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Abstract Background This study aims to identify risk factors associated with Methicillin-resistant Staphylococcus aureus (MRSA) infection in children diagnosed with acute osteomyelitis (AO) and to elucidate the laboratory characteristics of these MRSA-infected children to enhance early targeted therapeutic interventions. Methods We conducted a retrospective analysis involving 123 children with acute osteomyelitis treated at our hospital. Upon admission, we measured white blood cell (WBC) counts, C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), and platelet counts. Patients were categorized into two groups: the non-MRSA group (n = 73) and the MRSA group (n = 50), with values assigned as follows (non-MRSA group = 0, MRSA group = 1). Results The MRSA group had a significantly higher average age compared to the non-MRSA group (P 10.95 × 10^9/L, CRP > 49.56 µg/mL, age > 3.5 years, and the absence of suppurative arthritis suggests a heightened risk of MRSA infection.

【Objective】The study was carried out to establish a technical system suitable for tissue culture and rapid propagation of Pholidota chinensis Lindl.【Method】With the whole plant of P. chinensis Lindl as test material, the growth of explants was studied, the best explant and culture medium were selected, and the culture conditions such as seed germination and seedling proliferation were optimized.【Result】The best explant for tissue culture of P. chinensis Lindl. was the seed, and its roots, rhizomes and pseudobulbs did not germinate, but the seeds could germinate. The optimum culture formula of P. chinensis Lindl. was 1/2MS + 6-BA 1.5 mg/L + NAA 0.8 mg/L+6-KT 0.1 mg/L and the protocorm of P. chinensis Lindl. turned green under this condition. The organic matter selection of strong seedlings was conducted by adding banana puree (50 g/L), mashed potato (50 g/L) and coconut water (50 mL/L) to the basal medium, and it was found that the overall growth of P. chinensis Lindl. in the medium with banana puree was good and uniform with many pseudobulbs, and the plant height and leaf length were better than those of the P. chinensis Lindl. with mashed potato or coconut water added to the medium. Finally, 50 g/L banana puree was selected as the best organic matter added to the medium in the subsequent experiment. The best culture formula for the optimization of strong seedlings was 1/2MS + 50 g/L banana puree + 6-BA 0.5 mg/L + NAA 0.5 mg/L + 6-KT 0.3 mg/ L. Under this condition, the P. chinensis Lindl. grew well and the plant height was better. The best medium formula for rooting of strong seedlings was MS + 50 g/L banana puree + IBA 0.5 mg/L + NAA 0.5 mg/L. Under this condition, there were more pseudobulbs and more aerial roots on the seedlings.【Conclusion】To establish a technical system suitable for tissue culture and rapid propagation of P.chinensis Lindl. seeds, the best formula for the germination culture of P. chinensis Lindl. seeds is 1/2MS + 6-BA 1.5 mg/L + NAA 0.8 mg/L+6-KT 0.1 mg/L; the optimum culture formula for the optimization of strong seedlings is 1/2MS + 50 g/L banana puree + 6-BA 0.5 mg/L + NAA 0.5 mg/L + 6-KT 0.3 mg/L; the best medium formula for rooting is MS + 50 g/L banana puree + IBA 0.5 mg/L + NAA 0.5 mg/L. The study results lay a foundation for the resource conservation and utilization of P. chinensis Lindl. and its large-scale production.

To provide a method for the production of 124I by using a medical cyclotron and the method of 124I labeling, 124I was prepared using a nuclear reaction of 124Te (p，n) 124I. Firstly，a 124TeO2/Al2O3 target was obtained by pressing，and then bombarded with a cyclotron for 3-8 hours. After 12 hours，impurity nuclides produced by the side reaction were removed. Finally，a Na124I solution was obtained by iodine sublimation radiochemical separation method. Analyze the purity of Na124I and label it with anti-mesothelin (MSLN) antibody，then inject it into the tail vein of KM mice to observe the distribution of 124I-anti-MSLN. The obtained 124TeO2/Al2O3 target was bombarded with 12.5 MeV energy and 20 μA proton beam to obtain 340.4-1121.1 MBq nuclide products，and after purification，274.2-758.5 MBq of high-purity Na124I solution was obtained. The final radioactive concentration of the obtained Na124I solution was greater than 54840 Bq/μL. Using the Na124I solution to label an anti-MSLN antibody，124I-anti-MSLN probe with a radiochemical purity greater than 99% was obtained. The probe was injected into KM mice via the tail vein，and significant uptake of the probe was observed in the thyroid region of the mice through Micro-PET/CT imaging. This uptake can be blocked by feeding 0.5% KI solution 3 days in advance，and the metabolic behavior conforms to the metabolic pattern of the 124I labeled antibody probe in KM mice. This study summarized the purification of 124I samples of 25 batches in our unit，and tthe equipment and methods involved in the purification process and the use of Na124I after purification were summarized. In order to provide reference for the production and efficient purification of 124I. The results showed that the purified 124I had high nuclear purity and chemical purity，which met the requirements of radiolabeling. The average recovery rate was higher than 70%，and the automatic purification process was safe and reliable.

Abstract Background Mitochondrial (mt) heteroplasmy can cause adverse biological consequences when deleterious mtDNA mutations accumulate disrupting “normal” mt-driven processes and cellular functions. To investigate the heteroplasmy of such mtDNA changes, we developed a moderate throughput mt isolation procedure to quantify the mt single-nucleotide variant (SNV) landscape in individual mouse neurons and astrocytes. In this study, we amplified mt-genomes from 1645 single mitochondria isolated from mouse single astrocytes and neurons to (1) determine the distribution and proportion of mt-SNVs as well as mutation pattern in specific target regions across the mt-genome, (2) assess differences in mtDNA SNVs between neurons and astrocytes, and (3) study co-segregation of variants in the mouse mtDNA. Results (1) The data show that specific sites of the mt-genome are permissive to SNV presentation while others appear to be under stringent purifying selection. Nested hierarchical analysis at the levels of mitochondrion, cell, and mouse reveals distinct patterns of inter- and intra-cellular variation for mt-SNVs at different sites. (2) Further, differences in the SNV incidence were observed between mouse neurons and astrocytes for two mt-SNV 9027:G > A and 9419:C > T showing variation in the mutational propensity between these cell types. Purifying selection was observed in neurons as shown by the Ka/Ks statistic, suggesting that neurons are under stronger evolutionary constraint as compared to astrocytes. (3) Intriguingly, these data show strong linkage between the SNV sites at nucleotide positions 9027 and 9461. Conclusions This study suggests that segregation as well as clonal expansion of mt-SNVs is specific to individual genomic loci, which is important foundational data in understanding of heteroplasmy and disease thresholds for mutation of pathogenic variants.

Abstract This study investigates the role of circular RNAs (circRNAs) in the context of Varicella-Zoster Virus (VZV) lytic infection. We employ two sequencing technologies, short-read sequencing and long-read sequencing, following RNase R treatment on VZV-infected neuroblastoma cells to identify and characterize both cellular and viral circRNAs. Our large scanning analysis identifies and subsequent experiments confirm 200 VZV circRNAs. Moreover, we discover numerous VZV latency-associated transcripts (VLTs)-like circRNAs (circVLTslytic), which contain multiple exons and different isoforms within the same back-splicing breakpoint. To understand the functional significance of these circVLTslytic, we utilize the Bacteria Artificial Chromosome system to disrupt the expression of viral circRNAs in genomic DNA location. We reveal that the sequence flanking circVLTs’ 5’ splice donor plays a pivotal role as a cis-acting element in the formation of circVLTslytic. The circVLTslytic is dispensable for VZV replication, but the mutation downstream of circVLTslytic exon 5 leads to increased acyclovir sensitivity in VZV infection models. This suggests that circVLTslytic may have a role in modulating the sensitivity to antiviral treatment. The findings shed new insight into the regulation of cellular and viral transcription during VZV lytic infection, emphasizing the intricate interplay between circRNAs and viral processes.

