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Abstract With the increasing demand for heat dissipation of engineering vehicles, a dual-cycle cooling system is introduced in this paper to prevent the adverse effects of engineering vehicles’ equipment when operating at the overheating temperature. The performance of the new system is analyzed through tests, and the results show that the dual-cycle cooling system can meet the thermal balance requirements of the engineering vehicle during the shovel operation. Compared with the traditional cooling system, the new cooling system improved performance in terms of volume, engine energy consumption and working oil efficiency. The oil consumption of a wheel loader using the dual-cycle cooling system is reduced by 1% per hour, and the temperature of its transmission oil and hydraulic oil is reduced by more than 10 °C. The new cooling system has bright future in energy saving and emission reduction of engineering vehicles.

Abstract Background the salutogenic theory is essential to explain an individual’s ability to maintain health during the perinatal period. While previous studies mainly focused on the perspectives from a family-level orientation and a global orientation, the purpose of the present study was to develop and validate a scale, the childbearing sense of coherence scale (CSOC-scale) from the individual’s perceptions of the stresses, resources, and meaningfulness of childbearing. Methods A total of 3 separate studies contributed to the development of the CSOC-scale between July 2022 and February 2023. In study 1, the initial item pool based on the conceptual framework of the childbearing sense of coherence and the salutogenic theory was developed. Delphi expert consultation was conducted to revise and improve items. Studies 2 and 3 were cross-sectional studies. In study 2, item analysis and explore factor analysis (EFA) (N = 351 for women, N = 256 for men) were used to screen items. In study 3, confirmatory factor analysis (CFA) and reliability analysis (N = 366 for women, N = 308 for men) were used to test the fit indices and reliability of the final scale. Results final analysis suggested the CSOC-scale includes three factors, consisting of 13 items. Confirmatory factor analysis demonstrated good model fit (χ 2 = 157.448, df = 62, χ 2 / df = 2.539, RMSEA = 0.065, CFI = 0.974, TLI = 0.968, SRMR = 0.029 for women; χ 2 = 181.363, df = 62, χ 2 / df = 2.925, RMSEA = 0.079, CFI = 0.968, TLI = 0.960, SRMR = 0.033 for men) and high factor loadings (from 0.751 to 0.929 for women; from 0.746 to 0.947 for men). Internal consistency (Cronbach’s α ranging from 0.895 to 0.933 for women and 0.881 to 0.945 for men in three dimensions; Cronbach’s α was 0.919 for women and 0.821 for men in the entire instrument) and split-half reliability (Spearman-Brown coefficients ranging from 0.876 to 0.921 for women and 0.841 to 0.937 for men in three dimensions; Spearman-Brown coefficient was 0.744 for women and 0.785 for men in the entire instrument) were excellent. Conclusions the CSOC-scale has robust psychometric properties. It is reliable and valid in evaluating the childbearing sense of coherence in women and men during pregnancy. Utilisation of this scale can help healthcare professionals understand the health maintenance competencies of couples during the transition of parenthood and provide health promotion services from a salutogenic perspective.

Abstract Background Oral frailty has become a worldwide problem among older adults. Although researchers have conducted various studies on oral frailty, its definition remains controversial. Purpose To clarify the concept of oral frailty. Methods Online databases PubMed, Web of Science, CINAHL, Cochrane Library, ProQuest, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang database were searched from inception to September 20, 2023. The reference lists of relevant studies were searched manually. Eligible articles, theses, and books were analyzed using Walker & Avant’s concept analysis model. Results The attributes of oral frailty were abnormal oral structure and/or decline in multi-faceted oral function and coexisting decline in physical, cognitive and social functions. Its antecedents were aging, social frailty, and severe periodontitis, whereas its consequences were decline in physical health and mental health, social withdrawal, lower quality of life and systemic frailty. Conclusion Oral frailty could result in worse conditions among older adults physically, psychologically and socially. Tools based on the concept analysis need to be developed to comprehensively assess oral frailty.

Abstract Background Streptomyces is renowned for its robust biosynthetic capacity in producing medically relevant natural products. However, the majority of natural products biosynthetic gene clusters (BGCs) either yield low amounts of natural products or remain cryptic under standard laboratory conditions. Various heterologous production hosts have been engineered to address these challenges, and yet the successful activation of BGCs has still been limited. In our search for a valuable addition to the heterologous host panel, we identified the strain Streptomyces sp. A4420, which exhibited rapid initial growth and a high metabolic capacity, prompting further exploration of its potential. Results We engineered a polyketide-focused chassis strain based on Streptomyces sp. A4420 (CH strain) by deleting 9 native polyketide BGCs. The resulting metabolically simplified organism exhibited consistent sporulation and growth, surpassing the performance of most existing Streptomyces based chassis strains in standard liquid growth media. Four distinct polyketide BGCs were chosen and expressed in various heterologous hosts, including the Streptomyces sp. A4420 wild-type and CH strains, alongside Streptomyces coelicolor M1152, Streptomyces lividans TK24, Streptomyces albus J1074, and Streptomyces venezuelae NRRL B-65442. Remarkably, only the Streptomyces sp. A4420 CH strain demonstrated the capability to produce all metabolites under every condition outperforming its parental strain and other tested organisms. To enhance visualization and comparison of the tested strains, we developed a matrix-like analysis involving 15 parameters. This comprehensive analysis unequivocally illustrated the significant potential of the new strain to become a popular heterologous host. Conclusion Our engineered Streptomyces sp. A4420 CH strain exhibits promising attributes for the heterologous expression of natural products with a focus on polyketides, offering an alternative choice in the arsenal of heterologous production strains. As genomics and cloning strategies progress, establishment of a diverse panel of heterologous production hosts will be crucial for expediting the discovery and production of medically relevant natural products derived from Streptomyces.

Abstract Background The oleaginous yeast Rhodotorula toruloides is a promising chassis organism for the biomanufacturing of value-added bioproducts. It can accumulate lipids at a high fraction of biomass. However, metabolic engineering efforts in this organism have progressed at a slower pace than those in more extensively studied yeasts. Few studies have investigated the lipid accumulation phenotype exhibited by R. toruloides under nitrogen limitation conditions. Consequently, there have been only a few studies exploiting the lipid metabolism for higher product titers. Results We performed a multi-omic investigation of the lipid accumulation phenotype under nitrogen limitation. Specifically, we performed comparative transcriptomic and lipidomic analysis of the oleaginous yeast under nitrogen-sufficient and nitrogen deficient conditions. Clustering analysis of transcriptomic data was used to identify the growth phase where nitrogen-deficient cultures diverged from the baseline conditions. Independently, lipidomic data was used to identify that lipid fractions shifted from mostly phospholipids to mostly storage lipids under the nitrogen-deficient phenotype. Through an integrative lens of transcriptomic and lipidomic analysis, we discovered that R. toruloides undergoes lipid remodeling during nitrogen limitation, wherein the pool of phospholipids gets remodeled to mostly storage lipids. We identify specific mRNAs and pathways that are strongly correlated with an increase in lipid levels, thus identifying putative targets for engineering greater lipid accumulation in R. toruloides. One surprising pathway identified was related to inositol phosphate metabolism, suggesting further inquiry into its role in lipid accumulation. Conclusions Integrative analysis identified the specific biosynthetic pathways that are differentially regulated during lipid remodeling. This insight into the mechanisms of lipid accumulation can lead to the success of future metabolic engineering strategies for overproduction of oleochemicals.

