Search

Abstract The DC multi‐port converter's applications are increasing owing to its favourable features, including variable control mode, high power density, and bi‐directional power supply. On the other hand, the impedance interaction between each port of the electrolytic capacitor‐less DC multi‐port converter may generate an instability. To address the above mentioned problem, a method is proposed in this paper for reshaping the impedances of the energy storage converter by constructing a virtual impedance connected in parallel with the output impedance of the electrolytic capacitor‐less DC multi‐port converter. Furthermore, this paper introduces the stability criterion based on the unified impedance theory, which classifies a converter as either the bus current‐controlled converter or the bus voltage‐controlled converter. The proposed control approaches raise the magnitude of the output impedance of the electrolytic capacitor‐less DC multi‐port converter to satisfy the unified impedance theory criterion without modifying each port. The simulation results show that the proposed method is better than the traditional methods, and comprehensive experimental results are provided to validate the proposed methods.

In this work, the various amount of Nb powder was mechanically mixed into the Cu–Al–Mn shape memory alloys (SMAs) to prepare quaternary SMAs by laser powder bed fusion (LPBF). Altered microstructure, transformation behaviour of alloys and its underlying mechanisms were analyzed. Corresponding shape memory effect (SME) was also studied. Result shows that Nb content has significant effect on the microstructure, phase transition temperatures (TTs) and SME. The microstructure of the alloy was refined by addition of appropriate Nb content. The formation of precipitates and massive grain boundaries after the addition of Nb caused a reduction of TTs and wide thermal hysteresis. Sample with 1 at%Nb containing fine and small volume fraction precipitate shows the best available strain.

Stroke is a major cause of adult disability worldwide, often involving disruption of the blood-brain barrier (BBB). Repairing the BBB is crucial for stroke recovery, and pericytes, essential components of the BBB, are potential intervention targets. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for functional impairments after stroke, with potential effects on BBB integrity. However, the underlying mechanisms remain unclear. In this study using a transient middle cerebral artery occlusion (tMCAO) rat model, we investigated the impact of rTMS on post-stroke BBB. Through single-cell sequencing (ScRNAs), we observed developmental relationships among pericytes, endothelial cells, and vascular smooth muscle cells, suggesting the differentiation potential of pericytes. A distinct subcluster of pericytes emerged as a potential therapeutic target for stroke. Additionally, our results revealed enhanced cellular communication among these cell types, enriching signaling pathways such as IGF, TNF, NOTCH, and ICAM. Analysis of differentially expressed genes highlighted processes related to stress, differentiation, and development. Notably, rTMS intervention upregulated Reck in vascular smooth muscle cells, implicating its role in the classical Wnt signaling pathway. Overall, our bioinformatics findings suggest that rTMS may modulate BBB permeability and promote vascular regeneration following stroke. This might happen through 20 Hz rTMS promoting pericyte differentiation into vascular smooth muscle cells, upregulating Reck, then activating the classical Wnt signaling pathway, and facilitating vascular regeneration and BBB stability.

BackgroundThis Mendelian randomization (MR) study aimed to explore the causal relationship between the genetic predisposition to type 2 diabetes mellitus (T2DM) and aortic dissection (AD), and to assess associations with genetically predicted glycemic traits. The study sought to verify the inverse relationship between T2DM and AD using a more robust and unbiased method, building on the observational studies previously established.Materials and methodsThe study employed a two-sample and multivariable MR approach to analyze genetic data from the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) with 74,124 cases and 824,006 controls, and the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) involving up to 196,991 individuals. For AD data, FinnGen Release 10 was used, including 967 cases and 381,977 controls. The research focused on three foundational MR assumptions and controlled for confounders like hypertension. Genetic instruments were selected for their genome-wide significance, and multiple MR methods and sensitivity analyses were conducted.ResultsThe study revealed no significant effect of genetic predisposition to T2DM on the risk of AD. Even after adjusting for potential confounders, the results were consistent, indicating no causal relationship. Additionally, glycemic traits such as fasting glucose, fasting insulin, and HbA1c levels did not show a significant impact on AD susceptibility. The findings remained stable across various MR models and sensitivity analyses. In contrast, genetic liability to T2DM and glycemic traits showed a significant association with coronary artery disease (CAD), aligning with the established understanding.ConclusionContrary to previous observational studies, this study concludes that genetic predisposition to T2DM does not confer protection against AD. These findings underscore the imperative for further research, particularly in exploring the preventative potential of T2DM treatments against AD and to facilitate the development of novel therapeutic interventions.

Abstract Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. We isolated and cultured cow lamellar keratinocytes using the Dispase II and collagenase methods. We purified them by differential digestion and differential velocity adherent methods at each passaging and identified them by keratin 14 immunofluorescence. We established an in vitro model of inflammation in laminar keratinocytes using LPS and investigated whether chicoric acid protects against inflammatory responses by inhibiting the activation of the TLR4/MAPK/NF-κB signaling pathway. The results showed that cow lamellar keratinocytes were successfully isolated and cultured by Dispase II combined with the collagenase method. In the in vitro inflammation model established by LPS, the Chicoric acid decreased the concentration of inflammatory mediators (TNF-α, IL-1β, and IL-6), down-regulated the mRNA expression of TLR4 and MyD88 (P

With the demand for the miniaturization and integration of wireless power transfer (WPT) systems, higher frequency is gradually becoming the trend; thus, the power electronic device has become one of the main reasons for limiting the development. Therefore, further research on high-frequency inverters and purposeful design according to the characteristics of WPT systems are of great significance to promote the development of high-frequency WPT technology. There is still no literature that summarizes all the inverter circuits that can be applied to WPT systems, which makes it extremely difficult to find an inverter that meets the designer’s requirements. This paper reviews the high-frequency inverters for WPT systems, summarizes the derived topologies based on power amplifiers and H-bridge inverters, investigates the main factors restricting the development of high-frequency inverters, and analyzes the research directions for future development.

Cooperative and self-enforceable water allocation is a key instrument to manage geopolitical conflict induced by water scarcity, which necessitates the cooperative willingness of the agents and considers their heterogeneity in geography, climate, hydrology, environment and social economy. Based on a multi-indicator system that contains asymmetric information on water volume contribution, current water consumption, water economic efficiency and efforts for eco-environmental protection, this study proposed a water allocation framework by combining the asymmetric power index approach with bankruptcy theory for solving the transboundary water allocation problem under scarcity. The proposed method was applied to the Yellow River Basin in northern China, which is mainly shared by nine provincial districts and frequently suffers from severe water shortages, and its results were compared with six alternative methods. The results highlight the necessity of quantifying agents’ willingness to cooperate under the condition of asymmetric negotiation power when making decisions on transboundary water allocations. The proposed method allows for transboundary water allocations through simultaneous consideration of the agent’s willingness to cooperate and asymmetric negotiation power, as well as disagreement allocation points, which ensure the stability, fairness and self-enforceability of allocation results. Therefore, it can offer practical and valuable decision-making insights for transboundary water management under water scarcity.

This paper provides a comprehensive analysis of the electric-drive-wheel (EDW) with idler gear. From the perspective of automotive engineering, the EDW is an integrated execution unit that combines the function of powertrain and suspension. As a result, the research on EDW involves the intersection of multiple disciplines. The evolution of idler gear configuration requires some geometric constraints. Under this premise, the longitudinal and vertical dynamic characteristics of the system were studied, respectively. There are several factors that influence the system performance, such as the gear parameters, the position of the electric motor, and the suspension K&C value. The principles of each parameter on the output indicators were studied, with an optimized plan and simulation comparison to check the correctness of theory. In the end, the prototype was equipped with a test bench, covering a wide range of working operations to examine the expected performance of EDW design. The step response test of the EDW result showed a balanced performance in transmission smoothness and responsiveness agility.

