Challenges and Suggestions of Ethical Review on Clinical Research Involving Brain-Computer Interfaces

Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.

Recent progress in MOFs-based nanozymes for biosensing

Nanozymes are nanomaterials with enzyme-mimicking catalytic activity.Compared to natural enzymes,nanozymes show various properties such as easy to manufacture,stable,adjustable,and inexpensive.Nanozymes play key roles in biosensing,biocatalysis,and disease treatment.As an important kind of nanozymes,metal-organic framework(MOF)-based nanozymes are receiving a lot of attention due to their structural properties and composition.Rationally developing MOF with enzymes-like catalytic properties has opened new perspectives in biosensing.This review summarizes the up-to-date developments in synthesizing two-dimensional and three-dimensional MOF-based nanozymes and their applications in biosensing.Firstly,classification of nanozymes obtained by MOFs is categorized,and different properties of MOF-based nanozymes are described.Then,the distinctive applications of MOF-based nanozymes in identifying various analytes are thoroughly summarized.Finally,the recent challenges and progressive directions in this area are highlighted.

Upconversion Nanoparticles-Encoded Hydrogel Microbeads-Based Multiplexed Protein Detection

Fluorescently encoded microbeads are in demand for multiplexed applications in different fields.Compared to organic dye-based commercially available Luminex's x MAP technology, upconversion nanoparticles(UCNPs) are better alternatives due to their large antiStokes shift, photostability, nil background, and single wavelength excitation. Here, we developed a new multiplexed detection system using UCNPs for encoding poly(ethylene glycol) diacrylate(PEGDA) microbeads as well as for labeling reporter antibody. However, to prepare UCNPs-encoded microbeads, currently used swellingbased encapsulation leads to non-uniformity, which is undesirable for fluorescence-based multiplexing. Hence,we utilized droplet microfluidics to obtain encoded microbeads of uniform size, shape, and UCNPs distribution inside. Additionally, PEGDA microbeads lack functionality for probe antibodies conjugation on their surface.Methods to functionalize the surface of PEGDA microbeads(acrylic acid incorporation, polydopamine coating)reported thus far quench the fluorescence of UCNPs. Here,PEGDA microbeads surface was coated with silica followed by carboxyl modification without compromising the fluorescence intensity of UCNPs. In this study, droplet microfluidics-assisted UCNPs-encoded microbeads of uniform shape, size, and fluorescence were prepared.Multiple color codes were generated by mixing UCNPs emitting red and green colors at different ratios prior to encapsulation. UCNPs emitting blue color were used to label the reporter antibody. Probe antibodies were covalently immobilized on red UCNPs-encoded microbeads for specific capture of human serum albumin(HSA) as a model protein. The system was also demonstrated for multiplexed detection of both human C-reactive protein(hCRP) and HSA protein by immobilizing anti-h CRP antibodies on green UCNPs.

Genetic association study of P2x7 A1513C(rs 3751143) polymorphism and susceptibility to pulmonary tuberculosis: A meta-analysis based on the findings of 11 case-control studies

Objective:To summarize the precise association between pulmonary tuberculosis(PTB) and P2x7 A1513 C gene polymorphism.Methods:PubMed and Google Scholar web-databases were searched for the studies reporting the association of P2x7 A1513 C polymorphism and PTB risk.A meta-analysis was performed for the selected case-control studies and pooled odds ratios(ORs) and 95%confidence intervals(95%CIs) were calculated for all the genetic models.Results:Eleven studies comprising 2 678 controls and 2 113 PTB cases were included in this meta-analysis.We observed overall no significant risk in all the five genetic models.When stratified population by the ethnicity,Caucasian population failed to show any risk of PTB in all the genetics models.In Asian ethnicity,variant allele(C vs.A:P=0.001;QR=1.375,95%CI=1.159-1.632) and heterozygous genotype(AC vs.AA:P=0.001;OR=1.570,95%CI=1.269-1.944) demonstrated significant increased risk of PTB.Likewise,recessive genetic model(CC+AC vs.AA:P=0.001;OR=1.540,95%CI= 1.255-1.890) also demonstrated increased risk of PTB in Asians.Conclusions:Our meta-analysis did not suggest the association of P2x7 A1513 C polymorphism with PTB risk in overall or separately in Caucasian population.However,it plays a significant risk factor for predisposing PTB in Asians.Future larger sample and expression studies are needed to validate this association.

