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Donor-Acceptor (D-A) polymer field-effect transistors (pFETs) are at the cutting edge of organic electronics. However, some fundamental cognition of interface states remains unquantified, particularly at different dynamic scales. In this study, the interface states of D-A polymer transistors are quantified using the dynamic pumping method. The experimental results indicate that the interface state density of the transistor is insensitive to the measurement pulse condition and stays within the range of $ {10}^{ {12}}\,\,\sim \,\, {10}^{ {13}}\,\,\rm {cm}^{ {-2}}$ . The experiments described in this paper provide a quantitative analysis of interface states. This analysis can serve as effective guidance for optimizing future devices.

Background: In the past few years, U-Net based U-shaped architecture and skip-connections have made incredible progress in the field of medical image segmentation. U2-Net achieves good performance in computer vision. However, in the medical image segmentation task, U2-Net with over nesting is easy to overfit. Purpose: A 2D network structure TransU2-Net combining transformer and a lighter weight U2-Net is proposed for automatic segmentation of brain tumor magnetic resonance image (MRI). Methods: The light-weight U2-Net architecture not only obtains multi-scale information but also reduces redundant feature extraction. Meanwhile, the transformer block embedded in the stacked convolutional layer obtains more global information; the transformer with skip-connection enhances spatial domain information representation. A new multi-scale feature map fusion strategy as a postprocessing method was proposed for better fusing high and low-dimensional spatial information. Results: Our proposed model TransU2-Net achieves better segmentation results, on the BraTS2021 dataset, our method achieves an average dice coefficient of 88.17%; Evaluation on the publicly available MSD dataset, we perform tumor evaluation, we achieve a dice coefficient of 74.69%; in addition to comparing the TransU2-Net results are compared with previously proposed 2D segmentation methods. Conclusions: We propose an automatic medical image segmentation method combining transformers and U2-Net, which has good performance and is of clinical importance. The experimental results show that the proposed method outperforms other 2D medical image segmentation methods. Clinical Translation Statement: We use the BarTS2021 dataset and the MSD dataset which are publicly available databases. All experiments in this paper are in accordance with medical ethics.

For a class of discrete-time bidirectional associative memory neural networks (DTBAMNNs) with multiple time-varying delays, the issue of state estimation is studied. By propose a mathematical induction method, we first investigate novel delay-dependent and -independent global exponential stability (GES) criteria of the error system. The obtained GES criteria are described by linear scalar inequalities. Then, a state observer is derived via the theory of generalized matrix inverses. These exponential stability conditions are very simple, which is convenient to verify based on the standard software tools (for example, YALMIP). Finally, we present two illustrative examples to present the effectiveness of the theoretical results.

In practical applications, the raw input to a Knowledge Based Question Answering (KBQA) system may vary in forms, expressions, sources, etc. As a result, the actual input to the system may contain various errors caused by various noise in raw data and processes of transmission, transformation, translation, etc. As a result, it is significant to evaluate and enhance the robustness of a KBQA model to various noisy questions. In this paper, we generate 29 datasets of various noisy questions based on the original SimpleQuestions dataset to evaluate and enhance the robustness of a KBQA model, and propose a model which is more robust to various noisy questions. Compared with traditional methods, the main contribution in this paper is that we propose a method of generating datasets of different noisy questions to evaluate the robustness of a KBQA model, and propose a KBQA model which contains incremental learning and Mask Language Model (MLM) in the question answering process, so that our model is less affected by different kinds of noise in questions and achieves higher accuracies on datasets of different noisy questions, which shows its robustness. Experimental results show that our model achieves an average accuracy of 78.1% on these datasets and outperforms the baseline BERT-based model by an average margin of 5.0% with the similar training cost. In addition, further experiments show that our model is compatible with other pre-trained models such as ALBERT and ELECTRA.

Brassinolide (BL) is one of the most active compounds among phytohormone brassinosteroids (BRs) and can be used for plant growth and development regulation. Here, the authors report the construction of an artificial pathway in baker’s yeast for scalable production of 24-epi-ergosterol, a precursor for BL semi-synthesis.

Abstract Background Brucellosis, caused by Brucella spp., is a major zoonotic public health threat. Although several Brucella vaccines have been demonstrated for use in animals, Brucella spp. can cause human infection and to date, there are no human‐use vaccines licensed by any agency. Recently, methods in vaccine informatics have made major breakthroughs in peptide‐based epitopes, opening up a new avenue of vaccine development. Objectives The purpose of this article was to identify potential antigenic peptides in Brucella by proteome and peptidome analyses. Methods Mouse infection models were first established by injection with Brucella and spleen protein profiles were then analysed. Subsequently, the major histocompatibility complex class I or II (major histocompatibility complex [MHC]‐I/II)‐binding peptides in blood samples were collected by immunoprecipitation and peptides derived from Brucella proteins were identified through liquid chromatography–mass spectrometry (LC‐MS/MS). These peptides were then evaluated in a variety of ways, such as in terms of conservation in Brucella and synchronicity in predicted peptides (similarity and coverage), which allowed us to more effectively measure their antigenic potential. Results The expression of the inflammatory cytokines IL1B and IFN‐γ was significantly altered in the spleen of infected mice and some Brucella proteins, such as Muri, AcpP and GroES, were also detected. Meanwhile, in blood, 35 peptides were identified and most showed high conservation, highlighting their potential as antigen epitopes for vaccine development. In particular, we identified four proteins containing both MHC‐I‐ and MHC‐II‐binding peptides including AtpA, AtpD, DnaK and BAbS19_II02030. They were also compared with the predicted peptides to estimate their reliability. Conclusions The peptides we screened could bind to MHC molecules. After being stimulated with antigen T epitopes, Memory T cells can stimulate T cell activation and promote immune responses. Our results indicated that the peptides we identified may be good candidate targets for the design of subunit vaccines and these results pave the way for the study of safer vaccines against Brucella.

Abstract Background Thyme derived essential oil and its components have numerous applications in pharmaceutical, food, and cosmetic industries, owing to their antibacterial, antifungal, and antiviral properties. To obtain thyme essential oil with different terpene composition, we developed new germplasm resources using the conventional hybridization approach. Results Phenotypic characteristics, including essential oil yield and composition, glandular trichome density, plant type, and fertility, of three wild Chinese and seven European thyme species were evaluated. Male-sterile and male-fertile thyme species were crossed in different combinations, and two F1 populations derived from Thymus longicaulis (Tl) × T. vulgaris ‘Fragrantissimus’ (Tvf) and T. vulgaris ‘Elsbeth’ (Tve) × T. quinquecostatus (Tq) crosses were selected, with essential oil yield and terpene content as the main breeding goals. Simultaneously, simple sequence repeat (SSR) primers were developed based on the whole-genome sequence of T. quinquecostatus to authenticate the F1 hybrids. A total of 300 primer pairs were selected, and polymerase chain reaction (PCR) was carried out on the parents of the two hybrid populations (Tl, Tvf, Tve, and Tq). Based on the chemotype of the parents and their F1 progenies, we examined the expression of genes encoding two γ-terpinene synthases, one α-terpineol synthase, and maybe one geraniol synthase in all genotypes by quantitative real-time PCR (qRT-PCR). Conclusion We used hybridization to create new germplasm resources of thyme, developed SSR markers based on the whole-genome sequence of T. quinquecostatus, and screened the expression of monoterpene synthase genes in thyme. The results of this study provide a strong foundation for the creation of new germplasm resources, construction of the genetic linkage maps, and identification of quantitative trait loci (QTLs), and help gain insight into the mechanism of monoterpenoids biosynthesis in thyme.

