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Abstract Background Presently, there is no comprehensive analysis of the transcription regulation network in hematopoiesis. Comparison of networks arising from gene co-expression across species can facilitate an understanding of the conservation of functional gene modules in hematopoiesis. Results We used single-cell RNA sequencing to profile bone marrow from human and mouse, and inferred transcription regulatory networks in each species in order to characterize transcriptional programs governing hematopoietic stem cell differentiation. We designed an algorithm for network reconstruction to conduct comparative transcriptomic analysis of hematopoietic gene co-expression and transcription regulation in human and mouse bone marrow cells. Co-expression network connectivity of hematopoiesis-related genes was found to be well conserved between mouse and human. The co-expression network showed “small-world” and “scale-free” architecture. The gene regulatory network formed a hierarchical structure, and hematopoiesis transcription factors localized to the hierarchy’s middle level. Conclusions Transcriptional regulatory networks are well conserved between human and mouse. The hierarchical organization of transcription factors may provide insights into hematopoietic cell lineage commitment, and to signal processing, cell survival and disease initiation.

Glomerulosclerosis is a pathomorphological feature of glomerular lesions. Early detection, accurate judgement and effective prevention of the glomeruli is crucial not only for people with kidney disease, but also for the general population. We proposed a method in combination of traditional image analysis with modern machine learning diagnosis system model based on GoogLeNet for recognizing and distinguishing different categories of glomerulus in order to efficiently capture the important structures as well as to minimize manual effort and supervision. We proposed a novel deep learning model based on GoogLeNet with added batch-normalization layers to extract useful features and subsequently entered the features into SoftMax for classification. We also incorporated Bayesian Optimization algorithm and k-fold cross validation in this system for achieving a more reliable result. Our method has eventually achieved an overall accuracy of 95.04±4.99%, and F1 score of 94.44±3.11% for no glomerulus category, 96.73±5.23% for normal glomerulus category and 93.66±7.82% for globally sclerosed glomerulus category, which means this method can accurately determine the degree of glomerulosclerosis with little supervision. The experimental result also shows that this method has better performance when compared with other state-of art methods.

Photodynamic therapy (PDT) utilizes the photogeneration of reactive oxygen species (ROS) with high cytotoxicity to kill cancer cells, holding great promise for cancer treatment. Fractionated delivery of singlet oxygen (1O2) is a wise approach to relieving hypoxia, thus enhancing the therapeutic efficacy. In this article, an anthracene-functionalized semiconducting compound (DPPA) has been designed and synthesized. With irradiation, the compound is able to undergo efficient intersystem crossing (ISC) and non-radioactive decay for photodynamic/photothermal synergistic therapy. In addition, the anthracene module is able to capture and release 1O2 reversibly with or without irradiation. DPPA nanoparticles (NPs) obtained by nanoprecipitation with DSPE-PEG exhibit considerable high phototoxicity on human kidney cancer cells (A498), and the half maximum inhibitory concentration (IC50) is 15.8 μg/ml. Furthermore, an in vivo study demonstrates that complete tumor suppression was observed when the mice were administered DPPA NPs with the help of laser, compared with the control and dark groups. The H&E analysis of the normal tissues (the heart, liver, spleen, lungs, and kidney) indicates that such NPs cause no side effects, indicating the biosafety of DPPA NPs. The results provide a strategy to design a heavy-atom–free photosensitizer for photothermal and fractionated PDT against kidney tumors.

BackgroundDefinitions of declined left ventricular ejection fraction (LVEF) vary across studies and research results concerning the association of mortality with declined LVEF are inconsistent. Thus, this study aimed to assess the impact of early worsening LVEF on mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and to establish independent predictors of early worsening LVEF.Methods and ResultsA total of 1,418 consecutive patients with HFpEF with LVEF remeasurement from the Cardiorenal Improvement registry were included in this study. Worsening LVEF was defined as an absolute decline ≥ 5% from baseline LVEF within 3 to 12 months after discharge. The Cox and logistic regression analyses were performed to assess prognostic effects and predictors for worsening LVEF, respectively. Among 1,418 patients with HFpEF, 457 (32.2%) patients exhibited worsening LVEF. During a median follow-up of 3.2 years (interquartile range: 2.3–4.0 years), 92 (6.5%) patients died. Patients with HFpEF with worsening LVEF had higher mortality relative to those with nonworsening LVEF [9.2 vs. 5.2%; adjusted hazard ratio (aHR): 2.18, 95% CI: 1.35–3.52]. In the multivariate binary logistic regression analysis, baseline left ventricular end-diastolic dimension (LVEDD), LVEF, high-density lipoprotein cholesterol (HDL-C), atrial fibrillation (AF), and diabetes mellitus (DM) emerged as predictive factors of worsening LVEF.ConclusionThis study demonstrated that about one out of three patients with HFpEF experiences worsening LVEF during follow-up, which is associated with 2.2-fold increased mortality. Increased LVEDD and LVEF, low HDL-C levels, AF, and DM were predictors of worsening LVEF. Further studies are needed to prospectively assess the efficacy of early active management on prognosis in patients with HF with worsening LVEF.RegistrationClinicalTrials.gov, identifier NCT04407936.

