bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Density Plasmonic Nanopores for DNA Sensing at Ultra‐Low Concentrations by Plasmon‐Enhanced Raman Spectroscopy
Authors: Iarossi Marzia , Darvill Daniel , Hubarevich Aliaksandr , Huang Jian‐An , Zhao Yingqi , De Fazio Angela Federica , O'Neill Devin B. , Tantussi Francesco , De Angelis Francesco
Published: June 2023

Solid‐state nanopores are implemented in new and promising platforms that are capable of sensing fundamental biomolecular constituents at the single‐molecule level. However, several limitations and drawbacks remain. For example, the current strategies based on both electrical and optical sensing suffer from low analyte capture rates and challenging nanofabrication procedures. In addition, their limited discrimination power hinders their application in the detection of complex molecular constructs. In contrast, Raman spectroscopy has recently demonstrated the ability to discriminate both nucleotides and amino acids. Herein, a plasmonic nanoassembly is proposed supporting nanopores at high density, in the order of 100 pores per µm2. These findings demonstrate that the device has a high capture rate in the range of a few fm. The pore size is ≈10 nm in diameter and provides an amplification of the electromagnetic field exceeding 103 in intensity at 785 nm. Owing to these features, single‐molecule detection is achieved by means of surface‐enhanced Raman scattering from a solution containing 50 fm DNA molecules (≈4.4 kilobase pairs). Notably, the reported spectra show an average number of 2.5 Raman counts per nucleotide. From this perspective, this number is not far from what is necessary to discriminate the DNA sequence.
Self‐Powered Piezoelectric Actuation Systems Based on Triboelectric Nanogenerator
Authors: Zheng Zhipeng , Wang Binquan , Yin Hao , Chen Yujie , Bao Yi , Guo Yiping
Published: June 2023

Sustainable power supply via triboelectric nanogenerator (TENG) is attractive for self‐powered actuation systems in the era of the Internet of Things (IoTs). Herein, a low‐power actuation scheme enabled by the multilayered TENG for piezoelectric actuators, including the stack, unimorph, and micro‐fiber composite (MFC) actuator, is reported. The working principles of TENG‐powered piezoelectric actuators and their displacement characteristics in direct current (DC) and alternating current (AC) modes are theoretically investigated. Compared with conventional high‐voltage power sources, the multilayered TENG delivers a maximum power of only 10.17 mW, providing a low‐power alternative for piezoelectric actuator with self‐powered capability and operational safety. Meanwhile, the hysteresis of the stack actuator that is critical in precise positioning control is reduced by 58.1%. A precise positioning system is demonstrated by utilizing the TENG‐powered stack actuator as an object stage for microscope focusing applications. The feasibility of vibration control with a 76.7% reduction in vibration amplitude is also verified via two TENG‐powered MFC actuators. A rectifying control circuit comprising the rectifier and gas discharging tube is established to implement AC–DC conversion and discharging control, achieving a larger displacement of the unimorph actuator. The TENG‐powered piezoelectric micropump demonstrates its potential application in liquid transport through straightforward operation.
Long Duration Persistent Photocurrent in 3 nm Thin Doped Indium Oxide for Integrated Light Sensing and In‐Sensor Neuromorphic Computation
Authors: Mazumder Aishani , Nguyen Chung Kim , Aung Thiha , Low Mei Xian , Rahman Md. Ataur , Russo Salvy P. , Tawfik Sherif Abdulkader , Wang Shifan , Bullock James , Krishnamurthi Vaishnavi , Syed Nitu , Ranjan Abhishek , Zavabeti Ali , Abidi Irfan H. , Guo Xiangyang , Li Yongxiang , Ahmed Taimur , Daeneke Torben , Al‐Hourani Akram , Balendhran Sivacarendran , Walia Sumeet
Published: June 2023

Miniaturization and energy consumption by computational systems remain major challenges to address. Optoelectronics based synaptic and light sensing provide an exciting platform for neuromorphic processing and vision applications offering several advantages. It is highly desirable to achieve single‐element image sensors that allow reception of information and execution of in‐memory computing processes while maintaining memory for much longer durations without the need for frequent electrical or optical rehearsals. In this work, ultra‐thin (<3 nm) doped indium oxide (In2O3) layers are engineered to demonstrate a monolithic two‐terminal ultraviolet (UV) sensing and processing system with long optical state retention operating at 50 mV. This endows features of several conductance states within the persistent photocurrent window that are harnessed to show learning capabilities and significantly reduce the number of rehearsals. The atomically thin sheets are implemented as a focal plane array (FPA) for UV spectrum based proof‐of‐concept vision system capable of pattern recognition and memorization required for imaging and detection applications. This integrated light sensing and memory system is deployed to illustrate capabilities for real‐time, in‐sensor memorization, and recognition tasks. This study provides an important template to engineer miniaturized and low operating voltage neuromorphic platforms across the light spectrum based on application demand.
Durable Integrated K‐Metal Anode with Enhanced Mass Transport through Potassiphilic Porous Interconnected Mediator
Authors: Zhao Lu‐Kang , Gao Xuan‐Wen , Mu Jianjia , Luo Wen‐Bin , Liu Zhaomeng , Sun Zhenhua , Gu Qin‐Fen , Li Feng
Published: June 2023

