RHO-interacting protein (MPRIP), is associated with PDA metastases, altered cytoskeletal organization and the induction of focal adhesion formation. Our results implicate the splicing-regulatory function of RBFOX2 as a tumour suppressor in PDA and suggest a therapeutic approach for metastatic PDA., (© 2023. The Author(s).)

RAS, the most frequently mutated oncogene that drives tumorigenesis by promoting cell proliferation, survival, and motility, has been perceived as undruggable for the past three decades. However, intense research in the past has mainly focused on KRAS mutations, and targeted therapy for NRAS mutations remains an unmet medical need. NRAS mutation is frequently observed in several cancer types, including melanoma (15-20%), leukemia (10%), and occasionally other cancer types. Here, we report using miRNA-708, which targets the distinct 3' untranslated region (3'UTR) of NRAS, to develop miRNA-based precision medicine to treat NRAS mutation-driven cancers. We first confirmed that NRAS is a direct target of miRNA-708. Overexpression of miRNA-708 successfully reduced NRAS protein levels in melanoma, leukemia, and lung cancer cell lines with NRAS mutations, resulting in suppressed cell proliferation, anchorage-independent growth, and promotion of reactive oxygen species-induced apoptosis. Consistent with the functional data, the activities of NRAS-downstream effectors, the PI3K-AKT-mTOR or RAF-MEK-ERK signaling pathway, were impaired in miR-708 overexpressing cells. On the other hand, cell proliferation was not disturbed by miRNA-708 in cell lines carrying wild-type NRAS. Collectively, our data unveil the therapeutic potential of using miRNA-708 in NRAS mutation-driven cancers through direct depletion of constitutively active NRAS and thus inhibition of its downstream effectors to decelerate cancer progression. Harnessing the beneficial effects of miR-708 may therefore offer a potential avenue for small RNA-mediated precision medicine in cancer treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pang 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.)

Background: Citizen science is a research approach that involves collaboration between professional scientists and non-professional volunteers. The utilisation of recent online citizen-science platforms (e.g. social networking services) has greatly revolutionised the accessibility of biodiversity data by providing opportunities for connecting professional and citizen scientists worldwide. Meteorusstellatus Fujie, Shimizu & Maeto, 2021 (Hymenoptera, Braconidae, Euphorinae) has been recorded from the Oriental Islands of Japan and known to be a gregarious endoparasitoid of two macro-sized sphingid moths of Macroglossum , Ma.passalus (Drury) and Ma.pyrrhosticta Butler. It constructs characteristic star-shaped communal cocoons, suspended by a long cable. Although M.stellatus has been reported only from the Oriental Islands of Japan, the authors recognise its occurrence and ecological data from Taiwan and the Palaearctic Island of Japan through posts on online citizen-science groups about Taiwanese Insects on Facebook and an article on a Japanese citizen-scientist's website., New Information: Through collaboration between professional and citizen scientists via social media (Facebook groups) and websites, the following new biodiversity and ecological data associated with M.stellatus are provided: Meteorusstellatus is recorded for the first time from Taiwan and the Palaearctic Region (Yakushima Is., Japan). Cechetraminor (Butler, 1875), Hippotioncelerio (Linnaeus, 1758) and Macroglossumsitiene (Walker, 1856) (Lepidoptera, Sphingidae) are recorded for the first time as hosts of M.stellatus and two of which ( C.minor and H.celerio ) represent the first genus-level host records for M.stellatus . Mesochorus sp. (Hymenoptera, Ichneumonidae), indeterminate species of Pteromalidae and Trichogrammatidae (Hymenoptera), are recognised as hyperparasitoid wasps of M.stellatus . Parapolybiavaria (Fabricius, 1787) (Hymenoptera, Vespidae) is reported as a predator of pendulous communal cocoons of M.stellatus . The nature of suspended large-sized communal cocoons of M.stellatus and the importance and limitations of digital occurrence data and online citizen science are briefly discussed., (So Shimizu, Hsuan-Pu Chen, Kai-Ti Lin, Ren-Jye Chen, Shunpei Fujie, Su-Chuan Hung, Mei-Ling Lo, Ke-Hsiung Tsai, Kaoru Maeto.)

