Combining TSS-MPRA and sensitive TSS profile dissimilarity scoring to study the sequence determinants of transcription initiation.

Cis-regulatory elements (CREs) can be classified by the shapes of their transcription start site (TSS) profiles, which are indicative of distinct regulatory mechanisms. Massively parallel reporter assays (MPRAs) are increasingly being used to study CRE regulatory mechanisms, yet the degree to which MPRAs replicate individual endogenous TSS profiles has not been determined. Here, we present a new low-input MPRA protocol (TSS-MPRA) that enables measuring TSS profiles of episomal reporters as well as after lentiviral reporter chromatinization. To sensitively compare MPRA and endogenous TSS profiles, we developed a novel dissimilarity scoring algorithm (WIP score) that outperforms the frequently used earth mover's distance on experimental data. Using TSS-MPRA and WIP scoring on 500 unique reporter inserts, we found that short (153 bp) MPRA promoter inserts replicate the endogenous TSS patterns of ∼60% of promoters. Lentiviral reporter chromatinization did not improve fidelity of TSS-MPRA initiation patterns, and increasing insert size frequently led to activation of extraneous TSS in the MPRA that are not active in vivo. We discuss the implications of our findings, which highlight important caveats when using MPRAs to study transcription mechanisms. Finally, we illustrate how TSS-MPRA and WIP scoring can provide novel insights into the impact of transcription factor motif mutations and genetic variants on TSS patterns and transcription levels.

VThunter: a database for single-cell screening of virus target cells in the animal kingdom.

Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.

Temperature and Twist Sensor Based on the Sagnac Interferometer with Long-Period Grating in Polarization-Maintaining Fiber.

We utilized a CO2 laser to carve long-period fiber gratings (LPFGs) on polarization-maintaining fibers (PMFs) along the fast and slow axes. Based on the spectra of LPFGs written along two different directions, we found that when LPFG was written along the fast axis, the spectrum had lower insertion loss and fewer side lobes. We investigated the temperature and twist characteristics of the embedded structure of the LPFG and Sagnac loop and ultimately obtained a temperature sensitivity of -0.295 nm/°C and a twist sensitivity of 0.87 nm/(rad/m) for the LPFG. Compared to the single LPFG, the embedded structure of the LPFG and Sagnac loop demonstrates a significant improvement in temperature and twist sensitivities. Additionally, it also possesses the capability to discern the direction of the twist. The embedded structure displays numerous advantages, including easy fabrication, low cost, good robustness, a wide range, and high sensitivity. These features make it highly suitable for applications in structural health monitoring and other related fields.

Investigating K+ Storage Behavior of Highly Graphitized Carbon Fibers as Anodes for a Potassium-Ion Battery.

Many problems of potassium-ion batteries (PIBs) are hidden under a low mass load of the active material. However, developing research based on areal capacity is challenging for PIBs, due to the lack of an anode capable of delivering a stable capacity of more than 1 mAh cm-2. This work investigates the K+ storage behavior of highly graphitized carbon fibers (HG-CF), which exhibit automatic structural adjustments to mitigate voltage polarization. The created defects and residual K+ in the structure favor the reversible insertion/deinsertion of K+. HG-GF after structural adjustment realizes a capacity of 2 mAh (1.13 cm-2) without K deposition and a stable cyclic stability (>500 h). In situ X-ray diffraction and in situ Raman spectra were used to detect defect formation and structural evolution during cycles. This work demonstrates the feasibility of HG-GF as an anode for PIBs and provides a suitable anode for further research of PIBs based on areal capacity.

Application of Autogenous Dermis Combined With Local Flap Transplantation in Repair of Titanium Mesh Exposure After Cranioplasty.

OBJECTIVES: To investigate the clinical outcome of autogenous dermis combined with local flap transplantation in the treatment of titanium mesh exposure after cranioplasty. METHODS: We studied a total of 8 patients with titanium mesh exposure after cranioplasty. After debridement of the head wound, the autogenous dermal tissue from the lateral thigh was transplanted to the surface of titanium mesh, and the local skin flap was then applied after suturing and fixation to repair the wound on the surface of the dermis. To repair the lateral thigh dermal tissue area, a local skin flap was obtained, and a blade thick skin graft was used. RESULTS: Both dermal tissue and local skin flap survived. In the meanwhile, the donor skin area of the lateral thigh healed well, with only slight scar hyperplasia, and the titanium mesh was preserved. There was no recurrence after 6 months of follow-up. CONCLUSIONS: The application of autogenous dermis combined with local skin flap to repair titanium mesh exposure can effectively avoid skin flap necrosis, potential re-exposure of titanium mesh, sub-flap effusion, infection, and other problems. This method has an ideal effect, has easy access to materials, and reduces patients' economic burden. It is worth popularizing.

