Role of contacts in long-range protein conductance.

Proteins are widely regarded as insulators, despite reports of electrical conductivity. Here we use measurements of single proteins between electrodes, in their natural aqueous environment to show that the factor controlling measured conductance is the nature of the electrical contact to the protein, and that specific ligands make highly selective electrical contacts. Using six proteins that lack known electrochemical activity, and measuring in a potential region where no ion current flows, we find characteristic peaks in the distributions of measured single-molecule conductances. These peaks depend on the contact chemistry, and hence, on the current path through the protein. In consequence, the measured conductance distribution is sensitive to changes in this path caused by ligand binding, as shown with streptavidin-biotin complexes. Measured conductances are on the order of nanosiemens over distances of many nanometers, orders of magnitude more than could be accounted for by electron tunneling. The current is dominated by contact resistance, so the conductance for a given path is independent of the distance between electrodes, as long as the contact points on the protein can span the gap between electrodes. While there is no currently known biological role for high electronic conductance, its dependence on specific contacts has important technological implications, because no current is observed at all without at least one strongly bonded contact, so direct electrical detection is a highly selective and label-free single-molecule detection method. We demonstrate single-molecule, highly specific, label- and background free-electronic detection of IgG antibodies to HIV and Ebola viruses.

The interaction of micro/nano plastics and the environment: Effects of ecological corona on the toxicity to aquatic organisms.

Concerns about the micro/nano plastics (MNPs) exposure risks have risen in recent years. The ecological corona (EC), which is generated by the interaction between MNPs and environmental substances, has a significant impact on their environmental fate and ecological risks. As the largest sink of MNPs, the aquatic environment is of great significance for understanding the environmental behaviour of MNPs. Transmission Electron Microscope (TME), Fourier Transform Infra-Red (FTIR), Scanning Electron Microscope (SEM), Dynamic Light Scattering (DLS) and other analytical methods have been used as effective methods to analyse the formation process of EC and detect the existing EC directly or indirectly on the surface of MNPs. The physicochemical properties of MNPs, complex aquatic environments and ageing time have been identified as the key factors affecting EC formation in aquatic environments. Moreover, the EC absorbed on MNPs significantly changed their environmental behaviour and toxicity to aquatic organisms. This review gives a full understanding of the EC formation progress on the surface of MNPs and different analytical methods for EC have been summarised which can further assist the ecological risk assessment of MNPs in the aquatic environment.

[Study on Feasibility and Countermeasures of Social Third-party EMC Testing for Medical Device Registration].

In view of the background that the regulation of medical device supervision and management is about to cancel the registration and inspection, this paper analyses the risk of electromagnetic compatibility of medical devices, combs the current situation of electromagnetic compatibility testing, discusses the factors to be considered in the approval of third-party testing reports, and gives relevant solutions suitable for China's national conditions.

A Y-Shaped Three-Arm Structure for Probing Bivalent Interactions between Protein Receptor-Ligand Using AFM and SPR.

The goal of this research was to develop linkage chemistry for the study of bivalent interactions between a receptor and its ligand using atomic force microscopy (AFM) and surface plasmon resonance (SPR). We conceived a three-arm structure composed of flexible chains connected to a large rigid core with orthogonal functional groups at their ends for formation and attachment (or immobilization) of bivalent ligands. To demonstrate the principle, we chose the well-known biotin-streptavidin interaction as a model system. On the basis of a crystal structure of the biotin-streptavidin complex, we designed and synthesized a bisbiotin ligand to have a Y shape with two biotin motifs on its arms for binding and a functional group on its stem for immobilization or attachment, referred to as y-bisbiotin. First, we found that the y-bisbiotin ligand stabilized the streptavidin more than its monobiotin counterpart did in solution, which indicates that the bivalent interaction was synergistic. The y-bisbiotin was attached to AFM tips through a click reaction for the force measurement experiments, which showed that unbinding the bisbiotin from streptavidin needed twice the force of unbinding a monobiotin. For the SPR study, we added a ω-thiolated alkyl chain to y-bisbiotin for its incorporation into a monolayer. The SPR data indicated that the streptavidin dissociated from a mixed monolayer bearing y-bisbiotin much slower than from the one bearing monobiotin. This work demonstrates unique chemistry for the study of bivalent interactions using AFM and SPR.

