Unsupervised Non-rigid Histological Image Registration Guided by Keypoint Correspondences Based on Learnable Deep Features with Iterative Training.

Histological image registration is a fundamental task in histological image analysis. It is challenging because of substantial appearance differences due to multiple staining. Keypoint correspondences, i.e., matched keypoint pairs, have been introduced to guide unsupervised deep learning (DL) based registration methods to handle such a registration task. This paper proposes an iterative keypoint correspondence-guided (IKCG) unsupervised network for non-rigid histological image registration. Fixed deep features and learnable deep features are introduced as keypoint descriptors to automatically establish keypoint correspondences, the distance between which is used as a loss function to train the registration network. Fixed deep features extracted from DL networks that are pre-trained on natural image datasets are more discriminative than handcrafted ones, benefiting from the deep and hierarchical nature of DL networks. The intermediate layer outputs of the registration networks trained on histological image datasets are extracted as learnable deep features, which reveal unique information for histological images. An iterative training strategy is adopted to train the registration network and optimize learnable deep features jointly. Benefiting from the excellent matching ability of learnable deep features optimized with the iterative training strategy, the proposed method can solve the local non-rigid large displacement problem, an inevitable problem usually caused by misoperation, such as tears in producing tissue slices. The proposed method is evaluated on the Automatic Non-rigid Histology Image Registration (ANHIR) website and AutomatiC Registration Of Breast cAncer Tissue (ACROBAT) website. It ranked 1st on both websites as of August 6th, 2024.

Cloning and expression profiling of voltage-gated sodium channel gene (VGSC) from Spodoptera frugiperda.

Spodoptera frugiperda is a long-distance migratory pest with strong dispersal ability, fast reproduction speed and destructive feeding, so it is difficult to prevent and control. Pyrethroid insecticides are commonly used in pest insects control, And since the voltage-gated sodium channel (VGSC) serves as a major target of pyrethroids, it is important to study this gene for pest control. VGSC is an integral transmembrane protein consisting of approximately 2,000 amino acid residues found in neurons, myocytes, endocrine cells, and ovarian cells and involved in the initiation and propagation of excitable cellular action potentials. In this study, the cDNA sequence of the VGSC was identified from S. frugiperda by rapid amplification of cDNA ends (RACE) which contained an open reading frame of 6,261 bp encoding a protein of 2,086 amino acids. The molecular weight of this protein was predicted to be 236 kDa, and the theoretical isoelectric point was 5.21. A phylogenetic tree constructed based on lepidopteran insects showed that the VGSC of S. frugiperda was most closely relative to that of Spodoptera litura. VGSC is a highly conserved protein with Ion channel conserved structural domains of transmembrane proteins. qPCR showed that the VGSC gene was highly expressed in the epidermis of 2nd instar larvae, and its expression level was low in other tissues, such as the foregut and Malpighian tubules. In addition, VGSC was also detected in the prepupal stage, then gradually increased in abundance after entering the adult stage, peaked at the adult males on the 4th day of pupal stage, and decreased afterwards. The recombinant plasmid of pSumo-mut-VGSC was constructed and induced to express a His tag fused VGSC protein. Polyclonal antibodies were prepared from purified recombinant VGSC protein. The antibody was ELISA-titered, and the western blotting results showed that it specifically recognized VGSC, whether it was recombinant or endogenous protein. These results have laid the foundation for future studies on the physiological function of this gene in the growth and development of S. frugiperda.

A systematic review and meta-analysis of canine enteric coronavirus prevalence in dogs of mainland China.

