Neural Biomarkers for Identifying Atopic Dermatitis and Assessing Acupuncture Treatment Response Using Resting-State fMRI.

Purpose: Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We aimed to develop a deep learning model-based neural signature which can extract the relevant temporal dynamics, discriminate between AD and healthy control (HC), and between AD patients who responded well to acupuncture treatment and those who did not. Patients and Methods: We recruited 41 AD patients (22 male, age mean ± SD: 24.34 ± 5.29) and 40 HCs (20 male, age mean ± SD: 26.4 ± 5.32), and measured resting-state functional MRI signals. After preprocessing, 38 functional regions of interest were applied to the functional MRI signals. A long short-term memory (LSTM) was used to extract the relevant temporal dynamics for classification and train the prediction model. Bootstrapping and 4-fold cross-validation were used to examine the significance of the models. Results: For the identification of AD patients and HC, we found that the supplementary motor area (SMA), posterior cingulate cortex (PCC), temporal pole, precuneus, and dorsolateral prefrontal cortex showed significantly greater prediction accuracy than the chance level. For the identification of high and low responder to acupuncture treatment, we found that the lingual-parahippocampal-fusiform gyrus, SMA, frontal gyrus, PCC and precuneus, paracentral lobule, and primary motor and somatosensory cortex showed significantly greater prediction accuracy than the chance level. Conclusion: We developed and evaluated a deep learning model-based neural biomarker that can distinguish between AD and HC as well as between AD patients who respond well and those who respond less to acupuncture. Using the intrinsic neurological abnormalities, it is possible to diagnose AD patients and provide personalized treatment regimens.

Recent Research Trends in Stem Cells Using CRISPR/Cas-Based Genome Editing Methods.

The clustered regularly interspaced short palindromic repeats (CRISPR) system, a rapidly advancing genome editing technology, allows DNA alterations into the genome of organisms. Gene editing using the CRISPR system enables more precise and diverse editing, such as single nucleotide conversion, precise knock-in of target sequences or genes, chromosomal rearrangement, or gene disruption by simple cutting. Moreover, CRISPR systems comprising transcriptional activators/repressors can be used for epigenetic regulation without DNA damage. Stem cell DNA engineering based on gene editing tools has enormous potential to provide clues regarding the pathogenesis of diseases and to study the mechanisms and treatments of incurable diseases. Here, we review the latest trends in stem cell research using various CRISPR/Cas technologies and discuss their future prospects in treating various diseases.

Precise base editing without unintended indels in human cells and mouse primary myoblasts.

Base editors are powerful tools for making precise single-nucleotide changes in the genome. However, they can lead to unintended insertions and deletions at the target sites, which is a significant limitation for clinical applications. In this study, we aimed to eliminate unwanted indels at the target sites caused by various evolved base editors. Accordingly, we applied dead Cas9 instead of nickase Cas9 in the base editors to induce accurate substitutions without indels. Additionally, we tested the use of chromatin-modulating peptides in the base editors to improve nucleotide conversion efficiency. We found that using both dead Cas9 and chromatin-modulating peptides in base editing improved the nucleotide substitution efficiency without unintended indel mutations at the desired target sites in human cell lines and mouse primary myoblasts. Furthermore, the proposed scheme had fewer off-target effects than conventional base editors at the DNA level. These results indicate that the suggested approach is promising for the development of more accurate and safer base editing techniques for use in clinical applications.

Graded brain fMRI response to somatic and visual acupuncture stimulation.

Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as "dosage" has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.

A prospective observational study of optimal acupoint selection on patients with functional gastrointestinal disorders.

INTRODUCTION: Functional gastrointestinal disorders (FGIDs), which include irritable bowel syndrome (IBS) and functional dyspepsia (FD), are common gastrointestinal (GI) diseases that have a large financial impact on patients' quality of life (QoL). Traditional Korean medicine has a particular diagnostic pattern for treating FGIDs. However, FGIDs have not been thoroughly explored because of their complexity. In this proposed study, we will investigate the acupoint selection pattern for FGID patients with various disease patterns, and further determine the best acupoints for treating FGID patients using a machine-learning algorithm. METHODS: We will collect clinical data from 15 multi-center Korean medical clinics that treat FGID as part of an observational study registry. Patients who meet the criteria will be added to the registry after screening. They will receive a maximum 4-week treatment, and they will respond 3 times to a series of questions. We will investigate how doctors of FGID patients with diverse disease patterns choose the acupoints, and we will use a machine learning technique to identify the best acupoints for treating FGID patients. DISCUSSION: This will be the first multi-center observational registry study to assess how traditional Korean medical practitioners diagnose and treat patients in the real world. The findings will shed light on how traditional Korean medicine treats FGIDs and demonstrate the rationale for the diagnostic and acupuncture treatment flow.