High-Sensitivity Temperature Sensor Based on Fiber Fabry-Pérot Interferometer with UV Glue-Filled Hollow Capillary Fiber.

Optical fiber Fabry-Pérot (FP) interferometer sensors have long been the focus of researchers in sensing applications because of their simple light path, low cost, compact size and convenient manufacturing methods. A miniature and highly sensitive optic fiber temperature sensor using an ultraviolet glue-filled FP cavity in a hollow capillary fiber is proposed. The sensor is fabricated by fusion splicing a single-mode fiber with a hollow capillary fiber, which is filled with ultraviolet glue to form a FP cavity. The sensor has a good linear response in the temperature testing and high-temperature sensitivity, which can be increased with the length of the FP cavity. The experimental results show that the temperature sensitivity reaches 1.174 nm/°C with a high linear response in the range of 30-60 °C. In addition, this sensor is insensitive to pressure and can be highly suitable for real-time water temperature monitoring for ocean research. The proposed ultraviolet glue-filled structure has the advantages of easy fabrication, high-temperature sensitivity, low cost and an arbitrary length of capillary, which has broad application prospects for marine survey technology, biological diagnostics and environmental monitoring.

How can China achieve its goal of peaking carbon emissions at minimal cost? A research perspective from shadow price and optimal allocation of carbon emissions.

The Chinese government has declared a determination at the 75th United Nations General Assembly that China will improve its independent contribution and adopt more powerful measures to peak the carbon emissions before 2030. However, such strict implementation of carbon reduction policies is bound to bring the cost of sacrificing economic development. In such a context, this paper tries to use shadow price to measure the average social cost of emission reduction, marginal abatement cost to depict the pressure to reduce carbon emissions based on non-radial distance function, and provides an optimal scheme for provincial emission reduction to minimize the national cost of emission reduction based on variable-coefficient model. Results show that: First, the average value of shadow price is 15.91 and varies widely among regions, which means on average reducing one unit of carbon emissions will sacrifice 15.914 yuan RMB of economic output, and there exists possibility of carbon transactions across regions; Second, on the one hand, marginal abatement cost of carbon emission for most regions presents an upward tendency over time, which means greater economic costs have to be sacrificed with economic development in the future; On the other hand, marginal abatement cost is much higher in regions with high economic level than that in the economically undeveloped areas, which indicates reducing carbon emissions is becoming increasingly difficult and would pay more economical cost in economically developed regions; Third, the optional allocation scheme of CO2 reduction derived from this research is better than administrative ways of Grandfathering and Benchmarking in terms of minimizing emission reduction cost. Results of this paper indicate that larger carbon trading market can be implemented in China to economically fulfill the commitment of peaking carbon emissions.

Comparison of genetic characteristics between captive and wild giant pandas based on 13 mitochondrial coding genes.

BACKGROUND: Research on genetic diversity based on mitochondrial DNA of giant pandas mainly focused on a single marker or a few genes. OBJECTIVE: To provide a more comprehensive assessment of the genetic diversity on giant pandas based on 13 mitochondrial protein coding genes. METHODS: We assembled 13 protein coding genes in the mitochondrial genome of the giant panda based on the whole genome sequencing data, including ND1, ND2, COX1, COX2, ATP8, ATP6, COX3, ND3, ND4L, ND4, ND5, ND6 and Cyt b. RESULTS: We successfully obtained long sequence of 11,416 base pairs with all 13 genes for 110 giant panda individual, accounting for 67.93% in length of the mitochondrial reference genome. Haplotype diversity was 0.9518 ± 0.009 and nucleotide diversity (π) was 0.00157 ± 0.00014. We detected three new haplotypes, including GPC10 and GPC21 for the CR sequence and GPB12 for the Cyt b gene. CONCLUSION: These multi-gene sequences provided more genetic variable information to compare captive and wild giant panda population.

Clinicopathological features of neuronal intranuclear inclusion disease diagnosed by skin biopsy.