BACKGROUND: Canine enteric coronavirus (CECoV) is a prevalent infectious disease among dogs worldwide, yet its epidemiology in mainland China remains poorly understood. This systematic review and meta-analysis aimed to assess the prevalence of CECoV in mainland China and identify factors influencing its prevalence. METHODS: A comprehensive literature search was conducted across multiple databases for studies regarding CECoV epidemiology of China. PubMed, CNKI, Wanfang, and CQVIP were searched to obtain the studies. Eligible studies were selected based on predefined criteria, and data were extracted and synthesized. The quality the studies was assessed using the JBI assessment tool. Heterogeneity was checked using I2 test statistics followed by subgroup and sensitivity analysis. Subgroup analyses were performed to explore variations in CECoV prevalence by factors such as year, region, season, health status, social housing type, gender, age, and breed. Publication bias was assessed using a funnel plot and eggers test that was followed by trim and fill analysis. RESULTS: A total of 27 studies involving 21,034 samples were included in the meta-analysis. The overall pooled prevalence of CECoV in mainland China was estimated to be 0.30 (95% CI 0.24-0.37), indicating persistent circulation of the virus. Subgroup analyses revealed higher prevalence rates in younger dogs, multi-dog households, apparently healthy dogs, and certain regions such as southwest China. Seasonal variations were observed, with lower prevalence rates in summer. However, no significant differences in prevalence were found by gender. CONCLUSIONS: This study provides valuable insights into the epidemiology of CECoV in mainland China, highlighting the persistent circulation of the virus and identifying factors associated with higher prevalence rates. Continuous monitoring and surveillance efforts, along with research into accurate detection methods and preventive measures, are essential for the effective control of CECoV and mitigation of its potential impact on animal and human health.

Modulating the Expression of Exercise-induced lncRNAs: Implications for Cardiovascular Disease Progression.

Recent research shows exercise is good for heart health, emphasizing the importance of physical activity. Sedentary behavior increases the risk of cardiovascular disease, while exercise can help prevent and treat it. Additionally, physical exercise can modulate the expression of lncRNAs, influencing cardiovascular disease progression. Therefore, understanding this relationship could help identify prospective biomarkers and therapeutic targets pertaining to cardiovascular ailments. This review has underscored recent advancements concerning the potential biomarkers of lncRNAs in cardiovascular diseases, while also summarizing existing knowledge regarding dysregulated lncRNAs and their plausible molecular mechanisms. Additionally, we have contributed novel perspectives on the underlying mechanisms of lncRNAs, which hold promise as potential biomarkers and therapeutic targets for cardiovascular conditions. The knowledge imparted in this review may prove valuable in guiding the design of future investigations and furthering the understanding of lncRNAs as diagnostic, prognostic, and therapeutic biomarkers for cardiovascular diseases.

A capture-recapture modeling framework emphasizing expert opinion in disease surveillance.

In disease surveillance, capture-recapture methods are commonly used to estimate the number of diseased cases in a defined target population. Since the number of cases never identified by any surveillance system cannot be observed, estimation of the case count typically requires at least one crucial assumption about the dependency between surveillance systems. However, such assumptions are generally unverifiable based on the observed data alone. In this paper, we advocate a modeling framework hinging on the choice of a key population-level parameter that reflects dependencies among surveillance streams. With the key dependency parameter as the focus, the proposed method offers the benefits of (a) incorporating expert opinion in the spirit of prior information to guide estimation; (b) providing accessible bias corrections, and (c) leveraging an adapted credible interval approach to facilitate inference. We apply the proposed framework to two real human immunodeficiency virus surveillance datasets exhibiting three-stream and four-stream capture-recapture-based case count estimation. Our approach enables estimation of the number of human immunodeficiency virus positive cases for both examples, under realistic assumptions that are under the investigator's control and can be readily interpreted. The proposed framework also permits principled uncertainty analyses through which a user can acknowledge their level of confidence in assumptions made about the key non-identifiable dependency parameter.

Intentions of healthcare seeking and self-isolation for MPOX among men who have sex with men in China: a national cross-sectional study.

Linking identified MPOX cases to care is essential for MPOX control. This study aims to investigate the intentions of healthcare seeking and self-isolation for MPOX among men who have sex with men (MSM) in China. A cross-sectional online survey was conducted in early August 2023 in China. Respondents were recruited by community-based organizations (CBOs), collecting information on demographics, health status, behavioural and psychological characteristics. Univariate and multivariate logistic regression analyses were performed to examine the predictors of intentions to seek healthcare and self-isolate for MPOX within the MSM population. A total of 7725 participants were recruited, with a median age of 30 years. 92.21% of the participants would seek healthcare for MPOX-like symptoms, but only 52.50% intended to self-isolate if diagnosed. Intentions to seek healthcare were lower among those with MPOX-like symptoms in the past 3 months (standardized prevalence ratio (SPRs) = 0.82, 95% CI: 0.74-0.89) and the willingness to self-isolate was reduced among those diagnosed with MPOX in the past 3 months (SPRs = 0.65, 95% CI: 0.48-0.87). Participants free of sexually transmitted infections (STIs) and those aware of their HIV status were more likely to seek healthcare and self-isolate than those with STIs or unaware of their HIV status. Regular followers of MPOX information and those perceiving a low risk of infection were more inclined to take preventive measures. These findings highlight the need for targeted MPOX prevention strategies for high-risk groups and the importance of addressing barriers in infectious disease prevention response.