A three-arm scaffold carrying affinity molecules for multiplex recognition imaging by atomic force microscopy: the synthesis, attachment to silicon tips, and detection of proteins.

We have developed a multiplex imaging method for detection of proteins using atomic force microscopy (AFM), which we call multiplex recognition imaging (mRI). AFM has been harnessed to identify protein using a tip functionalized with an affinity molecule at a single molecule level. However, many events in biochemistry require identification of colocated factors simultaneously, and this is not possible with only one type of affinity molecule on an AFM tip. To enable AFM detection of multiple analytes, we designed a recognition head made from conjugating two different affinity molecules to a three-arm linker. When it is attached to an AFM tip, the recognition head would allow the affinity molecules to function in concert. In the present study, we synthesized two recognition heads: one was composed of two nucleic acid aptamers, and the other one composed of an aptamer and a cyclic peptide. They were attached to AFM tips through a catalyst-free click reaction. Our imaging results show that each affinity unit in the recognition head can recognize its respective cognate in an AFM scanning process independently and specifically. The AFM method was sensitive, only requiring 2 to 3 µL of protein solution with a concentration of ∼2 ng/mL for the detection with our current setup. When a mixed sample was deposited on a surface, the ratio of proteins could be determined by counting numbers of the analytes. Thus, this mRI approach has the potential to be used as a label-free system for detection of low-abundance protein biomarkers.

Feasibility study of functional near-infrared spectroscopy in the ventral visual pathway for real-life applications.

Significance: fNIRS-based neuroenhancement depends on the feasible detection of hemodynamic responses in target brain regions. Using the lateral occipital complex (LOC) and the fusiform face area (FFA) in the ventral visual pathway as neurofeedback targets boosts performance in visual recognition. However, the feasibility of utilizing fNIRS to detect LOC and FFA activity in adults remains to be validated as the depth of these regions may exceed the detection limit of fNIRS. Aim: This study aims to investigate the feasibility of using fNIRS to measure hemodynamic responses in the ventral visual pathway, specifically in the LOC and FFA, in adults. Approach: We recorded the hemodynamic activities of the LOC and FFA regions in 35 subjects using a portable eight-channel fNIRS instrument. A standard one-back object and face recognition task was employed to elicit selective brain responses in the LOC and FFA regions. The placement of fNIRS optodes for LOC and FFA detection was guided by our group's transcranial brain atlas (TBA). Results: Our findings revealed selective activation of the LOC target channel (CH2) in response to objects, whereas the FFA target channel (CH7) did not exhibit selective activation in response to faces. Conclusions: Our findings indicate that, although fNIRS detection has limitations in capturing FFA activity, the LOC region emerges as a viable target for fNIRS-based detection. Furthermore, our results advocate for the adoption of the TBA-based method for setting the LOC target channel, offering a promising solution for optrode placement. This feasibility study stands as the inaugural validation of fNIRS for detecting cortical activity in the ventral visual pathway, underscoring its ecological validity. We suggest that our findings establish a pivotal technical groundwork for prospective real-life applications of fNIRS-based research.

Application of catalyst-free click reactions in attaching affinity molecules to tips of atomic force microscopy for detection of protein biomarkers.

