Search

Abstract Lung cancer (LC) remains the leading cause of cancer death globally. Recent reports have suggested that circulating microbial nucleic acids have potential as promising biomarkers for cancer liquid biopsies. However, circulating microbial profiles and their potential clinical value in LC patients remained unexplored. In this study, plasma samples from 76 LC patients, 9 liver cancer patients, 11 pancreatic cancer patients, and 53 healthy controls (HCs) were collected and underwent metagenomic analyses by whole genome sequencing. The composition and relative abundance of the microbial profiles were significantly different between the LC patients and HCs. A distinct plasma-based microbial profile was observed in LC patients. By differential analysis using MaAslin, 40 significant species between LC patients and HCs were identified. Five species were selected as optimal circulating microbial biomarkers for LC. The constructed classifier based on these five species showed an AUC of 0.9592, 0.9131, and 0.8077 in the discovery, validation, and additional validation cohorts, respectively. Furthermore, metagenomic profiles of 25 lung tumor tissue and plasma paired samples were analyzed and compared. The microbial diversity was significantly increased in plasma compared with the tumor tissue. Among the 13 shared core microbial species, 10 had no difference between the tumor tissue and paired plasma. In conclusion, circulating microbial nucleic acids in the plasma have potential as biomarkers for LC liquid biopsies. The microbiome in the tumor tissue was one of the possible sources of circulating microbial nucleic acids.

Pulmonary fibrosis (PF) is a lethal lung disease that predominantly affects older adults; however, whether and how aging triggers fibrosis remains unclear. To pinpoint the predominant initiating factors of PF, we first analyzed single-cell RNA sequencing (scRNA-seq) data from the lung tissues of 45 normal donors and 51 PF patients and found that aging might serve as the primary catalyst for PF development. To further investigate the influence of aging on PF formation, we conducted a comprehensive and thorough study employing a natural aging mouse model. We found that dynamic alterations in the quantity and types of collagen fibers during aging-induced PF progression, especially in collagenous (Col) I, emerged as the predominant driver of PF. We then investigated the regulation of Col I synthesis during aging using primary alveolar type 2 (AT2) cells and A549 cells line through conditioned media and Transwell coculture, and found that secretions—particularly plasminogen activator inhibitor (PAI)-1—from aged AT2 cells promoted fibrosis and enhanced collagen type I alpha 1 (Col1al) production via the transforming growth factor (TGF)-β/small mother against decapentaplegic (Smad)2/3 pathway. Furthermore, scRNA-seq and a histological analysis of human lung tissue demonstrated a significant upregulation of SERPINE1 (the gene encoding PAI-1) and PAI-1 expression in both aging lung tissue and AT2 cells, which was consistent with our findings from animal experiments, providing additional evidence for the pivotal role of PAI-1 during aging and the development of PF. Our research demonstrates that PAI-1, a crucial factor secreted by aging AT2 cells, exerts a pivotal role in promoting the synthesis of Col1a1 in fibroblasts, subsequently leading to Col I deposition, and in driving the progression of PF by mediating the TGF-β/Smad2/3 pathway. Our findings offer critical evidence for the involvement of epithelial dysfunction in age-related PF and provides potential novel therapeutic targets for clinical intervention.

Abstract Background Early diagnosis of large vessel occlusion (LVO) in acute stroke often requires CT angiography (CTA). Automated CT perfusion (CTP) software, which identifies blood flow abnormalities, enhances LVO diagnosis and patient selection for endovascular thrombectomy (EVT). This study evaluates the sensitivity of automated CTP images in detecting perfusion abnormalities in patients with acute ischemic stroke (AIS) and LVO or medium vessel occlusion (MeVO), compared to CTA. Methods We screened acute ischemic stroke patients presenting within 24 h who underwent CT, CTA, and CTP as per institutional protocol. RAPID AI software processed CTP images, while neuroradiologists reviewed CTA for intracranial arterial occlusions. Sensitivity, specificity, and accuracy of automated CTP maps in detecting occlusions were assessed. Results Of 790 screened patients, 31 were excluded due to lack of RAPID CTP data or poor‐quality scans, leaving 759 for analysis. The median age was 71 years (IQR: 61–81), with 47% female. Among them, 678 had AIS, and 81 had AIS ruled out. CTA identified arterial occlusion in 562 patients (74%), with corresponding CTP abnormalities in 537 patients (Tmax > 6 sec). In the 197 without occlusion, CTP was negative in 161. Automated CTP maps had a sensitivity of 95.55% (CI 95: 93.50–97.10%), specificity of 81.73% (CI 95: 75.61–86.86%), negative predictive value of 98.22% (CI 95: 97.39–98.79%), positive predictive value of 63.54% (CI 95: 56.46–70.09%), and overall accuracy of 85.18% (CI 95: 82.45–87.64%). Conclusions Automated CTP maps demonstrated high sensitivity and negative predictive value for LVOs and MeVOs, suggesting their usefulness as a rapid diagnostic tool, especially in settings without expert neuroradiologists.

For the problem of high temperature heat damage at 1012102 working face in Yuanzigou Mine, the best spray pressure and nozzle atomization parameters are determined by using the method of spray cooling experiment. The numerical simulation method is used to simulate and analyze the influence of different spray temperature and spray spacing conditions on the cooling effect, and the comfort of human body before and after spray is used to analyze by the linear regression method. The results show that: when the spraying system in the synthesized mining face adopts the group spacing of 10 m, the water temperature is 286 K, and the pressure is 6 MPa, the single group peak temperature reaches 1.3 ℃ compared with the conventional ventilation method. After the application in the field, the temperature of most areas on the sidewalk side of the working face was lower than 26 ℃, the maximum temperature dropped to below 27 ℃, the minimum temperature was as low as 24.7 ℃, which effectively realized the regional cool.

Abstract Background The activation of endoplasmic reticulum (ER) stress is an early pathological hallmark of Alzheimer’s disease (AD) brain, but how ER stress contributes to the onset and development of AD remains poorly characterized. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a non-canonical neurotrophic factor and an ER stress inducible protein. Previous studies reported that MANF is increased in the brains of both pre-symptomatic and symptomatic AD patients, but the consequence of the early rise in MANF protein is unknown. Methods We examined the expression of MANF in the brain of AD mouse models at different pathological stages. Through behavioral, electrophysiological, and neuropathological analyses, we assessed the level of synaptic dysfunctions in the MANF transgenic mouse model which overexpresses MANF in the brain and in wild type (WT) mice with MANF overexpression in the hippocampus. Using proteomic and transcriptomic screening, we identified and validated the molecular mechanism underlying the effects of MANF on synaptic function. Results We found that increased expression of MANF correlates with synapse loss in the hippocampus of AD mice. The ectopic expression of MANF in mice via transgenic or viral approaches causes synapse loss and defects in learning and memory. We also identified that MANF interacts with ELAV like RNA-binding protein 2 (ELAVL2) and affects its binding to RNA transcripts that are involved in synaptic functions. Increasing or decreasing MANF expression in the hippocampus of AD mice exacerbates or ameliorates the behavioral deficits and synaptic pathology, respectively. Conclusions Our study established MANF as a mechanistic link between ER stress and synapse loss in AD and hinted at MANF as a therapeutic target in AD treatment.

