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En-Yi Lin,1,2 Shao-Xi Hsu,1 Bing-Hua Wu,1 Yu-Chen Deng,1,3 Wei Wuli,1 Yuan-Sheng Li,3 Jui-Hao Lee,3 Shinn-Zong Lin,2,4 Horng-Jyh Harn,2,5 Tzyy-Wen Chiou1 1Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan; 2Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; 3Everfront Biotech Inc, Taipei, Taiwan; 4Department of Neurosurgery, Hualien Tzu Chi Hospital, Hualien, Taiwan; 5Department of Pathology, Hualien Tzu Chi Hospital, Hualien, TaiwanCorrespondence: Tzyy-Wen Chiou, Department of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Road, Shou-Feng, Hualien, Taiwan, Tel +886-3-890-3638, Email twchiou@gms.ndhu.edu.tw Horng-Jyh Harn, Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan, Tel +886-3-856-1825, Email arthewduke@gmail.comPurpose: Exosomes are membrane vesicles secreted by various cells and play a crucial role in intercellular communication. They can be excellent delivery vehicles for oligonucleotide drugs, such as microRNAs, due to their high biocompatibility. MicroRNAs have been shown to be more stable when incorporated into exosomes; however, the lack of targeting and immune evasion is still the obstacle to the use of these microRNA-containing nanocarriers in clinical settings. Our goal was to produce functional exosomes loaded with target ligands, immune evasion ligand, and oligonucleotide drug through genetic engineering in order to achieve more precise medical effects.Methods: To address the problem, we designed engineered exosomes with exogenous cholecystokinin (CCK) or somatostatin (SST) as the targeting ligand to direct the exosomes to the brain, as well as transduced CD47 proteins to reduce the elimination or phagocytosis of the targeted exosomes. MicroRNA-29b-2 was the tested oligonucleotide drug for delivery because our previous research showed that this type of microRNA was capable of reducing presenilin 1 (PSEN1) gene expression and decreasing the β-amyloid accumulation for Alzheimer’s disease (AD) in vitro and in vivo.Results: The engineered exosomes, containing miR29b-2 and expressing SST and CD47, were produced by gene-modified dendritic cells and used in the subsequent experiments. In comparison with CD47-CCK exosomes, CD47-SST exosomes showed a more significant increase in delivery efficiency. In addition, CD47-SST exosomes led to a higher delivery level of exosomes to the brains of nude mice when administered intravenously. Moreover, it was found that the miR29b-2-loaded CD47-SST exosomes could effectively reduce PSEN1 in translational levels, which resulted in an inhibition of beta-amyloid oligomers production both in the cell model and in the 3xTg-AD animal model.Conclusion: Our results demonstrated the feasibility of the designed engineered exosomes. The application of this exosomal nanocarrier platform can be extended to the delivery of other oligonucleotide drugs to specific tissues for the treatment of diseases while evading the immune system.Keywords: oligonucleotide drug, functional nanocarriers, hippocampus, SH-SY5Y, 3xTG-AD

Shi-Ze Lin,1,2 Yan-Kun Wu,2–4 Yun-Ai Su,2–4 Tian-Mei Si2–41Quanzhou Mental Health Center, The Third Hospital of Quanzhou, Quanzhou, Fujian Province, People’s Republic of China; 2Institute of Mental Health, Peking University Sixth Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, People’s Republic of China; 4NHC Key Laboratory of Mental Health, Peking University, Beijing, People’s Republic of ChinaAbstract: Prospective memory (PM) could be impaired in the non-psychotic first-degree relatives of patients with schizophrenia. This meta-analysis systematically examined the PM of non-psychotic first-degree relatives of patients with schizophrenia. Both Chinese and English databases were systematically searched for articles from the inception of the databases through November 13, 2018. Case-control studies of PM in non-psychotic first-degree relatives of patients with schizophrenia were included in the analyses. Confidence intervals (CIs) and standardized mean differences (SMDs) were calculated utilizing the random effects model. Four studies (n=268) that compared PM performance between non-psychotic first-degree relatives of patients with schizophrenia (n=136) and healthy controls (n=132) were included. Three studies were rated as “high quality”, while the quality of evidence of the three outcomes included in this meta-analysis was moderate. Compared with the healthy controls, the non-psychotic first-degree relatives of patients with schizophrenia showed impairments in overall PM (two studies, n=127; SMD: −0.46; 95% CI=−0.82, −0.11, P=0.01; I=0%), event-based PM (EBPM) (four studies, n=268; SMD: −0.56; 95% CI=−0.80, −0.31, P