Abstract The CRISPR-Cas12a system is more advantageous than the widely used CRISPR-Cas9 system in terms of specificity and multiplexibility. However, its on-target editing efficiency is typically much lower than that of the CRISPR-Cas9 system. Here we improved its on-target editing efficiency by simply incorporating 2-aminoadenine (base Z, which alters canonical Watson-Crick base pairing) into the crRNA to increase the binding affinity between crRNA and its complementary DNA target. The resulting CRISPR-Cas12a (named zCRISPR-Cas12a thereafter) shows an on-target editing efficiency comparable to that of the CRISPR-Cas9 system but with much lower off-target effects than the CRISPR-Cas9 system in mammalian cells. In addition, zCRISPR-Cas12a can be used for precise gene knock-in and highly efficient multiplex genome editing. Overall, the zCRISPR-Cas12a system is superior to the CRISPR-Cas9 system, and our simple crRNA engineering strategy may be extended to other CRISPR-Cas family members as well as their derivatives.

Honey badger algorithm (HBA) is a recent swarm-based metaheuristic algorithm that excels in simplicity and high exploitation capability. However, it suffers from some limitations including weak exploration capacity and an imbalance between exploration and exploitation. In this paper, an improved honey badger algorithm called ODEHBA is proposed to improve the performance of basic HBA. Firstly, an improved orthogonal opposition-based learning technique is employed to assist population in escaping local optimum. Secondly, differential evolution is utilized to ensure the enrichment of population diversity and to enhance convergence speed. Finally, the exploration capability of ODEHBA is boosted by an equilibrium pool strategy. To validate the efficacy of proposed ODEHBA, it is compared with 13 well-known metaheuristic algorithms on CEC2022 benchmark test sets. Friedman test and Wilcoxon rank-sum test are utilized to assess the performance of ODEHBA. Furthermore, three engineering design problems and Internet of Vehicles (IoV) routing problem are applied to validate the capability of ODEHBA. The simulation results demonstrate that ODEHBA excels in solving complex numerical problems, engineering design, and IoV routing problems. This holds significant practical implications for cost reduction and improved resource utilization.

In order to carry out osmotic purification of black and odorous water and solve the problems of low water flux, reverse solute diffusion and biological pollution affecting the forward osmosis performance, the author proposed the application of graphene nickel oxide nanocomposites in the treatment of black and odorous water. The hydrophilic metal-organic framework (UiO-66 nanoparticle) is embedded into the lamellar structure of graphene nickel oxide as a microporous filler, form ultra-thin “sandwich” film to improve FO performance. The added UiO-66 nano-particles introduce a uniform and suitable nano-channel, which can effectively let water penetrate, at the same time, block the reverse diffusion of Na+. The results show that the film with nanometer thickness formed by GO layer can prevent biological pollution, and the bacteriostatic effect can reach 90 %. In the FO model, the water flux of UiO-66/GO membrane is 29.16 LMH, which is 270 % higher than the original pure graphene nickel oxide membrane, and the reverse solute diffusion is 83.5 % lower (12.86 gMH). It is proved that this study provides an attempt for the application of MOF/GO film in FO process. Combining the excellent overall performance of UiO-66/GO film and the designable features of MOF structure, we expect that MOF/GO film will have broad application prospects as an advanced membrane material of FO technology.

Abstract Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. While there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation have been lacking. Here we describe the in vitro functional and structural characterization of PrnC, a flavin-dependent halogenase that can act on free-standing pyrroles. Computational modeling and site mutagenesis studies identified three key residues in the catalytic pocket. A moderate resolution map using single-particle cryogenic electron microscopy reveals PrnC to be a dimer. This native PrnC can halogenate a library of structurally diverse pyrrolic heterocycles in a site-selective manner and be applied in the chemoenzymatic synthesis of a chlorinated analog of the agrochemical fungicide Fludioxonil.

Since the fault dynamic of droop-controlled inverter is different from synchronous generators (SGs), protection devices may become invalid, and the fault overcurrent may damage power electronic devices and threaten the safety of the microgrid. Therefore, it is imperative to conduct a comprehensive fault analysis of the inverter to guide the design of protection schemes. However, due to the complexity of droop control strategy, existing literatures have simplified asymmetric fault analysis of droop-controlled inverters to varying degrees. Therefore, accurate fault analysis of a droop-controlled inverter is needed. In this paper, by analyzing the control system, an accurate fault model is established. Based on this, a calculation method for instantaneous asymmetrical fault current is proposed. In addition, the current components and current characteristics are analyzed. It was determined that fault currents are affected by control loops, fault types, fault distance and nonlinear limiters. In particular, the influences of limiters on the fault model, fault current calculation and fault current characteristics were analyzed. Through detailed analysis, it was found that dynamics of the control loop cannot be ignored, the fault type and fault distance determine fault current level, and part of the limiters will totally change the fault current trend. Finally, calculation and experimental results verify the correctness of the proposed method.

Abstract Background Caffeic acid O-methyltransferase (COMT) is a key enzyme that regulates melatonin synthesis and is involved in regulating the growth, development, and response to abiotic stress in plants. Tea plant is a popular beverage consumed worldwide, has been used for centuries for its medicinal properties, including its ability to reduce inflammation, improve digestion, and boost immune function. By analyzing genetic variation within the COMT family, while helping tea plants resist adversity, it is also possible to gain a deeper understanding of how different tea varieties produce and metabolize catechins, then be used to develop new tea cultivars with desired flavor profiles and health benefits. Results In this study, a total of 25 CsCOMT genes were identified based on the high-quality tea (Camellia sinensis) plant genome database. Phylogenetic tree analysis of CsCOMTs with COMTs from other species showed that COMTs divided into four subfamilies (Class I, II, III, IV), and CsCOMTs was distributed in Class I, Class II, Class III. CsCOMTs not only undergoes large-scale gene recombination in pairs internally in tea plant, but also shares 2 and 7 collinear genes with Arabidopsis thaliana and poplar (Populus trichocarpa), respectively. The promoter region of CsCOMTs was found to be rich in cis-acting elements associated with plant growth and stress response. By analyzing the previously transcriptome data, it was found that some members of CsCOMT family exhibited significant tissue-specific expression and differential expression under different stress treatments. Subsequently, we selected six CsCOMTs to further validated their expression levels in different tissues organ using qRT-PCR. In addition, we silenced the CsCOMT19 through virus-induced gene silencing (VIGS) method and found that CsCOMT19 positively regulates the synthesis of melatonin in tea plant. Conclusion These results will contribute to the understanding the functions of CsCOMT gene family and provide valuable information for further research on the role of CsCOMT genes in regulating tea plant growth, development, and response to abiotic stress.