Lama1 upregulation prolongs the lifespan of the dyH/dyH mouse model of LAMA2-related congenital muscular dystrophy.

LAMA2-related congenital muscular dystrophy (LAMA2-CMD), characterized by laminin-α2 deficiency, is debilitating and ultimately fatal. To date, no effective therapy has been clinically available. Laminin-α1, which shares significant similarities with laminin-α2, has been proven as a viable compensatory modifier. To evaluate its clinical applicability, we establish a Lama2 exon-3 deletion mouse model (dyH/dyH). The dyH/dyH mice exhibit early lethality and typical LAMA2-CMD phenotypes, allowing the evaluation of various endpoints. In dyH/dyH mice treated with synergistic activation mediator-based CRISPRa-mediated Lama1 upregulation, a nearly doubled median survival is observed, as well as improvements in weight and grip. Significant therapeutical effects are revealed by MRI, serum biochemical indices, and muscle pathology studies. Treating LAMA2-CMD with LAMA1 upregulation is feasible and that early intervention can alleviate symptoms and extend lifespan. Additionally, we reveal limitations of LAMA1 upregulation, including high-dose mortality and non-sustained expression, which require further optimization in future studies.

Mediation role of DNA methylation in association between handgrip strength and cognitive function in monozygotic twins.

Handgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59 monozygotic twin pairs to explore the potential mediating effect of DNA methylation (DNAm) on the association between handgrip strength and cognitive function. The initial step was the implementation of an epigenome-wide association analysis (EWAS) in the study participants, with the aim of identifying DNAm variations that are associated with handgrip strength. Following that, we conducted an assessment of the mediated effect of DNAm by the use of mediation analysis. In order to do an ontology enrichment study for CpGs, the GREAT program was used. There was a significant positive association between handgrip strength and cognitive function (ß = 0.194, P < 0.001). The association between handgrip strength and DNAm of 124 CpGs was found to be statistically significant at a significance level of P < 1 × 10-4. Fifteen differentially methylated regions (DMRs) related to handgrip strength were found in genes such as SNTG2, KLB, CDH11, and PANX2. Of the 124 CpGs, 4 within KRBA1, and TRAK1 mediated the association between handgrip strength and cognitive function: each 1 kg increase in handgrip strength was associated with a potential decrease of 0.050 points in cognitive function scores, mediated by modifications in DNAm. The parallel mediating effect of these 4 CpGs was -0.081. The presence of DNAm variation associated with handgrip strength may play a mediated role in the association between handgrip strength and cognitive function.

Enhanced Inference for Finite Population Sampling-Based Prevalence Estimation with Misclassification Errors.

Epidemiologic screening programs often make use of tests with small, but non-zero probabilities of misdiagnosis. In this article, we assume the target population is finite with a fixed number of true cases, and that we apply an imperfect test with known sensitivity and specificity to a sample of individuals from the population. In this setting, we propose an enhanced inferential approach for use in conjunction with sampling-based bias-corrected prevalence estimation. While ignoring the finite nature of the population can yield markedly conservative estimates, direct application of a standard finite population correction (FPC) conversely leads to underestimation of variance. We uncover a way to leverage the typical FPC indirectly toward valid statistical inference. In particular, we derive a readily estimable extra variance component induced by misclassification in this specific but arguably common diagnostic testing scenario. Our approach yields a standard error estimate that properly captures the sampling variability of the usual bias-corrected maximum likelihood estimator of disease prevalence. Finally, we develop an adapted Bayesian credible interval for the true prevalence that offers improved frequentist properties (i.e., coverage and width) relative to a Wald-type confidence interval. We report the simulation results to demonstrate the enhanced performance of the proposed inferential methods.

