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Objective Hyperlipidemia plays a crucial role in increasing the risk of cardiovascular diseases such as atherosclerosis. Recent studies have established that inclisiran positively influences lipid regulation. Nevertheless, its effectiveness in comparison to conventional treatments is still questionable. Hence, a methodical assessment of its effectiveness and safety is required. This research evaluates the efficacy and safety of inclisiran, PCSK9 inhibitors, and the combination of statins with ezetimibe in the treatment of hyperlipidemia via a network meta-analysis of randomized controlled trials (RCTs). Methods We performed an extensive search of English-language publications in the PubMed, Medline, Embase, and Cochrane Library databases until April 2024. We conducted a web-based meta-analysis and reported in accordance with the guidelines. We selected the percentage change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) as efficacy evaluation metrics and the incidence of adverse events as safety evaluation metrics for analysis and comparison. Result We incorporated 33 studies involving 23,375 patients, evaluating three interventions regarding their effects on LDL-C, TC, TG, HDL-C, and adverse events. All treatments improved metrics over placebo. Inclisiran significantly reduced LDL-C compared to statins (mean − 15.21, 95% CI [-25.19, -5.23]) but showed no significant difference from statin + ezetimibe. Surface under the cumulative ranking curve (SUCRA) rankings placed inclisiran highest for LDL-C reduction (26.2%). The combination of statin and ezetimibe was the most efficacious for triglyceride reduction (mean 17.2, 95% CI [10.22, 24.19]; mean 15.61, 95% CI [16.87, 24.35]). The safety profiles were comparable across treatments. Conclusion Inclisiran with its superior LDL-C reduction and low frequency of administration, appears promising for hyperlipidemia treatment, particularly for patients with adherence issues or side effects from other medications. Systematic review registration CRD42024550852

Abstract Autophagy is a highly conserved degradative process that has been linked to various functions, including defending host cells against pathogens. Although the involvement of autophagy in porcine circovirus 2 (PCV2) infection has become apparent, it remains unclear whether selective autophagy plays a critical role in PCV2 restriction. Here we show that retinol-binding protein 4 (RBP4), an adipokine for retinol carrier, initiates the autophagic degradation of PCV2 ORF1 protein. PCV2 infection increases RBP4 protein levels through MAPK-eIF4E axis in living cells. Ectopic expression of RBP4 or recombinant RBP4 treatment promotes the degradation of ORF1 protein. Mechanistically, RBP4 activates TRAF6 to induce K63-linked ubiquitination of ORF1, leading to SQSTM1/p62-mediated selective autophagy for degradation. Consequently, RBP4 deficiency increases viral loads and exacerbates the pathogenicity of PCV2 in vivo. Collectively, these results identify RBP4 as a key host restriction factor of PCV2 and reveal a previously undescribed antiviral mechanism against PCV2 in infected cells.

Abstract With the development of brain–computer interfaces in recent years, deep learning models have been widely used in EEG-based personal identification. The training of complex models requires a large amount of data, but the acquisition of EEG signals is very time-consuming and energy-consuming. EEG data augmentation can reduce the overhead of EEG data acquisition and provide the data volume required by various complex models, which is conducive to applying EEG identification in practice. The generative adversarial network (GAN) has been applied to augment EEG data features. But the augmentation of temporal EEG signals is less studied. Therefore, this paper proposes a method of temporal EEG data augmentation based on an attention mechanism time series generative adversarial network (ATGAN), which can expand the original EEG dataset to facilitate the training of downstream deep learning classifiers. The experiment is conducted on the BCI Competition IV 2a dataset. The ATGAN model is trained with the temporal EEG signals after preprocessing, and the generated augmentation data by ATGAN is used to expand the original dataset. The accuracy of the EEG-based identification task on the augmented dataset is 7.78% higher than that on the original dataset, which proves the effectiveness of the proposed method.

Abstract Two-dimensional conjugated coordination polymers exhibit remarkable charge transport properties, with copper-based benzenehexathiol (Cu-BHT) being a rare superconductor. However, the atomic structure of Cu-BHT has remained unresolved, hindering a deeper understanding of the superconductivity in such materials. Here, we show the synthesis of single crystals of Cu3BHT with high crystallinity, revealing a quasi-two-dimensional kagome structure with non-van der Waals interlayer Cu-S covalent bonds. These crystals exhibit intrinsic metallic behavior, with conductivity reaching 103 S/cm at 300 K and 104 S/cm at 2 K. Notably, superconductivity in Cu3BHT crystals is observed at 0.25 K, attributed to enhanced electron-electron interactions and electron-phonon coupling in the non-van der Waals structure. The discovery of this clear correlation between atomic-level crystal structure and electrical properties provides a crucial foundation for advancing superconductor coordination polymers, with potential to revolutionize future quantum devices.

Abstract Hypoxic-ischemic encephalopathy (HIE) is a diffuse brain tissue injury caused by acute ischemia and hypoxia, and it is most commonly found in newborn infants but can also occur in adults. Mesenchymal stem cell (MSC) therapies have showed improved outcomes for treating HIE-induced neuronal defects. However, many key issues associated with poor cell viability and tolerance of grafted MSCs after HIE remain to be resolved. Genetic engineering could endow MSCs with more robust regenerative capacities. Our research, along with that of other scientists, has found that the expression of intracellular erythropoietin (EPO) in human umbilical cord MSCs (hUC-MSCs) increases proportionally with the duration of hypoxia exposure. Furthermore, we observed that EPO, when introduced into the EPO gene-modified hUC-MSCs, can be secreted into the extracellular space. However, the underlying mechanisms that support the neuroprotective effects of EPO-MSCs remain unclear. EPO-MSCs, hUC-MSCs, and NC-MSCs were identified by flow cytometry, osteogenic, and adipogenic differentiation assays. The oxygen-glucose deprivation (OGD)-induced SH-SY5Y cell-line was established, and five groups were set up: control, 24-h ischemia-hypoxia, co-cultured with hUC-MSCs, NC-MSCs, and EPO-MSCs after hypoxia. LEGENDplex™ multi-factor flow cytometry was used to detect the secretion of inflammatory factors in cell supernatants and cerebrospinal fluid. Chromosome-targeted excision and tagging (CUT&Tag) sequencing was applied to detect genomic H3K4me2 modifications, and conjoint analysis with transcriptome sequencing (RNA-seq) was performed. Lentiviral vector infection was used to construct SH-SY5Y cells with stable knockdown of RE1-silencing transcription factor (REST), and flow cytometry was used to detect alterations in apoptosis. Finally, the molecular mechanism underlying the neuroprotective and anti-apoptotic effects of EPO-MSCs was investigated using RNA sequencing, qRT-PCR, and western blot assays. Our results suggest that EPO-MSCs are genetically engineered to secrete significantly more EPO. EPO-MSCs treatment has anti-apoptotic properties and offers neuronal protection during ischemic-hypoxic injury. Furthermore, RNA-seq results suggest that multiple inflammation-related genes were down-regulated after EPO-MSCs treatment. Application of RNA-seq and CUT&Tag combined analysis found that the expressions of REST were significantly up-regulated. Lentiviral vector infection to construct REST knockdown SH-SY5Y failed to rescue apoptosis after hypoxia and co-culture with EPO-MSCs, and SETD2-mediated H3K36me3 protein level expression was reduced. EPO-MSCs may promote neuronal survival by affecting H3K4me2 and thus activating the expression of REST and TET3. EPO-MSCs also upregulated the modification level of SETD2-mediated H3K36me3 and regulated the expression of inflammation-related genes such as PLCG2, as well as apoptosis genes BCL2A1. To investigate the neuroprotective effects of EPO-modified hUC-MSCs and the underlying epigenetic regulatory mechanisms, this study aims to provide a theoretical foundation for the potential application of EPO gene-modified hUC-MSCs in the treatment of HIE.

