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Abstract This study examines tuberculosis (TB) incidence among students in Jilin Province, China, focusing on spatial, temporal, and demographic dynamics in areas of social inequality. Variation in incidence rate of TB was analyzed using the joinpoint regression method. Spatial analyses techniques included the global and local Moran indices and Getis-Ord Gi* analysis. Demographic changes in new cases were analyzed descriptively, and the Geodetector method measured the influence of risk factors on student TB incidence. The analysis revealed a declining trend in TB cases, particularly among male students. TB incidence showed geographical heterogeneity, with lower rates in underdeveloped rural areas compared to urban regions. Significant spatial correlations were observed, with high-high clusters forming in central Jilin Province. Hotspots of student TB transmission were primarily concentrated in the southwestern and central regions from 2008 to 2018. Socio-economic factors exhibited nonlinear enhancement effects on incidence rates, with a dominant bifactor effect. High-risk zones were predominantly located in urban centers, with university and high school students showing higher incidences than other educational stages. The study revealed economic determinants as being especially important in affecting TB incidence among students, with these factors having nonlinear interacting effects on student TB incidence.

Objective Shield tunneling may cause displacement and deformation of the nearby viaduct foundation and reduce its bearing capacity. Therefore, the deformation effect caused by shield tunnel closely side-passing viaduct foundation is studied based on an actual project. Method Relying on the project of Hefei Metro Line 5 in which the shield tunnel passes the pile foundation of the viaduct on the side, a three-dimensional numerical model is established to analyze the horizontal displacement,the longitudinal displacement and the settlement pattern of the pile foundation caused by shield construction. Result & Conclusion The research results show that the horizontal displacement at the pile bottom presents dynamic changes of leaving, approaching and leaving the tunnel. The horizontal displacement of the pile body is similar to a C shape flexture curve. The displacement increases first and then decreases along with the pile depths, and the extreme value is located at the pile depth of 9~10 m. The longitudinal displacement at the pile bottom （parallel to the tunnel axis） shows a bimodal curve. After the shield passing the pile foundation, the pile body undergoes longitudinal deformation in the opposite direction of the excavation. After the shield passing through the pile foundation for 12m and further, the horizontal displacement of the pile body in longitudinal direction rebounds, indicating that the influence of shield tunneling on the longitudinal deformation of the pile foundation is reversible to a certain extent. The settlement of the pile foundation presents a steep trend. The closer the pile foundation at the same side is to the tunnel, the greater the settlement. Moreover, the excavation of the far side tunnel will cause secondary settlement of the pile top. The maximum settlement occurs at the bottom of the No.4 pile foundation, and the settlement value is 4.94 mm.

Objective: To investigate the potential role of the regulator of G protein signaling 20 (RGS20) in radioresistance of non-small cell lung cancer (NSCLC). Methods: A total of 35 lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA), who underwent radiotherapy, were enrolled and divided into radiosensitive (n ​= ​16) and radioresistant (n ​= ​19) groups based on clinical prognosis. The expression and prognosis of RGS20 were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) database. A radioresistant cell line (A549R) was constructed by irradiating A549 ​cells with 6 ​Gy X-rays for 10 fractions. Cell survival was measured by colony formation assay. The regulatory effect of RGS20 on pyroptosis were verified by LDH release and Western blot assay, and the underlying mechanism was investigated by transfecting RGS20 siRNA and applying a GSDMD inhibitor). Results: A total of 2,181 differentially expressed genes (DEGs) were identified by analyzing the data of radiosensitive and radioresistant individuals from the TCGA-LUAD dataset. These DEGs were enriched in G alpha (z) signalling events analyzed by Reactome database. RGS20 exhibited significant upregulation among the DEGs, and its higher expression predicted poor prognosis in LUAD patients. In vitro, the expression of RGS20 protein was increased by irradiation in A549 ​cells, whereas it remained at much high levels in A549R cells regardless of irradiation. After irradiation, the expressions of pyroptosis-related proteins were significantly increased in A549 cells (P ＜ 0.05), with no significant changes were observed in A549R cells. Treatment with LDC7559 significantly reduced LDH release (P ＜ 0.01) and improved the survival rate of irradiated A549 cells (P ＜ 0.01). Furthermore, knockdown of RGS20 gene in A549R cells significantly increased LDH release (P ＜ 0.001) and enhanced radiosensitivity (P ＜ 0.01), while LDC7559 administration reversed LDH release (P ＜0.01) and radiation-induced cell death increased by siRGS20 (P ＜0.05). Meantime, the increased expression level of GSDMD-NT was observed in A549 and A549R cells transfected with siRGS20 (P ＜ 0.05). Conclusion: RGS20 contributes to the radioresistance of NSCLC cells, which might be a potential target for NSCLC radiotherapy.

Abstract Background Kawasaki disease (KD) is a pyretic ailment predominantly observed in children aged below 5 years. There is currently a dearth of precise markers for timely identification of incomplete Kawasaki disease (IKD). It is imperative to develop updated, comprehensive, and evidence-based guidelines to effectively direct clinical practice. Methods The guideline development group comprised individuals with diverse expertise in both content and methodology and carried out an extensive exploration of the following digital repositories: CNKI, VIP, Wanfang Data, UpToDate, BMJ, Clinical Evidence, National Guideline Clearinghouse, Joanna Briggs Institute Library, Cochrane Library, and PubMed. The entire period from the establishment of these databases until January 1, 2024 was covered. To evaluate IKD, systematic reviews and randomised controlled trials were assessed using the risk of prejudice instrument specified in the Cochrane Handbook, along with the evidence robustness framework established by the GRADE group. The recommendations were formulated based on the findings, considering the evidence strength. After several iterations of expert consensus, the relevant professional committees in China endorsed the ultimate guideline. Results These guidelines address clinical questions regarding the classification and definition of KD, diagnosis of IKD, treatment during the acute phase of IKD, and follow-up of IKD. Conclusions To provide healthcare professionals with guidance and decision-making bases for the diagnosis and treatment of IKD in China, 13 recommendations were formulated based on expert consensus and evidence of best practices.

Abstract This study aims to refine clinical designs within clear aligner therapy, exploring the appropriate ratio of anterior tooth retraction to intrusion under maximum anchorage. Using a three-dimensional finite element model and evaluating 19 load scenarios with first premolar extraction, the research identifies the optimal force angle for anterior tooth retraction as 45 to 55°. For clinical planning, it is recommended to design a retraction of 0.19 mm combined with an intrusion of 0.16 mm to achieve anterior tooth retraction. This investigation is crucial for enhancing understanding of biomechanical principles in clear aligner orthodontics, offering significant insights for effective treatments.

Abstract Background Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature. Case presentation In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy. Conclusion This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.