Objective Pigs, an ideal biomedical model for human diseases, suffer from about 50% early embryonic and fetal death, a major cause of fertility loss worldwide. However, identifying the causal variant remains a huge challenge. This study aimed to detect single nucleotide polymorphisms (SNPs) and candidate genes for the number of mummified (NM) piglets using the imputed whole-genome sequence (WGS) and validate the potential candidate genes. Methods The imputed WGS was introduced from genotyping-by-sequencing (GBS) using a multi-breed reference population. We performed genome-wide association studies (GWAS) for NM piglets at birth from a Landrace pig populatiGWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase on. A total of 300 Landrace pigs were genotyped by GBS. The whole-genome variants were imputed, and 4,252,858 SNPs were obtained. Various molecular experiments were conducted to determine how the genes affected NM in pigs. Results A strong GWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase 8 (CDK8) gene, which plays a crucial role in embryonic retardation and lethality. Based on the molecular experiments, we found that Y-box binding protein 1 (YBX1) was a crucial transcription factor for CDK8, which mediated the effect of CDK8 in the proliferation of porcine ovarian granulosa cells via transforming growth factor beta/small mother against decapentaplegic signaling pathway, and, as a consequence, affected embryo quality, indicating that this pathway may be contributing to mummified fetal in pigs. Conclusion A powerful imputation-based association study was performed to identify genes associated with NM in pigs. CDK8 was suggested as a functional gene for the proliferation of porcine ovarian granulosa cells, but further studies are required to determine causative mutations and the effect of loci on NM in pigs.

Abstract Background To evaluate the performance of diffusion-relaxation correlation spectrum imaging (DR-CSI) with support vector machine (SVM) in detecting prostate cancer (PCa). Methods In total, 114 patients (mean age, 66 years, range, 48–87 years) who received a prostate MRI and underwent biopsy were enrolled in three stages. Thirty-nine were assigned for the exploration stage to establish the model, 18 for the validation stage to choose the appropriate scale for mapping and 57 for the test stage to compare the diagnostic performance of the DR-CSI and PI-RADS. Results In the exploration stage, the DR-CSI model was established and performed better than the ADC and T2 values (both P

Abstract As an indigenous breed, the Tibetan chicken is found in highland regions and shows physiological adaptations to high altitude; however, the genetic changes that determine these adaptations remain elusive. We assumed that the microevolution of the Tibetan chicken occurred from lowland to highland regions with a continuous elevation range. In this study, we analyzed the genome of 188 chickens from lowland areas to the high‐altitude regions of the Tibetan plateau with four altitudinal levels. Phylogenetic analysis revealed that Tibetan chickens are significantly different from other altitude chicken populations. Reconstruction of the demographic history showed that the migration and admixture events of the Tibetan chicken occurred at different times. The genome of the Tibetan chicken was also used to analyze positive selection pressure that is associated with high‐altitude adaptation, revealing the well‐known candidate gene that participates in oxygen binding (HBAD), as well as other novel potential genes (e.g., HRG and ANK2) that are related to blood coagulation and cardiovascular efficiency. Our study provides novel insights regarding the evolutionary history and microevolution mechanisms of the high‐altitude adaptation in the Tibetan chicken.

Arabidopsis SPINDLY (SPY) is a nucleocytoplasmic protein O-fucosyltransferase. Here, the authors present a crystal structure of Arabidopsis SPY/GDP complex, reveal SPY’s substrate recognition and enzyme mechanism, and provide insights into the glycan donor substrate selection in GT41 proteins.

Clinical manifestations of tuberculosis range from asymptomatic infection to a life-threatening disease such as tuberculous meningitis (TBM). Recent studies showed that the spectrum of disease severity could be related to genetic diversity among clinical strains of Mycobacterium tuberculosis (Mtb). Certain strains are reported to preferentially invade the central nervous system, thus earning the label “hypervirulent strains”.However, specific genetic mutations that accounted for enhanced mycobacterial virulence are still unknown. We previously identified a set of 17 mutations in a hypervirulent Mtb strain that was from TBM patient and exhibited significantly better intracellular survivability. These mutations were also commonly shared by a cluster of globally circulating hyper-virulent strains. Here, we aimed to validate the impact of these hypervirulent-specific mutations on the dysregulation of gene networks associated with virulence in Mtb via multi-omic analysis. We surveyed transcriptomic and proteomic differences between the hyper-virulent and low-virulent strains using RNA-sequencing and label-free quantitative LC-MS/MS approach, respectively. We identified 25 genes consistently differentially expressed between the strains at both transcript and protein level, regardless the strains were growing in a nutrient-rich or a physiologically relevant multi-stress condition (acidic pH, limited nutrients, nitrosative stress, and hypoxia). Based on integrated genomic-transcriptomic and proteomic comparisons, the hypervirulent-specific mutations in FadE5 (g. 295,746 C >T), Rv0178 (p. asp150glu), higB (p. asp30glu), and pip (IS6110-insertion) were linked to deregulated expression of the respective genes and their functionally downstream regulons. The result validated the connections between mutations, gene expression, and mycobacterial pathogenicity, and identified new possible virulence-associated pathways in Mtb.

As next-generation pathogen detection methods, CRISPR-Cas-based detection methods can perform single-nucleotide polymorphism (SNP) level detection with high sensitivity and good specificity. They do not require any particular equipment, which opens up new possibilities for the accurate detection and identification of Bacillus anthracis. In this study, we developed a complete detection system for B. anthracis based on Cas12a. We used two chromosomally located SNP targets and two plasmid targets to identify B. anthracis with high accuracy. The CR5 target is completely new. The entire detection process can be completed within 90 min without electrical power and with single-copy level sensitivity. We also developed an unaided-eye visualization system based on G4-DNAzyme for use with our CRISPR-Cas12a detection system. This visualization system has good prospects for deployment in field-based point-of-care detection. We used the antisense nucleic acid CatG4R as the detection probe, which showed stronger resistance to interference from components of the solution. CatG4R can also be designed as an RNA molecule for adaptation to Cas13a detection, thereby broadening the scope of the detection system.

Using the method of static game analysis, the potential risk and responsibility across the entire pork supply chain are discussed from the perspective of all stakeholders involved. Included in the analysis are pig suppliers, slaughterers, pork processors, pork sellers and consumers. The results indicate the following: firstly, the lower the probability of inspections on downstream businesses and the higher the single inspection fee, the greater the probability of harmful substances used by upstream businesses and the higher the costs. Secondly, businesses that actively manufacture and transfer harmful substances in the supply chain cannot add extra costs. Finally, the quality and risk factors in pork production may not follow a strictly linear growth. This study might explain the unique problems that occur in pork supply chain management in large developing countries such as China.

Abstract This case reports describe a rare disease, mid‐aortic syndrome (MAS), that can cause severe heart failure and hypertension in infancy. The typical images, key points of diagnosis, and therapy methods of the disease have also been presented. We report two critical thoracoabdominal aortic coarctation cases in infants aged 2 and 11 months with severe heart failure. The patients were initially misdiagnosed as dilated myocardiopathy, with the correct diagnosis confirmed through imaging. Both patients underwent balloon angioplasty; one patient also had bare‐metal stents implanted. The patient treated with balloon angioplasty alone died after the procedure, whereas the other patient recovered well. In conclusion, careful physical examinations, especially upper and lower extremity blood pressure differences and palpation of upper and lower limb pulses, are critical in unexplained infant heart failure cases. Stent implantation may be a safer and more effective treatment than simple balloon angioplasty in infants with MAS.