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a clinically critical pathogen that causes severe infection. Due to improper antibiotic administration, the prevalence of CRKP infection has been increasing considerably. In recent years, the utilization of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has enabled the identification of bacterial isolates at the families and species level. Moreover, machine learning (ML) classifiers based on MALDI-TOF MS have been recently considered a novel method to detect clinical antimicrobial-resistant pathogens., Methods: A total of 2683 isolates (369 CRKP cases and 2314 carbapenem-susceptible Klebsiella pneumoniae [CSKP]) collected in the clinical laboratories of Taipei Medical University Hospital (TMUH) were included in this study, and 80% of data was split into the training data set that were submitted for the ML model. The remaining 20% of data was used as the independent data set for external validation. In this study, we established an artificial neural network (ANN) model to analyze all potential peaks on mass spectrum simultaneously., Results: Our artificial neural network model for detecting CRKP isolates showed the best performance of area under the receiver operating characteristic curve (AUROC = 0.91) and of area under precision-recall curve (AUPRC = 0.90). Furthermore, we proposed the top 15 potential biomarkers in probable CRKP isolates at 2480, 4967, 12,362, 12,506, 12,855, 14,790, 15,730, 16,176, 16,218, 16,758, 16,919, 17,091, 18,142, 18,998, and 19,095 Da., Conclusions: Compared with the prior MALDI-TOF and machine learning studies of CRKP, the amount of data in our study was more sufficient and allowing us to conduct external validation. With better generalization abilities, our artificial neural network model can serve as a reliable screening tool for CRKP isolates in clinical practice. Integrating our model into the current workflow of clinical laboratories can assist the rapid identification of CRKP before the completion of traditional antimicrobial susceptibility testing. The combination of MADLI-TOF MS and machine learning techniques can support physicians in selecting suitable antibiotics, which has the potential to enhance the patients' outcomes and lower the prevalence of antimicrobial resistance., (© 2023. The Author(s).)

Breast cancer is the leading cause of cancer-related death in women. Among breast cancer types, triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers with aggressive tumor behavior. By using bioinformatic approaches, we observed that the microRNA-708 promoter is highly methylated in breast carcinomas, and this methylation is linked to a poor prognosis. Moreover, microRNA-708 expression correlates with better clinical outcomes in TNBC patients. Combination treatment with the hypomethylating agent decitabine and synthetic glucocorticoid significantly increased the expression of microRNA-708, reactivated DNMT-suppressed pathways, and decreased the expression of multiple metastasis-promoting genes such as matrix metalloproteinases (MMPs) and IL-1β, leading to the suppression of breast cancer cell proliferation, migration, and invasion, as well as reduced tumor growth and distant metastasis in the TNBC xenograft mouse model. Overall, our study reveals a therapeutic opportunity in which a combined regimen of decitabine with glucocorticoid may have therapeutic potential in treating TNBC patients., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (© 2023 The Author(s).)

Passive scattering-type, scanning near-field optical microscopy (s-SNOM) has been employed to study localized, long-wavelength infrared (LWIR) surface waves without external illumination. Here, we develop a cryogenic passive s-SNOM instrument in a vacuum chamber with 4 K liquid-helium cooling. Notably, the extremely low-temperature environment inside the chamber enables the realization of passive near-field detection with low background thermal noise. The technique mainly utilizes a highly sensitive LWIR confocal optical system and a tuning fork-based atomic force microscope, and the near-field detection was performed at a wavelength of 10.2 ± 0.9 µm. In this paper, we discuss the cryogenic s-SNOM implementation in detail and report the investigation of thermally excited surface electromagnetic fields on a self-heated NiCr wire deposited on SiO 2 at a temperature of 5 K. The origin of the surface electromagnetic fields was established to be the thermally excited fluctuating charges of the conduction electrons. The cryogenic s-SNOM method presented herein shows significant promise for application in a variety of spheres, including hot-carrier dissipation in ballistic conductors.