Utilization of post-exposure prophylaxis potentially contributed to the changes of risk behaviors among men who have sex with men in China.

Background: The HIV infection status among men who have sex with men (MSM) in China is a cause for concern. Post-exposure prophylaxis (PEP) serves as a highly effective biomedical preventive measure against HIV infection. Substantial evidence has established an association between PEP utilization and risk behaviors among MSM, but whether the utilization of PEP has an impact on risk behaviors remains unknown. This study sought to elucidate the impact of PEP usage on risk behaviors among MSM and provide recommendations for developing targeted HIV prevention programs. Methods: A cohort study was conducted in Qingdao, China, from April 2021 to January 2022. Participants were enlisted by volunteers from community-based organizations through a snowball sampling method. Face-to-face interviews were conducted to collect sociodemographic and behavioral information of participants. The study encompassed a retrospective investigation, baseline survey, and follow-up survey, representing periods before, during, and after PEP usage, respectively. Generalized estimating equations, fitting a Poisson regression model, were applied to scrutinize changes in risk behaviors of MSM during and after PEP usage, in comparison to before PEP usage. Results: A total of 341 MSM were recruited in the cohort study, with 179 individuals completing the follow-up survey. In comparison to before PEP usage, there was a significant increase in the proportion of Rush Popper usage (17.6% vs. 23.8% vs. 29.6%) and commercial sexual partners (10.9% vs. 17.6% vs. 21.8%) among MSM during and after PEP usage. Before PEP usage, 88.7% of MSM reported having ≥3 temporary sexual partners in the last 6 months. This proportion exhibited no significant change during PEP usage (91.8%), but it significantly increased to 97.8% after PEP usage (P < 0.05). Notably, there was a significant decrease in group sex during and after PEP usage compared to before PEP usage (30.8% vs. 21.4% vs. 21.2%). Conclusion: The utilization of PEP may impact risk behaviors among MSM, potentially leading to increased Rush Popper usage, temporary sexual partners, and commercial sexual partners after PEP usage, accompanied by a decrease in group sex. Further research is imperative to elucidate the impact of PEP utilization on MSM and develop targeted HIV prevention programs.

The Effectiveness of Cognitive Behavioral Therapy-Based Intervention on Improving Sleep-Related Outcomes for People with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Sleep-related outcomes in people with diabetes are poor, which is closely linked to reducing the development of diabetes. Cognitive behavioral therapy (CBT) based intervention presents innovative solutions that can help improve sleep-related outcomes. Aim: This synthesis aims to assess the effectiveness of CBT-based intervention compared to controls in Randomized Controlled Trials (RCTs) for sleep-related outcomes among people with diabetes. Methods: Eight electronic databases were systematically searched: PubMed, EMBASE, Cochrane library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), and Wan Fang database. We examined CBT-based intervention's effectiveness on sleep-related outcomes in people with diabetes in RCTs identified in these databases from their inception to 1st November 2023, and updated on 15 January 2024. The risk of bias was assessed using the Cochrane Risk of Bias tool by two reviewers. The meta-analysis of included studies was conducted by RevMan 5.3 software. Results: Seven studies in total (n = 2633 participants) were included in this systematic review based on our inclusion criteria. The systematic review found CBT-based intervention significantly improved sleep quality (Pittsburgh Sleep Quality Index, PSQI scores) at immediate post-intervention [95% CI=(-1.31 to -0.32), p = 0.001], six months [95% CI=(-0.75 to -0.22), p = 0.0003], and 12 months [95% CI=(-0.72 to -0.24), <0.0001], compared to control groups. Furthermore, our findings demonstrated that six sessions [95% CI= (-0.38 to -0.13), p < 0.0001] or more than six sessions [95% CI=(-1.76 to -0.02), p = 0.05] of CBT-based intervention could improve sleep quality compared to controls (I2=0%). Interestingly, CBT-based intervention improves total sleep time at post-intervention in people with diabetes compared to the control group [95% CI= (-0.57 to -0.12), p = 0.003]. However, there was no significant that CBT-based intervention is beneficial to time to fall asleep [95% CI (-1.89 to 0.43), p = 0.22] and sleep efficiency [95% CI (-1.27 to 0.27), p = 0.20] after intervention, compared to control group. Conclusion: CBT-based intervention appears to have a beneficial effect on improving sleep quality and total sleep time among people with diabetes. CBT-based intervention could be considered a strategy among healthcare providers to enhance sleep quality and total sleep time for people with diabetes. More RCTs with rigorous designs and long-term follow-up are warranted to provide conclusive evidence of the CBT-based intervention on sleep-related outcomes and to explore the mechanisms by which the CBT-based interventions improve sleep-related outcomes.