Abstract WHIRLY (WHY) family proteins, a small family of single-stranded DNA (ssDNA) binding proteins, are widely found in plants and have multiple functions to regulate plant growth and development. However, WHY in rice has received less attention. In this study, we continued our previous study on OsTRX z that is important for chloroplast development. OsTRX z was discovered to interact with OsWHY1, which was confirmed using yeast two-hybrid, pull-down, and BiFC assays. Subsequently, the oswhy1 mutants were obtained by CRISPR/Cas9, which exhibited an albino phenotype and died after the three-leaf stage. Consistent with this albino phenotype, low amounts of Chl a, Chl b, and Car were detected in the oswhy1-1 mutant. Moreover, the oswhy1-1 mutant had chloroplasts with disrupted architecture and no stacked grana and thylakoid membranes. Subcellular localization showed that the OsWHY1-GFP fusion protein was targeted to the chloroplast. What’s more, OsWHY1 was found to be preferentially expressed in young leaves and was involved in chloroplast RNA editing and splicing. Mutation of OsWHY1 significantly affected the expression of chloroplast and ribosome development-related and chlorophyll synthesis-related genes. In conclusion, OsWHY1 contributes to early chloroplast development and normal seedling survival in rice. These results will further elucidate the molecular mechanism of chloroplast development and expand our understanding of WHY1 functions.

Abstract Background High-altitude cerebral edema (HACE) is a serious and potentially fatal brain injury that is caused by acute hypobaric hypoxia (HH) exposure. Vasogenic edema is the main pathological factor of this condition. Hypoxia-induced disruptions of tight junctions in the endothelium trigger blood‒brain barrier (BBB) damage and induce vasogenic edema. Nuclear respiratory factor 1 (NRF1) acts as a major regulator of hypoxia-induced endothelial cell injury, and caveolin-1 (CAV-1) is upregulated as its downstream gene in hypoxic endothelial cells. This study aimed to investigate whether CAV-1 is involved in HACE progression and the underlying mechanism. Methods C57BL/6 mice were exposed to HH (7600 m above sea level) for 24 h, and BBB injury was assessed by brain water content, Evans blue staining and FITC-dextran leakage. Immunofluorescence, transmission electron microscope, transendothelial electrical resistance (TEER), transcytosis assays, and western blotting were performed to confirm the role and underlying mechanism of CAV-1 in the disruption of tight junctions and BBB permeability. Mice or bEnd.3 cells were pretreated with MβCD, a specific blocker of CAV-1, and the effect of CAV-1 on claudin-5 internalization under hypoxic conditions was detected by immunofluorescence, western blotting, and TEER. The expression of NRF1 was knocked down, and the regulation of CAV-1 by NRF1 under hypoxic conditions was examined by qPCR, western blotting, and immunofluorescence. Results The BBB was severely damaged and was accompanied by a significant loss of vascular tight junction proteins in HACE mice. CAV-1 was significantly upregulated in endothelial cells, and claudin-5 explicitly colocalized with CAV-1. During the in vitro experiments, hypoxia increased cell permeability, CAV-1 expression, and claudin-5 internalization and downregulated tight junction proteins. Simultaneously, hypoxia induced the upregulation of CAV-1 by activating NRF1. Blocking CAV-1-mediated intracellular transport improved the integrity of TJs in hypoxic endothelial cells and effectively inhibited the increase in BBB permeability and brain water content in HH animals. Conclusions Hypoxia upregulated CAV-1 transcription via the activation of NRF1 in endothelial cells, thus inducing the internalization and autophagic degradation of claudin-5. These effects lead to the destruction of the BBB and trigger HACE. Therefore, CAV-1 may be a potential therapeutic target for HACE. Video abstract

Objective This work was to determine coat inheritance and evaluate production performance for crossbred pigs from Berkshire×Chenghua (BC) compared with Chinese indigenous Chenghua (CH) pigs. Methods The coat color phenotypes were recorded for more than 16,000 pigs, and the genotypes of melanocortin 1 receptor (MCIR) gene were identified by sequencing. The reproductive performance of 927 crossbred BC F4 gilts and 320 purebred CH gilts was recorded. Sixty pigs of each breed were randomly selected at approximately 60 days of age to determine growth performance during fattening period, which lasted for 150 days for BC pigs and 240 days for CH pigs. At the end of the fattening period, 30 pigs of each breed were slaughtered to determine carcass composition and meat quality. Results The coat color of BC pigs exhibits a “dominant black” hereditary pattern, and all piglets derived from boars or sows genotyped ED1ED1 homozygous for MC1R gene showed a uniform black coat phenotype. The BC F4 gilts displayed a good reproductive performance, showing a higher litter and tear size and were heavier at farrowing litter and at weaning litter than the CH gilts, but they reached puberty later than the CH gilts. BC F4 pigs exhibited improved growth and carcass characteristics with a higher average daily live weight gain, lower feed-to-gain ratio, and higher carcass lean meat rate than CH pigs. Like CH pigs, BC F4 pigs produced superior meat-quality characteristics, showing ideal pH and meat-color values, high intramuscular fat content and water-holding capacity, and acceptable muscle-fiber parameters. C18:1, C16:0, C18:0, and C18:2 were the main fatty acids in M. longissimus lumborum in the two breeds, and a remarkably high polyunsaturated/saturated fatty acid ratio of ~0.39 was observed in the BC F4 pigs. Conclusion The BC F4 pigs exhibit a uniform black coat pattern and acceptable total production performance.

Abstract Background Orthodontic tooth movement inevitably induces cementum resorption, which is an urgent problem for orthodontists to confront. Human periodontal ligament stem cells (hPDLSCs) exert an important role in the orthodontic tooth movement and exhibit multidirectional differentiation ability in cementum regeneration. Connective tissue growth factor (CTGF) is an important extracellular matrix protein for bone homeostasis and cell differentiation. The purpose of our study was to explore the role of CTGF in cementum repair and cementogenesis and to elucidate its underlying mechanism. Methods A cementum defect model was established by tooth movement with heavy forces, and the cementum repair effect of CTGF was observed via micro-CT, HE staining and immunohistochemical staining. RT‒qPCR, western blotting (WB), alizarin red staining and ALP activity experiments verified the mineralization ability of hPDLSCs stimulated with CTGF. The expression of Cx43 in periodontal ligament cells was detected by WB and immunofluorescence (IF) experiments after CTGF stimulation in vivo and in vitro. Subsequently, the mineralization ability of hPDLSCs was observed after application of CTGF and the small interfering RNA Si-Cx43. Additionally, co-intervention via application of the small interfering RNA Si-CTGF and the Cx43 agonist ATRA in hPDLSCs was performed to deepen the mechanistic study. Next, WB, IF experiments and co-immunoprecipitation were conducted to confirm whether CTGF triggers the Cx43/β-catenin axis to regulate cementoblast differentiation of hPDLSCs. Results Local oral administration of CTGF to the cementum defects in vivo facilitated cementum repair. CTGF facilitated the cementogenesis of hPDLSCs in a concentration-dependent manner. Cx43 acted as a downstream effector of CTGF to regulate cementoblast differentiation. Si-Cx43 reduced CTGF-induced cementoblast differentiation. The Cx43 agonist ATRA restored the low differentiation capacity induced by Si-CTGF. Further mechanistic studies showed that CTGF triggered the activation of β-catenin in a dose-dependent manner. In addition, co-localization IF analysis and co-immunoprecipitation demonstrated that Cx43 interacted with β-catenin at cell‒cell connections. Si-Cx43 attenuated the substantial expression of β-catenin induced by CTGF. The Cx43 agonist reversed the inhibition of β-catenin induced by Si-CTGF. IF demonstrated that the nuclear importation of β-catenin was related to the immense expression of Cx43 at cell‒cell junctions. Conclusions Taken together, these data demonstrate that CTGF promotes cementum repair and cementogenesis through activation of the Cx43/β-catenin signalling axis.

Highlights The proportion of CD4+CD25−Foxp3+ T cells was elevated in untreated RA. CD4+CD25−Foxp3+ T cells expressed decreased Helios compared with Treg cells in both RA patients and HCs. CD4+CD25−Foxp3+ T cells produced increased IFN-γ compared with Tregs in RA patients. Elevated CD4+CD25−Foxp3+ T cells were positively correlated with DAS28 score, anti-IgG titer and anti-CCP titer.