Atomic force microscopy (AFM) has been extensively used in studies of biological interactions. Particularly, AFM based force spectroscopy and recognition imaging can sense biomolecules on a single molecule level, having great potential to become a tool for molecular diagnostics in clinics. These techniques, however, require affinity molecules to be attached to AFM tips in order to specifically detect their targets. The attachment chemistry currently used on silicon tips involves multiple steps of reactions and moisture sensitive chemicals, such as (3-aminopropyl)triethoxysilane (APTES) and N-hydroxysuccinimide (NHS) ester, making the process difficult to operate in aqueous solutions. In the present study, we have developed a user-friendly protocol to functionalize the AFM tips with affinity molecules. A key feature of it is that all reactions are carried out in aqueous solutions. In summary, we first synthesized a molecular anchor composed of cyclooctyne and silatrane for introduction of a chemically reactive function to AFM tips and a bifunctional polyethylene glycol linker that harnesses two orthogonal click reactions, copper free alkyne-azide cycloaddition and thiol-vinylsulfone Michael addition, for attaching affinity molecules to AFM tips. The attachment chemistry was then validated by attaching antithrombin DNA aptamers and cyclo-RGD peptides to silicon nitride (SiN) tips, respectively, and measuring forces of unbinding these affinity molecules from their protein cognates human α-thrombin and human α5ß1-integrin immobilized on mica surfaces. In turn, we used the same attachment chemistry to functionalize silicon tips with the same affinity molecules for AFM based recognition imaging, showing that the disease-relevant biomarkers such as α-thrombin and α5ß1-integrin can be detected with high sensitivity and specificity by the single molecule technique. These studies demonstrate the feasibility of our attachment chemistry for the use in functionalization of AFM tips with affinity molecules.

Efficacy of nonpharmacological interventions targeting social function in children and adults with autism spectrum disorder: A systematic review and meta-analysis.

BACKGROUND AND AIMS: This paper aimed to evaluate the use of nonpharmacological interventions for the management of autism spectrum disorder (ASD). The effects of acupuncture and behavioural therapy, two nonpharmalogical interventions, on social function in ASD patients are still controversial. This meta-analysis investigated the impact of these two treatments and compared their effects. METHODS: Seven electronic databases were systematically searched to identify randomized controlled trials (RCTs) on the use of acupuncture or behavioural therapy for ASD. A meta-analysis was carried out using Review Manager 5.4 software. Continuous data are reported as mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs). An assessment of methodological quality using the Cochrane risk-of-bias (ROB) tool for trials was carried out. The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) was applied to evaluate the quality (certainty) of evidence for results regarding social function indicators. RESULTS: Thirty RCTs on acupuncture and 36 on behavioural therapy were included. Compared with the control condition, body acupuncture (SMD: 0.76, 95% CI: [0.52, 1.01]; low certainty), modern acupuncture technology (SMD: 0.84, 95% CI: [0.32, 1.35]; low certainty), cognitive behavioural therapy (SMD: 0.42, 95% CI: [0.26, 0.58]; high certainty), the Denver model (SMD: 0.61, 95% CI: [0.23, 0.99]; moderate certainty) and social skills training (SMD: 0.56, 95% CI: [0.41, 0.71]; moderate certainty) improved social functioning. CONCLUSION: Behavioural therapies (such as CBT, the Denver model, social skills training), improved the social functioning of patients with ASD in the short and long term, as supported by high- and moderate-quality evidence. Acupuncture (including scalp acupuncture, body acupuncture and use of modern acupuncture technology) also improved social functioning, as supported by low- and very low-quality evidence. More high-quality evidence is needed to confirm the effect of acupoint catgut embedding and Early Intensive Behavioural Intervention (EIBI).

Analysis of influence of surgical instruments on accuracy of magnetic navigation system for craniofacial surgery robots.

