Sperm gain fertilization ability and forward movement characteristics during epididymal transport. Sperm maturation is inseparable from the processing of the epididymis. Compared with other reproductive organs, relatively little is known about the epididymis. However, with the development of molecular biology and the improvement of single-cell sequence technology, we gradually realized that we should re-examine the importance of the epididymis for sperm mat-uration and for the entire male reproductive system. Recently, epididymis related reports have tended to be more regionalized and more refined. We can understand cell distribution and gene expression from the perspective of a single cell. It has been reported that different regions of the epididymis have different functions and different cell compositions, which may be determined by gene expression. Here, we comprehensively reviewed the epididymal studies. From the ana-tomical structure of the epididymis to the division of its regions, we focused on the cell compo-sition and region-specific genes differentially expressed in the epididymis. The gene expression of the epididymis extends to a series of biological processes of sperm in the epididymal cavity, and the serious effects of epididymal diseases on reproduction are discussed. Therefore, the importance of the epididymis in male reproduction is emphasized. With the maturity of single-cell spatial transcriptomics, it is hoped that the technology can be applied to epididymal research and bring about the spatiotemporal landscape of the epididymis at the single-cell level.

The first years of an infant’s life represent a sensitive period for neurodevelopment and see the emergence of nascent forms of executive function (EF), which are required to support complex cognition. Few tests exist for measuring EF during infancy, and the available tests require painstaking manual coding of infant behaviour. In modern clinical and research practice, human coders collect data on EF performance by manually labelling video recordings of infant behaviour during toy or social interaction. Besides being extremely time-consuming, video annotation is known to be rater-dependent and subjective. To address these issues, starting from existing cognitive flexibility research protocols, we developed instrumented toys as a new task instrumentation and data collection tool suitable for infant use. A commercially available device comprising a Barometer and Inertial Measurement Unit (IMU) embedded in a 3D-printed lattice structure was used to detect when and how the infant interacts with the toy. The data collected using the instrumented toys provides a rich dataset describing the sequence of toy interaction and individual toy interaction patterns, from which EF-relevant aspects of infant cognition may be inferred. Such a tool potentially provides an objective, reliable, and scalable method of collecting early developmental data in socially interactive contexts.

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Magnesium and its alloys are not normally used as bio-resorbable temporary implants due to their high and uncontrolled degradation rate in physiological liquid environment. The improvement of corrosion resistance to simulated body fluids (SBF) of a Magnesium alloy (AZ31) coated with poly-β-hydroxybutyrate (PHB) was investigated. Scanning electron microscopy, Fourier transform infrared spectrometer, and contact angle measurements were used to characterize surface morphology, material composition and wettability, respectively. pH modification of the SBF corroding medium, mass of Mg2+ ions released, and weight loss of the samples exposed to the SBF solution, and electrochemical experiment were used to describe the corrosion process and its kinetics. Materials biocompatibility was described by evaluating the effect of corrosion by products collected in the SBF equilibrating solution on hemolysis ratio, cytotoxicity, Nitric Oxide (NO), and total antioxidant capacity (T-AOC). The results showed that the PHB coating can diffusively control the degradation rate of Magnesium alloy improving its biocompatibility: hemolysis rate of materials was lower than 5%, while in vitro Human Umbilical Vein Endothelial Cells（HUVECs) compatibility experiments showed that PHB coated Mg alloy promoted cell proliferation and had no effect on the NO content, the T-AOC was enhanced compared with the normal group and bare AZ31 alloy. PHB coated AZ31 Magnesium alloy extraction fluids have a less toxic behavior due to the lower concentration of corrosion by-products deriving from the diffusion control exerted by the PHB coating films both from metal surface to the solution and vice versa. These findings provide more reference value for the selection of such system as tunable bioresorbable prosthetic materials

Background: Genome-wide association studies have identified the chromosome 9p21 locus as one of the most important genetic risk factors for cardiovascular disease. However, the mechanism by which this locus promotes disease remains unclear due to difficulty identifying the causal genes and lack of a suitable animal model. Methods and Results: A total of 180 coronary artery autopsy specimens were analyzed histopathologically. The genotype of 9p21 (rs1333049) was not associated with any coronary risk factors nor the vulnerable plaque phenotype, but carriers of 9p21 risk allele did demonstrate more lesional calcification. To extend these studies into an animal model, mice with a targeted deletion of the orthologous 70-kb non-coding interval on chromosome 4 (chr4^D70kb/D70kb) were bred onto ApoE^-/- and fed with high fat diet. Targeted deletion of the 9p21 risk interval increased susceptibility to atherosclerotic plaque progression, but did not affect plaque rupture in the tandem stenosis model. Coronary risk factors such as body weight, blood pressure, lipid, and glucose levels did not differ between genotypes. Von Kossa staining revealed that chr4^D70kb/D70kb, ApoE^-/- developed more calcification in the plaque compared with chr4^+/+, ApoE^-/- mice, and that this this change was accompanied by increased aortic mRNA expression of Runx2, a key osteogenic transcription factor. Primarily cultured smooth muscle cells from chr4^D70kb/D70kb were hyperproliferative, and showed a calcification-prone phenotype after exposure to high-phosphate medium. Treatment with Palbociclib, a selective inhibitor of cyclin-dependent kinase 4/6, reduced mRNA expression of osteogenic genes in smooth muscle cells. Conclusion: Results from human and mouse studies indicate that the 9p21 non coding risk interval is associated with larger atherosclerotic plaque burden, but not with plaque rupture. 9p21 may promote lesion expansion by inducing the proliferation of de-differentiated and osteogenic smooth muscle cells.

Cotton is one of the most important economic crops in the world, whereas insect attacks is a prime cause of its losses on yield and quality. Despite it is important, little is known about the mechanism of cotton response to insect. In this study, we simulated insect feeding by applying insect oral secretions (OS) to wounds, and combined transcriptome and metabolome analysis to comprehensively investigate how OS from two major pest species (Helicoverpa armigera and Spodoptera litura) affect cotton defense responses. Obvious differences were observed that 12,668 and 13,379 genes differently expressed respectively in cotton after being treated with different OS when compared with wounding along. Upon the addition of OS, JA-signaling pathway were rapidly and strongly induced, however SA-biosynthesis related gens were significantly down-regulated. By constructing the co-expression gene network, we identified a hub gene which encoding a leucine-rich repeat receptor kinase may play important role in recognition and signal transduction at early stage. We also found that OS from different insect species altered abundance of flavonoid related compound with different patterns. Interestingly, Gossypol which is a well-known anti-insect compound was kept a relative low content after OS application relative to wounding which implied the existence of the suppression effects of OS to cotton defense response. This study illustrated the transcriptional and metabolic changes of cotton in responding to OS from two chewing insect species, identified potential key gene during the interaction process and finds the evidence for OS’s inhibition effects on cotton defense response.

Background: Oral squamous cell carcinoma (OSCC), with poor prognosis and high mortality rates, is one of the most diagnosed head and neck cancers. Cancer stem cells (CSCs) - epithelial-to-mesenchymal transition (EMT) loop is increasingly implicated in the therapy-resistance, relapse, and metastasis of OSCC patients. Accumulating evidence indicate that aberrantly expressed CD47 is associated with cell-death evasion, invasion and cancer metastasis; however, the role of CD47 in the modulation of CSCs-like phenotypes, including therapy-resistance and metastasis, with its underlying mechanism in OSCC remains largely underexplored. Methods: This study investigated the CSCs- modulating potential of CD47 in OSCC cell lines SAS, TW2.6, HSC-3 and FaDu using bioinformatics approach, immunoblotting, immunofluorescence staining, migration, invasion, colony and orosphere formation, as well as radiosensitivity assays. Results: We demonstrated that the characteristic ectopic expression of CD47 in OSCC patients was associated with ~ 20% 2-year survival disadvantage (p = 0.01) and positively correlated with the expression of pluripotency factors; while shRNA silencing of CD47 significantly suppressed cell viability and markedly inhibited orosphere formation, resulting in smaller and fewer orospheres, and downregulated CD133, SOX2, OCT4 and c-Myc mRNA and protein expression levels. We also showed that CD47 downregulation attenuates EMT, migration and clonogenicity of OSCC cells, with associated E-cadherin upregulation and suppression of Vimentin, Slug, Snail, and N-cadherin expression. Conclusion: Of therapeutic relevance, combined with radiotherapy, CD47 knockdown enhanced the anti-OSCC effect of radiotherapy. Thus, we demonstrate the therapeutic feasibility of a CD47-mediated anti-CSCs strategy, and suggest a role for CD47 suppression in potentiating the therapeutic efficacy of radiation therapy in OSCC patients.

Both ricin and R. communis agglutinin (RCA120), belonging to the type II ribosome-inactivating proteins (RIPs-Ⅱ), are derived from the seeds of castor bean plant. They share very similar amino acid sequences, but ricin is much more toxic than RCA120. It is urgently necessary to distinguish ricin and RCA120 in response to public safety. Currently, mass spectrometric assays are well established for unambiguous identification of ricin by accurate analysis of differentiated amino acid residues after trypsin digestion. However, diagnostic peptides are relatively limited for unambiguous identification of trace ricin, especially in complex matrices. Here, we demonstrate a digestion strategy of multiple proteinases to produce novel peptide markers for unambiguous identification of ricin. LC-HRMS was used to verified the resulting peptides, among which only the peptides with uniqueness and good MS response were selected as peptide markers. Seven novel peptide markers were obtained from tandem digestion of trypsin and endoproteinase Glu-C in PBS buffer. From the chymotrypsin digestion under reduction and non-reduction conditions, eight and seven novel peptides were selected respectively. Using pepsin under pH 1~2 and proteinase K digestion, 6 and 5 peptides were selected as novel peptide markers. In conclusion, the obtained novel peptides from the established digestion methods can be recommended for the unambiguous identification of ricin during the investigation of illegal use of the toxin.

As a universal pathogen leading to neonatal defects and transplant failure, Human cytomegalovirus (HCMV) has strict species specificity that the inability to using this virus in animals has hampered its pathogenesis study. However, the mechanism of cross-species barrier remains elusive that no non-human cell model has been established to fill this knowledge gap. We observed that primary dermis fibroblasts (TSDF) isolated from the Chinese tree shrew (Tupaia belangeri chinensis), a small laboratory animal with close affinity to primates, were permissive to HCMV replication. In TSDF infected with GFP-expressing HCMV, the green fluorescence and cytopathic effect were observed and the expression of 3 kinetic genes and replication of viral genome were detected. The cell-free viruses produced in TSDF reached 103 pfu/mL at 96 hpi, which were 10-fold lower than in primary human foreskin fibroblasts. Our results demonstrated that TSDF supported low level of lytic replication of HCMV. The TSDF model provides a useful platform for the mechanism study of species barrier of HCMV.

Developing and utilising of underground space is an vital direction for urban growth. Underground commercial streets, as a significant component of underground space accommodating extensive human social activities, and consequently necessitate the creation of human-scale spaces. In the evolution of urban design development towards greater refinement, applying architectural theories and excessively subjective designs has resulted in a deficiency of human-centered design and a disordered spatial environment. This study merges environmental psychology and architectural theory to determine the appropriate length of spatial scale. Two experiments focusing on spatial perception evaluation were conducted using a virtual experimental platform that featured varying dimensions of spatial scale combinations. These quantified combinations were correlated with perception evaluation, and regression analysis was employed to identify appropriate scale ranges, which were superimposed on the range of length selection. Finally, the optimal length and scale combination for underground commercial street spaces were established, providing a reference for the human-centered design of these environments.