Gut microbiota play an important role in the gut ecology and development of pigs, which is always regulated by nutrients. This study investigated the effect of L-Citrulline on growth performance, carcass characteristics, and its potential regulatory mechanism. The results showed that 1% dietary L-Citrulline supplementation for 52 days significantly increased final weight, liveweight gain, carcass weight, and average backfat and markedly decreased drip loss (p

Ti3C2/TiO2 hybrids are environment-friendly and exhibit excellent photocatalytic and hydrogen-generating power characteristics. Herein, a novel single-step method is proposed for fabricating multilayer structures in which TiO2, generated from (NH4)2TiF6, wraps the Ti3C2 MXene by etching Ti3AlC2 with (NH4)2TiF6. The optimal reaction conditions for the etching of Ti3AlC2 with (NH4)2TiF6 were systematically studied. The phase composition, morphology, and photophysical properties of the Ti3C2/TiO2 hybrids were investigated using X-ray diffraction, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and UV–vis spectrophotometry. The thermal stability of the hybrids was investigated using thermogravimetric and differential thermal analyses. Along with the formation of Ti3C2 MXene, Ti3AlC2 reacted with (NH4)2TiF6 at 60 °C for 24 h to form hybrids surrounded by NH4TiOF3 crystals. Subsequent reactions of these hybrids with H3BO3 resulted in the conversion of NH4TiOF3 crystals into TiO2 and eventually into Ti3C2/TiO2 hybrids. Furthermore, the photocatalytic activity of the Ti3C2/TiO2 hybrids was measured by monitoring the photodegradation of methylene blue under ultraviolet light, which showed that the photocatalytic activity of the Ti3C2/TiO2 hybrids was higher than that of the commercial anatase TiO2 nanoparticles.

IntroductionEvery-other-day fasting (EODF) is a classical intermittent fasting (IF) mode with neuroprotective effects that promotes motor function recovery after spinal cord injury (SCI) in rats. However, its dynamic effects on the gut microbiota and spinal cord transcriptome remain unknown.MethodsIn this study, 16S rRNA sequencing and RNA-seq analysis were used to investigate the effects of ad libitum (AL) and EODF dietary modes on the structural characteristics of rat gut microbiota in rats and the spinal cord transcriptome at various time points after SCI induction.ResultsOur results showed that both dietary modes affected the bacterial community composition in SCI rats, with EODF treatment inducing and suppressing dynamic changes in the abundances of potentially anti-inflammatory and pro-inflammatory bacteria. Furthermore, the differentially expressed genes (DEGs) enriched after EODF intervention in SCI rats were associated with various biological events, including immune inflammatory response, cell differentiation, protein modification, neural growth, and apoptosis. In particular, significant spatiotemporal differences were apparent in the DEGs associated with neuroprotection between the EODF and AL interventions. These DGEs were mainly focused on days 1, 3, and 7 after SCI. The relative abundance of certain genera was significantly correlated with DEGs associated with neuroprotective effects in the EODF-SCI group.DiscussionOur results showed that EODF treatment may exert neuroprotective effects by modulating the transcriptome expression profile following SCI in rats. Furthermore, gut microbiota may be partially involved in mediating these effects.

Summary: Type VI secretion system is widely used in Gram-negative bacteria for injecting toxic effectors into neighboring prokaryotic or eukaryotic cells. Various effectors can be loaded onto the T6SS delivery tube via its core components: Hcp, VgrG, or PAAR. Here, we report 2.8-Å resolution cryo-EM structure of intact T6SS Hcp5-VgrG-PAAR cargo delivery system and crystal structure of unbound Hcp5 from B. fragilis NCTC 9343. Loading of Hcp5 hexameric ring onto VgrG causes expansion of its inner cavity and external surface, explaining how structural changes could be propagated to regulate co-polymerization and surrounding contractile sheath. High-affinity binding between Hcp and VgrG causes entropically unfavorable structuring of long loops. Furthermore, interactions between VgrG trimer and Hcp hexamer are asymmetric, with three of the six Hcp monomers exhibiting a major loop flip. Our study provides insights into the assembly, loading, and firing of T6SS nanomachine that contributes to bacterial inter-species competition and host interactions.

Abstract On 20–22 July 2012, a severe rainstorm occurred in the Sichuan basin of Southwest China and in the Beijing area of North China. This rainstorm was related to the activities of a Tibetan Plateau vortex (TPV) and Southwest China vortex (SWCV). By using radiosonde, satellite brightness temperature, and NCEP_FNL data, we investigated the helicity characteristics nearly the vortexes and their effect on convection. Results showed that (1) strong precipitation in the Sichuan basin was mainly related to the interaction between the TPV and SWCV, while strong precipitation in the Beijing area was related to the northward movement of a cyclonic vortex caused by a split in the SWCV. (2) During the occurrence of the rainstorm, four mesoscale convection systems (MCSs) were observed. Their vertical structure showed a positive vorticity–negative divergence in the lower levels, and negative vorticity–positive divergence in the upper levels, accompanied by vertical upward movement. This was an important factor in the development and maintenance of MCSs, as well as one of the mechanisms for producing heavy precipitation. On this basis, we further discussed the effect of helicity on the MCSs in the atmospheric environment with rotational characteristics. Results showed that the increase in negative water vapour helicity and storm‐relative helicity were more likely to cause a strong development of MCSs.

IntroductionIn this study, we aimed to estimate the genetic parameters of the reproductive traits in three popular commercial pig breeds: Duroc, Landrace, and Yorkshire. Additionally, we evaluated the factors that influence these traits.MethodWe collected data from a large number of litters, including 1,887 Duroc, 21,787 Landrace, and 74,796 Yorkshire litters. Using the ASReml-R software to analyze 11 traits, which included: total number of pigs born (TNB); number of piglets born alive (NBA); number of piglets born healthy (NBH); number of piglets born weak (NBW); number of new stillborn piglets (NS); number of old stillborn piglets (OS); number of piglets born with malformation (NBM); number of mummified piglets (NM); total litter birthweight (LBW); litter average weight (LAW); duration of gestational period (GP). We investigated the effects of 4 fixed factors on the genetic parameters of these traits.ResultsAmong the 11 reproductive-related traits, the gestational period belonged to the medium heritability traits (0.251–0.430), while remaining traits showed low heritability, ranging from 0.005 to 0.159. TNB, NBA, NBH, LBW had positive genetic correlation (0.737 ~ 0.981) and phenotype correlation (0.711 ~ 0.951). There was a negative genetic correlation between NBW and LAW (−0.452 ~ −0.978) and phenotypic correlation (−0.380 ~ −0.873). LBW was considered one of the most reasonable reproductive traits that could be used for breeding improvement. Repeatability of the three varieties was within the range of 0.000–0.097. In addition, the fixed effect selected in this study had a significant effect on Landrace and Yorkshire (p

BackgroundDisease control is a primary treatment goal for patients with chronic rhinosinusitis (CRS). This study aims to summarize the evaluation parameters of disease control and then identify predictors of poorly controlled CRS.MethodsA systematic review of the literature was performed on PubMed, Google Scholar, Scopus, and Cochrane databases to identify studies relating to disease control in CRS.ResultsThe concept of disease control in patients with CRS involved the longitudinal assessment of the disease state and was also an important goal of treatment. As a metric of the disease state, the disease control reflected the ability to keep disease manifestations within certain limits, the efficacy after treatment, and the impact on quality of life. Validated measurements, such as EPOS2012 criteria, EPOS2020 criteria, Sinus Control Test, and patient/physician-reported global level of CRS control, have been utilized in clinical practice. These existing disease control instruments incorporated various disease manifestations and categorized patients into two (well-controlled and poor-controlled), three (uncontrolled, partly controlled, and controlled), or five (not at all, a little, somewhat, very, and completely) control categories. Eosinophilia, high computerized tomography score, bilateral sinonasal disease, asthma, allergic rhinitis, female gender, aspirin intolerance, revision surgery, low serum amyloid A, and specific T cell subtype would predict poorly controlled CRS.ConclusionThe concept of disease control and its application were gradually developed in patients with CRS. The existing disease control instruments demonstrated a lack of uniformity regarding the controlled criteria and included parameters.