Acupuncture and Acupoints for Low Back Pain: Systematic Review and Meta-Analysis.

Acupuncture has been used as a therapeutic intervention for the treatment of numerous diseases and symptoms for thousands of years, and low back pain has been studied and treated the most in acupuncture clinics. Traditional theory strongly suggests that the selection of acupoints will influence their clinical effects and combinations (e.g., the clinical effects of a particular acupoint or combination on reducing pain), but this idea was not considered in earlier systematic reviews and meta-analyses. We performed a systematic review, meta-analysis, and network analysis to evaluate the magnitude of the effects of acupoints used to treat low back pain in randomized controlled clinical trials. We found that acupuncture significantly reduced pain in patients with low back pain compared with the control group. The most frequently prescribed acupoints were BL23, GV3, BL20, BL40, and BL25, whereas the acupoints with the highest average effect size scores were BL20, GV3, GB30, GB34, and BL25. Further, the combinations of BL23-BL40, BL23-B25, and BL23-BL60 were the most frequently prescribed, while BL23-GV3, BL40-GV4, and BL23-BL25 showed the largest average effect size. By calculating clinical outcomes based on average effect sizes, we found that the most popular acupoints might not always be associated with the best results. Although a more thorough investigation is necessary to determine the clinical effects of each acupoint and combination on patients, we suggest that our approach may offer a fresh perspective that will be useful for future research.

Comparison of the acupuncture manipulation properties of traditional East Asian medicine and Western medical acupuncture.

Background: Acupuncture treatments frequently use manipulation techniques. The therapeutic advantages of acupuncture differ depending on the acupuncture manipulation. The purpose of this article was to compare manipulation techniques in traditional East Asian medicine (TEAM) and Western medical acupuncture (WMA). Methods: Manipulation techniques in TEAM and WMA were compared according to purpose, modulating parameters, and indications. The practical understanding of manipulation in terms of acupuncture stimulation intensity was also explored. The TEAM manipulation techniques of twirling and lifting and thrusting are discussed in terms of the objectives of tonification and sedation. Results: The main therapeutic effect of WMA is mediated through activation of the nervous system, which is achieved with adequate intensity of needling. The TEAM tonification and sedation techniques were designed to produce mild or intense stimulation, respectively, to elicit varying degrees of deqi sensation. Conclusions: Further research is needed to clarify the differences between the TEAM and WMA practices, and to determine whether different needling manipulations affect treatment outcomes.

Efficient, Selective CO2 Photoreduction Enabled by Facet-Resolved Redox-Active Sites on Colloidal CdS Nanosheets.

Advances in nanotechnology have enabled precise design of catalytic sites for CO2 photoreduction, pushing product selectivity to near unity. However, activity of most nanostructured photocatalysts remains underwhelming due to fast recombination of photogenerated electron-hole pairs and sluggish hole transfer. To address these issues, we construct colloidal CdS nanosheets (NSs) with the large basal planes terminated by S2- atomic layers as intrinsic photocatalysts (CdS-S2- NSs). Experimental investigation reveals that the S2- termination endows ultrathin CdS-S2- NSs with facet-resolved redox-catalytic sites: oxidation occurs on S2--terminated large basal facets and reduction happens on side facets. Such an allocation of redox sites not only promotes spatial separation of photoinduced electrons and holes but also facilitates balanced extraction of holes and electrons by shortening the hole diffusion distance along the (001) direction of the ultrathin NSs. Consequently, the CdS-S2- NSs exhibit superb performance for photocatalytic CO2-to-CO conversion, which was verified by the isotope-labeled experiments to be a record-breaking performance: a CO selectivity of 99%, a CO formation rate of 2.13 mol g-1 h-1, and an effective apparent quantum efficiency of 42.1% under the irradiation (340 to 450 nm) of a solar simulator (AM 1.5G). The breakthrough performance achieved in this work provides novel insights into the precise design of nanostructures for selective and efficient CO2 photoreduction.

Identifying Dose Components of Manual Acupuncture to Determine the Dose-Response Relationship of Acupuncture Treatment: A Systematic Review.