STUDY OBJECTIVES: Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder, with complex and diverse of clinical manifestations characterized by eosinophilic hyaline inclusions in neurons and somatic cells. Due to the improvement in diagnostic methods, NIID is being increasingly diagnosed. METHODS: Herein, we reported three NIID cases, which were diagnosed by skin biopsy and FMR1 gene, after DWI showed the characteristic corticomedullary junction hyperintensity. Then we reviewed all the published cases of NIID in PubMed, which were diagnosed by the same method. RESULTS: We discussed 15 NIID cases, including three cases diagnosed by us. The average age was 63.4 ± 14.0 years. The average time from onset of symptom to diagnosis was 5.4 ± 7.9 years. Nine cases had dementia or cognitive impairment. Three cases presented with encephalitis. Three cases showed bladder dysfunction and two cases only presented with dizziness and headache. Two cases showed acute neurological deficit mimicking stroke. All cases were diagnosed by skin biopsy, after DWI showed abnormal corticomedullary junction hyperintensity. Ten cases showed inclusions in sweat gland cells, and seven cases in adipocytes, sweat gland cells, and fibroblasts. EMG was performed in five cases, four of whom had abnormal results, showing simultaneous involvement of motor and sensory nerves. CONCLUSIONS: The results indicated that inclusions were more easily detected in sweat gland cells in skin biopsy. The early stage of NIID could only characterized by autonomic nerve function involvement. Combined autonomic nerve dysfunction might be another relatively common manifestation in NIID.

Noninvasive Brain Stimulation for Poststroke Dysphagia: A Meta-Analysis for Randomized Controlled Trials.

BACKGROUND: Past research has indicated that repetitive transcranial magnetic stimulation (rTMS) on the pharyngeal motor cortex may be beneficial to poststroke dysphagic patients. In addition, some studies have supported that transcranial direct current stimulation (tDCS) over the pharyngeal motor cortex can improve swallowing function in poststroke dysphagia. However, some studies showed that rTMS and tDCS show no effect on poststroke dysphagia. This study aims to make a meta-analysis to investigate the therapy effect of rTMS and tDCS on poststroke dysphagia in randomized controlled trials (RCTs). METHODS: We searched for studies published before March 2021 in databases (PubMed, Web of Science, MEDLINE, EMBASE, and Google Scholar). Meta-analysis was made to compute the results of included studies using STATA 12.0 software. RESULTS: The present study shows a significant increase in the swallowing function in poststroke dysphagia given rTMS compared to those given sham rTMS (standardized mean difference [SMD] = 1.08, 95% confidence interval [CI] = 0.37-1.80, I2 = 81.2%, p < 0.001). In addition, the study shows a significant increase in the swallowing function in poststroke dysphagia given tDCS (combined or not combined with conventional swallowing therapy), compared to those given sham tDCS (combined or not combined with conventional swallowing therapy) (SMD = 1.43, 95% CI = 0.73-2.13, I2 = 77.6%, p < 0.001). CONCLUSIONS: The study demonstrates that rTMS and tDCS over the pharyngeal motor cortex show therapy effects on poststroke dysphagia. Many more large-scale, blinded RCTs are essential to investigate the effect of rTMS and tDCS on poststroke dysphagia.

Synthesis of 1-substituted phenazines as novel antichlamydial agents.

A novel series of 1-substituted phenazines 4a-4l were designed and synthesized via Palladium-catalyzed reactions from 1-phenazine trifluoromethanesulfonate. These phenazines showed antichlamydial activity with IC50 values from 1 to 10 µM. Among them, compounds 4c and 4i exhibited the best antichlamydial activity with IC50 values from 2.06 to 2.74 µM without apparent cytotoxicity to host cells.

Machine Vision Automated Chiral Molecule Detection and Classification in Molecular Imaging.

Scanning probe microscopy (SPM) is recognized as an essential characterization tool in a broad range of applications, allowing for real-space atomic imaging of solid surfaces, nanomaterials, and molecular systems. Recently, the imaging of chiral molecular nanostructures via SPM has become a matter of increased scientific and technological interest due to their imminent use as functional platforms in a wide scope of applications, including nonlinear chiroptics, enantioselective catalysis, and enantiospecific sensing. Due to the time-consuming and error-prone image analysis process, a highly efficient analytic framework capable of identifying complex chiral patterns in SPM images is needed. Here, we adopted a state-of-the-art machine vision algorithm to develop a one-image-one-system deep learning framework for the analysis of SPM images. To demonstrate its accuracy and versatility, we employed it to determine the chirality of the molecules comprising two supramolecular self-assemblies with two distinct chiral organization patterns. Our framework accurately detected the position and labeled the chirality of each molecule. This framework underpins the tremendous potential of machine learning algorithms for the automated recognition of complex SPM image patterns in a wide range of research disciplines.

Necrotizing Fasciitis Shock Syndrome by Group A Hemolytic Streptococcus: Report of 6 Cases and Clinical Management.