Different anatomical locations of the body skin show differences in their gene expression patterns depending on different origins, and the inherent heterogeneous information can be maintained in adults. However, highly resolvable cellular specialization is less well characterized in different anatomical regions of the skin. Pig is regarded as an excellent model animal for human skin research in view of its similar physiology to human. In this study, single-cell RNA sequencing was performed on pig skin tissues from six different anatomical regions of Chenghua (CH) pigs, with a superior skin thickness trait, and the back site of large white (LW) pigs. We obtained 233,715 cells, representing seven cell types, among which we primarily characterized the heterogeneity of the top three cell types, including smooth muscle cells (SMCs), endothelial cells (ECs), and fibroblasts (FBs). Then, we further identified several subtypes of SMCs, ECs, and FBs, and discovered the expression patterns of site-specific genes involved in some important pathways such as the immune response and extracellular matrix (ECM) synthesis in different anatomical regions. By comparing differentially expressed genes of skin FBs among different anatomical regions, we considered TNN, COL11A1, and INHBA as candidate genes for facilitating ECM accumulation. These findings of heterogeneity in the main skin cell types from different anatomical sites will contribute to a better understanding of inherent skin information and place the potential focus on skin generation, transmission, and transplantation, paving the foundation for human skin priming.

The influence of polysialic acid (PSA) and sialic acid (SA) on the gut microbial community composition and metabolites in healthy humans was investigated using a bionic gastrointestinal reactor. The results indicated that PSA and SA significantly changed the gut microbiota and metabolites to different degrees. PSA can increase the relative abundances of Faecalibacterium and Allisonella, whereas SA can increase those of Bifidobacterium and Megamonas. Both can significantly increase the content of short-chain fatty acids. The results of metabolome analysis showed that PSA can upregulate ergosterol peroxide and gallic acid and downregulate the harmful metabolite N-acetylputrescine. SA can upregulate 4-pyridoxic acid and lipoic acid. PSA and SA affect gut microbiota and metabolites in different ways and have positive effects on human health. These results will provide a reference for the further development of PSA- and SA-related functional foods and health products.

Grain size in rice (Oryza sativa L.) shapes yield and quality, but the underlying molecular mechanism is not fully understood. We functionally characterized GRAIN NUMBER AND LARGE GRAIN SIZE 44 (GNL44), encoding a RING-type protein that localizes to the cytoplasm. The gnl44 mutant has fewer but enlarged grains compared to the wild type. GNL44 is mainly expressed in panicles and developing grains. Grain chalkiness was higher in the gnl44 mutant than in the wild type, short-chain amylopectin content was lower, middle-chain amylopectin content was higher, and appearance quality was worse. The amylose content and gel consistency of gnl44 were lower, and protein content was higher compared to the wild type. Rapid Visco Analyzer results showed that the texture of cooked gnl44 rice changed, and that the taste value of gnl44 was lower, making the eating and cooking quality of gnl44 worse than that of the wild type. We used gnl44, qgl3, and gs3 monogenic and two-gene near-isogenic lines to study the effects of different combinations of genes affecting grain size on rice quality-related traits. Our results revealed additive effects for these three genes on grain quality. These findings enrich the genetic resources available for rice breeders.

The isoquinoline alkaloid berberine, derived from Coptidis rhizoma, exhibits antibacterial, hypoglycemic, and anti-inflammatory properties. Canagliflozin is a sodium–glucose cotransporter 2 (SGLT2) inhibitor. We synthesized compounds B9OC and B9OBU by conjugating canagliflozin and n-butane at the C9 position of berberine, aiming to develop antimicrobial agents for combating bacterial infections worldwide. We utilized clinically prevalent pathogenic bacteria, namely Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, to investigate the antibacterial efficacy of B9OC. This was accomplished through the determination of the MIC80 values, analysis of bacterial growth curves, evaluation of biofilm formation using crystal violet staining, assessment of impact on bacterial proteins via SDS-PAGE analysis, and observation of alterations in bacterial morphology utilizing field emission scanning electron microscopy. Meanwhile, the ADMET of compound B9OC was predicted using a computer-aided method. The findings revealed that B9OC exhibited lower minimal inhibitory concentrations against all three bacteria compared to berberine alone or in combination with canagliflozin. The minimal inhibitory concentrations (MICs) of B9OC against the three experimental strains were determined to be 0.035, 0.258, and 0.331 mM. However, B9OBu exhibited a lower level of antimicrobial activity compared to berberine. The compound B9OC exhibits a broad spectrum of antibacterial activity by disrupting the integrity of bacterial cell walls, leading to cellular rupture and the subsequent degradation of intracellular proteins.

Microalgae are a sustainable source for the production of biofuels and bioactive compounds. This review discusses significant research on innovative extraction techniques using dimethyl ether (DME) as a green subcritical fluid. DME, which is characterized by its low boiling point and safety as an organic solvent, exhibits remarkable properties that enable high extraction rates of various active compounds, including lipids and bioactive compounds, from high-water-content microalgae without the need for drying. In this review, the superiority of liquefied DME extraction technology for microalgae over conventional methods is discussed in detail. In addition, we elucidate the extraction mechanism of this technology and address its safety for human health and the environment. This review also covers aspects related to extraction equipment, various applications of different extraction processes, and the estimation and trend analysis of the Hansen solubility parameters. In addition, we anticipate a promising trajectory for the expansion of this technology for the extraction of various resources.

Methamphetamine (METH) abuse inflicts both physical and psychological harm. While our previous research has established the regulatory role of miR-29c-3p in behavior sensitization, the underlying mechanisms and target genes remain incompletely understood. In this study, we employed the isobaric tags for relative and absolute quantitation (iTRAQ) technique in conjunction with Ingenuity pathway analysis (IPA) to probe the putative molecular mechanisms of METH sensitization through miR-29c-3p inhibition. Through a microinjection of AAV-anti-miR-29c-3p into the nucleus accumbens (NAc) of mice, we observed the attenuation of METH-induced locomotor effects. Subsequent iTRAQ analysis identified 70 differentially expressed proteins (DEPs), with 22 up-regulated potential target proteins identified through miR-29c-3p target gene prediction and IPA analysis. Our focus extended to the number of neuronal branches, the excitatory synapse count, and locomotion-related pathways. Notably, GPR37, NPC1, and IREB2 emerged as potential target molecules for miR-29c-3p regulation, suggesting their involvement in the modulation of METH sensitization. Quantitative PCR confirmed the METH-induced aberrant expression of Gpr37, Npc1, and Ireb2 in the NAc of mice. Specifically, the over-expression of miR-29c-3p led to a significant reduction in the mRNA level of Gpr37, while the inhibition of miR-29c-3p resulted in a significant increase in the mRNA level of Gpr37, consistent with the regulatory principle of miRNAs modulating target gene expression. This suggests that miR-29c-3p potentially influences METH sensitization through its regulation of neuroplasticity. Our research indicates that miR-29c-3p plays a crucial role in regulating METH-induced sensitization, and it identified the potential molecular of miR-29c-3p in regulating METH-induced sensitization.