Abstract SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared with its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated the immune resistance of SARS-CoV-2 JN.1 but additional factors are speculated to contribute to its global dominance, which remain elusive until today. Here, we find that SARS-CoV-2 JN.1 has a higher infectivity than BA.2.86 in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, we demonstrate that the gained infectivity of SARS-CoV-2 JN.1 over BA.2.86 associates with increased entry efficiency conferred by L455S and better spike cleavage in hNECs. Structurally, S455 altered the mode of binding of JN.1 spike protein to ACE2 when compared to BA.2.86 spike at ACE2H34, and modified the internal structure of JN.1 spike protein by increasing the number of hydrogen bonds with neighboring residues. These findings indicate that a single mutation (L455S) enhances virus entry in hNECs and increases immune evasiveness, which contribute to the robust transmissibility of SARS-CoV-2 JN.1. We further evaluate the in vitro and in vivo virological characteristics between SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3, and identify key lineage-specific features of the two Omicron sublineages that contribute to our understanding on Omicron antigenicity, transmissibility, and pathogenicity.

Abstract Owing to high pixel density and brightness, gallium nitride (GaN) based micro-light-emitting diodes (Micro-LEDs) are considered revolutionary display technology and have important application prospects in the fields of micro-display and virtual display. However, Micro-LEDs with pixel sizes smaller than 10 μm still encounter technical challenges such as sidewall damage and limited light extraction efficiency, resulting in reduced luminous efficiency and severe brightness non-uniformity. Here, we reported high-brightness green Micro-displays with a 5 μm pixel utilizing high-quality GaN-on-Si epilayers. Four-inch wafer-scale uniform green GaN epilayer is first grown on silicon substrate, which possesses a low dislocation density of 5.25 × 108 cm− 2, small wafer bowing of 16.7 μm, and high wavelength uniformity (standard deviation STDEV

Begonia pedatifida has persistently been utilized as a traditional folk herbal medicine. This study has sequenced the chloroplast genome of B. pedatifida to establish its genomic characteristics and to discern its phylogenetic relationships with other closely related species. The chloroplast genome structure of B. pedatifida reveals a circular molecule with a length of 169,606 bp, including a large single copy (LSC) region of 76,086 bp, a small single copy (SSC) region of 18,314 bp, and a pair of inverted repeats (IRS) region of 37,603 bp. The entire genome contains 138 genes, which consist of 88 protein-coding genes, 42 tRNA genes, and 8 rRNA genes. Phylogenetic analysis suggests that B. pedatifida is closely related to Begonia emeiensis, Begonia jinyunensis, and Begonia pulchrifolia, sharing a common ancestor and forming sister lineages. This research provides genetic information for further study on B. pedatifida.

Abstract Moso bamboo (Phyllostachys edulis), an ecologically and economically important forest species in East Asia, plays vital roles in carbon sequestration and climate change mitigation. However, intensifying climate change threatens moso bamboo survival. Here we generate high-quality haplotype-based pangenome assemblies for 16 representative moso bamboo accessions and integrated these assemblies with 427 previously resequenced accessions. Characterization of the haplotype-based pangenome reveals extensive genetic variation, predominantly between haplotypes rather than within accessions. Many genes with allele-specific expression patterns are implicated in climate responses. Integrating spatiotemporal climate data reveals more than 1050 variations associated with pivotal climate factors, including temperature and precipitation. Climate-associated variations enable the prediction of increased genetic risk across the northern and western regions of China under future emissions scenarios, underscoring the threats posed by rising temperatures. Our integrated haplotype-based pangenome elucidates moso bamboo’s local climate adaptation mechanisms and provides critical genomic resources for addressing intensifying climate pressures on this essential bamboo. More broadly, this study demonstrates the power of long-read sequencing in dissecting adaptive traits in climate-sensitive species, advancing evolutionary knowledge to support conservation.

Abstract Horticultural crops yield considerable economic benefits, vital for supply stability and income enhancement. Plant breeders' rights (PBR) form a foundation, offering breeders essential safeguards to secure benefits and sustain breeding efforts. Therefore, comprehending the status and challenges in horticultural crop variety protection is vital for advancing horticulture. These crops encompass five primary categories: ornamental plants, fruit trees, vegetables, tea, and edible fungi. This article reviews the distinctness, uniformity, and stability (DUS) testing guidelines and progress in molecular identification research for Chinese horticultural crops from 1999 to 2022. Additionally, it statistically analyzes data from the Chinese Ministry of Agriculture and Rural Affairs and the Forestry Knowledge Service System on PBR applications and grants for all horticultural crop breeders. This review aims to provide a comprehensive understanding of the current state of horticultural crop variety protection in China. By thoroughly analyzing the existing status and challenges, the article seeks to enhance the international standing of plant variety protection in Chinese horticulture.