Accurate measurement of water vapor is essential for researches and applications of meteorology, climatology and hydrology. Based on the BeiDou PPP-B2b service, real-time precipitable water vapor (PWV) is retrieved with the precise point positioning (PPP) software. The experiment was conducted in Beijing in January, 2023. Three solutions are designed with PPP using the BeiDou system only, the GPS system only and the BeiDou-GPS combined solution. Real-time PWVs for the 3 solutions are validated with the ERA5 reanalysis data. Between PWVs from single BeiDou and ERA, there are a bias of 0.7 mm and a RMSE of 1.8 mm. While for the GPS case, the bias is 0.73 mm and RMSE is 1.97 mm. The biases are less than 1 mm and RMSEs are less than 2mm. Both the BeiDou and the GPS processing performs very well. But little improvement is found for the BeiDou-GPS combined solution, comparing with the BeiDou system only and the GPS system only solution. This may be due to the poor handling of two different kinds of errors for the GPS and the BeiDou systems in our PPP software. A better PWV estimation with the two systems is to estimate PWV with single system at first step, and then to obtain the optimization by Bayesian model averaging.

Hydroxamic acid (HA) derivates displayed antibacterial and antifungal activities. HA with various numbers of carbon atoms (C2, C6, C8, C10, C12 and C17), complexed to different metal ions Fe(II/III), Ni(II), Cu(II) and Zn(II) were evaluated for their antimycobacterial activities and their anti-biofilm activities. Some derivates, among others HA12Fe2, inhibited the development of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium marinum biofilms and could even attack pre-formed Pseudomonas aeruginosa biofilm. Proteomic profiles showed that the potential targets of HA10FeCl were mainly related to mycobacteria stress adaptation, involving cell wall lipid biosynthesis, drug resistance and tolerance, siderophore metabolism. This study provides new insights regarding the antimycobacterial activities of the HA and their complexes, especially about their potential antibiofilm activities.

Background: The major histocompatibility complex (MHC) plays a key role in the adaptive immune response to pathogens due to its extraordinary polymorphism. However, the spatial patterns of MHC variation in the striped hamster remain unclear, particularly regarding the relative contribution of balancing selection in shaping MHC population and diversity compared to neutral forces. Methods: In this study, we investigated the immunogenic variation of the striped hamster in four wild populations in Inner Mongolia, which experience heterogeneous parasitic stress. Our goal was to identify local adaptation by comparing the genetic structure at MHC with that at seven microsatellite loci, taking into account neutral processes. Results: We observed significant variation in parasite pressure among sites, with parasite burden showing a correlation with temperature and precipitation. Molecular analysis revealed a similar co-structure between MHC and microsatellite loci. We observed lower genetic differentiation at MHC loci compared to microsatellite loci, and no correlation was found between the two. Conclusions: Overall, these results suggest a complex interplay between neutral evolutionary forces and balancing selection in shaping the spatial patterns of MHC variation. Local adaptation was not detected at a small scale but may be applicable at a larger scale.

Nitrogen (N) strongly affects plant growth and metabolism. For shikonin biosynthesis, although the ammonium toxicity phenomenon has been reported, the effects of nitrogen on the shikonin synthesis remains obscure. In this study, we carried out four different concentrations of NH4+ treatments on Arnebia euchroma hairy roots (AEHR) to clarify the influence of NH4+ on the growth and shikonin accumulation in A. euchroma and the possible mechanism. The results showed that compared with the 0% NH4+ treatment (only nitrate as nitrogen source), 10% NH4+ treatment increased the fresh weight and the dry weight of AEHR, and promoted the synthesis of shikonins; 20% NH4+ treatment started to show the inhibition effects on growth and shikonin accumulation of AEHR and 30% NH4+ treatment exhibited the strongest inhibition effects. With increased percentage of NH4+, AEHRs became shorter and thicker with more branches. To further elucidate the mechanism, we analyzed the time-course of nitrogen assimilation, gene expression level of key enzymes involved in the shikonin biosynthesis pathway, and contents of various endogenous hormones under NH4+ toxicity condition. Results indicated that auxin and cytokinin might regulate the growth and architecture of AEHR under NH4+ toxicity, and jasmonate level was reduced along with the inhibition of shikonin biosynthesis. This first comprehensive investigation into the effects of ammonium/nitrate ratio on shikonin biosynthesis not only provided valuable data for optimizing the in vitro culture and shikonin production in A. euchroma, but also suggested potential fertilizer strategies for its cultivation.

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Here, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2-3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal com-partments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular Doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diag-nosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Single nanowires (NWs) are of great importance for optoelectronic applications, especially solar cells serving as powering nanoscale devices. However, weak off-resonant absorption can limit its light-harvesting capability. Here, we propose a single NW coated with the graded-index dual shells (DSNW). We demonstrate that with appropriate thickness and refractive index of the inner shell, the DSNW exhibits significantly enhanced light trapping compared with the bare NW (BNW), and the NW only coated with the outer shell (OSNW) and the inner shell (ISNW), which can be attributed to the optimal off-resonant absorption mode profiles due to the improved coupling between the reemitted light of the transition modes of the leak mode resonances of the Si core and the nanofocusing light from the dual shells with the graded refractive index. We found that the light absorption can be engineered via tuning the thickness and the refractive index of the inner shell, the photocurrent density is significantly enhanced by 134% (56%, 12%) in comparison with that of the BNW (OSNW, ISNW). This work advances our understanding of how to improve off-resonant absorption by applying graded dual-shell design and provides a new choice for designing high-efficiency single NW photovoltaic devices.

A focal plane array (FPA) detector was used for hyperspectral imaging in the infrared (IR) spectral region using thermal and synchrotron light sources. FPA Fourier-transform IR (FTIR) imaging microspectroscopy will be able to monitor real time changes at specific absorption bands when combined with high brightness synchrotron source. In this study, several types of samples with unique structural motifs were selected and used for assessing the capability of the FPA-FTIR imaging technique. It was shown that the time required for polariscopy at IR wavelengths can be substantially reduced by the FPA-FTIR imaging approach. By using natural and laser fabricated polymers with sub-wavelength features, alignment of absorbing molecular dipoles was revealed as well as higher order patterns (laser fabricated structures). Micro-spectroscopy of absorber orientation reveals alignment patterns even when they are not spatially resolved.

Thyroid nodules (TNs) are common thyroid lesions in older population. Few studies focused on the prevalence of TNs and its relationship to lifestyle characteristics and dietary habits in centenarians. The current study aimed to determine the prevalence of TNs in Chinese centenarians using high-resolution ultrasound equipment and investigate its relationship to lifestyles and dietary habits. The current study was part of China Hainan Centenarian Cohort Study (CHCCS) which conducted in Hainan, an iodine sufficient region in China. A total of 874 permanent residents aged 100 years or older (mean age, 102.8 ± 2.8 years) without any missing data were included in the analysis. Among the participants, 649 of them were detected at least one thyroid nodule under the ultrasound examinations. The overall prevalence rate of TNs was 74.3%. The prevalence of TNs was higher in participants who were females, hypertension, diabetes, and underweight than their counterparts. Multivariate logistic regression analyses showed that being female, hypertension, diabetes, betel quid consumption, red meat consumption were independent risk factors, while being underweight, and nut consumption were independent protective factors for TNs. Our findings indicate that the presence of thyroid nodules was highly prevalent in Chinese centenarians, particularly in females. In addition to gender, hypertension, diabetes, and underweight, the presence of TNs was independently associated with betel quid, red meat, and nut consumptions. Further prospective studies are warranted to verify these associations in population from different age strata, races, cultures, and iodine backgrounds.

Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. Aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. The therapeutical peptide and proteins are remarkable therapeutic agents in today’s world that allows the treatment of severe, chronic and life‐threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis in an easy manner. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. The primary objective of this article is to review current issues concerned with the therapeutics peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. The article will also review literature concerning classification of hydrogels on different basis, polymers used, release mechanisms their physical and chemical characteristics and diverse applications.

A novel binary toxin-positive non-027, non-078 Clostridium difficile strain designated LC693 whose sequence type was ST201 was isolated from the fecal sample of a patient with severe diarrhea in China. To understand the pathogenesis basis of C. difficile ST201, this recently recovered isolate LC693 was then chosen for whole genome sequencing. The project finally generated an estimated genome size of approximately 4.07 Mbp. The genome sequence was then analyzed together with the other two ST201 strains VL-0104 and VL-0391 and compared to the epidemic 027/ST1 and 078/ST11 strains. Phylogenetic analysis demonstrated that the ST201 strains belonged to clade 3. Genome size of the three ST201 strains ranged from 4.07 Mb~4.16 Mb, with an average GC content between 28.5%~28.9%. The ST201 genomes contained more than 40 antibiotic resistance genes and 15 of them were predicted to be associated with vancomycin-resistance, suggesting that they may have a strong antibiotic resistance. The ST201 strains contained a typical clade 3 specific PaLoc with a Tn6218 element inserted, and those genes harbored on their PaLoc that participated in the toxin expression and regulation were highly homologues to the epidemic 027 and 078 strains, with the exception of tcdC. A truncated TcdC was found in the ST201 strains, which is suggestive to have a contribution to the toxin production of the ST201 strains. In addition, the ST201 strains contained intact binary toxin coding and regulation genes, which is also proposed to contribute to the virulence. Genome comparison of the ST201 strains with the epidemic 027 and 078 strain identified 641 genes specific for the C. difficile ST201, and a number of them were predicted as fitness and virulence associated genes. The identification of those genes also contributes to the pathogenesis of the ST201 strain. To our knowledge, this is the first study that the genome sequence of C. difficile ST201 was discussed in detail, and the present study would have a contribution to understanding the pathogenesis basis of C. difficile ST201.

Recently, design of electric scooters (ESs) has commonly adopted brushless DC motors (BLDCMs) in place of brushed DC motors. This invention develops a new anti-lock braking system (ABS), based on a slip-ratio estimator, for ES utilizing the braking force generated by the BLDCM when electrical energy releases to the load yielding an analogous effect of ABS control in gas-engine vehicles. Comparing to mechanical ABS, the design possesses the advantages of rapid torque responses due to fast actuating response. The electrical ABS is realized by associating with kinematic and Short-circuit braking. A current controller is used to adjust the braking force, while the sliding mode control strategy is adopted to regulate the slip ratio for best road adhesion while braking. Real-world experiments have been conducted for functional and performance verification.

Objective To investigate the functional and biological significance of telomere-related active genes in cholangiocarcinoma (CCA) using single-cell sequencing and cell communication analysis. Methods First, we identified and annotated different cell types in CCA samples using single-cell sequencing data. Pseudotime analysis revealed the transcriptional status and differentiation process of CCA cells. We then explored interactions between CCA cells and their regulatory pathways through cell communication analysis. 47 key genes related to telomere activity were identified, and GO and KEGG pathway enrichment analysis was performed. Additionally, we constructed a prognostic model and verified the model's predictive efficacy. Finally, we identified genes associated with drug sensitivity in CCA patients and identified pathways associated with CCA prognosis through tumor TMB analysis. Results We identified 452 active telomere-associated cells. Then, we assessed telomere associated gene activity, obtaining 47 differentially expressed telomere genes by intersecting with CCA differentially expressed genes. Major up-regulated signaling pathways, including MIF-(CD74+CXCR4) and HLA-A-CD8A, were identified through pseudotime analysis. Three telomere-associated prognostic genes were identified using LASSO analysis, and prognostic-related models were built. In addition, PBRM1 mutation load was found to be highest in the high-risk group, making it a potential diagnostic target. Finally, drug sensitivity analysis revealed higher sensitivity to certain therapeutic drugs in the high-risk group, providing guidance for tailored CCA treatment. Conclusion The MIF-(CD74+CXCR4) and HLA-A-CD8A signaling pathways appear to be major pathways for CCA cell proliferation. Prognostic models based on telomere-associated genes show promise for application, indicating the biological and clinical significance of telomere activity genes in CCA.