Yu-Shuan Chen,1–3 Yu-Han Chiu,3 Yuan-Sheng Li,3 En-Yi Lin,3,4 Dean-Kuo Hsieh,5 Chia-Hung Lee,3 Mao-Hsuan Huang,1 Hong-Meng Chuang,1 Shinn-Zong Lin,1,6 Horng-Jyh Harn,1,7,* Tzyy-Wen Chiou3,*1Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, Republic of China; 2Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, Republic of China; 3Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China; 4Department of Chemistry, National Dong Hwa University, Hualien, Taiwan, Republic of China; 5Department and Graduate Institute of Applied Chemistry, Chaoyang University of Technology, Taichung, Taiwan, Republic of China; 6Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, Republic of China; 7Department of Pathology, Hualien Tzu Chi Hospital, Tzu Chi University, Hualien, Taiwan, Republic of China*These authors contributed equally to this workIntroduction: Kolliphor® EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation.Methods: In this study, a formulation for intranasal administration of butylidenephthalide (Bdph), a candidate drug against glioblastoma (GBM), was prepared. Physical characteristics of the formulation such as particle size, zeta potential, conductivity, and viscosity were assessed, as well as its cytotoxicity and permeability, in order to optimize the formulation and improve its drug loading capacity.Results: The optimized formulation involved the integration of polyethylene glycol 400 (PEG 400) in K-EL to encapsulate Bdph dissolved in dimethyl sulfoxide (DMSO), and it exhibited higher drug loading capacity and drug solubility in water than the old formulation, which did not contain PEG 400. Incorporation of PEG 400 as a co-surfactant increased Bdph loading capacity to up to 50% (v/v), even in formulations using Kolliphor® HS 15 (K-HS15) as a surfactant, which is less compatible with Bdph than K-EL. The optimized Bdph formulation presented 5- and 2.5-fold higher permeability and cytotoxicity, respectively, in human GBM than stock Bdph. This could be attributed to the high drug loading capacity and the high polarity index due to DMSO, which increases the compatibility between the drug and the cell. Rats bearing a brain glioma treated with 160 mg/kg intranasal emulsified Bdph had a mean survival of 37 days, which is the same survival time achieved by treatment with 320 mg/kg stock Bdph. This implies that the optimized emulsified formulation required only half the Bdph dose to achieve an efficacy similar to that of stock Bdph in the treatment of animals with malignant brain tumor.Keywords: glioblastoma, polyethylene glycol 400, butylidenephthalide, loading capacity, permeability, intranasal administration

