Showing papers by "National Cheng Kung University published in 2021"

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Artificial intelligence and machine learning in design of mechanical materials

Abstract: Artificial intelligence, especially machine learning (ML) and deep learning (DL) algorithms, is becoming an important tool in the fields of materials and mechanical engineering, attributed to its power to predict materials properties, design de novo materials and discover new mechanisms beyond intuitions. As the structural complexity of novel materials soars, the material design problem to optimize mechanical behaviors can involve massive design spaces that are intractable for conventional methods. Addressing this challenge, ML models trained from large material datasets that relate structure, properties and function at multiple hierarchical levels have offered new avenues for fast exploration of the design spaces. The performance of a ML-based materials design approach relies on the collection or generation of a large dataset that is properly preprocessed using the domain knowledge of materials science underlying chemical and physical concepts, and a suitable selection of the applied ML model. Recent breakthroughs in ML techniques have created vast opportunities for not only overcoming long-standing mechanics problems but also for developing unprecedented materials design strategies. In this review, we first present a brief introduction of state-of-the-art ML models, algorithms and structures. Then, we discuss the importance of data collection, generation and preprocessing. The applications in mechanical property prediction, materials design and computational methods using ML-based approaches are summarized, followed by perspectives on opportunities and open challenges in this emerging and exciting field.

Genomic insights into the formation of human populations in East Asia

Abstract: The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 bc), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 bc) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet—where it forms approximately 84% of the gene pool in some groups—and to the Central Plain, where it has contributed around 59–84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 bc to ad 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai–Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 bc but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 bc with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan. Genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and from 46 present-day groups provide insights into the histories of mixture and migration of human populations in East Asia.

Economic, Mental Health, HIV Prevention and HIV Treatment Impacts of COVID-19 and the COVID-19 Response on a Global Sample of Cisgender Gay Men and Other Men Who Have Sex with Men.

Abstract: There is an urgent need to measure the impacts of COVID-19 among gay men and other men who have sex with men (MSM). We conducted a cross-sectional survey with a global sample of gay men and other MSM (n = 2732) from April 16, 2020 to May 4, 2020, through a social networking app. We characterized the economic, mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response, and examined whether sub-groups of our study population are disproportionately impacted by COVID-19. Many gay men and other MSM not only reported economic and mental health consequences, but also interruptions to HIV prevention and testing, and HIV care and treatment services. These consequences were significantly greater among people living with HIV, racial/ethnic minorities, immigrants, sex workers, and socio-economically disadvantaged groups. These findings highlight the urgent need to mitigate the negative impacts of COVID-19 among gay men and other MSM.

Waste biorefinery towards a sustainable circular bioeconomy: a solution to global issues

Abstract: Global issues such as environmental problems and food security are currently of concern to all of us Circular bioeconomy is a promising approach towards resolving these global issues The production of bioenergy and biomaterials can sustain the energy–environment nexus as well as substitute the devoid of petroleum as the production feedstock, thereby contributing to a cleaner and low carbon environment In addition, assimilation of waste into bioprocesses for the production of useful products and metabolites lead towards a sustainable circular bioeconomy This review aims to highlight the waste biorefinery as a sustainable bio-based circular economy, and, therefore, promoting a greener environment Several case studies on the bioprocesses utilising waste for biopolymers and bio-lipids production as well as bioprocesses incorporated with wastewater treatment are well discussed The strategy of waste biorefinery integrated with circular bioeconomy in the perspectives of unravelling the global issues can help to tackle carbon management and greenhouse gas emissions A waste biorefinery–circular bioeconomy strategy represents a low carbon economy by reducing greenhouse gases footprint, and holds great prospects for a sustainable and greener world

Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials.