BACKGROUND: To explore the comprehensive treatment of group A streptococcus haemolyticus complicated with streptococcal toxic shock syndrome (STSS) in surgery. METHODS: Six patients with Type II necrotizing fasciitis complicated with STSS were enrolled from September 2018 to October 2019 in the Burn Department at Quanzhou First Hospital. The patients were treated with early incision and reduction of tension, anti-shock, anti-infection, primary debridement and vacuum suction, maintenance of organ function, and adjustment of internal environment, secondary autologous skin graft, and early rehabilitation. RESULTS: Five patients were healed, while one elderly patient refused treatment. CONCLUSIONS: We should be alert to necrotizing fasciitis caused by group A hemolytic streptococcus (GAS) infection and effectively avoid the occurrence of STSS. By making an incision to reduce tension, adopting the principle of anti-infection, and actively anti-shock, maintaining the function of internal organs and the stability of internal environment, debridement and vacuum suction in early and effective stage, followed by selfskin graft to seal the wound and early rehabilitation the treatment of Type II NF and STSS can be effectively improved.

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway.

BACKGROUND: Constitutively activated nuclear factor kappa B (NF-κB) signalling plays vital roles in bladder urothelial carcinoma (BC) progression. We investigate the effect of receptor-interacting protein kinase 4 (RIPK4) on NF-κB activation and BC progression. METHODS: The expression of RIPK4 was examined in 25 cryopreserved paired bladder samples and 112 paraffin BC specimens. In vivo and in vitro assays were performed to validate effect of RIPK4 on NF-κB pathway-mediated BC progression. RESULTS: High expression of RIPK4 was observed in BC tissues and was an independent predictor for poor overall survival. Up or downregulating the expression of RIPK4 enhanced or inhibited, respectively, the migration and invasion of BC cells in vitro and in vivo. Mechanistically, RIPK4 promoted K63-linked polyubiquitination of tumour necrosis factor receptor-associated factor 2 (TRAF2), receptor-interacting protein (RIP) and NF-κB essential modulator (NEMO). RIPK4 also promoted nuclear localisation of NF-κB-p65, and maintained activation of NF-κB substantially, leading to upregulation of VEGF-A, ultimately promoting BC cell aggressiveness. CONCLUSIONS: Our data highlighted the molecular aetiology and clinical significance of RIPK4 in BC: upregulation of RIPK4 contributes to NF-κB activation, and upregulates VEGF-A, and BC progression. Targeting RIPK4 might represent a new therapeutic strategy to improve survival for patients with BC.

An Optimal Enhanced Kalman Filter for a ZUPT-Aided Pedestrian Positioning Coupling Model.

Aimed at overcoming the problems of cumulative errors and low positioning accuracy in single Inertial Navigation Systems (INS), an Optimal Enhanced Kalman Filter (OEKF) is proposed in this paper to achieve accurate positioning of pedestrians within an enclosed environment. Firstly, the errors of the inertial sensors are analyzed, modeled, and reconstructed. Secondly, the cumulative errors in attitude and velocity are corrected using the attitude fusion filtering algorithm and Zero Velocity Update algorithm (ZUPT), respectively. Then, the OEKF algorithm is described in detail. Finally, a pedestrian indoor positioning experimental platform is established to verify the performance of the proposed positioning system. Experimental results show that the accuracy of the pedestrian indoor positioning system can reach 0.243 m, giving it a high practical value.

Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis.

We selected 42 early-stage primary biliary cirrhosis (PBC) patients and 30 healthy controls (HC). Metagenomic sequencing of the 16S rRNA gene was used to characterize the fecal microbiome. UPLC-MS/MS assaying of small molecules was used to characterize the metabolomes of the serum, urine and feces. Liquid chip assaying of serum cytokines was used to characterize the immune profiles. The gut of PBC patients were depleted of some potentially beneficial bacteria, such as Acidobacteria, Lachnobacterium sp., Bacteroides eggerthii and Ruminococcus bromii, but were enriched in some bacterial taxa containing opportunistic pathogens, such as γ-Proteobacteria, Enterobacteriaceae, Neisseriaceae, Spirochaetaceae, Veillonella, Streptococcus, Klebsiella, Actinobacillus pleuropneumoniae, Anaeroglobus geminatus, Enterobacter asburiae, Haemophilus parainfluenzae, Megasphaera micronuciformis and Paraprevotella clara. Several altered gut bacterial taxa exhibited potential interactions with PBC through their associations with altered metabolism, immunity and liver function indicators, such as those of Klebsiella with IL-2A and Neisseriaceae with urinary indoleacrylate. Many gut bacteria, such as some members of Bacteroides, were altered in their associations with the immunity and metabolism of PBC patients, although their relative abundances were unchanged. Consequently, the gut microbiome is altered and may be critical for the onset or development of PBC by interacting with metabolism and immunity.