K‐metal batteries have become one of the promising candidates for the large‐scale energy storage owing to the virtually inexhaustible and widely potassium resources. The uneven K+ deposition and dendrite growth on the anode causes the batteries prematurely failure to limit the further application. An integrated K‐metal anode is constructed by cold‐rolling K metal with a potassiphilic porous interconnected mediator. Based on the experimental results and theoretical calculations, it demonstrates that the potassiphilic porous interconnected mediator boosts the mass transportation of K‐metal anode by the K affinity enhancement, which decreases the concentration polarization and makes a dendrite‐free K‐metal anode interface. The interconnected porous structure mitigates the internal stress generated during repetitive deposition/stripping, enabling minimized the generation of electrode collapse. As a result, a durable K‐metal anode with excellent cycling ability of exceed 1, 000 h at 1 mA cm−2/1 mAh cm−2 and lower polarization voltage in carbonate electrolyte is obtained. This proposed integrated anode with fast K+ kinetics fabricated by a repeated cold rolling and folding process provides a new avenue for constructing a high‐performance dendrites‐free anode for K‐metal batteries.
Recent Advances on Cerium Oxide‐Based Biomaterials: Toward the Next Generation of Intelligent Theranostics Platforms
Authors: Huang Yongkang , Zhang Mengzhen , Jin Mengdie , Ma Tengfei , Guo Jialiang , Zhai Xinyun , Du Yaping
Published: June 2023

Disease or organ damage due to unhealthy living habits, or accidents, is inevitable. Discovering an efficient strategy to address these problems is urgently needed in the clinic. In recent years, the biological applications of nanotechnology have received extensive attention. Among them, as a widely used rare earth oxide, cerium oxide (CeO2) has shown good application prospects in biomedical fields due to its attractive physical and chemical properties. Here, the enzyme‐like mechanism of CeO2 is elucidated, and the latest research progress in the biomedical field is reviewed. At the nanoscale, Ce ions in CeO2 can be reversibly converted between +3 and +4. The conversion process is accompanied by the generation and elimination of oxygen vacancies, which give CeO2 the performance of dual redox properties. This property facilitates nano‐CeO2 to catalyze the scavenging of excess free radicals in organisms, hence providing a possibility for the treatment of oxidative stress diseases such as diabetic foot, arthritis, degenerative neurological diseases, and cancer. In addition, relying on its excellent catalytic properties, customizable life‐signaling factor detectors based on electrochemical techniques are developed. At the end of this review, an outlook on the opportunities and challenges of CeO2 in various fields is provided.
Enzyme‐Triggered Intestine‐Specific Targeting Adhesive Platform for Universal Oral Drug Delivery
Authors: Li Ying , Lee Jung Seung , Kirtane Ameya R. , Li Mengyuan , Coffey Charles William , Hess Kaitlyn , Lopes Aaron , Collins Joy , Tamang Siddartha , Ishida Keiko , Hayward Alison , Wainer Jacob , Wentworth Adam J. , Traverso Giovanni
Published: June 2023

Patient adherence to chronic therapies can be suboptimal, leading to poor therapeutic outcomes. Dosage forms that enable reduction in dosing frequency stand to improve patient adherence. Variation in gastrointestinal transit time, inter‐individual differences in gastrointestinal physiology and differences in physicochemical properties of drugs represent challenges to the development of such systems. To this end, a small intestine‐targeted drug delivery system is developed, where prolonged gastrointestinal retention and sustained release are achieved through tissue adhesion of drug pills mediated by an essential intestinal enzyme catalase. Here proof‐of‐concept pharmacokinetics is demonstrated in the swine model for two drugs, hydrophilic amoxicillin and hydrophobic levodopa. It is anticipated that this system can be applicable for many drugs with a diverse of physicochemical characteristics.
PdNi Biatomic Clusters from Metallene Unlock Record‐Low Onset Dehydrogenation Temperature for Bulk‐MgH2
Authors: Xu Nuo , Wang Kaiwen , Zhu Yunfeng , Zhang Yao
Published: June 2023

Hydrogen storage has long been a priority on the renewable energy research agenda. Due to its high volumetric and gravimetric hydrogen density, MgH2 is a desirable candidate for solid‐state hydrogen storage. However, its practical use is constrained by high thermal stability and sluggish kinetics. Here, PdNi bilayer metallenes are reported as catalysts for hydrogen storage of bulk‐MgH2 near ambient temperature. Unprecedented 422 K beginning dehydrogenation temperature and up to 6.36 wt.% reliable hydrogen storage capacity are achieved. Fast hydrogen desorption is also provided by the system (5.49 wt.% in 1 h, 523 K). The in situ generated PdNi alloy clusters with suitable d‐band centers are identified as the main active sites during the de/re‐hydrogenation process by aberration‐corrected transmission electron microscopy and theoretical simulations, while other active species including Pd/Ni pure phase clusters and Pd/Ni single atoms obtained via metallene ball milling, also enhance the reaction. These findings present fundamental insights into active species identification and rational design of highly efficient hydrogen storage materials.
Component Distribution Regulation in Sn‐Pb Perovskite Solar Cells through Selective Molecular Interaction
Authors: Zhang Wenxiao , Yuan Haobo , Li Xiaodong , Guo Xuemin , Lu Chunyan , Liu Acan , Yang Hui , Xu Lin , Shi Xueliang , Fang Zhiwei , Yang Haibo , Cheng Ya , Fang Junfeng
Published: June 2023