This study aimed to investigate the characteristics of, exposure to, and factors influencing gas-phase and PM 2.5 -bound phthalates (PAEs) in nail salons. Data on both indoor and outdoor gas-phase and PM 2.5 -bound PAEs, carbon dioxide (CO 2 ), temperature, and relative humidity were collected in nail salons. We also used questionnaires to survey building characteristics and occupants' behaviors. The average total gas-phase and PM 2.5 -bound PAE concentrations indoors were higher than those outdoors by 6 and 3 times, respectively. Diethyl phthalate, diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and di-(2-ethylhexyl) phthalate (DEHP) were the predominant compounds among both the gas-phase and PM 2.5 -bound PAEs in indoor air. The volume of the salon's space or the difference of indoor and outdoor CO 2 concentrations (dCO 2 ) was significantly associated with indoor PAE concentrations. The ratios of PM 2.5 -bound to gas-phase PAEs, especially high-molecular-weight PAEs, were positively associated with the dCO 2 concentrations. Higher ratios of indoor to outdoor PM 2.5 -bound DiBP, DnBP, and DEHP concentrations were discovered when more clients visited each day. Building characteristics, ventilation conditions, and occupants' activities have influences on the gas-phase and particle-phase PAEs. The study identifies the characteristics of gas-phase and PM 2.5 -bound PAEs in nail salons and their influencing factors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accurate and simultaneous multiposition near-field measurements are essential to study the time-dependent local dynamics, including heat and carrier transfer. The existing passive long-wavelength infrared (LWIR) scattering-type scanning near-field optical microscopy (s-SNOM) systems with a single probe cannot perform precise near-field measurements of the heat or carrier transporting process at the nanoscale level. Therefore, in this study, we developed a passive LWIR s-SNOM system with two probes. To test the effectiveness of the proposed passive LWIR dual-probe s-SNOM system, each probe was precisely controlled using a shear-force feedback system, and the mechanical interference between the probes was used to monitor the distance between the probes. We achieved simultaneous near-field measurements at two different positions 500 nm apart using the proposed passive LWIR dual-probe s-SNOM system. The simultaneously detected near-field signals from two different points were extracted individually, making this technique an effective nanoscale analysis tool for local carrier dynamics.

Loading quantum information deterministically onto a quantum node is an important step toward a quantum network. Here, we demonstrate that coherent-state microwave photons with an optimal temporal waveform can be efficiently loaded onto a single superconducting artificial atom in a semi-infinite one-dimensional (1D) transmission-line waveguide. Using a weak coherent state (the number of photons ( N ) contained in the pulse ≪1) with an exponentially rising waveform, whose time constant matches the decoherence time of the artificial atom, we demonstrate a loading efficiency of 94.2% ± 0.7% from 1D semifree space to the artificial atom. The high loading efficiency is due to time-reversal symmetry: the overlap between the incoming wave and the time-reversed emitted wave is up to 97.1% ± 0.4%. Our results open up promising applications in realizing quantum networks based on waveguide quantum electrodynamics.

The outstanding chemical and physical properties of 2D materials, together with their atomically thin nature, make them ideal candidates for metaphotonic device integration and construction, which requires deep subwavelength light-matter interaction to achieve optical functionalities beyond conventional optical phenomena observed in naturally available materials. In addition to their intrinsic properties, the possibility to further manipulate the properties of 2D materials via chemical or physical engineering dramatically enhances their capability, evoking new science on light-matter interaction, leading to leaped performance of existing functional devices and giving birth to new metaphotonic devices that were unattainable previously. Comprehensive understanding of the intrinsic properties of 2D materials, approaches and capabilities for chemical and physical engineering methods, the resulting property modifications and novel functionalities, and applications of metaphotonic devices are provided in this review. Through reviewing the detailed progress in each aspect and the state-of-the-art achievement, insightful analyses of the outstanding challenges and future directions are elucidated in this cross-disciplinary comprehensive review with the aim to provide an overall development picture in the field of 2D material metaphotonics and promote rapid progress in this fast emerging and prosperous field.