Cross-sectional survey following a longitudinal study on mental health and insomnia of people with sporadic COVID-19

BACKGROUNDIn the post-pandemic era, the emergence of sporadic cases of coronavirus disease 2019 (COVID-19) and the scale of the pandemic are unpredictable. Therefore, the impact ofsporadic cases of COVID-19 and isolation measures on mental health and sleep in different groupsof people need to be analyzed.AIMTo clarify the severity of psychological problems and insomnia of staff and community residentsaround a hospital with sporadic cases of COVID-19, and their relationship with quarantinelocation and long-term changes.METHODSA cross-sectional survey was conducted on community residents and medical staff. Many of thesemedical staff had been subjected to different places of quarantine. Community residents did notexperience quarantine. Hospital anxiety and depression scale (HADS), acute stress disorder scale(ASDS) and insomnia severity index (ISI) were used to evaluate anxiety and depression, acutestress disorder symptoms, and the severity of insomnia. Additionally, we conducted a 1-yearfollow-up study on medical staff, with related scales measurement immediately after and one yearafter the 2-wk quarantine period.RESULTSWe included 406 medical staff and 226 community residents. The total scores of ISI and subscale inHADS of community residents were significantly higher than that of medical staff. Furtheranalysis of medical staff who experienced quarantine showed that 134 were quarantined in hotels,70 in hospitals and 48 at home. Among all subjects, the proportions of HADS, ASDS and ISI scoresabove normal cutoff value were 51.94%, 19.17% and 31.11%, respectively. Multivariable logisticregression analysis found that subjects with higher total ASDS scores had a greater risk to developanxiety and depression. The total ISI score for medical staff in hotel quarantine was significantlyhigher than those in home quarantine. Total 199 doctors and nurses who completed the 1-yearfollow-up study. Compared with baseline, HADS and ASDS scores decreased significantly oneyear after the end of quarantine, while ISI scores did not change significantly.CONCLUSIONSporadic COVID-19 cases had a greater psychological impact on residents in surroundingcommunities, mainly manifested as insomnia and depressive symptoms. Hotel quarantineaggravated the severity of insomnia in medical staff, whose symptoms lasted ≥ 1 year.

Study protocol:A cross-sectional study on psychology and behavior investigation of Chinese residents,PBICR

Objective:This study protocol identifies the basic research route and framework of psychological and behavioral surveys among Chinese residents,aims establishing a database through a multicenter,large-sample cross-sectional survey in China to provide strong data support for research development in various fields and a more comprehensive and systematic understanding of the physical and mental health status of the public.Method:The study was conducted from June 20,2022 to August 31,2022,using stratified sampling and quota sampling methods,a total of 148 cities,202 districts and counties,390 townships/towns/sub-districts,and 780 communities/villages(excluding Hong Kong,Macao,and Taiwan)from 23 provinces,5 autonomous regions,and 4 municipalities directly under the central government in China were selected.The questionnaire was distributed one-on-one and face-to-face to the public by trained investigators,and the questionnaire included eight aspects:personal basic information,personal health status,family basic information,social environment in which they were located,psychological level scale,behavioral level scale,other scales,and attitude towards social hot issues.Data analysis will be performed after questionnaire return.Results:Data collection is ongoing.These findings will support physical and mental health research and strategy development in China and even globally,guiding policy-makers and health care organizations to reform their programs to ensure the best interests of residents and their families.

Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease

Hepatic mitochondrial dysfunction contributes to the progression of nonalcoholic fatty liver disease(NAFLD).However,the factors that maintain mitochondrial homeostasis,especially in hepatocytes,are largely unknown.Hepatocytes synthesize various high-level plasma proteins,among which albumin is most abundant.In this study,we found that pre-folding albumin in the cytoplasm is completely different from folded albumin in the serum.

Mirror-enhanced scanning light-field microscopy for long-term high-speed 3D imaging with isotropic resolution

Various biological behaviors can only be observed in 3D at high speed over the long term with low phototoxicity.Light-field microscopy(LFM)provides an elegant compact solution to record 3D information in a tomographic manner simultaneously,which can facilitate high photon efficiency.However,LFM still suffers from the missing-cone problem,leading to degraded axial resolution and ringing effects after deconvolution.Here,we propose a mirrorenhanced scanning LFM(MiSLFM)to achieve long-term high-speed 3D imaging at super-resolved axial resolution with a single objective,by fully exploiting the extended depth of field of LFM with a tilted mirror placed below samples.To establish the unique capabilities of MiSLFM,we performed extensive experiments,we observed various organelle interactions and intercellular interactions in different types of photosensitive cells under extremely low light conditions.Moreover,we demonstrated that superior axial resolution facilitates more robust blood cell tracking in zebrafish larvae at high speed.