BackgroundThe mechanism by which high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) improves swallowing function by regulating intestinal flora remains unexplored. We aimed to evaluate this using fecal metabolomics and 16S rRNA sequencing.MethodsA Post-stroke dysphagia (PSD) rat model was established by middle cerebral artery occlusion. The magnetic stimulation group received HF-rTMS from the 7th day post-operation up to 14th day post-surgery. Swallowing function was assessed using a videofluoroscopic swallowing study (VFSS). Hematoxylin-eosin (H&E) staining was used to assess histopathological changes in the intestinal tissue. Intestinal flora levels were evaluated by sequencing the 16S rRNA V3-V4 region. Metabolite changes within the intestinal flora were evaluated by fecal metabolomics using liquid chromatography-tandem mass spectrometry.ResultsVFSS showed that the bolus area and pharyngeal bolus speed were significantly decreased in PSD rats, while the bolus area increased and pharyngeal transit time decreased after HF-rTMS administration (p < 0.05). In the PSD groups, H&E staining revealed damaged surface epithelial cells and disrupted cryptal glands, whereas HF-rTMS reinforced the integrity of the intestinal epithelial cells. 16S rRNA sequencing indicated that PSD can disturb the intestinal flora and its associated metabolites, whereas HF-rTMS can significantly regulate the composition of the intestinal microflora. Firmicutes and Lactobacillus abundances were lower in the PSD group than in the baseline group at the phylum and genus levels, respectively; however, both increased after HF-rTMS administration. Levels of ceramides (Cer), free fatty acids (FA), phosphatidylethanolamine (PE), triacylglycerol (TAG), and sulfoquinovosyl diacylglycerol were increased in the PSD group. The Cer, FA, and DG levels decreased after HF-rTMS treatment, whereas the TAG levels increased. Peptococcaceae was negatively correlated with Cer, Streptococcus was negatively correlated with DG, and Acutalibacter was positively correlated with FA and Cer. However, these changes were effectively restored by HF-rTMS, resulting in recovery from dysphagia.ConclusionThese findings suggest a synergistic role for the gut microbiota and fecal metabolites in the development of PSD and the therapeutic mechanisms underlying HF-rTMS.

In this paper, a novel design strategy for l-PBFed AlMnMgScZr/TiN composites with ultrahigh strength was proposed. TiN particles can not only function as ceramic reinforcement, but also decompose and reprecipitate to form a large density of L12-precipitates at a high melting temperature during l-PBF. Meanwhile, the primary L12-Al3X (X=Ti/Sc/Zr) phase promotes the columnar-to-equiaxed grain transition effect, creating a fine bi-modal grain structure in the as-built sample. A high volume fraction of L12 nanoparticles are additionally precipitated from Al matrix during post heat treatment. In this regard, effective grain refinement and precipitation hardening mechanism contribute to an excellent tensile performance with a combination of an ultimate tensile strength of 681±4 MPa, a yield strength of 677±4 MPa, and an elongation rate of 5.4 ± 1.2%. The yield strength of 677 MPa is particularly the highest among all previously reported l-PBFed Al matrix composites and Al alloys.

[Introduction] With the rapid development of power electronic equipment and artificial intelligence and other high-tech, DC (Direct Current) system has been popularized and applied in substations. The grounding fault of the substation DC system has become an important factor affecting the safe and stable operation of the substation. [Method] Firstly, the DC system of the substation was introduced, and its components, typical types of DC ground faults and their adverse effects were analyzed. Then, the principle of five common DC ground fault finding strategies was emphasized. [Result] Based on their respective research status and application scenarios, the advantages and disadvantages of various finding strategy are compared and analyzed. [Conclusion] Combined with the existing problems and technical development trends, the future research directions of DC grounding fault detection at home and abroad are prospected from the perspectives of accurate fault location, complex fault identification, finding accuracy and the improvement of the endurance of portable insulation detection device.

Mechanical and corrosion behaviors perpendicular to build direction (XOY) and along build direction (XOZ) of UNS S31803 duplex stainless steel (DSS) fabricated by laser powder bed fusion (LPBF) were investigated. With the post-annealing, the steel exhibited a ferrite-austenite microstructure. For XOY plane, austenite displayed a primarily texture while ferrite kept preferred orientation, and mainly held a Nishiyama-Wassermann orientation relationship. However, for XOZ plane, austenite showed a mixed texture. The average size of ferrite grains was larger for XOZ plane than XOY. The austenite in XOY plane was mostly island morphology grains, while in XOZ plane, there were a large number of coarse columnar grains. A higher geometrically necessary dislocation density and proportion of low-angle grain boundaries on XOY plane were observed. The yield strength and ultimate tensile strength values perpendicular to build direction were higher than those along build direction. While the total elongation perpendicular to build direction was lower. Moreover, the XOY plane shows slightly better corrosion resistance than the XOZ.

Fission yeast, a single-cell eukaryotic organism, shares many fundamental cellular processes with higher eukaryotes, including gene transcription and regulation, cell cycle regulation, vesicular transport and membrane trafficking, and cell death resulting from the cellular stress response. As a result, fission yeast has proven to be a versatile model organism for studying human physiology and diseases such as cell cycle dysregulation and cancer, as well as autophagy and neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s diseases. Given that viruses are obligate intracellular parasites that rely on host cellular machinery to replicate and produce, fission yeast could serve as a surrogate to identify viral proteins that affect host cellular processes. This approach could facilitate the study of virus–host interactions and help identify potential viral targets for antiviral therapy. Using fission yeast for functional characterization of viral genomes offers several advantages, including a well-characterized and haploid genome, robustness, cost-effectiveness, ease of maintenance, and rapid doubling time. Therefore, fission yeast emerges as a valuable surrogate system for rapid and comprehensive functional characterization of viral proteins, aiding in the identification of therapeutic antiviral targets or viral proteins that impact highly conserved host cellular functions with significant virologic implications. Importantly, this approach has a proven track record of success in studying various human and plant viruses. In this protocol, we present a streamlined and scalable molecular cloning strategy tailored for genome-wide and comprehensive functional characterization of viral proteins in fission yeast.

Hepatic ischemia/reperfusion injury (IRI) is an important factor affecting liver regeneration and functional recovery postoperatively. Many studies have suggested that mesenchymal stem cells (MSCs) contribute to hepatic tissue repair and functional recovery through paracrine mechanisms mediated by exosomes. Minipigs exhibit much more similar characteristics of the liver to those of humans than rodents. This study aimed to explore whether exosomes from adipose-derived MSCs (ADSCs-exo) could actively promote liver regeneration after hepatectomy combined with HIRI in minipigs and the role they play in the cell proliferation process. This study also compared the effects and differences in the role of ADSCs and ADSCs-exo in the inflammatory response and liver regeneration. The results showed that ADSCs-exo suppressed histopathological changes and reduced inflammatory infiltration in the liver; significantly decreased levels of ALT, TBIL, HA, and the pro-inflammatory cytokines TNF-α, IL-6, and CRP; increased levels of the anti-inflammatory cytokine IL-10 and the pro-regeneration factors Ki67, PCNA, CyclinD1, HGF, STAT3, VEGF, ANG1, ANG2; and decreased levels of the anti-regeneration factors SOCS3 and TGF-β. These indicators above showed similar changes with the ADSCs intervention group. Indicating that ADSCs-exo can exert the same role as ADSCs in regulating inflammatory responses and promoting liver regeneration. Our findings provide experimental evidence for the possibility that ADSCs-exo could be considered a safe and effective cell-free therapy to promote regeneration of injured livers.

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF3a protein plays a vital role in viral pathogenesis and coronavirus disease 2019 (COVID-19). Like the spike protein, ORF3a mutates frequently, and certain variants are associated with the severity of COVID-19. Given the clinical significance and functional implications of ORF3a mutations, we conducted a comprehensive mutagenesis study targeting various known functional elements and revealed two distinctive types of ORF3a proteins based on their subcellular localizations: ORF3a proteins primarily localize on the lysosomal membrane (L-ORF3a) and those present in the endoplasmic reticulum (E-ORF3a). The objective of this study was to contrast the functional and mechanistic distinctions between these two types of ORF3a proteins. We examined six distinct ORF3a mutants and assessed their effects on cellular oxidative stress, nuclear factor kappa B-induced cytokine production, and cell death. Mechanistically, we explored ORF3a-induced ER stress, autophagy, and interactions with relevant cellular proteins. Our findings indicate that ORF3a proteins induce cytopathic effects through a similar mechanism, irrespective of their subcellular location. However, E-ORF3a proteins elicit more pronounced cytopathic effects despite their lower abundance and minimal impact on ER stress and autophagy when compared to L-ORF3a proteins. This discrepancy is attributed to ER-associated degradation since ORF3a proteins bind to a ubiquitin E3 ligase TRIM59. Inhibition of the 26S proteasome partially restores the protein levels of E-ORF3a and cellular ER stress response. This suggests that even a small quantity of ORF3a can lead to significant cytopathic effects due to the delicate nature of ER. Our study underscores the intricate interplay of dynamic cellular signaling within these two subcellular compartments in response to ORF3a.IMPORTANCEThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has tragically claimed millions of lives through coronavirus disease 2019 (COVID-19), and there remains a critical gap in our understanding of the precise molecular mechanisms responsible for the associated fatality. One key viral factor of interest is the SARS-CoV-2 ORF3a protein, which has been identified as a potent inducer of host cellular proinflammatory responses capable of triggering the catastrophic cytokine storm, a primary contributor to COVID-19-related deaths. Moreover, ORF3a, much like the spike protein, exhibits a propensity for frequent mutations, with certain variants linked to the severity of COVID-19. Our previous research unveiled two distinct types of ORF3a mutant proteins, categorized by their subcellular localizations, setting the stage for a comparative investigation into the functional and mechanistic disparities between these two types of ORF3a variants. Given the clinical significance and functional implications of the natural ORF3a mutations, the findings of this study promise to provide invaluable insights into the potential roles undertaken by these mutant ORF3a proteins in the pathogenesis of COVID-19.