The dose-response relationship is a hallmark of pharmacological studies. However, this relationship has not been fully established in acupuncture research. This systematic review aims to provide the characteristics of the dose-response relationship in acupuncture research. We further summarized the differences in acupuncture effects according to dose components. Dose components of acupuncture were categorized into three groups: number of needles, stimulation intensity, and total number/frequency of treatments. The PubMed database was used to identify studies examining the effects of different doses of acupuncture from the establishment of the database to August 13, 2020. Dose components and responses were extracted from each study, and the results of low- and high-dose conditions were compared. Fourteen studies were included in this study. Of the included studies, 37.5% showed statistically significant enhanced responses to acupuncture treatment under high-dose conditions compared to low-dose conditions. Significant differences between high- and low-dose conditions were observed most frequently in studies that used various stimulation intensities (four out of six studies), followed in order by studies that used various numbers of needles (two out of seven studies), and those that used various numbers or frequencies of treatment (none of the three studies). Responses were categorized into symptom changes, physiological changes, experimentally induced pain/stimuli perception, and needling sensation. Stimulation intensity, which is considered one of the most important needling components, might indeed have a great impact on clinical responses to acupuncture.

Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor.

Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and improve the efficiency of prime-editing. Herein, we introduce two strategies to improve the editing efficiency using proximal dead sgRNA and chromatin-modulating peptides. We used enhanced prime-editing to generate Igf2 mutant mice with editing frequencies of up to 47% and observed germline transmission, no off-target effects, and a dwarf phenotype. This improved prime-editing method can be efficiently applied to cell research and to generate mouse models.

Commonality and Specificity of Acupuncture Point Selections.

OBJECTIVE: Because individual acupoints have a wide variety of indications, it is difficult to accurately identify the associations between acupoints and specific diseases. Thus, the present study aimed at revealing the commonality and specificity of acupoint selections using virtual medical diagnoses based on several cases. METHODS: Eighty currently practicing Korean Medicine doctors were asked to prescribe acupoints for virtual acupuncture treatment after being presented with medical information extracted from 10 case reports. The acupoints prescribed for each case were quantified; the data were normalised and compared among the 10 cases using z-scores. A hierarchical cluster analysis was conducted to categorise diseases treated based on the acupoint prescription patterns. Additionally, network analyses were performed on the acupoint prescriptions, at the individual case and cluster level. RESULTS: Acupoints ST36, LI4, and LR3 were most commonly prescribed across all diseases. Regarding the specific acupoints prescribed in each cluster, acupoints around the disease site (knee and lower back) were frequently used in cluster A (musculoskeletal symptoms), acupoints LI4, LR3, PC6, and KI3 were frequently used in cluster B (psychiatric symptoms), and acupoints ST36, LI4, LR3, PC6, CV12, and SP6 were frequently used in cluster C (several symptoms of diseases of internal medicine). CONCLUSIONS: The present study identified the commonality and specificity of acupoint selections based on virtual acupuncture treatments prescribed by practicing clinicians. Acupoint selection patterns, which were defined using a top-down approach in previous studies and classical medical texts, may be further elucidated using a bottom-up approach based on patient medical records.

Ligands as a universal molecular toolkit in synthesis and assembly of semiconductor nanocrystals.

Successful exploitation of semiconductor nanocrystals (NCs) in commercial products is due to the remarkable progress in the wet-chemical synthesis and controlled assembly of NCs. Central to the cadence of this progress is the ability to understand how NC growth and assembly can be controlled kinetically and thermodynamically. The arrested precipitation strategy offers a wide opportunity for materials selection, size uniformity, and morphology control. In this colloidal approach, capping ligands play an instrumental role in determining growth parameters and inter-NC interactions. The impetus for exquisite control over the size and shape of NCs and orientation of NCs in an ensemble has called for the use of two or more types of ligands in the system. In multiple ligand approaches, ligands with different functionalities confer extended tunability, hinting at the possibility of atomic-precision growth and long-range ordering of desired superlattices. Here, we highlight the progress in understanding the roles of ligands in size and shape control and assembly of NCs. We discuss the implication of the advances in the context of optoelectronic applications.

Genome editing methods in animal models.

Genetically engineered animal models that reproduce human diseases are very important for the pathological study of various conditions. The development of the clustered regularly interspaced short palindromic repeats (CRISPR) system has enabled a faster and cheaper production of animal models compared with traditional gene-targeting methods using embryonic stem cells. Genome editing tools based on the CRISPR-Cas9 system are a breakthrough technology that allows the precise introduction of mutations at the target DNA sequences. In particular, this accelerated the creation of animal models, and greatly contributed to the research that utilized them. In this review, we introduce various strategies based on the CRISPR-Cas9 system for building animal models of human diseases and describe various in vivo delivery methods of CRISPR-Cas9 that are applied to disease models for therapeutic purposes. In addition, we summarize the currently available animal models of human diseases that were generated using the CRISPR-Cas9 system and discuss future directions.