Tin‐lead (Sn‐Pb) perovskite solar cells (PSCs) with near‐ideal bandgap still lag behind the pure lead PSCs. Disordered heterojunctions caused by inhomogeneous Sn/Pb ratio in the binary perovskite film induce large recombination loss. Here, an Sn‐Pb perovskite film is reported with homogeneous component and energy distribution by introducing hydrazine sulfate (HS) in Sn perovskite precursor. HS can form hydrogen bond network and coordinate with FASnI3 thus no longer bond with Pb2+, which reduces the crystallization rate of tin perovskite to the level of lead analog. The strong bonding between SO42− and Sn2+ can also suppress its oxidation. As a result, the Sn‐Pb PSCs with HS exhibit a significantly improved VOC of 0.91 V along with a high efficiency of 23.17%. Meanwhile, the hydrogen bond interaction network, strong bonding between Sn2+ and sulfate ion also improve the thermal, storage, and air stability of resulting devices.
Piezo‐Phototronic In2Se3 Nanosheets as a Material Platform for Printable Electronics toward Multifunctional Sensing Applications
Authors: Polyzoidis Christos , Rogdakis Konstantinos , Veisakis George , Tsikritzis Dimitris , Hashemi Payam , Yang Hyejung , Sofer Zdeněk , Shaygan Nia Ali , Feng Xinliang , Kymakis Emmanuel
Published: June 2023

A facile, ultralow‐cost, and up‐scalable printable manufacturing process of flexible, multifunctional sensors that respond to more than one external stimulus could have a pivotal role in low‐cost wearables and portable systems for Industry 4.0. Herein, using a low capex, in‐house spray coating system, the fabrication of a low‐cost photodetector that is tuneable by mechanical strain exploiting the piezo‐phototronic nature of defect‐free 2D In2Se3 nanosheets is reported. Moreover, force sensors that respond to different levels of applied force are spray‐coated by using In2Se3 nanosheets. Regarding the photodetector, a nonmonotonic and asymmetric effect of strain on photocurrent response is shown exhibiting a local maximum at the 23°–32° compressive angle range and a slight hysteresis. Forward compressive bending leads to a photocurrent enhancement by 27% at 32° and reverse by 31% at 23°, while tensile strain leads to a current suppression by 8–10% at 23°–32° angle. The resulting force sensor repeatably demonstrates discrete piezoelectric voltages in the millivolt scale upon different mass loads, opening the path for force and tactile sensing applications. Applying industrially compatible materials for the underlying flexible substrate and electrodes, combined with spray coating, removes manufacturing complexities that engage costly and energy intensive fabrication.
CsPbX3 Based X‐Ray Detectors
Authors: Shi Shenghuan , Yao Huanhuan , Chen Daixie , Li Zhizai , Xu Zhuang , Wang Qian
Published: June 2023

In recent years, X‐ray detectors have been widely applied in industrial non‐destructive testing, medical diagnostics, scientific research, and so on. CsPbX3 has become a dazzling star material because of its high X‐ray absorption coefficient, low trap density, long carrier diffusion length, and other excellent photoelectric characteristics. This review first presents the crystal structure of CsPbX3 and then systematically introduces three single crystal growth methods and two quantum dot synthesis methods. Next, the research progress of X‐ray detection is introduced for different material types and detector types. Finally, the challenges and development prospects of CsPbX3 are discussed.
Dual‐Mode Operando Raman Spectroscopy and Upconversion Thermometry for Probing Thermal Contributions to Plasmonic Photocatalysis
Authors: Ye Ziyang , Bommidi Dinesh Kumar , Pickel Andrea Danielle
Published: June 2023

Operando thermometry can help resolve open questions about the importance of thermal contributions to plasmonic photocatalysis, but identifying high‐fidelity thermometers with the requisite chemical inertness, thermal stability, and spatial resolution remains challenging. Here, it is demonstrated that a single near‐infrared laser can simultaneously excite upconverting nanoparticles (UCNPs) that serve as luminescent thermometers and photocatalyze the dimerization of 4‐nitrothiophenol (4‐NTP), which is employed as a model reaction. Due to its large anti‐Stokes shift, the UCNP thermometry signal naturally separates from the 4‐NTP Raman signal, which is used to monitor the chemical reaction, in the spectral domain. The surface temperature rise of plasmonic substrates under varying illumination intensity is systematically correlated with the reaction progress. Temperature rises exceeding 40 K are recorded at the maximum intensity used, yet lower intensities combined with external heating to achieve the same temperature rise are shown to catalyze the reaction less effectively. Furthermore, measurements performed using equivalent external heating and an intensity too low to photocatalyze the reaction display no evidence of the reaction occurring. By providing high‐fidelity operando surface temperature measurements, this method offers a valuable tool for elucidating thermal contributions to plasmonic photocatalysis.
Multifunction Tunable Piezoelectric‐Actuated Metasurface at Millimeter‐Waves
Authors: Vassos Evangelos , Feresidis Alexandros
Published: June 2023

Free space (also termed quasi‐optical) metasurfaces have recently been designed and proposed as new types of polarizers that allow polarization control of an impinging wave in ways that are not possible with conventional designs. However, existing methods for tunable metasurface polarizers are not able to fully control the polarization dynamically; additionally, at mm‐wave and submillimeter bands, they typically suffer from high losses, which are predominantly produced by the inherent limitations of the tuning elements or materials. An electromechanically tunable reﬂection polariser that has the ability to fully control the polarization of an impinging wave has been designed, fabricated, and experimentally tested in a frequency band centered at 57 GHz. The proposed technique utilizes a variable air cavity between a periodic metasurface array and a ground plane, controlled by a piezoelectric actuator. The periodic metasurface element consists of two slightly different cross‐shaped metallic elements arranged in a periodic triangular lattice. Full‐wave simulations are presented and experimentally validated with measurements. The proposed approach is scalable from microwave up to THz frequencies with low‐loss performance due to the nature of the tuning technology whereby the tuning element is not interfering with the electromagnetic waves in the structure.
PDGF‐BB‐Dependent Neurogenesis Buffers Depressive‐Like Behaviors by Inhibition of GABAergic Projection from Medial Septum to Dentate Gyrus
Authors: Li Hou‐Hong , Liu Yang , Chen Hong‐Sheng , Wang Ji , Li Yu‐Ke , Zhao Yang , Sun Rui , He Jin‐Gang , Wang Fang , Chen Jian‐Guo
Published: June 2023