Hepatic ischemia-reperfusion injury (HIRI) is a complication of hepatectomy that affects the functional recovery of the remnant liver, which has been demonstrated to be associated with pyroptosis and apoptosis. Mesenchymal stem cells (MSCs) can protect against HIRI in rodents. Paracrine mechanisms of MSCs indicated that MSCs-derived exosomes (MSCs-exo) are one of the important components within the paracrine substances of MSCs. Moreover, miniature pigs are ideal experimental animals in comparative medicine compared to rodents. Accordingly, this study aimed to investigate whether hepatectomy combined with HIRI in miniature pigs would induce pyroptosis and whether adipose-derived MSCs (ADSCs) and their exosomes (ADSCs-exo) could positively mitigate apoptosis and pyroptosis. The study also compared the differences in the effects and the role of ADSCs and ADSCs-exo in pyroptosis and apoptosis. Results showed that severe ultrastructure damage occurred in liver tissues and systemic inflammatory response was induced after surgery, with TLR4/MyD88/NFκB/HMGB1 activation, NLRP3-ASC-Caspase1 complex generation, GSDMD revitalization, and IL-1β, IL-18, and LDH elevation in the serum. Furthermore, expression of Fas-Fasl-Caspase8 and CytC-APAF1-Caspase9 was increased in the liver. The ADSCs or ADSCs-exo intervention could inhibit the expression of these indicators and improve the ultrastructural pathological changes and systemic inflammatory response. There was no significant difference between the two intervention groups. In summary, ADSCs-exo could effectively inhibit pyroptosis and apoptosis similar to ADSCs and may be considered a safe and effective cell-free therapy to protect against liver injury.

This study investigated the efficacy of a composite probiotics composed of lactobacillus plantarum, lactobacillus reuteri, and bifidobacterium longum in alleviating oxidative stress in weaned piglets and pregnant sows. Evaluations of growth, oxidative stress, inflammation, intestinal barrier, and fecal microbiota were conducted. Results showed that the composite probiotic significantly promoted average daily gain in piglets (p < 0.05). It effectively attenuated inflammatory responses (p < 0.05) and oxidative stress (p < 0.05) while enhancing intestinal barrier function in piglets (p < 0.01). Fecal microbiota analysis revealed an increase in the abundance of beneficial bacteria such as faecalibacterium, parabacteroides, clostridium, blautia, and phascolarctobacterium in piglet feces and lactobacillus, parabacteroides, fibrobacter, and phascolarctobacterium in sow feces, with a decrease in harmful bacteria such as bacteroides and desulfovibrio in sow feces upon probiotic supplementation. Correlation analysis indicated significant negative associations of blautia with inflammation and oxidative stress in piglet feces, while treponema and coprococcus showed significant positive associations. In sow feces, lactobacillus, prevotella, treponema, and CF231 exhibited significant negative associations, while turicibacter showed a significant positive association. Therefore, the composite probiotic alleviated oxidative stress in weaned piglets and pregnant sows by modulating fecal microbiota composition.

Stable boundary layer height (SBLH) is an important parameter to characterize the characteristics and vertical structure of the nocturnal lower atmosphere at night. The distribution of SBLH has obvious spatial and temporal differences, and there are many meteorological factors affecting the SBLH, but at present, there are few quantitative studies on the effects of near-surface meteorological factors on the SBLH in the desert hinterland. This study was based on GPS sounding balloon data, near-surface meteorological observation data, and ERA5 data from Tazhong Station (TZ) in the Taklamakan Desert (TD) collected in July 2017, 2019, and 2021. The variation characteristics of the SBLH and its relationship with near-surface meteorological factors are described. We quantitatively analyzed the degree of influence of near-surface meteorological factors affecting the SBLH and verified it using a model. The study also elucidates the possible formation mechanism of the SBLH in the TD hinterland. The SBLH in the TD hinterland trended upward in July 2017, 2019, and 2021, which is consistent with the changes in meteorological factors, according to the near-surface meteorological observation and ERA5 data. Therefore, we think that an inherent connection exists between near-surface meteorological factors and the SBLH. The results of correlation analysis show that complex internal connections and interactions exist among the meteorological factors near the ground; some thermal, dynamic, and other meteorological factors strongly correlate with the SBLH. Having established the change in SBLH (ΔSBLH) and in major thermal, dynamic, and other meteorological factors (Δ), the linear regression equation between them revealed that near-surface meteorological factors can affect the SBLH. The dynamic factors have a stronger influence on the ΔSBLH than thermal and other factors. The results of model validation based on the variable importance projection (VIP) also confirmed that the SBLH in the TD hinterland is jointly affected by dynamic and thermal factors, but the dynamic factors have a stronger impact. The mechanism through which the SBLH forms is relatively complex. At night, surface radiative cooling promotes the formation of a surface inversion layer, and low-level jets strengthen wind shear, reducing atmospheric stability. The combined effects of heat and dynamics play an important role in dynamically shaping the SBLH. This study helps us with accurately predicting and understanding the characteristics of the changes in and the factors influencing the SBLH in the TD hinterland, providing a reference for understanding the mechanism through which the SBLH forms in this area. At the same time, it provides a scientific basis for regional weather and climate simulation, meteorological disaster defense, air quality forecasting, and model parameterization improvement.

The Galileo satellite navigation system now provides initial services. With further satellite launches, the performance of Galileo will gradually improve, and new services will be introduced. This study aims to provide a comprehensive analysis of Galileo Single Point Positioning (SPP) using different broadcast ephemeris data sources. This study investigates the completeness of Galileo navigation message records from different institutions. The results show that IGS provides the best completeness across different data sources (ECR > 70%), while IGN exhibits the lowest completeness. Analyze the proportions of different data sources within the Galileo navigation message in the broadcast ephemeris files provided by IGS during the study period. The proportions of FNAV_258, INAV_513, INAV_516, and INAV_517 during the study period are 25.83%, 24.76%, 23.61%, and 25.80%, respectively, suggesting better data completeness for FNAV_258 and INAV_517 and poorer completeness for INAV_513 and INAV_516. Finally, this study explores SPP solutions for GPS and Galileo systems using different data sources. The results indicate that a higher ECR corresponds to better positioning performance. Although GPS exhibits smaller error fluctuations and smoother positioning results, Galileo’s SPP positioning accuracy surpasses that of GPS. The introduction of dual-frequency observations effectively reduces data dispersion and enhances vertical positioning accuracy.

Sesame is one of the important oil seed crops grown for the high-quality oil. Its growth, development, and yield are significantly affected by the changing climate conditions. Evaluating the sesame climatic suitability is crucial to optimize sesame cultivation patterns and planting distribution, and to aid strategic decision making for future agricultural adaptation. Based on agricultural climatic suitability theory and the fuzzy mathematics method, in this study, we established the temperature, precipitation, sunshine, and comprehensive suitability model. Then, we assessed the spatial distribution and chronological changes in climatic suitability under two periods, 1978–1998 (earlier 21 years) and 1999–2019 (latter 21 years). The results showed that compared with the meteorological data in the earlier 21 years, the mean temperature during the sesame-growing season in the latter 21 years increased from 24.48 °C to 25.05 °C, and the cumulative precipitation increased from 744.38 mm to 754.81 mm; however, the sunshine hours decreased from 6.05 h to 5.55 h. Temperature, precipitation, sunshine, and comprehensive suitability during the sesame-growing season in the main sesame-producing areas of China all had a downward trend. The distribution of temperature and comprehensive suitability in the north is higher than that in the south, while the precipitation and sunshine suitability had an uneven distribution. The area of high-temperature suitability and high-precipitation suitability increased from 43.45 × 106 ha to 46.34 × 106 ha and from 3.20 × 106 ha to 7.97 × 106 ha, respectively, whereas the area of high-sunshine suitability decreased from 4.04 × 106 ha to 2.09 × 106 ha. The climate change was more beneficial to sesame cultivation in northeast Anhui where the area of high climatic suitability clearly expanded, and in eastern Jiangxi where the area of the general climatic suitability increased. In contrast, it is worth noting that the area of high climatic suitability in northern Henan decreased and the area of low climatic suitability in Hubei increased. Our results have important implications for improving agricultural production to cope with ongoing climate change.