Revealing Associations between Diagnosis Patterns and Acupoint Prescriptions Using Medical Data Extracted from Case Reports.

OBJECTIVE: The optimal acupoints for a particular disease can be determined by analysis of diagnosis patterns. The objective of this study was to reveal the association between such patterns and the acupoints prescribed in clinical practice using medical data extracted from case reports. METHODS: This study evaluated online virtual diagnoses made by currently practicing Korean medical doctors (N = 80). The doctors were presented with 10 case reports published in Korean medical journals and were asked to diagnose the patients and prescribe acupoints accordingly. A network analysis and the term frequency-inverse document frequency (tf-idf) method were used to analyse and quantify the relationship between diagnosis patterns and prescribed acupoints. RESULTS: The network analysis showed that ST36, LI4, LR3, and SP6 were the most frequently used acupoints across all diagnoses. The tf-idf values showed the acupoints used for specific diseases, such as BL40 for bladder disease and LU9 for lung disease. CONCLUSIONS: The associations between diagnosis patterns and prescribed acupoints were identified using an online virtual diagnosis modality. Network and text mining analyses revealed commonly applied and disease-specific acupoints in both qualitative and quantitative terms.

Direct cation exchange of CdSe nanocrystals into ZnSe enabled by controlled binding between guest cations and organic ligands.

Zn chalcogenides are suitable candidates for blue-emitting fluorophores in light-emitting devices. In particular, the efforts to grow ZnSe nanocrystals (NCs) with fine control over size and shape via bottom-up approaches have faced challenges because of the slow decomposition of Zn precursors. In this study, we report direct cation exchange from CdSe NCs to ZnSe. Absorption spectroscopy and density functional theory (DFT) analysis reveal that the reactivity of cation exchange depends on the degree of complexation between organic ligands and Zn halides. We controlled the binding strength of Zn complexes by changing the organic ligands and halogen species that bind with Zn. Appropriate binding strength allows for the release of Zn ions and their facile incorporation into CdSe seed NCs. Under our experimental conditions, trioctylphosphine oxide (TOPO)-ZnI2 drives the efficient cation exchange reaction whereas TOPO-ZnCl2 induces no cation exchange of CdSe NCs. In addition, functional groups vary the binding strength between Zn and ligands. Oleylamine (OLAm)-ZnI2, which has a weaker ligand-ZnI2 binding than TOPO-ZnI2, breaks down the original morphologies of host CdSe NCs due to the very fast exchange rate. On the other hand, the TOPO-ZnI2 complex induces a mild exchange rate, leading to transformation into various morphologies such as CdSe nanorods (NRs) and nanoplatelets (NPLs) into CdSe/ZnSe heterostructures inaccessible via other synthesis methods. The incorporation of Zn into various morphologies of CdSe results in tunable optical transitions in blue-UV regions. The synthesis of heterostructured NCs in an elongated morphology is possible, opening opportunities in photocatalysis, light emitting diodes, and luminescent solar concentrators.

Exceptionally stable quantum dot/siloxane hybrid encapsulation material for white light-emitting diodes with a wide color gamut.

Herein, we report a luminescent light-emitting diode (LED) encapsulating material using a thermally curable quantum dot (QD)/siloxane hybrid (TSE-QD) color converter, which has superior long-term stability even at elevated temperatures, in high humidity, and in various chemicals. The TSE-QD is cured by a thermal-induced hydrosilylation reaction of an in situ sol-gel synthesized QD dispersed siloxane resin (QD/siloxane resin) without additional ligand-exchange processes. QDs are successfully encapsulated by highly condensed and linear structured siloxane networks with additional chemical linkages between the surface ligands of the QDs and organic functional groups of the siloxane matrix. Moreover, QDs are uniformly distributed within the siloxane matrix retaining their optical properties during the fabrication processes of the TSE-QD. The result is that the stability, as evaluated by the photoluminescence (PL) quantum yield (QY), is greatly improved under harsh conditions, for example, 120 °C/5% relative humidity (RH), ethanol and acetone for 30 days. Based on the exceptionally stable TSE-QD, we demonstrate a white LED using a blue LED chip directly encapsulated by a yellow emitting TSE-QD that shows excellent spectral stability, outstanding reliability at 85 °C/85% RH and a wide color gamut (116% of NTSC).