Abstract Background Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and is closely related to the early development and differentiation of neuroendocrine (NE) cells. The disease is mainly represented by high-risk NB, which has the characteristics of high mortality and difficult treatment. The survival rate of high-risk NB patients is not ideal. In this article, we not only conducted a comprehensive study of NB through single-cell RNA sequencing (scRNA-seq) but also further analyzed cuproptosis, a new cell death pathway, in order to find clinical treatment targets from a new perspective. Materials and Methods The Seurat software was employed to process the scRNA-seq data. This was followed by the utilization of GO enrichment analysis and GSEA to unveil pertinent enriched pathways. The inferCNV software package was harnessed to investigate chromosomal copy number variations. pseudotime analyses involved the use of Monocle 2, CytoTRACE, and Slingshot software. CellChat was employed to analyze the intercellular communication network for NB. Furthermore, PySCENIC was deployed to review the profile of transcription factors. Result Using scRNA-seq, we studied cells from patients with NB. NE cells exhibited superior specificity in contrast to other cell types. Among NE cells, C1 PCLAF + NE cells showed a close correlation with the genesis and advancement of NB. The key marker genes, cognate receptor pairing, developmental trajectories, metabolic pathways, transcription factors, and enrichment pathways in C1 PCLAF + NE cells, as well as the expression of cuproptosis in C1 PCLAF + NE cells, provided new ideas for exploring new therapeutic targets for NB. Conclusion The results revealed the specificity of malignant NE cells in NB, especially the key subset of C1 PCLAF + NE cells, which enhanced our understanding of the key role of the tumor microenvironment in the complexity of cancer progression. Of course, cell death played an important role in the progression of NB, which also promoted our research on new targets. The scrutiny of these findings proved advantageous in uncovering innovative therapeutic targets, thereby bolstering clinical interventions.

Unmanned Aerial Vehicles (UAVs) are gaining increasing attention in many fields, such as military, logistics, and hazardous site mapping. Utilizing UAVs to assist communications is one of the promising applications and research directions. The future Industrial Internet places higher demands on communication quality. The easy deployment, dynamic mobility, and low cost of UAVs make them a viable tool for wireless communication in the Industrial Internet. Therefore, UAVs are considered as an integral part of Industry 4.0. In this article, three typical use cases of UAVs-assisted communications in Industrial Internet are first summarized. Then, the state-of-the-art technologies for drone-assisted communication in support of the Industrial Internet are presented. According to the current research, it can be assumed that UAV-assisted communication can support the future Industrial Internet to a certain extent. Finally, the potential research directions and open challenges in UAV-assisted communications in the upcoming future Industrial Internet are discussed.

Abstract Combining high surface area and efficient charge transport, electrically conductive metal−organic frameworks (MOFs) find wide applications in energy storage, sensing, and electrocatalysis. Reliable characterization of electrical conductivity, the key metric for assessing this class of materials, remains challenging due to its high sensitivity to the atmosphere. Herein, through electrical characterization of an exemplary MOF, Cd2(TTFTB) (TTFTB4− = tetrathiafulvalene tetrabenzoate), under various controlled atmospheres, we show that adsorption of water in humid air or N2 improves the apparent room-temperature electrical conductivity by one to two orders of magnitude compared to the values observed in dry atmospheres. This observation in conjunction with spectroscopic characterization, structural analysis, and band structure calculations indicates significant contribution of water-mediated proton conductivity and/or proton-electron coupling to the apparent electrical conductivity. Thus, controlling and reporting atmospheres in electrical conductivity measurements of MOFs is critical to improve their reproducibility and to gain insights into electrical conduction mechanisms.

Abstract Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion. Furthermore, our investigations reveal that this compact antibody displays enhanced permeability across the blood-brain barrier (BBB) and demonstrates superior efficacy in eliminating pseudovirus within the brain in a murine model of Nipah virus infection, particularly compared to the well-characterized antibody m102.4 in an IgG1 format. Consequently, this single-domain antibody holds promise as a therapeutic candidate to prevent Nipah virus infections and has potential implications for vaccine development.

To improve the quality of summer-autumn tea, the fermentation of summer-autumn tea was investigated by using Eurotium cristatum. The contents of tea polyphenols, total free amino acids, total flavonoids, water leachate, and sensory scores of summer-autumn tea were used as the indicators for the one-way experiment, and four factors and three levels were selected for orthogonal experiments to optimize the fermentation process. The volatile compounds of fermented summer-autumn tea under the optimal process were analyzed by gas chromatography-mass spectrometry (GC-MS) technology. The results showed that the optimal fermentation process was 30% water content, 15% inoculum of Eurotium cristatum, fermentation time of 9 d, and fermentation temperature of 30 ℃, and the water leachate content of summer-autumn tea processed under these conditions was significantly increased by 22.51% (P

Abstract Jumbo phages are a group of tailed bacteriophages with large genomes and capsids. As a prototype of jumbo phage, ΦKZ infects Pseudomonas aeruginosa, a multi-drug-resistant (MDR) opportunistic pathogen leading to acute or chronic infection in immunocompromised individuals. It holds potential to be used as an antimicrobial agent and as a model for uncovering basic phage biology. Although previous low-resolution structural studies have indicated that jumbo phages may have more complicated capsid structures than smaller phages such as HK97, the detailed structures and the assembly mechanism of their capsids remain largely unknown. Here, we report a 3.5-Å-resolution cryo-EM structure of the ΦKZ capsid. The structure unveiled ten minor capsid proteins, with some decorating the outer surface of the capsid and the others forming a complex network attached to the capsid’s inner surface. This network seems to play roles in driving capsid assembly and capsid stabilization. Similar mechanisms of capsid assembly and stabilization are probably employed by many other jumbo viruses.

Owing to the increasing complexity of task execution and a wide range of variability in environmental conditions, a single unmanned aerial vehicle (UAV) is insufficient to meet practical mission requirements. Multi-UAV systems have vast potential for applications in areas such as search and rescue. During search and rescue missions, UAVs acquire the location of the target to be rescued and subsequently plan a path that circumvents obstacles and leads to the target. Traditional path-planning algorithms require prior knowledge of obstacle distribution on the map, which may be difficult to obtain in real-world missions. To address the issue of traditional path-planning algorithms that rely on prior map information, this paper proposes a reinforcement learning-based approach for the collaborative exploration of multiple UAVs in unknown environments. First, a Markov decision process is employed to establish a game model and task objectives for the UAV cluster, considering the characteristics of collaborative exploration tasks and various constraints of UAV clusters. To maximize the search and rescue success rate, UAVs must satisfy dynamic and obstacle-avoidance constraints during mission execution. Second, a reinforcement learning-based method for the collaborative exploration of multiple UAVs is proposed. The multiagent soft actor–critic (MASAC) algorithm is used to iteratively train the UAVs’ collaborative exploration strategies. The actor network generates UAV actions, while the critic network evaluates the quality of these strategies. To enhance the algorithm’s generalization capability, training is conducted in randomly generated map environments. To avoid UAVs being obstructed by concave obstacles, a breadth-first search algorithm is used to calculate rewards based on the path distance between the UAVs and targets rather than the linear distance. During the exploration process, each UAV continuously collects and shares the map information with all other UAVs. They make individual action decisions based on the environment and information obtained from other UAVs, and the mission is considered successful if multiple UAVs hover above the target. Finally, a virtual simulation platform for algorithm validation is developed using the Unity game engine. The proposed algorithm is implemented using PyTorch, and bidirectional interaction between the Unity environment and Python algorithm is achieved through the ML-Agents (Machine learning agents) framework. Comparative experiments are conducted on the virtual simulation platform to compare the proposed algorithm with a non-cooperative single-agent SAC algorithm. The proposed method exhibits advantages in terms of task success rate, task completion efficiency, and episode rewards, validating the feasibility and effectiveness of the proposed approach.