Pea shoots is a popular vegetable in certain regions of the world due to their unique taste and abundance of health-promoting phytochemicals. The perishable nature and susceptibility of root rot of pea shoots necessitate a new soilless production system located close to the market. This study compared the growth of pea shoots using various cultivation methods in LED plant factory. The results showed that early topping (4 days after transplanting, ET) promoted early harvest compared to later topping (20 days after transplanting, LT) and increased the number of harvested shoots by extending the harvest time to 2.8 times, ultimately resulting in a substantial yield improvement. Moreover, the yield of ET with lower planting density (72 plants m-2, ET-LD) was 8.7% higher than ET with higher planting density (126 plants m-2, ET-HD). Particularly, the average fresh weight of individual pea shoots under ET-LD exceeded that of ET-HD by 48.9%. It is advisable to consider adopting ET-LD for the cultivation of pea shoots in LED plant factory. Based on ET-LD, the yield, nutritional quality, and light use efficiency of pea shoots were further explored at different stages under three levels of light intensity (50, 100, 150 μmol m-2 s-1). Contrasted against the light intensity of 50 μmol m-2 s-1, the average fresh weight per pea shoots, number of harvested, and total fresh yield under light intensity of 150 μmol m-2 s-1 treatment increased by 60.2%, 62.8%, and 165.1%, respectively. Meanwhile, the fresh weight per pea shoots, photosynthetic capacity, soluble sugar and vitamin C levels in leaves, as well as light use efficiency and photon yield, initially increased and then decreased with the extension of the planting period. Among these, soluble sugar, LUE, and PY started to decrease after reaching the maximum value at 60-70 days after transplanting. In conclusion, light intensity of 150 μmol m-2 s-1 with a photoperiod of 16 h d-1 using LEDs, combined with early topping within a planting period of 60-70 days, proves to be suitable for the hydroponic production of pea shoots in LED plant factory.

Traditional lithium-ion batteries cannot meet the high flexibility and bendability requirements of modern flexible electronic devices due to the limitations of their electrode materials. Therefore, the development of high-performance flexible energy storage devices is of great significance for promoting flexible electronics. In recent years, one-dimensional flexible fiber lithium-ion batteries have been rapidly developed due to the advantages of high flexibility and bendability. However, it is still a big challenge to realize 1D flexible fiber lithium-ion batteries with excellent electro-chemical properties and good mechanical performance. In this work, a reduced graphene ox-ide-based printing ink is proposed to fabricate flexible Li4Ti5O12/graphene fiber electrodes through a 3D printing assembly strategy. It is noteworthy that the green reducing agent vitamin C was used to reduce graphene oxide in one step, which improved the conductivity of the fiber elec-trode. Furthermore, a 3D conductive network is constructed inside the fiber electrodes due to the high specific surface area of reduced graphene oxide, which enhances the electronic conductivity and ion mobility. The fiber electrode not only has good mechanical performance, but also has ex-cellent electrochemical properties. Equally important, the method is simple and efficient, and the working environment is flexible. It can precisely control the shape, size and structure of the one-dimensional fiber flexible electrode, which is of great significance for the development of fu-ture flexible electronic devices.

Cardiac complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been well-identified since the beginning of the current coronavirus disease 2019 (COVID-19) pandemic. Such conditions can occur of various etiologies, such as respiratory failure and hypoxemia, direct cardiac tissue damage due to viral replication, indirect myocarditis as systemic inflammation, and the interaction of different medications. Recently, with the start of the COVID-19 vaccination programs, COVID-19 vaccine-associated cardiac adverse events (AEs) have emerged and are increasingly being reported. Although these AEs are usually mild and self-limited, they can sometimes cause severe, catastrophic outcomes. This review compares the pathophysiology, diagnosis, and treatment of the de novo SARS-CoV-2 infection-related and COVID-19 vaccine-related myocarditis and pericarditis.

Plant height is significantly correlated with grain traits, which is a component of wheat yield. The purpose of this study is to investigate the main QTLs that control plant height and grain-related traits in multiple environments. In this study, we constructed a high-density genetic linkage map using the Wheat50K SNP Array to map quantitative trait loci (QTLs) for these traits in 198 recombinant inbred lines (RILs). The two ends of the chromosome were identified as re-combination-rich areas in all chromosomes except chromosome 1B. The middle area of the chro-mosomes was identified as the recombination-barren area. Both the genetic map and the physical map showed a significant correlation when p=0.001, with a correlation coefficient between 0.63 and 0.99. However, there was almost no recombination between 1RS and 1BS. In terms of plant height, 1RS contributed to the reduction of plant height by 3.43cm. In terms of grain length, 1RS contributed to the elongation of grain by 0.11mm. A total of 43 QTLs were identified, including 8 QTLs for Plant height(PH), 11 QTLs thousand grain weight(TGW), 15 QTLs for grain length(GL),and 9 QTLs for grain width(GW), which explained 1.36%–33.08% of the phenotypic variation. Seven were environment-stable QTLs, including two loci Qph.nwafu-4B and Qph.nwafu-4D that determined plant height. The explanation rates of phenotypic variation were 7.39%-12.26% and 20.11%-27.08%, respectively. One QTL, Qtgw.nwafu-4B, which influenced TGW, showed an explanation rate of 3.43%-6.85% for phenotypic variation, two co-segregating KASP markers were developed, the physical locations corresponding to KASP_AX-109316968 and KASP_AX-109519968 were 25.888344 MB and 25.847691 MB. Another QTL, Qgw.nwafu-4D, which determined grain width, had an explanation rate of 3.43%-6.85%. Three loci that affected the grain length were Qgl.nwafu-5A, Qgl.nwafu-5D.2 and Qgl.nwafu-6B, illustrating the explana-tion rates of phenotypic variation as 6.72%-9.59%, 5.62%-7.75%, and 6.68%-10.73%, respectively. Two QTL clusters were identified on chromosomes 4B and 4D.

Immune checkpoint inhibitors (ICI) have been widely used in melanoma, but to identify melanoma patients with survival benefit from ICI is still a big challenge. There is an urgent need for prognostic signatures improving the prediction of immunotherapy responses of cancer patients. We used data from EMBL-EBI database and analyzed RNA-seq information and clinical profiles in melanoma. Weighted gene co-expression network analysis (WGCNA) was used to identify the key module, then nonnegative matrix factorization (NMF) was conducted to cluster patients into two different cluster and compared them regarding overall survival (OS) and progression-free survival (PFS). Subsequently, the differentially expressed genes (DEGs) between different clusters were identified, and their function and pathway annotation were performed. 91 melanoma biopsies with complete survival information were included in our analyses and we first identified the key module (magenta) by WGCNA, then identified nine prognostic lncRNAs (ENSG00000258869, ENSG00000179840, ENSG00000206344, ENSG00000226777, ENSG00000205018, ENSG00000204261, ENSG00000163597, ENSG00000197536, and ENSG00000263069) signature that predicted for OS and PFS in patients treated with ICI by NMF. Finally, enrichment analysis showed that the functions of DEGs between two consensus clusters were mainly related to the immune process and treatment. In summary, the nine lncRNAs signature is a novel effective predictor for OS and PFS in melanoma patients treated with ICI.

Establishment of diagnostic methods with low detection limits plays a critical role in the maintenance of early diagnosis, prevention of serious neurological complications, and control of the spread of ZIKA. In this study, we established the micro-droplet digital polymerase chain reaction (ddPCR) and real-time fluorescent quantification PCR (qPCR) protocols for the detection of Zika virus based on the NS5 gene. For the Zika standard plasmid, the standard curve of R² was 0.999, and the amplification efficiency was 92.203%, as determined by qPCR. Both ddPCR and qPCR were positive for cell culture of Zika nucleic acid.The minimum detection limit of ddPCR is 1–2 times lower than qPCR. Moreover, all tests of Dengue virus (1–4 serotypes) were negative in cell culture. Overall, these results suggested than ddPCR may have a lower limit of detection than qPCR.

Tea (Camellia sinenesis) is a health beneficial beverage and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of hetero-polysaccharides bounded with proteins. There were tests showing that TPS had various bioactivities, such as antioxidant, antitumors, antihyperglycemia, anti-inflammation and improving immunity. However, inconsistent results concerning chemical composition and bioactivity of TPS were published in recent years. The advances in chemical composition and bioactivities of TPS were reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS were also discussed.

Nucleoside analogs are commonly used drugs for the treatment of cancer and viral infections. Nucleoside deoxyribosyltransferase (NDT) is one of the key enzymes required for the biosynthesis of deoxynucleotides. The feasibility of biochemical transformation processes is usually greatly dependent on the cost of biocatalysts. Therefore, immobilizing and reusing biocatalysts is an approach to be considered to bring biotransformations closer to industrial feasibility, since it not only allows enzymes to be reused but can also improve their stability under several reaction conditions. In this work, histidine tags have been successfully fused to a Nucleoside deoxyribosyltransferase from Lactobacillus reuteri (LrDNT), which has been produced in a bench-scale reactor using a facile araBAD promoter-based protein expression system in an industrial microorganism, the E. coli BL21(DE3) strain. The overexpressed LrNDT was bound to a nickel-chelating agarose affinity chromatography medium via a one-step purification and immobilization process with a 99% yield, retaining about 97% of its initial activity. The optimal conditions for the immobilized LrNDT maintain high enzyme activity within the range of 20-45°C and pH 6.0-7.5. Finally, the immobilized enzyme reactor (IMER) of LrNDT was applied for the continuous-flow biosynthesis of 2'-deoxyadenosine and retained 90% of its activity after 16 hours, providing a theoretical basis for the industrial production of nucleoside analogs.

A fluorescent probe, N'-((3-methyl-5-oxo-1-phenyl-4, 5-dihydro-1H-pyrazol-4-yl) methylene)-2-oxo-2H-chromene-3-carbohydrazide (MPMC), was synthesized and characterized. Characterizations of the synthetic MPMC were conducted by proton nuclear magnetic resonance (1HNMR) spectroscopy and carbon-13 nuclear magnetic resonance spectroscopy (13C NMR). The fluorescence emission behaviors of probe MPMC towards diverse metal ions were detected and the probe exhibited high sensitivity and selectivity towards Cu2+ over other metal ions via quenching of its fluorescence. Furthermore, the existence of other metal actions made no difference on the fluorescence intensity of the MPMC-Cu2+ system apparently, that is, MPMC displayed a good anti-interference ability. Job’s plot of MPMC and copper ions indicated the detection limit was 15.16 nM (R2=0.9612) for the assayed actions, with a stoichiometric ratio of 1:1 for MPMC and Cu2+. Additionally, the color of MPMC probe solution changed from nearly colorless to yellow in the presence of Cu2+ in visible light, which the color change could be observed by the naked eye. Similarly, the color resolved bright yellow into blue in ultraviolet light. Also reusability studies indicated that MPMC probe was reusable. The pH effect of probe MPMC to Cu2+ had a broad range of pH detection 4.0 to 11.0. The response time of MPMC probe for determining Cu2+ was within 1 min. The recognition of Cu2+ by MPMC performed on pre-treated paper under sunlight and UV light both had a distinct colour change. Thus, the solid-state method for detecting Cu2+ with the naked-eye, was both economical and convenient.

Kluyveromyces marxianus (K. marxianus) is a newly emerging industrially relevant yeast. It is known to possess a highly efficient Non-Homologous End Joining (NHEJ) pathway that promotes random integration of non-homologous DNA fragments into its genome. The nature of the integration events was traditionally analyzed by Southern blot hybridization. However, the precise DNA sequence at the insertion sites were not fully explored. We transformed a PCR product of the Saccharomyces cerevisiae URA3 gene (ScURA3) into an uracil auxotroph K. marxianus wildtype strain and picked 24 stable Ura+ transformants for sequencing analysis. We took advantage of rapid advances in DNA sequencing technologies and developed a method using a combination of Illumina MiSeq and Oxford Nanopore sequencing. This approach enables us to uncover the Gross Chromosomal Rearrangements (GCRs) that are associated with the ScURA3 random integration. Moreover, it will shine a light on understanding DNA repair mechanisms in Eukaryotes, which could potentially provide insights for cancer research.