Abstract: Importance Immunotherapy has been associated with improved outcomes among patients who have received previous treatment for microsatellite instability-high (MSI-H) tumors Objective To evaluate the antitumor activity of pembrolizumab therapy vs chemotherapy among patients with MSI-H advanced gastric or gastroesophageal junction (G/GEJ) cancer regardless of the line of therapy in which it was received Design, setting, and participants This post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial and the phase 3 KEYNOTE-061 (second-line treatment) and KEYNOTE-062 (first-line treatment) randomized trials included patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062 Patients were enrolled from March 2, 2015, to March 26, 2016, in KEYNOTE-059; from June 4, 2015, to July 26, 2016, in KEYNOTE-061; and from September 18, 2015, to May 26, 2017, in KEYNOTE-062, with data cutoff dates of August 8, 2018; October 26, 2017; and March 26, 2019; respectively Interventions Pembrolizumab monotherapy in KEYNOTE-059, pembrolizumab monotherapy or chemotherapy (paclitaxel) in KEYNOTE-061, and pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin and 5-fluorouracil or capecitabine), or chemotherapy alone in KEYNOTE-062 Main outcomes and measures Response was assessed centrally using Response Evaluation Criteria in Solid Tumours (RECIST), version 11; MSI-H status was determined centrally by polymerase chain reaction testing Results At data cutoff, 7 of 174 patients (40%) in KEYNOTE-059, 27 of 514 patients (53%) in KEYNOTE-061, and 50 of 682 patients (73%) in KEYNOTE-062 had MSI-H tumors Among those with MSI-H tumors, the median overall survival was not reached (NR) for pembrolizumab in KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 or for pembrolizumab plus chemotherapy in KEYNOTE-062 The median progression-free survival (PFS) for pembrolizumab was NR (95% CI, 11 months to NR) in KEYNOTE-059 and 178 months (95% CI, 27 months to NR) in KEYNOTE-061 (vs 35 months [95% CI, 20-98 months] for chemotherapy) In KEYNOTE-062, the median PFS was 112 months (95% CI, 15 months to NR) for pembrolizumab, NR (95% CI, 36 months to NR) for pembrolizumab plus chemotherapy, and 66 months (95% CI, 44-83 months) for chemotherapy The objective response rate (ORR) for pembrolizumab was 571% in KEYNOTE-059 and 467% (vs 167% for chemotherapy) in KEYNOTE-061 In KEYNOTE-062, the ORR was 571% for pembrolizumab , 647% for pembrolizumab plus chemotherapy, and 368% for chemotherapy Conclusions and relevance Findings from this study indicate that MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced G/GEJ cancer regardless of the line of therapy in which it was received Trial registration ClinicalTrialsgov Identifiers: NCT02335411, NCT02370498, and NCT02494583

Room-temperature intrinsic ferromagnetism in epitaxial CrTe2 ultrathin films

Abstract: While the discovery of two-dimensional (2D) magnets opens the door for fundamental physics and next-generation spintronics, it is technically challenging to achieve the room-temperature ferromagnetic (FM) order in a way compatible with potential device applications. Here, we report the growth and properties of single- and few-layer CrTe2, a van der Waals (vdW) material, on bilayer graphene by molecular beam epitaxy (MBE). Intrinsic ferromagnetism with a Curie temperature (TC) up to 300 K, an atomic magnetic moment of ~0.21 $${\mu }_{{\rm{B}}}$$ /Cr and perpendicular magnetic anisotropy (PMA) constant (Ku) of 4.89 × 105 erg/cm3 at room temperature in these few-monolayer films have been unambiguously evidenced by superconducting quantum interference device and X-ray magnetic circular dichroism. This intrinsic ferromagnetism has also been identified by the splitting of majority and minority band dispersions with ~0.2 eV at Г point using angle-resolved photoemission spectroscopy. The FM order is preserved with the film thickness down to a monolayer (TC ~ 200 K), benefiting from the strong PMA and weak interlayer coupling. The successful MBE growth of 2D FM CrTe2 films with room-temperature ferromagnetism opens a new avenue for developing large-scale 2D magnet-based spintronics devices. The emergence of two dimensional ferromagnetism suffers from an inherent fragility to thermal fluctuations, which typically restricts the Curie temperature to below room temperature. Here, Zhang et al present CrTe2 thin films grown via molecular beam epitaxy with a Curie temperature exceeding 300 K.

Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial.

Abstract: Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase 3 trial (ClinicalTrials.gov identifier: NCT03581786), 289 patients with RM-NPC and no previous chemotherapy for recurrent or metastatic disease were randomized (1/1) to receive either toripalimab, a monoclonal antibody against human programmed death-1 (PD-1), or placebo in combination with GP every 3 weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee according to RECIST v.1.1. At the prespecified interim PFS analysis, a significant improvement in PFS was detected in the toripalimab arm compared to the placebo arm: median PFS of 11.7 versus 8.0 months, hazard ratio (HR) = 0.52 (95% confidence interval (CI): 0.36–0.74), P = 0.0003. An improvement in PFS was observed across key subgroups, including PD-L1 expression. As of 18 February 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.603 (95% CI: 0.364–0.997)). The incidence of grade ≥3 adverse events (AEs) (89.0 versus 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5 versus 4.9%) and fatal AEs (2.7 versus 2.8%) was similar between the two arms; however, immune-related AEs (39.7 versus 18.9%) and grade ≥3 infusion reactions (7.5 versus 0.7%) were more frequent in the toripalimab arm. In conclusion, the addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS compared to GP alone, and with a manageable safety profile. Interim analysis from the randomized phase 3 JUPITER-02 trial shows that the addition of anti-PD-1 toripalimab to standard gemcitabine/cisplatin as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma has manageable toxicity and improves progression-free survival, suggesting a potential new treatment standard in this setting.

COVID-19 Vaccine Hesitancy in the United States: A Systematic Review

Abstract: Vaccine hesitancy in the US throughout the pandemic has revealed inconsistent results. This systematic review has compared COVID-19 vaccine uptake across US and investigated predictors of vaccine hesitancy and acceptance across different groups. A search of PubMed database was conducted till 17th July,2021. Articles that met the inclusion criteria were screened and 65 studies were selected for a qualitative analysis. The overall vaccine acceptance rate ranged from 12% to 91.4%, the willingness of studies using the 10-point scale ranged from 3.58-5.12. Increased unwillingness towards COVID-19 vaccine and Black/African Americans were found to be correlated. Sex, race, age, education level, income status were identified as determining factors of having a low or high COVID-19 vaccine uptake. A change in vaccine acceptance in the US population was observed in two studies, an increase of 10.8% and 7.4% respectively between 2020-2021. Our results confirm that hesitancy exists in the US population, highest in Black/African Americans, pregnant or breastfeeding women and low in the male sex. It is imperative for regulatory bodies to acknowledge these statistics and consequently, exert efforts to mitigate the burden of unvaccinated individuals and revise vaccine delivery plans, according to different vulnerable subgroups, across the country.

Observation of single-defect memristor in an MoS2 atomic sheet.

Abstract: Non-volatile resistive switching, also known as memristor1 effect, where an electric field switches the resistance states of a two-terminal device, has emerged as an important concept in the development of high-density information storage, computing and reconfigurable systems2–9. The past decade has witnessed substantial advances in non-volatile resistive switching materials such as metal oxides and solid electrolytes. It was long believed that leakage currents would prevent the observation of this phenomenon for nanometre-thin insulating layers. However, the recent discovery of non-volatile resistive switching in two-dimensional monolayers of transition metal dichalcogenide10,11 and hexagonal boron nitride12 sandwich structures (also known as atomristors) has refuted this belief and added a new materials dimension owing to the benefits of size scaling10,13. Here we elucidate the origin of the switching mechanism in atomic sheets using monolayer MoS2 as a model system. Atomistic imaging and spectroscopy reveal that metal substitution into a sulfur vacancy results in a non-volatile change in the resistance, which is corroborated by computational studies of defect structures and electronic states. These findings provide an atomistic understanding of non-volatile switching and open a new direction in precision defect engineering, down to a single defect, towards achieving the smallest memristor for applications in ultra-dense memory, neuromorphic computing and radio-frequency communication systems2,3,11. A combination of atomistic imaging and spectroscopy reveals that metal substitution into a sulfur vacancy is the underlying mechanism for resistive switching in transition metal dichalcogenide monolayers.