Advances in nanotechnology have provided novel avenues for the diagnosis and treatment of multiple myeloma (MM), a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. This review elucidates the potential of nanotechnology to revolutionize myeloma therapy, focusing on nanoparticle-based drug delivery systems, nanoscale imaging techniques, and nano-immunotherapy. Nanoparticle-based drug delivery systems offer enhanced drug targeting, reduced systemic toxicity, and improved therapeutic efficacy. We discuss the latest developments in nanocarriers, such as liposomes, polymeric nanoparticles, and inorganic nanoparticles, used for the delivery of chemotherapeutic agents, siRNA, and miRNA in MM treatment. We delve into nanoscale imaging techniques which provide spatial multi-omic data, offering a holistic view of the tumor microenvironment. This spatial resolution can help decipher the complex interplay between cancer cells and their surrounding environment, facilitating the development of highly targeted therapies. Lastly, we explore the burgeoning field of nano-immunotherapy, which employs nanoparticles to modulate the immune system for myeloma treatment. Specifically, we consider how nanoparticles can be used to deliver tumor antigens to antigen-presenting cells, thus enhancing the body’s immune response against myeloma cells. In conclusion, nanotechnology holds great promise for improving the prognosis and quality of life of MM patients. However, several challenges remain, including the need for further preclinical and clinical trials to assess the safety and efficacy of these emerging strategies. Future research should also focus on developing personalized nanomedicine approaches, which could tailor treatments to individual patients based on their genetic and molecular profiles.

Power outages and poor thermal conditions are common in emergency shelters. In light of this, a novel design for a solar-powered emergency shelter (SPES) with flexible photovoltaics is proposed and investigated in this paper. Firstly, the space and structure of SPES are designed based on ergonomic and easy open-and-close requirements. Then, considering the finishing strength of the building and the convenience and economy of the processing design, the construction of solid models using a 1:2 equal scale, and three double-top SPES were developed, in which internal roofs are canvas, polyethylene(PE), and polyvinyl chloride(PVC). Finally, measurements and ANSYS-Fluent simulations are employed for testing the dynamic fluctuation of the electrothermal performance of SPES. It is found that the maximum differences between the inner roof interior side temperature (IRIST) and the outdoor ambient environment temperature (OAET) for Sref, Dsc, Dpe, and Dpvc are 33.3 °C, 32.9 °C, 28.1 °C, and 25.9 °C, respectively, in winter conditions in China cold zone. The optimized design parameters of SPES in Poso City, Indonesia, characterized by equatorial humid climatic conditions, recommended that the air interlayer be 0.2 meters thick and the exhaust air volume be 0.3 m3/s. Mechanical ventilation coupled with evaporative conditioners can further reduce indoor temperatures effectively. This research offers a novel solution to the problems of indoor thermal environments and power outages for post-disaster resettlement.

High-efficiency fertilizers suitable for mechanical spraying can improve the fertilizer application and utilization efficiency. In this study, two types of granular compound fertilizers suitable for unmanned air vehicle spraying were developed using urea, potassium chloride, humic acid, and an amino acid synergist according to the fertilization requirements of rice at the booting stage. The physical and chemical properties of the compound fertilizers were analyzed by Fourier transform infrared spectroscopy and scanning electron microscopy. The release kinetics of the fertilizer was studied via a soil column leaching experiment. The effect of fertilizer particles on unmanned air vehicle spraying uniformity was studied via an orthogonal simulation experiment. Results showed that the chemical interaction between compound-fertilizer raw materials formed complexes such as C-NH-C and -CO-NH-, which caused a change in fertilizer particle morphology. This led to chemical monolayer adsorption or internal fertilizer diffusion, which in turn delayed the fertilizer release by 5−10 d. A simulation bench test showed that the fertilizer particle hardness and roundness exceeded 20 N and 85%, respectively, while the particle size was in the range of 2.07−5.13 mm, which resulted in good unmanned air vehicle spraying uniformity with a lateral variation coefficient of less than 15%. Finally, the experimental field results demonstrated that the new compound fertilizers, when sprayed by an unmanned air vehicle, could improve the economic benefit by 916−2742 CNY ha−1 without reducing the nitrogen utilization rate and rice yield. The new compound fertilizers exhibit delayed release, good spraying uniformity, and improved economic benefit, rendering them suitable for large-scale promotion and application.

Abstract Evidence is mounting that chronic high‐fructose diets (HFrD) can lead to metabolic abnormalities and cause a variety of diseases. However, the underlying mechanism by which long‐term high fructose intake influencing systemic metabolism remains unclarified. This study, therefore, attempted to investigate the impact of a high‐fructose diet on metabolic profile. Four‐week‐old male C57BL/6 mice were fed with 15% fructose solution as their only source of water for 8 weeks. Afterward, gas chromatography–mass spectrometry (GC–MS) was employed to investigate the comprehensive metabolic profile of serum, muscle, liver, heart, white adipose, brain, and kidney tissues, and multivariate analyses including principal component analysis (PCA) and orthogonal partial least squared‐discriminant analysis (OPLS‐DA) were applied to screen for differential metabolite expression between the HFrD and control groups. Furthermore, the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (KEGG; http://www.kegg.jp) were employed to portray a detailed metabolic network. This study identified 62 metabolites related to HFrD and 10 disturbed metabolic pathways. The results indicated that high fructose intake mainly influenced amino acid metabolism and biosynthesis (glycine, serine, and threonine metabolism; aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and arginine biosynthesis pathways), glutathione metabolism, sphingolipid metabolism, and glyoxylate and dicarboxylate metabolism in serum, whereas these pathways were suppressed in the brain. Starch and sucrose metabolism in muscle was also disrupted. These results elucidate the effects of long‐term high fructose consumption on the metabolic profiles of various tissues and provide new insight for the identification of potential metabolic biomarkers and pathways disrupted by high fructose.

The development of rice cultivars with improved nitrogen use efficiency (NUE) is desirable for sustainable agriculture. Achieving this goal depends in part on understanding how rice responds to low soil nitrogen (N) and identifying causative genes underlying this trait. To identify quantitative trait loci (QTL) or genes associated with low N response, we conducted a genome-wide association study (GWAS) using a diverse panel of 230 rice accessions and performed a transcriptomic investigation of rice accessions with differential responses to low N stress at two N levels. We detected 411 GWAS-associated genes in 5 QTL and 2722 differentially expressed genes in response to low N, of which 24 were identified by both methods and ranked according to gene annotations, literature queries, gene expression, and genetic diversity analysis. The large-scale datasets obtained from this study reveal low N-responsive characteristics and provide insights towards understanding the regulatory mechanisms of N-deficiency tolerance in rice, and the candidate genes or QTL would be valuable resources for increasing rice NUE via molecular biotechnology.

Abstract Background Concurrent chemoradiotherapy is currently the standard of care for patients with locally advanced cervical cancer. However, even with the application of modern radiotherapy techniques, a considerable number of patients still develop distant metastases. PD-L1 inhibitors show good efficacy in cervical cancer. This single-arm phase II study aims to explore the efficacy and tolerability of combining PD-L1 inhibitor with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. Methods/design The primary endpoint of the study was the objective response rate assessed according to RECIST v1.1 criteria. The inclusion criteria were previously untreated patients aged 18–75 years with stage III-IVA (FIGO 2018 staging system) locally advanced cervical cancer. During concurrent chemoradiotherapy and consolidation chemotherapy, the enrolled patients will receive toripalimab (240 mg) every 3 weeks. After consolidation chemotherapy, the enrolled patients will be treated with toripalimab (240 mg) once every 6 weeks until the whole treatment cycle reaches 1 year. Intensity modulated radiotherapy was used for external beam radiation, and high-dose rate brachytherapy was delivered under image-guidance. Weekly DDP (40 mg/m2) was given concurrently with radiotherapy while 6 cycles of consolidated chemotherapy (paclitaxel plus DDP) were given after radiotherapy every three weeks. Secondary objectives included safety and tolerability, toxicity profile, progression-free survival, and overall survival. Discussion PD-L1 inhibitor has shown good efficacy in recurrent/metastatic cervical cancer. However, there is still a lack of evidence about its combination with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. The purpose of this study is to explore the efficacy and tolerance of this combination therapy, so as to lay the foundation for the future phase III randomized study. Trial registration clinicaltrials.gov NCT05084677 . Retrospectively registered on Octorber 07, 2021.