Objective: This systematic review and meta-analysis aimed to systematically evaluate the prediction models for the risk of post-thrombotic syndrome (PTS) in deep vein thrombosis (DVT) patients. Methods: This systematic review and meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A systematic search on the following electronic database: PubMed/MEDLINE, EMBASE, and Cochrane Library, and Chinese databases such as WANFANG and CNKI was conducted to look for relevant articles based on the research question. The risk of bias for each studies included was carried out based on Prediction Model Risk of Bias Assessment Tool (PROBAST). Results: We identified 10 studies that developed a total of 13 clinical prediction models for PTS risk in DVT patients, 3 models were externally validated, 2 models were temporally validated. The top 5 predictors were: BMI (N = 9), Varicose vein (N = 6), Baseline Villalta Score (N = 6), Iliofemoral thrombosis (N = 5), and Age (N = 4). The high risk of bias was from the analysis domain, which the number of participants and selection of predictors often did not meet the requirements of PROBAST. A random-effects meta-analysis of C-statistics was conducted, the pooled discrimination was C-statistic 0.75, 95%CI (0.69, 0.81). Conclusion: Among the 13 PTS risk prediction models reported in this study, no prediction model has been applied to clinical practice due to the lack of external validation. In the development of prediction models, most models were not standardized in data analysis. It is recommended that future studies on the design and implementation of prediction models refer to Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) and PROBAST.

IntroductionAs a vital component within glacier systems, the occurrences of glacial lake disasters in high mountain regions have progressively emerged as one of the most destructive natural calamities amid the backdrop of global warming. The swift advancement of glacial lake identification techniques offers a pivotal perspective for forecasting and mitigating the perils of glacial lake outburst disasters.MethodsTo evaluate the thematic evolution, research focal points, and forthcoming directions within the glacier identification domain, a comprehensive bibliometric analysis was conducted on glacial lake identification-related literature from 1991 to 2023 in the Web of Science Core Collection database.Results1) The United States, the United Kingdom, and China stand as principal nations propelling the field's advancement. The Chinese Academy of Sciences demonstrates the highest activity in terms of article publications and international collaborations. 2) Climate change, compilation of glacial lake inventories, methodologies for risk assessment, glacial lake outburst floods, comprehensive disaster management strategies, and hydrodynamic models constitute the domain's research hotspots. It is a typical multidisciplinary field. 3) Persistently high-impact topics over an extended period include “hazard”, “Late Pleistocene”, “environmental change”, “ice sheet”, and “lake sediments”. Keywords indicating the present cutting-edge research encompass “inventory”, “glacial lake outburst flood”, “risk”, “dynamics”, “Tibetan Plateau”, “evolution”, and “high mountain Asia”.DiscussionThis paper delves into the current status and pivotal concerns of glacial lake identification techniques, methodologies, and the scale of identification research themes. Further Research should concentrate on avenues like “recognition methods grounded in machine learning and deep learning”, “multisource data fusion datasets”, “novel algorithms and technologies adaptable to scale transformation and data expansion”, as well as “enhancing spatiotemporal data resolution”. This will ultimately enable precise, prolonged, and multiscalar identification of glacial lakes. his study provides valuable guidance and reference for future research in the field of glacial lake identification.

Abstract Background The technology of cotton defoliation is essential for mechanical cotton harvesting. Agricultural unmanned aerial vehicle (UAV) spraying has the advantages of low cost, high efficiency and no mechanical damage to cotton and has been favored and widely used by cotton planters in China. However, there are also some problems of low cotton defoliation rates and high impurity rates caused by unclear spraying amounts of cotton defoliants. The chemical rate recommendation and application should be based upon crop canopy volume rather than on land area. Plant height and leaf area index (LAI) is directly connected to plant canopy structure. Accurate dynamic monitoring of plant height and LAI provides important information for evaluating cotton growth and production. The traditional method to obtain plant height and LAI was s a time-consuming and labor-intensive task. It is very difficult and unrealistic to use the traditional measurement method to make the temporal and spatial variation map of plant height and LAI of large cotton fields. With the application of UAV in agriculture, remote sensing by UAV is currently regarded as an effective technology for monitoring and estimating plant height and LAI. Results In this paper, we used UAV RGB photos to build dense point clouds to estimate cotton plant height and LAI following cotton defoliant spraying. The results indicate that the proposed method was able to dynamically monitor the changes in the LAI of cotton at different times. At 3 days after defoliant spraying, the correlation between the plant height estimated based on the constructed dense point cloud and the measured plant height was strong, with $$R^2$$ R 2 and RMSE values of 0.962 and 0.913, respectively. At 10 days after defoliant spraying, the correlation became weaker over time, with $$R^2$$ R 2 and RMSE values of 0.018 and 0.027, respectively. Comparing the actual manually measured LAI with the estimated LAI based on the dense point cloud, the $$R^2$$ R 2 and RMSE were 0.872 and 0.814 and 0.132 and 0.173 at 3 and 10 days after defoliant spraying, respectively. Conclusions Dense point cloud construction based on UAV remote sensing is a potential alternative to plant height and LAI estimation. The accuracy of LAI estimation can be improved by considering both plant height and planting density.

Abstract Immune checkpoint inhibitor (ICI) therapy is an emerging and effective approach to the treatment of gastric cancer (GC). However, the low response rate of GC patients to ICI therapy is a major limitation of ICI therapy. We investigated the transcriptomic signature of immune genes in GC could provide a comprehensive understanding of the tumor microenvironment (TME) and identify a valuable biomarker to predict the response of GC patients receiving immunotherapy. We performed the weighted gene co-expression network analysis (WGCNA) to determine immune-related hub genes that differentially expressed in the GC dataset based on The Cancer Genome Atlas (TCGA). After that, univariate and multivariate Cox regression was performed to recognize prognostic genes associated with overall survival and to develop an immune-related gene prognostic index (IRGPI). Furthermore, we explored the possible correlation between IRGPI and immune cell infiltration and immunotherapy efficacy. Notably, IRGPI can predict the prognosis of GC patients, as well as the response to immunotherapy. IRGPI as an immune-related prognostic biomarker might bring some potential implications for immunotherapy strategies in GC.

In this study, the Cu-11.85Al-3.88Mn-1.6Nb (wt.%) shape memory alloy with low cost and a highly functional response was manufactured by selective laser melting(SLM). The effects of energy inputs (123–185J/mm3) on their microstructure, mechanical, and shape memory properties were investigated. It was observed that all of the samples were composed of 18R and 2H martensite, and the nanosized (Cu, Mn)3Al3Nd4 phase was formed during selective laser melting(SLM). In addition, the good compressive fracture strength and strain were 1652Mpa, and 15.1% respectively. An excellent shape memory effect of 99.26% recovery ratio and 5.32% shape memory strain was obtained by SLM.

BackgroundHepatocellular carcinoma (HCC) represents a prominent gastrointestinal malignancy with a grim clinical outlook. In this regard, the discovery of novel early biomarkers holds substantial promise for ameliorating HCC-associated mortality. Efferocytosis, a vital immunological process, assumes a central position in the elimination of apoptotic cells. However, comprehensive investigations exploring the role of efferocytosis-related genes (EFRGs) in HCC are sparse, and their regulatory influence on HCC immunotherapy and targeted drug interventions remain poorly understood.MethodsRNA sequencing data and clinical characteristics of HCC patients were acquired from the TCGA database. To identify prognostically significant genes in HCC, we performed the limma package and conducted univariate Cox regression analysis. Subsequently, machine learning algorithms were employed to identify hub genes. To assess the immunological landscape of different HCC subtypes, we employed the CIBERSORT algorithm. Furthermore, single-cell RNA sequencing (scRNA-seq) was utilized to investigate the expression levels of ERFGs in immune cells and to explore intercellular communication within HCC tissues. The migratory capacity of HCC cells was evaluated using CCK-8 assays, while drug sensitivity prediction reliability was determined through wound-healing assays.ResultsWe have successfully identified a set of nine genes, termed EFRGs, that hold significant potential for the establishment of a hepatocellular carcinoma-specific prognostic model. Furthermore, leveraging the individual risk scores derived from this model, we were able to stratify patients into two distinct risk groups, unveiling notable disparities in terms of immune infiltration patterns and response to immunotherapy. Notably, the model’s capacity to accurately predict drug responses was substantiated through comprehensive experimental investigations, encompassing wound-healing assay, and CCK8 experiments conducted on the HepG2 and Huh7 cell lines.ConclusionsWe constructed an EFRGs model that serves as valuable tools for prognostic assessment and decision-making support in the context of immunotherapy and chemotherapy.