Hippocampal circuitry stimulation is sufficient to regulate adult hippocampal neurogenesis and ameliorate depressive‐like behavior, but its underlying mechanism remains unclear. Here, it is shown that inhibition of medial septum (MS)‐dentate gyrus (DG) circuit reverses the chronic social defeat stress (CSDS)‐induced depression‐like behavior. Further analysis exhibits that inhibition of gamma‐aminobutyric acidergic neurons in MS projecting to the DG (MSGABA+‐DG) increases the expression of platelet‐derived growth factor‐BB (PDGF‐BB) in somatostatin (SOM) positive interneurons of DG, which contributes to the antidepressant‐like effects. Overexpression of the PDGF‐BB or exogenous administration of PDGF‐BB in DG rescues the effect of chronic stress on the inhibition of neural stem cells (NSCs) proliferation and dendritic growth of adult‐born hippocampal neurons, as well as on depressive‐like behaviors. Conversely, knockdown of PDGF‐BB facilitates CSDS‐induced deficit of hippocampal neurogenesis and promotes the susceptibility to chronic stress in mice. Finally, conditional knockdown platelet‐derived growth factor receptor beta (PDGFRβ) in NSCs blocks an increase in NSCs proliferation and the antidepressant effects of PDGF‐BB. These results delineate a previously unidentified PDGF‐BB/PDGFRβ signaling in regulating depressive‐like behaviors and identify a novel mechanism by which the MSGABA+‐DG pathway regulates the expression of PDGF‐BB in SOM‐positive interneurons.
Self‐Powered Embedded‐Sensory Adjustment for Flow Batteries
Authors: Wang Yifei , Xu Zhizhao , Cao Ran , Xiong Yao , Yang Jiahong , Lei Yanqiang , Ding Mei , Jia Chuankun , Wang Zhong Lin , Sun Qijun
Published: June 2023

Flow batteries (FBs) are one of the most promising strategies for large‐scale energy storage, in which the flow rates of electrolytes are critical to the redox reaction efficiency. However, low‐power and energy‐efficient strategies to effectively monitor and adjust the flow rates of FBs are great challenges. Here, a liquid metal based thin‐film and self‐powered triboelectric sensor (LM‐TS) to monitor and adjust the real‐time electrolyte flow rates in FBs is developed. By integrating the LM‐TS with a peristaltic pump (flow rate control unit in FB), the flow rates of electrolytes can be converted into readable electrical output signals. Furthermore, a logical and a control module are adopted to adjust the flow rates of electrolytes automatically after receiving those electrical signals, which are available to guarantee the optimal working condition of FBs. Benefiting from the high conductivity and outstanding ductility of ultrathin LM film, the self‐powered LM‐TS is endowed with high sensitivity, short response time (9.1 ms), and remarkable cyclic stability (> 20000 cycles) without affecting the normal operation of FBs. This is the first prototype of self‐powered adjustment sensor for FBs, which is readily extended to scaled‐up FB equipment for intermediate trial and large‐scale energy‐storage demonstration.
Robust Sandwiched B/TM/B Structures by Metal Intercalating into Bilayer Borophene Leading to Excellent Hydrogen Evolution Reaction
Authors: Chang Yuan , Liu Jiaxu , Liu Hongsheng , Zhang Yong‐Wei , Gao Junfeng , Zhao Jijun
Published: June 2023

Bilayer borophene, very recently synthesized on Ag and Cu, possesses an extremely flat large surface and excellent conductivity. The van der Waals gap of bilayer borophene can be intercalated by metal atoms, tailoring the properties of bilayer borophene. Herein, sandwiched B/TM/B (transition metal, TM = Co, Ni, Cu, Pd) is proposed as a new 2D formation with both energetic, structural, and thermal stability by TM atoms intercalated into bilayer borophene. In addition, it is a novel platform for the electrocatalytic hydrogen evolution reaction (HER). The intercalation metal atom serves as a single‐atomic catalyst. The TM is protected by outside boron layers from being corroded by acidic/alkaline solutions. B/Cux/B, B/Pdx/B, and B/Alx/B with different metal coverage exhibit defect‐independent extremely low HER free energy in the range of approximately −0.162 to 0.179, −0.134 to 0.183, and −0.082 to 0.086 eV which are comparable to the noble metal Pt. Combining excellent conduction, high structural and thermal stability, low resistance to intercalated behavior, an effortless water splitting process, excellent defect‐independent catalytic performance, cheapness and abundance of raw materials, and corrosion resistance, 2D sandwiched B/TM/B (TM = Co, Ni, Cu, Pd) is believed to be promising for electrocatalysis applications.
Rapid Identification of Enamine‐based Organocatalysts for Quaternary Carbon‐containing Aldol Reactions via Fluorescence‐based Screening
Authors: Ito Hiroshi , Yoshida Yuya , Masuda Tsuguya , Sasaki Aiko , Imoto Kyosuke , Sato Kohei , Narumi Tetsuo , Mase Nobuyuki
Published: June 2023