Qin Guo,1,* Jie Cai,1,2,* Pengyu Li,1 Dongling Xu,1 Xiaomin Ni,1 Hui Wen,3 Dan Liu,3 Suizhen Lin,3 Haiyan Hu1 1School of Pharmaceutical Sciences, Sun Yat-sen University, 2Guangzhou First People’s Hospital, Guangzhou Medical University, 3Guangzhou Cellprotek Pharmaceutical Co., Ltd., Science Park, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Androst-3β,5α,6β-triol (Triol) is a promising neuroprotective agent, but its poor solubility restricts its development into parenteral preparations. In this study, Triol is significantly solubilized by bile salt/phosphatidylcholine mixed micelles (BS/PC-MM). All BS/PC-MM systems are tested to remarkably improve the drug solubility with various stabilities after drug loading. Among them, the sodium glycocholate (SGC)/egg phosphatidylcholine (EPC) system with 2:1 ratio in weight and the total concentration of SGC and EPC of 100 mg/mL is proved to produce stable mixed micelles with high drug loading. It is found that the stability of drug-loaded mixed micelles is quite different, which might be related to the change in critical micelle concentration (CMC) after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC) remain transparent under accelerated conditions and manifest a decreased CMC (dropping from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively). In contrast, swine bile acid-sodium salt (SBA-Na)/PC and sodium deoxycholate (SDC)/PC are accompanied by drug precipitation and reached the maximum CMC on the first and the third days, respectively. Interestingly, the variation of CMC under accelerated testing conditions highly matches the drug-precipitating event in the primary stability experiment. In brief, the bile salt/phosphatidylcholine system exists as a potential strategy of improving sterol drug solubility. CMC variation under accelerated testing conditions might be a simple and easy method to predict the stability of drug-loaded mixed micelles. Keywords: bile salt/phosphatidylcholine, mixed micelles, sterols, solubilizing, stability

Shu-Her Chiao,1* Siou-Hong Lin,1* Ching-I Shen,2* Jiunn-Wang Liao,3 I-Jiuan Bau,1 Jiun-Chiou Wei,4 Li-Ping Tseng,1 Shan-hui Hsu,4 Ping-Shan Lai,2 Shinn-Zong Lin,5–7 Jiang-Jen Lin,4 Hong-Lin Su,1,8 1Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, 2Department of Chemistry, Agricultural Biotechnology Center, National Chung Hsing University, 3Graduate Institute of Veterinary Pathobiology, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan; 4Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan; 5Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan; 6Department of Neurosurgery, China Medical University Beigan Hospital, Yunlin, Taiwan; 7Graduate Institute of Immunology, China Medical University, Taichung, Taiwan; 8Department of Physical Therapy, China Medical University, Taichung, Taiwan*These three authors contributed equallyAbstract: Developing effective and safe drugs is imperative for replacing antibiotics and controlling multidrug-resistant microbes. Nanoscale silicate platelet (NSP) and its nanohybrid, silver nanoparticle/NSP (AgNP/NSP), have been developed, and the nanohybrids show a strong and general antibacterial activity in vitro. Here, their efficacy for protecting Salmonella-infected chicks from fatality and septicemia was evaluated. Both orally administrated NSP and AgNP/NSP, but not AgNPs alone, effectively reduced the systemic Salmonella infection and mortality. In addition, quantitative Ag analyses demonstrated that Ag deposition from AgNP/NSP in the intestines was less than that from conventional AgNPs, indicating that the presence of NSP for immobilizing AgNPs reduced Ag accumulation in tissue and improved the safety of AgNPs. These in vivo results illustrated that both NSP and AgNP/NSP nanohybrid represent potential agents for controlling enteric bacterial infections.Keywords: silver, nanoparticle, biocompatibility, infection, cytotoxicity

The efficient generation, manipulation and detection of magnetic skyrmions are important for the development of future spintronic devices. One approach is to use electric-current-induced spin torques. Recently, thermally induced skyrmion motion has also been observed, but wider experimental evidence and its capabilities remain limited. Here we report the thermal generation, manipulation and thermoelectric detection of nanoscale skyrmions in microstructured metallic multilayers integrated with on-chip heaters. The local application of heat can facilitate a domain morphological transition and the formation of skyrmions at the device edge, where a low energy barrier exists. We observe the unidirectional diffusion of skyrmions from hot regions to cold regions, which is due to the interplay among the repulsive forces between skyrmions, thermal spin–orbit torques, entropic forces and magnonic spin torques. The thermally generated skyrmions can also be electrically detected via the Nernst voltage.