Identification of transcriptional isoforms associated with survival in cancer patient

The Cancer Genome Atlas(TCGA) project produced RNA-Seq data for tens of thousands of cancer and non-cancer samples with clinical survival information,providing an unprecedented opportunity for analyzing prognostic genes and their isoforms.In this study,we performed the first large-scale identification of transcriptional isoforms that are specifically associated with patient prognosis,even without gene-level association.These specific isoforms are defined as Transcripts Associated with Patient Prognosis(TAPPs).Although a group of TAPPs are the principal isoforms of their genes with intact functional protein domains,another group of TAPPs lack important protein domains found in their canonical gene isoforms.This dichotomy in the distribution of protein domains may indicate different patterns of TAPPs association with cancer.TAPPs in protein-coding genes,especially those with altered protein domains,are rich in known cancer driver genes.We further identified multiple types of cancer recurrent TAPPs,such as DCAF17-201,providing a new approach for the detection of cancer-associated events.In order to make the wide research community to study prognostic isoforms,we developed a portal named GESUR(http://gesur.cancer-pku.cn/),which illustrates the detailed prognostic characteristics of TAPPs and other isoforms.Overall,our integrated analysis of gene expression and clinical parameters provides a new perspective for understanding the applications of different gene isoforms in tumor progression.

Recognition for avian influenza virus proteins based on support vector machine and linear discriminant analysis

Total 200 properties related to structural characteristics were employed to represent structures of 400 HA coded proteins of influenza virus as training samples. Some recognition models for HA proteins of avian influenza virus (AIV) were developed using support vector machine (SVM) and linear discriminant analysis (LDA). The results obtained from LDA are as follows: the identification accuracy (Ria) for training samples is 99.8% and Ria by leave one out cross validation is 99.5%. Both Ria of 99.8% for training samples and Ria of 99.3% by leave one out cross validation are obtained using SVM model, respectively. External 200 HA proteins of influenza virus were used to validate the external predictive power of the resulting model. The external Ria for them is 95.5% by LDA and 96.5% by SVM, respectively, which shows that HA proteins of AIVs are preferably recognized by SVM and LDA, and the performances by SVM are superior to those by LDA.

Integration of genetic virtual screening patterns and latent multivariate modeling techniques for QSAR optimization based on combinations and/or interactions between peptides and proteins

Both the concept and the model of snug quantitative structure-activity relationship (QSAR) were pro-posed and developed for molecular design through constructing QSAR based on some known mode of receptor/ligand interactions. Many disadvantages of traditional models can be avoided by using the proposed method because the traditional models only determined upon molecular structural features in sample sets themselves. A genetic virtual screening of peptide/protein combinations (GVSPPC) is proposed for the first time by utilizing this idea to examine peptide/protein affinity activities. A genetic algorithm (GA) was developed for screening combinative targets with an interaction mode for virtual receptors. GVSPPC succeeds in disposing difficulties in rational QSAR,in order to search for the ligand/receptor interactions on conditions of unknown structures. Some bioactive oligo-/poly-peptide systems covering 58 angiotensin converting enzyme (ACE) inhibitors and 18 double site mutation residues in camel antibody protein cAb-Lys3 were investigated by GVSPPC with satisfactory results (R 2 cu>0.91,Q 2 cv > 0.86,ERMS=0.19-0.95),respectively,which demonstrates that GVSPPC is more inter-pretable in the ligand-receptor interaction than the traditional QSAR method.

Engagement of TLR and Dectin-1/Syk Signaling Is Required for Activation of Notch Targets in Dendritic Cells

Pattern-recognition receptors,such as toll-like receptors(TLRs),detect a wide range of microbial products and initiate innate immune responses leading to the production of inflammatory mediators.In addition,TLR signaling also activates expression of Notch target genes that play crucial roles in suppression of TLR-triggered inflammatory responses.However,whether TLR signaling pathways engaged by other classes of pattern-recognition receptors induce expression of Notch target genes remains unclear.Here we demonstrate that zymosan,a stimulus for TLR2 and dectin-1,strongly induces expression of multiple Notch target genes in both human and murine dendritic cells.Mechanistically,induction of Notch targets by zymosan is both TLR2-and Syk-dependent through activation of mitogen-activated protein kinases and the transcription factor c-Fos.Hence,our data reveals a novel mechanism that efficient induction of Notch target genes requires engagement of TLR and dectin-1/Syk signaling pathways.

An Analysis of Crosswalks from Research Data Schemas to Schema.org

The increased number of data repositories has greatly increased the availability of open data.To enable broad discovery and access to research dataset,some data repositories have begun leveraging the web architecture by embedding structured metadata markup in dataset web landing pages using vocabularies from Schema.org and extensions.This paper aims to examine metadata interoperability for supporting global data discovery.Specifically,the paper reports a survey on which metadata schema has been adopted by participating data repositories,and presents an analysis of crosswalks from fourteen research data schemas to Schema.org.The analysis indicates most descriptive metadata are interoperable among the schemas,the most inconsistent mapping is the rights metadata,and a large gap exists in the structural metadata and controlled vocabularies to specify various property values.The analysis and collated crosswalks can serve as a reference for data repositories when they develop crosswalks from their own schemas to Schema.org,and provide the research data community a benchmark of structured metadata implementation.