One new cassane diterpene possessing an unusual N bridge between C-19 and C-20 named caesalsappanin R (1), as well as another new diterpene caesalsappanin S (2), were isolated from the seeds of Caesalpinia sappan with methanol extract. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Their biological activities were profiled by their antiplasmodial activity.

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proved to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in treatment of HCC. This review summarizes impact of hypoxia on HCC tumor biology, adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC.

Despite the partial disclosure of driving scenario knowledge graphs, they still fail to meet the comprehensive needs of intelligent connected vehicles for driving knowledge. Current issues include the high complexity of pattern layer construction, insufficient accuracy of information extraction and fusion, and limited performance of knowledge reasoning models. To address these challenges, a hybrid knowledge graph method was adopted in the construction of the Driving Scenario Knowledge Graph (DSKG). Firstly, core concepts in the field were systematically sorted and classified, laying the foundation for the construction of a multi-level classified knowledge graph top-level ontology. Subsequently, by deeply exploring and analyzing the Traffic Genome data, 34 entities and 51 relations were extracted and integrated with the ontology layer, achieving the expansion and updating of the knowledge graph. Then, in terms of knowledge reasoning models, an analysis of the training results of the TransE, Complex, Distmult, and Rotate models in the entity linking prediction task of DSKG revealed that the Distmult model performed the best in metrics such as hit rate, making it more suitable for inference in DSKG. Finally, a standardized and widely applicable Driving Scenario Knowledge Graph was proposed. The DSKG and related materials have been publicly released for use by industry and academia.

Transcription of glycine-rich RNA-binding protein 2 (PeGRP2) transiently increased in root and shoot of Populus euphratica (salt-resistant poplar) upon initial salt exposure and tended to decrease after long-term NaCl stress (100 mM, 12 days). PeGRP2 overexpression in the hybrid Populus tremula × P. alba ‘717-1B4’ (P. × canescens) increased salt sensitivity, which was reflected in plant growth and photosynthesis. PeGRP2 contains a conserved RNA recognition motif domain at the N-terminus, and RNA affinity purification (RAP) sequencing was developed to enrich target mRNAs that physically interact with PeGRP2 in P. × canescens. RAP sequencing combined with RT-qPCR revealed that NaCl decreased the transcripts of PeGRP2-interacting mRNAs encoding photosynthetic proteins, antioxidative enzymes, ATPases, and Na+/H+ antiporters in transgenic poplar. Particularly, PeGRP2 negatively affected the stability of target mRNAs encoding photosynthetic proteins (PETC and RBCMT), antioxidant enzymes (SOD[Mn], CDSP32 and CYB1-2), ATPases (AHA11, ACA8 and ACA9), and Na+/H+ antiporter (NHA1). This resulted in (i) a greater reduction in Fv/Fm, YII, ETR and Pn, (ii) a less pronounced salt activation of antioxidative enzymes, and (iii) a reduced ability to maintain Na+ homeostasis in transgenic poplars during long-term salt stress, leading to a lowered ability to tolerate salinity stress.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

Pretilachlor is a chloroacetamide herbicide, mainly used for the control of weeds and broadleaf weeds in rice, and widely used in China. For the detection of residues of pretilachlor in the en-vironment and food, a highly sensitive and specific monoclonal antibody against pretilachlor was prepared, and the half maximum inhibitory concentration (IC50) of the monoclonal antibody was validated to be 31.47±2.35 μg/L. An indirect competitive ELISA (ic-ELISA) based on the antibody with a linear range of 6.25~100 μg/L was developed for the detection of pretilachlor residues in the environment and food crops. The specificity of the antibody was explained by computer simula-tions and experimental validation. No cross-reactivity of this monoclonal antibody to alachlor, acetochlor and metalaxyl, and it cross-reacted less than 3.0% to both butachlor and propisochlor. The limits of detection (LOD) for pretilachlor in lake, rice, and soil samples were 4.83~5.23 μg/L. The recoveries of all samples were 78.3%~91.3%. The ic-ELISA method was validated by high-performance liquid chromatography, thus, it can be used for residue detection of pretilachlor in the environment and grains.

Skeletal muscle is a specialized tissue consisting of nondividing and multinucleated muscle fibers. Skeletal muscle-specific myostatin (MSTN) is a secreted protein that acts as a negative regulator of muscle mass by inhibiting proliferation and differentiation of myoblasts. In this study, we established a screening platform to monitor myostatin promoter activity in rat L8 myoblasts. Extract of Glycyrrhiza uralensis (GUE), an oriental herbal medicine, was identified through this screening platform and, the active fractions of GUE were identified by process-scale liquid column chromatography system. For in vivo study, the GUE as a feed additive was investigated in growth-finishing pigs. The results showed that GUE significantly increased body weight, carcass weight and lean content in pigs. Microbiota analysis indicated that GUE did not affect the composition of gut microbiota in pigs. In summary, this established rodent myoblast screening platform was used to identify a myogenesis-related phytogenic, GUE, and further demonstrated that the active fractions inhibited MSTN expression. These finding suggest a novel application for GUE in growth performance enhancement through modulation of MSTN expression. Furthermore, this established screening platform has great potential for identification and evaluation of a wide variety of phytogenics involving in myogenesis.

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via the whole-genome genotyping with genetic markers and linkage assay in a family suffering AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89-cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. Exome-wide sequencing assay unveiled that at the defined locus, solely the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), co-segregated with AF in the family. Additionally, Sanger sequencing assay of TBX20 in another family suffering AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations was observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while without effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-causative gene, shedding light on the mechanism underlying AF and suggesting clinical significance for allele-specific treatment of AF patients.

The effective integration of aerial remote sensing data and ground multi-source data has always been one of the difficulties of quantitative remote sensing. A new monitoring mode is designed which installs the hyperspectral imager on the UAV and places a buoy spectrometer on the river. Water samples are collected simultaneously to obtain in situ assay data of total phosphorus, total nitrogen, COD, turbidity and chlorophyll during data collection. The cross correlogram spectral matching (CCSM) algorithm is used to match the data of the buoy spectrometer with the UAV spectral data to reduce the UAV data noise significantly. An absorption characteristics recognition algorithm (ACR) is designed to realize a new method for comparing UAV data with laboratory data. This method takes into account the spectral characteristics and the correlation characteristics of test data synchronously. It is concluded that the most accurate water quality parameters can be calculated by using the regression method under five scales after the regression tests of multiple linear regression method (MLR), support vector machine method (SVM) and neural network (NN) method. This new working mode of integrating spectral imager data with point spectrometer data will become a trend in water quality monitoring.

Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); N=5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; N=15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (N=5/group) or fludrocortisone (N=15/group) into male ApoE -/- mice fed a normal laboratory diet or LDL receptor -/- mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE -/- mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor -/- mice fed normal diet, 5 had ascending/arch pathologies, 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor -/- mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Given the low incidence, only ascending aortic diameter in LDLR -/- mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. The findings in mouse studies have the potential to provide caution to people who are taking or have taken fludrocortisone that could have an increased risk of aortic pathologies.

Osteosarcoma (OSA) is the most common primary malignant bone tumor. More than 40% of patients with OSA have poor prognoses. We aimed to discover a biomarker for patient stratification and therapeutic targets for these high-risk patients. Using Single Sample Gene Set Enrichment Analysis (ssGSEA) and univariate Cox analysis, six hallmarks were identified as significant prognostic factors for overall survival (OS). Three were selected to construct a multivariate Cox model. Then, WGCNA, univariate Cox regression, Kaplan-Meier (KM) survival analyses, and multivariate Cox analyses were combined to filter promising candidates and establish a seven-gene signature to predict OS, whose prognostic value was validated internally and externally. Subsequently, Differential Expression Analysis was conducted between high- and low-risk patients, and the Robust Rank Aggregation algorithm was used to determine the robust DEGs. Metascape was used to perform pathway and process enrichment analyses as well as construct protein-protein interaction (PPI) networks. Finally, RPS28 was identified as an independent risk factor by using univariate and multivariate Cox regression, which was preliminarily validated as a promising therapeutic target by using RNA interference. In conclusion, we might contribute to optimizing risk stratification and an excellent therapeutic target for high-risk patients with OSA.

Background Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methods and principal findings We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 18 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FED-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animals hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03 – 0.48) with FED-SD showing highest sensitivity (0.89, 95% CI: 0.65 – 1.00). Conclusions and significance Our findings suggest that the parasitologic technique FEA-SD and the molecular technique, qPCR, are the most promising field-applicable techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

Although the spanwise periodicity within the gap between two tandem circular cylinders has been observed by some researchers, there is a lack of systematic study on the properties of this pe-riodicity. For the spanwise periodicity within the gap, this study aims to ascertain its characteris-tics, its influences on the flow field, and its variation trend with increasing spacing ratio. By nu-merically simulating the flow around two tandem circular cylinders with a diameter ratio of d/D=0.6 and seventeen spacing ratios (L/D=1.00~6.00) at Re=3900, this study shows four flow re-gimes: Reattachment Flow (L/D=1.00~3.15), Bi-stable Flow (L/D=3.24), Intermittent Lock-in Co-shedding (L/D= 3.30~3.50) and Subharmonic Lock-in Co-shedding (L/D=4.00~6.00). Further, de-pending on the spanwise periodicity length of the time-averaged flow structures (i.e. Pz) within the gap, Reattachment Flow is, for the first time, subdivided into three new sub-flow regimes: Small-scale Periodic Reattachment (L/D=1.00~1.50, Pz/D=(0, 4]), Large-scale Periodic Reattachment (L/D=2.00~2.25, Pz/D>4) and Non-periodic Reattachment (L/D=2.50~3.15, no spanwise periodicity). The formation mechanisms are elaborated by analyzing the combined effect of both the L/D value and the spanwise-averaged time-averaged reattachment angle of the downstream cylinder. Moreover, this study proves that the newly-defined Small-scale Periodic Reattachment and Large-scale Periodic Reattachment are responsible for the pronounced asymmetry of the flow along the transverse direction within the gap. In addition, detailed flow properties and statistical pa-rameters are provided for each flow regime, such as velocity, vorticity, force coefficient, separa-tion/reattachment angle, Strouhal number and Q-criterion.

The intelligent morphing wing structure has the characteristics of flexibility, large deformation and adaptive change, which are different from those of the conventional wing. The motion law of the variable-camber leading edge is analysed by the numerical simulation method based on kinematics theory to solve the problem of verifying the motion function and structural strength of the variable camber wing. The driving deformation and aerodynamic load simulation of the variable camber leading edge are realised by designing a follow-up load test apparatus. Based on the numerical simulation of the mechanical boundary, the motion trajectory of the upper and lower wing loading points was predicted, and a multi-point cooperative control system was developed. Multi-sensor iteration was used to ensure the loading accuracy of the test control. The test results show that the average error of the deflection angle is 4.59% in the variable camber leading edge motion test. In the variable camber leading edge strength test, the average error of applied load magnitude and direction is 0.54% and 0.24%, respectively.

The artificial intelligence (AI) refers to the science and engineering of creating intelligent machines for imitating and expanding human intelligence. Given the ongoing evolution of the multidisciplinary integration trend in modern medicine, numerous studies have investigated the power of AI to address orthopaedic-specific problems. One particular area of investigation focuses on the shoulder pathology, which is a range of disorders or abnormalities of shoulder joint, causing pain, inflammation, stiffness, weakness, and reduced range of motion. There has not yet been a comprehensive review of the recent advancements in this field. Therefore, the purpose of this review is to evaluate the current AI applications in the shoulder pathology. This review mainly summarizes several crucial stages of the clinical practice, including predictive models and prognosis, diagnosis, treatment, and physical therapy. In addition, the challenges and future development of AI are also discussed.