The COVID-19 pandemic caused by SARS-CoV-2 has posed unparalleled challenges due to its rapid transmission, ability to mutate, high mortality and morbidity, and enduring health complications. Vaccines have exhibited effectiveness, but their efficacy diminishes over time while new variants continue to emerge. Antiviral medications offer a viable alternative, but their success has been inconsistent. Therefore, there remains an ongoing need to identify innovative antiviral drugs for treating COVID-19 and its post-infection complications. The ORF3a (open reading frame 3a) protein found in SARS-CoV-2, represents a promising target for antiviral treatment due to its multifaceted role in viral pathogenesis, cytokine storms, disease severity, and mortality. ORF3a contributes significantly to viral pathogenesis by facilitating viral assembly and release, essential processes in the viral life cycle, while also suppressing the body’s antiviral responses, thus aiding viral replication. ORF3a also has been implicated in triggering excessive inflammation, characterized by NF-κB-mediated cytokine production, ultimately leading to apoptotic cell death and tissue damage in the lungs, kidneys, and the central nervous system. Additionally, ORF3a triggers the activation of the NLRP3 inflammasome, inciting a cytokine storm, which is a major contributor to the severity of the disease and subsequent mortality. As with the spike protein, ORF3a also undergoes mutations, and certain mutant variants correlate with heightened disease severity in COVID-19. These mutations may influence viral replication and host cellular inflammatory responses. While establishing a direct link between ORF3a and mortality is difficult, its involvement in promoting inflammation and exacerbating disease severity likely contributes to higher mortality rates in severe COVID-19 cases. This review offers a comprehensive and detailed exploration of ORF3a’s potential as an innovative antiviral drug target. Additionally, we outline potential strategies for discovering and developing ORF3a inhibitor drugs to counteract its harmful effects, alleviate tissue damage, and reduce the severity of COVID-19 and its lingering complications.

Abstract Dual windings parallel (DWP) coils are often used in high‐power wireless charging applications to reduce current stress and internal resistance. Due to the inconsistent self‐inductance and strong coupling of the two windings, the advantages of the DWP coils cannot be fully utilized. In particular, the current stresses of the two windings are different, which will cause one of the stress to exceed the limit, and the temperature rise is too high. The reason for the current imbalance in the two windings is analysed in this work, and a distributed capacitor compensation method is proposed to balance the current stress in the two windings. Finally, a WPT system with the DWP transmitting coil was built as an example to demonstrate the effectiveness of the proposed method. The experimental results show that the current ratio in two windings decreased from 1.70 to 1.05 after using the proposed compensation method.

Background: Acute respiratory distress syndrome (ARDS) could account for a considerable proportion of neonatal death, while the genetic etiology and pathophysiology of neonatal ARDS remain elusive. In this case-control study, 515 neonates were enrolled in the China Neonatal Genomes Project (CNGP, NCT03931707) from August 2016 to June 2021, including 196 ARDS and 319 non-ARDS matched by sex, gestational age, birth weight, perinatal asphyxia, pneumonia, sepsis, and necrotizing enterocolitis. Clinical exome sequencing was used to detect genetic variants. Collapsing analyses together with permutation tests were used to identify ARDS risk genes enriched for rare variants in ARDS samples. In silico functional interaction analysis and expression pattern studies at different stages of lung development were used to investigate the biological functions of the risk genes. Results: Collapsing analyses identified that rare variants were significantly abundant in the genes associated with the precursor of the lamellar body and there were eight predicted risk genes with strong confidence (P

Pancreatic cancer (PC) is a highly fatal disease correlated with an inferior prognosis. The tumor protein p53 (TP53) is one of the frequent mutant genes in PC and has been implicated in prognosis. We collected somatic mutation data, RNA sequencing data, and clinical information of PC samples in the Cancer Genome Atlas (TCGA) database. TP53 mutation was an independent prognostic predictor of PC patients. According to TP53 status, Gene set enrichment analysis (GSEA) suggested that TP53 mutations were related to the immunophenotype of pancreatic cancer. We identified 102 differentially expressed immune genes (DEIGs) based on TP53 mutation status and developed a TP53-associated immune prognostic model (TIPM), including Epiregulin (EREG) and Prolactin receptor (PRLR). TIPM identified the high-risk group with poor outcomes and more significant response potential to cisplatin, gemcitabine, and paclitaxel therapies. And we verified the TIPM in the International Cancer Genome Consortium (ICGC) cohort (PACA-AU) and Gene Expression Omnibus (GEO) cohort (GSE78229 and GSE28735). Finally, we developed a nomogram that reliably predicts overall survival in PC patients on the bias of TIPM and other clinicopathological factors. Our study indicates that the TIPM derived from TP53 mutation patterns might be an underlying prognostic therapeutic target. But more comprehensive researches with a large sample size is necessary to confirm the potential.

Background: Angiogenesis is one of the most prominent markers of cancer progression and contributes to tumor metastasis and prognosis. Anti-angiogenic drugs have proven effective in treating metastatic colorectal cancer. However, there is some uncertainty regarding the potential role of angiogenesis-related genes in the tumor microenvironment.Methods: We analyzed 1,214 colorectal cancer samples to identify alterations in angiogenesis-related genes (ARGs), and then correlated angiogenesis with clinical features, prognosis, and TME. The ARGs expression profiles in colorectal cancer were analyzed using three computational methods (CIBERSORT, ssGSEA, and MCPcounter) and provided a systematic immune landscape. Patients with CRC were classified into two subtypes based on consensus clustering analysis of angiogenesis-related genes. The revealed differentially expressed genes between the two subtypes were used to create and validate ARGscore prognostic models. In addition, we collected eight colorectal cancer patient specimens and performed RT-qPCR to validate the signature gene expression.Results: We assessed the expression patterns of ARGs in colorectal cancer. We identified two molecular subtypes and confirmed that the expression of ARGs was associated with prognosis and TME characteristics. Based on differentially expressed genes between subtypes, we constructed ARGscore and evaluated their predictive power for the survival of colorectal cancer patients. We also developed an accurate nomogram to make the ARGscore more clinically useful. In addition, ARGscore was significantly correlated with microsatellite instability, cancer stem cells, and chemotherapeutic drug sensitivity. Patients with ARGscore-low characterized by immune activation and microsatellite instability high had a better prognosis.Conclusion: ARGs expression influenced the prognosis, clinicopathological features, and tumor stromal immune microenvironment in colorectal cancer. We developed a new risk model, ARGscore, for the treatment and prognosis of CRC patients and validated its promising predictive power. These findings will enable us to understand colorectal cancer better, assess prognoses, and develop more effective treatment options.

BackgroundUlcerative colitis (UC) is a chronic inflammatory disease of the intestinal mucosa, the incidence of which has increased worldwide. There is still a lack of clear understanding of the pathogenesis of ulcerative colitis that ultimately leads to colitis-associated colorectal cancer.MethodWe download UC transcriptome data from the GEO database and pass the limma package in order to identify differentially expressed genes. Gene Set Enrichment Analysis (GSEA) was used to identify potential biological pathways. We identified immune cells associated with UC by CIBERSORT and Weighted co-expression network analysis (WGCNA). We used validation cohorts and mouse models to verify the expression of the hub genes and the role of neutrophils.ResultWe identified 65 differentially expressed genes in UC samples and healthy controls. GSEA, KEGG, and GO analyses displayed that DEGs were enriched in immune-related pathways. CIBERSORT analysis revealed increased infiltration of neutrophils in UC tissues. The red module, obtained by WGCNA analysis, was considered to be the most relevant module for neutrophils.Based on neutrophil-associated differentially expressed genes, UC patients were classified into two subtypes of neutrophil infiltration. We discovered that the highly neutrophil-infiltrated subtype B of UC patients had a higher risk of developing CAC. Five genes were identified as biomarkers by searching for DEGs between distinct subtypes. Finally, using the mouse model, we determined the expression of these five genes in the control, DSS, and AOM/DSS groups. The degree of neutrophil infiltration in mice and the percentage of MPO and pSTAT3 expression in neutrophils were analyzed by flow cytometry. In the AOM/DSS model, MPO and pSTAT3 expressions were significantly increased.ConclusionsThese findings suggested neutrophils might promote the conversion of UC into CAC. These findings improve our understanding of the pathogenesis of CAC and provide new and more effective insights into the prevention and treatment of CAC.