Abstract Settlement of roads or railway caused by traffic loading has a serious effect on the safety and service performance of transport infrastructures constructed on soft marine clay. While simple cyclic triaxial test with constant confining pressure (CCP) were used in most of the previous studies, a series of cyclic triaxial tests with variable confining pressure (VCP) were carried out on normally consolidated (NC) and overconsolidated (OC) reconstituted Wenzhou soft clay in this paper to study the undrained behavior of soft marine clay due to surcharge preloading as well as cyclic traffic loading. VCP test is able to approximate the complicated stress path than CCP test caused by traffic loading. The test results indicate that NC specimens show significantly different pore water pressure (u) evolution compared with OC specimens. However, a change in the overconsolidation ratio (OCR) of OC specimens does not have a significant influence on variation of u with identical cyclic stress ratio (CSR) and total stress path (η). The slope of the effective stress path is dependent on the total stress path under which the specimen was loaded cyclically, regardless of the OCR and whether variable confining pressure was applied. The slope of the effective stress path is broadly in line with the slope of corresponding total stress path. In addition, the development of permanent axial strain (ε p a ) due to one-way cyclic loading was shown to depend significantly on the values of η and OCR. Both the variable confining pressure and OCR limited the strain accumulation of saturated marine clay under undrained one-way cyclic loading. Finally, the effects of η and OCR on the magnitude of ε p a after 1000 loading cycles are quantified and incorporated in a power law function for the permanent deformation prediction of soft marine clay due to traffic loading.

Abstract The Omicron subvariants BQ.1.1, XBB.1.5, and XBB.1.16 of SARS-CoV-2 are known for their adeptness at evading immune responses. Here, we isolate a neutralizing antibody, 7F3, with the capacity to neutralize all tested SARS-CoV-2 variants, including BQ.1.1, XBB.1.5, and XBB.1.16. 7F3 targets the receptor-binding motif (RBM) region and exhibits broad binding to a panel of 37 RBD mutant proteins. We develop the IgG-like bispecific antibody G7-Fc using 7F3 and the cross-neutralizing antibody GW01. G7-Fc demonstrates robust neutralizing activity against all 28 tested SARS-CoV-2 variants and sarbecoviruses, providing potent prophylaxis and therapeutic efficacy against XBB.1 infection in both K18-ACE and BALB/c female mice. Cryo-EM structure analysis of the G7-Fc in complex with the Omicron XBB spike (S) trimer reveals a trimer-dimer conformation, with G7-Fc synergistically targeting two distinct RBD epitopes and blocking ACE2 binding. Comparative analysis of 7F3 and LY-CoV1404 epitopes highlights a distinct and highly conserved epitope in the RBM region bound by 7F3, facilitating neutralization of the immune-evasive Omicron variant XBB.1.16. G7-Fc holds promise as a potential prophylactic countermeasure against SARS-CoV-2, particularly against circulating and emerging variants.

A penetrating brain injury is a rare type of neurosurgical trauma associated with extremely high mortality and disability rates. Penetrating skull base injuries caused by arrows seldom occur because injuries caused by such weapons are more likely to be accidental. However, the number of self-inflicted injuries is increasing, and these injuries have varying patterns and high mortality rates. We report a case of a transoral penetrating craniocerebral injury caused by an arrow in a suicidal patient. Preoperative imaging is crucial for detecting and planning the surgical approach. Surgery is an effective treatment for this type of injury. Additionally, we reviewed previous case reports on this type of injury to provide recommendations for its clinical detection and treatment.

The reasonable generator start-up sequence (GSUS) strategy is beneficial to increasing the energy capacity of power systems after a blackout. Since the decision-making strategies of power systems are highly dependent on the cyber system, the denial of service (DoS) attack, as the most common type of cyber attacks, may prevent the generators from being re-started at their desired time and degrade performance of the optimal GSUS strategy in the power system restoration process, which has not been studied in the existing methods. To fill this gap, a bi-level GSUS optimization strategy against the DoS attack is proposed in this work. First, the effects of the DoS attack on the power generation of generators are analyzed and quantified by the generation energy loss. Then, a bi-level optimization model for the GSUS is proposed considering the DoS attack, where the upper-level model, referred to as the attacker model, aims to maximize the energy loss to prolong the restoration of generators by optimizing the time instant of the attack, while the lower-level model, referred to as the defender model, aims to maximize the energy generation by adjusting the optimal GSUS strategy in the restoration process. Both the upper-level and lower-level models are reformulated as mixed-integer linear programing problems, which can be efficiently solved by commercial solvers. Finally, the IEEE 39-bus power system and an actual power system in China are employed to verify the effectiveness of the proposed model.

Background The forkhead box (FOX) family members regulate gene transcription and expression. FOX family members regulate various biological processes, such as cell proliferation and tumorigenesis. FOXD, a FOX protein subfamily, is associated with poor prognosis for various cancers. However, the potential clinical value of FOXD subfamily members in colorectal cancer (CRC) has not yet been elucidated. Therefore, in this study, we aimed to determine the role of the FOXD subfamily members in CRC development. Methods Using HTSeq-count data, clinical data, and single-nucleotide polymorphisms (obtained from The Cancer Genome Atlas Project), and bioinformatics analyses (using DESEQ2 software), we identified differentially expressed genes (DEGs) in CRC. Next, each DEG expression was validated in vitro using reverse transcription-quantitative polymerase chain reaction, western blotting, and immunohistochemistry (IHC). Results Among the FOXD subfamily members, the area under the receiver operating characteristic curve of FOXD3 was 0.949, indicating that FOXD3 has a high overall diagnostic accuracy for CRC. Gene Set Enrichment Analysis revealed that FOXD-DEGs were mainly related to pathways such as cytokine, cytokine, and extracellular matrix receptor interactions. Kaplan–Meier curves and nomograms showed that FOXD1, FOXD3, and FOXD4 were prognostically significant. In conclusion, FOXD subfamily members (especially FOXD3) could serve as diagnostic and prognostic biomarkers for CRC and an immunotherapy target in patients with CRC.