IntroductionIn craniofacial surgery, magnetic navigation systems can effectively extend the doctor's limited visual range, improve their surgical precision, shorten the operation time, and reduce the incidence of surgical complications. Owing to the ease of magnetic navigation, the accuracy of the magnetic navigation system is affected by various equipment in the operating room. Therefore, its large-scale application is lacking because the navigation accuracy requirement can be extremely high during craniofacial surgery. Therefore, the accuracy of magnetic navigation systems is crucial. Various surgical instruments have been evaluated to effectively reduce the interference of magnetic navigation systems with surgical instruments. In craniofacial surgery, magnetic navigation systems can effectively extend the doctor's limited visual range, improve their surgical precision, shorten the operation time, and reduce the incidence of surgical complications. Owing to the ease of magnetic navigation, the accuracy of the magnetic navigation system is affected by various equipment in the operating room. Therefore, its large-scale application is lacking because the navigation accuracy requirement can be extremely high during craniofacial surgery. Therefore, the accuracy of magnetic navigation systems is crucial. Various surgical instruments have been evaluated to effectively reduce the interference of magnetic navigation systems with surgical instruments. In the surgical environment, the use of surgical instruments during mandibular surgery was simulated by selecting several conventional surgical instruments to record errors in the magnetic navigation system. The fluctuation values of the magnetic navigation errors were subsequently estimated and changes in its accuracy measured. MATLAB was used to calculate and analyze the fluctuations of the magnetic navigation errors. As results, the high-frequency electrosurgical system caused the greatest interference with the magnetic navigation system during surgery while powered on, with a maximum fluctuation error value of 1.8120 mm, and the maximum fluctuation error values of the stitch scissors, teeth forceps, and a needle holder were 1.3662, 1.3781, and 0.3912 mm, respectively. The closer the instrument is to the magnetic field generator or navigation target, the greater its impact. In conclusion, stitch scissors, teeth forceps, a needle holder, and the high-frequency electrosurgical system all affect magnetic navigation system accuracy. Therefore, it is necessary to avoid magnetic navigation system use and surgical instrument disturbances during surgery or select surgical instruments that do not interfere with the system. Surgical instruments must be evaluated for electromagnetic interference before they can be used in surgery with a magnetic navigation system.

Acupuncture-related therapies for protracted opioid abstinence syndrome:A systematic review and meta-analysis.

Background: An increasing amount of clinical evidence of acupuncture's effect on protracted opioid abstinence syndrome (POAS) has emerged in recent years. The aim of this study was to evaluating the evidence of efficacy of acupuncture for POAS. clinical and scientific research work. Methods: Four English-language databases (PubMed, Medline, Embase, Cochrane Libraries) and three Chinese-language databases (CNKI, WanFang and VIP Libraries) were searched, with coverage from database inception to March 31, 2022. Randomized clinical trials (RCTs) evaluating the effects of acupuncture and acupuncture-related therapies for prophylaxis or treatment of POAS were included. Data were screened and extracted independently according to pre-set tabular formats. RCT quality was assessed using risk of bias tool in the Cochrane Collaboration. The primary outcome was opiate withdrawal scale. The secondary outcomes are depression, anxiety for assessing protracted symptoms. The scores on the above scales are proportional to the severity of the symptoms. Results: Twenty-eight trials met the inclusion criteria and provided data for the meta-analysis. A total of only 3 studies (11%) were judged to be low-risk overall due to various biases in them. Acupuncture-related therapy showed statistical differences in improving protracted withdrawal symptom scores compared with sham acupuncture (5 studies, Standard mean difference (SMD), -1.85, 95% CI [-3.21, -0.50], P = 0.007), western medicine(7 studies, SMD, -0.72, 95% CI [-1.22, -0.21], P = 0.005)and no treatment(3 studies, SMD,-2.26, 95% CI [-3.82, -0.69], P = 0.005)with high heterogeneity. Conclusions: Acupuncture maybe safe and effective in relieving POAS individuals' protracted withdrawal symptoms. However, the results of our review should be interpreted with caution because of the high risk of bias of the included trials. Study registration: The protocol of this review has been registered at PROSPERO (CRD42022335505).

A Meta-Analysis on the Efficacy of Acupuncture as an Adjuvant Therapy for Schizophrenia.