Cooling in buildings is vital to human well-being but inevitability consumes significant energy, adding pressure on achieving carbon neutrality. Thermally superinsulating aerogels are promising to isolate the heat for more energy-efficient cooling. However, most aerogels tend to absorb the sunlight for unwanted solar heat gain, and it is challenging to scale up the aerogel fabrication while maintaining consistent properties. Herein, we develop a thermally insulating, solar-reflective anisotropic cooling aerogel panel containing in-plane aligned pores with engineered pore walls using boron nitride nanosheets by an additive freeze-casting technique. The additive freeze-casting offers highly controllable and cumulative freezing dynamics for fabricating decimeter-scale aerogel panels with consistent in-plane pore alignments. The unique anisotropic thermo-optical properties of the nanosheets combined with in-plane pore channels enable the anisotropic cooling aerogel to deliver an ultralow out-of-plane thermal conductivity of 16.9 mW m -1 K -1 and a high solar reflectance of 97%. The excellent dual functionalities allow the anisotropic cooling aerogel to minimize both parasitic and solar heat gains when used as cooling panels under direct sunlight, achieving an up to 7 °C lower interior temperature than commercial silica aerogels. This work offers a new paradigm for the bottom-up fabrication of scalable anisotropic aerogels towards practical energy-efficient cooling applications., (© 2022. The Author(s).)

Application of B-cell receptor (BCR) pathway inhibitor ibrutinib for chronic lymphocytic leukemia (CLL) is a major breakthrough, yet the downstream effects following inhibition of BCR signaling and during relapse await further clarification. By comparative phosphoproteomic profiling of B cells from patients with CLL and healthy donors, as well as CLL B cells collected at multiple time points during the course of ibrutinib treatment, we provided the landscape of dysregulated phosphoproteome in CLL and its dynamic alterations associated with ibrutinib treatment. Particularly, differential phosphorylation events associated with several signaling pathways, including BCR pathway, were enriched in patient CLL cells. A constitutively elevated phosphorylation level of KAP1 at serine 473 (S473) was found in the majority of CLL samples prior to treatment. Further verification showed that BCR activation promoted KAP1 S473 phosphorylation, whereas ibrutinib treatment abolished it. Depletion of KAP1 in primary CLL cells decelerated cell-cycle progression and ectopic expression of a KAP1 S473 phospho-mimicking mutant accelerated G2-M cell-cycle transition of CLL cells. Moreover, temporal phosphoproteomic profiles using a series of CLL cells isolated from one patient during the ibrutinib treatment revealed the dynamic changes of several molecules associated with BCR signaling in the ibrutinib responsive and recurrent stages., Implications: This phosphoproteomic analysis and functional validation illuminated the phosphorylation of KAP1 at S473 as an important downstream BCR signaling event and a potential indicator for the success of ibrutinib treatment in CLL., (©2022 American Association for Cancer Research.)

Thermochromic materials have been widely applied in energy-efficient buildings, aerospace, textiles, and sensors. Conventional thermochromic materials rely on material phase or structure changes upon thermal stimuli, which only enable a few colors, greatly limiting their applicability. Here, we propose and demonstrate the concept of dynamically tunable thermochromic graphene metamaterials (TGMs), which can achieve continuous color tunability (380-800 nm) with fast (<100 ms) response times. The TGMs are composed of an ultrathin graphene oxide (GO) film on a flexible metal substrate. We demonstrated that external thermal energy can dynamically adjust the water contents in the GO film to manipulate the color of TGMs. An impressive thermochromic sensitivity of 1.11 nm/°C covering a large percentage of the color space has been achieved. Prototype applications for a cup and smartphone have been demonstrated. The reversible TGMs promise great potential for practical applications of temperature sensing in optoelectronic devices, environmental monitoring, and dynamic color modulation.