Abstract Background There are very limited reports on anti-metabolic glutamate receptor5 (mGluR5) encephalitis, especially lacking of pediatric research. The disease was mostly accompanied by tumors, mainly Hodgkin's lymphoma. No reports of other tumors, such as gangliocytoma have been reported to associate with anti-mGluR5 encephalitis so far. Case presentation and literature reviews We reported a case of a 12-year-old boy with anti-mGluR5 encephalitis complicated with gangliocytoma. The patient suffered from mental disorders including auditory hallucination, and sleep disorders. His cranial magnetic resonance imaging (MRI) showed an abnormality in the right insular lobe. Autoimmune encephalitis antibodies testing was positive for mGluR5 IgG antibody both in cerebrospinal fluid and serum (1:3.2, 1:100 respectively). Abdominal CT indicated a mass in left retroperitoneal confirmed with gangliocytoma via pathology. The patient underwent resection of gangliocytoma. After first-line immunotherapy (glucocorticoid, gamma globulin), his condition was improved. Furthermore, we provide a summary of 6 pediatric cases of Anti-mGluR5 encephalitis. Most of them complicated with Hodgkin's lymphoma, except the case currently reported comorbid with gangliocytoma. The curative effect is satisfactory. Conclusions We report the first patient with anti-mGlur5 encephalitis complicated with gangliocytoma. It suggests that in addition to paying attention to the common lymphoma associated with anti-mGlur5 encephalitis, we should also screen the possibility of other tumors for early detection of the cause, active treatment and prevention of recurrence.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS–USP25 protein–protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS–USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS–USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Abstract Background Although childbearing health care is wellness-based and promotes normal physiology, it is in a medical model and focuses on risk aversion and disease prevention. The salutogenic theory might provide an alternative perspective to health care concerning childbearing, supporting health-promoting factors, not solely on avoiding adverse events. However, there is a dearth of qualitative research exploring couples’ perceptions of childbearing from the salutogenic lens. This study aimed to explore perceptions and experiences concerning childbearing among couples in the perinatal period and identify salutogenic aspects of it. Methods The qualitative descriptive study adopted a directed content analysis to analyse data from a semi-structured and individual interview with 25 purposively selected Chinese couples between July 2022 and December 2022. The concepts of the sense of coherence (SOC) from the salutogenic theory were used as the theory framework for coding. Results Definitions and content for the salutogenic aspects of Chinese couples’ perception of childbearing sense of coherence were developed. For comprehensibility of childbearing, four subthemes were extracted (the challenge to health and endurance; transition to and identification with the new role; conflict and reconciliation in relationships; resistance and compromise between social culture and personal development). For manageability of childbearing, two subthemes were extracted (helplessness and hope of childbearing; self-doubt and self-assurance of childbearing). For meaningfulness of childbearing, three subthemes were extracted (personal realisation; family bonding and harmony; the continuation of life). Conclusions The findings of this study could give a greater understanding in maintaining couples’ health in the perinatal period from the salutogenic lens and provide a guide to further research that the salutogenic theory could bring a health and wellness-focused agenda in practice and policy-making in the perinatal period.

The aim of this experiment was to investigate the effects of exogenous sprays of 5-aminolevulinic acid (5-ALA) and 2-Diethylaminoethyl hexanoate (DTA-6) on the growth and salt tolerance of rice (Oryza sativa L.) seedlings. This study was conducted in a solar greenhouse at Guangdong Ocean University, where ‘Huanghuazhan’ was selected as the test material, and 40 mg/L 5-ALA and 30 mg/L DTA-6 were applied as foliar sprays at the three-leaf-one-heart stage of rice, followed by treatment with 0.3% NaCl (W/W) 24 h later. A total of six treatments were set up as follows: (1) CK: control, (2) A: 40 mg⋅ L−1 5-ALA, (3) D: 30 mg⋅ L−1 DTA-6, (4) S: 0.3% NaCl, (5) AS: 40 mg⋅ L−1 5-ALA + 0.3% NaCl, and (6) DS: 30 mg⋅ L−1 DTA-6+0.3% NaCl. Samples were taken at 1, 4, 7, 10, and 13 d after NaCl treatment to determine the morphology and physiological and biochemical indices of rice roots. The results showed that NaCl stress significantly inhibited rice growth; disrupted the antioxidant system; increased the rates of malondialdehyde, hydrogen peroxide, and superoxide anion production; and affected the content of related hormones. Malondialdehyde content, hydrogen peroxide content, and superoxide anion production rate significantly increased from 12.57% to 21.82%, 18.12% to 63.10%, and 7.17% to 56.20%, respectively, in the S treatment group compared to the CK group. Under salt stress, foliar sprays of both 5-ALA and DTA-6 increased antioxidant enzyme activities and osmoregulatory substance content; expanded non-enzymatic antioxidant AsA and GSH content; reduced reactive oxygen species (ROS) accumulation; lowered malondialdehyde content; increased endogenous hormones GA3, JA, IAA, SA, and ZR content; and lowered ABA content in the rice root system. The MDA, H2O2, and O2− contents were reduced from 35.64% to 56.92%, 22.30% to 53.47%, and 7.06% to 20.01%, respectively, in the AS treatment group compared with the S treatment group. In the DS treatment group, the MDA, H2O2, and O2− contents were reduced from 24.60% to 51.09%, 12.14% to 59.05%, and 12.70% to 45.20%. In summary, NaCl stress exerted an inhibitory effect on the rice root system, both foliar sprays of 5-ALA and DTA-6 alleviated damage from NaCl stress on the rice root system, and the effect of 5-ALA was better than that of DTA-6.

Aiming at the problems of local dehazing distortion and incomplete global dehazing of existing algorithms in real airborne cockpit environments, a two-stage dehazing method PhysiFormer combining physical a priori with a Transformer oriented flight perspective was proposed. The first stage used synthetic pairwise data to pre-train the dehazing model. First, a pyramid pooling module (PPM) was introduced in the Transformer for multiscale feature extraction to solve the problem of poor recovery of local details, then a global context fusion mechanism was used to enable the model to better perceive global information. Finally, considering that combining the physical a priori needs to rely on the estimation of the atmosphere light, an encoding-decoding structure based on the residual blocks was used to estimate the atmosphere light, which was then used for dehazing through the atmospheric scattering model for dehazing. The second stage used real images combined with physical priori to optimize the model to better fit the real airborne environment. The experimental results show that the proposed method has better naturalness image quality evaluator (NIQE) and blind/referenceless image spatial quality evaluator (BRISQUE) indexes and exhibits the best dehazing visual effect in the tests of dense haze, non-uniform haze and real haze images, which effectively improves the problems of color distortion and haze residue.