Abstract Background Early detection through screening dramatically improves lung cancer survival rates, including among war Veterans, who are at heightened risk. The effectiveness of low dose computed tomography scans in lung cancer screening (LCS) prompted the Veteran’s Affairs Lung Precision Oncology Program (VA LPOP) to increase screening rates. We aimed to develop an adaptive population health tool to determine adequate resource allocation for the program, with a specific focus on primary care providers, nurse navigators, and radiologists. Methods We developed a tool using C + + that uses inputs that represents the process of the VA LCS program in Ann Arbor, Michigan to calculate FTEs of human resource needs to screen a given population. Further, we performed a sensitivity analysis to understand how resource needs are impacted by changes in population, screening eligibility, and time allocated for the nurse navigators’ tasks. Results Using estimates from the VA LCS Program as demonstrative inputs, we determined that the greatest number of full-time equivalents required were for radiologists, followed by nurse navigators and then primary care providers, for a target population of 75,000. An increase in the population resulted in a linear increase of resource needs, with radiologists experiencing the greatest rate of increase, followed by nurse navigators and primary care providers. These resource requirements changed with primary care providers, nurse navigators and radiologists demonstrating the greatest increase when 1–20, 20–40 and > 40% of Veterans accepted to be screened respectively. Finally, when increasing the time allocated to check eligibility by the nurse navigator from zero to three minutes, there was a linear increase in the full-time equivalents required for the nurse navigator. Conclusion Variation of resource utilization demonstrated by our user facing tool emphasizes the importance of tailored strategies to accommodate specific population demographics and downstream work. We will continue to refine this tool by incorporating additional variability in system parameters, resource requirements following an abnormal test result, and resource distribution over time to reach steady state. While our tool is designed for a specific program in one center, it has wider applicability to other cancer screening programs.

Background: Takotsubo syndrome (TTS) is identified by its acute and transient impairment of left ventricular systolic function. Although recent research has highlighted occurrences of TTS among individuals with gastrointestinal diseases (GI diseases), comprehensive and systematic investigations focusing on this patient demographic are still scarce. Methods: This retrospective study analyzed case reports and series that documented an association between gastrointestinal diseases (GI diseases) and Takotsubo syndrome (TTS). We conducted comprehensive searches across PubMed, Embase, and the Cochrane Database to identify relevant cases. Results: In patients with gastrointestinal-induced Takotsubo syndrome (GI-TTS), the primary reasons for admission were pancreatitis (15.48 %), liver failure (10.71 %), bowel obstruction (5.95 %) and liver cirrhosis (5.95 %). It is noteworthy that the main triggers for Takotsubo syndrome are surgeries related to gastrointestinal diseases (29.76 %), including liver transplantation (15.48 %) and cholecystectomy (2.38 %). Dyspnea (45.71 %) was the most common symptom, followed by abdominal pain (35.71 %) and chest pain (34.29 %). The apical type was the most frequent TTS variant (81.25 %). Compared with the All-TTS cohort, GI-TTS patients were younger, and had a lower proportion of women (69.05 % vs. 89.77 %, P

Irradiation with X-rays has been widely utilized in the clinical treatment of solid tumors and certain hematopoietic malignancies. However, this method fails to completely distinguish between malignant and normal cells. Prolonged or repeated exposure to radiation, whether due to occupational hazards or therapeutical interventions, can cause damage to normal tissues, particularly impacting the hematopoietic system. Therefore, it is important to investigate the effects of total body irradiation on the hematopoietic system of mice and to compare the inhibitory effects of various doses of irradiation on this system. In this study, we primarily employed flow cytometry to analyze mature lineage cells in the peripheral blood, as well as immature hematopoietic stem and progenitor cells (HSPCs) in the bone marrow and spleen. Additionally, we evaluated the multilineage differentiation capacity of HSPCs through colony-forming cell assays. Our results indicated that peripheral B and T cells demonstrated increased sensitivity to irradiation, with significant cell death observed 1-day post-irradiation. Common lymphoid progenitor cells exhibited greater radiotolerance compared to other progenitor cell types, enabling them to maintain a certain population even at elevated doses. Moreover, notable differences were observed between intramedullary and extramedullary hematopoietic stem cells and common lymphoid progenitor cells regarding the extent of damage and recovery rate following irradiation. The multilineage differentiation capacity of HSPCs was also compromised during radiation exposure. In conclusion, different types of mature blood cells, along with immature HSPCs, exhibited varying degrees of sensitivity and tolerance to irradiation, resulting in distinct alterations in cell percentages and numbers.

Abstract The influence of precipitated nanophases on the mechanical properties of Fe-based amorphous nanocrystalline alloys is an urgent issue to be explored. Two amorphous nanocrystalline alloys, i.e., (Fe0.9Ni0.1)86B14 and (Fe0.7Ni0.3)86B14 containing nanophase of the body-centered cubic and face-centered cubic structures, respectively, were selected to investigate the effect of the structure and volume fraction of nanophase on their mechanical properties. The results of nanoindentation experiments and the calculation of the volume and size of the shear transition zone reveal that the two alloys show different mechanical properties. When the volume fraction of the nanophase in (Fe0.9Ni0.1)86B14 is larger than 50%, the elastic modulus is increased suddenly and the volume and size of the shear transition zone is decreased dramatically, while no dramatic change occurs in (Fe0.7Ni0.3)86B14. Moreover, it was found by using molecular dynamics simulations that the main reason for these abnormal mechanical properties is the change of cluster type in the system due to the incorporation of nanophases with different structures.

The effect of the volume fraction of nanocrystals on the macroscopic mechanical properties and microscopic atomic structure of Fe-based nanocrystalline alloys, as well as the relationship between the two, is an urgent issue to be explored. Seven nanocrystalline alloys with different volume fractions of nanocrystals were formed by annealing treatment of (Fe0·9Ni0.1)86B14 amorphous precursor. Through hardness, flat plate bending, and nanoindentation experiments, it is found that when the volume fraction of nanocrystals reaches the range of 45–55 %, there is an abrupt change in the macroscopic mechanical properties. Specifically, when the volume fraction is less than this range, the properties inherit the amorphous matrix, however, larger than this range, the properties are dominated by precipitated nanocrystalline phases. Meanwhile, based on the molecular dynamics simulation method, seven Fe90Ni10 amorphous nanocrystalline models with different volume fractions of body-centered cubic nanocrystals are established, and the deformation mechanism of models and the evolution of their microstructures during the nanoindentation process are obtained intuitively. Moreover, it is further revealed that the significant changes in the Voronoi polyhedral index, which represents the microscopic atomic structure in this range of nanocrystal volume fractions, are the main reason for the abrupt changes in the mechanical properties at the macroscopic level.

In order to solve the problem of high temperature and heat damage in the 10303 coal mining face of Jining No.2 Coal Mine, numerical analysis method was used to establish a physical model of the working face and to analyze the influence of multiple factors on the cooling system, such as the length of the wind pipe, the distance between the air outlet of the wind pipe and the temperature, and determine the temperature control parameters for different working conditions (production and shutdown), and then control the temperature of the air cooler air outlet through the automatic opening and closing of the temperature-control facilities, so that the required cooling capacity of the coal mining face is realized under different operations. The cooling capacity required by the working face is realized under different operations, and the problem of high-temperature heat damage in the working face is solved. The results show that the cooling effect of 100 m length of wind pipe and 50 m distance of wind pipe is the best. When the working face is under normal mining operation, the outlet temperature setting should be less than 16.5 ℃, and the average temperature of the working face will be reduced by 3.7 ℃; when the mining operation is stopped, the outlet temperature setting should be less than 20.5 ℃, and the average temperature of the working face will be reduced by 3.5 ℃, and the parameters of the two working conditions can achieve the temperature control target of the coal mining working face.