Microalgae are considered promising resources for producing a variety of high-value-added products, especially for lipids and pigments. Alkalophilic microalgae have more advantages than other microalgae when cultured outdoors on a large scale. The present study investigated the comprehensive effects of different nitrogen concentrations on fucoxanthin (Fx), lipids accumulation and the fatty acid profile of the alkaliphilic microalgae Nitzschia sp. NW129 to evaluate the potential for simultaneous production of Fx and biofuels. Fx and Lipids amassed in a coordinated growth-dependent manner in response to various concentrations, reaching 18.18 mg g–1 and 40.67% dry weight (DW), respectively. The biomass of Nitzschia sp. NW129 was 0.58 ± 0.02 g L–1 in the medium at the concentration of 117.65 mM. The highest productivities of Fx (1.44 mg L–1 d–1) and lipid (19.95 ± 1.29 mg L–1 d–1) were obtained concurrently at this concentration. Furthermore, the fatty acid methyl esters revealed excellent biofuel properties with an appropriate value of the degree unsaturation (49.97), cetane number (62.72), and cold filter plugging point (2.37), which met the European standards for biofuel production (EN14214). These results provided a reliable strategy for further industrialization and comprehensive production of biofuel and Fx by using the alkaliphilic microalgal Nitzschia sp. NW129.

In this study, Ti-22Al-25Nb intermetallic compound alloys are fabricated through selective laser melting (SLM) at four scanning speeds (600, 700, 800, and 900 mm/s). The microstructure and mechanical properties of the selective laser melting fabricated alloys are systematically evaluated. The results indicate that scanning speed significantly affects microstructure characteristics (e.g., relative density, grain size, texture density, and the precipitation of secondary phases). The variation laws of the relative density, grain size, and texture density are likewise affected by scanning speed. The relative density, grain size, and texture density increase and then decrease with the increase in scanning speed. The alloy fabricated with the lowest scanning speed (600 mm/s) exhibits the maximum relative density, grain size, and texture density. By contrast, the alloy with the highest scanning speed (900 mm/s) exhibits the minimum relative density, grain size, and texture density. Furthermore, the precipitations of the O phase and Ti3Al phase are primarily distributed in regions with a high strain concentration near the pool boundary. The alloy fabricated with a 600 mm/s scanning speed simultaneously achieves the highest strength and elongation, which is closely correlated with the uniform distribution of secondary phases.

In this paper, we propose a Fuzzy Window with the Gaussian Processed Label (FW-GPL) method to mitigate the overlap problem in the neighboring ordinal category when scoring images. Many published conventional methods treat this challenge as a traditional regression problem and make a strong assumption that each ordinal category owns an adequate intrinsic rank to outline its distribution. Our FW-GPL method aims to refine the ordinal label pattern by using two novel techniques: (1) assembling fuzzy logic to the fully connected layer of convolution neural networks and (2) transforming the ordinal labels with a Gaussian process. Specifically, it incorporates a heuristic fuzzy logic from the ordinal characteristic and simultaneously plugs in ordinal distribution shapes that penalize the difference between the targeted label and its neighbors to ensure a concentrated regional distribution. Accordingly, the function of these proposed windows is leveraged to minimize the influence of majority classes that mislead the prediction of minority samples. Our model is specifically designed to carefully avoid partially missing continuous facial-age segments. It can perform competitively when using the whole continuous facial-age dataset. Extensive experimental results on three facial-aging datasets and one ambiguous medical dataset demonstrate that our FW-GPL can achieve compelling performance results compared to the State-Of-The-Art (SOTA).

Nowadays, with the rapid development of biotechnology, the CRISPR/Cas technology in particular has produced many new traits and products. Therefore, rapid and high-resolution detection methods for biotechnology products are urgently needed, which is extremely important for safety regulation. Recently, in addition to being gene editing tools, CRISPR/Cas systems have also been used in detection of various targets. CRISPR/Cas systems can be successfully used to detect nucleic acids, proteins, metal ions and others in combination with a variety of technologies, with great application prospects in the future. However, there are still some challenges need to be addressed. In this review, we will list some detection methods of genetically modified (GM) crops, gene-edited crops and single-nucleotide polymorphisms (SNPs) based on CRISPR/Cas systems, hoping to bring some inspiration or ideas to readers.