Distinctive pathways characterize A. actinomycetemcomitans and P. gingivalis.

The study aimed to compare the molecular mechanism of Porphuromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans). With microarray dataset (GSE9723) from Gene Expression Omnibus, differentially expressed genes (DEGs) were identified comparing normal cell samples with A. actinomycetemcomitans-infected and P. gingivalis-infected periodontitis cell samples, respectively (|logFC| > 1, p value <0.01), followed by hierarchical cluster analysis using Cluster software. Network topological features of A. actinomycetemcomitans-related and P. gingivalis-related protein-protein interaction networks, and background network, which included average shortest path length (ASPL), degree, closeness centrality (CC), eccentricity (EC), betweenness centrality (BC) and topological coefficient (TC) were compared using network analysis plugin of Cytoscape, followed by pathway enrichment analysis (p value <0.05) using FISHER hyper-geometric algorithm and calculation of pathway alter scores using LIMMA. Totally, 839 DEGs and 251 DEGs were screened for A. actinomycetemcomitans and P. gingivalis, respectively. A. actinomycetemcomitans-related network had lower ASPL, degree and EC but higher CC and TC (p < 0.01), while P. gingivalis-related network had lower EC but higher CC and BC (p < 0.01) compared to background network. P. gingivalis-related network had lower ASPL, degree and EC, but higher CC than the A. actinomycetemcomitans-related network (p < 0.05). A. actinomycetemcomitans was associated with the pathways relating to endothelial cells function, while neuroactive ligand-receptor interaction and MAPK pathways were important for P. gingivalis, which had higher alter scores in hematopoietic cell lineage, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy pathways than A. actinomycetemcomitans. Genes and pathways of the two pathogens were distinctive. The findings aided in preventing and treating relevant diseases.

Avian-origin influenza A(H7N9) infection in influenza A(H7N9)-affected areas of China: a serological study.

Serological surveillance conducted in areas of an outbreak of influenza A(H7N9) infection in China found no seropositivity for antibodies specific for avian-origin influenza A(H7N9) among 1129 individuals of the general population, whereas >6% of 396 poultry workers were positive (on the basis of a hemagglutination inhibition titer of ≥ 80) for this subtype, confirming that infected poultry is the principal source of human infections and that subclinical infections are possible. Fourteen days after symptom onset, elevated levels of antibodies to A(H7N9) were found in 65.8% of patients (25/38) who survived but in only 28.6% of those (2/7) who died, suggesting that the presence of antibodies may improve clinical outcome in infected patients.

Oxide Ionic Neuro-Transistors for Bio-inspired Computing.

Current computing systems rely on Boolean logic and von Neumann architecture, where computing cells are based on high-speed electron-conducting complementary metal-oxide-semiconductor (CMOS) transistors. In contrast, ions play an essential role in biological neural computing. Compared with CMOS units, the synapse/neuron computing speed is much lower, but the human brain performs much better in many tasks such as pattern recognition and decision-making. Recently, ionic dynamics in oxide electrolyte-gated transistors have attracted increasing attention in the field of neuromorphic computing, which is more similar to the computing modality in the biological brain. In this review article, we start with the introduction of some ionic processes in biological brain computing. Then, electrolyte-gated ionic transistors, especially oxide ionic transistors, are briefly introduced. Later, we review the state-of-the-art progress in oxide electrolyte-gated transistors for ionic neuromorphic computing including dynamic synaptic plasticity emulation, spatiotemporal information processing, and artificial sensory neuron function implementation. Finally, we will address the current challenges and offer recommendations along with potential research directions.

Human-level few-shot concept induction through minimax entropy learning.

Humans learn concepts both from labeled supervision and by unsupervised observation of patterns, a process machines are being taught to mimic by training on large annotated datasets-a method quite different from the human pathway, wherein few examples with no supervision suffice to induce an unfamiliar relational concept. We introduce a computational model designed to emulate human inductive reasoning on abstract reasoning tasks, such as those in IQ tests, using a minimax entropy approach. This method combines identifying the most effective constraints on data via minimum entropy with determining the best combination of them via maximum entropy. Our model, which applies this unsupervised technique, induces concepts from just one instance, reaching human-level performance on tasks of Raven's Progressive Matrices (RPM), Machine Number Sense (MNS), and Odd-One-Out (O3). These results demonstrate the potential of minimax entropy learning for enabling machines to learn relational concepts efficiently with minimal input.