Pancreatic cancer is one of the most aggressive malignancies in the digestive system, characterized by vague early symptoms and rapid disease progression. Currently, treatment options for pancreatic cancer are limited, with unsatisfactory outcomes and poor prognosis, as the overall 5-year survival rate is less than 10%. Therefore, it is crucial to identify new biomarkers for pancreatic cancer.We analyzed the differential expression of EFNA5 at the mRNA level using data from the TCGA, GTEX, and GEO databases, followed by validation of EFNA5 protein expression differences through immunohistochemistry. Kaplan-Meier survival analysis and Cox regression analysis were used to explore the prognostic value of EFNA5. KEGG, GO enrichment analyses, and GSEA were employed to predict the biological functions of EFNA5. Bioinformatics algorithms were utilized to analyze the impact of EFNA5 on drug sensitivity, immune cell infiltration, and tumor mutational burden. Finally, we conducted cell phenotype experiments to investigate the effects of EFNA5 on the proliferation, migration, and invasion of pancreatic cancer cells. Bioinformatics data showed that the mRNA level of EFNA5 was higher in pancreatic cancer tissues compared to normal tissues. Immunohistochemistry experiments confirmed that the protein expression level of EFNA5 was significantly higher in pancreatic cancer tissues (n = 19) than in adjacent normal tissues (n = 19). Survival analysis indicated that the overall survival (OS) and progression-free survival (PFS) were worse in the high EFNA5 expression group compared to the low expression group. Univariate and multivariate Cox regression analyses demonstrated that EFNA5 is a risk factor affecting the prognosis of pancreatic cancer patients. KEGG pathway enrichment analysis revealed that differentially expressed genes (DEGs) between high and low EFNA5 expression groups were primarily enriched in pathways such as PI3K/Akt, axon guidance, and focal adhesion. GO enrichment analysis showed that DEGs were mainly associated with functions like epidermis development, cell adhesion, and intercellular junctions. Immune cell infiltration analysis found that EFNA5 expression was correlated with the infiltration levels of various immune cells. The tumor mutational burden was higher in the high EFNA5 expression group compared to the low expression group. Drug sensitivity analysis indicated that the high EFNA5 expression group had lower sensitivity to several commonly used chemotherapy drugs for pancreatic cancer. Cellular experiments demonstrated that knocking down EFNA5 inhibited the proliferation, invasion, and migration of pancreatic cancer cells. EFNA5 is overexpressed in pancreatic cancer tissues, and its high expression is associated with poor prognosis in pancreatic cancer patients. Downregulation of EFNA5 reduces the proliferation, migration, and invasion capabilities of the pancreatic cancer cell line BxPC-3. EFNA5 is closely related to the occurrence, development, prognosis, immune infiltration, and drug sensitivity of pancreatic cancer. Our study suggests that EFNA5 is a potential biomarker and therapeutic target.

Understanding plant transpiration responses to rainfall in semi-arid regions is vital for grasping climate change impacts on ecohydrological processes. This study categorized 105 rainfall events in Horqin Sandy Land (2018–2019) into three types: Category I (short-term, light rain), Category II (short-term, heavy rain), and Category III (long-term, moderate rain). It focused on Caragana microphylla Lam. (a sand-fixing shrub) and Populus L. (arbors), analyzing sap flow (SF), photosynthesis, and meteorological data. SF rates in both species were primarily influenced by net solar radiation (Rn), air temperature (Ta), relative humidity (RH), and vapor pressure deficit (VPD) (P < 0.05). The analysis indicated that potential evapotranspiration (PET) can be used as a composite influencing factor to explain the changes in SF. The results showed that under different rainfall types, the changing trends of SF and PET of Populus L. were generally consistent, However, as rainfall intensity increased, the effect of PET on SF of Populus L. weakened. Conversely, the effect of PET on the SF rate of Caragana microphylla Lam. increased with the increase of rainfall intensity. Notably, whether the SWC at the two test sites is effectively recharged or oversaturated due to rainfall is also an important factor affecting SF. Specifically, the SF of Caragana microphylla Lam. is generally affected by the combined effects of PET and stomatal conductance (Gs); when SWC is less than the field capacity, the inhibitory effect of Gs is obvious; when SWC exceeds field capacity, the inhibitory effect of Gs is significantly reduced, and the SF of Caragana microphylla Lam. is mainly controlled by PET. In contrast, as the SF of Populus L. increases from the field capacity to the saturated water holding capacity of SWC, the influence of PET on the SF of Populus L. weakens, and the influence of Gs on SF becomes more prominent.

Summary: The gut microbiome is crucial for nutrient metabolism, immune regulation, and intestinal homeostasis with changes in its composition linked to complex diseases like inflammatory bowel disease (IBD). Although the precise host-microbial mechanisms in disease pathogenesis remain unclear, high-throughput sequencing have opened new ways to unravel the role of interspecies interactions in IBD. Systems biology—a holistic computational framework for modeling complex biological systems—is critical for leveraging multi-omics datasets to identify disease mechanisms. This review highlights the significance of multi-omics data in IBD research and provides an overview of state-of-the-art systems biology resources and computational tools for data integration. We explore gaps, challenges, and future directions in the research field aiming to uncover novel biomarkers and therapeutic targets, ultimately advancing personalized treatment strategies. While focusing on IBD, the proposed approaches are applicable for other complex diseases, like cancer, and neurodegenerative diseases, where the microbiome has also been implicated.

In recent years, global attention has increasingly turned towards the urgent goal of eliminating carbon emissions. Evaluating new methods may be the key to achieving environmentally responsible growth. This study examines the impact of China's public-private energy partnerships on CO2 emissions from 1990Q1 to 2022Q4, employing Dynamic Ordinary Least Squares (DOLS) and fuzzy multi-objective least squares (FMOLS) econometric regression methods. Our analysis incorporates sustainability efforts, renewable energy sources, environmentally sound finance, and technological advancements to provide a comprehensive understanding of CO2 emissions dynamics. Our findings reveal that expanding access to credit has facilitated the development of green financing, resulting in a favorable environmental impact of China's economic growth and public-private partnerships. The reduction in carbon dioxide emissions is counter balanced by the positive effects of technological progress, increased utilization of renewable energy sources, and enhanced power efficiency. We highlight the multiplying effect of these factors, underscoring the need for global public-private collaborations in the energy sector to significantly lower carbon emissions and to achieve sustainable development goals. We assert that policymakers tasked with facilitating China's transition to renewable energy sources must prioritize environmental preservation, technological advancement, and the optimal utilization of renewable resources to achieve lasting sustainability.