There are more than 7000 described rare diseases, most lacking specific treatment. Autosomal-dominant hyper-IgE syndrome (AD-HIES, also known as Job's syndrome) is caused by mutations in STAT3. These patients present with immunodeficiency accompanied by severe nonimmunological features, including skeletal, connective tissue, and vascular abnormalities, poor postinfection lung healing, and subsequent pulmonary failure. No specific therapies are available for these abnormalities. Here, we investigated underlying mechanisms in order to identify therapeutic targets. Histological analysis of skin wounds demonstrated delayed granulation tissue formation and vascularization during skin-wound healing in AD-HIES patients. Global gene expression analysis in AD-HIES patient skin fibroblasts identified deficiencies in a STAT3-controlled transcriptional network regulating extracellular matrix (ECM) remodeling and angiogenesis, with hypoxia-inducible factor 1[alpha] (HIF-1[alpha]) being a major contributor. Consistent with this, histological analysis of skin wounds and coronary arteries from AD-HIES patients showed decreased HIF-1[alpha] expression and revealed abnormal organization of the ECM and altered formation of the coronary vasa vasorum. Disease modeling using cell culture and mouse models of angiogenesis and wound healing confirmed these predicted deficiencies and demonstrated therapeutic benefit of HIF-1[alpha]-stabilizing drugs. The study provides mechanistic insights into AD-HIES pathophysiology and suggests potential treatment options for this rare disease., Introduction There are more than 7000 identified rare diseases that affect fewer than 1 person per 2000 and in most cases are caused by the altered function of a single [...]

Keywords: HIV; NCD; integrated care; LMICs; epidemiological and clinical data; computational modelling; capacity building, Remarkable advances in HIV prevention, care and treatment, made through the discovery of antiretroviral drugs, have enabled people living with HIV (PLHIV) to live longer lives [1]. Yet, as they [...]

Maize (Zea mays L.) is a food crop with the largest planting area and the highest yield in the world, and it plays a vital role in ensuring global food security. Conventional breeding methods are costly, time-consuming, and ineffective in maize breeding. In recent years, CRISPR-Cas editing technology has been used to quickly generate new varieties with high yield and improved grain quality and stress resistance by precisely modifying key genes involved in specific traits, thus becoming a new engine for promoting crop breeding and the competitiveness of seed industries. Using CRISPR-Cas, a range of new maize materials with high yield, improved grain quality, ideal plant type and flowering period, male sterility, and stress resistance have been created. Moreover, many patents have been filed worldwide, reflecting the huge practical application prospects and commercial value. Based on the existing patent data, we analyzed the development process, current status, and prospects of CRISPR-Cas technology in dissecting gene function and creating new germplasm in maize, providing information for future basic research and commercial production.

Biochar-derived water-extractable organic matter (WEOM) was obtained under low-temperature pyrolysis (300 °C) using corncob as raw material. WEOM may affect the mobility and bioavailability of soil heavy metals (HMs) through complexation when biochar was used for soil HM remediation. Herein, the characteristics of complexation between HMs (Cr(III) and Cu(II)) and biochar-derived WEOM were investigated by using spectroscopic techniques in conjunction with parallel factor (PARAFAC) analysis and two-dimensional correlation spectroscopy (2D–COS). Six components were identified by PARAFAC modeling, in which protein-, fulvic- and humic-like components accounted for 48.86%, 25.63% and 25.51%, respectively. A nonlinear model was employed to determine the conditional stability constant (KM) and total ligand concentration (CL) of WEOM-HM complexes. The log KM values were in the range of 4.02–5.04 for WEOM-Cr(III) and 4.04–6.58 for WEOM-Cu(II). The 2D–COS in conjunction with log-transformed synchronous fluorescence spectroscopy (SFS) suggested that WEOM components were preferentially complexed with HMs in the following order: 433/270, 433/335, 496/270, 496/335, 370/335, 433/402, 496/402, 335/290, 402/290 for Cr(III), and 290/280, 390/280, 433/280, 496/280, 433/335, 496/335, 390/335, 433/420, 496/402, 335/290, 316/290 for Cu(II). The results of 2D–FTIR–COS suggested a preferential bonding of Cr(III) to the C–N group of alkyl, and Cu(II) to the CO group of alcohols, ethers and esters. Meanwhile, the CO group of ethers and the CN group of alkyl indicated preferential susceptibilities for the addition of Cr(III) and Cu(II) at different concentrations. In addition, protein-like components had remarkably higher total ligand concentration (CL) than fulvic- or humic-like components.