A critical review on various feedstocks as sustainable substrates for biosurfactants production: a way towards cleaner production.

Abstract: The quest for a chemical surfactant substitute has been fuelled by increased environmental awareness. The benefits that biosurfactants present like biodegradability, and biocompatibility over their chemical and synthetic counterparts has contributed immensely to their popularity and use in various industries such as petrochemicals, mining, metallurgy, agrochemicals, fertilizers, beverages, cosmetics, etc. With the growing demand for biosurfactants, researchers are looking for low-cost waste materials to use them as substrates, which will lower the manufacturing costs while providing waste management services as an add-on benefit. The use of low-cost substrates will significantly reduce the cost of producing biosurfactants. This paper discusses the use of various feedstocks in the production of biosurfactants, which not only reduces the cost of waste treatment but also provides an opportunity to profit from the sale of the biosurfactant. Furthermore, it includes state-of-the-art information about employing municipal solid waste as a sustainable feedstock for biosurfactant production, which has not been simultaneously covered in many published literatures on biosurfactant production from different feedstocks. It also addresses the myriad of other issues associated with the processing of biosurfactants, as well as the methods used to address these issues and perspectives, which will move society towards cleaner production.

Nonmonotonic Energy Dependence of Net-Proton Number Fluctuations

Abstract: Nonmonotonic variation with collision energy (sqrt[s_{NN}]) of the moments of the net-baryon number distribution in heavy-ion collisions, related to the correlation length and the susceptibilities of the system, is suggested as a signature for the quantum chromodynamics critical point. We report the first evidence of a nonmonotonic variation in the kurtosis times variance of the net-proton number (proxy for net-baryon number) distribution as a function of sqrt[s_{NN}] with 3.1 σ significance for head-on (central) gold-on-gold (Au+Au) collisions measured solenoidal tracker at Relativistic Heavy Ion Collider. Data in noncentral Au+Au collisions and models of heavy-ion collisions without a critical point show a monotonic variation as a function of sqrt[s_{NN}].

Rapid SARS-CoV-2 Spike Protein Detection by Carbon Nanotube-Based Near-Infrared Nanosensors.

Abstract: To effectively track and eliminate COVID-19, it is critical to develop tools for rapid and accessible diagnosis of actively infected individuals. Here, we introduce a single-walled carbon nanotube (SWCNT)-based optical sensing approach toward this end. We construct a nanosensor based on SWCNTs noncovalently functionalized with ACE2, a host protein with high binding affinity for the SARS-CoV-2 spike protein. The presence of the SARS-CoV-2 spike protein elicits a robust, 2-fold nanosensor fluorescence increase within 90 min of spike protein exposure. We characterize the nanosensor stability and sensing mechanism and passivate the nanosensor to preserve sensing response in saliva and viral transport medium. We further demonstrate that these ACE2-SWCNT nanosensors retain sensing capacity in a surface-immobilized format, exhibiting a 73% fluorescence turn-on response within 5 s of exposure to 35 mg/L SARS-CoV-2 virus-like particles. Our data demonstrate that ACE2-SWCNT nanosensors can be developed into an optical tool for rapid SARS-CoV-2 detection.

Microbiota regulate social behaviour via stress response neurons in the brain.