The simulation and early warning of cyanobacterial blooms in lakes are of great significance. Controlling the growth of cyanobacteria in plateau lakes is challenging due to the unique geographical environment, climatic conditions, and impact of anthropogenic activities. Therefore, conducting simulations and early warning is crucial to effectively control cyanobacterial blooms in plateau lakes. This study aimed to investigate Xingyun Lake, a representative plateau lake in China, using the logistic growth model to analyze cyanobacterial growth patterns and assess the effects of control projects, along with the influence of meteorological and environmental factors. Moreover, the study proposed a method for establishing control curves and ranges for managing cyanobacterial blooms. The results demonstrated that the chlorophyll-a concentration in the effluent decreased by an average of 97.74% compared with that in the influent after implementing the integrated “deep-well pressure algal control” and “ecological purification for algae-water separation” processes in Xingyun Lake. The total annual decrease in chlorophyll-a was approximately 3.40 times the lake's total chlorophyll-a content. The growth of cyanobacteria in Xingyun Lake followed a logistic pattern during the blooming period, before and after implementing control projects (from 2018 to 2022), with the overall growth trend from 2010 to 2022 aligning with the logistic growth model. The study identified lower temperatures and precipitation, reduced nitrogen and phosphorus loads, and a higher nitrogen-to‑phosphorus ratio as the main environmental factors inhibiting cyanobacterial growth. Establishing logistic control curves for cyanobacterial blooms and sustaining the algal control project before the transition point effectively reduced the maximum chlorophyll-a concentration and attenuated cyanobacterial growth rate throughout the year. This study offered novel perspectives for preventing and controlling cyanobacterial blooms, offering practical guidance for lake management, especially in plateau regions.

Objective: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH). Methods: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo. Results: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in MASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Esrra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of MASH. Conclusions: Esrra regulation of Rplp1-mediated translation of lysosome/autolysosome proteins was downregulated during MASH. Alternate day fasting activated this novel pathway and improved MASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for MASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1.

The past century has witnessed the flourishing of organic radical chemistry. Stable organic radicals are highly valuable for quantum technologies thanks to their inherent room temperature quantum coherence, atomic-level designability, and fine tunability. In this comprehensive review, we highlight the potential of stable organic radicals as high-temperature qubits and explore their applications in quantum information science, which remain largely underexplored. Firstly, we summarize known spin dynamic properties of stable organic radicals and examine factors that influence their electron spin relaxation and decoherence times. This examination reveals their design principles and optimal operating conditions. We further discuss their integration in solid-state materials and surface structures, and present their state-of-the-art applications in quantum computing, quantum memory, and quantum sensing. Finally, we analyze the primary challenges associated with stable organic radical qubits and provide tentative insights to future research directions.

Abstract Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.

Straw mulching is a widespread practice for reducing the soil carbon loss caused by erosion. However, the effects of straw mulching on dissolved organic matter (DOM) runoff loss from black soil are not well studied. How straw mulching affects the composition and loss of runoff DOM by changing soil aggregates remains largely unclear. Here, a straw mulching treatment was compared to a no mulching treatment (as a control) on sloping farmland with black soil erosion in Northeast China. We divided the soil into large macroaggregates (>2 mm), small macroaggregates (0.25–2 mm), and microaggregates (

Objective: To compare the quantitative parameters of lung HRCT and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive idiopathic inflammatory myopathy (IIM) patients with different prognoses. Methods: The clinical and imaging data of 19 MDA5 antibody-positive IIM patients admitted to Beijing Shijitan Hospital Affiliated with Capital Medical University between February 2017 and November 2022 were retrospectively analyzed. According to the prognoses, the patients were divided into the good prognoses group (14 cases) and the poor prognoses (intubation or death) group (5 cases). The clinical and laboratory indexes, types of interstitial lung disease (ILD), and CT quantitative indexes were compared between the two groups. Results: There were significant differences in gender; carcinoembryonic antigen; blood oxygen saturation; and the percentages of lymphocytes, monocytes, neutrophils, lymphocytes, and neutrophils between the good versus the poor prognoses groups. The proportion of abnormal respiratory system changes was higher in the poor prognoses group. In terms of the type of ILD, acute interstitial pneumonia (AIP)-like lesions were the main type in the poor prognoses group, and nonspecific interstitial pneumonia (AIP) lesions were the main type in the good prognoses group. For NSIP-like lesions, there was a statistically significant difference between the two groups. The semi-quantitative score of the poor prognoses group was higher, and the volume of whole lung lesions as well as the proportion of whole lung lesions were also higher. Spearman correlation analysis showed that the blood oxygen saturation, monocyte percentage, semi-quantitative score, whole lung lesion volume, and proportion of whole lung lesion were negatively correlated, while carcinoembryonic antigen, neutrophil percentage, and neutrophils were positively correlated with the semi-quantitative score, whole lung lesion volume, and proportion of whole lung lesion. Conclusions: The lung HRCT quantitative indicators, clinical manifestations, and laboratory indicators are different in MDA5 antibody-positive IIM patients with different prognoses. Early evaluation of HRCT imaging manifestations, clinical manifestations, and laboratory indicators is of great significance in determining the prognosis of MDA5 antibody-positive IIM patients, which provides corresponding support for clinical diagnosis and treatment.

To address the issue of non-standard grain sizes and difficult control of uniformity in the manufacturing of large, complex-shaped nuclear power pipelines. In this paper, double wedge-shaped samples of X2 CrNiMo 18.12 (CN) austenitic stainless steel were hot deformed at 1000 °C, 1100 °C, and 1180 °C to obtain deformation samples with a gradient strain, and the deformation sample at 1180 °C was subjected to solid solution treatment at 1060 °C × 4 h (water quenching; the measured cooling rate of water cooling was approximately 4400 °C/min). Large-area electron backscattered diffraction mapping technology was used to characterize the 80 mm × 5 mm full-area range of samples. The initiation sequence of various dynamic recrystallization mechanisms and the grain evolution under continuous effective strain conditions at a hot deformation temperature of 1000–1180 °C were investigated. The influence of the hot deformation process parameters on the grains after solid solution treatment was examined, the process interval for the generation of severe mixed grains was determined. The results show that the recrystallization behavior of X2 CrNiMo 18.12 (CN) austenitic stainless steel is mainly determined by a combination of recrystallization mechanisms dominated by discontinuous dynamic recrystallization, supplemented by continuous dynamic recrystallization, twinning-induced dynamic recrystallization, and geometrical dynamic recrystallization during the hot deformation process at 1000–1180 °C. The effective strain intervals of the solid solution sample that produces severely mixed grains are in the range of 0.11–0.22 mm/mm, with the probability of producing severely mixed grains with an effective strain in the range of 0.13–0.14 mm/mm reaching 74%.