Fluorescent sensors can directly monitor the progression of chemical transformations through increases in fluorescence intensity to allow rapid identification of superior organocatalytic systems. Based on data from more than 4,000 screenings, a combination of pyrrolidine and isophthalic acid was identified as a catalyst template for the quaternary carbon‐containing aldol reaction. Following fine‐tuning of the catalyst template, 5‐hydroxy isophthalic acid was confirmed as an additive with high reactivity.
Correlation between cognitive tests with scales, vestibular exam and questionnaires for dizziness in the elderly
Authors: Ribeiro Marlon Bruno Nunes , Mancini Patricia Cotta , Bicalho Maria Aparecida Camargo
Published: June 2023

Background

The vestibular system interacts with various cognitive functions, including spatial navigation processes, spatial perception, body representation, mental images, attention, memory, risk perception and social cognition. Studies inform that cognitive impairment is an important risk factor for changes in motor performance and body balance.

Method

Cross‐sectional, observational and analytical study. The sample consisted of 38 elderly people with vestibular dysfunction confirmed by cervical and ocular VEMP exams and/or Video Head Impulse Test (v‐HIT). The procedures of this research were approved by the Ethics Committee of the University under the number CAAE 49714221.0.0000.5149. All participants signed the Informed Consent Form (FICF). Cognitive tests were applied in a room with the patient seated. Paper and pencil were used and all cognitive tests, scales and vestibular exams were performed by the same trained researcher. Analysis using the SPSS program ‐ version 22.0. The distribution of variables was verified using the Kolmogorov‐Smirnov test. Correlation analysis was performed using the Pearson test. We adopted a significance level of 5% (p<0.05).

Result

A positive correlation was found between the MMSE with the gain of the left semicircular canal and negative with the asymmetry of the lateral canals. The Frontal Assessment Battery was negatively correlated with the VAS and positively correlated with the left semicircular canal. The Pfeffer questionnaire showed a positive correlation with the VAS, DHI and its functional and emotional subscales, in addition to a negative correlation with the Berg balance scale. The geriatric depression scale correlated negatively with the VAS and the Berg balance scale and positively correlated with the total DHI and its functional and emotional subscales.

Conclusion

In this study, cognitive aspects, depressive symptoms and functionality were correlated with decreased gain of the left semicircular canal, greater asymmetry of the lateral canals, higher scores on the visual analogue scale, greater impact of dizziness on quality of life and greater risk of falls.
Inflammation and the Vulnerable Brain: Understanding Postoperative Delirium and its Associated Long‐Term Cognitive Outcomes
Authors: Vasunilashorn Sarinnapha M
Published: June 2023

Background

Although growing evidence highlights inflammation as a common biological mechanism of delirium and Alzheimer’s disease (AD), not all individuals with high inflammation develop delirium, AD, and/or cognitive decline. Therefore other predisposing factors (e.g., brain vulnerability) likely influence the effect of inflammation on the brain.

Method

We used the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥65 who underwent elective surgery under spinal anesthesia (n = 40), to investigate the interaction of brain vulnerability and inflammation on persistent neuronal injury. Brain vulnerability was examined from preoperative cerebrospinal fluid: 1) amyloid status, and 2) ATN classification (ATN+ vs. negative for all groups [ATN‐]). Plasma levels of C‐reactive protein (CRP), interleukin‐6, and chitinase 3‐like protein (CHI3L1/YKL‐40), previously associated with delirium, were assigned values of 1‐4 for each marker within sample‐based quartiles. For each patient, we summed these values for the three markers to create an inflammation score (range 0‐12). Persistent neuronal injury, measured using postoperative 1 month (PO1MO) plasma, was measured from neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Linear regression models examined the association between inflammation score and neuronal injury, stratified by brain vulnerability.

Result

On average, participants were age 75 years, 65% female, and 7% had Charlson scores ≥2. We identified a brain vulnerability x inflammation interaction on neuronal injury. Among amyloid+ patients, those in the highest inflammation score tertile [T3] vs T1 had 0.16 pg/ml higher GFAP (p<.05); however, among amyloid‐ patients, no inflammation and GFAP association was observed. No differences between inflammation and neuronal injury, by ATN classification, was observed.

Conclusion

The association between inflammation and persistent neuronal injury differs by amyloid pathology, suggesting the potential value of identifying older patients vulnerable to adverse postoperative cognitive outcomes who may benefit from interventions under conditions of high inflammation.
Systematic assessment of microRNA‐132 therapeutic targeting in Alzheimer’s disease
Authors: Penning Amber , Tosoni Giorgia , Walgrave Hannah , Snoeck Sarah , Balusu Sriram , Salta Evgenia
Published: June 2023

Background

Mapping the mechanistic heterogeneity and multifactorial nature of AD is a key challenge for therapeutic development and the main reason why network biology and multi‐modal therapies begin to attract attention also in AD research. miRNA‐targeted therapeutics are particularly suited for such purposes, as they regulate multiple components of several molecular cascades converging on disease‐relevant patho‐phenotypes. MicroRNA‐132 (miR‐132), a potent neuroimmune regulator, has been identified as the most robustly and significantly downregulated microRNA in the brain of Alzheimer’s Disease (AD) patients and its deficiency has been functionally linked to amyloid deposition, TAU hyperphosphorylation, neuronal cell death and memory decline, in human and rodents. Of note, miR‐132 can explain a higher percentage of the observed variance in histopathological AD phenotypes than APOE e4, a major risk factor for AD, while more recent evidence functionally links miR‐132 to neuroinflammation. These observations suggest that miR‐132‐dependent network‐based gene regulation in human AD brain converges onto biological pathways that can drive disease endophenotypes. Direct miR‐132 infusion in the AD mouse brain can counteract several aspects of pathology and memory deficits, providing a proof‐of‐concept of its therapeutic relevance. Despite the great benefit of the multi‐targeting nature of microRNAs for treating multifactorial diseases such as AD, this approach also entails the risk of on‐ and off‐ target toxicity, highlighting the importance of systematic genome‐wide target validation. While specific miR‐132 targets with direct implications in amyloid and TAU pathologies have been previously identified, the complex multicellular miR‐132 targetome involved in the disease progression of AD remains elusive, and is a crucial requirement for therapeutic targeting.