Abstract Media bias widely exists in the articles published by news media, influencing their readers’ perceptions, and bringing prejudice or injustice to society. However, current analysis methods usually rely on human efforts or only focus on a specific type of bias, which cannot capture the varying magnitudes, connections, and dynamics of multiple biases, thus remaining insufficient to provide a deep insight into media bias. Inspired by the Cognitive Miser and Semantic Differential theories in psychology, and leveraging embedding techniques in the field of natural language processing, this study proposes a general media bias analysis framework that can uncover biased information in the semantic embedding space on a large scale and objectively quantify it on diverse topics. More than 8 million event records and 1.2 million news articles are collected to conduct this study. The findings indicate that media bias is highly regional and sensitive to popular events at the time, such as the Russia-Ukraine conflict. Furthermore, the results reveal some notable phenomena of media bias among multiple U.S. news outlets. While they exhibit diverse biases on different topics, some stereotypes are common, such as gender bias. This framework will be instrumental in helping people have a clearer insight into media bias and then fight against it to create a more fair and objective news environment.

Abstract The epidermal growth factor (EGF)-like factors, comprising amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), play a critical role in regulating the ovulatory process. Pentraxin 3 (PTX3), an essential ovulatory protein, is necessary for maintaining extracellular matrix (ECM) stability during cumulus expansion. The aim of this study was to investigate the impact of EGF-like factors, AREG, BTC, and EREG on the expression and production of PTX3 in human granulosa-lutein (hGL) cells and the molecular mechanisms involved. Our results demonstrated that AREG, BTC, and EREG could regulate follicular function by upregulating the expression and increasing the production of PTX3 in both primary (obtained from 20 consenting patients undergoing IVF treatment) and immortalized hGL cells. The upregulation of PTX3 expression was primarily facilitated by the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway, induced by these EGF-like factors. In addition, we found that the upregulation of PTX3 expression triggered by the EGF-like factors was completely reversed by either pretreatment with the epidermal growth factor receptor (EGFR) inhibitor, AG1478, or knockdown of EGFR, suggesting that EGFR is crucial for activating the ERK1/2 signaling pathway in hGL cells. Overall, our findings indicate that AREG, BTC, and EREG may modulate human cumulus expansion during the periovulatory stage through the upregulation of PTX3.

The koi carp is an ornamental fish that was obtained through artificial selection from the common carp (Cyprinus carpio L.). The most economically important traits of koi are their beautiful skin patterns in bright colors. As seasonality is an important factor in the biology and ecology of fish, we thus assumed that seasonal changes are involved in regulating the formation of skin color and patterns of koi carp. The white, red, cyan, and black skin colors from four varieties of scaleless koi carp (Doitsu Shiromuji (W), Doitsu Kohaku (WR), Doitsu Showa Sanke (WRI), and Kumonryu (WI)) were evaluated using the CIELab color space (lightness, redness, and yellowness) in different seasons. Compared to winter, the yellowness of the white color in all koi varieties decreased in summer and autumn. The black skin color areas in WRI and WI koi increased in summer and autumn compared to winter. The yellowness of the red color decreased only in WRI koi, while no changes were observed in WR koi. Targeted metabolomics analysis revealed that the levels of the structural pigment guanine of all koi varieties showed significant seasonal variation. Of seven detected carotenoids, the zeaxanthin and tunaxanthin contents in W, WI, and WRI koi changed with the seasons, while none of the carotenoids in WR koi were altered. Of the seven potential regulatory metabolites, epinephrine, melatonin, and cyclic adenosine monophosphate (cAMP) in all four koi varieties showed the highest levels in winter. A correlation analysis suggested that the seasonal changes in white skin color occurred through the epinephrine-cAMP pathway; melanin-dependent and carotenoid-dependent skin color changes occurred through melatonin in koi carp. This study demonstrated the seasonal plasticity of skin color in koi carp regulated by melatonin and epinephrine, associating with variety and color specificity.

This is a case report of a 6-year-old girl with relapsed B cell acute lymphoblastic leukemia in which adoptive cell therapy was applied successfully to treat refractory human parvovirus (HPV) B19 infection. Allogenic chimeric antigen receptor (CAR) T-cell therapy (bispecific CD19/CD22) was bridged to hematopoietic stem cell transplantation (HSCT) using a haploidentical paternal donor. However, HPV B19 DNAemia progressed and transfusion-related graft versus host disease occurred. After finding a third-party related donor with a better HLA match, haploidentical HPV B19-seropositive CD45RA+ depleted cells (16.5 × 106/kg) were administered and paternal TCRαβ+ depleted stem cell were retransplanted. The HPV B19 DNAemia became negative within 1 week and the reticulocyte, neutrophil, hemoglobin, and platelet counts gradually normalized. The patient remained stable during the 1-year outpatient follow-up period. Thus, our case report highlights that persistent B19 infection can lead to pancytopenia, aplastic crisis, and graft rejection and TCRαβ+ depleted haplo-HSCT is an effective means of hematopoiesis recovery. CD45RO memory T-cell therapy is the key to treating and preventing the development of refractory severe HPV B19 infection.

Light is a key factor affecting the growth and quality formation of Dendrobium officinale Kimura et Migo. In this study, we used D. officinale under different light conditions as experimental materials to explore the key genes that regulate its polysaccharide content. In addition, we cloned the UGPase gene and validated the gene by bioinformatics analysis and real-time quantitative PCR. Compared with the natural light control group, 494, 1630 and 599 differentially expressed genes were screened under different light quality conditions of red, blue and yellow, respectively. GO and KEGG enrichment analyses of these differentially expressed genes showed that the differentially expressed genes were enriched in the light signal transduction process under different light quality conditions. Bioinformatics analyses showed that the sequences of the genes were highly conserved with the sequences of the UGPase genes of other species, and had the highest sequence similarity with Phalaenopsis, which is also a member of the orchid family. Real-time quantitative PCR results showed that red light had the most significant promoting effect on the UGPase gene of D. officinale. In this study, we applied high-throughput sequencing technology to establish a transcriptome database of D. officinale under different light conditions and obtained a large amount of transcriptional information about D. officinale. The related genes affecting the quality of D. officinale were analysed at the transcriptional level, and the D. officinale UGPase gene was cloned, and its expression was analysed in different tissues and under different light conditions.

Honokiol, a naturally occurring compound from Magnolia obovata Thunb., has many biological activities, but its anti-α-glucosidase activity is still unclear. Therefore, we determined its inhibitory effects against α-glucosidase. Activity assays showed that honokiol was a reversible mixed-type inhibitor of α-glucosidase, and its IC50 value was 317.11 ± 12.86 μM. Fluorescence results indicated that the binding of honokiol to α-glucosidase caused a reduction in α-glucosidase activity. 3D fluorescence and CD spectra results indicated that the binding of honokiol to α-glucosidase caused conformational change in α-glucosidase. Docking simulated the detailed interactions between honokiol and α-glucosidase, including hydrogen and hydrophobic bonds. All findings showed that honokiol could be used as a natural inhibitor to develop α-glucosidase agents.

In recent years, convolutional neural network (CNN) has achieved great success in the field of network security protection. With the popularization of smart terminals and the gradual increase of power grid informatization and digitization, the protection of power monitoring systems from various cybersecurity threads is a current scientific problem that needs to be solved urgently. To this end, this paper proposes a malware detection method based on genetic algorithm optimization of the CNN-SENet network, which firstly introduces the SENet attention mechanism into the convolutional neural network to enhance the spatial feature extraction capability of the model; then, the application programming interface (API) sequences corresponding to different software behaviors are processed by segmentation and de-duplication, which in turn leads to the sequence feature extraction through the CNN-SENet model; finally, genetic algorithm is used to optimize the hyperparameters of CNN-SENet network to reduce the computational overhead of CNN and to achieve the recognition and classification of different malware at the output layer. The examples under the public dataset containing 8 kinds of malware show that the proposed method is better than the traditional algorithmic model, and can accurately and efficiently achieve malware detection with strong generalization ability.