Objective: To systematically evaluate the efficacy of acupuncture in the treatment of schizophrenia. Methods: We searched China National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Chinese Science and Technology Periodical Database (VIP), China Biology Medicine Database (CBM), PubMed, Embase, Web of Science, Cochrane Library for relevant literature on the acupuncture treatment of schizophrenia published from database inception to May 17, 2023. The evaluation criteria included total effective rate, incidence of adverse reactions, TESS scale, PANSS scale, BPRS scale, SANA scale, SAPS scale. Two researchers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. The RevMan 5.4 software was used for meta-analysis, risk of bias (ROB) evaluation tool was used to evaluate the risk of bias of the studies, and the GRADE evaluation tool was used to evaluate the quality of evidence. The study was registered on PROSPERO, CRD42023416438. Results: A total of 38 RCTs involving 3143 patients were included in the meta-analysis. The results showed that acupuncture can improve the total effective rate [OR=3.43 (95% CI: 2.71, 4.35), moderate credibility], reduce the incidence of adverse reactions [OR=0.45 (95% CI: 0.32, 0.63), moderate credibility], reduce the TESS score (side effect scale) [MD=-1.83 (95% CI: -2.94, -0.71), very low credibility]. Acupuncture also reduced the PANSS total score [MD=-5.75 (95% CI: -8.08, -3.42), very low credibility], SANA score [MD=-2.66 (95% CI: -6.84, 1.51), very low credibility], SAPS score [MD=-1.26 (95% CI: -2.55, -0.02), very low credibility], and BPRS score [MD=-7.02 (95% CI: -10.59, -3.46), very low credibility]. Conclusion: Existing evidence indicates that acupuncture as an adjunctive therapy can improve the total effective rate of SZ patients, reduce the incidence of adverse reactions, improve clinical symptoms, and alleviate depression and anxiety in SZ patients. However, more high-quality clinical research evidence is still needed to support these findings.

Acupoint stimulation for alcohol use disorder: A systematic review and meta-analysis.

BACKGROUND: To assess the effect of acupoint stimulation for Alcohol use disorders (AUD). METHODS: AUD is a complex disease that threatens the health of the global population. Acupoint stimulation, a sort of therapy applying stimulation on acupoints to produce a therapeutic effect without side effects, has been widely used in AUD patients, but its efficacy remains controversial. Electronic databases (the Cochrane Library, EMBASE, PubMed, CNKI, VIP, Wan-Fang) were systematically searched for randomized controlled trials (RCTs) on acupoint stimulation for AUD from database inception to September 30, 2022. A meta-analysis was performed using Review Manager 5.4 software. Continuous data (scales) were expressed as mean differences (MDs) or standardized mean difference (SMD) with 95% confidence intervals (95% CI). Study methodological quality was assessed according to the Cochrane risk-of-bias tool for trials. The grading of recommendations assessment, development and evaluation was used to assess the certainty of evidence for outcomes. RESULTS: A total of 16 RCTs with 1097 participants were included. Compared to psychotherapy or drug therapy alone, the combination of acupoint stimulation and other sorts of therapies presented advantages in alleviating alcohol craving (SMD = -1.09, 95% CI = -1.40 to -0.77, df = 2, P < .00001, grading of recommendations assessment, development and evaluation very low certainty), (SMD = -2.25, 95% CI = -3.17 to -1.34, df = 3, P < .00001, low certainty) and the severity of alcohol withdrawal symptoms (MD = -1.21, 95% CI = -2.32 to -0.1, df = 2, P = .03, low certainty), as well as improving anxiety (MD = -3.41, 95% CI = -4.06 to -2.76, df = 4, P < .00001, very low certainty) and depression levels (MD = -3.27, 95% CI = -4.92 to -1.62, df = 4, P = .0001, very low certainty) on patients with AUD. In addition, a greater effect was also found with the 4-week treatment courses in reducing craving (SMD = -2.18, 95% CI = -2.61 to -1.75, P < .00001, low certainty). CONCLUSION: Acupoint stimulation and its combined therapy may better relieve AUD symptoms effectively and the treatment duration should be set at more than 2 weeks. However, due to the low-quality of the included RCTs, high-quality studies are needed to further confirm it in the future.