Objective/hypothesis: This study correlated audiological results with magnetic resonance (MR) images to predict positive cochlear endolymphatic hydrops (EH) on MR images in patients with Meniere's disease (MD)., Study Design: Retrospective study., Methods: Twenty definite MD patients with positive cochlear EH on MR images were assigned to Group A. Another 20 definite MD patients with negative cochlear EH on MR images were assigned to Group B. All patients underwent an inner ear test battery followed by MR imaging using HRDROPS-Mi2 technique., Results: The mean hearing levels (MHLs) at frequencies of 125, 250, 500 and 1000 Hz revealed significantly worse in Group A than Group B. Significantly deteriorated MHLs were noted from Grades 0 to II at low frequency (125, 250, and 500 Hz), but not at mid-frequency and high frequency. The respective cutoff hearing thresholds at frequencies of 125, 250, and 500 Hz were 27.5, 32.5, and 40 dBHL, which help predict positive cochlear EH on MR images. By using the sum (27.5 + 32.5 + 40 = 100 dBHL) of cutoff thresholds from three low frequencies as a cutoff value, Group A (80%) showed significantly more ears with sum of low-frequency hearing threshold >100 dBHL than Group B (30%)., Conclusion: When sum of three low-frequency (125, 250, and 500 Hz) hearing levels is >100 dBHL, positive cochlear EH may be shown on MR images in definite MD patients. In contrast, those MD patients with sum of three low-frequency hearing levels <100 dBHL, MR imaging should be postponed because resolution of EH may cause negative MR images. Level of evidence: 4., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Introduction: According to the Chinese Health Commission guidelines, coronavirus disease 2019 (COVID-19) severity is classified as mild, moderate, severe, or critical. The mortality rate of COVID-19 is higher among patients with severe and critical diseases; therefore, early identification of COVID-19 prevents disease progression and improves patient survival. Computed tomography (CT) radiomics, as a machine learning method, provides an objective and mathematical evaluation of COVID-19 pneumonia. As CT-based radiomics research has recently focused on COVID-19 diagnosis and severity analysis, this meta-analysis aimed to investigate the predictive power of a CT-based radiomics model in determining COVID-19 severity., Materials and Methods: This study followed the diagnostic version of PRISMA guidelines. PubMed, Embase databases and the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched to identify relevant articles in the meta-analysis from inception until July 16, 2021. The sensitivity and specificity were analyzed using forest plots. The overall predictive power was calculated using the summary receiver operating characteristic curve. The bias was evaluated using a funnel plot. The quality of the included literature was assessed using the radiomics quality score and quality assessment of diagnostic accuracy studies tool., Results: The radiomics quality scores ranged from 7 to 16 (achievable score: 2212 8 to 36). The pooled sensitivity and specificity were 0.800 (95% confidence interval [CI] 0.662-0.891) and 0.874 (95% CI 0.773-0.934), respectively. The pooled area under the receiver operating characteristic curve was 0.908. The quality assessment tool showed favorable results., Conclusion: This meta-analysis demonstrated that CT-based radiomics models might be helpful for predicting the severity of COVID-19 pneumonia., (© 2022. Italian Society of Medical Radiology.)