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Abstract The evolution of Artificial Intelligence of Things (AIoT) pushes connectivity from human‐to‐things and things‐to‐things, to AI‐to‐things, has resulted in more complex physical networks and logical associations. This has driven the demand for Internet of Things (IoT) devices with powerful edge data processing capabilities, leading to exponential growth in device quantity and data generation. However, conventional data preprocessing methods, such as data compression and encoding, often require edge devices to allocate computational resources for decoding. Additionally, some lossy compression methods, like JPEG, may result in the loss of important information, which has negative impact on the AI training. To address these challenges, this paper proposes a two‐step attribute reduction approach, targeting devices and dimensions, to reduce the massive amount of data in the AIoT network while avoiding unnecessary utilization of edge device resources for decoding. The device‐oriented and dimension‐oriented attribute reductions identify important devices and dimensions, respectively, to mitigate the multimodal interference caused by the large‐scale devices in the AIoT network and the curse of dimensionality associated with high‐dimensional AIoT data. Numerical results and analysis show that this approach effectively eliminates redundant devices and numerous dimensions in the AIoT network while maintaining the basic data correlation.

Abstract Lung cancer stands as the most prevalent form of cancer globally, posing a significant threat to human well-being. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still a potential means of eradicating lung cancer, patients with advanced lung cancer usually miss the best chance for surgical treatment, and even after surgical resection patients may still experience tumor recurrence. Additionally, chemotherapy, the mainstay of treatment for patients with advanced lung cancer, has the potential to be chemo-resistant, resulting in poor clinical outcomes. The emergence of liquid biopsies has garnered considerable attention owing to their noninvasive nature and the ability for continuous sampling. Technological advancements have propelled circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), tumor metabolites, tumor-educated platelets (TEPs), and tumor-associated antigens (TAA) to the forefront as key liquid biopsy biomarkers, demonstrating intriguing and encouraging results for early diagnosis and prognostic evaluation of lung cancer. This review provides an overview of molecular biomarkers and assays utilized in liquid biopsies for lung cancer, encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, tumor metabolites, TAAs and TEPs. Furthermore, we expound on the practical applications of liquid biopsies, including early diagnosis, treatment response monitoring, prognostic evaluation, and recurrence monitoring in the context of lung cancer.

The inertial navigation system (INS), which is frequently used in emergency rescue operations and other situations, has the benefits of not relying on infrastructure, high positioning frequency, and strong real-time performance. However, the intricate and unpredictable pedestrian motion patterns lead the INS localization error to significantly diverge with time. This paper aims to enhance the accuracy of zero-velocity interval (ZVI) detection and reduce the heading and altitude drift of foot-mounted INS via deep learning and equation constraint of dual feet. Aiming at the observational noise problem of low-cost inertial sensors, we utilize a denoising autoencoder to automatically eliminate the inherent noise. Aiming at the problem that inaccurate detection of the ZVI detection results in obvious displacement error, we propose a sample-level ZVI detection algorithm based on the U-Net neural network, which effectively solves the problem of mislabeling caused by sliding windows. Aiming at the problem that Zero-Velocity Update (ZUPT) cannot suppress heading and altitude error, we propose a bipedal INS method based on the equation constraint and ellipsoid constraint, which uses foot-to-foot distance as a new observation to correct heading and altitude error. We conduct extensive and well-designed experiments to evaluate the performance of the proposed method. The experimental results indicate that the position error of our proposed method did not exceed 0.83% of the total traveled distance.

Abstract Ultrasound is an acoustic wave which can noninvasively penetrate the skull to deep brain regions, enabling neuromodulation. However, conventional ultrasound’s spatial resolution is diffraction-limited and low-precision. Here, we report acoustic nanobubble-mediated ultrasound stimulation capable of localizing ultrasound’s effects to only the desired brain region in male mice. By varying the delivery site of nanobubbles, ultrasound could activate specific regions of the mouse motor cortex, evoking EMG signaling and limb movement, and could also, separately, activate one of two nearby deep brain regions to elicit distinct behaviors (freezing or rotation). Sonicated neurons displayed reversible, low-latency calcium responses and increased c-Fos expression in the sub-millimeter-scale region with nanobubbles present. Ultrasound stimulation of the relevant region also modified depression-like behavior in a mouse model. We also provide evidence of a role for mechanosensitive ion channels. Altogether, our treatment scheme allows spatially-targetable, repeatable and temporally-precise activation of deep brain circuits for neuromodulation without needing genetic modification.

In this study, 0.3 wt% Ti nanoparticles (Ti NPs) were incorporated into Sn1.0Ag0.5Cu (SAC105) solder, and vacuum thermo-compression soldering was employed to fabricate two distinct solder joints: Cu/SAC105/Cu and Cu/SAC105-0.3Ti/Cu. The research delved into how altering bonding pressures and durations affects the development of interfacial intermetallic compounds (IMCs) and, consequently, the mechanical characteristics of solder joints. The thickness of the solder joints exhibited a gradual decrease with increasing bonding pressure, reaching approximately 13 μm at a bonding pressure of 1.0 MPa. The incorporation of Ti NPs demonstrated an effective inhibition of the interfacial IMC layer growth. This led to a notable decrease in the thickness of the IMC layer in the Cu/SAC105-0.3Ti/Cu solder joints. Furthermore, the introduction of Ti NPs did not cause a notable alteration in the fracture path of the solder joints. Exceptionally high shear strengths exceeding 38 MPa were achieved for both solder joints at a bonding pressure of 0.6 MPa. Moreover, the shear strength of the Cu/SAC105-0.3Ti/Cu solder joints slightly surpassed that of the Cu/SAC105/Cu solder joints. However, at a bonding pressure of 1.0 MPa, the aggregation of Ti NPs in the solder joints adversely affected the microstructure, leading to a deterioration in shear strength.

Abstract Background The rose is one of the most important ornamental flowers in the world for its aesthetic beauty but can be attacked by many pests such as aphids. Aphid infestation causes tremendous damage on plant tissues leading to harmed petals and leaves. Rose cultivars express different levels of resistance to aphid infestation yet the information remains unclear. Not only that, studies about the transcriptional analysis on defending mechanisms against aphids in rose are limited so far. Results In this study, the aphid resistance of 20 rose cultivars was evaluated, and they could be sorted into six levels based on the number ratio of aphids. And then, a transcriptome analysis was conducted after aphid infestation in one high resistance (R, Harmonie) and one highly susceptibility (S, Carefree Wonder) rose cultivar. In open environment the majority of rose cultivars had the highest aphid number at May 6th or May 15th in 2020 and the resistance to infestation could be classified into six levels. Differential expression analysis revealed that there were 1,626 upregulated and 767 downregulated genes in the R cultivar and 481 upregulated and 63 downregulated genes in the S cultivar after aphid infestation. Pathway enrichment analysis of the differentially expressed genes revealed that upregulated genes in R and S cultivars were both enriched in defense response, biosynthesis of secondary metabolites (phenylpropanoid, alkaloid, and flavonoid), carbohydrate metabolism (galactose, starch, and sucrose metabolism) and lipid processing (alpha-linolenic acid and linolenic acid metabolism) pathways. In the jasmonic acid metabolic pathway, linoleate 13S-lipoxygenase was specifically upregulated in the R cultivar, while genes encoding other crucial enzymes, allene oxide synthase, allene oxide cyclase, and 12-oxophytodienoate reductase were upregulated in both cultivars. Transcription factor analysis and transcription factor binding search showed that WRKY transcription factors play a pivotal role during aphid infestation in the R cultivar. Conclusions Our study indicated the potential roles of jasmonic acid metabolism and WRKY transcription factors during aphid resistance in rose, providing clues for future research.