Global prevalence estimates of poststroke fatigue: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Poststroke fatigue (PSF) is a common complication after stroke. However, information on the global prevalence of PSF and how this varies geographically and by population is lacking. Our aim was to examine the global prevalence of PSF and identify sources of heterogeneity in the published literature. METHODS: Four medical databases (PubMed, EMBASE, PsycINFO, and Cochrane Database of Systematic Reviews) were searched from their inception to 28 February 2022. The Joanna Briggs Institute Critical Appraisal Instrument for studies reporting prevalence data (JBI) was used to assess the risk of bias (ROB) of the included studies. The primary outcome was the prevalence of PSF determined using a random-effects model. Subgroup analysis and meta-regression models were used to define the source of heterogeneity. RESULTS: In all, 66 studies with 11,697 patients were included in this meta-analysis. The overall quality of the included studies was medium. The global pooled prevalence of PSF in stroke survivors was 46.79% (95% confidence interval (CI), 43.41-50.18%). The prevalence estimates of PSF based on the Fatigue Severity Scale (FSS), Multidimensional Fatigue Inventory-20 (MFI-20), and Fatigue Assessment Scale (FAS) were 47.44% (95% CI, 43.20-51.67%), 51.69% (95% CI, 44.54-58.83%), and 36.13% (95% CI, 23.07-49.18%), respectively. Prevalence rates of PSF were higher in females (53.19%; 95% CI, 46.46-59.92%), in hemorrhagic stroke (57.54%; 95% CI, 40.55-74.53%), in those with a college degree or higher (53.18%; 95% CI, 42.82-63.54%), and in those with unmarried or divorced status (59.78%; 95% CI, 44.72-74.83%). CONCLUSIONS: The prevalence of PSF in stroke survivors is high, affecting almost half of all stroke sufferers. PSF rates were higher with female gender, being unmarried or divorced, having a higher educational level, and being hemorrhagic compared to ischemic stroke. TRIAL REGISTRATION: PROSPERO (CRD42021269441).

Comparative efficacy of psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment: A network meta-analysis.

AIMS: To estimate the efficacy of multiple psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment (MMT). METHODS: Systematic review and network meta-analysis of randomized controlled trials (RCTs) reporting the effect of psychosocial intervention for opioid-dependent people receiving MMT in outpatient clinics. We searched multiple data sources (Medline, Embase, Web of Science, PsycINFO and Cochrane Library) from inception to January 2022, finding 21 RCTs evaluating a total of 2862 people with opioid dependence receiving MMT. The primary outcome was the opioid-positive rate (assessed by urinalysis) and the secondary outcome was treatment discontinuation (the number of patients who terminated the study for any reason). We performed random-effects Bayesian meta-analysis. We used relative ranking using surface under the cumulative ranking method and certainty of evidence using grading of recommendations, assessment, development and evaluations. RESULTS: Cognitive-behavioral therapy (CBT) [odds ratio (OR) = 0.66, 95% credible interval (CI) = 0.66-0.96; low certainty] and educational and behavioral counseling (EBC) (OR = 0.28, 95% CI = 0.12-0.25; high certainty) were more effective than treatment as usual (TAU) in efficacy. In terms of treatment discontinuation, at the end of the follow-up period there was no statistical significance among psychosocial interventions. According to the ranking probabilities, EBC might be the most effective treatment and behavioral couples' therapy (BCT) might be the best discontinuation treatment. CONCLUSIONS: Educational and behavioral counseling and cognitive-behavioral therapy appear to be the most effective psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment.