Sauce-flavor Baijiu shows a typical sauce flavor, with a delicate mouthfeel. Its fermentation process consists of seven cycles, and each cycle produces one kind of base liquor. The fourth cycle liquor has a rich flavor and excellent quality. During the fermentation process, microorganisms are in a dynamic state, while flavor substances differ. This study investigated the microbial changes of Jiupei in the fourth cycle and their impact on flavor substances. Species diversity analysis was conducted on the fourth cycle Jiupei sample using high-throughput sequencing. Flavor substances were analyzed using headspace solid-phase microextraction combined with gas chromatography-mass spectrometry. Results showed that the dominant bacteria in the Jiupei were Lactobacillus, Virgibacillus, and Kroppenstedtia, while dominant fungi were Thermoascus, Aspergillus, and Issatchenkia. The microbial community in the Jiupei showed significant dynamic changes during the later stage of fermentation. The Jiupei showed the richest variety of alcohol and ester substances at the beginning of fermentation, with the relative content of alcohol, ester, and acid compounds showing a pattern of increasing firstly and then gradually decreased during fermentation. This study conducted a correlation analysis between fungi and bacteria at the genus level and flavor substances, revealing that Monascus, Lactobacillus, and Wickerhamomyces were positively correlated with key flavor substances, such as ethyl acetate, ethyl lactate, and ethyl hexanoate, respectively. The data provided a basis for comparing the microorganisms and flavor substances in the fourth cycle of sauce-flavor Baijiu, and offered a theoretical basis for improving the quality of Baijiu.

Abstract Background Epigenetics plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Some studies have reported that YAP is involved in inflammatory response and can regulate target genes through epigenetic modifications. JMJD3, a histone H3K27me3 demethylase, is associated with some inflammatory diseases. In this study, we investigated the role of YAP in the development of IBD and the underlying epigenetic mechanisms. Results YAP expression was significantly increased in both in vitro and in vivo colitis models as well as in patients with IBD. Epithelial-specific knockout of YAP aggravates disease progression in dextran sodium sulfate (DSS)-induced murine colitis. In the TNF-α-activated cellular inflammation model, YAP knockdown significantly increased JMJD3 expression. Coimmunoprecipitation experiments showed that YAP and EZH2 bind to each other, and chromatin immunoprecipitation-PCR (ChIP-PCR) assay indicated that silencing of YAP or EZH2 decreases H3K27me3 enrichment on the promoter of JMJD3. Finally, administration of the JMJD3 pharmacological inhibitor GSK-J4 alleviated the progression of DSS-induced murine colitis. Conclusion Our findings elucidate an epigenetic mechanism by which YAP inhibits the inflammatory response in colitis through epigenetic silencing of JMJD3 by recruiting EZH2.

Abstract Background To analyze the factors affecting the loss of correction effect in patients with congenital scoliosis after one stage posterior hemivertebra resection, orthosis, fusion and internal fixation. Methods Thirty-nine patients with congenital scoliosis (CS) who underwent one-stage posterior hemivertebra resection, orthosis, fusion and internal fixation were retrospectively included in Hebei Children’s Hospital General demographic information of patients was collected. Preoperative and postoperative imaging indicators were compared, Including cobb Angle of the main curvature of the spine, segmental Cobb Angle, compensatory cephalic curve, compensatory curve on the caudal side, segmental kyphosis, coronal balance, sagittal balance, thoracic kyphosis, lumbar lordosis, and apical vertebra translation. Correlation analysis is used to evaluate the factors affecting the loss of judgment and correction effect, and the correlation indicators are included in the multi-factor Logistics regression. Results In terms of radiographic indicators in the coronal plane, compared to preoperative values, significant improvements were observed in postoperative Cobb Angle of main curve (8.00°±4.62° vs. 33.30°±9.86°), Segmental Cobb angle (11.87°±6.55° vs. 31.29°±10.03°), Compensatory cephalic curve (6.22°±6.33° vs. 14.75°±12.50°), Compensatory curve on the caudal side (5.58°±3.43° vs. 12.61°±8.72°), coronal balance (10.95 mm ± 8.65 mm vs. 13.52 mm ± 11.03 mm), and apical vertebra translation (5.96 mm ± 5.07 mm vs. 16.55 mm ± 8.39 mm) (all P 10° (OR = 0.011, 95%CI:0.001–0.234, P = 0.004), associated spinal cord anomalies (OR = 24.369, 95%CI:1.057-561.793, P = 0.046), and preoperative apical translation > 10 mm (OR = 0.012, 95%CI:0.000-0.438, P = 0.016) were influential factors in the progression of the main curve Cobb angle. Conclusion The one-stage posterior hemivertebra resection and short-segment corrective fusion with internal fixation are effective means to treat congenital scoliosis. However, attention should be paid to the loss of correction and curve progression during follow-up. Patients with spinal cord malformation and a large preoperative apical vertebra translation have a greater risk of losing the correction after surgery.

The implementation of differentiated governance for agricultural water pollution (AWP) plays a significant role in alleviating the pressure on agricultural water resources. However, research that comprehensively assesses AWP and its influencing factors from a multidimensional perspective remains relatively limited. This study utilized the grey water footprint (GWF) model to quantify the agricultural grey water footprint (AGWF), agricultural grey water footprint efficiency (AGWFE), agricultural grey water footprint intensity (AGWFI), and agricultural water pollution level (AWPL) in Zhejiang from 2010 to 2020. Subsequently, we applied the standard deviational ellipse (SDE), the kernel density estimation (KDE), and the Dagum Gini coefficient to delve into the dynamic evolution and regional disparities of these indicators. Ultimately, we leveraged both the random forest model and the panel regression model to identify and examine the key factors shaping AGWF-related indicators. The results show that: (1) From 2010 to 2020, in Zhejiang, both AGWF and AGWFI exhibit a trend of first increasing and then decreasing, peaking in 2012. In contrast, AGWFE has consistently increased over the years, reaching an increase of 54.56 CNY/m3 by 2020. Meanwhile, despite fluctuations, AWPL in Zhejiang shows an overall gradual decline. (2) The centroids of relevant indicators for AWP in Zhejiang are primarily located in Jinhua (for AGWF and AGWFI), Shaoxing (for AWPL), and in the area where AGWFE converge. (3) Compared to 2010, the regional disparities in AGWF and AWPL have shrunk significantly in 2020, whereas the regional differences in AGWFE and AGWFI have increased to some extent. In most years, the regional disparities in AGWF, AGWFI, and AWPL are more pronounced in Northeastern Zhejiang compared to the southwestern part. (4) The influencing factors of AGWF, AGWFE, and AGWFI exhibit significant regional heterogeneity. In Northeastern Zhejiang, the primary factors influencing them are technological innovation, resource endowment, and crop-cultivation methods. Conversely, in the southwestern region, the primary factors exerting the same influence are the application intensities of fertilizers, pesticides, and agricultural film application. The primary drivers of AWPL in Zhejiang are grain yield, water resource availability, and crop-planting structure. Notably, these factors do not exhibit regional heterogeneity. The paper proposes AWP control policies from both a comprehensive and multi-dimensional perspective.

Background: Several studies have tried to find a link between timing of lung transplant surgery and patient outcomes. However, there has been conflicting results. This study sought to evaluate the association of operative times and recipient outcomes. Methods: Primary adults lung transplants were identified from the United Network for Organ Sharing Database. Patients were stratified based on time of lung transplant: T1 (12 AM-6 AM); T2 (6 AM-12 PM); T3 (12 PM-6 PM); T4 (6 PM-12 AM). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Results: Within the T4 group, there was a significant increase in length of stay and incidence of primary graft dysfunction, though minor. Unadjusted survival analysis with Kaplan-Meier methods demonstrated that there was no significant difference in long-term survival among the 4 groups (p = 0.55). Following adjustment, no operative time was independently associated with decreased long-term mortality. Variables that were significantly associated with increased long-term mortality included recipient diabetes, creatinine, hospitalization status, intensive care unit status, cigarette use, and donation after circulatory death donor status. Conclusions: Though operative times during the T4 period were associated with increased peri-operative complications, this had no effect on long-term survival. While thoracic transplantation can safely occur no matter what time of day, transplantation should preferentially be performed during normal surgical work hours for the longevity and work life balance of transplant providers and surgeons.