Population studies have suggested that viral infections may be contributing to risk of ischemic stroke, although the mechanisms for this are unclear. In this review, we examine the epidemiological evidence supporting the involvement of viral diseases, including influenza, COVID‐19, chronic herpesvirus infections, and hepatitis C in current trends of stroke incidence. To support these associations, we highlight the virus–host interactions that are critical in the context of stroke, including direct effects of acute and persistent viral infections on vascular function, inflammation, and thrombosis. Additionally, we evaluate the systemic changes that occur during viral infection that can predispose individuals to ischemic stroke, including alterations in blood pressure regulation, coagulation, and lipid metabolism. Our review emphasizes the need to further elucidate precise mechanisms involved in viral infections and stroke risk. Future research will inform the development of targeted interventions for stroke prevention in the context of viral diseases.

Abstract Huntington’s disease (HD) is a monogenic neurodegenerative disease, caused by the CAG trinucleotide repeat expansion in exon 1 of the Huntingtin (HTT) gene. The HTT gene encodes a large protein known to interact with many proteins. Huntingtin-associated protein 40 (HAP40) is one that shows high binding affinity with HTT and functions to maintain HTT conformation in vitro. However, the potential role of HAP40 in HD pathogenesis remains unknown. In this study, we found that the expression level of HAP40 is in parallel with HTT but inversely correlates with mutant HTT aggregates in mouse brains. Depletion of endogenous HAP40 in the striatum of HD140Q knock-in (KI) mice leads to enhanced mutant HTT aggregation and neuronal loss. Consistently, overexpression of HAP40 in the striatum of HD140Q KI mice reduced mutant HTT aggregation and ameliorated the behavioral deficits. Mechanistically, HAP40 preferentially binds to mutant HTT and promotes Lysine 48-linked ubiquitination of mutant HTT. Our results revealed that HAP40 is an important regulator of HTT protein homeostasis in vivo and hinted at HAP40 as a therapeutic target in HD treatment.

Abstract Objectives Homopolymer (HP) sequencing is error-prone in next-generation sequencing (NGS) assays, and may induce false insertion/deletions and substitutions. This study aimed to evaluate the performance of dichromatic and tetrachromatic fluorogenic NGS platforms when sequencing homopolymeric regions. Results A HP-containing plasmid was constructed and diluted to serial frequencies (3%, 10%, 30%, 60%) to determine the performance of an MGISEQ-2000, MGISEQ-200, and NextSeq 2000 in HP sequencing. An evident negative correlation was observed between the detected frequencies of four nucleotide HPs and the HP length. Significantly decreased rates (P

Abstract With the development of cloud computing, users are more inclined to outsource complex computing tasks to cloud servers with strong computing capacity, and the cloud returns the final calculation results. However, the cloud is not completely trustworthy, which may leak the data of user and even return incorrect calculations on purpose. Therefore, it is important to verify the results of computing tasks without revealing the privacy of the users. Among all the computing tasks, the polynomial calculation is widely used in information security, linear algebra, signal processing and other fields. Most existing polynomial-based verifiable computation schemes require that the input of the polynomial function must come from a single data source, which means that the data must be signed by a single user. However, the input of the polynomial may come from multiple users in the practical application. In order to solve this problem, the researchers have proposed some schemes for multi-source outsourced data, but these schemes have the common problem of low efficiency. To improve the efficiency, this paper proposes an efficient polynomial-based verifiable computation scheme on multi-source outsourced data. We optimize the polynomials using Horner’s method to increase the speed of verification, in which the addition gate and the multiplication gate can be interleaved to represent the polynomial function. In order to adapt to this structure, we design the corresponding homomorphic verification tag, so that the input of the polynomial can come from multiple data sources. We prove the correctness and rationality of the scheme, and carry out numerical analysis and evaluation research to verify the efficiency of the scheme. The experimental indicate that data contributors can sign 1000 new data in merely 2 s, while the verification of a delegated polynomial function with a power of 100 requires only 18 ms. These results confirm that the proposed scheme is better than the existing scheme.

Abstract Agriculture contributes to a decline in local species diversity and to above- and below-ground biotic homogenization. Here, we conduct a continental survey using 1185 soil samples and compare microbial communities from natural ecosystems (forest, grassland, and wetland) with converted agricultural land. We combine our continental survey results with a global meta-analysis of available sequencing data that cover more than 2400 samples across six continents. Our combined results demonstrate that land conversion to agricultural land results in taxonomic and functional homogenization of soil bacteria, mainly driven by the increase in the geographic ranges of taxa in croplands. We find that 20% of phylotypes are decreased and 23% are increased by land conversion, with croplands enriched in Chloroflexi, Gemmatimonadota, Planctomycetota, Myxcoccota and Latescibacterota. Although there is no significant difference in functional composition between natural ecosystems and agricultural land, functional genes involved in nitrogen fixation, phosphorus mineralization and transportation are depleted in cropland. Our results provide a global insight into the consequences of land-use change on soil microbial taxonomic and functional diversity.

Abstract Background Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. Results We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation “blacklist” in the BED region to reduce errors in downstream analyses. Conclusions We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.

This study examined the mediating role of job satisfaction in the associations among workplace support, job autonomy, and turnover intention among child welfare workers in China. The differential effects of several sources of workplace support (coworkers, supervisors, and organization leaders) on worker turnover intention were also examined. Using data drawn from the Chinese Social Work Longitudinal survey 2019, a series of path analyses were conducted. The results indicated that job satisfaction partially mediated the effects of workplace support and job autonomy on turnover intention. When the effects of workplace support from different sources were examined, the mediating effect of job satisfaction was significant only for the association between support from organization leaders and turnover intention. Greater workplace support from organization leaders and supervisors directly predicted lower turnover intention, while workplace support from coworkers was not significantly associated with turnover intention. The findings suggest that policies and programs that promote workplace support from organization leaders and supervisors and enhance job autonomy and satisfaction may be critical to address high turnover rates among child welfare workers.

BackgroundAnemia is prevalent among patients with cardiovascular disease and is associated with adverse outcomes. However, data regarding the impact of anemia in high-risk percutaneous coronary intervention (HRPCI) are limited.ObjectivesThis study aimed to evaluate the impact of anemia in patients undergoing Impella-supported HRPCI in the PROTECT III study.MethodsPatients undergoing Impella-supported HRPCI in the multicenter PROTECT III study were assessed for anemia based on baseline hemoglobin levels according to World Health Organization criteria. Patients were stratified into three groups, namely, no anemia, mild anemia, and moderate or severe anemia. Major adverse cardiovascular and cerebrovascular events (MACCE: all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) at 30 and 90 days, and major bleeding events were compared across groups.ResultsOf 1,071 patients with baseline hemoglobin data, 37.9% had no anemia, 43.4% had mild anemia, and 18.7% had moderate or severe anemia. Anemic patients were older and more likely to have comorbidities. Anemia was associated with higher MACCE rates at 30 days (moderate to severe, 12.3%; mild, 9.8%; no anemia, 5.4%; p = 0.02) and at 90 days (moderate to severe, 18.7%; mild, 14.6%; none, 8.3%; p = 0.004). These differences persisted after adjustment for potential confounders at 30 and 90 days, and sensitivity analysis excluding dialysis showed similar results. Major bleeding at 30 days was also higher in anemic patients (5.5% vs. 1.2%, p = 0.002).ConclusionBaseline anemia in Impella-supported HRPCI is common and independently associated with MACCE and major bleeding, emphasizing its significance as a prognostic factor. Specific management strategies to reduce anemia-associated MACCE risk after HRPCI should be examined.Clinical Trial InformationTrial Name: The Global cVAD Study (cVAD)ClinicalTrial.gov Identifier: NCT04136392URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2

This study investigates the feasibility and challenges of transferring traffic signal control schemes from the macroscopic signal timing optimization tool Synchro to the microscopic traffic simulator SUMO, focusing on Downtown Seattle as a case study. The research assesses the process of sharing and importing traffic signal timing plans, a crucial aspect of transportation simulations, between these two platforms. We conduct a detailed analysis of the traffic signal characteristics and data formats unique to each simulator and identify elements suitable for conversion. Subsequently, a four-stage framework is developed for semi-automatic integration of traffic signal control between the two. Our results indicate a successful conversion rate of approximately 85% of signalized intersections from Synchro to SUMO. This research not only illustrates the challenges and solutions in converting signal control across different platforms but also paves the way for future studies aimed at improving the interoperability of various traffic simulation tools.