Panax notoginseng is a traditional Chinese medicine, and saponins are its main active ingredients. The content of saponins in flower of P. notoginseng is the highest in the whole plant. Minor ginsenosides have stronger pharmacological activity than main ginsenosides, but its content in nature is very low. We can use extracted total saponins from P. notoginseng flower as the substrate to produce minor ginsenosides by biotransformation method. In this study, we used the fungus Talaromyces flavus and its crude enzymes to transform the extracted total saponins of P. notoginseng flower. Through the qualitative and quantitative analysis of the transformation substrates and products, it was found that minor ginsenosides Gyp-XVII, ginsenosides C-Mc1, C-Mx1, F2, Rg3, 20(R)-Rg3, Rk1 and Rg5 were found in the products and the conversion rate of the major saponins in P. notoginseng flower ranged from 44.16 to 55.22%, the yields of the minor ginsenosides ranged from 0.05 to 3.24%. This study provided a good experimental idea, greatly increased the utilization rate of total saponins in P. notoginseng flower, and laid a foundation for promoting the wide application of minor saponins.

Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). And Arabidopsis Long Hy-pocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in plant stress response signal network remains unknown. Here, we described the func-tion of the HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2 which positively mediated the expression of downstream stress-related genes of RD29A, RD29B and DREB2A. Further quantitative proteomics showed the patterns of 7,391 proteins under salt stress. HY2 was then found to specifically regulate 215 differentially regulated proteins (DRPs) which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic & metabolic, hormone response (SA, JA, ABA, ethylene), reactive oxygen spe-cies (ROS) metabolic, photosynthesis and detoxification pathway to respond to salt stress. More importantly, ANNAT1-ANNAT2-ANNAT3-ANNAT4 and GSTU19-GSTF10-RPL5A-RPL5B-AT2G32060, two protein interaction networks specifi-cally-regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to re-sist salt stress.

The Human immunodeficiency virus-1 (HIV-1) matrix (MA) domain is involved in the highly regulated assembly process of the virus particles that occur at the host cell’s plasma membrane. High-resolution structures of the MA domain determined using cryo X-ray crystallography have provided initial insights into the possible steps in the viral assembly process. However, these structural studies have relied on large and frozen crystals in order to reduce radiation damage caused by the intense X-rays. Here, we report the first XFEL study of the HIV-1 MA domain’s interaction with inositol hexaphosphate (IP6), a phospholipid headgroup mimic. We also describe the purification, characterization and microcrystallization of two MA crystal forms obtained in the presence of IP6. In addition, we describe the capabilities of serial femtosecond X-ray crystallography (SFX) using X-ray free-electron laser (XFEL) to elucidate the diffraction data of MA-IP6 complex microcrystals in liquid suspension at ambient temperature. Two different microcrystal forms of MA-IP6 complex both diffracted to beyond 3.5 Å resolution, demonstrating the feasibility of using SFX to study the complexes of MA domain of HIV-1 Gag polyprotein with IP6 at near-physiological temperatures. Further optimization of the experimental and data analysis procedures will lead to better understanding of the MA domain of HIV-1 Gag and IP6 interaction at high resolution and provide basis for optimization of the lead compounds for efficient inhibition of the Gag protein recruitment to the plasma membrane prior to virion formation.

The standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information of early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cfDNA, methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (High versus Low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6%–99.3%) and 94.1% (95% CI: 82.3%–100%). In addition, in patients with normal renal function [eGFR ≥ 90], the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be picked up by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90 % of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Here, we investigate the effects of CBFA2T2 on CSCs regulation in RCC, as well as to elucidate the possible mechanisms. We showed that CBFA2T2 expression can significantly predict the survival of RCC patients. Functional assays showed that knocking-down of CBFA2T2 can inhibit cell migration and invasion in 786-O and A-498 cells in vitro, and reduce ALDH^high CSCs populations. Furthermore, CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines. Collectively, our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of “stemness” through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

Cu₆Sn₅ whiskers precipitated in Sn3.0Ag0.5Cu/Cu interconnection in concentrator silicon solar cells solder layer were found and investigated after reflow soldering and during aging. Ag₃Sn fibers can be observed around Cu₆Sn₅ whiskers in the matrix microstructure, which can play an active effect on the reliability of interconnection. Different morphologies of Cu₆Sn₅ whiskers can be observed, and hexagonal rod structure is the main morphology of Cu₆Sn₅ whiskers. A hollow structure can be observed in hexagonal Cu₆Sn₅ whiskers, and a screw dislocation mechanism was used to represent the Cu₆Sn₅ growth. Based on mechanical property testing and finite element simulation, Cu₆Sn₅ whiskers were regarded as having a negative effect on the durability of Sn3.0Ag0.5Cu/Cu interconnection in concentrator silicon solar cells solder layer.

Optimizing the NACA0015 airfoil which is widely applied in small-scale vertical axis wind turbine to make it has a better aerodynamic performance. In the optimization process, using CST parameterization method to perturb the airfoil geometry, the thickness and camber of the airfoil are selected as the constraint, and the value of the maximum tangential force coefficient is chosen as the objective function, the genetic algorithm based on non-dominated sorting (NSGA-II)is selected as an optimization method, calculates the aerodynamic performance of the airfoil by applying the approach of combining XFOIL program and Viterna-Corrigan post-stall mode ,and establishes the optimizing process by the optimization software modefrontier for NACA0015 airfoil’s muti-point optimization, validate the airfoil’s performance with CFD finally. The result illustrates that, by comparing with the NACA0015 airfoil, the optimized airfoil’s lift to drag ratio is improved over a wide range of attack angles, the stall performance is more gentle. The maximum lift coefficient, the maximum lift-drag ratio and the maximum tangential force coefficient are increased by 7.5%,9 and 8.87%, respectively. The optimized airfoil has a wide variable condition performance, more suitable for the operating conditions of a vertical axis wind turbine. Finally, predict the rotor efficiency with optimized airfoil and NACA0015 airfoil for different tip speed ratios and different solidities with multiple streamtube model, the result shows the rotor with optimized airfoil has a higher efficiency.

A challenge in building large-scale superconducting quantum processors is the precise control and manipulation of the qubit state. However, the crosstalk between the microwave control lines impedes the parallel execution of high-fidelity digital and analog quantum operations. Here, we propose and demonstrate a universal compensation protocol for calibrating the microwave signal crosstalk. We also introduce amplified error sequences to optimize the accuracy. Furthermore, we show a definitive improvement in parallel gate operations with crosstalk cancellation, demonstrating the technique's effectiveness. This work paves the way for superconducting hardware that features automated calibration of microwave crosstalk, leading to enhanced fidelities in multiqubit circuits.

(1) Background: Ectopic pregnancy (EP) is when fertilized ovum implanted outside of uterine cavity. The incidence was 1.5% to 2.0% of all pregnancies [1, 2]. EP decreases fertility ability [3]. This study focused on the pregnancy rate after EP and various parameters influencing pregnancy. (2) Methods: The data was extracted from National Health Insurance Research Database (NHIRD) during 2000-2013. The study group enrolled women with one EP history. Those who did not have EP was put into the control group. Chi-square/Fisher exact test was performed on category variable and t-test was used on continue variables. (3) Results: The EP group had a higher cumulative rate of conceive, 41.55% than control group, 37.14% and 1.16 times higher risk in developing pregnancy (P&lt;0.001). The conceiving rate was lower than the control group in the first 5 years, but higher than the control group in the 10th to 14th years. (4) Conclusions: The fecundability after EP is lower at the beginning, but regained after long term follow.

B4GALNT2 is a vital candidate gene that affects the growth traits litter size in and growth traits of sheep, but whether it has the same function in goats remains to be further investigated. In this study, we utilized 348 Nanjiang Yellow goats as experimental subjects, conducted a whole exon, and the conserved the non-coding region SNP scanning of the B4GALNT2 gene. Our results revealed the presence of a synonymous mutation, rs672215506, within the exon of the B4GALNT2 gene in the Nanjiang Yellow goat population. This mutation was found to be associated with reduced mRNA stability of the B4GALNT2 gene. The results of SNPs detection of conserved non-coding region of B4GALNT2 gene showed that there were five potential regulatory SNPs in the Nanjiang Yellow goat population, except for rs66095343, the ~500 bp fragments of four SNPs (rs649127714, rs649573228, rs652899012 and rs639183528) could significantly increase luciferase activity both in goat skeletal muscle cells and 293T cells . Genetic diversity indexes indicated low or intermediate levels for all six SNPs analyzed, each conforming to Hardy-Weinberg equilibrium regarding genotypic frequencies. Association analysis indicated that rs660965343, rs649127714 and rs649573228 were significantly correlated with growth traits in the later stage of growth and development of Nanjiang Yellow goat. The haplotype combinations of H2H3 and H2H2 had higher body weight and greater body size; moreover, H2H2 haplotype combinations were significantly correlated with the litter size of Nanjiang Yellow goat. The results of our study demonstrate the potential utility of the B4GALNT2 gene as a functional genetic marker in breeding programs for Nanjiang Yellow goats.

Verticillium wilt (VW) is a soil borne fungal diseases caused by Verticillium dahliae Kleb, and lead to serious damage to cotton production annually in the world. In our previous study, a transmembrane protein 214 protein (TMEM214) gene associated with VW resistance was map-based cloned from Gossypium barbadense (G. barbadense). TMEM214 proteins are a kind of transmembrane protein, but their function in plants is rarely studied. To reveal the function of TMEM214s in VW resistance, all six TMEM214s were cloned from G. barbadense in this study. These genes were named as GbTMEM214-1, GbTMEM214-4 and GbTMEM214-7 according to their location on the chromosomes, and the encoded proteins are all located on cell membrane. TMEM214 genes were all induced by Verticillium dahliae inoculation and showed significant differences between resistant and susceptible varieties, but the expression patterns of GbTMEM214s under different hormone treatments were significantly different. Virus-induced gene silencing analysis showed the resistance to VW of GbTMEM214s-silenced lines decreased significantly, which further proves the important role of GbTMEM214s in the resistance to Verticillium dahliae. Our study provides an insight into the involvement of GbTMEM214s in VW resistance, which was helpful to better understand the disease resistance mechanism of plants.

Ebola virus (EBOV) is a negative-sense RNA virus that can infect humans and nonhuman primates with severe health consequences. Development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. The goal of this study was to further characterize EBOV disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. Rhesus macaques were intramuscularly exposed to EBOV and one group was euthanized at predetermined time points to characterize progression of disease. A second group was not scheduled for euthanasia in order to analyze survival, changes in physiology, clinical pathology, terminal pathology, and telemetry kinetics. On day 3, sporadic viremia was observed and pathological evidence was noted in lymph nodes. By day 5, viremia was detected in all EBOV exposed animals and pathological evidence was noted in the liver, spleen, and gastrointestinal tissues. These data support the notion that EBOV infection in rhesus macaques is a rapid systemic disease similar to infection in humans, under a compressed time scale. Biomarkers that correlated with disease progression at the earliest stages of infection were observed thereby identifying potential “trigger--to-treat” for use in therapeutic studies.

The one-dimensional MoS₂/carbon nanofibers (1D MoS₂/CNFs) are synthesized by electrospinning using exfoliated MoS₂ nanosheets and polyacrylonitrile as raw materials. The exfoliated MoS₂ nanosheets with size of about 150 nm are encapsulated in carbon nanofibers, and the free-standing MoS₂/CNFs can be easily cut into flexible tablet and directly used as binder-free anode for lithium storage. The resultant 1D MoS₂/CNFs exhibit a very high reversible capacity of 700 mAh g^-1 at 100 mA g^-1 after 50 cycles, high rate capacity (450 mAh g^-1 at 1000 mA g^-1 after 200 cycles) and good cycle stability.