Synthesis, physicochemical properties, and hydrogen bonding of 4(5)-substituted 1-H-imidazole-2-carboxamide, a potential universal reader for DNA sequencing by recognition tunneling.

We have developed a chemical reagent that recognizes all naturally occurring DNA bases, a so called universal reader, for DNA sequencing by recognition tunneling in nanopores.1 The primary requirements for this type of molecules are the ability to form non-covalent complexes with individual DNA bases and to generate recognizable electronic signatures under an electrical bias. 1-H-imidazole-2-carboxamide was designed as such a recognition moiety to interact with the DNA bases through hydrogen bonding. In the present study, we first furnished a synthetic route to 1-H-imidazole-2-carboxamide containing a short ω-functionalized alkyl chain at its 4(5) position for its attachment to metal and carbon electrodes. The acid dissociation constants of the imidazole-2-carboxamide were then determined by UV spectroscopy. The data show that the 1-H-imidazole-2-carboxamide exists in a neutral form between pH 6-10. Density functional theory (DFT) and NMR studies indicate that the imidazole ring exists in prototropic tautomers. We propose an intramolecular mechanism for tautomerization of 1-H-imidazole-2-carboxamide. In addition, the imidazole-2-carboxamide can self-associate to form hydrogen bonded dimers. NMR titration found that naturally occurring nucleosides interacted with 1-H-imidazole-2-carboxamide through hydrogen bonding in a tendency of dG>dC≫dT>dA. These studies are indispensable to assisting us in understanding the molecular recognition that takes place in the nanopore where routinely used analytical tools such as NMR and FTIR cannot be conveniently applied.

1,8-Naphthyridine-2,7-diamine: a potential universal reader of Watson-Crick base pairs for DNA sequencing by electron tunneling.

With the aid of Density Functional Theory (DFT), we designed 1,8-naphthyridine-2,7-diamine as a recognition molecule to read DNA base pairs for genomic sequencing by electron tunneling. NMR studies show that it can form stable triplets with both A : T and G : C base pairs through hydrogen bonding. Our results suggest that the naphthyridine molecule should be able to function as a universal base pair reader in a tunneling gap, generating distinguishable signatures under electrical bias for each of DNA base pairs.

Palladium electrodes for molecular tunnel junctions.

Gold has been the metal of choice for research on molecular tunneling junctions, but it is incompatible with complementary metal-oxide-semiconductor fabrication because it forms deep level traps in silicon. Palladium electrodes do not contaminate silicon, and also give higher tunnel current signals in the molecular tunnel junctions that we have studied. The result is cleaner signals in a recognition-tunneling junction that recognizes the four natural DNA bases as well as 5-methyl cytosine, with no spurious background signals. More than 75% of all the recorded signal peaks indicate the base correctly.

Chemical recognition and binding kinetics in a functionalized tunnel junction.

4(5)-(2-mercaptoethyl)-1H-imidazole-2-carboxamide is a molecule that has multiple hydrogen bonding sites and a short flexible linker. When tethered to a pair of electrodes, it traps target molecules in a tunnel junction. Surprisingly large recognition-tunneling signals are generated for all naturally occurring DNA bases A, C, G, T and 5-methyl-cytosine. Tunnel current spikes are stochastic and broadly distributed, but characteristic enough so that individual bases can be identified as a tunneling probe is scanned over DNA oligomers. Each base yields a recognizable burst of signal, the duration of which is controlled entirely by the probe speed, down to speeds of 1 nm s -1, implying a maximum off-rate of 3 s -1 for the recognition complex. The same measurements yield a lower bound on the on-rate of 1 M -1 s -1. Despite the stochastic nature of the signals, an optimized multiparameter fit allows base calling from a single signal peak with an accuracy that can exceed 80% when a single type of nucleotide is present in the junction, meaning that recognition-tunneling is capable of true single-molecule analysis. The accuracy increases to 95% when multiple spikes in a signal cluster are analyzed.