Background/purpose: This study utilized the recently advanced technique in MR imaging to establish its role on diagnosing all types of endolymphatic hydrops (EH)., Methods: Twenty-two patients (26 ears) with clinical EH were admitted due to acute hearing loss and/or vertiginous attack. Each patient underwent an inner ear test battery comprising audiometry, cervical and ocular vestibular-evoked myogenic potential tests, and caloric test, followed by MR imaging for confirmation., Results: Of the 22 clinical EH patients, 12 patients were referred to primary EH (Meniere's disease), 8 patients were secondary EH (including delayed EH in 5), and 2 patients were EH of embryopathic origin. MR imaging of 26 affected ears demonstrated EH in the cochlea only for 14 ears, in the utricle and saccule only for 1 ear, and in all three endorgans for 3 ears, accounting for a sensitivity of 69% (18/26). The 8 affected ears showing negative MR images were EH patients with hearing recovery 1, just after vertiginous attack 3, and chronic low-tone hearing loss 4. In contrast, 3 out of 18 unaffected ears demonstrated asymptomatic EH in the cochlea, representing a specificity of 83% (15/18)., Conclusion: The sensitivity and specificity of MR imaging for confirming all types of EH were 69% and 83%, respectively. Although diagnostic criteria can identify primary and delayed EH, MR imaging may provide a supplementary tool for diagnosing secondary, embryopathic, or asymptomatic EH, if patients are not with hearing recovery, chronic low-tone hearing loss, or just after vertiginous attack., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

OLA1 is a P-loop ATPase, implicated in centrosome duplication through the interactions with tumor suppressors BRCA1 and BARD1. Disruption of the interaction of OLA1 with BARD1 results in centrosome amplification. However, the molecular interplay and mechanism of the OLA1-BARD1 complex remain elusive. Here, we use a battery of biophysical, biochemical, and structural analyses to elucidate the molecular basis of the OLA1-BARD1 interaction. Our structural and enzyme kinetics analyses show this nucleotide-dependent interaction enhances the ATPase activity of OLA1 by increasing the turnover number (k cat ). Unlike canonical GTPase activating proteins that act directly on the catalytic G domain, the BARD1 BRCT domain binds to the OLA1 TGS domain via a highly conserved BUDR motif. A cancer related mutation V695L on BARD1 is known to associate with centrosome abnormality. The V695L mutation reduces the BARD1 BRCT-mediated activation of OLA1. Crystallographic snapshot of the BRCT V695L mutant at 1.88 Å reveals this mutation perturbs the OLA1 binding site, resulting in reduced interaction. Altogether, our findings suggest the BARD1 BRCT domain serves as an ATPase activating protein to control OLA1 allosterically., (Copyright © 2022 Elsevier B.V. All rights reserved.)

With the increasing incidence and mortality of human hepatocellular carcinoma (HCC) worldwide, revealing innovative targets to improve therapeutic strategies is crucial for prolonging the lives of patients. To identify innovative targets, we conducted a comprehensive comparative transcriptome analysis of 5,410 human HCCs and 974 mouse liver cancers to identify concordantly expressed genes associated with patient survival. Among the 664 identified prognostic comparative HCC (pcHCC) genes, upregulated pcHCC genes were associated with prognostic clinical features, including large tumor size, vascular invasion and late HCC stages. Interestingly, after validating HCC patient prognoses in multiple independent datasets, we matched the 664 aberrant pcHCC genes with the sorafenib-altered genes in TCGA&#95;LIHC patients and found these 664 pcHCC genes were enriched in sorafenib-related functions, such as downregulated xenobiotic and lipid metabolism and upregulated cell proliferation. Therapeutic agents targeting aberrant pcHCC genes presented divergent molecular mechanisms, including suppression of sorafenib-unrelated oncogenic pathways, induction of sorafenib-unrelated ferroptosis, and modulation of sorafenib transportation and metabolism, to potentiate sorafenib therapeutic effects in HCC combination therapy. Moreover, the pcHCC genes NCAPG and CENPW, which have not been targeted in combination with sorafenib treatment, were knocked down and combined with sorafenib treatment, which reduced HCC cell viability based on disruption to the p38/STAT3 axis, thereby hypersensitizing HCC cells. Together, our results provide important resources and reveal that 664 pcHCC genes represent innovative targets suitable for developing therapeutic strategies in combination with sorafenib based on the divergent synergistic mechanisms for HCC tumor suppression., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors.)