The ongoing SARS-CoV-2/COVID-19 pandemic caused a global public health crisis. Yet, everyone’s response to SARS-CoV-2 infection varies, and different viral variants confer diverse pathogenicity. Thus, it is imperative to understand how viral determinants contribute to COVID-19. Viral ORF3a protein is one of those viral determinants, as its functions are linked to induction of cell and tissues damages, disease severity and cytokine storm that is a major cause of COVID-19-related death. ORF3a is a membrane-associated protein. Upon synthesis, it is transported from endoplasmic reticulum, Golgi apparatus to plasma membrane and subcellular endomembranes including endosomes and lysosomes. However, how ORF3a is transported intracellularly remains elusive. The goal of this study was to carry out a systematic mutagenesis study to determine the structural relationship of ORF3a protein with its subcellular locations. Single amino acid (aa) and deletion mutations were generated in the putative function-relevant motifs and other regions of interest. Immunofluorescence and ImageJ analyses were used to determine and quantitate subcellular locations of ORF3a mutants in comparison with wildtype ORF3a. The wildtype ORF3a localizes predominantly (Pearson’s coefficients about 0.8) on the membranes of endosomes and lysosomes. Consistent with earlier findings, deletion of the YXXΦ motif, which is required for protein export, retained ORF3a in the Golgi apparatus. Interestingly, mutations in a double glycine (diG) region (aa 187–188) displayed a similar phenotype to the YXXΦ deletion, implicating a similar role of the diG motif in intracellular transport. Indeed, interrupting any one of the two glycine residues such as deletion of a single (dG188), both (dG187/dG188) or substitution (G188Y) of these residues led to ORF3a retention in the Golgi apparatus (Pearson’s coefficients ≥0.8). Structural analyses further suggest that the diG motif supports a type-II β-turn between the anti-parallel β4 and β5 sheets and connects to the YXXΦ motif via hydrogen bonds between two monomers. The diG- YXXΦ interaction forms a hand-in-hand configuration that could facilitate dimerization. Together, these observations suggest a functional role of the diG motif in intracellular transport of ORF3a.

Abstract To investigate the relationship among summer atmospheric boundary layer (ABL) over the Taklimakan Desert (TD), its land surface parameters and large scale meteorological field, the Urumqi Institute of Desert Meteorology of China Meteorological Administration conducted a comprehensive observation of boundary layer in Tazhong, the hinterland of TD from July 1 to 31, 2016. The correlations between the ABL height and surface sensible heat, latent heat, air temperature, turbulent kinetic energy (TKE) and buoyancy term are analyzed by using the observed GPS sounding data, the surface layer micro meteorological data in the hinterland of the TD and ERA5 reanalysis data so as to study the correlation of the ABL height and Eurasian circulation field. The research results indicate: (1) The height of summer ABL over the TD does not fully correspond with the variation tendency of surface sensible heat flux. In addition to surface sensible heat, large scale advection and residual mixed layer (RML) are also crucial factor influencing ABL. (2) The surface TKE over the TD is consistent with ABL height variation, with the correlation coefficient of 0.62. Hence the equation of ABL height and TKE is expressed as: Y = 1609.2X4 – 12,828X3 + 35,617X2 –39,514X + 15,858. (3) When the ABL height over the TD is quite high, 500 hPa altitude in Xinjiang is mostly controlled by anticyclone circulation, and the easterly low level jet (LLJ) tends to be formed at 850 hPa the next night. (4) The high correlation areas of summer ABL height over the TD and Eurasian temperature field are Xinjiang and Balkash Lake region. Significant positive correlation is identified between the ABL height and the temperature field at 850, 700, and 500 hPa of the above regions. The maximum correlation coefficient reaches 0.7. The study deepens the understanding of the relationship among the ABL process over the TD, land surface parameters and Eurasian circulation.

Osteoarthritis (OA) is a common chronic musculoskeletal disease reported in veterinary clinics that severely reduces the quality of life of animals. The natural product, bilobalide, has positive effects on chondroprotection but its exact mechanism of action is unclear. This study aimed to investigate the antioxidant and anti-matrix degradation activities of bilobalide in a rabbit model of OA and its protective effects on joints. We also investigated the possible mechanisms underlying these effects. The rabbit OA model was established by intra-articular injection of 4% papain. Thirty healthy male New Zealand rabbits were randomly divided into control, untreated OA, Cel (100 mg/kg celecoxib intervention as a positive control), BB-L and BB-H (40 mg /kg and 80 mg /kg bilobalide gavage treatment, respectively) groups. Two weeks after surgical induction, bilobalide or celecoxib was administered by gavage daily for 8 weeks. After 8 weeks of bilobalide intervention, cartilage macroscopic observation and histopathological images showed alleviation of cartilage damage after bilobalide treatment, and the Osteoarthritis Research Society International (OARSI) score was significantly lower than that in the OA group. Bilobalide reduced the expression of metalloproteinase 3 (MMP-3) and MMP-13 in cartilage tissue of OA rabbits and reversed the levels of serum C-telopeptides of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP), interleukin 1(IL-1), and tumor necrosis factor (TNF-α). Bilobalide (80 mg/kg) could improve the biomechanical properties and microstructural changes in subchondral bone in the early stage of OA in rabbits, thereby delaying subchondral bone damage. Mechanistically, bilobalide exerted antioxidant and anti-matrix degradation effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and inhibiting cartilage degeneration in rabbit OA. We thus speculate that bilobalide supplements recovery from OA damage.

Osteoarthritis (OA) is driven by chronic low-grade inflammation and subsequent cartilage degradation. OA is the most prevalent degenerative joint disease worldwide, and its treatment remains a challenge. The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of ginkgolide C (GC). Protective effects of GC on hydrogen peroxide (H2O2)-treated rat chondrocytes were evaluated using ELISA, qPCR, western blot analysis, flow cytometry, ROS detection and immunofluorescence in vitro. Ameliorating effects of GC on cartilage degeneration in rats were evaluated through behavioral assays, microcomputed tomography, histopathological analysis, western blot analysis and ELISA in vivo. In vitro, GC treatment inhibited the release of pro-apoptotic factors induced by H2O2 and promoted the release of the anti-apoptotic proteins. In addition, GC decreased the expression of matrix metalloproteinase (MMP3 and MMP13), thrombospondin motifs 4 (ADAMTS4), and inflammatory mediators inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and SOX9 thereby inhibiting extracellular matrix (ECM) degradation. Mechanistically, GC exerts its anti-apoptotic and anti-inflammatory effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and preventing p65 from binding to DNA. Similarly, In a rat model with post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT), GC inhibited joint pain, cartilage destruction, and abnormal bone remodeling of subchondral bone. GC inhibited H2O2-induced chondrocyte apoptosis through Nrf2/HO-1 and NF-κB axis, exerted anti-inflammatory effects, and inhibited cartilage degeneration in rat OA. Our findings advanced the concept that GC may contribute to cartilage metabolism through anti-inflammatory and anti-apoptotic effects, and the identified GC is a potential therapeutic agent for the treatment of OA.

Land–atmosphere interactions are influenced by the earth’s complex underlying subsurface, which in turn indirectly affects atmospheric motion and climate change. Human activities are increasingly exerting an influence on desert ecosystems, and artificial green land with clear functional orientation has been established in many desert areas. Consequently, the previously dominant, shifting, sand-covered, underlying surface in these desert regions is gradually transforming. This transformation has significant implications for the characteristics of land–atmosphere interactions, causing them to deviate from their original state. At present, existing studies still have not presented a systematic understanding of this change and have ignored the impact of human activities on land–atmosphere interactions in artificial green land. To address these research gaps, this study specifically targets artificial green land in the Tazhong region of Taklamakan Desert. We carried out observation experiments on land–atmosphere interactions in three different functional units from outside to inside: natural shifting sands, the shelter forest, and the living area. We also analyzed the differences and attribution of land–atmosphere interactions characteristics of different functional units. Compared with the natural shifting sands, the daily average maximum values of wind speed in the shelter forest decreased by 78%, and the daily average maximum air temperature and soil (0 cm) temperature decreased by 2.6 °C and 7 °C, respectively. Additionally, the soil moisture level was significantly increased throughout the green land due to the shelter forest. The surface albedo experienced a decrease, with an annual average of 0.21. Furthermore, the aerodynamic roughness and bulk transport coefficient increased by two orders of magnitude. The daily average maximum values of sensible heat flux and soil heat flux (G05) decreased by 18.7% and 75%, respectively, and the daily average maximum value of latent heat flux increased by 70.3%. This effectively improved the microclimate environment of the green land. The living area was greatly reduced by the shelter forest coverage and influenced by the buildings. Consequently, the environmental improvement was not as large as it was inside the shelter forest. However, it still provided a good shelter for production and living in the desert area. Throughout the year, a total of 4.60 × 105 t water was consumed through evapotranspiration in the artificial green land. The findings of this study have the potential to enhance our comprehension of land–atmosphere interactions in desert regions, thereby offering valuable insights for the establishment and effective management of artificial desert green lands.