Method

In order to systematically profile the mechanisms underpinning the regulatory effects of miR‐132 in AD, we employed an RNA‐sequencing approach to assess transcriptomic responses to changes in the levels of miR‐132 in AD‐relevant study systems, such as human iPSC‐derived neurons and microglia‐like cells.

Result

We identify novel miR‐132 targets with putative neuroimmune functions possibly involved in AD pathophysiology.

Conclusion

Our results shed light on the involvement of miR‐132 in AD and further add to the systematic profiling of miR‐132 targetome, a prerequisite for successful translation of miR‐132 supplementation in AD.
Diminishment of High PD‐1 Expressing Peripheral Cytotoxic T Lymphocytes in Behavioral and Psychological Symptoms of Alzheimer’s Disease
Authors: Chu Cheng‐I , Wu Ching‐Tse , Wang Feng‐Yu , Yang Hui‐Yu , Chang Chien‐Chung , Chang Chuang‐Rung
Published: June 2023

Background

Behavioral and psychological symptoms of dementia (BPSD) are troublesome in managing Alzheimer’s disease (AD). Growing research strongly suggests the relationship between AD and immunity of peripheral blood. Immunotherapy with blockade of PD‐L1/PD‐1 axis restored cognitive performance in the murine tauopathy model. We analyzed cytotoxic T lymphocyte (CTL) activity or possibility to be regulated, expression of PD‐1 of peripheral blood, and tried to find the correlation between PD‐1 expression and BPSD severity of AD patients.

Method

16 AD patients meeting NIA‐AA criteria for probable AD dementia (mean age = 80.1, 5 males,11 females) were enrolled in our study. Cognitive function was assessed by clinical dementia rating scale (CDR) and clinical dementia rating scale sum of box (CDR‐SOB). BPSD was evaluated by total neuropsychiatric inventory (NPI) scores. Higher total NPI scores suggested more serious BPSD.

Histograms of CTL PD‐1 median fluorescence intensity (MFI) of 16 AD patients were compared head‐to‐head to determine a cutoff MFI value. CTL with high and low PD‐1 expressing populations were seperated. Correlation between total NPI score and CTL PD‐1 expressing population was further analyzed.

Result

The CTL subset located at the peak with the lowest MFI was defined as PD‐1dim CTL, and this subset was positively correlated to total NPI score. The other CTL subset was defined as PD‐1bright CTL, which was negatively correlated to total NPI score. No correlation was found between PD‐1 expression and CDR‐SOB (data not shown)

Conclusion

Our results revealed that the PD‐1 expression level of CTL decreased with enlarged total NPI scores. Interestingly, CDR‐SOB positively correlated with AD disease progression, yet BPSD could happen in even mild cognitive impairment (MCI) and very early AD stage. Although our study had limitations in sex distribution and small sample size, the results raised concern that CTL might participate in clinical manifestations of BPSD. PD‐1 expressing CTL might not correlate to global dementia progression.

Further studies are expected to evaluate how peripheral CTL interplays with inflammatory molecules, excitatory and inhibitory neurons, cerebral blood perfusion, and gating of choroid plexus in the demented brain.
Single‐Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer’s Disease
Authors: Xu Hui , Jia Jianping
Published: June 2023

Background

Alzheimer’s disease (AD) pathogenesis involves various immune‐related phenomena both in central nervous system and peripheral blood. However, the characteristics of peripheral immune cells is poorly defined in AD at a single cell level.

Method

We profile 36,849 peripheral blood mononuclear cells (PBMC) from AD patients with amyloid positive (Aβ+) and normal controls with amyloid negative (Aβ‐) by 5' single‐cell transcriptome and immune repertoire sequencing with cell ranger standard analysis procedure. Based on the gene expression profile, immune cells were clustered and visualized by t‐distributed stochastic neighbour embedding (tSNE). In addition, we described the features of T cell receptor (TCR) and B cell receptor (BCR) repertoire from clonotypes, V gene and J gene skewed usage, amino acid length, and diversity of complementarity determining region 3 (CDR3).

Result

We revealed five immune cell subsets, CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and monocytes‐macrophages cells, disentangled the characteristic alterations of cell subset proportion and gene expression patterns in AD. A total of 31 cell‐type‐specific key genes, comprising abundant human leucocyte antigen genes, and multiple immune related pathways were identified by protein‐protein interaction network and pathway enrichment analysis. We also found High‐frequency amplification clonotypes in T cells and B cells and the decreased diversity in T cells were detected in AD.