Stroke is the fifth leading cause of death worldwide, and the functional status of the gut plays a key role in patients' prognosis. Recent publications have explored the gut association with stroke, but few articles have been published that specifically address a comprehensive bibliometric analysis of the gut microbiota and its association with stroke. To address this gap, we used bibliometric methods to examine the landscape of research concerning the gut and stroke over approximately two decades, utilizing the Web of Science Core Collection (WoSCC). On November 1, 2022, a search was conducted for English-language articles published between 2002 and 2022, with only including original articles. Visual and statistical analyses were performed using CiteSpace, VOSviewer, and Bibliometrix 4.1.0 Package. After screening relevant articles, the results revealed that the number of articles published in this field has progressively increased during the last two decades. In particular, the total number of publications rapidly increased year by year from 2014. Among them, China ranked first in the world with a total of 227 publications. Authorship analysis highlighted Wang Z as the most prolific author, with 18 publications and an H-index of 14, highlighting significant contributions to this field. Meanwhile, the Southern Medical University of China was identified as the most productive institution. Moreover, analysis of keywords revealed that ‘cerebral ischemia’, ‘intestinal microbiota’, ‘gut microbiota’, and ‘trimethylamine N-oxide’ were popular topics searched, and research on the relationship between stroke and the gut continues to be a research hotspot. In summary, this study presents an overview of the progress and emerging trends in research on the relationship between stroke and gut health over the past two decades, providing a valuable resource for researchers aiming to understand the current state of the field and identify potential directions for future studies.

Abstract In this article, the construction principle of rotary engine and sliding vane internal combustion engine is carefully analyzed, and the concept of micro‐rotary cam internal combustion engine is proposed by integrating and innovating on them. Overall design, theoretical analysis, and model making of miniature rotary cam internal combustion engine and its supporting system. The effects of different air intake modes and different ignition advance angles on the combustion and emission characteristics of internal combustion engines were studied. Through the study of the flow field, combustion and emission characteristics of small rotating internal combustion engines, it is found that the intake form has a great influence on the cylinder smoothness of rotating internal combustion engines. The vortex formed by the end cover inlet air in the middle of the combustion chamber can fully mix the fuel and air in the cylinder, and the mixture is evenly distributed in the combustion chamber to effectively promote the spread of flame. Compared with the surrounding air intake structure, the heat release should be increased by 4.3%, and the total amount of HC and CO generated was 26.8% and 15.7% less, respectively. By studying the turbulent kinetic energy, combustion heat release, peak temperature and pressure in the cylinder, fuel consumption rate and emission characteristics of small rotary internal combustion engine, it is found that when the ignition advance angle of the small rotating internal combustion engine is 5°, the peak pressure in the cylinder is increased by 2.3% compared with other schemes, the fuel consumption rate is high, and the combustion is more complete. In addition, in terms of emission characteristics, the amount of CO and HC generated when the ignition advance angle is 5° are reduced by 35% and 35.3%, respectively.

Background. Outcomes in heart transplantation are affected by a variety of variables and patient factors. However, the impact of circadian rhythms, gene expression, and transcription remain underexplored. We thus evaluated the potential role of donor heart cross-clamp times on short-term and long-term outcomes after heart transplantation. Methods. A total of 31 713 heart transplants were identified from the United Network for Organ Sharing Database. Patients were first stratified on the basis of time of donor procurement: 12 am to 12 pm or 12 pm to 12 am. To evaluate a possible effect of circadian rhythms, donor time was further divided into 5 groups based on preclinical data: 4 am to 8 am; 8 am to 11 am; 11 am to 5 pm; 5 pm to 10 pm; 10 pm to 4 am. Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Results. Patients who received hearts recovered between 12 am and 12 pm had significantly higher survival than those who received hearts recovered between 12 pm and 12 am. This survival difference was observed in both unadjusted (P = 0.002) and adjusted analyses (hazard ratio [HR]: 0.93; 95% confidence interval [CI], 0.89-0.97; P

Procollagen c-protease enhancer protein (PCOLCE) performs an essential action in improving the recreation of procollagen c-protease and promoting the reconstruction of extracellular matrix. High PCOLCE expression was associated with a negative prognosis of stomach cancer, ovarian cancer, and osteosarcoma. The goal of this work is to investigate the function of PCOLCE in glioma. Multiple bioinformatics techniques have been employed to investigate the roles of PCOLCE in glioma, consisting of the correlation between PCOLCE and prognosis, immune checkpoints, immune cell infiltrates, and tumor microenvironment (TME). The gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the potential function of PCOLCE in glioma. PCOLCE was found to be increased in glioma. We revealed that PCOLCE was a potential prognostic factor and related to tumor grade. Up-regulated PCOLCE was related to poor prognosis in lower-grade glioma (LGG), glioblastoma multiforme (GBM), and recurrent glioma. PCOLCE was correlated with immune cell infiltration, particularly B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LGG, and DCs infiltration in GBM. PCOLCE was co-expressed with many genes related to the immune and the immune checkpoint. In addition, glioma patients with low expression of PCOLCE had a higher response to the immunological checkpoint blockade (ICB). Additionally, PCOLCE may exert its roles via several immune-related biological processes or pathways, such as leukocyte migration, activation of T cells, adaptive immune response, neutrophil-mediated immunity, NF-κB, and TNF signaling pathways. In conclusion, PCOLCE may be a new immune-related gene and regulate tumor development through immunological pathways.

The skin color of koi carp (Cyprinus carpio L.) is one of the traits that most influence their ornamental and economic values. The present study suggested the effects of temperature fluctuation on koi carp in terms of skin color and plasma carotenoids and related-metabolites. The main results were as follows. (1) The vulnerability of koi skin color to acute temperature stress was in the order of white koi> black koi> yellow koi. Both high- (25°C-30°C-25°C) and low-temperature (25°C-20°C-25°C) fluctuations tended to decrease the saturation of white koi. The temperature fluctuation had little effects on the skin color of black and yellow koi. (2) Targeted metabolomics analysis indicated that the effects of cooling stress on oxycarotenoids of all five koi varieties were reversible. The plasma oxycarotenoids in mirror koi with all colors were insensitive to acute heat stress. However, the cooling process from a high temperature (30°C-25°C) still made contributions to the increase of oxycarotenoids. (3) The principal component analysis confirmed the deviation of carotenoid-related metabolites after high temperature fluctuation and the reversibility after low temperature fluctuation. Finally, the correlation analysis revealed that koi skin brightness was negatively correlated with the plasma guanine content and that temperature fluctuations might change koi skin brightness via the L(-)-epinephrine-guanine pathway. The red hue and yellow hue were negatively correlated with the oxycarotenoids in plasma, suggesting that oxycarotenoids were favorable for enhancing koi skin color saturation. Overall, this study revealed the direct action of temperature fluctuations on the skin color and carotenoid-related metabolites of koi.