Abstract Effective watershed management hinges on understanding water sources and pollution origins. In the Hangbu Watershed of Chaohu Lake, China, we analyze pollution source patterns and propose an adaptive strategy. This adaptive strategy is defined as a flexible and dynamic approach that adjusts management practices and policies in response to evolving environmental conditions and emerging data on pollution sources. The analysis includes examining the trends, periodicity, and mutagenicity of pollution sources. The results demonstrated substantial variations in sources, with nitrogen and phosphorus. The adaptive approach enables prioritizing crucial pollution sources, with farmland identified as a significant contributor under varying conditions. Specific pollution sources with growth trends and control robustness have been recognized as vital contributors, even though their contributions to the nitrogen and phosphorus flux at the watershed outlets may not be the most prominent. The results of this study could guide the sustainable management of watersheds.

Energy systems are currently undergoing a transformation towards new paradigms characterized by decarbonization, decentralization, democratization, and digitalization. In this evolving context, energy blockchain, aiming to enhance efficiency, transparency, and security, emerges as an integrated technological solution designed to address the diverse challenges in this field. Data security is essential for the reliable and efficient functioning of energy blockchain. The pressing need to address challenges related to secure data storage, effective data management, and efficient data utilization is increasingly vital. This paper offers a comprehensive survey of academic discourse on energy blockchain data security over the past five years, adopting an all-encompassing perspective that spans data storage, management, and utilization. Our work systematically evaluates and contrasts the strengths and weaknesses of various research methodologies. Additionally, this paper proposes an integrated hierarchical on-chain and off-chain security energy blockchain architecture, specifically designed to meet the complex security requirements of multi-blockchain business environments. Concludingly, this paper identifies key directions for future research, particularly in advancing the integration of storage, management, and utilization of energy blockchain data security.

The Mammalian orthoreovirus (MRV) infects various mammals, including humans, and is linked to gastrointestinal, respiratory, and neurological diseases. A recent outbreak in Liuzhou, Guangxi, China, led to the isolation of a new MRV strain, GXLZ2301, from fecal samples. This strain replicates in multiple cell lines and forms lattice-like structures. Infected cells exhibit single-cell death and syncytia formation. The virus’s titers peaked at 107.2 TCID50/0.1 mL in PK-15 and BHK cells, with the lowest at 103.88 TCID50/0.1 mL in A549 cells. Electron microscopy showed no envelope with a diameter of about 70 nm. Genetic analysis revealed GXLZ2301 as a recombinant strain with gene segments from humans, cows, and pigs, similar to type 3 MRV strains from Italy (2015-2016). Pathogenicity tests indicated that while the bovine MRV strain did not cause clinical symptoms in mice, it caused significant damage to the gut, lungs, liver, kidneys, and brain. The emergence of this MRV strain may pose a threat to the health of animals and humans, and it is recommended that its epidemiology and recombination be closely monitored.

Objective: DNA damage response (DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation (DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor (ICI) therapy in gastrointestinal (GI) cancer. Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts. Results: The DRIA signature includes three genes (CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients (81.8% vs. 8.8%; P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve (AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer. Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pan-cancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Abstract Background and aims Epidemiological evidence suggests that the phenotype of glutathione S-transferase mu 1 (GSTM1), a hepatic high-expressed phase II detoxification enzyme, is closely associated with the incidence of alcohol-related liver disease (ALD). However, whether and how hepatic GSTM1 determines the development of ALD is largely unclear. This study was designed to elucidate the role and potential mechanism(s) of hepatic GSTM1 in the pathological process of ALD. Methods GSTM1 was detected in the liver of various ALD mice models and cultured hepatocytes. Liver-specific GSTM1 or/and micro (miR)-743a-3p deficiency mice were generated by adenoassociated virus-8 delivered shRNA, respectively. The potential signal pathways involving in alcohol-regulated GSTM1 and GSTM1-associated ALD were explored via both genetic manipulation and pharmacological approaches. Results GSTM1 was significantly upregulated in both chronic alcohol-induced mice liver and ethanol-exposed murine primary hepatocytes. Alcohol-reduced miR-743a-3p directly contributed to the upregulation of GSTM1, since liver specific silencing miR-743a-3p enhanced GSTM1 and miR-743a-3p loss protected alcohol-induced liver dysfunctions, which was significantly blocked by GSTM1 knockdown. GSTM1 loss robustly aggravated alcohol-induced hepatic steatosis, oxidative stress, inflammation, and early fibrotic-like changes, which was associated with the activation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), and p38. GSTM1 antagonized ASK1 phosphorylation and its downstream JNK/p38 signaling pathway upon chronic alcohol consumption via binding with ASK1. ASK1 blockage significantly rescued hepatic GSTM1 loss-enhanced disorders in alcohol-fed mice liver. Conclusions Chronic alcohol consumption-induced upregulation of GSTM1 in the liver provides a feedback protection against hepatic steatosis and liver injury by counteracting ASK1 activation. Down-regulation of miR-743a-3p improves alcohol intake-induced hepatic steatosis and liver injury via direct targeting on GSTM1. The miR-743a-3p–GSTM1 axis functions as an innate protective pathway to defend the early stage of ALD. Graphical Abstract

ABSTRACTDigital twin railway is a pivotal foundation for the intelligent construction and maintenance of railway engineering projects within extensive open spaces. Its essence is the integrated representation and association management of multi-granularity spatiotemporal data, executable analysis models, and professional knowledge. These elements are characterized by the prominent characteristics of multi-source, heterogeneity, and massive volume. However, current decentralized and independent management strategies often neglect the dynamic coupling relationships between them, and numerous multi-path joins and conversion aggregation operations exist across various spatial scale applications. Consequently, this results in challenges such as the inability to dynamically couple data-model-knowledge and conduct global association retrieval, thereby limiting the potential for real-time analysis and intelligent application capabilities. To address these problems, we first constructed a tripartite graph model ([Formula: see text]) that explicitly associates temporal, spatial, and interactive relationships. Subsequently, an association management architecture was proposed, accompanied by a global association graph index ([Formula: see text]) and a global-local indexing mechanism. Finally, a prototype system for railway data-model-knowledge association management was developed. The effectiveness of the distributed association management method was demonstrated by employing a case study of high-temperature safety risk analysis in railway tunnel engineering with multi-physics field coupling.

Penthorum chinense Pursh (P. chinense), a functional food, has been applied to protect the liver against alcohol-related fatty liver disease (ALD) for a long history in China. This study was designed to evaluate the ameliorative activity of the polyphenolic fraction in P. chinense (PGF) depending on the relief of ALD. The ALD mouse model was established by exposing the mice to a Lieber-DeCarli alcohol liquid diet. We found that PGF administration significantly ameliorated alcohol-induced liver injury, steatosis, oxidative stress, and inflammation in mice. Furthermore, alcohol-increased levels of the critical hepatic lipid synthesis proteins sterol regulatory element binding transcription factor (SREBP-1) and diacylglycerol o-acyltransferase 2 (DGAT2) were attenuated by PGF. Similarly, PGF inhibited the expression of the lipid transport protein very low-density lipoprotein receptor (VLDLR). Interestingly, PGF restored alcohol-inhibited expression of carnitine palmitoyltransferase 1 (CPT1) and peroxisome proliferator-activated receptor alpha (PPARα), essential fatty acid β-oxidation proteins. Mechanistic studies revealed that PGF protects against alcohol-induced hepatocyte injury and lipid deposition via the SIRT1/AMPK signaling pathway. In sum, this research clearly demonstrated the protective effects of PGF against ALD, which was mediated by activating SIRT1/AMPK pathways in hepatocytes. We provide a new theoretical basis for using P. chinense as a functional food in ALD.