Abstract Microbial production of succinic acid (SA) at an industrially relevant scale has been hindered by high downstream processing costs arising from neutral pH fermentation for over three decades. Here, we metabolically engineer the acid-tolerant yeast Issatchenkia orientalis for SA production, attaining the highest titers in sugar-based media at low pH (pH 3) in fed-batch fermentations, i.e. 109.5 g/L in minimal medium and 104.6 g/L in sugarcane juice medium. We further perform batch fermentation using sugarcane juice medium in a pilot-scale fermenter (300×) and achieve 63.1 g/L of SA, which can be directly crystallized with a yield of 64.0%. Finally, we simulate an end-to-end low-pH SA production pipeline, and techno-economic analysis and life cycle assessment indicate our process is financially viable and can reduce greenhouse gas emissions by 34–90% relative to fossil-based production processes. We expect I. orientalis can serve as a general industrial platform for production of organic acids.

Abstract Background With China's rapidly aging population, meeting the diverse care needs of senior citizens is becoming more challenging. Although voluntary social services have numerous advantages and are popular among older adults, there is little information on the need for assistance from volunteer-based social services, particularly those with a medical background, and influencing factors among urban home-based older adults. This study aimed to assess the need for assistance from voluntary services and related factors among urban home-based older adults in China. Methods A cross-sectional study was conducted in 2022 on communities in four cities in China. The 27-item Home-Based Older Adults Assistance Need Scale was used to measure the assistance needs of 498 participants aged 60 and above. Multiple linear regression models were conducted to identify salient variables associated with the need for assistance from voluntary services. Results The mean score of the need for assistance from voluntary services was 88.60 ± 24.37. The mean scores of the items examining four dimensions, namely, health maintenance, visiting communication, social intercourse, and daily life, were 3.64 ± 1.08, 3.49 ± 1.04, 3.33 ± 1.08, and 2.78 ± 1.08, respectively. The level of depression, willingness to assist older adults, attaching importance to health preservation, ability to self-comfort, desire to accept assistance from others, and the presence of more children or none at all were all positively correlated with the perceived need for assistance from voluntary services. In contrast, social care obtained from visiting medical institutions was negatively correlated. These seven factors explained 28.5% of the total variance. Conclusions Urban home-based older adults in China were found to have significant requirements for assistance from volunteer services, and several complex factors were associated with more significant assistance needs. These findings may encourage the extremely limited numbers of social volunteers, particularly those with a medical background, to identify priorities in providing assistance services to the large numbers of urban home-based older adults and thus improve service delivery.

Abstract Chromatin boundary elements contribute to the partitioning of mammalian genomes into topological domains to regulate gene expression. Certain boundary elements are adopted as DNA insulators for safe and stable transgene expression in mammalian cells. These elements, however, are ill-defined and less characterized in the non-coding genome, partially due to the lack of a platform to readily evaluate boundary-associated activities of putative DNA sequences. Here we report SHIELD (Site-specific Heterochromatin Insertion of Elements at Lamina-associated Domains), a platform tailored for the high-throughput screening of barrier-type DNA elements in human cells. SHIELD takes advantage of the high specificity of serine integrase at heterochromatin, and exploits the natural heterochromatin spreading inside lamina-associated domains (LADs) for the discovery of potent barrier elements. We adopt SHIELD to evaluate the barrier activity of 1000 DNA elements in a high-throughput manner and identify 8 candidates with barrier activities comparable to the core region of cHS4 element in human HCT116 cells. We anticipate SHIELD could facilitate the discovery of novel barrier DNA elements from the non-coding genome in human cells.

The current deep learning methods for copy–move forgery detection (CMFD) are mostly based on deep convolutional neural networks, which frequently discard a large amount of detail information throughout convolutional feature extraction and have poor long-range information extraction capabilities. The Transformer structure is adept at modeling global context information, but the patch-wise self-attention calculation still neglects the extraction of details in local regions that have been tampered with. A local-information-refined dual-branch network, LBRT (Local Branch Refinement Transformer), is designed in this study. It performs Transformer encoding on the global patches segmented from the image and local patches re-segmented from the global patches using a global modeling branch and a local refinement branch, respectively. The self-attention features from both branches are precisely fused, and the fused feature map is then up-sampled and decoded. Therefore, LBRT considers both global semantic information modeling and local detail information refinement. The experimental results show that LBRT outperforms several state-of-the-art CMFD methods on the USCISI dataset, CASIA CMFD dataset, and DEFACTO CMFD dataset.

The Broad Learning System (BLS) has demonstrated strong performance across a variety of problems. However, BLS based on the Minimum Mean Square Error (MMSE) criterion is highly sensitive to label noise. To enhance the robustness of BLS in environments with label noise, a function called Logarithm Kernel (LK) is designed to reweight the samples for outputting weights during the training of BLS in order to construct a Logarithm Kernel-based BLS (L-BLS) in this paper. Additionally, for image databases with numerous features, a Mixture Autoencoder (MAE) is designed to construct more representative feature nodes of BLS in complex label noise environments. For the MAE, two corresponding versions of BLS, MAEBLS, and L-MAEBLS were also developed. The extensive experiments validate the robustness and effectiveness of the proposed L-BLS, and MAE can provide more representative feature nodes for the corresponding version of BLS.

Abstract Background The availability of physical activity (PA) facilities in neighborhoods is hypothesized to influence cardiovascular disease (CVD), but evidence from individual-level long-term cohort studies is limited. We aimed to assess the association between neighborhood exposure to PA facilities and CVD incidence. Methods A total of 4658 participants from the Chinese Multi-provincial Cohort Study without CVD at baseline (2007–2008) were followed for the incidence of CVD, coronary heart disease (CHD), and stroke. Availability of PA facilities was defined as both the presence and the density of PA facilities within a 500-m buffer zone around the participants’ residential addresses. Time-dependent Cox regression models were performed to estimate the associations between the availability of PA facilities and risks of incident CVD, CHD, and stroke. Results During a median follow-up of 12.1 years, there were 518 CVD events, 188 CHD events, and 355 stroke events. Analyses with the presence indicator revealed significantly lower risks of CVD (hazard ratio [HR] 0.80, 95% confidence interval ([CI] 0.65–0.99) and stroke (HR 0.76, 95% CI 0.60–0.97) in participants with PA facilities in the 500-m buffer zone compared with participants with no nearby facilities in fully adjusted models. In analyses with the density indicator, exposure to 2 and ≥ 3 PA facilities was associated with 35% (HR 0.65, 95% CI 0.47–0.91) and 28% (HR 0.72, 95% CI 0.56–0.92) lower risks of CVD and 40% (HR 0.60, 95% CI 0.40–0.90) and 38% (HR 0.62, 95% CI 0.46–0.84) lower risks of stroke compared with those without any PA facilities in 500-m buffer, respectively. Effect modifications between presence of PA facilities and a history of hypertension for incident stroke (P = 0.049), and a history of diabetes for incident CVD (P = 0.013) and stroke (P = 0.009) were noted. Conclusions Residing in neighborhoods with better availability of PA facilities was associated with a lower risk of incident CVD. Urban planning intervention policies that increase the availability of PA facilities could contribute to CVD prevention.

Abstract Synthetic biology requires efficient systems that support the well-coordinated co-expression of multiple genes. Here, we discover a 9-bp nucleotide sequence that enables efficient polycistronic gene expression in yeasts and filamentous fungi. Coupling polycistronic expression to multiplexed, markerless, CRISPR/Cas9-based genome editing, we develop a strategy termed HACKing (Highly efficient and Accessible system by CracKing genes into the genome) for the assembly of multigene pathways. HACKing allows the expression level of each enzyme to be precalibrated by linking their translation to those of host proteins with predetermined abundances under the desired fermentation conditions. We validate HACKing by rapidly constructing highly efficient Saccharomyces cerevisiae cell factories that express 13 biosynthetic genes, and produce model endogenous (1,090.41 ± 80.92 mg L−1 squalene) or heterologous (1.04 ± 0.02 mg L−1 mogrol) terpenoid products. Thus, HACKing addresses the need of synthetic biology for predictability, simplicity, scalability, and speed upon fungal pathway engineering for valuable metabolites.

Salt stress is one of the major abiotic stresses that damage the structure and composition of cell walls. Alginate oligosaccharides (AOS) have been advocated to significantly improve plant stress tolerance. The metabolic mechanism by which AOS induces salt tolerance in rice cell walls remains unclear. Here, we report the impact of AOS foliar application on the cell wall composition of rice seedlings using the salt-tolerant rice variety FL478 and the salt-sensitive variety IR29. Data revealed that salt stress decreased biomass, stem basal width, stem breaking strength, and lodging resistance; however, it increased cell wall thickness. In leaves, exogenous AOS up-regulated the expression level of OSCESA8, increased abscisic acid (ABA) and brassinosteroids (BR) content, and increased β-galacturonic activity, polygalacturonase activity, xylanase activity, laccase activity, biomass, and cellulose content. Moreover, AOS down-regulated the expression levels of OSMYB46 and OSIRX10 and decreased cell wall hemicellulose, pectin, and lignin content to maintain cell wall stability under salt stress. In stems, AOS increased phenylalamine ammonia-lyase and tyrosine ammonia-lyase activities, while decreasing cellulase, laccase, and β-glucanase activities. Furthermore, AOS improved the biomass and stem basal width and also enhanced the cellulose, pectin, and lignin content of the stem, As a result, increased resistance to stem breakage strength and alleviated salt stress-induced damage, thus enhancing the lodging resistance. Under salt stress, AOS regulates phytohormones and modifies cellulose, hemicellulose, lignin, and pectin metabolism to maintain cell wall structure and improve stem resistance to lodging. This study aims to alleviate salt stress damage to rice cell walls, enhance resistance to lodging, and improve salt tolerance in rice by exogenous application of AOS.

Hyperspectral images contain abundant spectral and spatial information of the surface of the earth, but there are more difficulties in processing, analyzing, and sample-labeling these hyperspectral images. In this paper, local binary pattern (LBP), sparse representation and mixed logistic regression model are introduced to propose a sample labeling method based on neighborhood information and priority classifier discrimination. A new hyperspectral remote sensing image classification method based on texture features and semi-supervised learning is implemented. The LBP is employed to extract features of spatial texture information from remote sensing images and enrich the feature information of samples. The multivariate logistic regression model is used to select the unlabeled samples with the largest amount of information, and the unlabeled samples with neighborhood information and priority classifier discrimination are selected to obtain the pseudo-labeled samples after learning. By making full use of the advantages of sparse representation and mixed logistic regression model, a new classification method based on semi-supervised learning is proposed to effectively achieve accurate classification of hyperspectral images. The data of Indian Pines, Salinas scene and Pavia University are selected to verify the validity of the proposed method. The experiment results have demonstrated that the proposed classification method is able to gain a higher classification accuracy, a stronger timeliness, and the generalization ability.

Abstract Background Fertility intentions have been proved to be a reliable predictor of actual fertility behaviour. Also, childbirth-related fear (CBRF) has been proven to be negatively associated with childbirth readiness and fertility intentions among women, while childbirth readiness was positively related to fertility intentions. However, the associations and potential mechanisms between CBRF, childbirth readiness, and fertility intentions remain unknown. This study aimed to investigate the unique association between CBRF, childbirth readiness, and fertility intentions and whether childbirth readiness would mediate the relationship between CBRF and fertility intentions. Method A cross-sectional study of women (N = 1119, aged 16–53 years) who gave birth within 72 h was conducted. Using a convenience sampling, women were recruited from obstetric wards—10 comprehensive hospitals and 3 specialized hospitals in 7 provinces in mainland China. Pearson correlation was used to examine the relationship between CBRF, childbirth readiness, fertility intentions, and social support. Multivariate linear regression was further used to analyze the association between demographic and personal characteristics, CBRF, childbirth readiness, and fertility intentions. Mediation analysis was used to examine whether childbirth readiness mediates the relationship between CBRF and fertility intentions. Results Women with high childbirth readiness (β = 0.09, P = 0.002) had higher fertility intentions. However, women with high CBRF (β = − 0.17, P

RiPP discovery has expanded the scope of post-translational modification chemistry, but genome mining of RiPP classes remains an unsolved challenge. Here, the authors employed bioinformatics and synthetic biology approaches to discover and characterize an unknown class of RiPPs, defined by an unusual amino-modified C-terminus.

Summary: Chemically modified mRNAs hold great potential for therapeutic applications in vivo. Currently, the base modification scheme largely preserves the canonical Watson-Crick base pairing, thus missing one mode of mRNA modulation by altering its secondary structure. Here we report the incorporation of base Z (2-aminoadenine) into mRNA to create Z-mRNA with improved translational capacity, decreased cytotoxicity, and drastically reduced immunogenicity compared to the unmodified mRNA in mammalian cells. In particular, the A-to-Z substitution renders modified mRNAs less immunogenic than the state-of-the-art base modification N1-methylpseudouridine (m1ψ) in mouse embryonic fibroblast cells. As a proof of concept, we developed a Z-mRNA-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Antigen-encoding Z-mRNA elicited substantial humoral and cellular immune responses in vivo in mice, albeit with relatively lower efficacy than the state-of-the-art m1ψ-mRNA. Z-mRNA expands the scope of mRNA base modifications toward noncanonical bases and could offer an advantageous platform for mRNA-based therapeutics where minimal immunogenicity is desired.

Abstract Rhodosporidium toruloides is an oleaginous yeast under development with promising industrial applications. Since promoters of different strengths have been demonstrated as an efficient strategy to fine-tune gene expression in synthetic biology, a set of constitutive promoters with strengths varying over 2 orders of magnitude were identified in R. toruloides through transcriptome analysis under different growth conditions. Promoter candidates were first cloned and characterized using an enhanced green fluorescent protein (EGFP) as a reporter under eight conditions, and 31 promoters were identified with strength varied from 0.1 to 19.0 folds of the commonly used strong promoter of the glyceraldehyde-3-phosphate dehydrogenase gene (PGPD1). The resultant promoters were then used to optimize the linoleic acid biosynthetic pathway in R. toruloides in different media, including the use of lignocellulosic hydrolysate as the fermentation substrate, and improved the production of linoleic acid by up to 214.2% in minimal medium, with the highest production of 350.3 mg/L in Yeast Peptone Dextrose medium. This work has enriched the promoter library of R. toruloides, and helped develop R. toruloides as a platform organism for applications in biomanufacturing and synthetic biology.