In order to generate high-quality electromagnetic signal countermeasure examples, a fast Jacobian saliency map attack (FJSMA) method was proposed.The Jacobian matrix of the attack target class was calculated and feature saliency maps based on the matrix were generated, then the most salient feature points were iteratively selected and perturbations in their neighborhood were continuously added while introducing a single point perturbation constraint, finally adversarial examples were generated.Experimental results show that, compared with Jacobian saliency map attack method, FJSMA improves the generation speed by about 10 times while maintaining the same high attack success rate, and improves the similarity by more than 11%, and compared with other gradient-based methods, the attack success rate is improved by more than 20%, and the similarity is improved by 20% to 30%.

The present study employs regulatory focus theory (Higgins, 1997) to investigate the effects of L2 speakers’ chronic regulatory focus on their L2 pragmatic versus grammatical awareness. It involved the participation of 121 Chinese students, who are English language learners, at a university in the United States. Haws et al.’s (2010) questionnaire was used to examine the participants’ regulatory dispositions, and a judgment task was adapted from Bardovi-Harlig and Dörnyei (1998) to assess participants’ awareness of grammatical and pragmatic errors, as well as the severity of each type of error. Multiple regression results largely confirmed the predictions. Prevention regulatory focus, concerned with obligations, responsibilities, and negative outcomes, predicted L2 speakers’ recognition of grammatical errors and their severity. Conversely, promotion focus, which emphasizes growth, accomplishments, and positive outcomes, positively predicted L2 speakers’ perceptions of pragmatic error severity. These findings contribute to the understanding of how differences in chronic motivational orientations can lead to different L2 use patterns and characteristics.

Improving the accuracy of the six-axis force sensor Six-axis force sensors (hereafter collectively referred to as 6a-sensors) is a systematic problem, which mainly involves the optimization and improvement of three aspects: the design of the elastic body of the 6a-sensors, the acquisition and processing of the weak signal, and the decoupling of the inter-dimensional data of the force and torque of each dimension. To attain high stiffness, sensitivity, and minimal coupling, a design scheme of cross beam elastomer based on titanium alloy material is proposed. In order to realize the acquisition and processing of multi-channel weak differential signals with high gain, high linearity and precision, a high-speed programmable weak signal processing circuit design scheme is proposed. To efficiently address the interdependence issue among signal dimensions in the 6a-sensors. This paper innovatively proposes a BP-PSO decoupling algorithm using Particle Swarm Approach (PSO) to optimise the optimiser of BP neural network. To validate the algorithm’s effectiveness, comparative experiments are conducted with the 6a-sensors. designed and studied in this paper by sampling and self-designed calibration system. The sensitivity of the 6a-sensor designed in this paper reaches 4mV/V. In terms of accuracy, there is an improvement of about 1%. In terms of crosstalk, there is an improvement of about 0.2%. providing a new and improved idea for the six-dimensional force decoupling algorithm. In order to further verify the practicability of the algorithm, a flexible surface grinding robot based on six-axis force is developed based on Siasun robot platform. The grinding strength control is accurate, and the running trajectory is uniform and smooth, which can effectively meet the practical application requirements of flexible and intelligent control.

Phase-to-ground discharge of transmission lines due to ice cover is a common issue. To assess the risk of phase-to-ground discharge of overhead lines under complex ice-covering conditions, this study used finite element analysis to model the interaction between ground wire, conductor, and insulator. The study examined how different factors affect the minimum safe distance between the conductor and ground wire, as well as the risk coefficient of phase-to-ground discharge and the risk zone. The finding reveals that as icing thickness increases, conductor bouncing intensifies, reducing the phase-to-ground distance, and placing one half of the line span within the risk zone for the given conditions. For the same length of de-icing, the closer the de-icing region is to the midpoint, the greater is the maximum jump height of the conductor. When the span is extended to 600 m, the risk range covers approximately 70% of the total line length. Under strong winds, conductor lateral displacement increases with wind speed, which leads to a higher risk of discharge.

Background: Diabetic kidney disease (DKD) is a major complication of diabetes leading to kidney failure. Methods: This study investigates lipid metabolism profiles of long-standing DKD (LDKD, diabetes duration > 10 years) by integrative analysis of available single-cell RNA sequencing and spatial multi-omics data (focusing on spatial continuity samples) from the Kidney Precision Medicine Project. Results: Two injured cell types, an injured thick ascending limb (iTAL) and an injured proximal tubule (iPT), were identified and significantly elevated in LDKD samples. Both iTAL and iPT exhibit increased lipid metabolic and biosynthetic activities and decreased lipid and fatty acid oxidative processes compared to TAL/PT cells. Notably, compared to PT, iPT shows significant upregulation of specific injury and fibrosis-related genes, including FSHR and BMP7. Meanwhile, comparing iTAL to TAL, inflammatory-related genes such as ANXA3 and IGFBP2 are significantly upregulated. Furthermore, spatial metabolomics analysis reveals regionally distributed clusters in the kidney and notably differentially expressed lipid metabolites, such as triglycerides, glycerophospholipids, and sphingolipids, particularly pronounced in the inner medullary regions. Conclusions: These findings provide an integrative description of the lipid metabolism landscape in LDKD, highlighting injury-associated cellular processes and potential molecular mechanisms.

The flow dynamics of low-yield horizontal wells demonstrate considerable complexity and unpredictability, chiefly attributable to the structural attributes of the wellbore and the interplay of gas–water two-phase flow. In horizontal wellbores, precisely predicting flow patterns using conventional approaches is often problematic. Consequently, accurate monitoring and analysis of water holdup in gas–water two-phase flows are essential. This study performs a gas–water two-phase flow simulation experiment under diverse total flow and water cut conditions, utilizing air and tap water to represent downhole gas and formation water, respectively. The experiment relies on the measurement principles of an array fiber holdup meter (GAT) and the response characteristics of the sensors. In the experiment, GAT was utilized for real-time water holdup measurement, and the acquired sensor data were analyzed using three interpolation algorithms: simple linear interpolation, inverse distance weighted interpolation, and Gaussian radial basis function interpolation. The results were subsequently post-processed and visualized with 2020 version MATLAB software, generating two-dimensional representations of water holdup in the wellbore. The study findings demonstrate that, at total flow of 300 m3/d and 500 m3/d, the simple linear interpolation approach yields superior accuracy in water holdup calculations, with imaging outcomes closely aligning with the actual gas–water flow patterns and the authentic gas–water distribution. As total flow and water cut increase, the gas–water two-phase flow progressively shifts from stratified smooth flow to stratified wavy flow. In this paper, the Gaussian radial basis function and inverse distance weighted interpolation algorithms exhibit superior accuracy in water holdup calculations, effectively representing the fluctuating features of the gas–water interface and yielding imaging outcomes that align more closely with experimentally observed gas–water flow patterns.