Purely leptonic decays of the charged D meson have been studied using the reaction e+e- → D*+D- at a center of mass energy of 4.03 GeV. A search was performed for D → μνμ recoiling against a D0 or D+ which had been reconstructed from its hadronic decay products. A single event candidate was found in the reaction e+e- → D*+D-, where D*+ → π+D0 with the D0 → K-π+, and the recoiling D- decaying via D- → μ-ν̄μ. This yields a branching fraction value B(D → μνμ) = 0.08+0.16+0.05-0.05-0.02%, and a corresponding value of the pseudoscalar decay constant fD = 300+180+80-150-40 MeV. © 1998 Elsevier Science B.V. All rights reserved.

Purely leptonic decays of the charged D meson have been studied using the reaction e+e- → D*+D- at a center of mass energy of 4.03 GeV. A search was performed for D → μνμ recoiling against a D0 or D+ which had been reconstructed from its hadronic decay products. A single event candidate was found in the reaction e+e- → D*+D-, where D*+ → π+D0 with the D0 → K-π+, and the recoiling D- decaying via D- → μ-ν̄μ. This yields a branching fraction value B(D → μνμ) = 0.08+0.16+0.05-0.05-0.02%, and a corresponding value of the pseudoscalar decay constant fD = 300+180+80-150-40 MeV. © 1998 Elsevier Science B.V. All rights reserved.

The absolute inclusive branching fraction of (Formula presented) has been measured from data collected by the BES detector at a center-of-mass energy of 4.03 GeV, corresponding to an integrated luminosity of 22.3 pb(Formula presented). At this energy, direct pair production (Formula presented) has been observed. We have selected (Formula presented) candidate events by reconstructing five hadronic decay modes (Formula presented), (Formula presented), (Formula presented), (Formula presented) and (Formula presented) and have searched for inclusive (Formula presented)’s in the recoiling (Formula presented). We observed three recoiling (Formula presented)’s in the 166.4 (Formula presented) 31.8 (Formula presented) candidate events, which leads to the absolute branching fraction (Formula presented) and (Formula presented). © 1998 The American Physical Society.

The absolute inclusive branching fraction of (Formula presented) has been measured from data collected by the BES detector at a center-of-mass energy of 4.03 GeV, corresponding to an integrated luminosity of 22.3 pb(Formula presented). At this energy, direct pair production (Formula presented) has been observed. We have selected (Formula presented) candidate events by reconstructing five hadronic decay modes (Formula presented), (Formula presented), (Formula presented), (Formula presented) and (Formula presented) and have searched for inclusive (Formula presented)’s in the recoiling (Formula presented). We observed three recoiling (Formula presented)’s in the 166.4 (Formula presented) 31.8 (Formula presented) candidate events, which leads to the absolute branching fraction (Formula presented) and (Formula presented). © 1998 The American Physical Society.

The absolute inclusive semileptonic branching fraction of the [Formula presented] meson has been measured based on [Formula presented] of [Formula presented] collision data collected with the Beijing Spectrometer at [Formula presented] At this energy, the [Formula presented] are produced in pairs: [Formula presented] We reconstructed [Formula presented] [Formula presented] events in five hadronic decay modes. In the recoil system of these events, several [Formula presented] inclusive semileptonic decays were observed and the branching fraction is estimated to be [Formula presented] © 1997 The American Physical Society.

The absolute inclusive semileptonic branching fraction of the [Formula presented] meson has been measured based on [Formula presented] of [Formula presented] collision data collected with the Beijing Spectrometer at [Formula presented] At this energy, the [Formula presented] are produced in pairs: [Formula presented] We reconstructed [Formula presented] [Formula presented] events in five hadronic decay modes. In the recoil system of these events, several [Formula presented] inclusive semileptonic decays were observed and the branching fraction is estimated to be [Formula presented] © 1997 The American Physical Society.

The cross section for e+e-→ρπ has been measured by the BES detector at BEPC at center-of-mass energies covering a 40 MeV interval spanning the J/ψresonance. The data are used to search for the vector gluonium state hypothesized by Brodsky, Lepage, and Tuan as an explanation of the ρπ puzzle in charmonium physics. The shape of the ρπ cross section is compatible with that of the total hadronic cross section. No distortions indicating the presence of a vector glueball are seen. © 1996 The American Physical Society.