This study was aimed at determining the autophagy activity in the laminar tissue of dairy cows with oligofructose-induced laminitis. Twelve healthy non-pregnant Holstein cows were randomly divided into two groups of six cows each, entitled the control group and the oligofructose overload group (OF group), respectively. At 0 h, cows in the OF group were gavaged with oligofructose (17 g/kg BW) dissolved in warm deionized water (20 mL/kg BW) through an oral rumen tube, and the dairy cows in the control group were gavaged with the same volume of deionized water by the same method. At −72 h before, as well as 0 h, 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 60 h, and 72 h after perfusion, clinical evaluations of both groups were monitored. After 72 h, the laminar tissues of the dairy cows in both groups were collected to examine the genes and proteins. The gene expression of ATG5, ATG12, and Beclin1 significantly increased (p < 0.05), whereas that of P62 and mTOR significantly decreased (p < 0.01) in the OF group relative to the control group. The protein expression of Beclin-1 significantly increased (p < 0.05), while that of LC3II significantly decreased (p < 0.05) in the OF group relative to the control group. However, the protein expression of P62 non-significantly reduced (p > 0.05) in the OF group comparative to the control group. Furthermore, the distribution of the Beclin1 protein in the laminar tissue significantly increased (p < 0.01), while that of the P62 protein significantly decreased (p < 0.05) in the OF group than the control group. These findings indicate that the imbalanced gene and protein-level status of autophagy-related markers may be the basic cause for the failure of the epidermal attachment. However, a more detailed gene and protein-level study is needed to further clarify the role of autophagy in the pathogenesis of bovine laminitis.

Abstract Colorectal cancer (CRC) ranks fourth among the deadliest cancers globally, and the progression is highly affected by the tumor microenvironment (TME). This study explores the relationship between TME and colorectal cancer prognosis and identifies prognostic genes related to the CRC microenvironment. We collected the gene expression data from The Cancer Genome Atlas (TCGA) and calculated the scores of stromal/immune cells and their relations to clinical outcomes in colorectal cancer by the ESTIMATE algorithm. Lower immune scores were significantly related to the malignant progression of CRC (metastasis, p = 0.001). We screened 292 differentially expressed genes (DEGs) by dividing CRC cases into high and low stromal/immune score groups. Functional enrichment analyses and protein–protein interaction (PPI) networks illustrated that these DEGs were closely involved in immune response, cytokine–cytokine receptor interaction, and chemokine signaling pathway. Six DEGs (FABP4, MEOX2, MMP12, ERMN, TNFAIP6, and CHST11) with prognostic value were identified by survival analysis and validated in two independent cohorts (GSE17538 and GSE161158). The six DEGs were significantly related to immune cell infiltration levels based on the Tumor Immune Estimation Resource (TIMER). The results might contribute to discovering new diagnostic and prognostic biomarkers and new treatment targets for colorectal cancer.

Osteoarthritis (OA) is a degenerative disease that seriously affects an individual's quality of life. Oleanolic acid (OLA) is widely present in food and medicinal plants and has various pharmacological activities. Autophagy is an intracellular protective mechanism, and this study aimed to investigate the potential role of OLA targeting the autophagy pathway in the pathogenesis of OA. A rat OA model was established in vivo by intra-articular injection of Monosodium Iodoacetate (MIA), followed by ELISA, Western blot analysis, and behavioral assays. The results showed that OLA improved OA pain symptoms and inhibit cartilage degeneration. In vitro, OLA inhibited the secretion of inflammatory factors and matrix metalloproteinases in ATDC5 cells after induction with IL-1β (10 ng/mL). Meanwhile, Dansylcadaverine (MDC) staining, transmission electron microscopy (TEM), mRFP-GFP-LC3 immunofluorescence, Western blot analysis and RT-qPCR confirmed that OLA activates autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, OLA shows promise in the treatment of OA.

Abstract Metabolic genes have played a significant role in tumor development and prognosis. In this study, we constructed a metabolic risk model to predict the prognosis of colon cancer based on The Cancer Genome Atlas (TCGA) and validated the model by Gene Expression Omnibus (GEO). We extracted 753 metabolic genes and identified 139 differentially expressed genes (DEGs) from TCGA database. Then we conducted univariate cox regression analysis and Least Absolute Shrinkage and Selection Operator Cox regression analysis to identify prognosis-related genes and construct the metabolic risk model. An eleven-gene prognostic model was constructed after 1000 resamples. The gene signature has been proved to have an excellent ability to predict prognosis by Kaplan–Meier analysis, time-dependent receiver operating characteristic, risk score, univariate and multivariate cox regression analysis based on TCGA. Then we validated the model by Kaplan–Meier analysis and risk score based on GEO database. Finally, we performed a weighted gene co-expression network analysis and protein–protein interaction network on DEGs, and Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology enrichment analyses were conducted. The results of functional analyses showed that most significantly enriched pathways focused on metabolism, especially glucose and lipid metabolism pathways.

Bitterness is one of the basic tastes, and sensing bitterness plays a significant role in mammals recognizing toxic substances. The bitter taste of food and oral medicines may decrease consumer compliance. As a result, many efforts have been made to mask or decrease the bitterness in food and oral pharmaceutical products. The detection of bitterness is critical to evaluate how successful the taste-masking technology is, and many novel taste-sensing systems have been developed on the basis of various interaction mechanisms. In this review, we summarize the progress of bitterness response mechanisms and the development of novel sensors in detecting bitterness ranging from commercial electronic devices based on modified electrodes to micro-type sensors functionalized with taste cells, polymeric membranes, and other materials in the last two decades. The challenges and potential solutions to improve the taste sensor quality are also discussed.

Stem cell transplantation (SCT) holds great promise for overcoming diseases by regenerating damaged cells, tissues and organs. The potential for self-renewal and differentiation is the key to SCT. RNA methylation, a dynamic and reversible epigenetic modification, is able to regulate the ability of stem cells to differentiate and regenerate. N6-methyladenosine (m6A) is the richest form of RNA methylation in eukaryotes and is regulated by three classes of proteins: methyltransferase complexes, demethylase complexes and m6A binding proteins. Through the coordination of these proteins, RNA methylation precisely modulates the expression of important target genes by affecting mRNA stability, translation, selective splicing, processing and microRNA maturation. In this review, we summarize the most recent findings on the regulation of m6A modification in embryonic stem cells, induced pluripotent stem cells and adult stem cells, hoping to provide new insights into improving SCT technology.

The ongoing SARS-CoV-2 pandemic has shocked the world due to its persistence, COVID-19-related morbidity and mortality, and the high mutability of the virus. One of the major concerns is the emergence of new viral variants that may increase viral transmission and disease severity. In addition to mutations of spike protein, mutations of viral proteins that affect virulence, such as ORF3a, also must be considered. The purpose of this article is to review the current literature on ORF3a, to summarize the molecular actions of SARS-CoV-2 ORF3a, and its role in viral pathogenesis and COVID-19. ORF3a is a polymorphic, multifunctional viral protein that is specific to SARS-CoV/SARS-CoV-2. It was acquired from β-CoV lineage and likely originated from bats through viral evolution. SARS-CoV-2 ORF3a is a viroporin that interferes with ion channel activities in host plasma and endomembranes. It is likely a virion-associated protein that exerts its effect on the viral life cycle during viral entry through endocytosis, endomembrane-associated viral transcription and replication, and viral release through exocytosis. ORF3a induces cellular innate and pro-inflammatory immune responses that can trigger a cytokine storm, especially under hypoxic conditions, by activating NLRP3 inflammasomes, HMGB1, and HIF-1α to promote the production of pro-inflammatory cytokines and chemokines. ORF3a induces cell death through apoptosis, necrosis, and pyroptosis, which leads to tissue damage that affects the severity of COVID-19. ORF3a continues to evolve along with spike and other viral proteins to adapt in the human cellular environment. How the emerging ORF3a mutations alter the function of SARS-CoV-2 ORF3a and its role in viral pathogenesis and COVID-19 is largely unknown. This review provides an in-depth analysis of ORF3a protein’s structure, origin, evolution, and mutant variants, and how these characteristics affect its functional role in viral pathogenesis and COVID-19.