Multivariate ridge regression (MR), linear discriminant analysis (LDA) and extreme learning machine (ELM) have been widely used in hyperspectral image (HSI) classification. However, these methods do not consider the influence of noise in HSIs, spatial information, and the internal relationship between samples. As a result, the sample distribution is not ideal and the classification effect cannot be improved. This article extends LDA and MR to the field of tensors, that can not only use the spatial information of the sample, but also can make the distribution of homogeneous samples more concentrated. Besides, this article analyzes the relationship between the number of neurons in the hidden layer of ELM and the classification accuracy. Finally, singular spectral analysis (SSA) is chosen to improve classification accuracy. The tensor discriminant ridge regression model with ELM and SSA for HSI classification is proposed. Experiments show compared with tensor-based classifiers, ELM and other state-of-the-art methods, the proposed method is efficient and effective.

Compared with the traditional method based on hand-crafted features, deep neural network has achieved a certain degree of success on remote sensing (RS) image semantic segmentation. However, there are still serious holes, rough edge segmentation, and false detection or even missed detection due to the light and its shadow in the segmentation. Aiming at the above problems, this article proposes a RS semantic segmentation model SCG-TransNet that is a hybrid model of Swin transformer and Deeplabv3+, which includes Swin-Conv-Dspp (SCD) and global local transformer block (GLTB). First, the SCD module which can efficiently extract feature information from objects at different scales is used to mitigate the hole phenomenon, reducing the loss of detailed information. Second, we construct a GLTB with spatial pyramid pooling shuffle module to extract critical detail information from the limited visible pixels of the occluded objects, which alleviates the problem of difficult object recognition due to occlusion effectively. Finally, the experimental results show that our SCG-TransNet achieves a mean intersection over union of 70.29$\%$ on the Vaihingen datasets, which is 3$\%$ higher than the baseline model. It also achieved good results on POSDAM datasets. These demonstrate the effectiveness, robustness, and superiority of our proposed method compared with existing state-of-the-art methods.

Imaging non-repetitive loci in living cells remains challenging. Here, the authors engineered an inducible system whereby biomolecular assemblies can be guided to specific genomic loci by a nuclease-defective Cas9, allowing the simultaneous imaging and manipulation of the loci.

The transient responses of distributed energy resources (DERs) in a microgrid are dynamically correlated in spatial and temporal dimensions. Hence, the transient stability prediction in microgrids would require an effective modeling of time-varying correlations and the mining of spatial–temporal features of electrical data. This paper proposes a refined DER-level transient stability prediction method for microgrids considering the time-varying spatial–temporal correlations of DERs. First, the spatial–temporal dynamic correlation of DERs was extracted and modeled by an attention-based mechanism. Then, a spatial–temporal graph convolution network was proposed to predict the dynamics of unstable DERs and the instability severity trend in a microgrid. The TSP model consisted of three parts: (1) several stacked spatial–temporal convolution modules to simultaneously mine the spatial–temporal dynamic features of microgrids, (2) an unstable DER identification module to predict the microgrid system stability and identify unstable DERs, and (3) an instability severity trend prediction module for DERs in a microgrid. The test results on a realistic 16-bus 10-DER microgrid demonstrated that the proposed prediction method possessed the desirable reliability and interpretability and outperformed the state-of-the-art baselines in unstable DER identifications and DER instability severity trend predictions.

This study aimed to investigate whether presoaking with hemin (5 μmol·L−1) could alleviate NaCl stress during rapeseed seedlings’ growth and its role in the regulation of photosynthesis. In this experiment, ‘HUAYOUZA 62 (HYZ 62)’ and ‘HUAYOUZA 158R (158R)’ were used as materials for pot experiments to study the morphology, photosynthetic characteristics, antioxidant activity, and osmoregulatory factors of seedlings under different salt concentrations, as well as the regulatory effects of hemin-presoaked seeds. Our findings revealed that, compared the control, NaCl stress inhibited the growth of two rapeseed varieties, decreased the seedling emergence rate, and increased the content of malondialdehyde (MDA), the electrolyte leakage rate (EL) and antioxidant enzyme activity. Hemin soaking alleviated the adverse effects of salt stress and increased plant height, root elongation and dry matter accumulation. Compared with all NaCl treatments, hemin significantly enhanced photosynthetic indexes, including a percent increase of 12.99–24.36% and 5.39–16.52% in net photosynthetic rate (Pn), 17.86–48.08% and 8.6–23.44% in stomatal conductivity (Gs), and 15.42–37.94% and 11.09–19.08% in transpiration rate (Tr) for HYZ62 and 158R, respectively. Moreover, hemin soaking also increased antioxidant enzyme activities, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX), reducing the malondialdehyde, and thus resulting in the alleviation of oxidative damage caused by NaCl stress. Furthermore, hemin stimulated the formation of soluble protein, which effectively regulated the osmo-protective qualities. The current findings strongly elucidate that hemin soaking could effectively alleviate the negative impacts of NaCl stress by regulating the morphological, photosynthetic, and antioxidant traits. This study provides a new idea regarding the effect of Hemin on the salt tolerance of rapeseed, and provides a basis for the practical application of Hemin in saline–alkali soil to improve the salt tolerance of cultivated rapeseed.

The aroma characteristics of seven commercial Chinese sunflower seed oils were investigated in this study using descriptive analysis, headspace solid-phase microextraction coupled with GC-quadrupole-MS (LRMS, low-resolution mass spectrometry), and GC-Orbitrap-MS (HRMS, high-resolution mass spectrometry). GC-Orbitrap-MS quantified 96 compounds, including 18 alcohols, 12 esters, 7 ketones, 20 terpenoids, 11 pyrazines, 6 aldehydes, 6 furans, 6 benzene ring-containing compounds, 3 sulfides, 2 alkanes, and 5 nitrogen-containing compounds. Moreover, 22 compounds including 5 acids, 1 amide, and 16 aldehydes were quantified using GC-Quadrupole-MS. To our knowledge, 23 volatile compounds were reported for the first time in sunflower seed oil. All the seven samples were found to have a ‘roasted sunflower seeds’ note, ‘sunflower seeds aroma’ note and ‘burnt aroma’ note and only five of them had ‘fried instant noodles’ note, three had ‘sweet’ note and two had ‘puffed food’ note. Partial least squares regression was used to screen the candidate key volatiles that caused the aroma differences among these seven samples. It was observed that ‘roasted sunflower seeds’ note was positively correlated with 1-octen-3-ol, n-heptadehyde and dimethyl sulfone, whereas the ‘fried instant noodles’ and ‘puffed food’ demonstrated a positive correlation with pentanal, 3-methylbutanal, hexanal, (E)-2-hexenal and 2-pentylfuran. Our findings provide information to the producers and developers for quality control and improvement of sunflower seed oil.