Background and Objectives: The existing recommendations for female pelvic magnetic susceptibility weighted imaging MRI (FP-SWI) have not been optimized to capture the disease characteristics of the female pelvis. Therefore, it is imperative to explore acquisition parameters before conducting larger-scale studies. To establish optimized flip angle (FA) for acquiring FP-SWI to improve the image quality of female pelvic lesion sites. Materials and Methods: To evaluate signal quality and lesion conspicuity, regions of interest (ROIs) were manually drawn within the lesion on SWI sequences. Signal intensity was measured within the ROIs. Additionally, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for SWI sequences acquired at three FA: 10°, 15°, and 20°. Finally, a qualitative assessment of anatomical detail visualization, geometric distortion extent, artifacts, and lesion clarity was performed using a four-point scale. The Wilcoxon rank sum test was employed to compare the qualitative evaluation parameters. The intra-class correlation coefficient (ICC) was calculated to determine the consistency of subjective ratings between two observers. Results: FA=10° showed significantly higher SNR than FA=15° and 20° in most anatomical regions (P&lt;0.05), while the CNR was significantly higher than FA=15° and 20° (P&lt;0.05). Compared with FA=15° and 20°, the image quality of FA=10° was significantly higher, with less distortion and ghosting, and better image contrast (P&lt;0.05). Lesions with FA=10° exhibited higher clarity compared to FA=15° and 20° (P&lt;0.05). Conclusions: The image quality of FP-SWI images at FA=10° exceeds that at FA=15° and 20°. We recommend that when conducting SWI examination of the female pelvic cavity, the FA value should be set at 10° to stabilize the SWI sequence and improve image quality.

Ruminant animals naturally emit methane gas owing to anaerobic microbial fermentation in the rumen, and these gases are considered major contributors to global warming. Scientists worldwide are attempting to minimize methane emissions from ruminant animals. Some of these attempts include the manipulation of rumen microbes using antibiotics, synthetic chemicals, dietary interventions, probiotics, propionate enhancers, stimulation of acetogens, manipulation of rumination time, vaccination, and genetic selection of animals that produce low methane (CH4). The majority of synthetic additives are harmful to both beneficial rumen microbes and the host or only temporarily affect methanogenesis. Phytogenic feed additives (PFAs) have recently emerged as the best alternatives to antibiotics and synthetic chemicals because of growing public concerns regarding drug resistance and the negative impacts of antibiotics and synthetic chemicals on humans, livestock, and the environment. These additives reduce methane production and improve the volatile fatty acid profile. In this review, we provide an overview of PFA sources and how their bioactive components affect the rumen microbiome to reduce methane emissions. Additionally, we highlight the mechanisms of action of PFAs as a whole as well as some of their bioactive components.

Rural landscapes are acknowledged for their potential to restore human health due to their natural characteristics. However, few studies have systematically analysed the impact of naturalness, landscape types, and combinations of landscape elements on restorativeness using both subjective and objective measurements. This study investigated the restorative effects of various rural landscapes in Guangzhou, employing electroencephalography and eye-tracking technologies to record physiological responses and using the Restorative Components Scale and the Perceived Restorativeness and Naturalness Scale to evaluate psychological responses. The results indicated the following: (1) There was a significant positive correlation between perceived naturalness and restorativeness, surpassing the impact of actual naturalness. (2) Different landscape types had a varying impact on mental health at the equal perceived naturalness. Natural forest landscapes and artificial forest landscapes exhibited the most substantial restorative effects among the natural and semi-natural landscapes examined, respectively, while settlement landscapes showed the highest restorative potential among the artificial landscapes. (3) Restorative properties varied across landscape elements, with identical elements yielding different benefits in different environments. Trees and water significantly enhanced restorativeness, whereas constructed elements such as roads and infrastructure reduced it. This study provides a scientific basis for restorative rural landscape design to enhance mental health and well-being.

Deep learning has increasingly been employed to identify minerals. However, deep learning can only be used to identify minerals in the distribution of the training set, while any mineral outside the spectrum of the training set is inevitably categorized erroneously within a predetermined class from the training set. To solve this problem, the study introduces the approach that amalgamates One-Class Support Vector Machines (OCSVM) with the ResNet architecture for the out-of-distribution mineral detection. Initially, ResNet undergoes training using a training set comprising well-defined minerals. Subsequently, the earlier layers of the trained ResNet are employed to extract the discriminative features of the mineral under consideration. These extracted mineral features then become the input for OCSVM. When OCSVM discerns the mineral in the training set's distribution, it triggers the subsequent layers within the trained ResNet, facilitating the accurate classification of the mineral into one of the predefined categories encompassing the known minerals. In the event OCSVM identifies the mineral out of the training set's distribution, it is unequivocally categorized as an unclassified or 'unknown' mineral. Empirical results substantiate the method's capability to identify out-of-distribution minerals while concurrently maintaining a commendably high accuracy rate for the classification of the 36 in-distribution minerals.

Sialylated milk oligosaccharides (SMOs) is the most important oligosaccharides in human milk oligosaccharides (HMOs), and have a multifunctional health benefit, and the most abundant SMOs are sialyllactose (SLs). The previous studies indicate that the growth of tumor cells, and angiogenesis on tumor tissues with Lewis lung carcinoma, melanoma, and colon carcinoma cells could be prevented by SL. Thus, it has been proposed that SL might be an ideal candidate for the development of anti-angiogenic drugs without any side effects. It has been proposed that the Sialic acid (Sia) can be produced through SL’s hydrolysis, and the dietary Sia is further transported to the brain and other tissues though blood for formation of CMP-Sia, the activated precursor of Sia, and then is catalyzed by polysialyltransferases (polySTs) for synthesis of polysialic acid (polySia) or polysialylation of neural cell adhesion molecule (NCAM). Thus, it’s necessary to study and develop new inhibitors, which not only modulate a proper balance between the gut health and neuros system development, but also inhibit the overexpression of polySia, and thus block the tumor cell migration. In this study, we proposed that 3’-SL and 6’-SL may be more ideal inhibitors comparing with two previous inhibitors, the low molecular weight heparin (LMWH) and cytidine monophosphate (CMP) in the previous studies.

Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6] or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T cell epitope P2 (P2-VP8*) or expressed P2-VP8* as a fusion protein with lumazine synthase (LS-P2-VP8*) to allow the formation and secretion of protein particles that present VP8* on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as positive and negative control, respectively. Upon challenge with virulent Wa HRV, significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8*-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8*-specific IgG anti-body-secreting cells in ileum, spleen and blood seven days post-challenge as well as VP8*-specific IFN--producing T cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8* compared to P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for further development of mRNA-based rotavirus vaccines.

Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or biobanked sections/biopsy of lung tumors, PDXs, and pleural affusion. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and immune therapy agents. PDOs mainly recapitulated the genomic alterations, transcriptomic landscape and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remained, PDOs showed promise to screen novel therapy drugs. With the technical advance of high throughput, tumor-on-chip, combined microenvironment, and air-liquid interface (ALI), the drug screening using PDOs would serve better for precision care of lung cancer patients.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

In this paper, a method is developed for presenting a novel virtual torque sensor based on precise model and position measurements avoids the need of traditional strain gauges and amplifiers. More specifically, the harmonic drive compliance model and the Gaussian process regression (GPR) technique are used together to achieve virtual torque sensor measurement. While the harmonic drive compliance model provides the analytic part, the Gaussian process regression method is used to reconstruct the unmolded part based on motor-side and link-side joint angles as well as motor current. After an automatic offline calibration, the method allows for a lean online implementation. The virtual torque sensor measurement is compared with measurements of a commercial torque sensor, and the results have attested the effectiveness of the proposed method.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

This study analyses regional development in one of the poorest provinces in China, Guizhou Province, between 2000 and 2012 using a multiscale and multi-mechanism framework. In general, regional inequality has been declining since 2000. In addition, economic development in Guizhou Province presented spatial agglomeration and club convergence, which shows how the development pattern of one core area, two-wing areas and a contiguous area at the edge of the province have been developed between 2006 and 2012. Multilevel regression analysis revealed that industrialization and investment level were the primary driving forces of regional economic disparity in Guizhou Province. The influences of marketization and decentralization on regional economic disparity were relatively weak. Investment level reinforced regional economic disparity and the development of core-periphery structure in the province. However, investment level actually weakened the regional economic disparity in Guizhou Province when the variable of time was considered. In addition, both the topography and urban–rural differentiation were the two main reasons for forming a core-periphery structure in Guizhou Province.

To analyse Xuanwei ham flavour quality at different post-ripening times, and to elucidate its microbial diversity, we studied free amino acids and volatile flavouring compounds (VOCs) and their relationships. We determined microbial community changes in Xuanwei ham at 1, 2, 3 and 4 years (W1-4) by high-throughput sequencing, and simultaneously, VOCs and free amino acid contents by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC), respectively. Then heatmap analysis was used to determine correlations between microbial communities, free amino acids and VOCs. A total of 25 free amino acids were detected, among which W3 contained the fewest and most were generally lower than in hams in the other three years. Fifty-nine VOCs were detected, among which were 17 esters, and the highest ester content was found in W4. Atotal of 87508391 reads were obtained from the samples, of which 812844 were clean reads, and the bacterial Chao1 index and Shannon index were significantly higher in W3 than in the other three ham years. In differetly-aged Xuanwei hams, Pseudomonadota was the dominant bacterial phylum, and the most abundant genera were Sarocladium, Klebsiella and Vibrio. Klebsiella was the most abundant genus in W1, and Vibrio in W3, and the second most abundant genera were Sarocladium and Gammaretrovirus. We elucidated differences in Xuanwei ham microflora structures in different years and the main flavor-related microorganisms, thus providing a theoretical basis for subsequent Xuanwei ham storage, quality and improvement.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

The spectra and global distributions of the X-ray emissions generated by the solar wind charge-exchange (SWCX) process in the terrestrial magnetosheath are investigated based on a global hybrid model and a global geocoronal hydrogen model. The solar wind O6+ ions which are the primary charge state for oxygen ions in solar wind are considered. The line emissivity of the charge-exchange born O5+ ions are calculated by Spectral Analysis System for Astrophysical and Lab oratory (SASAL). It is found that the emission lines from the O5+ ranges from 105.607 to 118.291 eV with the strong line at 107.047 eV. We then simulated the magnetosheath X-ray emission intensity distributions with a virtual camera at two positions of north pole and dusk at six stages during the passing of a perpendicular interplanetary shock combined with a tangential discontinuity structure through the Earth’s magnetosphere. During this process, the X-ray emission intensity increases with time, and the maximum value is 27.11 keV cm-2 s-1 sr-1 on the dayside, which is 4.5 times that before the solar wind structure reaches the Earth. A clear shock structure can be seen in the magnetosheath and moves earthward. The maximum emission intensity seen at dusk is always higher than that seen at north pole.

The utilization of selective laser melting (SLM) for high entropy alloys (HEAs) holds significant promise in commercial applications, and substantial experimental research efforts have been directed toward this domain. To take advantage of the reported experimental data of SLM manufactured (SLM-ed) HEAs and reduce unnecessary experimentation, this study incorporates machine learning (ML) techniques for the phase and tensile properties prediction of SLM-ed HEAs, thus presenting a novel avenue for accelerating the discovery of new SLM-ed HEAs. Through the adjustment of material descriptors and machine learning models, a model has been developed with an impressive accuracy of 93.8% in distinguishing between face-centered cubic (FCC), body-centered cubic (BCC), and dual-phase (FCC+BCC). Additionally, optimized models have been devised for the prediction of tensile properties, namely ultimate tensile strength (UTS), yield strength (YS), and elongation (δ), achieving noteworthy MAPEs (mean absolute percentage errors) of 10.33%, 8.55%, and 28.48%, respectively. Furthermore, several HEAs were fabricated using SLM, and the experimental outcomes exhibited a favorable alignment with the predicted results. These efforts carry significant implications in advancing the utilization of SLM for HEAs.