A data-driven energy scan in the immediate vicinity of the τ pair production threshold has been performed using the Beijing Spectrometer at the Beijing Electron-Positron Collider. Approximately 5pb-1 of data, distributed over 12 scan points, have been collected. A previous mass value for the τ lepton, obtained using only the eµ final state, has been published. In this paper, the final BES result on the mass measurement is presented. The analysis is based on the combined data from the ee, eµ, eh, µµ, µh, and hh final states, where h denotes a charged Π or K. A maximum likelihood fit to the τ pair production cross section data yields the value mT=1776.96-0.21 -0.17+0.18+0.25. © 1995 The American Physical Society.

The Beijing Spectrometer (BES) experiment has observed purely leptonic decays of the Ds meson in the reaction e+e-→Ds+Ds- at a c.m. energy of 4.03 GeV. Three events are observed in which one Ds decays hadronically to φπ, K̄*0K, or K̄0K, and the other decays leptonically to μνμ or τντ. With the assumption of μ-τ universality, values of the branching fraction, B(Ds→μνμ)=(1.5-0.6-0.2+1.3+0.3)%, and the Ds pseudoscalar decay constant, fDs=(4.3-1.3-0.4+1.5+0.4)×102 MeV, are obtained. © 1995 The American Physical Society.

Microbial-induced carbonate precipitation (MICP) is a promising process with applications in various industries, including soil improvement, bioremediation, and concrete repair. However, comprehensive bibliometric analyses focusing on MICP research in hydrodynamics are lacking. This study analyses 1098 articles from the Scopus database (1999–2024) using VOSviewer and R Studio, identifying information on publications, citations, authors, countries, journals, keyword hotspots, and research terms. Global participation from 66 countries is noted, with China and the United States leading in terms of contributions. The top-cited papers discuss the utilisation of ureolytic microorganisms to enhance soil properties, MICP mechanisms, concrete deterioration mitigation, soil and groundwater flow enhancement, biomineral distribution, and MICP treatment effects on soil hydraulic properties under varying conditions. Keywords like calcium carbonate, permeability, and Sporosarcina pasteurii are pivotal in MICP research. The co-occurrence analysis reveals thematic clusters like microbial cementation and geological properties, advancing our understanding of MICP’s interdisciplinary nature and its role in addressing environmental challenges.

This article reports the design concept of a novel acoustic beam aperture modifier using butt-jointed gradient-index phononic crystals (GRIN PCs) consisting of steel cylinders embedded in a homogeneous epoxy background. By gradually tuning the period of a GRIN PC, the propagating direction of acoustic waves can be continuously bent to follow a sinusoidal trajectory in the structure. The aperture of an acoustic beam can therefore be shrunk or expanded through change of the gradient refractive index profiles of the butt-jointed GRIN PCs. Our computational results elucidate the effectiveness of the proposed acoustic beam aperture modifier. Such an acoustic device can be fabricated through a simple process and will be valuable in applications, such as biomedical imaging and surgery, nondestructive evaluation, communication, and acoustic absorbers. [ABSTRACT FROM AUTHOR]

We designed and simulated a beam aperture modifier and a beam deflector using two-dimensional parabolic gradient-index (GRIN) photonic crystals (PCs). The GRIN PCs are composed of dielectric columns with graded radii along the direction transverse to propagation. Both finite-difference time-domain methods and gradient optics analytical solutions were used to characterize the change in beam width and propagation direction. Multifunctional GRIN PCs combining both beam aperture modification and beam deflection were also designed and simulated. These GRIN PC based designs can be used as optical connectors and bidirectional waveguide couplers in applications such as miniaturized photonic integrated circuits. [ABSTRACT FROM AUTHOR]