Capturing the hierarchically assorted modules of protein–protein interactions in the organized nucleome

Nuclear proteins are major constituents and key regulators of nucleome topological organization and manipulators of nuclear events.To decipher the global connectivity of nuclear proteins and the hierarchically organized modules of their interactions,we conducted two rounds of cross-linking mass spectrometry(XL-MS)analysis,one of which followed a quantitative double chemical cross-linking mass spectrometry(in vivo qXL-MS)workflow,and identified 24,140 unique crosslinks in total from the nuclei of soybean seedlings.This in vivo quantitative interactomics enabled the identification of 5340 crosslinks that can be converted into 1297 nuclear protein–protein interactions(PPIs),1220(94%)of which were non-confirmative(or novel)nuclear PPIs compared with those in repositories.There were 250 and 26 novel interactors of histones and the nucleolar box C/D small nucleolar ribonucleoprotein complex,respectively.Modulomic analysis of orthologous Arabidopsis PPIs produced 27 and 24 master nuclear PPI modules(NPIMs)that contain the condensate-forming protein(s)and the intrinsically disordered region–containing proteins,respectively.These NPIMs successfully captured previously reported nuclear protein complexes and nuclear bodies in the nucleus.Surprisingly,these NPIMs were hierarchically assorted into four higher-order communities in a nucleomic graph,including genome and nucleolus communities.This combinatorial pipeline of 4C quantitative interactomics and PPI network modularization revealed 17 ethylene-specific module variants that participate in a broad range of nuclear events.The pipeline was able to capture both nuclear protein complexes and nuclear bodies,construct the topological architectures of PPI modules and module variants in the nucleome,and probably map the protein compositions of biomolecular condensates.

中国脑计划:从基础到临床

The complexity of the brain has attracted scientists from all over the world.Much effort has been paid to explore the mechanisms from genetics to molecules,from cells to circuits,and from Caenorhabditis elegans to humans.Brain research contributes to the development of new technologies,especially artificial intelligence(AI).According to the International Data Corporation,the global revenue of the AI market is expected to exceed$500 billion by 2023 and$900 billion by 2026,highlighting the great importance of brain research for social progress.

Haploidentical stem cell transplantation in patients with chronic myelomonocytic leukemia

Dear Editor,Chronic myelomonocytic leukemia (CMML) is a rare clonal hematological malignancy with both myelodysplastic and myeloproliferative features. Patients with CMML have a very poor prognosis。

COVID-19大流行中的精神心理问题与应对策略

The coronavirus disease-2019(COVID-19)pandemic has imposed a huge burden on global public health.Even before the pandemic,mental health disorders were among the leading reasons for the global health-related burden,and COVID-19 intensified this global crisis for mental health.Stressors such as fear of infection,persistent social distancing measures.

Erratum to:Migrasomes:the knowns,the known unknowns and the unknown unknowns:a personal perspective

The article“Migrasomes:the knowns,the known unknowns and the unknown unknowns:a personal perspective”written by Li Yu,was originally published Online First without Open Access.After publication online first,the author decided to opt for Open Choice and to make the article an Open Access publication.Therefore,the copyright of the article has been changed to©The Author(s)2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/),which permits use,duplication,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.

Migrasomes:the knowns,the known unknowns and the unknown unknowns:a personal perspective

I still remember the day.It was 2012.I was checking the transmission electron microscopy images from the previous day.Something unusual caught my eyes.A structure closely resembling an opened pomegranate stood outside a cell.In retrospect,I realized I had seen these structure before,but that particular image was unusual because there were several of these large structures outside the cell.

SARS-CoV-2 spike protein as a bacterial lipopolysaccharide delivery system in an overzealous inflammatory cascade

Accumulating evidence indicates a potential role for bacterial lipopolysaccharide(LPs)in the overactivation of the immune response during SARS-CoV-2 infection.LPS is recognized by Toll-like receptor 4,mediating proinflammatory effects.We previously reported that LPS directly interacts with SARS-CoV-2 spike(S)protein and enhances proinflammatory activities.Using native gel electrophoresis and hydrogen-deuterium exchange mass spectrometry,we showed that LPS binds to multiple hydrophobic pockets spanning both the S1 and S2 subunits of the S protein.Molecular simulations validated by a microscale thermophoresis binding assay revealed that LPS binds to the S2 pocket with a lower affinity compared to S1,suggesting a role as an intermediate in LPS transfer.Congruently,nuclear factor-kappa B(NF-kB)activation in monocytic THP-1 cells is strongly boosted by S2.Using NF-kB reporter mice followed by bioimaging,a boosting effect was observed for both S1 and S2,with the former potentially facilitated by proteolysis.The Omicron S variant binds to LPS,but with reduced affinity and LPS boosting in vitro and in vivo.Taken together,the data provide a molecular mechanism by which S protein augments LPS-mediated hyperinflammation.