It was necessary to research an efficient treatment process suitable for township domestic wastewater. In this paper, the performance of the cyclic activated sludge system (CASS) system for simultaneous carbon (C), nitrogen (N) and phosphorus (P) removal was investigated by changing the operation cycle of the CASS reactor. Four operating conditions were set up, T1, T2, T3 and T4, with cycle times of 6, 8, 12 and 8 h (with carbon source), respectively. The results showed that the CASS system had good simultaneous removal of C, N and P. The highest removal rates of COD, TN, NH4+ -N and TP were 87.69, 72.99, 98.60 and 98.38%, respectively, at a cycle time of 8 h. The TN removal rate could be increased to 82.51% after the addition of carbon source. Microbial community analysis showed that Proteobacteria, Bacteroidetes and Candidatus Saccharibacteria were the main phylum-level bacteria. Their presence facilitated the effectiveness of the CASS process for nitrogen removal and phosphorus removal. Functional analysis of genes revealed that the abundance values of genes associated with C, N and P metabolism were higher when the treatment was effective.

Abstract Background Yarrowia lipolytica, one of the most charming chassis cells in synthetic biology, is unable to use xylose and cellodextrins. Results Herein, we present work to tackle for the first time the engineering of Y. lipolytica to produce lipids from cellodextrins and xylose by employing rational and combinatorial strategies. This includes constructing a cellodextrin-phosphorolytic Y. lipolytica by overexpressing Neurospora crassa cellodextrin transporter, Clostridium thermocellum cellobiose/cellodextrin phosphorylase and Saccharomyces cerevisiae phosphoglucomutase. The effect of glucose repression on xylose consumption was relieved by installing a xylose uptake facilitator combined with enhanced PPP pathway and increased cytoplasmic NADPH supply. Further enhancing lipid production and interrupting its consumption conferred the obese phenotype to the engineered yeast. The strain is able to co-ferment glucose, xylose and cellodextrins efficiently, achieving a similar μmax of 0.19 h−1, a qs of 0.34 g-s/g-DCW/h and a YX/S of 0.54 DCW-g/g-s on these substrates, and an accumulation of up to 40% of lipids on the sugar mixture and on wheat straw hydrolysate. Conclusions Therefore, engineering Y. lipolytica capable of assimilating xylose and cellodextrins is a vital step towards a simultaneous saccharification and fermentation (SSF) process of LC biomass, allowing improved substrate conversion rate and reduced production cost due to low demand of external glucosidase.

Abstract N6-methyladenosine(m6A), is the most abundant post-transcriptional modification of mRNA in biology. When the first nucleotide after the m7G cap is adenosine, it is methylated at the N6 position to form N6,2-O-dimethyladenosine (m6Am). m6Am is a reversible modification located at the first transcribed nucleotide, which is present in about 30% of cellular mRNAs, thus m6Am can have a significant impact on gene expression in the transcriptome. Phosphorylated CTD interaction factor 1(PCIF1), the unique and specific methyltransferase of m6Am, has been shown to affect mRNA stability, transcription, and translation. Several studies have shown that PCIF1 is clearly associated with tumor, viral, and endocrine diseases. Moreover, PCIF1 may be related to the tumor microenvironment, immune cell typing, and programmed cell death protein 1(PD-1) drug resistance. Here, we summarize the mechanism of PCIF1 involvement in mRNA modifications, and outline m6Am modifications and diseases in which PCIF1 is involved. We also summarized the role of PCIF1 in immune and immune checkpoint blockade(ICB) treatment, and predicted the possibility of PCIF1 as a biomarker and therapeutic target.

Abstract Traumatic brain injury (TBI) accelerates fracture healing, but the underlying mechanism remains largely unknown. Accumulating evidence indicates that the central nervous system (CNS) plays a pivotal role in regulating immune system and skeletal homeostasis. However, the impact of CNS injury on hematopoiesis commitment was overlooked. Here, we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing; chemical sympathectomy blocks TBI-induced fracture healing. TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells (HSCs) and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days, which favor fracture healing. Knockout of β3- or β2-adrenergic receptor (AR) eliminate TBI-mediated anti-inflammation macrophage expansion and TBI-accelerated fracture healing. RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells. Importantly, flow cytometry confirmed that deletion of β2-AR inhibits M2 polarization of macrophages at 7th day and 14th day; and TBI-induced HSCs proliferation was impaired in β3-AR knockout mice. Moreover, β3- and β2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process. Thus, we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow. These results implicate that the adrenergic signals could serve as potential targets for fracture management.

Abstract Background Observational studies have reported an inverse association of type 2 diabetes (T2D) with thoracic aortic aneurysm (TAA). However, the causality of the association has not been established yet. The present study aims to clarify the causal relationship between T2D and TAA via a Mendelian randomization (MR) approach. Methods Causality of associations were assessed using a two-sample MR framework. Genome-wide association study (GWAS) summary statistics were obtained for T2D, glycated hemoglobin (HbA1c), fasting glucose (FG) and fasting insulin (FI) as exposures, and TAA, ascending aortic diameter (AAoD) and descending aortic diameter (DAoD) as outcomes. Four different methods (inverse variance weighted [IVW], weight median, MR-Egger and MR-PRESSO) were used to calculate causal estimates. Heterogeneity and horizontal pleiotropy were assessed using Cochran Q test and MR-Egger regression intercept, respectively. Results Genetically predicted T2D was inversely associated with the risk of TAA (OR: 0.931, 95% CI 0.870 to 0.997, p = 0.040, IVW method) and AAoD (Beta: -0.065, 95%CI −0.099 to − 0.031, p = 1.7e−04, IVW method), but not with DAoD (p > 0.05). Genetically predicted FG level was inversely associated with AAoD (Beta: −0.273, 95% CI −0.396 to –0.150, p = 1.41e−05, IVW method) and DAoD (Beta: −0.166, 95% CI −0.281 to −0.051, p = 0.005, IVW method), but not with TAA (p > 0.05). The effect of genetically predicted HbA1c and FI on TAA, AAoD and DAoD did not reach statistical significance (p > 0.05). Conclusions Genetic predisposition to T2D decreases the risk of TAA. Genetically predicted T2D is inversely associated with AAoD, but not with DAoD. Genetically predicted FG level was inversely associated with AAoD and DAoD.