Electro-Wetting-On-Dielectric (EWOD) based digital operations have demonstrated outstanding potential in actuating and manipulating liquid droplets. Here, we adapted the EWOD for extracting femtogram quantities of cell-free DNA (cf-DNA) from 1 μL of KSOM mouse embryo culture medium. Our group extracted the femtogram quantity of cf-DNA from 1 μL of mouse embryo culture medium in our previous work. Here, we initially explain a modification from our previous extraction protocol, which improves the extraction percentage to 36.74%. Though the modified extraction protocol improves the extraction percentage from our previously reported work, the quantity is still in the femtogram range. The cf-DNA in femtogram quantity is in subcritical/subthreshold concentration for any further analysis, such as sequencing. To the best of our knowledge, we need a minimum of picogram/nanogram DNA quantities for further analysis. We demonstrated a ground-breaking mechanism of this subcritical concentration of cf-DNA amplification to the nanogram range and performed DNA sequencing. Basic Local Alignment Search Tool (BLAST) is used as a sequence similarity search program to confirm the identity percentage between query and subject. More than 97% of nucleotide identities between query and subject sequences have been obtained from the sequencing result. Hence, we can use the methodology to amplify the subcritical concentration of extracted DNA for further analytics. Moreover, as we extract the cf-DNA from the embryo culture medium, the natural growth of the embryo has not been disrupted. This entire mechanism will pave a new path towards the lab-on-a-chip (LOC) concept.

The M2 pyruvate kinase (PKM2) isoform is upregulated in most cancers and plays a crucial role in regulation of the Warburg effect, which is characterized by the preference for aerobic glycolysis over oxidative phosphorylation for energy metabolism. PKM2 is an alternative-splice isoform of the PKM gene and is a potential therapeutic target. Antisense oligonucleotides (ASO) that switch PKM splicing from the cancer-associated PKM2 to the PKM1 isoform have been shown to induce apoptosis in cultured glioblastoma cells when delivered by lipofection. Here, we explore the potential of ASO-based PKM splice switching as a targeted therapy for liver cancer. A more potent lead constrained-ethyl (cEt)/DNA ASO induced PKM splice switching and inhibited the growth of cultured hepatocellular carcinoma (HCC) cells. This PKM isoform switch increased pyruvate-kinase activity and altered glucose metabolism. In an orthotopic HCC xenograft mouse model, the lead ASO and a second ASO targeting a nonoverlapping site inhibited tumor growth. Finally, in a genetic HCC mouse model, a surrogate mouse-specific ASO induced Pkm splice switching and inhibited tumorigenesis, without observable toxicity. These results lay the groundwork for a potential ASO-based splicing therapy for HCC., Significance: Antisense oligonucleotides are used to induce a change in PKM isoform usage in hepatocellular carcinoma, reversing the Warburg effect and inhibiting tumorigenesis., (©2021 American Association for Cancer Research.)

Airborne microplastic particles (MPs) are emerging contaminants. Although some studies have investigated the characteristics of indoor MPs in homes or offices, information regarding MPs in nail salons with potentially higher MP pollution is unavailable. In this study, we collected indoor and outdoor air samples from nail salons to analyze the concentrations, physical characteristics, and polymers of MPs and further assessed the exposure through inhalation and influencing factors. Our data displayed that the average indoor MP concentration was 46 ± 55 MPs/m 3 . The estimated average annual exposure to indoor MPs was 67,567 ± 81,782 MPs/year. The predominant shape and size of indoor MPs were fragment and <50 μm, respectively. The predominant polymer in indoor air was acrylic (27%), followed by rubber (21%), and polyurethane (13%). Air conditioner, nail treatment, ceiling and flooring with plastic materials, and number of occupants were factors affecting indoor MP concentrations. We concluded that MP pollution was more severe in nail salons and the physical characteristics and polymer compositions differed between nail salons and other indoor spaces reported in other studies. Air conditioner usage induced higher MP emission, and higher MP concentrations were observed in nail salons with plastic ceiling and flooring or more occupants., 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 © 2021 Elsevier B.V. All rights reserved.)