Abstract: Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence1,2. The gut microbiota contribute to social activity in mice3,4, but the gut–brain connections that regulate this complex behaviour and its underlying neural basis are unclear5,6. Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, which is primarily produced by activation of the hypothalamus–pituitary–adrenal (HPA) axis. Adrenalectomy, antagonism of glucocorticoid receptors, or pharmacological inhibition of corticosterone synthesis effectively corrects social deficits following microbiome depletion. Genetic ablation of glucocorticoid receptors in specific brain regions or chemogenetic inactivation of neurons in the paraventricular nucleus of the hypothalamus that produce corticotrophin-releasing hormone (CRH) reverse social impairments in antibiotic-treated mice. Conversely, specific activation of CRH-expressing neurons in the paraventricular nucleus induces social deficits in mice with a normal microbiome. Via microbiome profiling and in vivo selection, we identify a bacterial species, Enterococcus faecalis, that promotes social activity and reduces corticosterone levels in mice following social stress. These studies suggest that specific gut bacteria can restrain the activation of the HPA axis, and show that the microbiome can affect social behaviours through discrete neuronal circuits that mediate stress responses in the brain. The gut microbiota in mice can modulate social behaviour by influencing activity in stress-related brain areas.

Fear of COVID-19 Scale (FCV-19S) across countries: Measurement invariance issues.

Abstract: AIM: The threats of novel coronavirus disease 2019 (COVID-19) have caused fears worldwide. The Fear of COVID-19 Scale (FCV-19S) was recently developed to assess the fear of COVID-19. Although many studies found that the FCV-19S is psychometrically sound, it is unclear whether the FCV-19S is invariant across countries. The present study aimed to examine the measurement invariance of the FCV-19S across eleven countries. DESIGN: Cross-sectional study. METHODS: Using data collected from prior research on Bangladesh (N = 8,550), United Kingdom (N = 344), Brazil (N = 1,843), Taiwan (N = 539), Italy (N = 249), New Zealand (N = 317), Iran (N = 717), Cuba (N = 772), Pakistan (N = 937), Japan (N = 1,079) and France (N = 316), comprising a total 15,663 participants, the present study used the multigroup confirmatory factor analysis (CFA) and Rasch differential item functioning (DIF) to examine the measurement invariance of the FCV-19S across country, gender and age (children aged below 18 years, young to middle-aged adults aged between 18 and 60 years, and older people aged above 60 years). RESULTS: The unidimensional structure of the FCV-19S was confirmed. Multigroup CFA showed that FCV-19S was partially invariant across country and fully invariant across gender and age. DIF findings were consistent with the findings from multigroup CFA. Many DIF items were displayed for country, few DIF items were displayed for age, and no DIF items were displayed for gender. CONCLUSION: Based on the results of the present study, the FCV-19S is a good psychometric instrument to assess fear of COVID-19 during the pandemic period. Moreover, the use of FCV-19S is supported in at least ten countries with satisfactory psychometric properties.

Layer Hall effect in a 2D topological axion antiferromagnet

Abstract: Whereas ferromagnets have been known and used for millennia, antiferromagnets were only discovered in the 1930s1. At large scale, because of the absence of global magnetization, antiferromagnets may seem to behave like any non-magnetic material. At the microscopic level, however, the opposite alignment of spins forms a rich internal structure. In topological antiferromagnets, this internal structure leads to the possibility that the property known as the Berry phase can acquire distinct spatial textures2,3. Here we study this possibility in an antiferromagnetic axion insulator-even-layered, two-dimensional MnBi2Te4-in which spatial degrees of freedom correspond to different layers. We observe a type of Hall effect-the layer Hall effect-in which electrons from the top and bottom layers spontaneously deflect in opposite directions. Specifically, under zero electric field, even-layered MnBi2Te4 shows no anomalous Hall effect. However, applying an electric field leads to the emergence of a large, layer-polarized anomalous Hall effect of about 0.5e2/h (where e is the electron charge and h is Planck's constant). This layer Hall effect uncovers an unusual layer-locked Berry curvature, which serves to characterize the axion insulator state. Moreover, we find that the layer-locked Berry curvature can be manipulated by the axion field formed from the dot product of the electric and magnetic field vectors. Our results offer new pathways to detect and manipulate the internal spatial structure of fully compensated topological antiferromagnets4-9. The layer-locked Berry curvature represents a first step towards spatial engineering of the Berry phase through effects such as layer-specific moire potential.