Abstract Background The safety assessment and control of stacked transgenic crops is increasingly important due to continuous crop development and is urgently needed in China. The genetic stability of foreign genes and unintended effects are the primary problems encountered in safety assessment. Omics techniques are useful for addressing these problems. The stacked transgenic maize variety 12–5 × IE034, which has insect-resistant and glyphosate-tolerant traits, was developed via a breeding stack using 12–5 and IE034 as parents. Using 12–5 × IE034, its parents (12–5 and IE034), and different maize varieties as materials, we performed proteomic profiling, molecular characterization and a genetic stability analysis. Results Our results showed that the copy number of foreign genes in 12–5 × IE034 is identical to that of its parents 12–5 and IE034. Foreign genes can be stably inherited over different generations. Proteomic profiling analysis found no newly expressed proteins in 12–5 × IE034, and the differences in protein expression between 12 and 5 × IE034 and its parents were within the range of variation of conventional maize varieties. The expression levels of key enzymes participating in the shikimic acid pathway which is related to glyphosate tolerance of 12–5 × IE034 were not significantly different from those of its parents or five conventional maize varieties, which indicated that without selective pressure by glyphosate, the introduced EPSPS synthase is not has a pronounced impact on the synthesis of aromatic amino acids in maize. Conclusions Stacked-trait development via conventional breeding did not have an impact on the genetic stability of T-DNA, and the impact of stacked breeding on the maize proteome was less significant than that of genotypic differences. The results of this study provide a theoretical basis for the development of a safety assessment approach for stacked-trait transgenic crops in China.

Photodetectors based on two dimensional (2D) materials still suffer from low performance. Here, the authors tackle this issue by introducing a reconfigurable design enabled by locally tuning the doping of a 2D molybdenum disulfide film through the polarization of an underlying ferroelectric material.

A QoS-based network planning method for power fiber to the home was proposed.Firstly,the distribution structure of different buildings was combined to carry out targeted ODN line path design.Secondly,in the ONU packet cluster planning stage,in order to meet the QoS requirements of multi-service differentiation,the communication cost as the optimization goal was uesd,and the optimization problem model was established with the constraints of access capacity,reliability and delay.At the same time,intelligent algorithms were used to solve the optimization problem model.Finally,the optical path attenuation of the planned network was calculated to meet the actual application needs.The simulation results show that the proposed QoS-based network planning method for power fiber to the home can save network construction cost while ensuring service reliability and delay requirements.

Abstract Background Accumulating evidence suggests that epigenetic changes play key roles in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the dynamic regulation of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in diabetic peripheral blood DNA remains to be elucidated. Results We collected fasting blood samples (104 patients and 108 healthy controls) and glucose-stimulated blood samples at different time points (11 patients and 5 healthy controls underwent oral glucose tolerance test (OGTT)), as well as blood samples from six couples of diabetic and control rats. A HPLC-MS/MS system was used for quantifying global 5mC and 5hmC in genomic DNA from white blood cells (WBCs), and qPCR was performed for detecting mRNA expression of SIRT6 and TETs. We found that global 5mC decreased, while global 5hmC increased in both patients and diabetic rats, with lower 5mC being a risk factor of T2DM (OR = 0.524, 95%CI 0.402–0.683, p = 1.64 × 10−6). The OGTT data from patients showed that 5mC declined within 1 h and then returned to the fasting status at 2 h, while 5hmC rose from 0.5 h to 3 h with increasing glucose. However, the similar patterns were not found in the controls. The mRNA expression of TET2, TET3, and SIRT6 was upregulated in patients (p = 0.012, p = 0.026, and p = 0.035, respectively). The similar results were observed in diabetic OGTT and rats. Correlation analysis indicated that SIRT6 was positively correlated with TET2 in humans (r = 0.277, p

The design of assembly line layout is one of the most important influential factors for the company's performance. The inappropriate arrangement of the order of workstations in the assembly line could cause the excessive movement of the material. In order to increase productivity and reduce production cost, a multi-objective optimization model with minimum the transfer distance of semi-finished products and the total area of assembly line was established in this paper. The Non-dominated Sorting Genetic Algorithm-II was applied to obtain the results of this model. The coding method, genetic operation and fitness function for three different kinds of sewing assembly line layouts (multi-line, U-shape two-line and U-shape three-line) were studied, while the workstations were organized in three ways: the order of processes, the type of machines, and the components of garment. The efficiency of the model was verified by the practice of sewing assembly lines for men's shirt. The layout schemes are compared with other algorithms. The results illustrated that NSGA-II algorithm is an effective tool to solve the sewing assembly line layout problem. The transfer distances of semi-finished products in the multi-line and U-shape (three-line) layouts arranged by garment components workstation layout were short. The multi-line layout arranged by the type of machines workstation layout occupied the smallest area. The model is suitable for solving the layout problem of the garment sewing workshop in practice, shortening the production cycle, and reducing the production cost. A variety of assembly line layout schemes are provided for apparel manufacturers in this paper. Apparel manufacturers can select the appropriate assembly line layout based on the actual conditions of the workshop and product.