Photonic crystal (PC) composites are sequenced series of PCs that feature the same periods but different filling fractions. By properly tuning the filling fractions of the individual PCs and merging the working band of each PC into a continuous frequency range, wide-band self-collimation of optical signals can be realized. The band diagrams and the equal-frequency contours of the PC structures were calculated through the plane wave expansion method and the finite-difference time-domain method was employed to simulate the propagation of electromagnetic waves through the PC structures. Our results show that while a single PC can only collimate optical waves over a narrow frequency range, a PC composite exhibits a much wider collimation band. Such a wide-band optical collimation lens can be useful in applications that demand directional optical energy flow over a long distance, such as optical imaging and biosensing. [ABSTRACT FROM AUTHOR]

We report the design of a two-dimensional gradient-index phononic crystal (GRIN PC) structure, which effectively demonstrates the “acoustic mirage” effect on the wavelength scale. Using the GRIN PC, the propagating direction of acoustic waves can be continuously bent along an arc-shaped trajectory by gradually tuning the filling ratio of PCs. We investigate the acoustic mirage effect through both plane wave expansion and finite-difference time-domain methods. By controlling the incident angle or operating frequency, the arc-shaped trajectory of acoustic wave propagation can be dynamically adjusted. The GRIN PC structure is composed of steel cylinders, positioned in a square lattice, and immersed in an epoxy. It can be fabricated through a simple process and seamlessly integrated with existing acoustic devices. In addition, we establish that such an acoustic effect can be used in the design of tunable acoustic waveguides, which could find applications in acoustic switching, filtering, and biosensing. [ABSTRACT FROM AUTHOR]

As mental health (MH) disorders become increasingly prevalent, their multifaceted symptoms and comorbidities with other conditions introduce complexity to diagnosis, posing a risk of underdiagnosis. While machine learning (ML) has been explored to mitigate these challenges, we hypothesized that multiple data modalities support more comprehensive detection and that non-intrusive collection approaches better capture natural behaviors. To understand the current trends, we systematically reviewed 184 studies to assess feature extraction, feature fusion, and ML methodologies applied to detect MH disorders from passively sensed multimodal data, including audio and video recordings, social media, smartphones, and wearable devices. Our findings revealed varying correlations of modality-specific features in individualized contexts, potentially influenced by demographics and personalities. We also observed the growing adoption of neural network architectures for model-level fusion and as ML algorithms, which have demonstrated promising efficacy in handling high-dimensional features while modeling within and cross-modality relationships. This work provides future researchers with a clear taxonomy of methodological approaches to multimodal detection of MH disorders to inspire future methodological advancements. The comprehensive analysis also guides and supports future researchers in making informed decisions to select an optimal data source that aligns with specific use cases based on the MH disorder of interest.

Abstract Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwide. This scoping review was conducted to identify the most likely health effects of desert dust and sandstorms and the methods used to characterize desert dust exposure from the existing epidemiological literature. We systematically searched PubMed/MEDLINE, Web of Science, and Scopus to identify studies that reported the effects of desert dust and sandstorms on human health. Search terms referred to desert dust or sandstorm exposure, names of major deserts, and health outcomes. Health effects were cross‐tabulated with study design variables (e.g., epidemiological design and methods to quantify dust exposure), desert dust source, health outcomes and conditions. We identified 204 studies that met the inclusion criteria for the scoping review. More than half of the studies (52.9%) used a time‐series study design. However, we found a substantial variation in the methods used to identify and quantify desert dust exposure. The binary metric of dust exposure was more frequently used than the continuous metric for all desert dust source locations. Most studies (84.8%) reported significant associations between desert dust and adverse health effects, mainly for respiratory and cardiovascular mortality and morbidity causes. Although there is a large body of evidence on the health effects of desert dust and sandstorms, the existing epidemiological studies have significant limitations related to exposure measurement and statistical analysis that potentially contribute to inconsistencies in determining the effect of desert dust on human health.

Aim/purpose – This study explores how the content feature and source of eWOM affect people’s intentions and further analyses the effectiveness of eWOM on people’s intention to watch movies.