Fever is one of the most common clinical conditions and is characterized by pyrogenic infection, malignancy, inflammation, and tissue damage, among others. Ellagic acid (EA) can inhibit the expression of related proteins on the pathway by blocking the nuclear factor kappa-B(NF-κB) signaling pathway, inhibit the levels of pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), increase the level of anti-inflammatory factor IL-10, and effectively alleviate inflammatory symptoms. In addition, EA can also reduce the levels of malondialdehyde(MDA) and nitric oxide(NO) in the body, increase the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase(CAT), scavenge oxidative free radicals, inhibit lipid oxidation, and achieve antipyretic and anti-inflammatory effects. The purpose of this study was to establish the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, prostaglandin E2(PGE2), and cyclic adenosine monophosphate(cAMP), and clarify the mechanism of the cyclooxidase-2(COX-2)/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Compared to lipopolysaccharide (LPS)- treated animals, subsequent administration of EA significantly lowered the LPS-induced rectal temperature increase (p < 0.05 or p < 0.01), significantly increased serum SOD and GSH levels (p < 0.05 or p < 0.01), and significantly decreased serum MDA, IL-1β, IL-6, and TNF-α levels (p < 0.05 or p < 0.01). In addition, compared to LPS-treated animals, subsequent administration of EA significantly decreased cerebrospinal fluid cAMP and PGE2 levels (p < 0.05 or p < 0.01), significantly decreased cAMP, significantly increased 5-HT levels (p < 0.05 or p < 0.01), and significantly down-regulated p-NF-κB p65 and COX-2 protein levels in the hypothalamus. Subsequent gas chromatography mass spectrometry(GC-MS) metabolite analysis indicated that 12 differential metabolites were detected in serum isolated 4 h after LPS treatment, and 10 differential metabolites were detected in serum collected 7 h after LPS treatment. Next, Pearson correlation analysis was used to systematically characterize the relationship between the identified metabolites and TNF-α, IL-6, MDA, SOD, PGE2, and cAMP. The levels of propionic acid, pyridine, and L-valine were up-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α and increased the activity of GSH. The levels of inositol, urea, and 2-monopalmitin were down-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α, increased the activity of SOD and GSH, reduced the inflammatory response, and alleviated the oxidative stress state. Combined with the results of the metabolic pathway analysis, we suggest that the pathways of the galactose metabolism, synthesis and degradation of ketone bodies, as well as ascorbic acid and aldehyde acid metabolism are closely related to the antipyretic and anti-inflammatory effects of EA. Our study established the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, PGE2, and cAMP, and clarified the mechanism of the COX-2/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism.

Developing a comprehensive research framework that integrates the water–energy–carbon (WEC) system with economic development is crucial to fostering sustainable development. However, common evaluation indicators for sustainable development fail to cover the most up-to-date climate objectives and policies comprehensively and also lack a decoupling analysis between various subsystems and economic development. By incorporating the Tapio model and the coupling coordination degree model (CCDM), we introduce a novel water–energy–carbon–economy (WECE) framework to evaluate the sustainability of regional resources and the environment. Taking the Yangtze River Economic Belt (YREB) as an example, we have constructed a comprehensive water–energy–carbon (WEC) indicator system that aligns with China’s sustainable development objectives and its most recent carbon emission reduction strategies. Employing the indicator system, we conducted an assessment of the sustainable development within the YREB from 2010 to 2019. The results reveal that the YREB has yet to achieve full decoupling between water use, energy consumption, carbon emissions, and economic development, with a prevailing trend towards weak decoupling (WD). The WEC system within the YREB exhibited coordination from 2010 to 2019. Notably, only the WEC system in Sichuan attained good coordination in 2019, indicating the imperative for more extensive initiatives in resource and environmental development to realize sustainable objectives. Finally, we delve into the driving mechanism of the coupling coordination degree (CCD) of the WEC system. Our findings suggest that, from the perspective of system collaborative management, the integrated approach of the WEC system offers superior benefits compared to individual management components. Consequently, it is imperative to bolster collaboration and institute a comprehensive set of policies to ensure sustainable development within the region.

Abstract Hepatocellular carcinoma (HCC) is one of the deadliest malignancies worldwide, with late detection, ineffective treatment and poor overall survival. Immunotherapy, including immune checkpoint inhibitor (ICI) therapy, holds great potential for treatment of HCC. Although some patients respond well to ICIs, many fail to obtain a significant benefit. It is therefore of great interest to find appropriate markers to stratify patient responses to immunotherapy and to explore suitable targets for modulating the TME and immune cell infiltration. ATP6V1F encodes a constituent of vacuolar ATPase (V-ATPase). V-ATPase-mediated acidification of organelles is required for intracellular processes such as zymogen activation, receptor-mediated endocytosis, protein sorting and synaptic vesicle proton gradient generation. In this study, we confirmed for the first time that ATP6V1F is overexpressed in HCC and related to poor prognosis in these patients. We identified that overexpression of ATP6V1F is associated with infiltration of some immune cells and expression of several immune checkpoints. Furthermore, we explored the possible mechanisms of action of ATP6V1F. Finally, we conducted in vitro experiments, including wound healing, Transwell invasion, and apoptosis assays, to verify that ATP6V1F promotes development of HCC by promoting migration and invasion and inhibiting apoptosis of HCC cells. Our findings will contribute to providing precise immunotherapy to patients with HCC.

ABSTRACT Viral vector vaccine represents one of the important research directions of novel vaccines. Viral vectors can efficiently deliver foreign genes and drive robust transgene expression in vivo. Generally, viral vector vaccines can achieve high immunogenicity and rapid response to a new pandemic. However, few types of viral vectors have been thoroughly evaluated for vaccine development, and the application of viral vectors is often limited by packaging capacity, vector immunogenicity, or pre-existing immunity. Cytomegalovirus (CMV) has been regarded as a promising novel vaccine vector because it has the advantages of high package capacity, good safety profiles, and the capacity to induce long-lasting immune responses. In this study, a luciferase-tagged reporter murine CMV (MCMV) was constructed, and the viral dissemination feature in vivo was studied. Furthermore, MCMVs expressing three structural proteins of SARS-CoV-2 were constructed and used to immunize mice. The level of binding antibodies and neutralizing antibodies against the original Wuhan strain and the Omicron variant (BA.2) was compared. Moreover, the CMV vector’s transmission capacity and pre-existing immunity’s influence on CMV-vectored vaccine efficacy were studied. The results showed that CMV vector could only cause transient systemic, but not persistent, infection. Immunization of CMV-vectored vaccines was able to elicit neutralizing antibodies against the Omicron variant (BA.2). However, the titer of neutralizing antibodies against BA.2 is much lower when compared with the original strain. The studies also showed that the CMV vectors would not cause unexpected viral transmission, and pre-existing immunity might impair the immunogenicity of subsequent CMV-vectored vaccines. Collectively, the CMV-vectored vaccine represents a promising approach to developing novel vaccines against epidemic pathogens. IMPORTANCE Cytomegalovirus (CMV) has been used as a novel viral vector for vaccine development and gene therapy. Coronavirus disease 2019 is an infectious disease caused by the SARS-CoV-2 virus, which is highly mutable and is still circulating globally. The study showed that the CMV viral vector caused transient systemic infection and induced robust transgene expression in vivo. CMV vectors expressing different SARS-CoV-2 proteins were immunogenic and could elicit neutralizing antibodies against a highly mutated Omicron variant (BA.2). The expression level of receptor-binding domain (RBD) protein was higher than that of full-length S protein using CMV as a vaccine vector, and CMV vector expression RBD protein elicited higher RBD-binding and neutralizing antibodies. Moreover, the study showed that CMV-vectored vaccines would not cause unexpected viral transmission, and pre-existing immunity might impair the immunogenicity of subsequent CMV-vectored vaccines. These works provide meaningful insights for the development of a CMV-based vector vaccine platform and the prevention and control strategies for SARS-CoV-2 infection.

Chimeric antigen receptor (CAR-T) cell therapy has been widely used in hematological malignancies and has achieved remarkable results, but its long-term efficacy in solid tumors is greatly limited by factors such as the tumor microenvironment (TME). In this paper, we discuss the latest research and future views on CAR-T cell cancer immunotherapy, compare the different characteristics of traditional immunotherapy and CAR-T cell therapy, introduce the latest progress in CAR-T cell immunotherapy, and analyze the obstacles that hinder the efficacy of CAR-T cell therapy, including immunosuppressive factors, metabolic energy deficiency, and physical barriers. We then further discuss the latest therapeutic strategies to overcome these barriers, as well as management decisions regarding the possible safety issues of CAR-T cell therapy, to facilitate solutions to the limited use of CAR-T immunotherapy.