ABSTRACTOne-quarter of the world’s population is infected with Mycobacterium tuberculosis (Mtb). After initial exposure, more immune-competent persons develop asymptomatic latent tuberculosis infection (LTBI) but not active diseases, creates an extensive reservoir at risk of developing active tuberculosis. Previously, we constructed a novel recombinant Sendai virus (SeV)-vectored vaccine encoding two dominant antigens of Mtb, which elicited immune protection against acute Mtb infection. In this study, nine Mtb latency-associated antigens were screened as potential supplementary vaccine candidate antigens, and three antigens (Rv2029c, Rv2028c, and Rv3126c) were selected based on their immune-therapeutic effect in mice, and their elevated immune responses in LTBI human populations. Then, a recombinant SeV-vectored vaccine, termed SeV986A, that expresses three latency-associated antigens and Ag85A was constructed. In murine models, the doses, titers, and inoculation sites of SeV986A were optimized, and its immunogenicity in BCG-primed and BCG-naive mice were determined. Enhanced immune protection against the Mtb challenge was shown in both acute-infection and latent-infection murine models. The expression levels of several T-cell exhaustion markers were significantly lower in the SeV986A-vaccinated group, suggesting that the expression of latency-associated antigens inhibited the T-cell exhaustion process in LTBI infection. Hence, the multistage quarter-antigenic SeV986A vaccine holds considerable promise as a novel post-exposure prophylaxis vaccine against tuberculosis.

Ribosomally synthesized and post-translationally modified peptides are a source of antimicrobials. Here, the authors report a platform for the rapid evaluation and characterization of biosynthetic gene clusters that enables the identification of 30 structurally diverse modified peptides, including three showing antimicrobial activities.

ObjectiveAccumulating evidence shows that cognitive impairment (CI) in chronic heart failure (CHF) patients is related to brain network dysfunction. This study investigated brain network structure and rich-club organization in chronic heart failure patients with cognitive impairment based on graph analysis of diffusion tensor imaging data.MethodsThe brain structure networks of 30 CHF patients without CI and 30 CHF patients with CI were constructed. Using graph theory analysis and rich-club analysis, changes in global and local characteristics of the subjects’ brain network and rich-club organization were quantitatively calculated, and the correlation with cognitive function was analyzed.ResultsCompared to the CHF patients in the group without CI group, the CHF patients in the group with CI group had lower global efficiency, local efficiency, clustering coefficient, the small-world attribute, and increased shortest path length. The CHF patients with CI group showed lower nodal degree centrality in the fusiform gyrus on the right (FFG.R) and nodal efficiency in the orbital superior frontal gyrus on the left (ORB sup. L), the orbital inferior frontal gyrus on the left (ORB inf. L), and the posterior cingulate gyrus on the right (PCG.R) compared with CHF patients without CI group. The CHF patients with CI group showed a smaller fiber number of edges in specific regions. In CHF patients with CI, global efficiency, local efficiency and the connected edge of the orbital superior frontal gyrus on the right (ORB sup. R) to the orbital middle frontal gyrus on the right (ORB mid. R) were positively correlated with Visuospatial/Executive function. The connected edge of the orbital superior frontal gyrus on the right to the orbital inferior frontal gyrus on the right (ORB inf. R) is positively correlated to attention/calculation. Compared with the CHF patients without CI group, the connection strength of feeder connection and local connection in CHF patients with CI group was significantly reduced, although the strength of rich-club connection in CHF patients complicated with CI group was decreased compared with the control, there was no statistical difference. In addition, the rich-club connection strength was related to the orientation (direction force) of the Montreal cognitive assessment (MoCA) scale, and the feeder and local connection strength was related to Visuospatial/Executive function of MoCA scale in the CHF patients with CI.ConclusionChronic heart failure patients with CI exhibited lower global and local brain network properties, reduced white matter fiber connectivity, as well as a decreased strength in local and feeder connections in key brain regions. The disrupted brain network characteristics and connectivity was associated with cognitive impairment in CHF patients. Our findings suggest that impaired brain network properties and decreased connectivity, a feature of progressive disruption of brain networks, predict the development of cognitive impairment in patients with chronic heart failure.

Lycopene (LY) belongs to carotenoids and is abundant in red fruits and vegetables. Several previous studies suggested that LY is beneficial for ameliorating non-alcoholic fatty liver disease (NAFLD), while the potential mechanisms are unclear. The present study aimed to clarify the potential mechanisms of LY in preventing NAFLD via exploring the hepatic NF-κB/NLRP3 inflammasome pathway and intestinal microbiota composition in high-fat and high-fructose diet (HFFD)-fed mice. Fifty eight-week-old male C57BL/6J mice were randomly assigned into 5 groups: Normal control group (NC); HFFD group; HFFD with low dose of lycopene group (LLY, 20 mg/kg/d); HFFD with high dose of lycopene group (HLY, 60 mg/kg/d) and HFFD with resveratrol group (RSV, 50 mg/kg/d, positive control). After 8 weeks, feces were collected and the 12 h fasted mice were sacrificed to acquire tissues and blood for parameters measurement. The results showed that the mice in LLY, HLY and RSV groups had significantly lower body weight gain, weight of white adipose tissue, serum levels of high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), lipopolysaccharide (LPS), alanine aminotransferase (ALT), and hepatic concentrations of triglyceride (TG) and interleukin-6 (IL-6) than that in the HFFD group (p

IntroductionAccumulating evidence shows that epilepsy is a disease caused by brain network dysfunction. This study explored changes in brain network structure in epilepsy patients based on graph analysis of diffusion tensor imaging data.MethodsThe brain structure networks of 42 healthy control individuals and 26 epilepsy patients were constructed. Using graph theory analysis, global and local network topology parameters of the brain structure network were calculated, and changes in global and local characteristics of the brain network in epilepsy patients were quantitatively analyzed.ResultsCompared with the healthy control group, the epilepsy patient group showed lower global efficiency, local efficiency, clustering coefficient, and a longer shortest path length. Both healthy control individuals and epilepsy patients showed small-world attributes, with no significant difference between groups. The epilepsy patient group showed lower nodal local efficiency and nodal clustering coefficient in the right olfactory cortex and right rectus and lower nodal degree centrality in the right olfactory cortex and the left paracentral lobular compared with the healthy control group. In addition, the epilepsy patient group showed a smaller fiber number of edges in specific regions of the frontal lobe, temporal lobe, and default mode network, indicating reduced connection strength.DiscussionEpilepsy patients exhibited lower global and local brain network properties as well as reduced white matter fiber connectivity in key brain regions. These findings further support the idea that epilepsy is a brain network disorder.