The impact of HIV self-testing on risk behaviors among men who have sex with men: a mixed-methods study.

Background: Men who have sex with men (MSM) have a high prevalence of HIV and a low rate of HIV testing in China. HIV self-testing (HIVST) presents a viable strategy for expanding HIV testing among MSM. However, the impact of HIVST on risk behaviors among MSM remains controversial. Our study sought to ascertain this impact. Methods: From April 2021 to January 2022, a mixed-methods study was conducted in Qingdao City, employing both quantitative and qualitative methodologies. The quantitative component entailed a cohort study among MSM who had used HIVST. Generalized estimating equations fitting Poisson regressions were used to analyze the changes in risk behaviors of MSM in short time after HIVST (ST-HIVST) and longer time after HIVST (LT-HIVST) compared to before HIVST. Subsequently, we conducted in-depth interviews with 18 MSM who completed the follow-up to delve deeper into the impact of HIVST on MSM. Results: A total of 410 MSM were recruited in the cohort, of whom 83 were lost to follow-up. Compared to before HIVST, there were no significant changes in risk behaviors in ST-HIVST (p > 0.05), while the proportion of recreational drugs abuse (20.7% vs. 33.3%), commercial sex (14.6% vs. 22.9%), and unprotected anal sex (95.9% vs. 98.5%) increased significantly in LT-HIVST (p < 0.05). Specific changes varied across demographic characteristics. According to qualitative interviews, MSM might have decreased risk perception and increased risk behaviors after HIVST. Conclusion: The use of HIVST may promote MSM to engage in risk behaviors. In the future, customized HIVST promotion programs need to be developed to expand HIV testing among MSM and simultaneously control their risk behaviors.

Elevated levels of loneliness in migrant children compared to nonmigrant children in urban China: a systematic review and meta-analysis of comparative studies.

PURPOSE OF REVIEW: About one in four children in China is a migrant child. This population has a higher risk of experiencing loneliness. However, existing studies present conflicting findings regarding the levels of loneliness among migrant children as compared to local urban children in urban China. This review performs a meta-analysis of studies comparing loneliness levels between these two groups. RECENT FINDINGS: A literature search of major Chinese- and English-language databases revealed 27 eligible comparative studies. These studies reported the means and standardized deviations of loneliness scores for both migrant and nonmigrant children in urban China. Meta-analysis results showed that migrant children experienced significantly higher levels of loneliness than their urban nonmigrant counterparts [standardized mean difference (SMD) = 0.21, P  < 0.001]. Subgroup analysis revealed that studies enrolling migrant children from migrant children's schools had significantly higher pooled SMDs than those enrolling children from public schools (0.346 vs. 0.120, P  = 0.047). SUMMARY: Migrant children in urban China experience higher levels of loneliness compared to their local urban peers. Efforts to create a socially inclusive, migrant-friendly environment and reduce social isolation among migrant children are crucial to help alleviate their feelings of loneliness.

High Curie temperature ferromagnetic monolayer T-CrSH and valley physics of T-CrSH/WS2 heterostructure.

Two-dimensional magnetic materials are attracting widespread attention not only for their excellent applications in spintronic devices but also for their potential to regulate valley splitting, which is crucial for valleytronics. Herein, we design a monolayer Janus ferromagnetic semiconductor T-CrSH by using first-principles calculations. We reveal that monolayer T-CrSH has a magnetic moment of 3µB per unit cell, which is primarily contributed by the 3d orbitals of the Cr atom. Monte Carlo simulations suggest that the Curie temperature of T-CrSH is 193 K, and it can rise to 402 K when a 5% tensile strain is applied. Furthermore, the valley degeneracy of WS2 can be lifted when monolayer T-CrSH is used as a substrate. The obtained valley splitting in the conduction band is 13.7 meV and that in the valence band is 157.5 meV. In addition, the large valley polarization of 12.8 meV in the conduction band makes it easy to achieve an electron-doped valley Hall current and spin Hall current when performing in an in-plane electric field.