Sauce-flavor baijiu (SFB) is a traditional Chinese distilled liquor crafted through a distinctive brewing process, involving seven rounds of stack fermentation (SF) and pit fermentation (PF). To date, there remains a knowledge gap regarding the microbial succession and flavor throughout all rounds of SFB with distinctive northern characteristics. Through LEfSe analysis, Saccharopolyspora, Virgibacillus, Thermoascus and Thermomyces, and Lactobacillus and Issatchenkia were found to be the most differentially representative genera in SF and PF, respectively. A total of 93 volatile flavor compounds were found in base baijius through the gas-chromatography mass spectrometry. Moreover, 29 volatile flavor substances with significant difference in base baijius of different rounds were revealed using the OPLS-DA model and VIP values and Spearman correlation analysis shows that bacteria have a greater impact on differential flavor compounds than fungi. This study provides a new perspective and insight into the brewing of northern SFB.

Abstract Background The gap junction protein, connexin 43 (Cx43) is highly expressed in human granulosa-lutein (hGL) cells. The phosphorylation of certain amino acid residues in the Cx43 protein has been shown to be related to a decline in gap junction intercellular communication (GJIC), which subsequently affects oocyte meiotic resumption. As a member of the epidermal growth factor (EGF) family, betacellulin (BTC) mediates luteinizing hormone (LH)-induced oocyte maturation and cumulus cell expansion in mammalian follicles. Whether BTC can regulate Cx43 phosphorylation, which further reduces Cx43-coupled GJIC activity in hGL cells remains to be determined. Methods Immortalized human granulosa cells (SVOG cells) and primary human granulosa-lutein cells obtained from women undergoing in vitro fertilization in an academic research center were used as the study models. The expression levels of Cx43 and phosphorylated Cx43 were examined following cell incubation with BTC at different time points. Several kinase inhibitors (sotrastaurin, AG1478, and U0126) and small interfering RNAs targeting EGF receptor (EGFR) and receptor tyrosine-protein kinase 4 (ErbB4) were used to verify the specificity of the effects and to investigate the molecular mechanisms. Real-time-quantitative PCR and western blot analysis were used to detect the specific mRNA and protein levels, respectively. GJIC between SVOG cells were evaluated using a scrape loading and dye transfer assay. Results were analyzed by one-way analysis of variance. Results The results showed that BTC induced the rapid phosphorylation of Cx43 at serine368 without altering the expression of Cx43 in primary and immortalized hGL cells. Additionally, using a dual inhibition approach (kinase inhibitors and siRNA-based expression knockdown), we demonstrated that this effect was mainly mediated by the EGFR but not the ErbB4 receptor. Furthermore, using a protein kinase C (PKC) kinase assay and a scrape-loading and dye transfer assay, we revealed that PKC signaling is the downstream signaling pathway that mediates the increase in Cx43 phosphorylation and subsequent decrease in GJIC activity in response to BTC treatment in hGL cells. Conclusions BTC promptly induced the phosphorylation of connexin 43 at Ser368, leading to decreased GJIC activity in hGL cells. The BTC-induced cellular activities were most likely driven by the EGFR-mediated PKC-dependent signaling pathway. Our findings shed light on the detailed molecular mechanisms by which BTC regulates the process of oocyte meiotic resumption.

Abstract Chemotherapy remains the mainstay of treatment for patients with advanced liposarcoma (LPS), but response rates are only 25% and the overall survival at 5 years is dismal at 20–34%. Translation of other therapies have not been successful and there has been no significant improvement in prognosis for nearly 20 years. The aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in the aggressive clinical behavior LPS and in resistance to chemotherapy, but the precise mechanism remains elusive and efforts to target AKT clinically have failed. Here we show that the AKT-mediated phosphorylation of the transcription elongation factor IWS1, promotes the maintenance of cancer stem cells in both cell and xenograft models of LPS. In addition, phosphorylation of IWS1 by AKT contributes to a “metastable” cell phenotype, characterized by mesenchymal/epithelial plasticity. The expression of phosphorylated IWS1 also promotes anchorage-dependent and independent growth, cell migration, invasion, and tumor metastasis. In patients with LPS, IWS1 expression is associated with reduced overall survival, increased frequency of recurrence, and shorter time to relapse after resection. These findings indicate that IWS1-mediated transcription elongation is an important regulator of human LPS pathobiology in an AKT-dependent manner and implicate IWS1 as an important molecular target to treat LPS.

Claudin18.2 (CLDN18.2) is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer. It has been identified as a promising target and a potential biomarker to diagnose tumor, evaluate efficacy, and determine patient prognosis. TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2. In this study, we constructed a solid target radionuclide zirconium-89 (89Zr) labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines. The [89Zr]Zr-desferrioxamine (DFO)-TST001 showed high radiochemical purity (RCP, >99%) and specific activity (24.15 ± 1.34 GBq/μmol), and was stable in 5% human serum albumin, and phosphate buffer saline (>85% RCP at 96 h). The EC50 values of TST001 and DFO-TST001 were as high as 0.413 ± 0.055 and 0.361 ± 0.058 nM (P > 0.05), respectively. The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors (1.11 ± 0.02 vs. 0.49 ± 0.03, P = 0.0016) 2 days post injection (p.i.). BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i. with [89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups. Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive (+++) for CLDN18.2, while those in the BGC823 group did not express CLDN18.2 (−). The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice (2.05 ± 0.16 %ID/g) than BGC823 mice (0.69 ± 0.02 %ID/g) and blocking group (0.72 ± 0.02 %ID/g). A dosimetry estimation study showed that the effective dose of [89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq, which is within the range of acceptable doses for nuclear medicine research. Taken together, these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.

Abstract The gene expression profile of abdominal aortic aneurysm (AAA) neck is not fully understood. The etiology of AAA is considered to be related to atherosclerosis and the inflammatory response, involving congenital, genetic, metabolic, and other factors. The level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to those of cholesterol, oxidized low-density lipoprotein, and triglycerides. PCSK9 inhibitors have significant effects on lowering LDL-cholesterol, reversing atherosclerotic plaques, and reducing the risk of cardiovascular events and have been approved by several lipid-lowering guidelines. This work was aimed to investigate the potential role of PCSK9 in the neck of AAA. We extracted the expression dataset (GSE47472) containing 14 AAA patients and 8 donors and single-cell RNAseq (scRNA-seq) data (GSE164678) of CaCl2-induced (AAA) samples from the Gene Expression Omnibus dataset. Through bioinformatics methods, we found that PCSK9 was up-regulated in the proximal neck of human AAA. In AAA, PCSK9 was mainly expressed in fibroblasts. Additionally, immune check-point PDCD1LG2 was also expressed higher in AAA neck than donor, while CTLA4, PDCD1, and SIGLEC15 were down-regulated in AAA neck. The expression of PCSK was correlated with PDCD1LG2, LAG3, and CTLA4 in AAA neck. Additionally, some ferroptosis-related genes were also down-regulated in AAA neck. PCSK9 was also correlated with ferroptosis-related genes in AAA neck. In conclusion, PCSK9 was highly expressed in AAA neck, and may exert its role through interacting with immune check-points and ferroptosis-related genes.

Abstract Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field, and include new PET-labelling methods for 11C and 18F, the importance of choosing the proper chelator for a given radioactive metal ion, implications of total body PET on use of radiopharmaceuticals, legislation issues and radionuclide therapy including the emerging role of 161Tb.

Polysaccharides from Dendrobium officinale have garnered attention for their diverse and well-documented biological activities. In this study, we isolated three ethanol-fractionated polysaccharides from Dendrobium officinale (EPDO) and investigated their digestive properties and effects on gut microbiota regulation in vitro. The results indicated that after simulating digestion in saliva, gastric, and small intestinal fluids, three EPDOs, EPDO-40, EPDO-60 and EPDO-80, with molecular weights (Mw) of 442.6, 268.3 and 50.8 kDa, respectively, could reach the large intestine with a retention rate exceeding 95%. During in vitro fermentation, the EPDOs were broken down in a “melting” manner, resulting in a decrease in their Mw. EPDO-60 degraded more rapidly than EPDO-40, likely due to its moderate Mw. After 24 h, the total production of short-chain fatty acids (SCFAs) for EPDO-60 reached 51.2 ± 1.9 mmol/L, which was higher than that of EPDO-80. Additionally, there was an increase in the relative abundance of Bacteroides, which are capable of metabolizing polysaccharides. EPDO-60 also promoted the growth of specific microbiota, including Prevotella 9 and Parabacteroides, which could potentially benefit from these polysaccharides. Most notably, by comparing the gut microbiota produced by different fermentation carbon sources, we identified the eight most differential gut microbiota specialized in polysaccharide metabolism at the genus level. Functional prediction of these eight differential genera suggested roles in controlling replication and repair, regulating metabolism, and managing genetic information transmission. This provides a new reference for elucidating the specific mechanisms by which EPDOs influence the human body. These findings offer new evidence to explain how EPDOs differ in their digestive properties and contribute to the establishment of a healthy gut microbiota environment in the human body.

Arguments about the origin and evolution of the evergreen broad-leaved forests in East Asia exist generally, and are even contradictory in some cases. The origin and evolution of the flora of East Asia, especially in the evolutionary process, the formation time of the Asian monsoon, the implications of phylogenetic and biogeographic studies on some important taxa, and the implications of palaeobotanical evidence are debatable. Most research from different disciplines suggests that the monsoon in the Miocene was key to the diversification of East Asian flora and its evergreen broad-leaved forests. The common view is that the evergreen broad-leaved forests of East Asia are closely related to the monsoon’s intensity and developments, which were caused by the uplift of Himalaya–Tibet during or after the mid-Miocene. Analysis of the floristic elements show that the present subtropical evergreen broad-leaved forests in East Asia could have an early or ancient tropical origin and a tropical Asian affinity, but that their species are dominated by endemic Chinese or East Asian ones, many of which have tropical Asian affinity or are tropical sister species. The time of Himalayan uplift and the intensity of the monsoon climate are believed to be key to the formation of the evergreen broad-leaved forests in East Asia. Combined with existing paleobotanical findings, the uplift of the Himalayas and the formation of the monsoon climate, as well as floristic elements of the subtropical evergreen broad-leaved forests, we believe that they evolved from an Asian tropical rainforest after the mid-Miocene in the southeastern region of East Asia, while the ancient subtropical evergreen broad-leaved forests in the southwestern region continuously evolved into the present subtropical ones.

Background: The survival rate of hepatocellular carcinoma (HCC) is low and the prognosis is poor. Metabolic reprogramming is still an emerging hallmark of cancer, and reprogramming of cholesterol metabolism plays a crucial action in tumor pathogenesis. Increasing evidence suggests that cholesterol metabolism affects the cell proliferation, invasion, migration, and resistance to chemotherapy of HCC. To date, no long noncoding RNA (lncRNA) signature associated with cholesterol metabolism has been developed to predict the outcome of patients with HCC. Methods: The RNA-seq data as well as the prognostic and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We conducted univariate and multivariate analyses to assess cholesterol metabolism-related lncRNAs correlated with the prognosis of patients with HCC in order to construct a prognostic signature. Functional differences between low- and high-risk groups were investigated using genomic enrichment analysis (GSEA). Kaplan-Meier (KM) curves were applied to explore the overall survival (OS) of the low- and high-risk groups. Single-sample genomic enrichment analysis (ssGSEA) was applied to investigate the association between this predictive signature and immune function. We subsequently examined how this signature relates to treatment response in HCC patients. Results: A prognostic signature comprising six lncRNAs related to cholesterol metabolism was constructed (AC124798.1, AL031985.3, AC103760.1, NRAV, WAC-AS1 and AC022613.1). We found that low-risk groups showed a better prognosis than high-risk groups. In HCC patients, the cholesterol metabolism-related lncRNA signature may be served as an independent prognostic factor. Cholesterol metabolism-related lncRNA signature had higher diagnostic efficiency compared to clinicopathologic variables. After stratifying patients according to different clinicopathological variables, patients with low-risk had a longer OS compared with high-risk patients. The ssGSEA demonstrated that this signature was closely related to the immune status of HCC patients. GSEA analysis demonstrated that immune- and tumor-related pathways were predominantly enriched in the high-risk group. High-risk patients were more responsive to immune checkpoint inhibitors (ICIs) and conventional chemotherapeutic agents. Conclusions: This cholesterol metabolism-related lncRNA signature can predict the prognosis of HCC patients and guide the clinical management of HCC patients, including immunotherapy.

Widely occurred on diverse habitats from hot dry deep valleys to cold temperate mountains, the sclerophyllous evergreen broad-leaved forest dominated by Quercus species (Fagaceae), is an unique vegetation type in Yunnan. The forest is similar to sclerophyllous oak forests in the modern Mediterranean regions on physiognomy. It differs obviously from the other subtropical evergreen broad-leaved forests in Yunnan by its particular physiognomy, structure, characteristic tree species and geographical distribution, and is named as “sclerophyllous evergreen broad-leaved forest” in the vegetation classification of Yunnan. The sclerophyllous forest is a special vegetation type developed to adapt to the new environment during uplift of the Himalayas. The dominant tree species of the forest show Mediterranean floristic affinity, but they presently distribute mostly in southwestern China. Except for Quercus species, its floristic composition is the same as other neighbor vegetations. The community structure of sclerophyllous evergreen broad-leaved forest is simple. The typical forest community has a profile of tree-shrub-herb layers as common forests, but hemicryptophyte plants absolutely dominate in the communities on cold temperate mountains, and herbaceous plants dominate in the communities at hot dry valleys in its life form. The sclerophyllous oak species fossils recorded in moist tropical-subtropical evergreen broad-leaved forest in Tethys region before Miocene. Until Pliocene epoch, the modern Mediterranean climate formed and drought-resistant Mediterranean flora arose, the sclerophyllous evergreen broad-leaved forest evolved from the former tropical-subtropical evergreen broad-leaved forest with the Himalayas uplift.

Fault diagnosis is critical to maintaining the performance of rotating machinery and ensuring the safe operation of the equipment. Convolutional neural networks (CNNs) have recently shown great potential with excellent automatic feature learning and nonlinear mapping abilities in the field of rotating machinery fault diagnosis. However, the CNN-based methods still suffer from some defects, such as inadequate data utilization and uneconomical computational efficiency, which limit the further improvement of diagnosis performance. Therefore, this paper proposes a fault diagnosis method based on multi-sensor fusion and Convolutional Neural Network with Efficient Channel Attention (ECA-CNN). First, multi-sensor vibration signals are sampled, converted, and channel fused into multi-channel images with rich and comprehensive features. Then, the efficient channel attention mechanism is introduced into CNN to increase the feature learning ability by adaptively scoring and assigning weights to the channel features. The ECA-CNN is proposed to learn representative fault features from multi-sensor fusion data to achieve fault identification. Finally, two experimental cases on the bearing and gearbox datasets prove that the proposed method has excellent performance, strong generalization capability, and high computational efficiency.