Abstract The interrupted time series (ITS) design is widely used to examine the effects of large-scale public health interventions and has the highest level of evidence validity. However, there is a notable gap regarding methods that account for lag effects of interventions. To address this, we introduced activation functions (ReLU and Sigmoid) to into the classic segmented regression (CSR) of the ITS design during the lag period. This led to the proposal of proposed an optimized segmented regression (OSR), namely, OSR-ReLU and OSR-Sig. To compare the performance of the models, we simulated data under multiple scenarios, including positive or negative impacts of interventions, linear or nonlinear lag patterns, different lag lengths, and different fluctuation degrees of the outcome time series. Based on the simulated data, we examined the bias, mean relative error (MRE), mean square error (MSE), mean width of the 95% confidence interval (CI), and coverage rate of the 95% CI for the long-term impact estimates of interventions among different models. OSR-ReLU and OSR-Sig yielded approximately unbiased estimates of the long-term impacts across all scenarios, whereas CSR did not. In terms of accuracy, OSR-ReLU and OSR-Sig outperformed CSR, exhibiting lower values in MRE and MSE. With increasing lag length, the optimized models provided robust estimates of long-term impacts. Regarding precision, OSR-ReLU and OSR-Sig surpassed CSR, demonstrating narrower mean widths of 95% CI and higher coverage rates. Our optimized models are powerful tools, as they can model the lag effects of interventions and provide more accurate and precise estimates of the long-term impact of interventions. The introduction of an activation function provides new ideas for improving of the CSR model.

Abstract Background Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. Methods The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease–target–component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. Results We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. Conclusions This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.

Abstract Studying language evolution brings a crucial perspective to bear on questions of human prehistory. As the most linguistically diverse region on earth, East and Southeast Asia have witnessed extensive sociocultural and ethnic contacts among different language communities. Especially, the Kra-Dai language family exhibits tremendous socio-cultural importance in these regions. Due to limited historical accounts, however, there are several controversies on their linguistic relatedness, ambiguities regarding the divergence time, and uncertainties on the dispersal patterns. To address these issues, here we apply Bayesian phylogenetic methods to analyze the largest lexical dataset containing 646 cognate sets compiled for 100 Kra-Dai languages. Our dated phylogenetic tree showed their initial divergence occurring approximately 4000 years BP. Phylogeographic results supported the early Kra-Dai language dispersal from the Guangxi-Guangdong area of South China towards Mainland Southeast Asia. Coupled with genetic, archaeological, paleoecologic, and paleoclimatic data, we demonstrated that the Kra-Dai language diversification could have coincided with their demic diffusion and agricultural spread shaped by the global climate change in the late Holocene. The interdisciplinary alignments shed light on reconstructing the prehistory of Kra-Dai languages and provide an indispensable piece of the puzzle for further studying prehistoric human activities in East and Southeast Asia.

Abstract Properly integrating spatially resolved transcriptomics (SRT) generated from different batches into a unified gene-spatial coordinate system could enable the construction of a comprehensive spatial transcriptome atlas. Here, we propose SPIRAL, consisting of two consecutive modules: SPIRAL-integration, with graph domain adaptation-based data integration, and SPIRAL-alignment, with cluster-aware optimal transport-based coordination alignment. We verify SPIRAL with both synthetic and real SRT datasets. By encoding spatial correlations to gene expressions, SPIRAL-integration surpasses state-of-the-art methods in both batch effect removal and joint spatial domain identification. By aligning spots cluster-wise, SPIRAL-alignment achieves more accurate coordinate alignments than existing methods.

The acceleration of urbanization intensifies the urban heat island, outdoor activities (especially the road travel) are seriously affected by the overheating environment, and the comfort and safety of the bus shelter as an accessory facility of road travel are crucial to the passenger’s experience. This study investigated the basic information (e.g., distribution, orientation) of 373 bus shelters in Guangzhou and extracted the typical style by classifying the characteristics of these bus shelters. Additionally, we also measured the thermal environment of some bus shelters in summer and investigated the cooling behavior of passengers in such an environment. The results show that the typical style of bus shelters in the core area of Guangzhou is north–south orientation, with only one station board at the end of the bus, two backboards, two roofs (opaque green), and the underlying surface is made of red permeable brick. The air temperature and relative humidity under different bus shelters, tree shading areas, and open space in summer are 34–37 °C and 49–56%, respectively. For the bus shelters with heavy traffic loads, the air temperature is basically above 35.5 °C, and the thermal environment is not comfortable. During the hot summer, when there is no bus shelter or trees to shade the sun, the waiting people adjust their position with the sun’s height, azimuth angles, and direct solar radiation intensity to reduce the received radiation as much as possible, which brings great inconvenience to them. When only bus shelters provide shade, people tend to gather in the shaded space, and cooling measures such as umbrellas, hats, and small fans are still needed to alleviate thermal discomfort. However, the aforementioned various spontaneous cooling behaviors still cannot effectively alleviate overheating, and it is very important to increase auxiliary cooling facilities in bus shelters.

Astroviruses are single-stranded, positive-sense RNA viruses capable of infecting humans as well as a wide range of mammalian and avian species, with a length of approximately 6.6–7.7 kb. In this study, 139 goat fecal samples collected from the Guangxi province were used for the RT-PCR detection, and two of these were positive for goat astrovirus, with a positivity rate of 1.44% (2/139). The complete genome sequence of an astrovirus strain and the partial genome sequence of a strain astrovirus, named GX WZ 2023 and GX HC 2023, were amplified and sequenced, and their sequence lengths were 6284 nt and 6213 nt, respectively. Among them, the capsid protein of goat astrovirus GX HC 2023 showed the highest amino acid identity of 95.9% with ovine astrovirus GX, which belonged to the MAstV-2 genotype. However, the closest relative of the GX WZ 2023 strain was found to be the caprine astrovirus Sichuan, with a nucleotide sequence identity of 76.8%. The ORF1ab nonstructural protein of this strain showed the highest amino acid identities of 89.2 and 95.8% with the ovine astrovirus S5.1 and caprine astrovirus G5.1 strains, respectively. However, its ORF2 capsid protein has 68.4% amino acid identity with the bovine astrovirus (BAstV) 16 2021 CHN strain and only 21.9–64% amino acid identity with all available strains of goat astrovirus. The GX WZ 2023 strain was recombined with the Chinese (BAstV 16 2021 CHN) and Japanese bovine strains (BAstV JPN 2015) in the ORF2 region. Therefore, the goat astrovirus GX WZ 2023 is proposed as a new member of the family goat astroviridae based on the species classification criteria of the International Committee on Taxonomy of Viruses. These findings enhance our understanding of the prevalence and genetic evolution of goat astrovirus and provide a scientific basis for future studies of these viruses in other animals.