Abstract Background In addition to Mycoplasma haemocanis and Candidatus Mycoplasma haematoparvum, a few hemoplasma species that mainly infect other livestock have been detected in dogs. ‘Candidatus Mycoplasma haemobos’ (Ca. M. haemobos) has been found in a variety of animals in China. The present study was aimed to investigate the occurrence of ‘Ca. M. haemobos’ infections in dogs and ticks collected from the Henan province, China. Results Overall, 55 dog blood samples and 378 ticks on skins were collected from anemic and healthy dogs, and these samples were subjected to PCR, sequence analysis, and identification. The results showed that Haemaphysalis longicornis (266) and Rhipicephalus (Boophilus) microplus (112) were the only two parasitic ticks on dogs. Molecular detection revealed that 163 M. haemocanis, 88 ‘Ca. M. haemobos’ and 32 Anaplasma platys positive amplicons could be amplified from dogs, H. longicornis and R. (B.) microplus. In addition, co-infections (M. haemocanis + A. platys and ‘Ca. M. haemobos’+ A. platys) could be also detected. Conclusions To the best of our knowledge, this is the first molecular evidence of ‘Ca. M. haemobos’ natural infection in dogs and tick species identified as H. longicornis and R. (B.) microplus from China.

Abstract Pyroptosis, a type of inflammatory programmed cell death, is triggered by caspase cleavage of gasdermin family proteins. Based on accumulating evidence, pyroptosis is closely associated with tumour development, but the molecular mechanism underlying pyroptosis activation and the signalling pathways regulated by pyroptosis remain unclear. In this review, we first briefly introduce the definition, morphological characteristics, and activation pathways of pyroptosis and the effect of pyroptosis on anticancer immunity. Then we review recent progress concerning the complex role of pyroptosis in various tumours. Importantly, we summarise various FDA-approved chemotherapy drugs or natural compounds that exerted antitumor properties by inducing pyroptosis of cancer cells. Moreover, we also focus on the current application of nanotechnology-induced pyroptosis in tumour therapy. In addition, some unsolved problems and potential future research directions are also raised.

Healthy buildings are gaining crucial significance in construction and one health setting for promoting occupants’ health. However, the traditional design process for healthy buildings presents limitations with no specific guidelines. In contrast, the integrated design process (IDP) has proven to be effective in realizing high-performance buildings. However, the IDP shortfall of not having robust health strategy (HS) capability is a concern of interest. Thus, we posit further advancement of IDP in the context of incorporating HS in the prevailing IDP guidelines with a sequential iterative procedure. Moreover, a conceptual framework aimed at invigorating the implementation of HS in all IDP stages is proposed. The strategies within IDP that would reinforce achieving healthy building by addressing building process implementation are highlighted. The (IDP + HS) iterative framework herein advanced is intended to aid neophyte and experienced building professionals to reflect about the process of achieving healthy building while optimizing IDP for one’s health invigoration in construction industry.

Abstract Objective Discuss the application value of digital surgical technology in the reconstruction of head and neck defects after tumor resection and comprehensively evaluate time-economic-benefit cost. Methods A retrospective analysis of head and neck cancer patients who underwent reconstructive operations in head and neck surgery at Sichuan Cancer Hospital from January 2015 to January 2021 was performed. According to the inclusion and exclusion criteria, a total of 52 cases were included, including 25 cases using digital surgery (DS) and 27 cases using the conventional surgery (CS). The clinical-pathological characteristics, postoperative complications, functional aesthetic evaluation indexes, and time-cost-satisfaction evaluation indexes between the two groups were compared and statistically analyzed. Typical cases using digital surgery were shared. Results Outcomes between the two groups were comparable, and there was no significant difference in survival outcome and follow-up time between the two groups (P > 0.05). There was no significant difference between the two groups in the defect size, pathological type, other major clinicopathological features, or operation-related indicators (P > 0.05). The incidence of titanium plate displacement, deformation or exposure, and facial scar deformity in the DS group was significantly lower than that in the CS group (P < 0.05). However, there was no significant difference in other short-term or long-term complications (P > 0.05). The incidence of dysphagia and eating disorders in the DS group was significantly reduced (P < 0.05). The speech and social functions were improved, but not significantly (P > 0.05). Meanwhile, there was no significant difference in the evaluation index of facial aesthetics in this study (P > 0.05). Furthermore, the total operation time, preparation time of bone flap from the donor site, osteotomy time, and reconstruction time in the DS group were significantly lower than those in the traditional operation group (P < 0.05), but the shaping time and vascular anastomosis time of recipient area could not be shortened (P > 0.05). In addition, there was no significant difference in total hospitalization days between the DS group and CS group (P > 0.05), but the time of ICU treatment and postoperative intravenous nutrition support in the DS group were shorter than those in the CS group (P < 0.05). In particular, the preoperative doctor-patient communication of the DS group was more effective, and the treatment satisfaction of patients including their families was higher after operation (P < 0.05). Conclusion Comprehensive application of digital surgical technology (CAD, CAM, VR, MA, etc.) in the reconstruction of the head and neck after tumor resection is feasible in clinical practice, which can not only improve the accuracy of repair, decrease some surgical complications, better preserve and improve patient’s diet and speech function, and reduce the operation and hospitalization time, but also increase the treatment cost. Furthermore, it is conducive to doctor-patient communication and improves patient satisfaction.

Chenghua (CH) pig and Qingyu (QY) pig are typical Chinese native fatty breeds. CH pig is mainly distributed in Chengdu Plain, while QY pig is widely distributed throughout the mountain areas around the Sichuan Basin. There are significant differences in their phenotypic traits, including body image, growth performance, and meat quality. This study compared several meat quality traits of CH and QY pigs and conducted a genome-wide DNA methylation analysis using reduced representation bisulfite sequencing (RRBS). It was observed that the pH at 45 min (pH45min, P=5.22e–13), lightness at 45 min (L*45min, P=4.85e–5), and lightness at 24 h (L*24h, P=3.57e–5) of CH pigs were higher than those of QY pigs. We detected 10 699 differentially methylated cytosines (DMCs) and 2 760 differentially methylated genes (DMGs) associated with these DMCs. Functional analysis showed that these DMGs were mainly enriched in the AMPK signaling pathway, Type II diabetes mellitus, Insulin signaling pathway, mTOR signaling pathway, and Insulin resistance. Furthermore, 15 DMGs were associated with fat metabolism (ACACA, CAB39, CRADD, CRTC2, FASN, and GCK), muscle development (HK2, IKBKB, MTOR, PIK3CD, PPARGC1A, and RPTOR), or meat quality traits (PCK1, PRKAG2, and SLC2A4). The findings may help to understand further the epigenetic regulation mechanisms of meat quality traits in pigs and provide new basic data for the study of local pigs.

Abstract Background Sepsis is a life-threatening syndrome eliciting highly heterogeneous host responses. Current prognostic evaluation methods used in clinical practice are characterized by an inadequate effectiveness in predicting sepsis mortality. Rapid identification of patients with high mortality risk is urgently needed. The phenotyping of patients will assistant invaluably in tailoring treatments. Methods Machine learning and deep learning technology are used to characterize the patients’ phenotype and determine the sepsis severity. The database used in this study is MIMIC-III and MIMIC-IV (‘Medical information Mart for intensive care’) which is a large, public, and freely available database. The K-means clustering is used to classify the sepsis phenotype. Convolutional neural network (CNN) was used to predict the 28-day survival rate based on 35 blood test variables of the sepsis patients, whereas a double coefficient quadratic multivariate fitting function (DCQMFF) is utilized to predict the 28-day survival rate with only 11 features of sepsis patients. Results The patients were grouped into four clusters with a clear survival nomogram. The first cluster (C_1) was characterized by low white blood cell count, low neutrophil, and the highest lymphocyte proportion. C_2 obtained the lowest Sequential Organ Failure Assessment (SOFA) score and the highest survival rate. C_3 was characterized by significantly prolonged PTT, high SIC, and a higher proportion of patients using heparin than the patients in other clusters. The early mortality rate of patients in C_3 was high but with a better long-term survival rate than that in C_4. C_4 contained septic coagulation patients with the worst prognosis, characterized by slightly prolonged partial thromboplastin time (PTT), significantly prolonged prothrombin time (PT), and high septic coagulation disease score (SIC). The survival rate prediction accuracy of CNN and DCQMFF models reached 92% and 82%, respectively. The models were tested on an external dataset (MIMIC-IV) and achieved good performance. A DCQMFF-based application platform was established for fast prediction of the 28-day survival rate. Conclusion CNN and DCQMFF accurately predicted the sepsis patients’ survival, while K-means successfully identified the phenotype groups. The distinct phenotypes associated with survival, and significant features correlated with mortality were identified. The findings suggest that sepsis patients with abnormal coagulation had poor outcomes, abnormal coagulation increase mortality during sepsis. The anticoagulation effects of appropriate heparin sodium treatment may improve extensive micro thrombosis-caused organ failure.