Abstract Tactile perception plays a critical role in the interaction of humans and environment. It begins with the mechanical stimulation induced by friction and is processed in the somatosensory cortex. To quantify the tactile perceptions of textile fabrics, the mechanical properties of fabrics and the features extracted from the friction and vibration signals were correlated with the subjective sensation rated by questionnaires. Meanwhile, the technique of functional magnetic resonance imaging (fMRI) was used to identify the brain areas responsible for the tactile perception of textile fabrics. The results showed that during the tactile perception of textile fabrics, the coefficient of friction increased with the increasing normal load, indicating that the deformation mechanism of skin was relevant to the friction of skin against fabrics. The features of spectral centroid (SC), coefficient of friction, and diameter and critical buckling force of fiber had a strong correlation with the perceived fineness, slipperiness, and prickliness of fabrics, respectively. The postcentral gyrus, supramarginal gyrus, and precentral gyrus, with the corresponding functional regions of the primary somatosensory cortex (SI), secondary somatosensory cortex (SII), primary motor cortex (MI), and secondary motor cortex (MII), were involved with the perceptions of fabric textures. The fiber properties and fabric surface structures that caused the multidimensional feelings tended to induce the large area, intensity, and percent signal change (PSC) of brain activity. This study is meaning for evaluating the tactile stimulation of textile fabrics and understanding the cognitive mechanism in the tactile perception of textile fabrics.

MG53 is an essential component of the cell membrane repair machinery, participating in the healing of dermal wounds. Here we develop a novel delivery system using recombinant human MG53 (rhMG53) protein and a reactive oxygen species (ROS)-scavenging gel to treat diabetic wounds. Mice with ablation of MG53 display defective hair follicle structure, and topical application of rhMG53 can promote hair growth in the mg53−/− mice. Cell lineage tracing studies reveal a physiological function of MG53 in modulating the proliferation of hair follicle stem cells (HFSCs). We find that rhMG53 protects HFSCs from oxidative stress-induced apoptosis and stimulates differentiation of HSFCs into keratinocytes. The cytoprotective function of MG53 is mediated by STATs and MAPK signaling in HFSCs. The thermosensitive ROS-scavenging gel encapsulated with rhMG53 allows for sustained release of rhMG53 and promotes healing of chronic cutaneous wounds and hair follicle development in the db/db mice. These findings support the potential therapeutic value of using rhMG53 in combination with ROS-scavenging gel to treat diabetic wounds.

Although the etoposide and carboplatin (EP) combination strategy has been the first-line chemotherapy, patients with extensive-stage disease small-cell lung cancer (SCLC) still have poor survival outcomes. Our retrospective analysis revealed that 46 patients with SCLC only achieved medium overall survival (OS) of 11.6 months after treated by EP. Recently, it was demonstrated that combination therapy of PD1/PD-L1 immune checkpoint blocker and EP could significantly improve the OS of SCLC patients. However, the serious treatment-related toxicity leaded to a high rate of treatment-discontinuation or even death. In the present study, we have developed a novel TPP1-conjugated nanocomplex, abbreviated as TPP1NP-EP, which was co-loaded with carboplatin (CBP) and etoposide (VP16). The TPP1 was a PD-L1 targeting peptide and conjugated on the surface of nanocomplex by a matrix metalloproteinase (MMP-2/9)-cleavable peptide linker sequence PLGLAG. For dual-loading of CBP and VP16, the CBP was chemically conjugated with poly(ethylene glycol) (PEG)–poly(caprolactone) (PCL) by pH-sensitive hydrazone bond and the VP16 was physically encapsulated by emulsion-solvent evaporation method. In vitro and in vivo experiments demonstrated an excellent anti-tumor effect of TPP1NP-EP on SCLC and improved safety. In conclusion, the present study has provided a promising strategy for treatment of malignant SCLC.

Abstract Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a TH1 (T Helper type 1) cytokine profile and substantial CD4+ T cell responses in BALB/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.

Magnetron sputtering technology benefits from an easy process parameter adjustment strategy, good experimental reproducibility, and high-quality film formation; thus, it is widely used in thin-film electronic devices. In the present work, the thickness and morphology of the TiO2 electron transport layer were controlled by magnetron sputtering time, and based on this technology, planar heterojunction perovskite solar cells were prepared. The results showed that with an increase in the sputtering time, the surface roughness of the TiO2 film decreased, and the electrical homogeneity and square resistance of the film increased. Especially, the film transmittance showed a maximum value of 82.29% at 45 min of deposition, and the so prepared perovskite solar cells exhibited the highest photoelectric conversion efficiency of up to 12.42%.

Abstract Background and purpose Stroke is associated with high disability and mortality rates and increases the incidence of organ-related complications. Research has revealed that the outcomes and prognosis of stroke are regulated by the state of the intestinal microbiota. However, the possibility that the manipulation of the intestinal microbiota can alter sex-related stroke outcomes remain unknown. Methods To verify the different effects of microbiota from different sexes on stroke outcomes, we performed mouse fecal microbiota transplantation (FMT) and established a model of ischemic stroke. Male and female mice received either male or female microbiota through FMT. Ischemic stroke was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control. Over the next few weeks, the mice underwent neurological evaluation and metabolite and inflammatory level detection, and we collected fecal samples for 16S ribosomal RNA analysis. Results We found that when the female mice were not treated with FMT, the microbiota (especially the Firmicutes-to-Bacteroidetes ratio) and the levels of three main metabolites tended to resemble those of male mice after experimental stroke, indicating that stroke can induce an ecological imbalance in the biological community. Through intragastric administration, the gut microbiota of male and female mice was altered to resemble that of the other sex. In general, in female mice after MCAO, the survival rate was increased, the infarct area was reduced, behavioral test performance was improved, the release of beneficial metabolites was promoted and the level of inflammation was mitigated. In contrast, mice that received male microbiota were much more hampered in terms of protection against brain damage and the recovery of neurological function. Conclusion A female-like biological community reduces the level of systemic proinflammatory cytokines after ischemic stroke. Poor stroke outcomes can be positively modulated following supplementation with female gut microbiota.

Abstract Deregulation of NEK2(NIMA-related serine/threonine 2) confers chemotherapeutic resistance to apoptosis and is closely correlated with poor prognosis in hepatocellular carcinoma (HCC). Here, we find that nanoparticles are prepared through hemisynthesis from natural nitidine chloride (NC) with enhanced antitumor activity. Nitidine chloride nanoparticle (TPGS-FA/NC) treatment show good therapy effect in Li-7 hepatocellular carcinoma cells. Additionally, molecular docking technologies are aimed at NEK2 protein (PDB ID: 6SGD) to analyze the detailed binding interactions with the potent target. NC participates in interactions with Asp159 residue. These studies advance the understanding of the modification of nitidine chloride substituent and provide useful drug design information for liver cancer treatment.

The application of the valuable natural product thaxtomin A, a potent bioherbicide from the potato scab pathogenic Streptomyces strains, has been greatly hindered by the low yields from its native producers. Here, we developed an orthogonal transcription system, leveraging extra-cytoplasmic function (ECF) sigma (σ) factor 17 (ECF17) and its cognate promoter Pecf17, to express the thaxtomin gene cluster and improve the production of thaxtomin A. The minimal Pecf17 promoter was determined, and a Pecf17 promoter library with a wide range of strengths was constructed. Furthermore, a cumate inducible system was developed for precise temporal control of the ECF17 transcription system in S. venezuelae ISP5230. Theoretically, the switchable ECF17 transcription system could reduce the unwanted influences from host and alleviate the burdens introduced by overexpression of heterologous genes. The yield of thaxtomin A was significantly improved to 202.1 ± 15.3 μ g/mL using the switchable ECF17 transcription system for heterologous expression of the thaxtomin gene cluster in S. venezuelae ISP5230. Besides, the applicability of this transcription system was also tested in Streptomyces albus J1074, and the titer of thaxtomin A was raised to as high as 239.3 ± 30.6 μg/mL. Therefore, the inducible ECF17 transcription system could serve as a complement of the generally used transcription systems based on strong native constitutive promoters and housekeeping σ factors for the heterologous expression of valuable products in diverse Streptomyces hosts.