Defining morphologically and genetically distinct GABAergic/cholinergic amacrine cell subtypes in the vertebrate retina.

In mammals, retinal direction selectivity originates from GABAergic/cholinergic amacrine cells (ACs) specifically expressing the sox2 gene. However, the cellular diversity of GABAergic/cholinergic ACs of other vertebrate species remains largely unexplored. Here, we identified 2 morphologically and genetically distinct GABAergic/cholinergic AC types in zebrafish, a previously undescribed bhlhe22+ type and a mammalian counterpart sox2+ type. Notably, while sole sox2 disruption removed sox2+ type, the codisruption of bhlhe22 and bhlhe23 was required to remove bhlhe22+ type. Also, both types significantly differed in dendritic arbors, lamination, and soma position. Furthermore, in vivo two-photon calcium imaging and the behavior assay suggested the direction selectivity of both AC types. Nevertheless, the 2 types showed preferential responses to moving bars of different sizes. Thus, our findings provide new cellular diversity and functional characteristics of GABAergic/cholinergic ACs in the vertebrate retina.

Channel Prediction-Based Security Authentication for Artificial Intelligence of Things.

The emerging physical-layer unclonable attribute-aided authentication (PLUA) schemes are capable of outperforming traditional isolated approaches, with the advantage of having reliable fingerprints. However, conventional PLUA methods face new challenges in artificial intelligence of things (AIoT) applications owing to their limited flexibility. These challenges arise from the distributed nature of AIoT devices and the involved information, as well as the requirement for short end-to-end latency. To address these challenges, we propose a security authentication scheme that utilizes intelligent prediction mechanisms to detect spoofing attack. Our approach is based on a dynamic authentication method using long short term memory (LSTM), where the edge computing node observes and predicts the time-varying channel information of access devices to detect clone nodes. Additionally, we introduce a Savitzky-Golay filter-assisted high order cumulant feature extraction model (SGF-HOCM) for preprocessing channel information. By utilizing future channel attributes instead of relying solely on previous channel information, our proposed approach enables authentication decisions. We have conducted extensive experiments in actual industrial environments to validate our prediction-based security strategy, which has achieved an accuracy of 97%.

Experiences of healthcare workers following occupational exposure to COVID-19 at the early stages of the pandemic: A phenomenological qualitative study.

AIM: To explore the experiences of healthcare workers (HCWs) following occupational exposure to coronavirus disease 2019 (COVID-19) during the early stage of the pandemic. DESIGN: A Husserl descriptive phenomenological study design was employed. METHODS: Convenient and snowball sampling was used. In-depth semi-structured telephone interviews were conducted from February to March 2020 with the frontline HCWs who were exposed to COVID-19 during work. Data analysis was conducted following the 7-step analysis method developed by Colaizzi. RESULTS: Fifteen HCWs participated in the study. Four themes were identified, including (1) traumatic experiences since the occupational exposure; (2) getting through the hard time; (3) struggling to return to work; (4) reflections on occupational exposures. CONCLUSION: The HCWs had traumatic and painful experiences after the occupational exposure. But they returned to work with strong resilience, professional obligation and social support. Training and supervision, and adequate supply of personal protective equipment are suggested to prevent professional exposure. Social and organizational support should be provided for the exposed HCWs.

The landscape of regulatory genes in brain-wide neuronal phenotypes of a vertebrate brain.

Multidimensional landscapes of regulatory genes in neuronal phenotypes at whole-brain levels in the vertebrate remain elusive. We generated single-cell transcriptomes of ~67,000 region- and neurotransmitter/neuromodulator-identifiable cells from larval zebrafish brains. Hierarchical clustering based on effector gene profiles ('terminal features') distinguished major brain cell types. Sister clusters at hierarchical termini displayed similar terminal features. It was further verified by a population-level statistical method. Intriguingly, glutamatergic/GABAergic sister clusters mostly expressed distinct transcription factor (TF) profiles ('convergent pattern'), whereas neuromodulator-type sister clusters predominantly expressed the same TF profiles ('matched pattern'). Interestingly, glutamatergic/GABAergic clusters with similar TF profiles could also display different terminal features ('divergent pattern'). It led us to identify a library of RNA-binding proteins that differentially marked divergent pair clusters, suggesting the post-transcriptional regulation of neuron diversification. Thus, our findings reveal multidimensional landscapes of transcriptional and post-transcriptional regulators in whole-brain neuronal phenotypes in the zebrafish brain.