Objective: The objective of this study is to determine the epidemic dynamics and clinical features of COVID-19 in southern Hainan Island, China, and provide experience for other tropical areas of the world. Methods: This retrospective study included confirmed cases of COVID-19 in southern Hainan. All enrolled patients were treated in Sanya, and data on epidemiological and clinical features of the disease and infection prevention and control measures adopted by the local government during the epidemic were collected. Results: Of the 74 cases, 71 (95.95%) were imported from Wuhan, Hubei Province (47, 63.51%), other cities in Hubei Province (11, 14.86%), or provinces other than Hubei and Hainan (13, 17.57%). Three (4.06%) patients were infected in southern Hainan, including one autochthonous case in Sanya. Fifty-four cases (72.97%) were detected in Sanya, and 27 cases (27.03%) were diagnosed in other cities. The rate of severe or critical cases was 28.38% (21/74), and mortality was 2.7% (2/74). The serum lactate levels and base excess of severe-critical patients were higher than those of patients with mild-moderate disease. Multivariate logistic regression analysis showed that chronic conditions were risk factors for severe and critical COVID-19. Seventy-four patients were diagnosed with COVID-19 over a 22-day period in Sanya, and the epidemic period in the city was 48 days. The outbreak was controlled rapidly because the local government adopted strict infection prevention and control measures. Conclusions: The clinical characteristics of COVID-19 in Hainan Island were similar to those reported in other regions. In Sanya, the rate of severe and very severe cases was higher than in other regions; however, most cases were imported, and there was only one autochthonous case. The rapid control of the outbreak in Sanya may be related to the tropical climate, adoption of strict infection prevention and control measures, daily reporting of new cases, increased public awareness about the epidemic, and other emergency actions implemented by the local government.

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM), is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and with aggressive in the clinic. Thus, it’s important to select a proper drug to block tumor cell migration for clinic treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a more ideal candidate for inhibition of NCAM polysialylation comparing with CMP and low molecular weight heparin (LMWH), which were determined based on our NMR studies. On the other hand, because neutrophil extracellular traps (NET) is the most dramatic stage in cell death process, and NETs’ release are related to pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. In this study, the molecular mechanism of inhibition of NETs’ release using LFcinB11 as inhibitor was also determined. Based on these results, LFcinB11 is proposed to be bifunctional inhibitor for inhibiting both NCAM polysialylation and NETs releases.

Background: Coronavirus disease 2019 (COVID-19) is a new viral respiratory disease and whether pregnant women are at increased risk of infection is unknown. Viral pneumonia is an important indirect cause of maternal death. Little is known about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Objective: To describe the clinical characteristics of COVID-19 in pregnancy and their newborn infant, and we sought to explored whether the SARS-CoV-2 can be intrauterine vertically transmitted. Study Design: The study was a case series study conducted in the obstetric ward of Tongji Hospital affiliated to Huazhong University of science and technology, Wuhan, China. Demographic, clinical, laboratory and radiological profiles of the SARS-CoV-2 infection case series. A systematic testing procedure for SARS-CoV-2 infection using oropharyngeal swab, placenta tissue, vaginal mucus, and breast milk of mothers. and oropharyngeal swab, umbilical cord blood, and serum of newborns was conducted. Results: We have conducted the most thorough virological assessment to date, and we include a longer clinical observation in mother-infant dyads during hospitalization. The clinical course and outcomes of three pregnant women who acquired SARS-CoV-2 infection late pregnancy are described in mother-infant dyads. Two had caesarean delivery in their third trimester. All patients showed an uneventful perinatal course, and a successful outcome. No infants became infected by vertical transmission or during delivery. Conclusion: No evidence to suggest the potential risk of intrauterine vertical transmission in the case series and further in-depth study is needed. Both the pregnancy woman and infant showed fewer adverse maternal and neonatal outcomes.

Cadmium accumulation in rice grain poses a serious threat to people’s health. Understanding the genetic basis on grain cadmium accumulation facilitates efforts to reduce it. Here, we show that OsCd1 is involved in Cd uptake and contributes to grain accumulation in rice. Natural variation in OsCd1 with a missense mutation Val449Asp is responsible for the divergence of rice grain cadmium accumulation between japonica and indica. Notably, near-isogenic line tests confirmed that the indica variety carrying the OsCd1^V449 allele could reduce the grain cadmium accumulation. The favorable allele OsCd1^V449 may be an important genetic resource to reduce grain cadmium accumulation for indica.

The Tibetan Plateau(TP) is known as ‘the water tower of Asian’, its precipitation variation play an important role in the eco-hydrological processes and water resources regimes. based on the monthly mean precipitation data of 65 meteorological stations over the Tibetan Plateau and the surrounding areas from 1961-2015,variations, trends and temporal-spatial distribution were analyzed, furthermore, the possible reasons were also discussed preliminarily. The main results are summarized as follows: the annual mean precipitation in the TP is 465.54mm during 1961-2015, among four seasons, the precipitation in summer accounts for 60.1% of the annual precipitation, the precipitation in summer half year (May.- Oct.) accounts for 91.0% while that in winter half year (Nov.- Apr.) only accounts for 9.0%; During 1961-2015, the annual precipitation variability is 0.45mm/a and the seasonal precipitation variability is 0.31mm/a, 0.13mm/a, -0.04mm/a and 0.04mm/a in spring, summer, autumn and winter respectively on the TP; The spatial distribution of precipitation can be summarized as decreasing from southeast to northwest in the TP, the trend of precipitation is decreasing with the increase of altitude, but the correlation is not significant. The rising of air temperature and land cover changes may cause the precipitation by changing the hydrologic cycle and energy budget, furthermore, different pattern of atmospheric circulation can also influence on precipitation variability in different regions.

Ice accumulation poses considerable challenges in transportation, notably in the domain of general aviation. The present study combines the strengths and limitations of conventional aircraft de-icing techniques with the emerging trend toward all-electric aircraft. The study aims to utilize laser-induced graphene (LIG) technology to create a multifunctional surface, seamlessly integrating hydrophobic properties with efficient electrical heating to mitigate surface icing effectively. We investigated the utilization of a 10.6 μm CO2 laser for direct writing on polyimide (PI), a widely-used insulating encapsulation material. From the thermomechanical perspective, our initial analysis using COMSOL Multiphysics software revealed that when the laser power P exceeds 5 W, the PI substrate experience ablative damage. The experimental results show that when P ≤ 5W, an increase in power has a positive impact on the quality, surface porosity, roughness reduction, line-spacing reduction, and water contact-angle enhancement of the graphene. Conversely, when P &gt; 5 W, higher power negatively affects both the substrate and the graphene structure by inducing excessive ablation. However, it influences the graphene line height positively and is consistent with overall experimental-simulation congruence. Furthermore, the incorporation of high-quality graphene resulted in a surface that exhibited higher contact angles (CA &gt; 120°), lower energy consumption, and higher heating efficiency compared to the use of traditional electrically heated materials for anti-icing applications. The potential applications of this one-step fabrication method extend across various industries, particularly aviation, marine engineering, and other ice-prone domains. Moreover, the method has extensive prospects for addressing pivotal challenges associated with ice formation and serves an innovative and efficient anti-icing technology.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOC) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5,007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOC, including Alpha (n =714), Delta (n =1,877), and Omicron (n =1,802). Omicron isolates were further sub-typed as BA.1 (n =899), BA.2 (n =853), and BA.4/BA.5 (n =50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1,577/5,007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p &lt;0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p &lt;0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p &lt;0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. Cucumerinum (Foc) of cucumber is a destructive soil-borne disease in cucumber (Cucumis sativus.L). There is limited knowledge on molecular mechanisms to FW resistance-mediated defense responses in cucumber. In this study, metabolome and transcriptome profiling were carried out in two FW, resistant (NR) and susceptible (NS), near isogenic lines (NILs) before and after Foc inoculation. The NILs showed consistent and stable FW resistances in multiple greenhouse and laboratory screening tests. Widely targeted metabolomic analysis identified differentially accumulated metabolites (DMAs) with significantly more accumulation in NR in response to Foc infection including many phenolic acid and flavonoid compounds from the flavonoid biosynthesis pathway. Transcriptome analysis identified differentially expressed genes (DEGs) between the NILs upon Foc inoculation including genes for secondary metabolite biosynthesis in or transcription factor genes regulating the flavonoid biosynthesis pathway. Joint analysis of the metabolomic and transcriptomic data identified DAMs and DEGs closely associated with biosynthesis of phenolic acid and flavonoid DAMs. The association of these compounds with NR-conferred FW resistance was exemplified by in vivo assays in which two phenolic acid compounds, bis (2-ethylhexyl) phthalate and diisooctyl phthalate, and the flavonoid compound gallocatechin 3-O-gallate were shown to have significant inhibitory effect on Foc growth. The antifungal effect of three compounds seems to be a novel finding. We conclude that phenolic acids and flavonoids play an important role in NR mediated FW resistance in cucumber.

This study aimed to evaluate the early-childhood comorbidities of cerebral palsy (CP) in children with low birth weight (LBW) and assess the impact of maternal bio-psychosocial factors on the risk of CP in preterm infants across varying birth weights. Data for 15,181 prematurely born infants from 2009 to 2013 and 151,810 matched controls from Taiwan's National Health Insurance Research Database were analyzed. Period prevalence of CP, and comorbidities of LBW were verified, and odds ratios (ORs) were calculated. Results confirmed that increasing prematurity and low birth weight (LBW) rates in Taiwan. LBW was associated with higher CP prevalence. Maternal age extremes (&lt;20 and &gt;40 years) were significant risk factors of CP in LBW infants. LBW infants showed higher risks of respiratory, circulatory, and nervous system and psycho-developmental comorbidities compared to controls. Infants with the lowest birth weights had even higher ORs for these comorbidities. However, gastrointestinal and nutritional comorbidities were less prevalent in premature infants. Maternal factors such as family income, number of hospital admissions, and length of hospital stay were significantly correlated with birth weight and subsequent complications. Each additional gestational week significantly reduced the risk of complications in premature infants. Additionally, maternal bio-psychosocial factors were associated with birth weight and related outcomes in premature infants, emphasizing the importance of addressing these factors in prenatal care and interventions.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point-patterns were generated, which were then used to perform spatial analyses using a normalized Ripley's K function at a radius of 25μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups, and multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) <6 months, and therapy response was defined as PFS >9 months. CAFs exhibited higher cellular clustering with Ki-67+ cells than with caspase-3+ cells (nK(25): Ki-67 1.19; caspase-3 1.05; P = .04). The median nearest neighbor (NN) distance from CAFs to Ki-67+ cells was shorter compared to caspase-3+ cells (15 μm vs 37μm, respectively; P < .001). Multivariable Cox regression analyses demonstrated that both high Ki-67+ density and H-score were associated with worse OS, OS-IT, and OS-TT. Regarding CAFs, only a high H-score was associated with worse OS, OS-IT, and OS-TT. For caspase-3+, high H-score and density were associated with worse OS and OS-TT. Patients whose tumors were resistant to targeted therapy (TT) had higher Ki-67 density and H-scores than those who had TT response. Overall, this ex vivo geospatial analysis of CAF distribution suggests that close proximity clustering of tumor cells and CAFs potentiates tumor cell proliferation, resulting in worse OS and resistance to TT in metastatic ccRCC.

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at a histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach in addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

With its unique properties and potential applications, nanoparticle-based delivery platforms for vac-cines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery and improving stability, providing a new solution for drug and vaccine delivery. And in some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery system to enhance vaccine stability and immunogen-icity. Lipid nanoparticles have shown promising potential in preclinical and clinical studies to efficiently deliver antigens to immune cells. Moreover, lipid nanoparticles (LNPs) and other nanoparticles as nu-cleic acids especially mRNA delivery system, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles for mRNA nano-vaccine delivery vehicles. We introduce several novel nanoparticles delivery platforms for mRNA vac-cine such as lipid, polymer, protein-based nanoparticle and so on. In addition, we overview the an-ti-tumor immunity of nanovaccine against different tumors in cancer immunotherapy. Finally, we give an outlook future perspectives and remaining challenges for this promising technolo-gy-nanoparticle-based delivery platforms for vaccines.