Identifying neuroimaging biomarkers for psychogenic erectile dysfunction by fusing multi-level brain information: A resting-state functional magnetic resonance imaging study.

BACKGROUND: Psychogenic erectile dysfunction (pED) patients who are under their 40s in China consist of a major component of erectile dysfunction. Existing neuroimaging studies have demonstrated that pED is a functional disorder with aberrant neural representations on the local level, the regional level, and the global level, respectively. Therefore, it is reasonable to incorporate brain information from all these levels simultaneously into consideration when identifying neuroimaging biomarkers for pED. However, no such endeavors have been made in previous studies to fully disclose the central mechanism of pED. METHOD: To incorporate multi-level brain features to fully explore the neural representation of pED, a novel machine learning framework was proposed in the current study. Specifically, we used amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality as indices for local, regional, and global brain activity, respectively. A fully data-driven method, that is, support vector machine (SVM) with recursive feature elimination analyses, was used to investigate discriminative brain map between 48 pED patients and 39 healthy control subjects for resting state functional magnetic resonance imaging (rs-fMRI) data. RESULTS: By fusing multi-level brain features, our method led to a superb classification accuracy of 95.12% between two groups. Interestingly, the right anterior cingulate gyrus and the left precuneus showed abnormal representations at different levels simultaneously in pED patients, which also explicated highest discriminative power between groups. Moreover, the right insular, the left fusiform gyrus, the right inferior temporal gyrus, the right superior frontal gyrus, the right precentral gyrus, the bilateral parahippocampal gyrus, and the bilateral inferior frontal gyrus were discriminative for pED. Also, correlation analysis explicated that several core brain regions were associated with the clinical manifestations in pED patients. CONCLUSION: This is one of the first study investigating brain alterations on different levels simultaneously in pED patients. Our results suggested that pED involves multi-level aberrant brain representations in multi-dimensional neurobehavioral components, which closely interrelated with cognitive and psychosocial factors, that is, attention, appraisal, emotion, and sensorimotor. Our findings are likely to help foster new insights into the pathophysiological mechanisms of pED and the aberrant brain regions may serve as potential therapeutic targets for targeted therapy for brain.

A protocol for the integration of multi-omics bioinformatics: Mechanism of acupuncture as an adjunctive therapy for alcohol use disorder.

Background: Alcohol use disorder (AUD) has become a significant global factor in various diseases. As a non-pharmacological therapy, certain therapeutic potential has been found in acupuncture; however, in-depth mechanistic studies related to acupuncture for patients with AUD are still insufficient. Methods: Based on a randomized control design and a multi-omics analysis plan, this protocol details the recruitment (42 AUD patients), group allocation (21 in acupuncture group vs. 21 in sham acupuncture group), intervention and follow-up (replacement drugs as a normal treatment, 2 weeks acupuncture duration, and 3 month follow-up), and data collection and analytical processes. For the clinical outcomes, in addition to the time required for alcohol withdrawal symptoms to subside as the primary outcome, changes in the alcohol withdrawal symptoms, alcohol craving, mood dysfunction, sleep disorder, fatigue, self-efficacy, gastrointestinal symptoms, the quality of life, and the relapse outcomes will be compared between the groups to confirm the acupuncture clinical effectiveness on alcohol withdraw. The gut microbiome and the fecal metabolomics will also be assessed to explore the association of the structure and the function of gut microflora and the mediation of acupuncture effect on AUD fully utilizing gut microflora multi-modal data and clinical information, via the combination of multi-omics methods, feature screening algorithms and appropriate models. Discussion: The results of this study may help to strengthen clinical evidence of the mechanism of acupuncture intervention in patients with AUD, through understanding of the regulatory mechanism of acupuncture in the gut microbiome and its metabolism as well as AUD-related clinical manifestations. Trial registration: Chinese Clinical Trial Registry ChiCTR2200058120. Registered on 24 Mar 2022.