Abstract Background Gastric cancer (GC) is the leading cause of death worldwide and is closely related to metastasis. MRTF-A is one of the most well-characterized genetic markers in cancer. However, the mechanism whereby MRTF-A mediate gastric cancer (GC) tumorigenesis is not fully clear. Increasing evidence has confirmed that miRNA dysregulation is involved in MRTF-A-mediated tumorigenesis, supporting their potential as therapeutic targets for cancer. Although miR-155 has been reported as an upregulated miRNA, the interplay between miR-155 and MRTF-A-mediated gastric cancer progression remain largely elusive. Methods Real-time PCR was performed to determine miR-155 expression after transfected with MRTF-A encoding plasmids and siRNA. Potential target genes were identified by Western blot and luciferase reporter assay. Chip assay was proved that MRTF-A binds in the promoter region of miR-155. Transwell assay and Scratch-healing migration assay was used to investigate the role of MRTF-A and SOX1 in gastric cancer cell migration and invasion. Results MRTF-A can interact with the miR-155 promoter to promote histone acetylation and RNA polymerase II recruitment via the Wnt-β-catenin pathway. miR-155 promotes gastric cancer cell migration by suppressing SOX1 expressiom by targeting its 3′UTR in vitro and in vivo. MRTF-A inhibited the inhibitory effects of SOX1 on gastric cancer cell migration by promoting the express -ion of miR-155. Conclusion Our data therefore provide important and novel insights into how the MRTF-A/miR-155/SOX1 pathway mediates migration and invasion in GC.

Abstract Background Hoof disease is one of the three major diseases that often occur in dairy cows. The impact of this disease on dairy farming is second only to mastitis. Laminitis is a diffuse, aseptic, serous, non-purulent inflammation of the dermal papillae and vascular layers of the cow’s hoof wall. In the pasture, laminitis occurs mostly in the laminae, that is, inside the hoof shell. No lesions can be seen on the surface. Therefore, laminitis cannot attract the attention of veterinarians. However, laminitis has become a major factor that seriously affects the health and welfare of dairy cows, making it an important cause of hindering the performance of dairy cows. Methods The study was conducted at a dairy farm in Harbin, Heilongjiang province, China. We selected a sample of the laminitis cows based on the veterinary diagnosis, took blood from the jugular vein and then separated the plasma, and measured the index with the Elisa kit. In this study, the markers of inflammatory and vasoactive substances status in dairy cows consisted of subclinical laminitis (SCL, n = 20), chronic laminitis (CL, n = 20) and healthy dairy cows (CON, n = 20) under the local management conditions were investigated. Results Compared with healthy cattle, HIS, IL-6, LPS, and TNF-α in subclinical laminitis group significantly increased (P

ABSTRACT Therapeutic inhibition of critical viral functions is important for curtailing coronavirus disease 2019 (COVID-19). We sought to identify antiviral targets through the genome-wide characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins that are crucial for viral pathogenesis and that cause harmful cytopathogenic effects. All 29 viral proteins were tested in a fission yeast cell-based system using inducible gene expression. Twelve proteins, including eight nonstructural proteins (NSP1, NSP3, NSP4, NSP5, NSP6, NSP13, NSP14, and NSP15) and four accessory proteins (ORF3a, ORF6, ORF7a, and ORF7b), were identified that altered cellular proliferation and integrity and induced cell death. Cell death correlated with the activation of cellular oxidative stress. Of the 12 proteins, ORF3a was chosen for further study in mammalian cells because it plays an important role in viral pathogenesis and its activities are linked to lung tissue damage and a cytokine storm. In human pulmonary and kidney epithelial cells, ORF3a induced cellular oxidative stress associated with apoptosis and necrosis and caused activation of proinflammatory response with production of the cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IFN-β1, possibly through the activation of nuclear factor kappa B (NF-κB). To further characterize the mechanism, we tested a natural ORF3a Beta variant, Q57H, and a mutant with deletion of the highly conserved residue, ΔG188. Compared with wild-type ORF3a, the ΔG188 variant yielded more robust activation of cellular oxidative stress, cell death, and innate immune response. Since cellular oxidative stress and inflammation contribute to cell death and tissue damage linked to the severity of COVID-19, our findings suggest that ORF3a is a promising, novel therapeutic target against COVID-19. IMPORTANCE The ongoing COVID-19 pandemic caused by SARS-CoV-2 has claimed over 5.5 million lives with more than 300 million people infected worldwide. While vaccines are effective, the emergence of new viral variants could jeopardize vaccine protection. Treatment of COVID-19 by antiviral drugs provides an alternative to battle against the disease. The goal of this study was to identify viral therapeutic targets that can be used in antiviral drug discovery. Utilizing a genome-wide functional analysis in a fission yeast cell-based system, we identified 12 viral candidates, including ORF3a, which cause cellular oxidative stress, inflammation, apoptosis, and necrosis that contribute to cytopathogenicity and COVID-19. Our findings indicate that antiviral agents targeting ORF3a could have a great impact on COVID-19.

Although osteoarthritis (OA) significantly affects the quality of life of the elderly, there is still no effective treatment strategy. The standardized Ginkgo biloba L. extract preparation has been shown to have a wide range of therapeutic effects. Bilobalide, a unique ingredient of Ginkgo biloba, has anti-inflammatory and antioxidant pharmacological properties, but its mechanism of action on OA remains unknown. In this study, we investigated the effects of bilobalide on the development of OA through in vivo and in vitro experiments, as well as its potential anti-inflammatory mechanisms. The in vitro experiments demonstrated that bilobalide significantly inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinase 13 (MMP13) in ATDC5 chondrocytes induced by Interleukin-1β (IL-1β). At the molecular level, bilobalide induced chondrocyte autophagy by activating the AMPK/SIRT1/mTOR signaling pathway, which increased the expression of autophagy-related Atg genes, up-regulated the expression of LC3 protein, and reduced the expression of the p62 protein. In vivo, bilobalide exerted significant anti-inflammatory and anti-extracellular matrix (ECM) degradation effects in a rat model of post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT). Bilobalide could relieve joint pain in PTOA rats, inhibit the expression of iNOS and COX-2 protein in cartilage via the AMPK/SIRT1/mTOR pathway, and reduce the level of ECM degradation biomarkers in serum. In conclusion, bilobalide exhibits vigorous anti-inflammatory activity, presenting it as an interesting potential therapeutic agent for OA.

Understanding the vertical structures of cloud condensation nuclei (CCN) and ice-nucleating particle (INP) number concentrations in desert source regions is crucial for examining dust-cloud interactions and other related impacts. To explore the vertical profiles of the CCN and INP number concentrations and their possible atmospheric–dynamic influence factors at the center of the Taklimakan Desert, intensive observations were conducted by employing a ground-based polarization Raman lidar, sounding balloons, and a sun photometer in Tazhong (83.39° E, 38.58° N, 1103 m above sea level) during the summer of 2019. Based on the GRASP algorithm, the extinction-to-volume conversion factor of dust aerosols was 0.85 × 10−12 Mmm3 m−3, and the extinction-to-number conversion factor was predicted to be 0.20 Mm cm−3 on the basis of the sun photometer observations. Thus, the vertical CCN and INP number concentration profiles obtained with different parameterization schemes in the presence of various pollution levels were calculated by combining dust extinction coefficients retrieved by lidar and meteorological data observed by sounding balloon observations. The achieved results indicated that the CCN number concentration varied from 10−2 to 102 cm−3 and decreased from ground level to 12 km with an average value of 36.57 cm−3 at the 10–12 km height range, while the INP number concentration based on parameterization schemes D10 and D15 mainly varied from 10−1 to 102 L−1 and from 1 L−1 to 103 L−1, with average values of 3.50 L−1 and 7.80 L−1, respectively. Moreover, we observed a strong relationship between the INP number concentration of scheme D10 and the wind speed, with an R2 value of 0.72, but a weak relationship between the CCN number concentration and the relative humidity in the boundary layer, with a Spearman’s rank correlation coefficient R2 value of 0.38. The present study provides original and valuable information regarding the CCN and INP number concentrations and their related influencing factors at the center of the Taklimakan Desert and can improve our understanding of the vertical distributions of dust–cloud–atmosphere dynamic interactions, as well as of the roles of dust aerosols in the desert hydrological cycle.