Conclusion

We found abnormal immune infiltration and complex TCR and BCR alterations were presented in AD peripheral blood. As clone amplification suggested the activation of adaptive immune response against specific antigens, we speculated peripheral adaptive immune response, especially mediated by T cell, may have a role in the pathogenesis of AD. This finding may also contribute to further research regarding disease mechanism and development of immune related biomarkers or therapy.
Improving statistical modeling with a neuropathology‐based APOE genetic risk score
Authors: Deming Yuetiva , Vasiljevic Eva , Miao Jiacheng , Van Hulle Carol A. , Jonaitis Erin M. , Morrow Autumn Rose , Whitenack Vanessa M , Kollmorgen Gwendlyn , Suridjan Ivonne , Asthana Sanjay , Carlsson Cynthia M. , Johnson Sterling C. , Zetterberg Henrik , Blennow Kaj , Bendlin Barbara B , Lu Qiongshi , Engelman Corinne D
Published: June 2023

Background

The apolipoprotein E gene (APOE) is the predominant genetic risk factor for late‐onset Alzheimer disease (AD), with three alleles contributing to disease risk and strongly associated with many AD endophenotypes: ε2 (reduced risk), ε3 (reference), and ε4 (increased risk). Researchers often include APOE ε4 carrier status (ε4+/‐) in analyses to account for the genetic effect; however, this does not adequately account for the protective effects of APOE ε2 or the heterogeneous effect of different APOE genotypes (ε2ε2, ε2ε3, ε2ε4, ε3ε3, ε3ε4, and ε4ε4). We hypothesized that accounting for the effect of the full APOE genotype would better recapitulate the influence of APOE in statistical analyses than APOE ε4 status.

Method

To generate a weighted risk score for APOE genotype (APOE‐npscore), we log‐transformed the odds ratios from a recent study reporting APOE genetic risk for neuropathology‐confirmed AD. We regressed cerebrospinal fluid (CSF) AD endophenotypes on the APOE‐npscore using data from the Wisconsin Registry for Alzheimer’s Prevention (WRAP: 233 cognitively unimpaired (CU), 3 mild cognitive impairment (MCI‐AD)) and Wisconsin Alzheimer’s Disease Research Center (WADRC: 287 CU, 42 MCI‐AD, 48 dementia‐AD). In preliminary analyses, APOE‐npscores were tested against CSF amyloid‐beta1‐42 (Aβ42) and phosphorylated tau 181 (pTau181) measured using Elecsys® immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland).

Result

After adjusting for sex and age at lumbar puncture, the APOE‐npscore was associated with CSF Aβ42 (β = ‐115.9, p = 5.7e‐17) and pTau181 (β = 2.05, p = 4.7e‐8). APOE ε4 carrier status also associated with CSF Aβ42 (β = ‐238.0, p = 1.9e‐13) and pTau181 (β = 4.25, p = 1.1e‐6); however, models using APOE‐npscore explained 2.4% more variation in CSF Aβ42 and 0.8% more variation in CSF pTau181 than APOE ε4 status. These findings were similar in the subset of cognitively unimpaired participants.

Conclusion

Our preliminary results demonstrate the benefit of using a pseudo‐continuous variable like the neuropathology‐based APOE risk score instead of binary APOE ε4 status. The APOE‐npscore allows researchers to use a continuous measure to account for APOE genetic risk for AD that does not collapse important genotype categories. This increases statistical power, avoids modeling issues that result from small cell sizes, and allows for a more nuanced interpretation of the genetic effect in analyses.
Cell‐type deconvolution analysis of RNAseq data reveals cell‐specific glycosylation changes in the brains of Alzheimer’s Disease patients
Authors: Tang Xinyu , Lebrilla Carlito B. , Jin Lee‐Way , Maezawa Izumi , Harvey Danielle J. , Zivkovic Angela M.
Published: June 2023

Background

Intriguing evidence that glycosylation is disrupted in Alzheimer’s Disease (AD) has emerged. However, our knowledge of cell‐specific alterations in the expression of genes involved in glycosylation in the brains of AD patients is limited.

Method

In this study, we conducted cell type deconvolution analysis of whole‐tissue RNAseq data to characterize cell type compositional differences and alterations in the expression of glycosylation related genes in the brains of AD patients and those with no cognitive impairment (NCI). Single‐cell human brain RNA‐seq data were obtained from the Allen Brain Map Atlas, consisting of 76,533 total nuclei derived from the cortical tissue of 2 humans. The identified cell types included GABAergic neurons, glutamatergic neurons, astrocytes, oligodendrocytes, oligodendrocyte precursor cells (OPC), microglia, endothelial cells, and vascular leptomeningeal cell (VLMC). The cell‐type deconvolution package CIBERSORT was applied in relative mode with S‐mode (single‐cell mode) batch correction to impute cell fractions and cell‐type‐specific gene expression profiles for NCI and AD samples in the ROSMAP dataset. The differences between cell type fractions of NCI and AD were analyzed by linear mixed regression model and t‐test.

Result

In the dorsolateral prefrontal cortex, neuronal cells represented the highest proportion of cells (∼30‐33%), followed by astrocytes (∼30%), and oligodendrocytes (∼20%), endothelial cells (∼7%), microglia (∼7%), VLMC (∼2‐3%), and OPC (<1%). The overall cell type composition was not significantly different between NCI and AD patients, however, the proportion of microglia, VLMC, and OPC was significantly higher in AD patients (p<0.05). The proportion of glutamatergic neuronal cells was significantly lower in female AD patients (p<0.05) compared with NCI controls, but not in males after controlling for age. Microglia‐associated expression of the glycosyltransferases MGAT1, ST6GAL1, and ST6GALNAC3 was observed in AD patients but not in NCI controls. Glutamatergic neuronal cells and VLMC cells associated with the expression of GALNT10 was observed in AD patients but not in NCI controls. In contrast, GALNT11 expression associated with astrocytes was observed in NCI controls but not in AD patients.