OBJECTIVE: To investigate the value of serum inflammatory factor levels in acute ischemic stroke patients after revascularization therapy in assessing acute prognosis. METHODS: 94 patients with acute ischemic stroke who underwent revascularization therapy admitted to our hospital from January 01, 2022 to January 01, 2024 were studied. The main evaluation index was modified Rankin Scale score (mRS) after 3 months, and patients with mRS score >2 were categorized into the poor prognosis group, and the rest were the good prognosis group. As well as the treatment of revascularization in all patients was used as a division into a thrombus extraction group and an intravenous thrombolysis group. Logistic regression analysis was applied to explore the independent risk factors for the prognosis of patients treated with recanalization for acute ischemic stroke. RESULTS: Two groups with good (59 cases) and poor (35 cases) prognosis were divided according to the mRS score. There were some differences in age, gender, emergency GLU, INR, whether they had diabetes or hypertension and other contents between the two groups, but the differences were not statistically significant. The NIHSS score, hospitalization days, previous cardiac history, hospitalization days, LDL, fasting glucose, IL-6, and TNF-a at the time of admission were lower than those in the poor prognosis group, and the difference was statistically significant. In the patients in the embolization group, there were some differences in age, gender, emergency GLU, INR, whether they had diabetes or hypertension and other contents between the two groups, but the differences were not statistically significant. The pre-hospital NHISS score, IL-6, and TNF-a of patients in the good prognosis group were lower than those in the poor prognosis group, and the difference was statistically significant. CONCLUSION: IL-6 and TNF-α may be used as predictors of prognosis after revascularization therapy for acute ischemic stroke, and this conclusion also applies to patients in the embolization group.

Karst peaks and depressions are scattered in karst zones with strong spatial heterogeneity and fragile ecological environments and are crucial for determining the degree of karst geomorphologic development. However, realizing automatic depiction and extracting depressions with high accuracy is difficult because of their complex morphology. Herein, based on 12.5-m resolution DEM data, six typical karst peaks from depressions in southwest China were selected as the study areas and a revised terrain openness index method based on slope mutation points (ROBSMPs) was used to determine the degree of karst geomorphologic development and the boundary of karst depressions. The extent of depressions extracted by ROBSMPs and the terrain openness index method with the extent of depressions hand-drawn based on remote sensing images was compared and analyzed. The results show that compared with the topographic openness index method, the overall accuracy of karst depression extracted by ROBSMPs was improved and the perimeter, area, and raster displacement error indexes were reduced. ROBSMPs realized high-precision extraction of depressions, thereby strengthening the applicability of the topographic openness index method to karst peak zones. This study offers a new perspective and path toward the expansion of digital terrain analysis technology in karst mountainous areas and is expected to play a vital role in the extraction of similar geomorphic units in karst zones.

In this research, catalytic steam reforming acetic acid derived from the aqueous portion of bio-oil for hydrogen production was investigated by using different Ni/ATC (Attapulgite Clay) catalysts prepared by precipitation, impregnation and mechanical blending methods. The fresh and reduced catalysts were characterized by XRD, N₂ adsorption-desorption, TEM and H₂-TPR. The comprehensive results demonstrated that the interaction between active metallic Ni and ATC carrier was significantly improved in Ni/ATC catalyst prepared by precipitation method, and in which the mean Ni particle size was the smallest (~13 nm) resulted in the highest metal dispersion (7.5%). The catalytic performance of the three catalysts was evaluated through the process of steam reforming of acetic acid in a fixed-bed reactor under atmospheric pressure at two different temperatures, such as 550 ℃ and 650 ℃. Results showed that the Ni/ATC (PM-N/ATC) prepared by precipitation method, achieved the highest H₂ yield of ~82% and little lower acetic acid conversion efficiency of ~85% than that (~95%) of Ni/ATC (IM-NATC) prepared by impregnation method. In addition, the deactivation catalysts after reaction for 4 h were analyzed by XRD, TGA-DTG and TEM, which demonstrated that the catalyst deactivation was not caused by the amount of carbon deposition, but owed to the significant agglomeration and sintering of Ni particles in the carrier.

Exposure to malachite green (MG) may pose great health risks to humans, thus it is of prime importance to develop fast and robust methods to quantitatively screen the presence malachite green in environment. Herein application of extractive electrospray ionization mass spectrometry (EESI-MS) has been extended to the trace detection of MG within lake water and aquiculture water, due to the intensive use of MG as biocide in fisheries. This method has the advantage of obviating offline liquid-liquid extraction or tedious matrix separation prior to the measurement of malachite green in native aqueous medium. The experimental results indicate that the extrapolated detection limit for MG was ~3.8 ug L-1 (S/N=3) in lake water samples and ~ 0.5 ug L-1 in ultrapure water under optimized experimental conditions. The signal intensity of MG showed good linearity over the concentration range of 10–5000 ug L-1. Measurement of practical water samples fortified with MG at 0.01 and 0.1 mg L-1 gave a good validation of the established calibration curve. The average recoveries of malachite green in lake water and Carassius carassius fish farm effluent water were 114.9% (6.6% RSD) and 85.4% (9.2% RSD), respectively. Overall, the established EESI-MS/MS method has been demonstrated suitable for sensitive and rapid (<2 min per sample) quantitative detection of malachite green in various aqueous media, indicating its potential for online real-time monitoring of real life samples.

Background: The rise of new SARS-CoV-2 mutations brought challenges and progress in the global fight against COVID-19. Mutations in spike and accessory genes affect transmission, vaccine efficacy, treatments, testing, and public health strategies. Monitoring emerging variants is crucial to halt virus spread. Methods: 44 nasopharyngeal/oropharyngeal swabs from Kenyan patients were sequenced with the Illumina platform. Galaxy's bioinformatic tools were used for genomic analysis. SARS-CoV-2 genome classification was done using PANGOLIN and mutation annotation with the COVID-19 Annotator tool. Results: The study showed 5 clades to be circulating in the region. 38(86%) were BA.1.1; 2(5%) were BA.1.1.1; 1(2%) was BA.1; 1(2%) was BA.1.14 and 2(5%) were AY.46. These clades had a cumulative of 173 mutations among them with 50 novel mutations. Forty-eight of these novel mutations occurred in a low frequency of 2.3% of the sequences tested while the other two, S:R214R, and NSP2:A555A, were for 43.2% and 18.2% of the cases respectively. Conclusions: The high-frequency novel mutations were synonymous mutations, a phenomenon that was previously viewed as phenotypically silent but recent studies indicate they can affect viral fitness with potential functional associations. These findings add to the understanding of the SARS-CoV-2 virus future evolutionary and immunological dynamics in the region

Effects of oxygen content on microstructure and creep property of FGH96 superalloy were investigated. When oxygen content increased from 135ppm to 341ppm, prior particle boundary (PPB) rose from degree 2 to degree 3, and the size of γ′ phase on PPB enlarged from 1.07μm to 1.27μm, and MC carbide size grew from 77.4nm to 104.0nm. Meanwhile, the steady creep rate accelerated form 4.34×10-3 h-1 to 1.87×10-2 h-1, and the creep rupture life shortened from 176h to 94h, and the creep rupture mode transferred from intergranular and transgranular mixed fracture to along PPB fracture. During creep, the micro-twins formation and gliding will be restrained by ∑3 boundaries. FGH96 superalloy with higher oxygen content contains less ∑3 boundaries and its micro-twins cross slipped instead of single direction slip in lower oxygen content superalloy. Consequently, specimen with higher oxygen content creeped faster and raptured earlier.

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.

Numerous investigations have suggested that seismic source parameters and properties of the surrounding medium harbor valuable information regarding alterations in stress fields and medium properties at the focal depth. Monitoring the spatial and temporal evolution of these parameters can yield insights into variations in stress fields or medium properties within the seismogenic zone, offering a critical avenue to overcome the Earth's inaccessible nature. In recent years, modern seismic parameters such as seismic moment, focal mechanism solution, source stress drop, corner frequency, radiated seismic energy, rupture radius, and apparent stress have been increasingly used to characterize source characteristics. The Sichuan region is situated on the southeastern edge of the Qinghai-Tibet Plateau and is known for its strong eastward extrusion and structural deformation. The main fault zones in the area include the Xianshuihe Fault, Anninghe Zemuhe Fault, and Longmenshan Fault. This paper estimates source parameters of small to medium-sized earthquakes (ML 1.5-5.2) in the main fault zones and adjacent areas in Sichuan. A total of 4,310 earthquake stress drop measurements from 2019 to 2023 were analyzed to create a stress distribution image along the fault. This earthquake parameters training catalog provides insight into how coseismic stresses change and their relationship with other geophysical factors, as well as their spatial and temporal evolution.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

The marine region of the Zhongjieshan Islands is an essential component and location for enhancement and release in Zhoushan Fishing Ground. The scientific assessment of the target species' ecological carrying capacity serves as the foundation for augmentation and release efforts. Based on data from the 2021-2022 survey of biological resources in the waters of Zhongjieshan islands, the Ecopath model was built to analyze the trophic structure, energy flow, and overall characteristics of the ecosystem, as well as the ecological carrying capacity of the main enhancement and releasing species, Larimichthys crocea and Sepiella maindroni. The ecosystem's functional groups had trophic levels ranging from 1 to 3.48, with an average energy transfer efficiency of 8.11% and total flow of 2125.905 t·km-2. The ratio of total primary output to total respiration is 1.713. Zhongjieshan Islands' ecosystem was currently at an embryonic stage. The ecological carrying capacity of Larimichthys crocea and Sepiella maindroni was calculated to be 0.2325 t·km-2 and 0.1617 t·km-2, separately or individually. Larimichthys crocea and Sepiella maindroni showed enormous potential for development and release. The findings offered essential data for ecological studies on the waters of Zhongjieshan Islands, as well as a reference for enhancement and release efforts in this area.

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI, ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and VH: CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum significantly up-regulated in the NSB group, respectively. Additionally, SOD (p < 0.05) and T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05) showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, serum anti-inflammatory cytokines, regulating intestinal barrier function and antioxidant capacity, SCFAs content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition.

Insulin-like Growth Factor 2 mRNA binding Protein 1 (IGF2BP1) is a promising candidate gene for influencing economic traits in livestock and poultry. The second intronic region of IGF2BP1 is closely related to growth traits, although the exact mechanism remains unclear. The preliminary resequencing results of goats in our laboratory demonstrated that the IGF2BP1 gene region was subject to strong selection, then we selected multiple single nucleotide polymorphisms (SNPs) to identify. Seven SNPs were located in the conserved region of the second intron, and their functions and relationship with growth traits require further clarification. This study selected 348 Nanjiang Yellow goats as experimental subjects, and chose Time of Flight Mass Spectrometer (MALDI-TOF) as the main method. Our results showed that six SNPs were significantly correlated with the growth traits of the Nanjiang yellow goat by association analysis. Among them, the rs652062749(A>G) was identified as the primary locus affecting the later stage of growth traits of Nanjiang yellow goat. Moreover, there was a strong linkage among three SNPs, and the rs638185407 (T>A) mutant type was observed to increase the luciferase activity in H293T cells extremely significantly. The TTAACT, TTCCCC, and ATCACT combination genotypes were dominant combination genotypes, which provided theoretical references for further genetic co-breeding. The results of our study demonstrate the potential role of the IGF2BP1 gene as a functional genetic marker in the breeding programs of Nanjiang Yellow goats.