Vascular injury activates the ELK1/SND1/SRF pathway to promote vascular smooth muscle cell proliferative phenotype and neointimal hyperplasia.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation is the leading cause of vascular stenosis or restenosis. Therefore, investigating the molecular mechanisms and pivotal regulators of the proliferative VSMC phenotype is imperative for precisely preventing neointimal hyperplasia in vascular disease. METHODS: Wire-induced vascular injury and aortic culture models were used to detect the expression of staphylococcal nuclease domain-containing protein 1 (SND1). SMC-specific Snd1 knockout mice were used to assess the potential roles of SND1 after vascular injury. Primary VSMCs were cultured to evaluate SND1 function on VSMC phenotype switching, as well as to investigate the mechanism by which SND1 regulates the VSMC proliferative phenotype. RESULTS: Phenotype-switched proliferative VSMCs exhibited higher SND1 protein expression compared to the differentiated VSMCs. This result was replicated in primary VSMCs treated with platelet-derived growth factor (PDGF). In the injury model, specific knockout of Snd1 in mouse VSMCs reduced neointimal hyperplasia. We then revealed that ETS transcription factor ELK1 (ELK1) exhibited upregulation and activation in proliferative VSMCs, and acted as a novel transcription factor to induce the gene transcriptional activation of Snd1. Subsequently, the upregulated SND1 is associated with serum response factor (SRF) by competing with myocardin (MYOCD). As a co-activator of SRF, SND1 recruited the lysine acetyltransferase 2B (KAT2B) to the promoter regions leading to the histone acetylation, consequently promoted SRF to recognize the specific CArG motif, and enhanced the proliferation- and migration-related gene transcriptional activation. CONCLUSIONS: The present study identifies ELK1/SND1/SRF as a novel pathway in promoting the proliferative VSMC phenotype and neointimal hyperplasia in vascular injury, predisposing the vessels to pathological remodeling. This provides a potential therapeutic target for vascular stenosis.

A Design and Analytical Strategy for Monitoring Disease Positivity and Biomarker Levels in Accessible Closed Populations.

In this paper, we advocate and expand upon a previously described monitoring strategy for efficient and robust estimation of disease prevalence and case numbers within closed and enumerated populations such as schools, workplaces, or retirement communities. The proposed design relies largely on voluntary testing, which is notoriously biased (e.g., in the case of coronavirus disease 2019) due to nonrepresentative sampling. The approach yields unbiased and comparatively precise estimates with no assumptions about factors underlying selection of individuals for voluntary testing, building on the strength of what can be a small random sampling component. This component enables the use of a recently proposed "anchor stream" estimator, a well-calibrated alternative to classical capture-recapture (CRC) estimators based on 2 data streams. We show that this estimator is equivalent to a direct standardization based on "capture," that is, selection (or not) by the voluntary testing program, made possible by means of a key parameter identified by design. This equivalency simultaneously allows for novel 2-stream CRC-like estimation of general mean values (e.g., means of continuous variables like antibody levels or biomarkers). For inference, we propose adaptations of Bayesian credible intervals when estimating case counts and bootstrapping when estimating means of continuous variables. We use simulations to demonstrate significant precision benefits relative to random sampling alone.

Ultra-Large Scale Stitchless AFM: Advancing Nanoscale Characterization and Manipulation with Zero Stitching Error and High Throughput.

The atomic force microscopy (AFM) is an important tool capable of characterization, measurement, and manipulation at the nanoscale with a vertical resolution of less than 0.1 nm. However, the conventional AFMs' scanning range is around 100 µm, which limits their capability for processing cross-scale samples. In this study, it proposes a novel approach to overcome this limitation with an ultra-large scale stitchless AFM (ULSS-AFM) that allows for the high-throughput characterization of an area of up to 1 × 1 mm2 through a synergistic integration with a compliant nano-manipulator (CNM). Specifically, the compact CNM provides planar motion with nanoscale precision and millimeter range for the sample, while the probe of the ULSS-AFM interacts with the sample. Experimental results show that the proposed ULSS-AFM performs effectively in different scanning ranges under various scanning modes, resolutions, and frequencies. Compared with the conventional AFMs, the approach enables high-throughput characterization of ultra-large scale samples without stitching or bow errors, expanding the scanning area of conventional AFMs by two orders of magnitude. This advancement opens up important avenues for cross-scale scientific research and industrial applications in nano- and microscale.