Skermanella mucosa sp. nov., isolated from crude oil contaminated soil.

A novel Gram-stain negative, small rod-shaped bacterium (strain 8-14-6T) was isolated from hydrocarbon contaminated desert soil collected from Kuwait. Strain 8-14-6T grew at 5-37 °C, pH 6.0-8.8 and 0-2% (w/v) of NaCl concentration. Casein, starch, Tween 20 and Tween 80 were hydrolyzed while urea, chitin, DNA and carboxymethyl-cellulose were not hydrolyzed by strain 8-14-6T. The major cellular fatty acids were identified as C18:1ω6c/C18:1ω7c, C16:0 and iso-C16:1I/C14:03-OH. Strain 8-14-6T produced diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified phospholipids, two unidentified lipids and five unidentified amino lipids as polar lipids. Genomic G+C content was 73.5 mol %. 16S rRNA gene sequence comparisons indicated that strain 8-14-6T represents a member of the genus Skermanella within family Rhodospirillaceae of the class Alphaproteobacteria. Strain 8-14-6T has a sequence similarity of 98.9% with Skermanella rosea M1T, 97.4% with Skermanella aerolata 5416T-32T, 96.9% with Skermanella stibiiresistens SB22T and <95.4% with the other two known species of the genus Skermanella. The DNA-DNA relatedness values between strain 8-14-6T and the type strains of the closely related species were clearly below the 70% threshold. From the combination of phenotypic and genotypic characteristics and distinct phylogenetic position, the strain is considered to represent a novel species of the genus Skermanella, for which the name Skermanella mucosa sp. nov. is proposed. The type strain is 8-14-6T (=KEMB 2255-438T =JCM 31590T).

Quantum Dot/Siloxane Composite Film Exceptionally Stable against Oxidation under Heat and Moisture.

We report on the fabrication of a siloxane-encapsulated quantum dot (QD) film (QD-silox film), which exhibits stable emission intensity for over 1 month even at elevated temperature and humidity. QD-silox films are solidified via free radical addition reaction between oligosiloxane resin and ligand molecules on QDs. We prepare the QD-oligosiloxane resin by sol-gel condensation reaction of silane precursors with QDs blended in the precursor solution, forgoing ligand-exchange of QDs. The resulting QD-oligosiloxane resin remains optically clear after 40 days of storage, in contrast to other QD-containing resins which turn turbid and ultimately form sediments. QDs also disperse uniformly in the QD-silox film, whose photoluminescence (PL) quantum yield (QY) remains nearly unaltered under harsh conditions; for example, 85 °C/5% relative humidity (RH), 85 °C/85% RH, strongly acidic, and strongly basic environments for 40 days. The QD-silox film appears to remain equally emissive even after being immersed into boiling water (100 °C). Interestingly, the PL QY of the QD-silox film noticeably increases when the film is exposed to a moist environment, which opens a new, facile avenue to curing dimmed QD-containing films. Given its excellent stability, we envision that the QD-silox film is best suited in display applications, particularly as a PL-type down-conversion layer.

Dependency of Electrochemical Performances of Silicon Lithium-Ion Batteries on Glycosidic Linkages of Polysaccharide Binders.

Molecular structures of polysaccharide binders determining mechanical properties were correlated to electrochemical performances of silicon anodes for lithium-ion batteries. Glycosidic linkages (α and ß) and side chains (-COOH and -OH) were selected and proven as the major factors of the molecular structures. Three different single-component polysaccharides were compared: pectin for α-linkages versus carboxylic methyl cellulose (CMC) for ß-linkages from the linkage's standpoint, and pectin as a COOH-containing polymer and amylose as its non-COOH counterpart from the side chain's standpoint. Pectin was remarkably superior to CMC and amylose in cyclability and rate capability of battery cells based on silicon anodes. The pectin binder allowed volume expansion of silicon electrodes with keeping high porosity during lithiation due to the elastic nature caused by the chair-to-boat conformation in α-linkages of its backbone. Physical integrity of pectin-based electrodes was not challenged during repeated lithiation/delithiation cycles without crack development that was observed in rigid CMC-based electrodes. Covalent bonds formed between carboxylic side chains of pectin and silicon surface oxide prevented active silicon mass from being detached away from electric pathways. However, hydrogen bonds between hydroxyl side chains of amylose and silicon surface oxide were not strong enough to keep the silicon mass electrochemically active after cyclability tests.