The accuracy of aerial work platform weighing is essential for safety. However, in practice, the same weight placed at different locations on the platform can yield varying readings, which is a phenomenon known as eccentric load. Measurement errors caused by eccentric loads can lead to missed detections and false alarms in the vehicle safety system, seriously affecting the safety of aerial work. To overcome the influence of eccentric load, the current engineering practice relies on multiple measurements at multiple points and averaging the results to eliminate the eccentric load, which greatly increases the work intensity of workers. To address the aforementioned issues, this paper proposes a three-dimensional force/torque shear force compensation scheme based on bending torque and torsional torque for pressure. The goal is to ensure that the sensor on the aerial work vehicle platform can accurately measure the anti-eccentric load under single-point measurement conditions. A three-box structure anti-eccentric load-weighing sensor for the aerial work platform was designed. Its structure has the advantages of high mechanical strength and no radial effect, ensuring the safety of aerial work, improvement of measurement sensitivity, and enabling of real-time and accurate acquisition of force/torque in three directions. In order to further improve the measurement accuracy of 3D force/torque compensation, a particle swarm optimization algorithm was adopted to optimize the 3D force/torque shear force compensation, thereby improving the safety of engineering operations. Through the verification of a self-made testing platform, the anti-eccentric load sensor designed in this study can ensure that the measurement error of objects at any position on the platform is less than 1.5%, effectively improving the safety of high-altitude platform engineering operations.

Within the classical convection–diffusion approximation, we show that the angular distribution of cosmic rays (CRs) in a highly turbulent flow may exhibit significant small-scale anisotropies. The CR intensity angular power spectrum C _ℓ is then a direct reflection of interstellar turbulence, from which one expects C _ℓ ∝ ℓ ^− ^γ ^−1 for ℓ ≫ 1, where γ is the power-law turbulence spectral index. Observations by IceCube and HAWC at TeV energies can be explained approximately with the Kolmogorov law γ = 5/3 with a convection velocity dispersion of 20 km s ^−1 on the scale of 10 pc.

Summary: Our previous work has established a knockin (KI) pig model of Huntington’s disease (HD) that can replicate the typical pathological features of HD, including selective striatal neuronal loss, reactive gliosis, and axonal degeneration. However, HD KI mice exhibit milder neuropathological phenotypes and lack overt neurodegeneration. By performing RNA sequencing to compare the gene expression profiles between HD KI pigs and mice, we find that genes related to interleukin-17 (IL-17) signaling are upregulated in the HD pig brains compared to the mouse brains. Delivery of IL-17 into the brain striatum of HD KI mice causes greater reactive gliosis and synaptic deficiency compared to HD KI mice that received PBS. These findings suggest that the upregulation of genes related to IL-17 signaling in HD pig brains contributes to severe glial pathology in HD and identify this as a potential therapeutic target for treating HD.

PurposeTOPBP1 interacting checkpoint and replication regulator (TICRR), a hub gene of the Cdk2-mediated initiation step of DNA replication, has been shown an essential role in tumorigenesis by accelerating the DNA replication of tumor cells.MethodsRT-qPCR was used to detect the mRNA expression of TICRR in LUAD tumors and adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database of LUAD were acquired to analyze the critical role of TICRR expression in survival prognosis and clinicopathology characters in LUAD. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed using the R package. The correlation of TICRR expression with immune cell infiltration, RNA epigenetic modification, DNA damage repair (DDR) pathway, and cell metabolism of LUAD was further explored to verify significant conclusions.ResultsTICRR was significantly upregulated in most cancer types, including LUAD, lung squamous cell carcinoma (LUSC), and others. Cox regression analysis indicated the overexpression of TICRR was associated with poor survival in several cancers. In LUAD, TICRR expression was positively correlated with tumor stage and was increased in smoking, male, and high tumor mutational burden (TMB) patients. Enrichment analysis revealed that TICRR could influence tumor proliferation and prognosis via activating pathways involving cell cycle, DNA repair, DNA replication, cysteine metabolism, oxidative phosphorylation, and ubiquitin-mediated proteolysis pathways. Interestingly, high TICRR expression correlated with DDR pathway signature (34 genes), 37 m6A/m5C regulated genes, and some metabolism-regulated genes. Silencing the TICRR gene affects cysteine metabolism and modifies cancer-related pathways, with decreased cell cycle and increased B/T cell receptor signaling. Our TICRR risk model accurately predicts LUAD patient prognosis, validated across GEO datasets, and is integrated with clinical characteristics via a nomogram, facilitating personalized treatment strategies and enhancing patient management.ConclusionsTaken together, TICRR has emerged as a promising prognostic biomarker in lung adenocarcinoma (LUAD), with implications in immune activation, cell cycle regulation, RNA modification, and tumor energy metabolism. These findings suggest that TICRR could serve as a viable therapeutic target and a reliable prognostic indicator for LUAD.

Biodiversity underpins grassland ecological functions and productive capacities. By studying the mechanisms for the maintenance of species diversity in animal communities, we can provide important theoretical guidance for the optimization of grazing management and biodiversity protection. The typical grassland of Xilingol in Inner Mongolia, China, was used as the experimental area, and a grazing intensity experiment was set up. This consisted of four gradient levels that were grazed by sheep, which were available for continuous monitoring, namely control standard sheep unit·day·hectare-1·year-1 (CK, 0 SSU·d·hm-2y-1), light grazing (LG, 170 SSU·d·hm-2·y-1), moderate grazing (MG, 340 SSU·d·hm-2·y-1), and high grazing (HG, 510 SSU·d·hm-2·y-1). Nine consecutive years of multi-indicator monitoring of vegetation was carried out from 2014–2022, using monitoring data coupled with time series and inter-annual climatic (relative moisture index, RMI) fluctuations. This was done to analyze the impacts of disturbances, such as grazing use and climatic fluctuations, on the diversity of species and above-ground productivity of the community, thereby exploring the relationship between diversity and productivity, and provide possible explanations for the emergence of a range of ecological responses. The statistical analysis methods used were One-way Analysis of Variance (ANOVA), general linear regression and mixed-effects models. The main conclusions of this study are as follows: (1) The grassland in the experimental area under CK had the highest diversity and productivity and the ecosystem was better able to buffer the negative impacts of climatic drought. Furthermore, the effect of climate on productivity and diversity weakened as the intensity of grazing increased. (2) LG to MG had a constant diversity. (3) Grazing utilization changed the relationship between community species diversity and aboveground productivity by releasing spatial community resources, altering the structure of plant communities, weakening competitive exclusion, and strengthening complementary effects. However, under all of the conditions there is a brief stage in the time series when diversity is stimulated to increase, and the higher the grazing intensity, the earlier this occurs.

In heat exchangers, solar collectors, and geophysical transport, the temperature difference is significant, so the linear form of the density-temperature approximation (the Boussinesq approximation) is inadequate to describe actual density variations. Thus, the current study took into account the effect of nonlinear buoyancy on the thermal performance of a homogeneous nanofluid with hybrid nanoparticles in a free convective inclined energy system. In addition, response surface methodology with central composite design (RSM-CCD) is implemented to build a quadratic model based on three factors and levels (Ha, α, ϕ). To perform thermal evaluation, the experimental correlations are utilized with dimensionless controlling parameters such as Rayleigh number (Ra = 103 to 106), Hartmann number (Ha = 0 to 50), nanoparticle volume fraction (ϕ = 0 to 0.02) and angle of inclination (α = 0 to π) using Galerkin finite element method (GFEM) with a refined mesh (degree of freedoms (DOFs) = 208977, domain elements = 25636 and boundary elements = 858) for grid independent results. According to RSM-CCD, the Hartmann number has a significant impact on the thermal behavior of energy system. Also, the maximum average Nusselt number (Nur = 5.4938) is achieved with the optimal combination of key parameters i.e., Ha=36.707, α=0.5236 and ϕ=0.001.