Due to the low-complexity implementation, direction-of-arrival (DOA) estimation-based one-bit quantized data are of interest, but also, signal processing struggles to obtain the demanded estimation accuracy. In this study, we injected a number of noise components into the receiving data before the uniform linear array (ULA) composed of one-bit quantizers. Then, based on this designed noise-boosted quantizer unit (NBQU), we propose an efficient one-bit multiple signal classification (MUSIC) method for estimating the DOA. Benefiting from the injected noise, the numerical results show that the proposed NBQU-based MUSIC method outperforms existing one-bit MUSIC methods in terms of estimation accuracy and resolution. Furthermore, with the optimal root mean square (RMS) of the injected noise, the estimation accuracy of the proposed method for estimating DOA can approach that of the MUSIC method based on the complete analog data.

Alzheimer’s disease (AD) is a high-incidence neurodegenerative disorder, characterized by cognitive impairment, memory loss, and psychiatric abnormalities. Ganoderma lucidum is a famous medicinal fungus with a long history of dietary intake, containing various bioactive components, and have been documented to exhibit antioxidant, anti-inflammatory, anti-tumor, anti-aging, and immunomodulatory effects, among others. Recent studies have shown that G. lucidum and its components have promising therapeutic potential against AD from various aspects, which can delay the progression of AD, improve cognitive function and quality of life. The underlying mechanisms mainly include inhibiting tau hyperphosphorylation, inhibiting Aβ formation, affecting activated microglia, regulating NF-κB/MAPK signalling pathway, inhibiting neuronal apoptosis, modulating immune system, and inhibiting acetylcholinesterase, etc. This paper systematically reviewed the relevant studies on the therapeutic potential of G. lucidum and its active components for treatment of AD, key points related with the mechanism studies and clinical trials have been discussed, and further perspectives have been proposed. Totally, as a natural medicinal mushroom, G. lucidum has the potential to be developed as effective adjuvant for AD treatment owing to its therapeutic efficacy against multiple pathogenesis of AD. Further mechanical investigation and clinical trials can help unlock the complete potential of G. lucidum as a therapeutic option for AD.

BackgroundBaseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests.Materials and methodsThis was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters.ResultsThe Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction

IntroductionMigraines are the leading cause of disability in the United States, and the use of non-pharmaceutical treatments like osteopathic manipulative treatment (OMT) has shown promise. Despite its potential, the lack of mechanistic understanding has hindered widespread adoption. This study aims to investigate the efficacy of OMT in treating acute migraines and unravel its underlying mechanisms of action.MethodsFemale rats were subjected to a “two-hit” approach to induce migraine-like pain. This involved bilateral injections of Complete Freund's Adjuvant (CFA) into the trapezius muscle (1st hit) followed by exposure to Umbellulone, a human migraine trigger, on Day 6 post-CFA (2nd hit). Soft tissue and articulatory techniques were applied to the cervical region for acute abortive or repeated prophylactic treatment. Cutaneous allodynia and trigeminal system activation were assessed through behavioral tests and immunohistochemical staining.ResultsFollowing Umbellulone inhalation, CFA-primed rats exhibited periorbital and hind paw allodynia. Immediate application of OMT after Umbellulone inhalation as an abortive treatment partially alleviated cutaneous allodynia. With OMT applied thrice as a prophylactic measure, complete suppression of tactile hypersensitivity was observed. Prophylactic OMT also prevented the increase of c-fos signals in the trigeminal nucleus caudalis and the elevation of calcitonin gene-related peptide expression in trigeminal ganglia induced by CFA and Umbellulone exposure at 2 h post-inhalation.DiscussionThese findings provide mechanistic insights into OMT's migraine-relief potential and underscore its viability as a non-pharmacological avenue for managing migraines.

Abstract Background The interrupted time series (ITS) design is a widely used approach to examine the effects of interventions. However, the classic segmented regression (CSR) method, the most popular statistical technique for analyzing ITS data, may not be adequate when there is a transitional period between the pre- and post-intervention phases. Methods To address this issue and better capture the distribution patterns of intervention effects during the transition period, we propose using different cumulative distribution functions in the CSR model and developing corresponding optimized segmented regression (OSR) models. This study illustrates the application of OSR models to estimate the long-term impact of a national free delivery service policy intervention in Ethiopia. Results Regardless of the choice of transition length ( $$L$$ L ) and distribution patterns of intervention effects, the OSR models outperformed the CSR model in terms of mean square error (MSE), indicating the existence of a transition period and the validity of our model’s assumptions. However, the estimates of long-term impacts using OSR models are sensitive to the selection of L, highlighting the importance of reasonable parameter specification. We propose a data-driven approach to select the transition period length to address this issue. Conclusions Overall, our OSR models provide a powerful tool for modeling intervention effects during the transition period, with a superior model fit and more accurate estimates of long-term impacts. Our study highlights the importance of appropriate statistical methods for analyzing ITS data and provides a useful framework for future research.

C-terminal Src kinase (CSK) is the major inhibitory kinase for Src family kinases (SFKs) through the phosphorylation of their C-tail tyrosine sites, and it regulates various types of cellular activity in association with SFK function. As a cytoplasmic protein, CSK needs be recruited to the plasma membrane to regulate SFKs’ activity. The regulatory mechanism behind CSK activity and its subcellular localization remains largely unclear. In this work, we developed a genetically encoded biosensor based on fluorescence resonance energy transfer (FRET) to visualize the CSK activity in live cells. The biosensor, with an optimized substrate peptide, confirmed the crucial Arg107 site in the CSK SH2 domain and displayed sensitivity and specificity to CSK activity, while showing minor responses to co-transfected Src and Fyn. FRET measurements showed that CSK had a relatively mild level of kinase activity in comparison to Src and Fyn in rat airway smooth muscle cells. The biosensor tagged with different submembrane-targeting signals detected CSK activity at both non-lipid raft and lipid raft microregions, while it showed a higher FRET level at non-lipid ones. Co-transfected receptor-type protein tyrosine phosphatase alpha (PTPα) had an inhibitory effect on the CSK FRET response. The biosensor did not detect obvious changes in CSK activity between metastatic cancer cells and normal ones. In conclusion, a novel FRET biosensor was generated to monitor CSK activity and demonstrated CSK activity existing in both non-lipid and lipid raft membrane microregions, being more present at non-lipid ones.

Shallow lake sediments have huge potential for carbon storage, but they are vulnerable to various environmental changes and are highly susceptible to becoming a source of carbon emissions. Understanding the amount of sediment carbon storage can provide information about the potential of shallow lakes in mitigating climate change. In this study, sediment sampling was conducted at 12 study sites in Chaohu Lake, China, and sediment water content, grain size, bulk density, and sediments organic carbon (SOC) content were examined in five layers along the vertical direction, respectively, and the distribution and storage of SOC were estimated. The results showed that the surface sediments in the west lake area of Chaohu Lake would release 66,300 t of SOC to the overlying water body in the future. The sediments in the middle lake area and the east lake area will absorb another 15,900 t and 17,300 t of TOC from the water body in the future, respectively. Overall, the lake-wide sediments will release 33,100 t of SOC into the water body in the future. In addition, the results of the study also indicate that human activities are another major influence on the change in organic carbon stocks in lake sediments, and therefore, proactive measures for the restoration and protection of lake sediments are essential because increasing the SOC stocks in the sediments and maintaining the lakes in a sustainable manner can contribute to the crucial role they play in mitigating climate change.

Abstract Background Interstitial lung diseases (ILDs) can be induced and even exacerbated by radiotherapy in thoracic cancer patients. The roles of immune responses underlying the development of these severe lung injuries are still obscure and need to be investigated. Methods A severe lung damage murine model was established by delivering 16 Gy X-rays to the chest of mice that had been pre-treated with bleomycin (BLM) and thus hold ILDs. Bioinformatic analyses were performed on the GEO datasets of radiation-induced lung injury (RILI) and BLM-induced pulmonary fibrosis (BIPF), and RNA-sequencing data of the severely damaged lung tissues. The screened differentially expressed genes (DEGs) were verified in lung epithelial cell lines by qRT-PCR assay. The injured lung tissue pathology was analyzed with H&E and Masson’s staining, and immunohistochemistry staining. The macrophage chemotaxis and activity promoted by the stressed epithelial cells were determined by using a cell co-culture system. The expressions of p21 in MLE-12 and Beas-2B cells were detected by qRT-PCR, western blot, and immunofluorescence. The concentration of CCL7 in cell supernatant was measured by ELISA assay. In some experiments, Beas-2B cells were transfected with p21-siRNA or CCL7-siRNA before irradiation and/or BLM treatment. Results After the treatment of irradiation and/or BLM, the inflammatory and immune responses, chemokine-mediated signaling pathways were steadily activated in the severely injured lung, and p21 was screened out by the bioinformatic analysis and further verified to be upregulated in both mouse and human lung epithelial cell lines. The expression of P21 was positively correlated with macrophage infiltration in the injured lung tissues. Co-culturing with stressed Beas-2B cells or its conditioned medium containing CCL7 protein, U937 macrophages were actively polarized to M1-phase and their migration ability was obviously increased along with the damage degree of Beas-2B cells. Furthermore, knockdown p21 reduced CCL7 expression in Beas-2B cells and then decreased the chemotaxis of co-cultured macrophages. Conclusions P21 promoted CCL7 release from the severely injured lung epithelial cell lines and contributed to the macrophage chemotaxis in vitro, which provides new insights for better understanding the inflammatory responses in lung injury.

Protocol state machine active inference is a technique that relies on active automata learning.However, the abstraction of the alphabet and the construction of the mapper present critical challenges.Due to the diversity of messages of the same type, the response types of the same type are different, causing the method of regarding the message types as the alphabet will result in the loss of states or state transitions.To address the issue, message types were refined into subtypes according to the different responses and a progressive active inference method was proposed.The proposed method extracted the state fields from the existing protocol data to construct the initial alphabet and the mapper, and obtained the initial state machine based on active automata learning.It then mutated the existing messages to explore the response sequences, which were inconsistent with the current state machine.The mutated message was regarded as a protocol subtype and added to the alphabet, and a new state machine was inferred progressively based on the new alphabet.In order to reduce the interactions, a pre-response query algorithm was proposed based on prefix matching for the caching mechanism in the active automata learning.The ProLearner tool was utilized to evaluate the proposed method in the context of the SMTP and RSTP protocols.It is verified that the pre-response query method can effectively reduce the number of actual interactions, with an average reduction rate of about 10%.

AbstractBackground Liver cirrhosis is a significant yet largely preventable and underappreciated cause of global health loss. This study aimed to profile the global and regional burdens of liver cirrhosis between 2010 and 2019 and the contributions of various aetiologies.Method Data on the incidence, mortality, and disability-adjusted life years (DALYs) of cirrhosis were obtained from the Global Burden of Disease 2019 study. The burden of cirrhosis was estimated by age, sex, region, aetiology, and socio-demographic index (SDI). The temporal trend was quantified using the annual percentage changes (APC.)Results Globally, there were 2.05 million new cases and 1.47 million deaths due to cirrhosis in 2019. From 2010 to 2019, the age-standardized incidence rate (ASIR) for cirrhosis increased slightly from 25.19 to 25.35 worldwide, while the age-standardized death rate (ASDR) and age-standardized DALYs (ASDALYs) decreased from 20.37 to 18.00 and 639.86 to 560.43, respectively. Cirrhosis incidence, mortality and DALYs were consistently higher in males than females. Stratification according to the socio-demographic index (SDI) revealed that low SDI countries had the highest ASDR and ASDALYs in 2019, while middle SDI countries had the highest ASIR. Regarding the aetiology of cirrhosis, hepatitis C accounted for the largest proportion of cirrhosis-related incidence (26.9%), death (26.8%) and DALYs (26.3%); however, non-alcoholic fatty liver disease (NAFLD) exhibited a rapidly growing cause of incident cirrhosis (+26.7%), cirrhosis-related death (+25.1%), and DALYs (+21.0%) worldwide during this period. The ASIR for NAFLD also significantly increased with APC 1.080 over the study period.Conclusions Albeit the global burden of cirrhosis incidence increased from 2010 to 2019, cirrhosis-associated deaths and DALYs declined significantly. Notably, NAFLD exhibited the most significant increase as a contributor to cirrhosis worldwide.

Objective: Although radiation workers are exposed to much lower doses of neutron-γ rays than those suffered in nuclear explosions and accidents, it does not mean that their health is not affected by radiation. Lower doses of radiation do not always cause morphological aberrations in chromosomes, so more sophisticated tests must be sought to specific alterations in the exposed cells. Our goal was to characterize the specific gene expression in lymphocytes from logging workers who were continuously exposed to low doses of neutron-γ radiation. We hypothesized that the combination of cell type-specific transcriptomes and open chromatin profiles would identify lymphocyte-specific gene alterations induced by long-term radiation with low-dose neutron-γ-rays and discover new regulatory pathways and transcriptional regulatory elements.Methods: Lymphocytes were extracted from workers who have been occupationally exposed to neutron-γ and workers unexposed to radiation in the same company. mRNA-seq and ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) were performed, followed integrative analysis to identify specific gene regulatory regions induced by neutron-γ radiation. A qPCR assay was then performed to verify the downregulation of RNA coding for ribosomal proteins and flow cytometry was used to detect ribosomal protein expression and cell cycle alterations.Results: We identified transcripts that were specifically induced by neutron-γ radiation and discovered differential open chromatin regions that correlated with these gene activation patterns. Notably, we observed a downward trend in the expression of both differentially expressed genes and open chromatin peaks. Our most significant finding was that the differential peak upregulated in ATAC-seq, while the differential gene was downregulated in the ribosome pathway. We confirmed that neutron-γ radiation leads to transcriptional inhibition by analyzing the most enriched promoters, examining RPS18 and RPS27A expression by qPCR, and analyzing protein-protein interactions of the differential genes. Ribosomal protein expression and cell cycle were also affected by neutron-γ as detected by flow cytometry.Conclusion: We have comprehensively analyzed the genetic landscape of human lymphocytes based on chromatin accessibility and transcript levels, enabling the identification of novel neutron-γ induced signature genes not previously known. By comparing fine-mapping of open chromatin and RNA reads, we have determined that neutron-γ specifically leads to downregulation of genes in the ribosome pathway, with pseudogenes potentially playing a crucial role.

Microglia are first responders to acute brain insults and initiate neuroinflammation to drive secondary tissue injury. Yet the key molecular switches in control of the inflammatory activity of microglia remain poorly understood. Intracerebral hemorrhage (ICH) is a devastating stroke subtype whereby a hematoma is formed within the brain parenchyma and associated with high mortality. Using a mouse model of ICH, we found upregulation of CD22 that predominantly occurred in microglia. Antibody blockade of CD22 led to a reduction in neurological deficits, brain lesion and hematoma volume. This was accompanied by reduced inflammatory activity, increased expression of alternative activation markers (CD206 and IL-10) and enhanced phagocytosis activity in microglia after ICH. CD22 blockade also led to an increase of phosphorylated SYK and AKT after ICH. Notably, the benefits of CD22 blockade were ablated in ICH mice subjected to microglial depletion with a colony-stimulating factor 1 receptor inhibitor PLX5622. Additionally, the protective effects of CD22 blockade was diminished in ICH mice receiving a SYK inhibitor R406. Together, our findings highlight CD22 as a key molecular switch to control the detrimental effects of microglia after acute brain injury, and provide a novel strategy to improve the outcome of ICH injury.

A scheme of integrated sensing and communication in an optical fibre (ISAC-OF) using the same wavelength channel for simultaneous high-speed data transmission and distributed vibration sensing.

Ventilator-induced lung injury (VILI) during mechanical ventilation (MV) has been attributed to airway remodeling involving increased airway smooth muscle cells (ASMCs), but the underlying mechanism is not fully understood. Thus, we aimed to investigate whether MV-associated high stretch (>10% strain) could modulate mechanosensitive Piezo1 expression and thereby alter cell migration of ASMCs as a potential pathway to increased ASMCs in VILI. C57BL/6 mice and ASMCs were subjected to MV at high tidal volume (VT, 18 mL/kg, 3 h) and high stretch (13% strain, 0.5 Hz, 72 h), respectively. Subsequently, the mice or cells were evaluated for Piezo1 and integrin mRNA expression by immunohistochemical staining and quantitative PCR (qPCR), and cell migration and adhesion by transwell and cell adhesion assays. Cells were either treated or not with Piezo1 siRNA, Piezo1-eGFP, Piezo1 knockin, Y27632, or blebbistatin to regulate Piezo1 mRNA expression or inhibit Rho-associated kinase (ROCK) signaling prior to migration or adhesion assessment. We found that expression of Piezo1 in in situ lung tissue, mRNA expression of Piezo1 and integrin αVβ1 and cell adhesion of ASMCs isolated from mice with MV were all reduced but the cell migration of primary ASMCs (pASMCs) isolated from mice with MV was greatly enhanced. Similarly, cell line mouse ASMCs (mASMCs) cultured in vitro with high stretch showed that mRNA expression of Piezo1 and integrin αVβ1 and cell adhesion were all reduced but cell migration was greatly enhanced. Interestingly, such effects of MV or high stretch on ASMCs could be either induced or abolished/reversed by down/up-regulation of Piezo1 mRNA expression and inhibition of ROCK signaling. High stretch associated with MV appears to be a mechanical modulator of Piezo1 mRNA expression and can, thus, promote cell migration of ASMCs during therapeutic MV. This may be a novel mechanism of detrimental airway remodeling associated with MV, and, therefore, a potential intervention target to treat VILI.

Dual-polarization division multiplexing (DPDM) is considered to be a potential method to boost the secure key rate (SKR) of the continuous-variable quantum key distribution (CV-QKD) system. In this article, we propose a pilot alternately assisted local local oscillator (LLO) CV-QKD scheme based on multi-dimensional multiplexing, where time division multiplexing and frequency division multiplexing are combined with dual-polarization multiplexing techniques to dramatically isolate the quantum signal from the pilot tone. We establish a general excess noise model for the LLO CV-QKD system to analyze the influence mechanism of various disturbances (e.g., time-domain diffusion, frequency-domain modulation residual, and polarization perturbation) on the key parameters, such as the channel transmittance and excess noise. Specifically, the photon leakage noise from the reference path to the quantum path and that between quantum signals with two different polarization paths are simultaneously analyzed in the dual-polarization LLO CV-QKD scheme for the first time. Furthermore, a series of simulations are established to verify the performance of the proposed scheme. The results show that the maximal isolation degree achieves 84.0 dB~90.4 dB, and the crosstalk between pilot tones and quantum signals can be suppressed to a very small range. By optimizing the system parameters (e.g., modulation variance and repetition frequency), the SKR with 12.801 Mbps@25 km is achieved under the infinite polarization extinction ratio (PER) and 30 dB residual ratio of the frequency modulation in the nanosecond-level pulse width. Moreover, the performance of the proposed DPDM CV-QKD scheme under relatively harsh conditions is simulated; the results show that the SKR with 1.02 Mbps@25 km is achieved under a relatively low PER of 17 dB with the nanosecond-level pulse width and 20 dB residual ratio of the frequency modulation. Our work lays an important theoretical foundation for the practical DPDM LLO CV-QKD system.

High stretch (>10% strain) of airway smooth muscle cells (ASMCs) due to mechanical ventilation (MV) is postulated to contribute to ventilator-induced lung injury (VILI), but the underlying mechanisms remain largely unknown. We hypothesized that ASMCs may respond to high stretch via regulatory miRNA–mRNA interactions, and thus we aimed to identify high stretch-responsive cellular events and related regulating miRNA–mRNA interactions in cultured human ASMCs with/without high stretch. RNA-Seq analysis of whole genome-wide miRNAs revealed 12 miRNAs differentially expressed (DE) in response to high stretch (7 up and 5 down, fold change >2), which target 283 DE-mRNAs as identified by a parallel mRNA sequencing and bioinformatics analysis. The KEGG and GO analysis further indicated that purine metabolism was the first enriched event in the cells during high stretch, which was linked to miR-370-5p–PDE4D/AK7. Since PDE4D/AK7 have been previously linked to cAMP/ATP metabolism in lung diseases and now to miR-370-5p in ASMCs, we thus evaluated the effect of high stretch on the cAMP/ATP level inside ASMCs. The results demonstrated that high stretch modulated the cAMP/ATP levels inside ASMCs, which could be largely abolished by miR-370-5p mimics. Together, these findings indicate that miR-370-5p–PDE4D/AK7 mediated high stretch-induced modulation of cAMP and ATP synthesis inside ASMCs. Furthermore, such interactive miRNA–mRNA pairs may provide new insights for the discovery of effective biomarkers/therapeutic targets for the diagnosis and treatment of VILI and other MV-associated respiratory diseases.

In East Asian archaeology, initial domestication and early dispersal of rice have continuously attracted scholarly interest in the recent decade, which has generated abundant new materials and revised opinions. This paper starts with a refreshed understanding of the domestication concept that emphasizes the dominant role of human behavior in the mutualistic relationship. A thorough review of the approaches to and data on reconstructing the rice story during 10,000–7,000 BP demonstrates the causally chained changes in phenotype, genotype, and human behavior in the establishment of domestication. Future studies will benefit from the revised paradigm, which has great potential to extract archaeological information to explain multiple mechanisms in rice domestication.

BackgroundUlcerative colitis (UC) is a chronic relapsing remitting disease of the colon. Appropriate monitoring of the disease status is necessary for patients to adopt optimal therapy and obtain a better prognosis. Finding an ideal non-invasive biomarker, which is suitable for long-term monitoring in clinical settings will bring a significant benefit to the individualized management of patients with UC. The aim of this study is to determine the clinical significance of a novel optimizing serological biomarker by integrating C-reactive protein (CRP) and bilirubin levels in monitoring disease activity.MethodsA total of 182 patients with UC were retrospectively enrolled. Clinical characteristics and laboratory parameters of the subjects were retrieved from the electronic medical record database of our hospital. The CRP-to-bilirubin ratio (CBR) was computed for clinical activity of UC defined by the partial Mayo score and endoscopic activity by the Mayo endoscopic score (MES).ResultsCBR was significantly elevated in patients with UC than that in healthy controls. Patients with clinically or endoscopically active UC showed evidently higher CBR levels compared to those with inactive disease, even in a subset of patients with normal CRP levels. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CBR was higher than that of CRP or bilirubin alone for determining clinical remission and endoscopic mucosal improvement. Furthermore, CBR levels were significantly decreased when patients achieved mucosal improvement compared with when they had active endoscopic inflammation.ConclusionCBR could be useful to reflect disease activity in patients with UC.

Acute myeloid leukemia (AML) is a complex mixed entity composed of malignant tumor cells, immune cells and stromal cells, with intra-tumor and inter-tumor heterogeneity. Single-cell RNA sequencing enables a comprehensive study of the highly complex tumor microenvironment, which is conducive to exploring the evolutionary trajectory of tumor cells. Herein, we carried out comprehensive analyses of aggrephagy-related cell clusters based on single-cell sequencing for patients with acute myeloid leukemia. A total of 11 specific cell types (T, NK, CMP, Myeloid, GMP, MEP, Promono, Plasma, HSC, B, and Erythroid cells) using t-SNE dimension reduction analysis. Several aggrephagy-related genes were highly expressed in the 11 specific cell types. Using Monocle analysis and NMF clustering analysis, six aggrephagy-related CD8+ T clusters, six aggrephagy-related NK clusters, and six aggrephagy-related Mac clusters were identified. We also evaluated the ligand-receptor links and Cell–cell communication using CellChat package and CellChatDB database. Furthermore, the transcription factors (TFs) of aggrephagy-mediated cell clusters for AML were assessed through pySCENIC package. Prognostic analysis of the aggrephagy-related cell clusters based on R package revealed the differences in prognosis of aggrephagy-mediated cell clusters. Immunotherapy of the aggrephagy-related cell clusters was investigated using TIDE algorithm and public immunotherapy cohorts. Our study revealed the significance of aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for AML.

BackgroundThis study aimed to gather evidence from clinical trials on the efficacy and safety of the available treatments for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) in children.MethodsThis work adopted the Newcastle–Ottawa scale to analyse the quality of the enrolled articles. A network meta-analysis was performed using clinical trials that compared drugs used to treat IVIG-resistant KD. Aggregate Data Drug Information System software v.1.16.5 was employed to analyse whether infliximab, second IVIG infusions, and intravenous pulse methylprednisolone (IVMP) were safe and effective.ResultsTen studies, involving 704 patients with IVIG-resistant KD, were identified and analysed. Overall, infliximab exhibited remarkable antipyretic activity compared with the second IVIG infusions (2.46, 1.00–6.94). According to the drug rank, infliximab was the best option against IVIG-resistant KD. Regarding adverse effects, the infliximab group was more prone to hepatomegaly. A second IVIG infusion was more likely to result in haemolytic anaemia. IVMP treatment was more susceptible to bradycardia, hyperglycaemia, hypertension, and hypothermia. In addition, infliximab, IVMP, and the second IVIG infusions showed no significant differences in the risk of developing a coronary artery aneurysm (CAA).ConclusionInfliximab was the best option against IVIG-resistant KD, and IVMP, infliximab, and second IVIG infusions have not significant differences of prevent CAA in patients with IVIG-resistant KD.Systematic Review RegistrationIdentifier: https://osf.io/3894y.

Abstract Background Cattle industry is critical for China’s livestock industry, whereas E. coli infection and relevant diseases could lead huge economic loss. Traditional mammalian models would be costly, time consuming and complicated to study pathological changes of bovine E. coli. There is an urgent need for a simple but efficient animal model to quantitatively evaluate the pathological changes of bovine-derived E. coli in vivo. Caenorhabditis elegans (C. elegans) has a broad host range of diverse E. coli strains with advantages, including a short life cycle, a simple structure, a transparent body which is easily visualized, a well-studied genetic map, an intrinsic immune system which is conservable with more complicated mammalians. Results Here, we considered that O126 was the dominant serotype, and a total of 19 virulence factors were identified from 41 common E. coli virulence factors. Different E. coli strains with diverse pathogenicity strengths were tested in C. elegans in E. coli with higher pathogenicity (EC3/10), Nsy-1, Sek-1 and Pmk-1 of the p38 MAPK signaling pathway cascade and the expression of the antimicrobial peptides Abf-3 and Clec-60 were significantly up-regulated comparing with other groups. E. coli with lower pathogenicity (EC5/13) only activated the expression of Nsy-1 and Sek-1 genes in the p38 MAPK signaling pathway, Additionally, both groups of E. coli strains caused significant upregulation of the antimicrobial peptide Spp-1. Conclusion Thirteen E. coli strains showed diverse pathogenicity in nematodes and the detection rate of virulence factors did not corresponding to the virulence in nematodes, indicating complex pathogenicity mechanisms. We approved that C. elegans is a fast and convenient detection model for pathogenic bacteria virulence examinations.

Abstract Chronic morphine administration alters gene expression in different brain regions, an effect which may contribute to plastic changes associated with addictive behavior. This change in gene expression is most possibly mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Our previous studies showed that chronic morphine-induced decrease of miR-105 in the medial prefrontal cortex (mPFC) contributed to context-induced retrieval of morphine withdrawal memory. However, how chronic morphine treatment decreases miR-105 in the mPFC still remains unknown. The present study shows that chronic morphine induces addiction-related change in miR-105 in the mPFC via two kinds of transcription factors: the first transcription factor is CREB activated by mu receptors-ERK-p90RSK signaling pathway and the second transcription factor is glucocorticoid receptor (GR), which as a negative transcription factor, mediates chronic morphine-induced decrease in miR-105 in the mPFC of rats.

Abstract Background Leukocyte phytohemagglutinin (PHA-L), derived from the L4 tetramer of PHA, has been frequently employed as a mitogen to induce T lymphocyte proliferation in vitro. The biological application of PHA-L in cancer diagnosis and treatment has gained traction in recent years. However, it has been noted that PHA-L obtained using traditional procedures has a massive amount of impurities or toxic components, which interfere with the activity of PHA-L. Preparation of a monoclonal antibody against active PHA-L is a significant tool for studying PHA-L's function and therapeutic potential. Results We successfully prepared monoclonal antibodies against the active components of PHA-L based on the whole PHA-L protein as an antigen, and found that monoclonal antibody 3C1C6G11 can be employed in western blot, immunofluorescence, and immunohistochemistry detection. Importantly, preliminary result shows that the mAb 3C1C6G11 may prevent PHA-L-induced cell aggregation and AICD (activation-induced cell death). Conclusions The monoclonal antibody mAb 3C1C6G11 prepared in this study can be used as an effective tool for detecting PHA-L active components, investigating PHA-L's function and antineoplastic application.

Abstract Background A raw starch-degrading α-amylase from Pontibacillus sp. ZY (AmyZ1), previously screened by our laboratory, showed a promising application potential for starch-processing industries. However, the AmyZ1 secretory production still under investigation, which seriously restricts its application in the starch-processing industry. On the other hand, Bacillus subtilis is widely used to achieve the extracellular expression of target proteins. Results AmyZ1 secretory production was achieved in B. subtilis and was enhanced by promoter engineering and translation initiation efficiency optimization. First, based on the different phase-dependent promoters, the dual-promoter P spoVG –P spoVG142 was constructed by combining dual-promoter engineering and promoter modification. The corresponding strain BZd34 showed an extracellular AmyZ1 activity of 1437.6 U/mL during shake flask cultivation, which was 3.11-fold higher than that of the original strain BZ1 (P groE ). Then, based on translation initiation efficiency optimization, the best strain BZd343 containing optimized 5'-proximal coding sequence (opt3) produced the highest extracellular α-amylase activity of 1691.1 U/mL, which was 3.65-fold higher than that of the strain BZ1. Finally, cultivation of BZd343 in 3-L fermenter exhibited an extracellular AmyZ1 activity of 14,012 U/mL at 48 h, with productivity of 291.9 U/mL·h. Conclusions This is the first report of recombinant expression of AmyZ1 in B. subtilis and the expression level of AmyZ1 represents the highest raw starch-degrading α-amylase level in B. subtilis to date. The high-level expression of AmyZ1 in this work provides a foundation for its industrial production. The strategies used in this study also provide a strategic reference for improving the secretory expression of other enzymes in B. subtilis.

With the continuous development of metropolitan broadband and network, the need of secure and faster transmission also increases. The authors demonstrate a single-carrier four-state continuous-variable quantum key distribution (CVQKD) with sub-Gbps key rate within metropolitan area and secure transmissions up to 25 km

Abstract Background The growth and development of muscle stem cells (MuSCs) are significant events known to affect muscle plasticity, disease, meat production, and meat quality, which involves the types and functions of mRNA and non-coding RNA. Here, MuSCs were cultured from Guangxi fetal cattle. RNA sequencing was used to analyze the RNA expression of mRNA and non-coding RNAs during the cell proliferation and differentiation phases. Results Two thousand one hundred forty-eight mRNAs and 888 non-coding RNAs were differentially expressed between cell proliferation and differentiation phases, including 113 miRNAs, 662 lncRNAs, and 113 circRNAs. RT-qPCR verified the differential expression levels of mRNAs and non-coding RNAs, and the differentially expressed circUBE2Q2 was subsequently characterized. Expression profile analysis revealed that circUBE2Q2 was abundant in muscle tissues and intramuscular fat. The expression of cricUBE2Q2 was also significantly upregulated during MuSCs myogenic differentiation and SVFs adipogenic differentiation and decreased with age in cattle muscle tissue. Finally, the molecular mechanism of circUBE2Q2 regulating MuSCs function that affects skeletal muscle development was investigated. The results showed that circUBE2Q2 could serve as a sponge for miR-133a, significantly promoting differentiation and apoptosis of cultured MuSCs, and inhibiting proliferation of MuSCs. Conclusions CircUBE2Q2 is associated with muscle growth and development and induces MuSCs myogenic differentiation through sponging miR-133a. This study will provide new clues for the mechanisms by which mRNAs and non-coding RNAs regulate skeletal muscle growth and development, affecting muscle quality and diseases.

Current drugs do not provide an absolute cure or modify the course of asthma. Hyssopus cuspidatus Boriss extract (SXCF) has been used as Uyghur medicine for several years to treat bronchial asthma. However, very limited research has been conducted on the therapeutic mechanisms of SXCF. Disruptions in the metabolic network of lipid mediators (LMs) are closely linked to the development of asthma. Here, we explored the therapeutic mechanism of SXCF in asthma based on the metabolic network of LMs, aiming to contribute to the understanding of SXCF in asthma treatment at the molecular level. The UHPLC-MRM strategy was used for the quantitative detection of LMs in the lung tissue and in the peripheral circulatory system (serum). ELISA was used to detect IgE in serum and cytokines in BALF. The lung tissue sections were stained with H&E to observe the infiltration of inflammatory cells, and behavioural changes in mice were observed and recorded throughout the animal experiment. In contrast to the asthma group, the opposite result was observed in the SXCF groups, where the perturbed LMs metabolic network was partly restored in a dose-dependent manner with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. As significant downregulation of IgE and pro-inflammatory cytokines was observed, IgE and cytokines analysis also supported the anti-inflammatory effects of SXCF. It was also noticed that SXCF treatment reduced the number of coughs and decreased the inflammatory cell infiltration around the bronchus in mice. These results suggested that SXCF has a significant ameliorative effect on ovalbumin (OVA)-induced asthma. The modulation of LMs is a possible underlying mechanism of the SXCF effects.

Objective This case–control study focused on the establishment and internal validation of a risk nomogram for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) using the Kawasaki Disease Database. Methods The Kawasaki Disease Database is the first public database for KD researchers. A prediction nomogram for IVIG-resistant KD was constructed using multivariable logistic regression. Then, the C-index was used to assess the discriminating ability of the proposed prediction model, a calibration plot was drawn to evaluate its calibration, and a decision curve analysis was adopted to assess its clinical usefulness. Bootstrapping validation was performed for interval validation. Results The median ages of IVIG-resistant and -sensitive KD groups were 3.3 and 2.9 years, respectively. Predicting factors incorporated into the nomogram were coronary artery lesions, C-reactive protein, percentage of neutrophils, platelets, aspartate aminotransferase, and alanine transaminase. Our constructed nomogram exhibited favorable discriminating ability (C-index: 0.742; 95% confidence interval: 0.673–0.812) and excellent calibration. Moreover, interval validation achieved a high C-index of 0.722. Conclusions The as-constructed new IVIG-resistant KD nomogram that incorporated C-reactive protein, coronary artery lesions, platelets, percentage of neutrophils, alanine transaminase, and aspartate aminotransferase may be adopted for predicting the risk of IVIG-resistant KD.