The brain harbors an astounding diversity of interconnected cells. Each cell contains the same basic set of genetic instructions, but only a fraction of the genome is used in each cell to assemble proteins. This selective gene expression gives rise to each cell's characteristic properties, such as their shape and location, or whether they can activate or inhibit neighbouring cells. How these defining features are encoded on a genetic level and selectively activated in cells to produce such diversity in the brain is not fully understood. One way to study gene expression in single cells involves profiling the transcriptome, the full range of intermediary RNA molecules a cell produces from its genes to make proteins. Zhang et al. used transcriptome profiling to better understand how thousands of regulatory genes encoding regulatory proteins called transcription factors create different types of neurons in the zebrafish brain, which is similar to but much simpler than the human brain. To do so, they analysed transcriptome data extracted from cell populations located in specific brain regions and displaying different properties. Zhang et al. identified distinct clusters of neurons in the larval zebrafish brain. Mathematical models then analysed the transcriptome profiles of these neuronal clusters with characteristic features. They revealed that neurons with similar characteristics did not necessarily share the same transcription factors. In other words, distinct sets of transcription factors gave rise to the same types of cells. Zhang et al. described this observation as a 'convergent' pattern. On the contrary, some neurons with dissimilar features expressed the same sorts of transcription factors, suggesting a 'divergent' developmental pattern also exists. In summary, this work sheds light on variable gene expression patterns akin to design principles that shape neuronal diversity in the brain. It gives a new appreciation of how neuronal subtypes result from a complex set of regulatory factors controlling gene expression.

A systematic review and meta-analysis of the effect of resistance exercise therapy on the prognosis of patients after percutaneous coronary intervention.

BACKGROUND: Exercise rehabilitation therapy after percutaneous coronary intervention (PCI) can accelerate physical recovery, improve cardiovascular work efficiency, and reduce the incidence of arterial restenosis. This study aimed to investigate the effect of resistance exercise therapy after PCI by literature search and meta-analysis. METHODS: The databases of Embase, Cochrane library, PubMed, and Ovid were searched for all published English language articles related to resistance exercise after PCI from January 2000 to January 2021. After screening the literature according to the inclusion and exclusion criteria and assessing the risk of bias, RevMan 5.4 software was used to analyze and obtain a forest plot and funnel plot. RESULTS: A total of 7 articles were included in this study for quantitative analysis, involving 776 patients all together. Meta-analysis showed that compared with conventional intervention methods, resistance exercise could reduce the maximum exercise load after PCI [mean difference (MD) =-25.27, 95% confidence interval (CI): -31.97 to -18.57, Z=7.39, P<0.00001], reduce the peak oxygen consumption of exercise after PCI (MD =-2.36, 95% CI: -3.09 to -1.64, Z=6.42, P<0.00001), increase left ventricular ejection fraction (LVEF; MD =4.06, 95% CI: 0.72 to 7.40, Z=2.38, P=0.02), increase the 6-minute walk distance (6MWD; MD =18.23, 95% CI: 0.22 to 36.23, Z=1.98, P=0.05), and improve the quality of life of patients after surgery (MD =5.81, 95% CI: 1.49 to 10.14, Z=2.63, P=0.008). DISCUSSION: Resistance training can improve the physical activity, cardiac function, and quality of life of patients after PCI.

Evidence-Based Analysis on Observation for Nursing Care of Patients with Intra-Aortic Balloon Pumping.

In this study, data analysis was performed on 52 patients. According to the different outcomes and discharge diagnosis of patients, data on sedative use, emotions, behavioral abnormalities, hearing loss, pain, total time on board the IABP (intra-aortic balloon pumping), and days of hospitalization of patients were collected. The data were subjected to frequency analysis, paired chi-square analysis, chi-square test, Poisson regression analysis, and stepwise regression analysis. Some findings of the analysis included the following: Between outcome and admission diagnosis, the analysis showed that significant differences existed between paired data. Patients with heart failure and acute myocardial infarction are in an unhealed state, and most patients with coronary atherosclerotic heart disease, myocarditis, and heart disease showed improvement. The samples taken by different sedatives showed no significant differences in the emotional and behavioral abnormalities, hearing loss, and pain. A total of 1 item of hospital stay had a significant negative impact on the total operation time of IABP. However, discharge diagnosis and admission diagnosis did not affect the total time on board the IABP. The dorsalis pedis artery pulse condition has a significant negative effect on the total time on board the IABP.

Enhanced Security Authentication Based on Convolutional-LSTM Networks.