Abstract Immune checkpoint blockade (ICB) is a promising treatment strategy for colorectal cancer (CRC) patients. However, most CRC patients do not response well to ICB therapy. Increasing evidence indicates that ferroptosis plays a critical role in immunotherapy. ICB efficacy may be enhanced by inducing tumor ferroptosis. Cytochrome P450 1B1 (CYP1B1) is a metabolic enzyme that participates in arachidonic acid metabolism. However, the role of CYP1B1 in ferroptosis remains unclear. In this study, we demonstrated that CYP1B1 derived 20-HETE activated the protein kinase C pathway to increase FBXO10 expression, which in turn promoted the ubiquitination and degradation of acyl-CoA synthetase long-chain family member 4 (ACSL4), ultimately inducing tumor cells resistance to ferroptosis. Furthermore, inhibiting CYP1B1 sensitized tumor cells to anti-PD-1 antibody in a mouce model. In addition, CYP1B1 expression was negatively correlated with ACSL4 expression, and high expression indicates poor prognosis in CRC. Taken together, our work identified CYP1B1 as a potential biomarker for enhancing anti-PD-1 therapy in CRC.

Abstract Limited numbers of available hematopoietic stem cells (HSCs) limit the widespread use of HSC-based therapies. Expansion systems for functional heterogenous HSCs remain to be optimized. Here, we present a convenient strategy for human HSC expansion based on a biomimetic Microniche. After demonstrating the expansion of HSC from different sources, we find that our Microniche-based system expands the therapeutically attractive megakaryocyte-biased HSC. We demonstrate scalable HSC expansion by applying this strategy in a stirred bioreactor. Moreover, we identify that the functional human megakaryocyte-biased HSCs are enriched in the CD34+CD38-CD45RA-CD90+CD49f lowCD62L-CD133+ subpopulation. Specifically, the expansion of megakaryocyte-biased HSCs is supported by a biomimetic niche-like microenvironment, which generates a suitable cytokine milieu and supplies the appropriate physical scaffolding. Thus, beyond clarifying the existence and immuno-phenotype of human megakaryocyte-biased HSC, our study demonstrates a flexible human HSC expansion strategy that could help realize the strong clinical promise of HSC-based therapies.

The synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted considerable attention in the field of cancer therapy because of its excellent anti-tumor effect. This work provides a novel pH/NIR responsive therapeutic nanoplatform, IrO2@ZIF-8/BSA-FA (Ce6), producing a synergistic effect of PTT-PDT in the treatment of osteosarcoma. Iridium dioxide nanoparticles (IrO2 NPs) with exceptional catalase-like activity and PTT effects were synthesized by a hydrolysis method and decorated with zeolitic imidazolate framework-8 (ZIF-8) shell layer to promote the physical absorption of Chlorin e6 (Ce6), and further functionalized with bovine serum albumin-folate acid (BSA-FA) for targeting tumor cells. The IrO2@ZIF-8/BSA-FA nanocomposite indicated an outstanding photothermal heating conversion efficiency of 62.1% upon laser irradiation. In addition, the Ce6 loading endows nanoplatform with the capability to induce cell apoptosis under 660 nm near-infrared (NIR) laser irradiation through a reactive oxygen species (ROS)-mediated mechanism. It was further testified that IrO2@ZIF-8/BSA-FA can function as a catalase and convert the endogenous hydrogen peroxide (H2O2) into oxygen (O2) to improve the local oxygen pressure under the acidic tumor microenvironment (TME), which could subsequently amplified PDT-mediated ROS cell-killing performance via relieving hypoxia microenvironment of tumor. Both in vitro and in vivo experimental results indicated that the nanomaterials were good biocompatibility, and could remarkably achieve tumor-specific and enhanced combination therapy outcomes as compared with the corresponding PTT or PDT monotherapy. Taken together, this work holds great potential to design an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

Abstract Arachidonic acid (AA), an n‐6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory‐related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.

Abstract Hematogenous metastasis is the main approach for colorectal cancer liver metastasis (CRCLM). However, as the gatekeepers in the tumor vessels, the role of TPCs in hematogenous metastasis remains largely unknown, which may be attributed to the lack of specific biomarkers for TPC isolation. Here, microdissection combined with a pericyte medium‐based approach is developed to obtain TPCs from CRC patients. Proteomic analysis reveals that TRP channel‐associated factor 2 (TCAF2), a partner protein of the transient receptor potential cation channel subfamily M member 8 (TRPM8), is overexpressed in TPCs from patients with CRCLM. TCAF2 in TPCs is correlated with liver metastasis, short overall survival, and disease‐free survival in CRC patients. Gain‐ and loss‐of‐function experiments validate that TCAF2 in TPCs promotes tumor cell motility, epithelial‐mesenchymal transition (EMT), and CRCLM, which is attenuated in pericyte‐conditional Tcaf2‐knockout mice. Mechanistically, TCAF2 inhibits the expression and activity of TRPM8, leading to Wnt5a secretion in TPCs, which facilitates EMT via the activation of the STAT3 signaling pathway in tumor cells. Menthol, a TRPM8 agonist, significantly suppresses Wnt5a secretion in TPCs and CRCLM. This study reveals the previously unidentified pro‐metastatic effects of TPCs from the perspective of cold‐sensory receptors, providing a promising diagnostic biomarker and therapeutic target for CRCLM.

The reciprocating plate column is a kind of column with the plates driven by a geared motor, and it has advantages in regard to efficiency compared to traditional columns in the extraction process, however, it comes with an increase in energy consumption. A new type of reciprocating plate column driven by electro-permanent magnet technology (EPM) is proposed in this paper to obtain a better performance with lower energy consumption. The feasibility and performance of the proposed column is studied by numerical simulation and experiments with a kerosene–water system. The electro-permanent magnet chuck could provide a maximum amplitude of 12 mm in this study. Kerosene was used as the dispersed phase, and deionized water was used as the continuous phase, in a laboratory-scale 35 mm diameter reciprocating plate column driven by EPM. Hydrodynamic performance experiments were carried out with different flowrates of both phases and reciprocating frequencies. The experimental results show that the electro-permanent magnet chuck, which serves as the driving device of the reciprocating plate column, plays the role of adding energy and increasing the droplet breakage. In addition, the energy consumption of the reciprocating plate column with traditional geared motor and electro-permanent magnet chuck is calculated respectively. Compared with the traditional geared motor, the energy saving of the electro-permanent magnet chuck is as high as 98.55%.

The proposed Ni–M/sepiolite (SEP) catalysts (M=Ce, Pr, and La) were developed to improve syngas production in biomass pyrolysis. A homogeneous precipitation method was used to synthesize these catalysts. These catalysts were characterized using X-ray fluorescence, X-ray diffraction, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and the Brunauer–Emmett–Teller method. A series of experiments were conducted to investigate the effects of catalyst types and M loading on gas composition and content in gas production. Simultaneously, the catalyst’s stability was tested. The experiments showed that the synthesized Ni–La/SEP catalyst with 12 wt% La and 20 wt% Ni loading had a high catalytic activity of improving gas quality compared with Ni–Pr/SEP, Ni–Ce/SEP, and Ni/SEP, giving a high hydrogen yield (41.18 vol.%) and CO yield (32.23 vol.%).