A proper load restoration method can speed up the load restoration phase and reduce the outage losses of power systems after natural disasters. Existing research assumes that transmission lines would not trip again in the load restoration phase, which is not always acceptable, especially in the outage scenario due to natural disasters. Besides, the feasibility of the load restoration scheme relies on an exact mathematical model of the load restoration problem, while the existing second-order cone programming (SOCP) based model is not suitable for transmission power systems due to the lack of voltage angle related arctangent constraints. To address these two main drawbacks in existing research on load restoration, a robust contingency-constrained load restoration model (CCLRM) for transmission systems considering the modified SOCP formulation of power flow is proposed with the objective of reducing the outage losses taking the worst contingency into account. To identify the worst contingency for the CCLRM, a bi-level worst contingency identification model (WOCIM) is proposed and reformulated into a single-level model by employing the duality theory to make the WOCIM solvable. The non-linear voltage angle related arctangent constraints in the modified SOCP based power flow expression in both models are studied and reformulated into the convex ones based on the convex envelope theory, thereby enhancing the accuracy of the presented models. Case studies on the IEEE 30-bus power system and IEEE 118-bus power system are conducted to illustrate the effectiveness of the proposed method.

The extracellular matrix (ECM) and cells are crucial components of natural tissue microenvironments, and they both demonstrate dynamic mechanical properties, particularly viscoelastic behaviors, when exposed to external stress or strain over time. The capacity to modify the mechanical properties of cells and ECM is crucial for gaining insight into the development, physiology, and pathophysiology of living organisms. As an illustration, researchers have developed hydrogels with diverse compositions to mimic the properties of the native ECM and use them as substrates for cell culture. The behavior of cultured cells can be regulated by modifying the viscoelasticity of hydrogels. Moreover, there is widespread interest across disciplines in accurately measuring the mechanical properties of cells and the surrounding ECM, as well as exploring the interactive relationship between these components. Nevertheless, the lack of standardized experimental methods, conditions, and other variables has hindered systematic comparisons and summaries of research findings on ECM and cell viscoelasticity. In this review, we delve into the origins of ECM and cell viscoelasticity, examine recently developed methods for measuring ECM and cell viscoelasticity, and summarize the potential interactions between cell and ECM viscoelasticity. Recent research has shown that both ECM and cell viscoelasticity experience alterations during in vivo pathogenesis, indicating the potential use of tailored viscoelastic ECM and cells in regenerative medicine.

The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.

AbstractPlatelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP’s bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP’s IL-1β levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

Background Human papillomavirus (HPV) is a risk factor for the occurrence of cervical cancer (CC). Here, we aimed to explore the role of HPV16 in CC and identify the underlying mechanism.Methods The expression of miR-23a, HPV16 E6/E7 and homeobox C8 (HOXC8) was measured by quantitative real-time PCR or western blot. Cell viability and migration were evaluated using cell counting kit-8, Transwell and wound healing assays. The targeting relationship between miR-23a and HOXC8 was revealed by dual-luciferase reporter assay.Results miR-23a was downregulated in HPV16-positive (HPV16+) CC tissues and HPV16+ and HPV18+ cells. Additionally, E6/E7 expression was increased in CC cells. Then, we found that E7, rather than E6, positively regulated miR-23a expression. miR-23a suppressed cell viability and migration, whereas E7 overexpression abrogated this suppression. miR-23a targeted HOXC8, which reversed miR-23a-mediated cell viability and migration.Conclusions HPV16 E7-mediated miR-23a suppressed CC cell viability and migration by targeting HOXC8, suggesting a novel mechanism of HPV-induced CC.

Biological monitoring using environmental DNA (eDNA) technology has expanded from micro- to macro-organisms. In aquatic eDNA studies, large volumes of water need to be filtered rapidly in the field, which requires development of effective eDNA collection devices. In this study, we introduce a novel portable eDNA collection system containing a GM dual-channel water filter and a DNA extraction kit adapted to large filter membranes (ø 100 mm). The water filter is powered by a high-capacity lithium battery (9,000 mA), which operates two peristaltic pumps and maintains a continuous filtration rate of up to 1 L/min for 5 h in outdoor settings. For sample collection, the optimum conditions are still water and turbidity below 8 nephelometric turbidity units. This allows for the filtration of 10 L of water within 10 min by use of a 0.22-μm filter. Metagenomic and 12S metabarcoding sequencing showed that the DNA extraction quality and species annotation accuracy of our custom DNA extraction kit, which was tailored for this system, rivaled the performance of established kits. The GM water filter’s enrichment mode gave consistent results with vacuum filtration, which greatly reduced the filtration time for large water samples, while accurately reproducing species annotations. This innovation streamlines the eDNA collection and annotation process and offers substantial benefits for biodiversity monitoring and conservation efforts.

A well-connected network formed by multi-scale fractures is a key factor in the formation of high-quality reservoirs and the achievement of high and stable oil and gas production in tight sandstones. Taking the Upper Paleozoic of the Qingshimao gas field in the Ordos Basin, China, as an example, based on data from image logs, cores, and thin sections, fine quantitative characterization of multi-scale natural fractures in tight sandstone reservoirs was carried out. We also established a method for dividing network patterns of multi-scale fractures and discussed the effect of each fracture network pattern on the gas enrichment and production capacity. Results indicate regular changes in the length, density, aperture, porosity, permeability, and connectivity of natural fractures at different scales. Based on the spatial combination patterns and connectivity of fractures of different scales, four types of fracture network patterns were established: multi-scale fracture network with high density and multi-orientations, multi-scale fracture network with moderate-high density and dual orientations, small-scale fracture network with moderate density and dual orientations, small-scale fracture network with low density and single orientation. The first fracture network pattern can destroy the integrity of the cap layer, causing natural gas leakage. The second fracture network pattern is a favorable area for natural gas enrichment. The third fracture network pattern requires the use of hydraulic fracturing to obtain commercial airflow. The fourth fracture network pattern has little effect on reservoir control and storage. The study of natural fractures in tight sandstone reservoirs is usually based on a single-scale perspective. Understanding the development characteristics of multi-scale fractures and their controlling effects on the reservoir helps to comprehensively understand the spatial configuration relationship of multi-scale fracture network structure patterns and promotes the development of multi-scale fractures in tight reservoir research.