The performance of classical security authentication models can be severely affected by imperfect channel estimation as well as time-varying communication links. The commonly used approach of statistical decisions for the physical layer authenticator faces significant challenges in a dynamically changing, non-stationary environment. To address this problem, this paper introduces a deep learning-based authentication approach to learn and track the variations of channel characteristics, and thus improving the adaptability and convergence of the physical layer authentication. Specifically, an intelligent detection framework based on a Convolutional-Long Short-Term Memory (Convolutional-LSTM) network is designed to deal with channel differences without knowing the statistical properties of the channel. Both the robustness and the detection performance of the learning authentication scheme are analyzed, and extensive simulations and experiments show that the detection accuracy in time-varying environments is significantly improved.

[Clinical screening and genetic diagnosis for Prader-Willi syndrome].

OBJECTIVE: To study the clinical screening and genetic diagnosis of children suspected of Prader-Willi syndrome (PWS), as well as the differences in the scores of clinical diagnostic criteria among the children with a confirmed diagnosis of PWS. METHODS: A total of 94 children suspected of PWS who were admitted from July 2016 to December 2018 were enrolled as subjects. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis. For the children with a confirmed diagnosis of PWS, the scores of clinical diagnostic criteria were determined, and the perinatal characteristics were analyzed. RESULTS: A total of 11 children with PWS were confirmed by MS-MLPA, with a detection rate of 12%, among whom there were 7 boys and 4 girls, with a median age of 3 years and 4 months (range 25 days to 6 years and 8 months) at the time of confirmed diagnosis. Among the 11 children with PWS, only 5 children (45%) met the criteria for clinical diagnosis. The main perinatal characteristics of the children with PWS were decreased fetal movement (9 cases, 82%), cesarean section birth (11 cases, 100%), hypotonia (11 cases, 100%), feeding difficulties (11 cases, 100%), and weak crying (11 cases, 100%). CONCLUSIONS: Gene testing should be performed as early as possible for children suspected of PWS by clinical screening. PWS may be missed if only based on the scores of clinical diagnostic criteria.

Could Ultrasound-Based Radiomics Noninvasively Predict Axillary Lymph Node Metastasis in Breast Cancer?

OBJECTIVES: This work aimed to investigate whether quantitative radiomics imaging features extracted from ultrasound (US) can noninvasively predict breast cancer (BC) metastasis to axillary lymph nodes (ALNs). METHODS: Presurgical B-mode US data of 196 patients with BC were retrospectively studied. The cases were divided into the training and validation cohorts (n = 141 versus 55). The elastic net regression technique was used for selecting features and building a signature in the training cohort. A linear combination of the selected features weighted by their respective coefficients produced a radiomics signature for each individual. A radiomics nomogram was established based on the radiomics signature and US-reported ALN status. In a receiver operating characteristic curve analysis, areas under the curves (AUCs) were determined for assessing the accuracy of the prediction model in predicting ALN metastasis in both cohorts. The clinical value was assessed by a decision curve analysis. RESULTS: In all, 843 radiomics features per case were obtained from expert-delineated lesions on US imaging in this study. Through radiomics feature selection, 21 features were selected to constitute the radiomics signature for predicting ALN metastasis. Area under the curve values of 0.778 and 0.725 were obtained in the training and validation cohorts, respectively, indicating moderate predictive ability. The radiomics nomogram comprising the radiomics signature and US-reported ALN status showed the best performance for ALN detection in the training cohort (AUC, 0.816) but moderate performance in the validation cohort (AUC, 0.759). The decision curve showed that both the radiomics signature and nomogram displayed good clinical utility. CONCLUSIONS: This pilot radiomics study provided a noninvasive method for predicting presurgical ALN metastasis status in BC.

Predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio in hepatocellular carcinoma patients with microvascular invasion.

BACKGROUND: Microvascular invasion (MVI) is an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). However, there is still a lack of preoperative markers to predict MVI in HCC. This study intends to explore the potential application value of the gamma-glutamyl transpeptidase (GGT) to lymphocyte count ratio (GLR) in predicting MVI in HCC and provide guidance for clinical diagnosis and treatment. METHODS: From March 2010 to December 2015, 230 HCC patients who underwent surgical treatment in the Affiliated Hospital of Guilin Medical University were selected. Clinicopathological parameters between the MVI group (n = 115) and the non-MVI group (n = 115) were comparatively analyzed. The GLR was used as the potential risk factor for HCC with MVI, and its optimal cut-off value was estimated by using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to analyze the survival of HCC patients, and univariate and multivariate Cox regression analyses were used to establish independent predictors affecting postoperative HCC patients. RESULTS: The GLR levels in the MVI group and non-MVI group were 84.83 ± 61.84 and 38.42 ± 33.52 (p <  0.001), respectively. According to ROC curve analysis, the optimal cut-off value of GLR was 56.0, and the area under the ROC curve (AUC) was 0.781 (95% CI, 0.719-0.833) for the risk prediction of MVI in HCC patients. Multivariate analysis showed that tumor size > 5 cm, HCC combined with MVI and GLR >  56.0 were independent risk factors for poor prognosis in HCC patients. In addition, compared with the non-MVI group, patients in the MVI group had shorter progression-free survival (PFS) and overall survival (OS). CONCLUSION: GLR could be a predictive biomarker of HCC after operation and a potential predictor of HCC combined with MVI.

How does contrast-enhanced ultrasonography influence Bosniak classification for complex cystic renal mass compared with conventional ultrasonography?

To analyze the degree and pattern of influence of contrast-enhanced ultrasonography (CEUS) on the Bosniak classification system for complex renal cystic mass as compared with conventional ultrasonography (US). One hundred two consecutive patients with complex renal cystic masses were retrospectively analyzed. The diagnostic performance of the Conventional US and CEUS were evaluated separately for malignant and benign lesions. The diagnostic concordance rates were calculated according to pathologic diagnoses. ROC curve analysis determined the confidence in the diagnostic accuracy by calculating the area under each ROC curve. Compared to the Conventional US, septae number, wall and/or septae thickness, solid component and the Bosniak classification changed in 17 (16.7%), 39 (38.2%), 31 (30.4%), and 67 (65.7%) patients as compared with 0 (0.0%), 21 (20.6%), 31 (30.4%), and 37 (36.3%) of the treatment strategy that changed after CEUS respectively. The diagnostic performance of CEUS showed overall higher in terms of sensitivity (100.0 vs 97.2%); specificity (90.9 vs 62.1%); positive predictive value (PPV) (85.7 vs 58.3%); negative predictive value (NPV) (100.0 vs 97.6%); and the concordance with pathology (kappa = 0.876 vs 0.515). CEUS had a higher diagnostic confidence (P < .05) according to the area under the ROC curve (AUC = 0.968 vs 0.799).CEUS performed better than the Conventional US in the diagnosis of complex renal cystic mass, and it might be considered as the first tool to evaluate a complex cystic renal mass, especially for these Bosniak III masses displaying the presence of hemorrhage or infection.

Regulation of energy homeostasis by the ubiquitin-independent REGγ proteasome.

Maintenance of energy homeostasis is essential for cell survival. Here, we report that the ATP- and ubiquitin-independent REGγ-proteasome system plays a role in maintaining energy homeostasis and cell survival during energy starvation via repressing rDNA transcription, a major intracellular energy-consuming process. Mechanistically, REGγ-proteasome limits cellular rDNA transcription and energy consumption by targeting the rDNA transcription activator SirT7 for ubiquitin-independent degradation under normal conditions. Moreover, energy starvation induces an AMPK-directed SirT7 phosphorylation and subsequent REGγ-dependent SirT7 subcellular redistribution and degradation, thereby further reducing rDNA transcription to save energy to overcome cell death. Energy starvation is a promising strategy for cancer therapy. Our report also shows that REGγ knockdown markedly improves the anti-tumour activity of energy metabolism inhibitors in mice. Our results underscore a control mechanism for an ubiquitin-independent process in maintaining energy homeostasis and cell viability under starvation conditions, suggesting that REGγ-proteasome inhibition has a potential to provide tumour-starving benefits.

Ultrasensitive electrogenerated chemiluminescence peptide-based method for the determination of cardiac troponin I incorporating amplification of signal reagent-encapsulated liposomes.

An ultrasensitive electrogenerated chemiluminescence peptide-based (ECL-PB) method for the determination of cardiac troponin I (TnI) incorporating amplification of signal reagent-encapsulated liposome was reported for the first time. A synthesized short linear specific binding peptide (FYSHSFHENWPSK) was employed as a molecular recognition element for TnI, which was a reliable biomarker for detecting cardiac injury. Liposomes assembled using a standard sonication procedure were designed as the carrier of ECL signal reagents [bis(2,2'-bipyridine)-4,4'-dicarboxybipyridine ruthenium-di(N-succinimidyl ester) bis(hexafluorophosphate)] for signal amplification. The magnetic capture peptides for the enrichment of the target protein and magnetic separation were synthesized by covalently attaching the peptides to the surface of magnetic beads via an acylation reaction, and the liposome peptides were synthesized by covalently attaching the peptides to the signal reagent-encapsulated liposomes. In the presence of TnI, sandwich-type conjugates were generated in incubation of the magnetic capture peptides and the liposome peptides. After a magnetic separation, the sandwich-type conjugates were treated with ethanol and, thus, a great number of the ECL reagents were released and measured by the ECL method at a bare glassy carbon electrode with a potential pulse of +1.15 V versus Ag/AgCl in the presence of tri-n-propylamine. The increased ECL intensity has good linearity with the logarithm of the TnI concentration in the range from 10 pg/mL to 5.0 ng/mL, with an extremely low detection limit of 4.5 pg/mL. The proposed ECL-PB method was successfully applied to the detection of TnI in human serum samples. This work demonstrated that the employment of the magnetic capture peptides for the enrichment of the target proteins and magnetic separation and the liposome peptides for the signal amplification and polyvalent binding motifs may open a new door to ultrasensitive detection of proteins in clinical analyses.

Reagent-less electrogenerated chemiluminescence peptide-based biosensor for the determination of prostate-specific antigen.

A novel electrogenerated chemiluminescence peptide-based (ECL-PB) biosensor for highly sensitive and selective determination of prostate-specific antigen (PSA) was developed. A helix peptide (CHSSKLQK) was served as a molecular recognition element and ruthenium bis(2,2'-bipyridine) (2,2'-bipyridine-4,4'-dicarboxylic acid)-N-hydroxysuccinimide ester (Ru(bpy)(2)(dcbpy)NHS) was used as an ECL label. The helix peptide was labeled with the ECL label at NH(2)-containing lysine and utilized as ECL probe (Ru-peptide). The ECL-PB biosensor was fabricated by immobilizing the ECL probe onto a gold electrode surface via self-assembling technique through a thiol-containing cysteine at the end of the peptide. The principle of ECL measurement is based on the specific proteolytic cleavage event of Ru-peptide on the gold electrode surface in the presence of PSA, resulting in a decrease of ECL signal. The decreased ECL intensity was directly linear to the concentration of PSA in the range from 1.0×10(-10) g/mL to 8.0×10(-9) g/mL with a detection limit of 3.8×10(-11) g/mL. This work demonstrates that the direct transduction of peptide cleavage events into an ECL signal provides a simple and sensitive method for detecting target protein.

[Cloning and expression of a 2-naphthoate monooxygenase gene (nmo) in Burkholderia sp. JT1500].

A 4.8kb DNA fragment from one blue colony of the pLARF1 gene library of Burkholderia sp. JT1500 was subcloned to pUC18, designated as pEK123. The sequence of the inserted 4.8kb DNA' of pEK123 was analyzed and submitted to EMBL nucleotide database, the accession # is AJ566333. The transformants of pEK123 could also become blue in LB agar and sequence analysis showed that three open reading frames and a putative promoter sequence were located in this inserted fragment. Then the 4.4kb insert fragment of pEK123 was double digested with Xba I / Kpn I and EcoR I / Xba I respectively to construct plamsids pXK3 and pEX12. The pXK3 contained only one 1158bp open reading frame (ORF) and pEX12 with other two ORFs. Unlike pEK123, the colonies of pEX12 did not show any blue color even incubated for 72h in LB agar, but the transformants of pXK3 did oxidize indole into indigo. The deduced 43kD protein of 1158bp ORF showed 64% homology of amino acid composition to Ralstonia eutropha HF39 hydroxylase (bec). Results of substrate transformation analysis showed that the transformants of pEK123 was able to catalyze the oxidation of 2-naphthoate but not other key intermediates in 2-naphthoate metabolic pathway. These results confirmed that the product of 1158bp ORF is 2-naphthoate monooxygenase. Though the oxygenase activity of pEK123 is much higher than that of pXK3, SDS-PAGE analysis found no difference between the amount of the band of monooxygenase produced by pXK3 or pEK123, but one more band was found produced by pEK123. According to the difference of substrate analysis between pXK3 and pEK123, it is supposed that the products of two open reading frames up stream of nmo gene had strong influence on the activity of the monooxygenase. Benzoate was oxidized by free-cell extracts of the transformants of pEK123 in the transformation experiment with different aromatic substrates. As the DNA sequence and amino acid sequence of 2-naphthoate monoxygenase (nmo) did no show any homology with the DNA sequence and amino acid sequence of benzoate oxygenases reported, the pathway of benzoate oxidation conducted by nmo is on the investigation.