Gene cloning, protein expression, and enzymatic characterization of a double-stranded RNA degrading enzyme in Apolygus lucorum.

RNA interference (RNAi) is a powerful tool that post-transcriptionally silences target genes in eukaryotic cells. However, silencing efficacy varies greatly among different insect species. Recently, we met with little success when attempting to knock down genes in the mirid bug Apolygus lucorum via dsRNA injection. The disappearance of double-stranded RNA (dsRNA) could be a potential factor that restricts RNAi efficiency. Here, we found that dsRNA can be degraded in midgut fluids, and a dsRNase of A. lucorum (AldsRNase) was identified and characterized. Sequence alignment indicated that its 6 key amino acid residues and the Mg2+ -binding site were similar to those of other insects' dsRNases. The signal peptide and endonuclease non-specific domain shared high sequence identity with the brown-winged green stinkbug Plautia stali dsRNase. AldsRNase showed high salivary gland and midgut expression and was continuously expressed through the whole life cycle, with peaks at the 4th instar ecdysis in the whole body. The purified AldsRNase protein obtained by heterologously expressed can rapidly degrade dsRNA. When comparing the substrate specificity of AldsRNase, 3 specific substrates (dsRNA, small interfering RNA, and dsDNA) were all degraded, and the most efficient degradation is dsRNA. Subsequently, immunofluorescence revealed that AldsRNase was expressed in the cytoplasm of midgut cells. Through cloning and functional study of AldsRNase, the enzyme activity and substrate specificity of the recombinant protein, as well as the subcellular localization of nuclease, the reason for the disappearance of dsRNA was explained, which was useful in improving RNAi efficiency in A. lucorum and related species.

Intravascular ultrasonography assisted carotid artery stenting for treatment of carotid stenosis: Two case reports.

BACKGROUND: Digital subtraction angiography (DSA), the gold standard of cerebrovascular disease diagnosis, is limited in its diagnostic ability to evaluate arterial diameter. Intravascular ultrasonography (IVUS) has advantages in assessing stenosis and plaque nature and improves the evaluation and effectiveness of carotid artery stenting (CAS). CASE SUMMARY: Case 1: A 65-year-old man presented with a five-year history of bilateral lower limb weakness due to stroke. Physical examination showed decreased strength (5-/5) in both lower limbs. Carotid artery ultrasound, magnetic resonance angiography, and computed tomography angiography (CTA) showed a right proximal internal carotid artery (ICA) stenosis (70%-99%), acute cerebral infarction, and severe right ICA stenosis, respectively. We performed IVUS-assisted CAS to measure the stenosis and detected a low-risk plaque at the site of stenosis prior to stent implantation. Post-stent balloon dilatation was performed and postoperative IVUS demonstrated successful expansion and adherence. CTA six months postoperatively showed no significant increase in in-stent stenosis. Case 2: A 36-year-old man was admitted with a right common carotid artery (CCA) dissection detected by ultrasound. Physical examination showed no positive neurological signs. Carotid ultrasound and CTA showed lumen dilation in the proximal CCA with an intima-like structure and bulging in the proximal segment of the right CCA with strip-like low-density shadow (dissection or carotid web). IVUS-assisted DSA confirmed right CCA dissection. CAS was performed and intraoperative IVUS suggested a large residual false lumen. Post-stent balloon dilatation was performed reducing the false lumen. DSA three months postoperatively indicated good stent expansion with mild stenosis. CONCLUSION: IVUS aids decision-making during CAS by accurately assessing carotid artery wall lesions and plaque nature preoperatively, dissection and stenosis morphology intraoperatively, and visualizing and confirming CAS postoperatively.

Immunogenicity and safety of a new hexavalent rotavirus vaccine in Chinese infants: A randomized, double-blind, placebo-controlled phase 2 clinical trial.

Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.