Abstract Skin thickness is closely related to the appearance of human skin, such as sagging and wrinkling, which primarily depends on the level of collagen I synthesized by dermal fibroblasts (DFs). Small extracellular vesicles (SEVs), especially those derived from human DFs (HDFs), are crucial orchestrators in shaping physiological and pathological development of skin. However, the limited supply of human skin prevents the production of a large amount of HDFs-SEVs, and pig skin is used as a model of human skin. In this study, SEVs derived from DFs of Chenghua pigs (CH-SEVs), considered to have superior skin thickness, and Large White pigs (LW-SEVs) were collected to compare their effects on DFs and skin tissue. Our results showed that, compared with LW-SEVs, CH-SEVs more effectively promoted fibroblast proliferation, migration, collagen synthesis and contraction; in addition, in mouse model injected with both SEVs, compared with LW-SEVs, CH-SEVs increased the skin thickness and collagen I content more effectively. Some differentially expressed miRNAs and proteins were found between CH-SEVs and LW-SEVs by small RNA-seq and LC–MS/MS analysis. Interestingly, we identified that CH-SEVs were enriched in miRNA-218 and ITGBL1 protein, which played important roles in promoting fibroblast activity via activation of the downstream TGFβ1-SMAD2/3 pathway in vitro. Furthermore, overexpression of miRNA-218 and ITGBL1 protein increased the thickness and collagen I content of mouse skin in vivo. These results indicate that CH-SEVs can effectively stimulate fibroblast activity and promote skin development and thus have the potential to protect against and repair skin damage. Graphical Abstract

BackgroundAging-related cognitive decline is associated with brain structural changes and synaptic loss. However, the molecular mechanisms of cognitive decline during normal aging remain elusive.ResultsUsing the GTEx transcriptomic data from 13 brain regions, we identified aging-associated molecular alterations and cell-type compositions in males and females. We further constructed gene co-expression networks and identified aging-associated modules and key regulators shared by both sexes or specific to males or females. A few brain regions such as the hippocampus and the hypothalamus show specific vulnerability in males, while the cerebellar hemisphere and the anterior cingulate cortex regions manifest greater vulnerability in females than in males. Immune response genes are positively correlated with age, whereas those involved in neurogenesis are negatively correlated with age. Aging-associated genes identified in the hippocampus and the frontal cortex are significantly enriched for gene signatures implicated in Alzheimer’s disease (AD) pathogenesis. In the hippocampus, a male-specific co-expression module is driven by key synaptic signaling regulators including VSNL1, INA, CHN1 and KCNH1; while in the cortex, a female-specific module is associated with neuron projection morphogenesis, which is driven by key regulators including SRPK2, REPS2 and FXYD1. In the cerebellar hemisphere, a myelination-associated module shared by males and females is driven by key regulators such as MOG, ENPP2, MYRF, ANLN, MAG and PLP1, which have been implicated in the development of AD and other neurodegenerative diseases.ConclusionsThis integrative network biology study systematically identifies molecular signatures and networks underlying brain regional vulnerability to aging in males and females. The findings pave the way for understanding the molecular mechanisms of gender differences in developing neurodegenerative diseases such as AD.

BackgroundThe evaluation of liver fibrosis is essential in the management of patients with autoimmune hepatitis (AIH). We aimed to establish and validate an easy-to-use nomogram to identify AIH patients with advanced liver fibrosis.MethodsAIH patients who underwent liver biopsies were included and randomly divided into a training set and a validation set. The least absolute shrinkage and selection operator (LASSO) regression was used to select independent predictors of advanced liver fibrosis from the training set, which were utilized to establish a nomogram. The performance of the nomogram was evaluated using the receiver characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).ResultsThe median age of 235 patients with AIH was 54 years old, with 83.0% of them being female. Six independent factors associated with advanced fibrosis, including sex, age, red cell distribution width, platelets, alkaline phosphatase, and prothrombin time, were combined to construct a predictive AIH fibrosis (AIHF)-nomogram. The AIHF-nomogram showed good agreement with real observations in the training and validation sets, according to the calibration curve. The AIHF-nomogram performed significantly better than the fibrosis-4 and aminotransferase-to-platelet ratio scores in the training and validation sets, with an area under the ROCs for predicting advanced fibrosis of 0.804 in the training set and 0.781 in the validation set. DCA indicated that the AIHFI-nomogram was clinically useful. The nomogram will be available at http://ndth-zzy.shinyapps.io/AIHF-nomogram/as a web-based calculator.ConclusionsThe novel, easy-to-use web-based AIHF-nomogram model provides an insightful and applicable tool to identify AIH patients with advanced liver fibrosis.

IntroductionHypoxia-induced neuronal damage is the primary cause of cognitive impairment induced by high-altitude exposure. Microglia play a crucial regulatory role in the central nervous system (CNS) homeostasis and synaptic plasticity. M1-type polarized microglia are suspected to be responsible for CNS injury under hypoxic conditions, but the exact molecular mechanism is still unelucidated.MethodsCX3CR1 knock out and wide type mice were exposed to a simulated plateau at 7000 m for 48 h to construct the model of hypobaric hypoxia-induced memory impairment. The memory impairment of mice was assessed by Morris water maze. The dendritic spine density in the hippocampus was examined by Golgi staining. The synapses in the CA1 region and the number of neurons in the DG region were examined by immunofluorescence staining. The synapses in microglia activation and phagocytosis were examined by immunofluorescence. The levels of CX3CL1/CX3CR1 and their downstream proteins were detected. CX3CR1 knockout primary microglia were treated with CX3CL1 combined with 1% O2. The levels of proteins related to microglial polarization, the uptake of synaptosome and phagocytotic ability of microglia were detected.ResultsIn this study, mice exposed to a simulated 7000 m altitude for 48 h developed significant amnesia for recent memories, but no significant change in their anxiety levels was observed. Hypobaric hypoxia exposure (7000 m altitude above sea level for 48 h) resulted in synapse loss in the CA1 region of the hippocampus, but no significant changes occurred in the total number of neurons. Meanwhile, microglia activation, increased phagocytosis of synapses by microglia, and CX3CL1/CX3CR1 signal activation were observed under hypobaric hypoxic exposure. Further, we found that after hypobaric hypoxia exposure, CX3CR1-deficient mice showed less amnesia, less synaptic loss in the CA1 region, and less increase in M1 microglia, compared to their wildtype siblings. CX3CR1-deficient microglia did not exhibit M1-type polarization in response to either hypoxia or CX3CL1 induction. Both hypoxia and CX3CL1 induced the phagocytosis of synapses by microglia through the upregulation of microglial phagocytosis.DiscussionThe current study demonstrates that CX3CL1/CX3CR1 signal mediates the M1-type polarization of microglia under high-altitude exposure and upregulates microglial phagocytosis, which increases the phagocytosis of synapses in the CA1 region of the hippocampus, causing synaptic loss and inducing forgetting.