Pharmacogenetic testing technology can effectively determine the individual differences among patients and scientifically assist doctors to select the most suitable drugs for each patient. In this study, an electrochemical biosensor based on magnetic α-Fe2O3/Fe3O4 heterogeneous nanosheets was constructed to detect Vitamin K epoxide reductase complex 1 type AA (VKORC1*2). Firstly, we fabricated magnetic α-Fe2O3/Fe3O4 heterogeneous nanosheets as the substrate material for electrochemical biosensors. Subsequently, the material surface was modified with Au nanoparticles to facilitate the connection of sensing probes and enhance current signal amplification. The electrochemical biosensor showed a negative linear relationship with the concentrations of target DNA (tDNA, VKORC1*2 gene) within 1 pM − 1 μM, a limit of detection was (LOD) = 0.36 pM, and a limit of quantification was (LOQ) = 1.19 pM. The biosensor demonstrated exceptional specificity, reproducibility, and stability. In real sample analysis, it exhibited a recovery range of 96.63 % − 110.57 % (RSD ≤ 3.07 %) for various tDNA concentrations, thereby indicating its promising potential in clinical diagnostics.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a type of liver metabolic syndrome. Employing multi-omics analyses encompassing the microbiome, metabolome and transcriptome is crucial for comprehensively elucidating the biological processes underlying NAFLD.MethodsHepatic tissue, blood and fecal samples were obtained from 9 NAFLD model mice and 8 normal control mice. Total fecal microbiota DNA was extracted, and 16S rRNA was amplified, to analyze alterations in the gut microbiota (GM) induced by NAFLD. Subsequently, diagnostic strains for NAFLD were screened, and their functional aspects were examined. Differential metabolites and differentially expressed genes were also screened, followed by enrichment analysis. Correlations between the differential microbiota and metabolites, as well as between the DEGs and differential metabolites were studied. A collinear network involving key genes-, microbiota-and metabolites was constructed.ResultsIleibacterium and Ruminococcaceae, both belonging to Firmicutes; Olsenella, Duncaniella and Paramuribaculum from Bacteroidota; and Bifidobacterium, Coriobacteriaceae_UCG_002 and Olsenella from Actinobacteriota were identified as characteristic strains associated with NAFLD. Additionally, differentially expressed metabolites were predominantly enriched in tryptophan, linoleic acid and methylhistidine metabolism pathways. The functions of 2,510 differentially expressed genes were found to be associated with disease occurrence. Furthermore, a network comprising 8 key strains, 14 key genes and 83 key metabolites was constructed.ConclusionThrough this study, we conducted a comprehensive analysis of NAFLD alterations, exploring the gut microbiota, genes and metabolites of the results offer insights into the speculated biological mechanisms underlying NAFLD.

In contemporary times, tumors have emerged as the primary cause of mortality in the global population. Ongoing research has shed light on the significance of neurotransmitters in the regulation of tumors. It has been established that neurotransmitters play a pivotal role in tumor cell angiogenesis by triggering the transformation of stromal cells into tumor cells, modulating receptors on tumor stem cells, and even inducing immunosuppression. These actions ultimately foster the proliferation and metastasis of tumor cells. Several major neurotransmitters have been found to exert modulatory effects on tumor cells, including the ability to restrict emergency hematopoiesis and bind to receptors on the postsynaptic membrane, thereby inhibiting malignant progression. The abnormal secretion of neurotransmitters is closely associated with tumor progression, suggesting that focusing on neurotransmitters may yield unexpected breakthroughs in tumor therapy. This article presents an analysis and outlook on the potential of targeting neurotransmitters in tumor therapy.

Resource flow supports the delivery of products and services and plays a vital role in the low-carbon urban distribution grid. Therefore, reasonable forecasting of the resource flow is essential for financial decision-making. Through the trained model, the resource flow forecasting process can be simplified and one-click forecasting can be realized. However, this method relies on the selection and optimization of model parameters, where poor parameter choices can significantly impact the forecasting accuracy. This paper first introduces a model for identifying key influencing factors in resource flow data, incorporating an elastic network and gray correlation analysis. Subsequently, a resource flow forecasting method based on improved support vector machines–long- and short term memory (SVM-LSTM) is proposed. Finally, the superior performance of the proposed method is validated through simulations.

COVID-19 patients often suffer from post-COVID-19 acute sequelae (PASC). Pulmonary fibrosis has the most significant long-term impact on the respiratory health of patients, known as post-COVID-19 pulmonary fibrosis (PC19-PF). PC19-PF can be caused by acute respiratory distress syndrome (ARDS) or COVID-19-induced pneumonia. Individuals who experience COVID-19 pneumonia symptoms (including cough, shortness of breath, dyspnea on exertion, and desaturation) for at least 12 weeks after diagnosis, almost all develop PC19-PF. Extracellular matrix molecules: laminin (LN), type IV collagen (IV Col), procollagen III N-terminal peptide (PIIINP), and hyaluronic acid (HA) are involved in the development and progression of PC19-PF. This study aimed to investigate the relationship between the progression of PC19-PF and serum levels of laminin, IV COL, PIIINP, and hyaluronic acid. This retrospective study included 162 PC19-PF patients treated and 160 healthy controls who received treatment at Shenzhen Longgang District Third People’s Hospital, Hebei PetroChina Central Hospital and Changzhi People’s Hospital from January 2021 to December 2023. Serum levels of LN, IV COL, PIIINP, and HA were detected by chemiluminescence immunoassay using commercial kits. Predicted forced vital capacity percentage (FVC% pred), predicted carbon monoxide lung diffusion capacity percentage (DLCO% pred), high-resolution computed tomography (HRCT) scores were assessed, and patient mortality was compared with healthy controls. Serum levels of LN, IV Col, PIIINP, and HA were significantly higher in PC19-PF or CTD-ILD patients than in healthy controls (all p < 0.05), and they were further elevated in acute exacerbation cases (all p < 0.01). In patients, HA was positively associated with HRCT scores and negatively associated with FVC% pred and DLCO% pred (all p < 0.05). Serum levels of LN, IV COL, PIIINP, and HA were significantly lower in surviving patients than in those who deceased (all p > 0.05). Serum levels of LN, IV C, PIIINP, and HA may affect the progression of PC19-PF and may serve as indicators of PC19-PF severity.

Abstract The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs.