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Aiming at the problems that the failure of members can change the stress state of the structure, and the building may be severely damaged or even collapsed due to aftershock sequences, the effect of aftershock sequences and link failure on the seismic performance of K-eccentrically braced steel frames (K-EBF) was investigated. Incremental dynamic analysis, fragility analysis, and collapse-resistant performance evaluations of 12-story and 18-story K-EBF were conducted by using the maximum inter-story drift as the seismic demand parameter and peak seismic acceleration as the ground motion intensity parameter. The results show that compared with non-considering the effect of aftershock sequences and link failure, under the fortification earthquakes, the two factors (aftershock sequences and link failure) make the θmax of the 12-story and 18-story K-EBF structures increase by 2.3% and 8.4%, and the probability of severe damage increase by 0.6% and 2.8%, respectively; Under rare earthquakes, the θmax of the 12-story and 18-story K-EBF structures increase by 21.0% and 42.1%, and the probability of severe damage failure increase by 11.6% and 19.4%, respectively; In addition, the minimum structural collapse reserve factor decreases by 32.1% and 31.2% for 12-story and 18-story structures, respectively; Overall, aftershock sequences will aggravate the structure damage accumulation, and the negative effect on the structure increases with the intensity of the earthquakes;The failure probabilities of different limit state will further increase after considering the link failure, which will result in a further decrease with the minimum structural collapse reserve factor; Therefore, the effects caused by aftershock sequences and link failure should be fully considered in the seismic performance analysis of K-EBF to reveal the structural real dynamic response under earthquakes. Taking both the damage failure of link failure and the effect of aftershocks into consideration can comprehensively analyze the seismic performance of K-EBF structures, which provides a more reliable basis for seismic design.

Abstract Introduction Previous randomized controlled trials (RCTs) and meta-analyses comparing Hemodiafiltration (HDF) with conventional hemodialysis (HD) on the effectiveness of HDF for mortality in end-stage renal disease (ESRD) patients have yielded contrasting results. Importantly, we sought to compile the available information to provide the most up-to-date and reliable evidence. Methods We systematically searched PubMed, Embase and Cochrane Library for RCTs up to January 14, 2024. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence. Results Our study involved 10 randomized controlled trials with 4654 chronic dialysis patients. Compared to hemodialysis, hemodiafiltration demonstrated a reduction in all-cause mortality (relative risk [RR] 0.84, 95% confidence intervals [CI] 0.72–0.99, P = 0.04) and cardiovascular mortality (RR 0.74, 95% CI 0.61–0.90, P = 0.002). However, it did not reduce the rate of sudden death (RR 0.92, 95% CI 0.64–1.34, P = 0.68) and infection-related mortality (RR 0.70, 95% CI 0.47–1.03, P = 0.07). A subgroup analysis revealed that HDF demonstrated superiority over high-flux hemodialysis in terms of all-cause mortality, while not over low-flux hemodialysis (RR 0.81, 95% CI 0.69–0.96, P = 0.01; RR 0.93, 95% CI 0.77–1.12, P = 0.44, respectively). Furthermore, a subgroup analysis for convection volume found that hemodiafiltration with a convection volume of 22 L or more reduced all-cause and cardiovascular mortality (RR 0.76, 95% CI 0.65–0.88, P = 0.0002, RR 0.73, 95% CI 0.54–0.94, P = 0.01, respectively). Conclusion In maintenance hemodialysis patients, hemodiafiltration can reduce mortality compared to conventional hemodialysis. Furthermore, this effect is more pronounced in HDF with high convection volume.

Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y6R mainly distributed in macrophages was significantly up-expressed in skin lesions from patients with psoriasis in the present study. Here, the severity of psoriasis was alleviated in imiquimod-treated mice with macrophages conditional knockout of P2Y6R, while the cell-chat algorithm showed there was a correlation between macrophage P2Y6R and Th1 cells mediated by IL-27. Mechanistically, P2Y6R enhanced PLCβ/p-PKC/MAPK activation to induce IL-27 release dependently, which subsequently regulated the differentiation of Th1 cells, leading to erythematous and scaly plaques of psoriasis. Interestingly, we developed a novel P2Y6R inhibitor FS-6, which bonds with the ARG266 side chain of P2Y6R, exhibited remarkable anti-psoriasis effects targeting P2Y6R. Our study provides insights into the role of P2Y6R in the pathogenesis of psoriasis and suggests its potential as a target for the development of therapeutic interventions. A novel P2Y6R inhibitor FS-6 could be developed as an anti-psoriasis drug candidate for the clinic.

Abstract Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.

Background: Inherited kidney diseases (IKDs) in children pose unique diagnostic and therapeutic challenges. IKD significantly impact patient quality of life, morbidity, mortality, and cost to the healthcare system. With over 150 genetic abnormalities, they account for approximately 30% of cases requiring renal replacement therapy. There is an urgent need to advance both diagnosis and treatment strategies. In this review, we present recent advances in diagnosis and treatment for facilitating personalized treatment approaches. Summary: The diagnostic landscape for IKDs have evolved significantly, emphasizing precise genetic identification and classification of these disorders. Recent advancements include the refinement of genetic testing techniques, such as whole exome sequencing, which has improved the accuracy of diagnosing specific diseases and facilitated early intervention strategies. Additionally, this review categorizes IKDs based on genetic abnormalities and clinical manifestations, enhancing understanding and management approaches. Finally, it summarizes the corresponding treatment, and lists the application of emerging therapeutic options such as gene therapy and organoids, which show promise in transforming treatment outcomes. Key Messages: This review summarizes the common types of IKDs in children, including their diagnosis and treatment advances, and provides an update on the status of gene therapy development for these disorders.

The uncertainties in microwave land surface emissivity (MLSE) measurements have long limited the use of spaceborne microwave radiometer data. As an emerging observation method, Global Navigation Satellite System Reflectometry (GNSS-R) has demonstrated great potential in several land and ocean applications. In this study, a method for obtaining daily MLSE dataset in the pan-tropical region from Cyclone GNSS (CYGNSS) observations is presented and evaluated. The CYGNSS observations are first aggregated into the Equal-Area-Scalable-Earth (EASE) 2.0 36 km grid by a combined weight function of distance, time, and signal-to-noise ratio variance. Then, the method employs a pixel-by-pixel regression algorithm to conduct the daily MLSE retrieval using reference emissivity derived from the Soil Moisture Active Passive (SMAP) brightness temperature. The CYGNSS MLSE shows good agreement with SMAP MLSE, delivering an overall root-mean-square error (RMSE) of 0.022 and 0.017 for horizontal and vertical polarization, respectively, during the training set spanning the whole year of 2018. Furthermore, on the test set from January 2019 to May 2019, the RMSE values amounted to 0.030 and 0.023 for horizontal and vertical polarization, respectively. Temperature records from the International Soil Moisture Network are employed to calculate the emissivity and for in-situ validation, which yield an RMSE of 0.034 and 0.026 for the two polarizations, respectively. The proposed algorithm provides an encouraging approach to obtain accurate daily MLSE dataset for microwave remote sensing. Compared to the SMAP MLSE, the CYGNSS MLSE has a remarkable improvement of 86% in temporal resolution, greatly complementing the existing microwave emissivity datasets.

The anaerobic membrane bioreactor (AnMBR) is a promising technology for not only water reclamation but also virus removal; however, the virus removal efficiency of AnMBR has not been fully investigated. Additionally, the removal efficiency estimation requires datasets of virus concentration in influent and effluent, but its monitoring is not easy to perform for practical operation because the virus quantification process is generally time-consuming and requires specialized equipment and trained personnel. Therefore, in this study, we aimed to identify the key, monitorable variables in AnMBR and establish the data-driven models using the selected variables to predict virus removal efficiency. We monitored operational and environmental conditions of AnMBR in Sendai, Japan and measured virus concentration once a week for six months. Spearman's rank correlation analysis revealed that the pH values of influent and mixed liquor suspended solids (MLSS) were strongly correlated with the log reduction value of pepper mild mottle virus, indicating that electrostatic interactions played a dominant role in AnMBR virus removal. Among the candidate models, the random forest model using selected variables including influent and MLSS pH outperformed the others. This study has demonstrated the potential of AnMBR as a viable option for municipal wastewater reclamation with high microbial safety. HIGHLIGHTS Virus removal efficiency in the AnMBR was monitored.; The data-driven model to predict virus removal efficiency was built.; The random forest model had the highest prediction performance.; The pH values of influent and MLSS strongly correlated with virus removal efficiency.;

Background: Face image animation generates a synthetic human face video that harmoniously integrates the identity derived from the source image and facial motion obtained from the driving video. This technology could be beneficial in multiple medical fields, such as diagnosis and privacy protection. Previous studies on face animation often relied on a single source image to generate an output video. With a significant pose difference between the source image and the driving frame, the quality of the generated video is likely to be suboptimal because the source image may not provide sufficient features for the warped feature map. Methods: In this study, we propose a novel face-animation scheme based on multiple sources and perspective alignment to address these issues. We first introduce a multiple-source sampling and selection module to screen the optimal source image set from the provided driving video. We then propose an inter-frame interpolation and alignment module to further eliminate the misalignment between the selected source image and the driving frame. Conclusions: The proposed method exhibits superior performance in terms of objective metrics and visual quality in large-angle animation scenes compared to other state-of-the-art face animation methods. It indicates the effectiveness of the proposed method in addressing the distortion issues in large-angle animation.

Abstract Cancer, a prevalent and complex disease, presents a significant challenge to the medical community. It is characterized by irregular cell differentiation, excessive proliferation, uncontrolled growth, invasion of nearby tissues, and spread to distant organs. Its progression involves a complex interplay of several elements and processes. Extracellular vesicles (EVs) serve as critical intermediaries in intercellular communication, transporting critical molecules such as lipids, RNA, membrane, and cytoplasmic proteins between cells. They significantly contribute to the progression, development, and dissemination of primary tumors by facilitating the exchange of information and transmitting signals that regulate tumor growth and metastasis. However, EVs do not have a singular impact on cancer; instead, they play a multifaceted dual role. Under specific circumstances, they can impede tumor growth and influence cancer by delivering oncogenic factors or triggering an immune response. Furthermore, EVs from different sources demonstrate distinct advantages in inhibiting cancer. This research examines the biological characteristics of EVs and their involvement in cancer development to establish a theoretical foundation for better understanding the connection between EVs and cancer. Here, we discuss the potential of EVs from various sources in cancer therapy, as well as the current status and future prospects of engineered EVs in developing more effective cancer treatments.

Abstract Photothermal microscopy is a highly sensitive pump-probe method for mapping nanostructures and molecules through the detection of local thermal gradients. While visible photothermal microscopy and mid-infrared photothermal microscopy techniques have been developed, they possess inherent limitations. These techniques either lack chemical specificity or encounter significant light attenuation caused by water absorption. Here, we present an overtone photothermal (OPT) microscopy technique that offers high chemical specificity, detection sensitivity, and spatial resolution by employing a visible probe for local heat detection in the C-H overtone region. We demonstrate its capability for high-fidelity chemical imaging of polymer nanostructures, depth-resolved intracellular chemical mapping of cancer cells, and imaging of multicellular C. elegans organisms and highly scattering brain tissues. By bridging the gap between visible and mid-infrared photothermal microscopy, OPT establishes a new modality for high-resolution and high-sensitivity chemical imaging. This advancement complements large-scale shortwave infrared imaging approaches, facilitating multiscale structural and chemical investigations of materials and biological metabolism.

The purpose of this study was to investigate the protective effect and underlying mechanism of orexin A on cerebral ischemia-reperfusion injury, specifically through vasodilation mediated by the hypoxia inducible factor-1α (HIF-1α)-Endothelin-1(ET-1)/endothelial nitric oxide synthase (eNOS) pathway. A model of middle cerebral artery occlusion was established in both wild-type SD rats with exogenous orexin A intervention and in orexin A transgenic rats. Neurological deficit scores and cerebral infarction areas were assessed, and ischemic cortical blood flow was monitored. Gene and protein expression levels of HIF-1α, HIF-2α, ET-1, and three types of NOS were detected using real-time RT-qPCR and Western blot analysis, respectively. Additionally, nitric oxide (NO) levels in the cortex were analyzed through biochemical detection methods. Orexin A demonstrated a protective effect by reducing cerebral infarction and improving neurological deficits, which was achieved by increasing cortical blood flow during reperfusion. This protective mechanism was associated with upregulated HIF-1α expression, downregulated ET-1 expression, upregulated eNOS expression, and increased NO production. This study demonstrates the protective effect of orexin A on cerebral ischemia-reperfusion injury, achieved by regulating the release of vasomotor substances to enhance cortical blood flow during reperfusion. These findings suggest that orexin A may represent a potential therapeutic strategy for ischemic stroke.

Abstract Purinergic signaling plays a causal role in the pathogenesis of inflammatory bowel disease. Among purinoceptors, only P2Y14R is positively correlated with inflammatory score in mucosal biopsies of ulcerative colitis patients, nevertheless, the role of P2Y14R in ulcerative colitis remains unclear. Here, based on the over-expressions of P2Y14R in the intestinal epithelium of mice with experimental colitis, we find that male mice lacking P2Y14R in intestinal epithelial cells exhibit less intestinal injury induced by dextran sulfate sodium. Mechanistically, P2Y14R deletion limits the transcriptional activity of cAMP-response element binding protein through cAMP/PKA axis, which binds to the promoter of Ripk1, inhibiting necroptosis of intestinal epithelial cells. Furthermore, we design a hierarchical strategy combining virtual screening and chemical optimization to develop a P2Y14R antagonist HDL-16, which exhibits remarkable anti-colitis effects. Summarily, our study elucidates a previously unknown mechanism whereby P2Y14R participates in ulcerative colitis, providing a promising therapeutic target for inflammatory bowel disease.

Objectives: To investigate the role of the intestinal flora and metabolites in the development of hyperuricemic renal injury in chronic kidney disease (CKD).Methods: Unilaterally nephrectomized mice were fed with adenine and potassium oxonate for 9 weeks. HE staining combined with plasma biochemical indicators was used to evaluate renal pathological and functional changes. We conducted 16S rRNA sequencing and untargeted metabolomics on feces and plasma samples to reveale changes in intestinal microbiota and metabolites.Result: Our analysis revealed significant differences in 15 bacterial genera, with 7 being upregulated and 8 being downregulated. Furthermore, metabolomic analysis revealed changes in the distribution of amino acid and biotin metabolites in basic metabolic pathways in both feces and serum. Specifically, differentially abundant metabolites in feces were associated primarily with histidine metabolism; the biosynthesis of phenylalanine, tyrosine, and tryptophan; and tyrosine metabolism. In plasma, the differentially abundant metabolites were involved in multiple metabolic pathways, including aminoacyl-tRNA biosynthesis; glycine, serine, and threonine amino acid metabolism; valine, leucine, and isoleucine biosynthesis; tyrosine biosynthesis and metabolism; biotin metabolism; and taurine and hypotaurine metabolism. Furthermore, correlation analysis revealed that Akkermansia, UCG-005, Lachnospiraceae_NK4A136_group, Lactococcus, and Butymonas were associated with various differentially abundant metabolites as well as renal function, oxidative stress, and mitophagy. The changes in the intestinal flora observed in hyperuricemia may lead to imbalances in amino acid and biotin metabolism in both the intestine and host, ultimately affecting oxidative stress and mitophagy in mice and accelerating the progression of CKD.Conclusion: Our findings provide insights into a potential pathogenic mechanism by which hyperuricemia exacerbates renal injury in mice with renal insufficiency. Understanding these pathways may offer new therapeutic strategies for managing hyperuricemic renal injury in CKD patients.

We propose an acoustic-mechanical metasurface with simultaneous sound absorption and vibration reduction functionalities. This acoustic-mechanical feature results from a nonlocal coupling effect in the designed composite meta-structure. A nonlocal meta-mesh is designed at the acoustic-mechanical interface and embedded in the metasurface array to connect adjacent unit cells, which can make a nonlocal coupling effect. This effect can improve the acoustic property, which strengthens sound absorption by 58.6 %, and the mechanical interface strengthens vibration acceleration reduction by 88.45 %. The resulting nonlocal acoustic-mechanical metasurface achieves an average absorption coefficient of higher than 0.9 within 267–638 Hz, and a vibration level difference of 18.75 dB within 490–920 Hz. The sample has an ultra-thin thickness of 8.5 cm (λ/14 for the lowest working frequency) and is lightweight (305.1 g), whose weight reduction reaches 42.8 % compared with conventional designs with similar functionalities. Our proposed design strategy will be enlightened for multi-functional acoustic-mechanical coupling meta-device.

This research investigates the dynamics of smoke dispersion in a subway train carriage with multiple lateral openings within a ventilated subway tunnel. Numerous extensive full-scale numerical simulations were conducted to analyze the thermal plume distribution within multiple lateral openings of a train carriage, and the longitudinal and transverse maximum excess ceiling temperature. The results reveal that the heat release rates have a greater impact on the airflow in the carriage than velocities ,even when the longitudinal ventilation velocity reaches 8 m/s or the heat release rate reaches 15 MW. The multiple lateral openings cause significant differences in smoke flow characteristics compared to tunnels with both ends open. Additionally, the transverse maximum ceiling excess temperature inclines towards the lateral opening side due to asymmetrical air entrainment. The analysis of longitudinal maximum ceiling excess temperature identified two regions based on the dimensionless heat release rate, showing a linear increase followed by a constant phase dependent on the heat release rate, with a maximum longitudinal excess gas temperature of 1242 K. Additionally, a relationship between the dimensionless heat release rate and the transverse dimensionless maximum ceiling excess temperature was established. This study can be used as a guide for smoke exhaust mitigation and fire safety measures in the event of subway train carriage fires.

While rapid development and roll out of COVID-19 vaccines is necessary in a pandemic, the process limits the ability of clinical trials to assess longer-term vaccine efficacy. We leveraged COVID-19 surveillance data in the U.S. to evaluate vaccine efficacy in U.S. Government-funded COVID-19 vaccine efficacy trials with a three-step estimation process. First, we used a compartmental epidemiological model informed by county-level surveillance data, a “population model”, to estimate SARS-CoV-2 incidence among the unvaccinated. Second, a “cohort model” was used to adjust the population SARS-CoV-2 incidence to the vaccine trial cohort, taking into account individual participant characteristics and the difference between SARS-CoV-2 infection and COVID-19 disease. Third, we fit a regression model estimating the offset between the cohort-model-based COVID-19 incidence in the unvaccinated with the placebo-group COVID-19 incidence in the trial during blinded follow-up. Counterfactual placebo COVID-19 incidence was estimated during open-label follow-up by adjusting the cohort-model-based incidence rate by the estimated offset. Vaccine efficacy during open-label follow-up was estimated by contrasting the vaccine group COVID-19 incidence with the counterfactual placebo COVID-19 incidence. We documented good performance of the methodology in a simulation study. We also applied the methodology to estimate vaccine efficacy for the two-dose AZD1222 COVID-19 vaccine using data from the phase 3 U.S. trial (ClinicalTrials.gov # NCT04516746). We estimated AZD1222 vaccine efficacy of 59.1% (95% uncertainty interval (UI): 40.4%–74.3%) in April, 2021 (mean 106 days post-second dose), which reduced to 35.7% (95% UI: 15.0%–51.7%) in July, 2021 (mean 198 days post-second-dose). We developed and evaluated a methodology for estimating longer-term vaccine efficacy. This methodology could be applied to estimating counterfactual placebo incidence for future placebo-controlled vaccine efficacy trials of emerging pathogens with early termination of blinded follow-up, to active-controlled or uncontrolled COVID-19 vaccine efficacy trials, and to other clinical endpoints influenced by vaccination.

Understanding nitrogen (N) uptake rates respect to nutrient availability and the biogeography of phytoplankton communities is crucial for untangling the complexities of marine ecosystems and the physical, biological, and chemical forces shaping them. In the summer of 2016, we conducted measurements of bulk microbial uptake rates for six 15N-labeled substrates: nitrate, nitrite, ammonium, urea, cyanate, and dissolve free amino acids across distinct marine provinces, including the continental shelf of the Mid-and South Atlantic Bights (MAB and SAB), the Slope Sea, and the Gulf Stream, marking the first instance of simultaneously measuring six different N uptake rates in this dynamic region. Total measured N uptake rates were lowest in the Gulf Stream followed by the SAB. Notably, the MAB exhibited significantly higher N uptake rates compared to the SAB, likely due to the excess levels of pre-existing phosphorus present in the MAB. Together, urea and nitrate uptake contributed approximately 50% of the total N uptake across the study region. Although cyanate uptake rates were consistently low, they accounted for up to 11% of the total measured N uptake at some Gulf Stream stations. Phytoplankton groups were identified based on specific pigment markers, revealing a dominance of diatoms in the shelf community, while Synechococcus, Prochlorococcus, and pico-eukaryotes dominated in oligotrophic Gulf Stream waters. The reported uptake rates in this study were mostly in agreement with previous studies conducted in coastal waters of the North Atlantic Ocean. This study suggests there are distinct regional patterns of N uptake in this physically dynamic region, correlating with nutrient availability and phytoplankton community composition. These findings contribute valuable insights into the intricate interplay of biological and chemical factors shaping N dynamics in disparate marine ecosystems.

China’s commitment to achieving the goal of carbon peak and carbon neutrality (CPCN) has attracted worldwide attention, and the efforts made by China are critical to realization of the 1.5 °C temperature control objective of the 2015 Paris Agreement. However, it is unclear whether long-term spatiotemporal changes in China’s carbon emissions and carbon sinks exhibit specific spatial patterns, such as the Hu Line, which might affect China’s future policymaking. Based on the emission factor, inventory, and eddy covariance methods, this study calculated China’s carbon emissions (2003–2018) and terrestrial carbon sinks (2003–2020). Results showed that the increase in carbon sinks is limited in comparison with the increase in carbon emissions, and that the carbon sequestration ratio remains deficient and generally maintained at around 10 %. The spatial pattern of carbon emissions and carbon sinks showed an unbalanced state across the Hu Line, mainly reflected in accelerated increase in both the carbon emission rankings and the proportion of emissions to China’s total carbon emissions of provinces on the northwestern side of the Hu Line. Despite this, the gross domestic product (GDP) rankings of those provinces have not improved substantially, whereas provinces on the southeastern side of the Hu Line have contributed most to China’s GDP and terrestrial carbon sinks. The findings of this study improve understanding of the spatiotemporal relationship between carbon emissions and terrestrial carbon sinks in China, and represent alternative insights that could support adjustment of carbon-related policies and promote realization of CPCN in China.

With the escalating challenges of climate change and the imperative for carbon neutrality, evaluating the carbon footprint of regional power systems becomes crucial. To address this issue, a low-carbon evaluation framework for regional power systems is developed. First, this study identifies the fundamental requirements that the index system for the low-carbon power system should follow and specifies the general direction for the index system’s creation. Second, an evaluation model for carbon reduction ability is proposed by considering generation side, grid side and load side of the power system. Then, a comparative evaluation model for the carbon reduction capability of multi-regional power systems is proposed to spatiotemporally compare the carbon reduction capability of different power systems. Next, a quantification method for the weights of low-carbon evaluation indicators is established based on the power system simulation of multi-scenario scheduling and index sensitivity analysis method. Finally, a low-carbon comprehensive score for regional power systems is created by combining the evaluation results of the system’s carbon reduction capacity with index weights. The practical research results in a region of Zhejiang province in China demonstrate that the proposed model can provide a reasonable and feasible evaluation plan for the low-carbon construction of regional power systems.

Landscape freeze–thaw (F/T) state parameters are an integral part of research on terrestrial hydrological processes, vegetation growth dynamics, and terrestrial–atmospheric trace gas exchange. Therefore, the development of large-scale, continuous, and rapid F/T observation records is essential. This study proposes a scheme to effectively retrieve quasi-global daily soil F/T states from spaceborne Global Navigation Satellite System Reflectometry (GNSS-R) observations. This method takes into account the GNSS-R surface reflectivity and its influence factor. Specifically, the method employed surface reflectivity derived from Cyclone Global Navigation Satellite System (CYGNSS) data from 2018 to 2020, along with vegetation opacity data from Soil Moisture Active Passive (SMAP) as input layers in random forests for F/T retrieval. This approach provides F/T results on a quasi-global scale, does not rely on continuous F/T observations, and employs the least ancillary data. To validate the retrieval results, SMAP F/T data over the same period and temperature data from more than 100 ground stations were also used as reference. Results showed that the F/T retrieval accuracy of CYGNSS was 95.5% and 82.0% with respect to the SMAP data and data from independent in situ stations, respectively. Given the high temporal coverage of the CYGNSS F/T results, the temporal coverage improvement is 23.3% compared with the actual SMAP observations on a daily scale. Furthermore, as gap-filling data complemented SMAP, CYGNSS data can effectively improve the SMAP F/T sample interval (accuracy improvement of 26.0%). More importantly, the F/T accuracy of the CYGNSS and SMAP combination based on monthly performance is 85.1%, i.e., 20.5% better than that of the existing SMAP daily F/T product. Overall, the quasi-global daily F/T results obtained from CYGNSS and SMAP measurements can complement existing databases with well-defined accuracy.

Mycobacterium tuberculosis causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival are crucial for the infection and dissemination process, yet the cellular mechanisms underlying these phenomena remain poorly understood. This study created a Bacillus Calmette–Guérin (BCG) transposon library using a MycomarT7 phage carrying a Himar1 Mariner transposon to identify genes related to mycobacteria adhesion and invasion. Using adhesion and invasion model screening, we found that the mutant strain B2909 lacked adhesion and invasion abilities because of an inactive fadD18 gene, which encodes a fatty-acyl CoA ligase, although the specific function of this gene remains unclear. To investigate the role of FadD18, we constructed a complementary strain and observed that fadD18 expression enhanced the colony size and promoted the formation of a stronger cord-like structure; FadD18 expression also inhibited BCG growth and reduced BCG intracellular survival in macrophages. Furthermore, FadD18 expression elevated levels of the proinflammatory cytokines IL-6, IL-1β, and TNF-α in infected macrophages by stimulating the NF-κB and MAPK signaling pathways. Overall, the FadD18 plays a key role in the adhesion and invasion abilities of mycobacteria while modulating the intracellular survival of BCG by influencing the production of proinflammatory cytokines.

Based on single-cell sequencing of the hippocampi of 5× familiar Alzheimer's disease (5× FAD) and wild type mice at 2-, 12-, and 24-month of age, we found an increased percentage of microglia in aging and Alzheimer's disease (AD) mice. Blood brain barrier injury may also have contributed to this increase. Immune regulation by microglia plays a major role in the progression of aging and AD, according to the functions of 41 intersecting differentially expressed genes in microglia. Signaling crosstalk between C−C motif chemokine ligand (CCL) and major histocompatibility complex-1 bridges intercellular communication in the hippocampus during aging and AD. The amyloid precursor protein (APP) and colony stimulating factor (CSF) signals drive 5× FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus. Microglia are involved in the progression of aging and AD can be divided into 10 functional types. The strength of the interaction among microglial subtypes weakened with aging, and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.

Abstract This study aimed to identify shared specific genes associated with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) through bioinformatic analysis and to examine the role of the gut microbiome in RA. The data were extracted from the 3 RA and 1 IBD gene expression datasets and 1 RA gut microbiome metagenomic dataset. Weighted correlation network analysis (WGCNA) and machine learnings was performed to identify candidate genes associated with RA and IBD. Differential analysis and two different machine learning algorithms were used to investigate RA’s gut microbiome characteristics. Subsequently, the shared specific genes related to the gut microbiome in RA were identified, and an interaction network was constructed utilizing the gutMGene, STITCH, and STRING databases. We identified 15 candidates shared genes through a joint analysis of the WGCNA for RA and IBD. The candidate gene CXCL10 was identified as the shared hub gene by the interaction network analysis of the corresponding WGCNA module gene to each disease, and CXCL10 was further identified as the shared specific gene by two machine learning algorithms. Additionally, we identified 3 RA-associated characteristic intestinal flora (Prevotella, Ruminococcus, and Ruminococcus bromii) and built a network of interactions between the microbiomes, genes, and pathways. Finally, it was discovered that the gene CXCL10 shared between IBD and RA was associated with the three gut microbiomes mentioned above. This study demonstrates the relationship between RA and IBD and provides a reference for research into the role of the gut microbiome in RA.

Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vehicles (EVs) have received significant attention in recent times as emerging biomarkers and subjects of transformational studies. The three main branches of liquid biopsy have evolved from the three primary tumor liquid biopsy detection targets—CTC, ctDNA, and EVs—each with distinct benefits. CTCs are derived from circulating cancer cells from the original tumor or metastases and may display global features of the tumor. ctDNA has been extensively analyzed and has been used to aid in the diagnosis, treatment, and prognosis of neoplastic diseases. EVs contain tumor-derived material such as DNA, RNA, proteins, lipids, sugar structures, and metabolites. The three provide different detection contents but have strong complementarity to a certain extent. Even though they have already been employed in several clinical trials, the clinical utility of three biomarkers is still being studied, with promising initial findings. This review thoroughly overviews established and emerging technologies for the isolation, characterization, and content detection of CTC, ctDNA, and EVs. Also discussed were the most recent developments in the study of potential liquid biopsy biomarkers for cancer diagnosis, therapeutic monitoring, and prognosis prediction. These included CTC, ctDNA, and EVs. Finally, the potential and challenges of employing liquid biopsy based on CTC, ctDNA, and EVs for precision medicine were evaluated.

The excessive accumulation of antibiotic residue in animal-derived foods pose a threat to our heath. Therefore, it is necessary to establish a rapid, simple, effective, safe and highly sensitive lincomycin (LIN) residues detection method by high-performance liquid chromatography equipped with ultraviolet. Here, due to the weak UV absorption of LIN, the p-Toluenesulfonyl isocyanate (PTSI, has a strong UV absorption) was binded to the hydroxyl group of LINs by using pre-column derivatization method, improving the UV absorption of LIN. This 9-min-run analytical method detects and quantifies LIN residues with acceptable validation performance parameters in terms of sensitivity, selectivity, linearity, the limit of quantification, accuracy, and precision.Our result showed that the limits of detection and quantification for LIN in samples were 25–40 μg/kg and 40–60 μg/kg, respectively, under the optimized conditions. Furthermore, the LIN recoveries ranged from 72.4 % to 96.7 %; the determination coefficients were 0.9912–0.9996, and the relative standard deviations were 5.6 %-12.7 %. Therefore, the HPLC-UVD method for detecting LIN residues in animal-derived food products has been established.

The Shangri-La region, located in southwest China, is known for its dry climate and intense UltraViolet (UV) radiation due to its high altitude. Research conducted in the past has demonstrated that UV radiation, particularly UV-B radiation, enhances plants' ability to withstand cold temperatures, diseases, and arid conditions. Indeed, the Cabernet Sauvignon grape variety, predominantly cultivated in Shangri-La where the UV intensity reaches 21–22w/m2, has displayed remarkable resilience in recent decades. However, the specific impact of UV-B radiation on Cabernet Sauvignon grape leaves has yet to be fully understood. Consequently, our objective is to investigate the influence of UV radiation on grapes grown at high altitudes. To gain insights into the short-term effects on grape leaves, we conducted a comprehensive investigation involving anatomical and photosynthetic changes. Additionally, we analyzed the transcriptomic and proteomic regulation associated with these changes following exposure to UV-B radiation at intensities ranging from 15–20w/m2 for durations of 3 and 7 days.The findings of our study demonstrated that exposure to UV-B radiation, particularly at intensities surpassing 10w/m2, led to noticeable changes in the morphology of epidermal and palisade tissue cells. Furthermore, after a 3-day exposure to UV-B, we observed an upregulation of proteins responsible for cytoskeletal organization and cell wall synthesis. Conversely, following a 7-day treatment, proteins associated with disease resistance and antioxidants showed increased expression. Transcriptomic analysis revealed a significant enrichment of proteins and genes linked to pathogen infection, defense mechanisms, and antioxidant processes. Overall, our research highlighted the positive impact of intense UV radiation at high altitudes on enhancing disease resistance and environmental adaptability in Cabernet Sauvignon grape plants.

Abstract Three-dimensional (3D) covalent organic frameworks (COFs) possess higher surface areas, more abundant pore channels, and lower density compared to their two-dimensional counterparts which makes the development of 3D COFs interesting from a fundamental and practical point of view. However, the construction of highly crystalline 3D COF remains challenging. At the same time, the choice of topologies in 3D COFs is limited by the crystallization problem, the lack of availability of suitable building blocks with appropriate reactivity and symmetries, and the difficulties in crystalline structure determination. Herein, we report two highly crystalline 3D COFs with pto and mhq-z topologies designed by rationally selecting rectangular-planar and trigonal-planar building blocks with appropriate conformational strains. The pto 3D COFs show a large pore size of 46 Å with an extremely low calculated density. The mhq-z net topology is solely constructed from totally face-enclosed organic polyhedra displaying a precise uniform micropore size of 1.0 nm. The 3D COFs show a high CO2 adsorption capacity at room temperature and can potentially serve as promising carbon capture adsorbents. This work expands the choice of accessible 3D COF topologies, enriching the structural versatility of COFs.

This paper designed a hollow filter rod using cellulose diacetate as the raw material. A combination method involving single factor test and orthogonal test was used to analyze the impact of forming factors on physical characteristics. The results showed that the circumference of filter rods was negatively related to vapor pressure. The hardness was both positively connected with vapor pressure and tow-filling amount, while it increased initially and then reduced with the increase of plasticizer content. The roundness and weight varied little with vapor pressure. However, roundness was associated with plasticizer content and negatively associated with tow-filling amount. Besides, weight was positively associated with both plasticizer content and tow-filling amount. The orthogonal test results revealed that the tow-filling amount was the most important factor influencing the performance of filter rods, with vapor pressure and plasticizer content being secondary considerations. The best parameter combination was vapor pressure of 0.18 MPa, plasticizer content of 20%, and tow-filling amount of 1.19 g. The improved cigarette filter rod had a hardness of 92.07%, which was 5.61% greater than the previous value and only 0.08% higher than the optimal value. The enhanced performance of filter rods was attributable to three-dimensional entangled structures formed by cellulose diacetates and rational arrangement of tows and voids.

Abstract Background Diabetes mellitus (DM) and atherosclerosis are multifactorial conditions and share a common inflammatory basis. Three-vessel disease (TVD) represents a major challenge for coronary intervention. Nonetheless, the predictive value of high-sensitivity C-reactive protein (hs-CRP) for TVD patients with or without type 2 DM remains unknown. Herein, we aimed to ascertain the long-term predictive value of hs-CRP in TVD patients according to type 2 DM status from a large cohort. Methods A total of 2734 TVD patients with (n = 1040, 38%) and without (n = 1694, 62%) type 2 diabetes were stratified based on the hs-CRP (

Abstract To provide backup and supplementation for the Global Navigation Satellite System (GNSS), Doppler shift from Low Earth Orbit (LEO) satellites can be used as signals of opportunity to provide positioning, navigation, and timing service. In this contribution, we first investigate the model and performance of instantaneous velocity determination and positioning with LEO satellites. Given a LEO constellation with 288 satellites, we simulate Doppler shift observations at nine multi-GNSS experiment stations. Owing to the lower orbit, the performance of LEO velocity determination is much more sensitive to the initial receiver position error than that of GNSS. Statistical results show that with the initial receiver position error increased from 0.1 to 10 m, the Root Mean Square Errors (RMSEs) increase from 0.73 to 2.65 cm/s, 0.68 to 2.96 cm/s, and 1.67 to 4.15 cm/s in the east, north, and up directions, respectively. The performances with GPS are compared with GPS + LEO, and it is found that LEO Doppler shift observations contribute to GPS velocity determination. As for LEO Doppler positioning, even if more than 30 visible LEO satellites are available, the position dilution of precision values can reach several hundreds. Assuming that the error of LEO Doppler measurements is 0.01 m/s, the instantaneous Doppler positioning accuracy can achieve about a few meters, which is comparable to that of GNSS pseudorange positioning. A constant velocity model is adopted for state transition. Static LEO Doppler positioning results show that an accuracy at centimeter to decimeter level can be achieved after solution convergence. For a static simulated kinematic positioning test, the RMSEs range from a few decimeters to several meters in different regions by giving different constraints. For a dynamic positioning test, the RMSEs are about 2–3 m in high latitude region.

This study aimed to investigate how diets supplemented with DHA-rich algae affect the expression of liver lipid synthesis genes in dairy goat bucks. The results revealed that when supplemented with DHA-rich algae, liver weight and serum HDL-C were significantly increased (p < 0.05), as well as serum LDL-C was significantly decreased (p < 0.05). Transcriptome sequencing indicated that algae supplementation alters liver gene expression. The differentially expressed genes were predominantly enriched in fatty acid metabolism and the biosynthesis of unsaturated fatty acids. The expression of fatty acid desaturation and transcription factors (SCD, FADS1, INSIG1), de novo synthesis fatty acids (FASN), fatty acid transport (LDLR), and cholesterol and steroid synthesis (HMGCR, HMGCS1, SQLE) genes were significantly increased (p < 0.05), and fatty acid oxidation (ALDH3B1) genes were significantly decreased (p < 0.05). In conclusion, this research provided preliminary evidence that supplementation with algae in dietary supplements altered the expression of the liver lipid synthesis genes in the Saanen dairy goat bucks.

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved into a dangerous pathogen resistant to beta-lactam antibiotics (BLAs) and has become a worrisome superbug. In this study, a strategy in which shikimic acid (SA), which has anti-inflammatory and antibacterial activity, is combined with BLAs to restart BLA activity was proposed for MRSA treatment. The synergistic effects of oxacillin combined with SA against oxacillin resistance in vitro and in vivo were investigated. The excellent synergistic effect of the oxacillin and SA combination was confirmed by performing the checkerboard assay, time-killing assay, live/dead bacterial cell viability assay, and assessing protein leakage. SEM showed that the cells in the control group had a regular, smooth, and intact surface. In contrast, oxacillin and SA or the combination treatment group exhibited different degrees of surface collapse. q-PCR indicated that the combination treatment group significantly inhibited the expression of the mecA gene. In vivo, we showed that the combination treatment increased the survival rate and decreased the bacterial load in mice. These results suggest that the combination of oxacillin with SA is considered an effective treatment option for MRSA, and the combination of SA with oxacillin in the treatment of MRSA is a novel strategy.

BackgroundMost of malignant external otitis (MEO) cases reported in the literature are attributed to Pseudomonas aeruginosa. Fungal infections in MEO are also likely but extremely rare. And conventional microbiology tests is difficult to diagnose.Case descriptionTwo patients were diagnosed with Fungal malignant external otitis (FMEO) due to Aspergillus by metagenomic Next-Generation Sequencing (mNGS) and recovered after comprehensive treatment including operation and voriconazole. The antifungal treatment was delayed due to repeated cultures of secretions being negative and pathological examination showed granulation tissue proliferation with extensive neutrophil infiltration.ConclusionmNGS might be helpful for patients suspected with FMEO, especially when conventional microbiology tests were negative.

Object: This study aims to investigate the changes in gut microbiota and metabolism of patients with chronic kidney disease (CKD) stage 1–2, as well as the potential impact of hyperuricemia (HUA) on these factors in CKD stage 1–2 patients. Methods: In this study, fecal samples were collected from CKD stage 1–2 without HUA patients (CKD-N group), CKD stage 1–2 with HUA patients (CKD-H group), and healthy people controls (HCs group). The samples were then subjected to the microbiome (16S rRNA gene sequencing) and metabolome (liquid chromatography-tandem mass spectrometry) analyses. The multi-omics datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches. Results: Gut microbial dysbiosis was found in CKD-N and CKD-H patients. At the phylum level, compared to HCs group, Bacteroidetes decreased but Proteobacteria increased in CKD-H group significantly. Fusobacteria in CKD-N group was significantly lower than HCs group. At genus level, [Eubacterium]_ventriosum_group, Fusobacterium, Agathobacter, Parabacteroides, and Roseburia significantly changed in CKD groups. [Ruminococcus]_gnavus_group was significantly lower in CKD-H group than CKD-N group. Moreover, the fecal metabolome of CKD-N and CKD-H altered significantly. d-glutamine and d-glutamate metabolism, arginine and proline metabolism, histidine metabolism, and lysine biosynthesis were down-regulated in the CKD-N group. Phenylalanine metabolism, arginine and proline metabolism, purine metabolism, and beta-alanine metabolism were up-regulated in the CKD-H group. There was a significant difference between the two CKD groups in phenylalanine metabolism. The abundance change of [Ruminococcus]_gnavus_group, [Eubacterium]_ventriosum_group, UCG-002, Alistipes, and Bifidobacterium had a close correlation with differential metabolites. Conclusion: The gut microbiota and metabolic status undergo significant changes in CKD patients compared to healthy people. Additionally, HUA has been found to impact the gut microbiota of CKD patients, as well as their metabolism. The close association between gut microbiota and metabolites suggests that the former plays a crucial role in metabolism.

Abstract The amount of data produced by genome sequencing experiments has been growing rapidly over the past several years, making compression important for efficient storage, transfer and analysis of the data. In recent years, nanopore sequencing technologies have seen increasing adoption since they are portable, real-time and provide long reads. However, there has been limited progress on compression of nanopore sequencing reads obtained in FASTQ files since most existing tools are either general-purpose or specialized for short read data. We present NanoSpring, a reference-free compressor for nanopore sequencing reads, relying on an approximate assembly approach. We evaluate NanoSpring on a variety of datasets including bacterial, metagenomic, plant, animal, and human whole genome data. For recently basecalled high quality nanopore datasets, NanoSpring, which focuses only on the base sequences in the FASTQ file, uses just 0.35–0.65 bits per base which is 3–6 $$\times$$ × lower than general purpose compressors like gzip. NanoSpring is competitive in compression ratio and compression resource usage with the state-of-the-art tool CoLoRd while being significantly faster at decompression when using multiple threads (> 4 $$\times$$ × faster decompression with 20 threads). NanoSpring is available on GitHub at https://github.com/qm2/NanoSpring .

Abstract Background Inhaled NO is a selective pulmonary vasodilator proven to be therapeutic for patients with pulmonary artery hypertension (PAH). The most common NO delivery system in clinical practice is cylinder-based, but unfortunately limited by its high costs, complicated delivery, and the requirement of an extensive supply chain, leaving vast unmet medical needs globally. Methods To address the need for rapid, affordable, and safe production of nitric oxide (NO) for in-home inhalation therapy in patients with PAH. We developed a novel portable device to derive NO from a nitrite complex solution with a copper(II)-ligand catalyst, and further examined its effectiveness in a porcine model of PAH. This model was established by using female Bama miniature pig and induced by monocrotaline (MCT) administration. Results This generator could rapidly and safely produce therapeutic NO at concentrations ranging from 0 to 100 parts per million (ppm) with the least disproportionated nitrogen dioxide (NO2) and byproducts. It could effectively alleviate pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in piglets with PAH, without causing major physiologic disruptions. Conclusions Our electrochemical NO generator is able to produce the desired NO doses for pulmonary vasodilation in a safe and sustainable way, with low costs, which paves the way for its subsequent clinical trials in the patient with PAH and other common cardiopulmonary conditions with a high disease burden around the world.

Luminescent iridium(III) complexes have several appealing properties such as wide color-tunability and high photo- and chemical stabilities, whereas the properties of related diiridium(II) systems are largely unexplored. Here, the authors synthesize and characterize a series of tetracationic dinuclear iridium(II) complexes, which feature unsupported Ir(II)–Ir(II) single bonds and exhibit photoluminescence in various media.

The vigorous development of renewable energy is an important way to achieve carbon neutrality in China, but the water and electricity consumption of renewable energy in its life cycle is still unclear. This study took the life cycle of photovoltaic (PV) industry as an example, combined the life cycle assessment method, Weibull model and water resources vulnerability index to evaluate the life cycle water and electricity consumptions of PV industry in 31 provinces and cities in China and further analyzed the effects of these consumptions on local resources. The results indicated that the PV industry consumed 7841.08 kg of water and 2580.6 kWh of electricity for 1 kWp. The discarded capacities of China will increase with growing installed capacities and reach nearly 13 GW in 2050, which will lead to significantly increasing usage of water and electricity of PV industry and exert pressure on water and electricity systems. Considering severe situation of water resources in central and northern China and huge demand for electricity in eastern China, the Chinese government should rationally arrange development of PV.

UV-B radiation and water deficit can challenge Pinot noir growth and fruit quality. The aim of this work is to determine the effects of UV-B and water deficit on the physiological indices, amino acids, and volatile compounds of Pinot noir vine and fruit. The results showed that both individual and combined treatments caused a decrease in the leaf SPAD, with the largest amplitude being observed in the combined treatment. Water deficit also decreased the leaf water potential and increased the juice δ13C‰ at harvest, which was the opposite of the latter under UV-B radiation. Interestingly, most of the physiological indices under combined stresses did not show significant changes compared with that under no UV-B and the well-watered control treatment. Moreover, the concentrations of amino acids and volatile compounds in the berries were determined at harvest. The amino acid contents were significantly increased by the combined treatment, particularly proline (Pro), aspartate (Arg), alanine (Ala), and threonine (Thr). There were slight increases in volatile compounds. This research substantially contributed to improve our scientific understanding of UV-B and water deficit responses in an important commercial species. In addition, it highlighted some future research to produce high-quality wines with the anticipated specific characteristics.

We report a monolithic heterodyne receiver that uses the AlGaN/GaN nonlinear transmission line as a local oscillator and a mixer simultaneously. This heterodyne receiver has a high RF bandwidth from 80 to 360 GHz and a high intermediate frequency bandwidth of 18 GHz. These results indicate that this nonlinear transmission line receiver has promising potential in broadband spectrum analysis.

The newly prepared monolayer (ML) SiAs is expected to be a candidate channel material for next-generation nano-electronic devices in virtue of its proper bandgap, high carrier mobility, and anisotropic properties. The interfacial properties in ML SiAs field-effect transistors are comprehensively studied with electrodes (graphene, V2CO2, Au, Ag, and Cu) by using ab initio electronic structure calculations and quantum transport simulation. It is found that ML SiAs forms a weak van der Waals interaction with graphene and V2CO2, while it forms a strong interaction with bulk metals (Au, Ag, and Cu). Although ML SiAs has strong anisotropy, it is not reflected in the contact property. Based on the quantum transport simulation, ML SiAs forms n-type lateral Schottky contact with Au, Ag, and Cu electrodes with the Schottky barrier height (SBH) of 0.28 (0.27), 0.40 (0.47), and 0.45 (0.33) eV along the a (b) direction, respectively, while it forms p-type lateral Schottky contact with a graphene electrode with a SBH of 0.34 (0.28) eV. Fortunately, ML SiAs forms an ideal Ohmic contact with the V2CO2 electrode. This study not only gives a deep understanding of the interfacial properties of ML SiAs with electrodes but also provides a guide for the design of ML SiAs devices.

Classifying sports videos is complex due to their dynamic nature. Traditional methods, like optical flow and the Histogram of Oriented Gradient (HOG), are limited by their need for expertise and lack of universality. Deep learning, particularly Convolutional Neural Networks (CNNs), offers more effective feature recognition in sports videos, but standard CNNs struggle with fast-paced or low-resolution sports videos. Our novel neural network model addresses these challenges. It begins by selecting important frames from sports footage and applying a fuzzy noise reduction algorithm to enhance video quality. The model then uses a bifurcated neural network to extract detailed features, leading to a densely connected neural network with a specific activation function for categorizing videos. We tested our model on a High-Definition Sports Video Dataset covering over 20 sports and a low-resolution dataset. Our model outperformed established classifiers like DenseNet, VggNet, Inception v3, and ResNet-50. It achieved high precision (0.9718), accuracy (0.9804), F-score (0.9761), and recall (0.9723) on the high-resolution dataset, and significantly better precision (0.8725) on the low-resolution dataset. Correspondingly, the highest values on the matrix of four traditional models are: precision (0.9690), accuracy (0.9781), F-score (0.9670), recall (0.9681) on the high-resolution dataset, and precision (0.8627) on the low-resolution dataset. This demonstrates our model’s superior performance in sports video classification under various conditions, including rapid motion and low resolution. It marks a significant step forward in sports data analytics and content categorization.

Abstract A cooperative vehicle‐infrastructure system (CVIS) can provide perception information beyond the visual range for autonomous vehicles via roadside directional sensors, such as cameras, millimeter‐wave radar, and lidar. The performance of roadside perception strongly depends on sensor placement, where physical occlusion between vehicles is inevitable. This paper proposes an occlusion degree model (ODM) to describe the dynamic occlusion between sensors, obstacles, and targets in a three‐dimensional space. The ODM is then integrated with microscopic traffic simulation to study the impacts of traffic density, vehicle model composition, and sensor configurations on vehicle detection and tracking performances. Based on the simulation, a multifactor regression model with a logistic growth curve is established to quantify the performance of roadside sensors with different factors, where the evaluation metrics are rigorously designed. Finally, an optimization model of roadside sensor placement with non‐linear constraints is formulated to reduce the construction cost under a coverage constraint and improve the perception accuracy within budget limitations. A case study of a highway scenario shows that the performance of the proposed approach improves by 5.63%, 6.55%, and 8.01%, respectively, under the worst possible condition with accuracy requirements of 0.97, 0.96, and 0.95 compared with the conventional placement scheme. The study provides a map of the performance of roadside perception with different influencing factors and guides the optimal roadside sensor placement for a CVIS.

Abstract Background The magneto-mechanical force killing cancer cells is an interesting and important strategy for cancer therapy. Results Novel magnetic microspheres composed of a Fe3O4 nanocore, a bovine serum albumin (BSA) matrix, and a rod-like SiO2 nanoshell, which had flagellum-like surface for force-mediated cancer therapy were developed. One such magnetic microsphere (Fe3O4/BSA/rSiO2) at a cancer cell (not leave the cell surface) under a low frequency vibrating magnetic field (VMF) could generate 6.17 pN force. Interestingly, this force could induce cancer cell to generate reactive oxygen species (ROS). The force and force-induced ROS could kill cancer cells. The cell killing efficiency of Fe3O4/BSA/rSiO2 exposed to a VMF was enhanced with increasing silica nanorod length, and the microspheres with straight nanorods exhibited stronger cell killing ability than those with curled nanorods. Fe3O4/BSA/rSiO2 triggered by a VMF could efficiently inhibit mouse tumor growth, while these microspheres without a VMF had no significant effect on the cell cycle distribution, cell viability, tumor growth, and mouse health. Conclusions These microspheres with unique morphological characteristics under VMF have great potential that can provide a new platform for treating solid tumors at superficial positions whether with hypoxia regions or multidrug resistance.

IntroductionMycoplasma pneumoniae (MP) is a major pathogen of community-acquired pneumonia in children. However, the specific pathogenesis of the progression of Mycoplasma pneumoniae pneumonia (MPP) is unclear. We aimed to reveal the landscape of microbiota and the host immune response in MPP.MethodsThis self-controlled study analyzed the microbiome and transcriptome of bronchoalveolar lavage fluid (BALF) from the severe side (SD) and opposite side (OD) of 41 children with MPP from January to December 2021 and revealed the differences of the peripheral blood neutrophil function among children with mild MPP, severe MPP, and healthy children through transcriptome sequencing.ResultsThe MP load or the pulmonary microbiota had no significant difference between the SD group and OD group, and the deterioration of MPP was related to the immune response, especially the intrinsic immune response.DiscussionThe immune response plays a role in MPP, which may inform treatment strategies for MPP.

BackgroundAlthough many efforts have been devoted to identify biomarkers to predict the responsiveness of immune checkpoint inhibitors, including expression of programmed death-ligand 1 (PD-L1) and major histocompatibility complex (MHC) I, microsatellite instability (MSI), mismatch repair (MMR) defect, tumor mutation burden (TMB), tertiary lymphoid structures (TLSs), and several transcriptional signatures, the sensitivity of these indicators remains to be further improved.Materials and methodsHere, we integrated T-cell spatial distribution and intratumor transcriptional signals in predicting the response to immune checkpoint therapy in MMR-deficient tumors including tumors of Lynch syndrome (LS).ResultsIn both cohorts, MMR-deficient tumors displayed personalized tumor immune signatures, including inflamed, immune excluded, and immune desert, which were not only individual-specific but also organ-specific. Furthermore, the immune desert tumor exhibited a more malignant phenotype characterized by low differentiation adenocarcinoma, larger tumor sizes, and higher metastasis rate. Moreover, the tumor immune signatures associated with distinct populations of infiltrating immune cells were comparable to TLSs and more sensitive than transcriptional signature gene expression profiles (GEPs) in immunotherapy prediction. Surprisingly, the tumor immune signatures might arise from the somatic mutations. Notably, patients with MMR deficiency had benefited from the typing of immune signatures and later immune checkpoint inhibition.ConclusionOur findings suggest that compared to PD-L1 expression, MMR, TMB, and GEPs, characterization of the tumor immune signatures in MMR-deficient tumors improves the efficiency of predicting the responsiveness of immune checkpoint inhibition.

Abstract As the modulation of serine/arginine-rich splicing factor 3 (SRSF3) may be therapeutically beneficial to colorectal cancer (CRC) treatment, the identification of novel SRSF3 inhibitors is highly anticipated. However, pharmaceutical agents targeting SRSF3 have not yet been discovered. Here, we propose a functional SRSF3 inhibitor for CRC therapy and elucidate its antitumor mechanisms. We found high expression of SRSF3 in 70.6% CRC tissues. Silencing SRSF3 markedly inhibits the proliferation and migration of CRC cells through suppression of its target gene 24-dehydrocholesterol reductase (DHCR24). This is evidenced by the links between SRSF3 and DHCR24 in CRC tissues. The novel SRSF3 inhibitor SFI003 exhibits potent antitumor efficacy in vitro and in vivo, which drives apoptosis of CRC cells via the SRSF3/DHCR24/reactive oxygen species (ROS) axis. Moreover, SFI003 is druggable with suitable pharmacokinetic properties, bioavailability, and tumor distribution. Thus, SRSF3 is a novel potential therapeutic target for CRC. Its inhibitor SFI003 may be developed as an anticancer therapeutic.

Abstract Background Colorectal adenoma (CA) is an important precancerous lesion and early screening target of colorectal cancer (CRC). Lipids with numerous physiological functions are proved to be involved in the development of CRC. However, there is no lipidomic study with large-scale serum samples on diagnostic biomarkers for CA. Methods The serum lipidomics of CA patients (n = 50) and normal control (NR) (n = 50) was performed by ultra high performance liquid chromatography-high resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Univariate and multivariate statistical analyses were utilized to screen the differential lipids between groups, and combining the constituent ratio analysis and diagnostic efficiency evaluation by receiver operating characteristic (ROC) curve disclosed the potential mechanism and biomarkers for CA. Results There were obvious differences in serum lipid profiles between CA and NR groups. Totally, 79 differential lipids were selected by criterion of P 1.5 or 60%, indicating these two lipid metabolic pathways showed evident disequilibrium, which could contribute to CA formation. Of them, 12 differential lipids had good diagnostic ability as candidate biomarkers for CA (AUC ≥ 0.900) by ROC analysis. Conclusions To our knowledge, this is the first attempt to profile serum lipidomics and explore lipid biomarkers of CA to help early screening of CRC. 12 differential lipids are obtained to act as potential diagnostic markers of CA. PCs and fatty acids were the main dysregulated biomarkers for CA in serum.

Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), remains a significant global health challenge. The survival of M. tb in hostile extracellular and intracellular microenvironments is crucial for its pathogenicity. In this study, we discovered a Bacillus Calmette–Guérin (BCG) mutant B1033 that potentially affected mycobacterium pathogenicity. This mutant contained an insertion mutation gene, fadD33, which is involved in lipid metabolism; however, its direct role in regulating M. tb infection is not well understood. Here, we found that the absence of fadD33 reduced BCG adhesion and invasion into human pulmonary alveolar epithelial cells and increased the permeability of the mycobacterial cell wall, allowing M. tb to survive in the low pH and membrane pressure extracellular microenvironment of the host cells. The absence of fadD33 also inhibited the survival of BCG in macrophages by promoting the release of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumors necrosis factor-α, through the mitogen-activated protein kinase p38 signaling pathway. Overall, these findings provide new insights into M. tb mechanisms to evade host defenses and might contribute to identifying potential therapeutic and vaccine targets for tuberculosis prevention.