Giardia duodenalis is a zoonotic intestinal protozoan parasite that may cause host diarrhea and chronic gastroenteritis, resulting in great economic losses annually and representing a significant public health burden across the world. However, thus far, our knowledge on the pathogenesis of Giardia and the related host cell responses is still extensively limited. The aim of this study is to assess the role of endoplasmic reticulum (ER) stress in regulating G0/G1 cell cycle arrest and apoptosis during in vitro infection of intestinal epithelial cells (IECs) with Giardia. The results showed that the mRNA levels of ER chaperone proteins and ER-associated degradation genes were increased and the expression levels of the main unfolded protein response (UPR)-related proteins (GRP78, p-PERK, ATF4, CHOP, p-IRE1, XBP1s and ATF6) were increased upon Giardia exposure. In addition, cell cycle arrest was determined to be induced by UPR signaling pathways (IRE1, PERK and ATF6) through upregulation of p21 and p27 levels and promotion of E2F1-RB complex formation. Upregulation of p21 and p27 expression was shown to be related to Ufd1-Skp2 signaling. Therefore, the cell cycle arrest was induced by ER stress when infected with Giardia. Furthermore, the apoptosis of the host cell was also assessed after exposure to Giardia. The results indicated that apoptosis would be promoted by UPR signaling (PERK and ATF6), but would be suppressed by the hyperphosphorylation of AKT and hypophosphorylation of JNK that were modulated by IRE1 pathway. Taken together, both of the cell cycle arrest and apoptosis of IECs induced by Giardia exposure involved the activation of the UPR signaling. The findings of this study will deepen our understanding of the pathogenesis of Giardia and the associated regulatory network.

The purpose of this paper is to establish a transition strategy for tilt-rotor vertical takeoff and landing (VTOL) unmanned aerial vehicles (UAVs) based on an optimal design method. Firstly, The flyable transition corridor was calculated based on both the UAV’s dynamic equations and its aerodynamic and dynamic characteristics. The dynamic equations of the UAV were organized into state equation forms. The initial and final value constraints of the control and state variables in the transition process were recorded, as were the constraints of the transition process. The transition strategy design problem was transformed into an optimal control problem with constraints, while the Gauss pseudospectral method (GPM) was employed to transform and solve the problem. In addition, performance indicators were designed based on the transition quality requirements for transition time, attitude stability, and control continuity. Sensitivity was analyzed according to different index terms with different dimensions and effects. Finally, the rationality of the transition strategy designed in this paper was verified according to different simulation scenarios.

Despite their broad utility, design and construction of plasmids remains laborious and time-consuming. Here the authors report a robust, versatile, and automated end-to-end platform that enables scarless construction of virtually any plasmid.

Liquid-liquid phase separation (LLPS) is reported to occur in the intracellular environment. Here the authors show that heparan sulphate serves as a platform for basic fibroblast growth factor to undergo LLPS on the cell surface, therefore facilitating downstream signalling

ObjectiveTo investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions.MethodsTwenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis.ResultsThe area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group.ConclusionThe topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease.

Fungal infection is a serious global health issue, causing approximately 1.5 million mortalities annually. However, clinically available anti-fungal drugs are limited, especially for multidrug-resistant fungal infections. Therefore, new antifungal drugs are urgently needed to address this clinical challenge. In this study, we proposed two non-antifungal drugs, auranofin and pentamidine, in combination to fight against multidrug-resistant C. albicans. The insufficient antifungal activity of anti-rheumatic drug auranofin is partially due to fungal membrane barrier preventing the drug uptake, and anti-protozoal drug pentamidine was used here to improve the permeability of membrane. The auranofin/pentamidine combination displayed synergistic inhibitory effect against both drug-susceptible and drug-resistant C. albicans, as well as biofilm, and significantly reduced the minimum inhibitory concentration of each drug. At non-antifungal concentration, pentamidine can disrupt the membrane integrity and increase membrane permeability, leading to enhanced cellular uptake of auranofin in C. albicans. This repurposing strategy using the combination of non-antifungal drugs with complementary antifungal mechanism may provide a novel approach for discovery of antifungal drugs to fight against multidrug-resistant fungal infections.

Abstract Background The oleaginous, carotenogenic yeast Rhodotorula toruloides has been increasingly explored as a platform organism for the production of terpenoids and fatty acid derivatives. Fatty alcohols, a fatty acid derivative widely used in the production of detergents and surfactants, can be produced microbially with the expression of a heterologous fatty acyl-CoA reductase. Due to its high lipid production, R. toruloides has high potential for fatty alcohol production, and in this study several metabolic engineering approaches were investigated to improve the titer of this product. Results Fatty acyl-CoA reductase from Marinobacter aqueolei was co-expressed with SpCas9 in R. toruloides IFO0880 and a panel of gene overexpressions and Cas9-mediated gene deletions were explored to increase the fatty alcohol production. Two overexpression targets (ACL1 and ACC1, improving cytosolic acetyl-CoA and malonyl-CoA production, respectively) and two deletion targets (the acyltransferases DGA1 and LRO1) resulted in significant (1.8 to 4.4-fold) increases to the fatty alcohol titer in culture tubes. Combinatorial exploration of these modifications in bioreactor fermentation culminated in a 3.7 g/L fatty alcohol titer in the LRO1Δ mutant. As LRO1 deletion was not found to be beneficial for fatty alcohol production in other yeasts, a lipidomic comparison of the DGA1 and LRO1 knockout mutants was performed, finding that DGA1 is the primary acyltransferase responsible for triacylglyceride production in R. toruloides, while LRO1 disruption simultaneously improved fatty alcohol production, increased diacylglyceride and triacylglyceride production, and increased glucose consumption. Conclusions The fatty alcohol titer of fatty acyl-CoA reductase-expressing R. toruloides was significantly improved through the deletion of LRO1, or the deletion of DGA1 combined with overexpression of ACC1 and ACL1. Disruption of LRO1 surprisingly increased both lipid and fatty alcohol production, creating a possible avenue for future study of the lipid metabolism of this yeast.

Hyperspectral images (HSI) feature rich spectral information in many narrow bands but at a cost of a relatively low spatial resolution. As such, various methods have been developed for enhancing the spatial resolution of the low-resolution HSI (Lr-HSI) by fusing it with high-resolution multispectral images (Hr-MSI). The difference in spectrum range and spatial dimensions between the Lr-HSI and Hr-MSI has been fundamental but challenging for multispectral/hyperspectral (MS/HS) fusion. In this article, a multiscale spatial fusion and regularization induced auxiliary task based convolutional neural network model is proposed for deep super-resolution of HSI, where an Lr-HSI is fused with an Hr-MSI to reconstruct a high-resolution HSI (Hr-HSI) counterpart. The multiscale fusion is used to efficiently address the discrepancy in spatial resolutions between the two inputs. Based on the general assumption that the acquired Hr-MSI and the reconstructed Hr-HSI share similar underlying characteristics, the auxiliary task is proposed to learn a representation for improved generality of the model and reduced overfitting. Experimental results on five public datasets have validated the effectiveness of our approach in comparison with several state-of-the-art methods.