Conclusion

Our findings indicate changes in cell‐type proportions and cell‐specific changes in glycosyltransferase gene expression in the brains of AD patients compared with NCI controls.
Cyclosorus terminans extract and pioglitazone equally alleviate metabolic disturbance and brain pathology in prediabetic rats
Authors: Pratchayasakul Wasana , Chattipakorn Kenneth , Siri‐Angkul Natthapat , Choovuthayakorn Jirachaya , Charumporn Thanapat , Ongnok Benjamin , Saiyasit Napatsorn , Janjek Sornram , Arunsak Busarin , Chunchai Titikorn , Songtrai Sujinda , Kaewsuwan Sireewan , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: June 2023

Background

Long‐term high‐fat diet consumption causes prediabetic conditions with brain pathology, as indicated by peripheral and brain insulin resistance, neuroinflammation, neuronal necroptosis, microglial and astrocyte hyperactivation and increased Alzheimer’s disease‐related proteins including amyloid precursor protein (APP). Although pioglitazone, a peroxisome proliferator‐activated receptor (PPAR)‐γ agonist clinically used to treat type 2 diabetes mellitus, has been shown to improve the metabolic and brain functions in prediabetic condition, this drug can lead to several adverse effects. Recently, an in vitro study showed that Cyclosorus terminans extract, which acts as a natural PPAR‐γ agonist, possessed anti‐diabetic and anti‐obesity properties in adipose‐derived stem cells. However, the comparative efficacy of Cyclosorus terminans extract and pioglitazone on metabolic and brain functions in the prediabetic model has not been elucidated.

Method

Thirty male rats were fed with either a normal diet (ND) or a high‐fat diet (HFD) for 14 weeks. At week 13, ND‐fed rats received vehicle (NDV; n = 6) for additional 2 weeks. HFD‐fed rats were divided into four subgroups to receive either vehicle (HFV; n = 6), 100 mg/kg/day of Cyclosorus terminans extract (I‐100; n = 6), 200 mg/kg/day of Cyclosorus terminans extract (I‐200; n = 6); or 20 mg/kg/day of pioglitazone (Pio; n = 6) for additional 2 weeks. At the end of experimental period, blood and brains were collected to determine metabolic and brain functions.

Result

HFD‐fed rats exhibited a prediabetic condition as characterized by obesity with peripheral insulin resistance. In addition, neuroinflammation, neuronal necroptosis, microglial and astrocyte hyperactivation, and APP expression significantly increased in HFD‐induced prediabetic rats. Cyclosorus terminans extract (100 mg/kg/day) did not attenuate the metabolic disturbance and brain pathologies in HFD‐induced prediabetic rats. Interestingly, 200 mg/kg/day of Cyclosorus terminans extract and pioglitazone equally attenuated peripheral insulin resistance, neuroinflammation, neuronal necroptosis, microglial and astrocyte hyperactivation, and APP expression in HFD‐induced prediabetic rats (P < 0.05, Figure 1).

Conclusion

These findings suggest that Cyclosorus terminans extract may be another therapeutic approach for improving metabolic and brain functions in prediabetic patients who have contraindications to pioglitazone therapy.
Free recall versus combined cued recall and recognition to detect true memory impairment on the Montreal Cognitive Assessment
Authors: Wit Liselotte De , Goldstein Felicia C , Loring David W.
Published: June 2023

Background

The Montreal Cognitive Assessment (MoCA) is widely used as a brief screening measure to characterize overall cognitive status. Although only delayed free recall of the brief 5‐item memory list contributes to widely used MoCA total scores, the optional cued recall and multiple‐choice recognition subtests may provide better diagnostic accuracy than free recall alone.

Method

Data on 719 individuals with Mild Cognitive Impairment and 601 cognitively unimpaired controls were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The Rey Auditory Verbal Learning Test (AVLT) delayed free recall condition was used to characterize level of memory performance. Participants with demographically adjusted T‐scores of ≤ 2 SDs below the mean were classified as ‘impaired.’ Binary logistic regressions assessed if combined MoCA cued/recognition performance was a significant predictor of impaired delayed recall on the AVLT beyond the contribution of free recall and while covarying for age, education, and gender. Sensitivity, specificity, and likelihood ratio values were also examined for the MoCA free recall and combined cued/recognition scores.

Result

Free recall on the MoCA was a significant predictor of delayed recall on the AVLT (b = ‐1.207, Wald χ2 (1) = 128.044, p < 0.001, OR = 0.299, 95%CI = [0.243, 0.369]. The addition of the combined MoCA cued recall/recognition conditions improved the overall model fit (χ2(1) = 30.616, p<.001) and predicted impaired AVLT recall such that for every additional word on combined MoCA cued recall/recognition, the likelihood of being in the AVLT memory impaired group decreased by 33% (b = ‐0.400, Wald χ2 (1) = 29.834, p < 0.001, OR = 0.670, 95%CI = [0. 581, 0.774]). Combined MoCA cued recall/recognition had both higher specificity and likelihood ratios in detecting AVLT memory impairment than MoCA free recall, while higher sensitivity values were present for MoCA free recall (see Table 1).

Conclusion

Use of combined cued/recognition memory conditions provides clinicians with improved diagnostic accuracy in detecting memory impairment. In settings where specificity in detecting memory impairment is important, administration of the MoCA free recall as well as cued recall and recognition conditions is recommended.