Autophagy regulates the maturation of hematopoietic precursors in the embryo

An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors.</p

Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma

This review systematically examines gender differences in hepatocellular carcinoma (HCC), identifying the influence of sex hormones, genetic variance, and environmental factors on the disease’s epidemiology and treatment outcomes. Recognizing the liver as a sexually dimorphic organ, we highlight how gender-specific risk factors, such as alcohol consumption and obesity, contribute differently to hepatocarcinogenesis in men and women. We explore molecular mechanisms, including the differential expression of androgen and estrogen receptors, which mediate diverse pathways in tumor biology such as cell proliferation, apoptosis, and DNA repair. Our analysis underscores the critical need for gender-specific research in liver cancer, from molecular studies to clinical trials, to improve diagnostic accuracy and therapeutic effectiveness. By incorporating a gender perspective into all facets of liver cancer research, we advocate for a more precise and personalized approach to cancer treatment that acknowledges gender as a significant factor in both the progression of HCC and its response to treatment. This review aims to foster a deeper understanding of the biological and molecular bases of gender differences in HCC and to promote the development of tailored interventions that enhance outcomes for all patients

Quantum critical point in SmO1−xFxFeAs and oxygen vacancy induced by high fluorine dopant

The local lattice and electronic structure of the high-T(c) superconductor SmO(1-x)F(x)FeAs as a function of F-doping have been investigated by Sm L(3)-edge X-ray absorption near-edge structure and multiple-scattering calculations. Experiments performed at the L(3)-edge show that the white line (WL) is very sensitive to F-doping. In the under-doped region (x ≤ 0.12) the WL intensity increases with doping and then it suddenly starts decreasing at x = 0.15. Meanwhile, the trend of the WL linewidth versus F-doping levels is just contrary to that of the intensity. The phenomenon is almost coincident with the quantum critical point occurring in SmO(1-x)F(x)FeAs at x ≃ 0.14. In the under-doped region the increase of the intensity is related to the localization of Sm-5d states, while theoretical calculations show that both the decreasing intensity and the consequent broadening of linewidth at high F-doping are associated with the content and distribution of oxygen vacancies

Determination of phosphorus fractions in animal protein ingredients

Phosphorus (P) is present in different chemical compounds in animal feeds, and the solubility and digestibility of these different compounds are known to differ significantly. Animal protein ingredients generally have a high P content and are major contributors to total P of feeds for fish and other domestic animals. Estimation of different P compounds in these ingredients could help to improve the accuracy of estimates of digestible P contents of feeds. Bone P and organic P contents were quantified in 32 animal protein ingredients, including 10 fish meals, 14 meat and bone meals, and 8 poultry byproducts meals, using a fractionation protocol. The total P contents of the ingredients ranged from 2.1 to 8.3% on a dry matter (DM) basis. Organic P contents varied between 0.3 and 1.3% of DM. Highly significant (p < 0.001) linear relationships were observed between total P and ash and between bone P and ash for all ingredients combined: total P (%) = 0.185 x ash (%) (R-2 = 0.88), and bone P (%) = 0.188 x ash (%) - 0.852 (R-2 = 0.94). These results suggest that bone P can be easily and reliably estimated on the basis of ash content in animal protein ingredients

Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury

Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors

Dynamic Formation Processes and Characteristics of “28 June 2012” Debris Flow in Aizi Valley, Ningnan County, Sichuan Province, China

On 28 June 2012, a large debris flow occurred in Aizi gully, Ningnan County, Sichuan Province, China. It was the most significant debris flow disaster at a construction site in 2012 in China, which left 40 people dead or missing. Field investigations and model calculations were conducted following the event in order to determine dynamic parameters and execute engineering mitigation measures. Analyzing the collected data, it is found that earthquake and drought play a dominant role in debris flow initiation, and from 1 January 1986 to 31 December 2010, 43 earthquakes with a magnitude greater than 3.0 occurred around the study area. Through calculation it was found that the inducive radius of 16 earthquakes was larger than the distance between the epicenter and the study area, and it proves that the study area is frequently affected by seismic activities. Furthermore, on the basis of calculation of rainfall anomaly index H from January 2011 to June 2012, it can be seen that the rainfall of 2011 is extremely low. The percentage of the rainfall anomaly index is almost less than −34%, which indicates that the drought in the basin is serious. Under the influences of repeated seismic activities and continuous droughts, the structure of soil was destroyed and its strength and permeability changed significantly, providing favorable conditions for debris flow initiation. On 28 June 2012, heavy rainfall with the intensity of 23.3 mm/h occurred, and the total amount of precipitation reached 66.1 mm before 6am of 28 June 2012. Debris flow was induced due to the triggering effect of the torrential rain. Studying the causes of the large-scale debris flows in construction sites can significantly facilitate the prevention and mitigation of future debris flow disasters, as well as reduce the potential of hazards caused by debris flows in major engineering areas

Mike 21 Model Based Numerical Simulation of the Operation Optimization Scheme of Sedimentation Basin

The sedimentation basin is an important part of hydraulic engineering. Because the prototype size is too large and not easy to analyze, Mike 21 has the advantages of easy input, conversion, analysis, and demonstration of data results, which are flexible and convenient; however, this method has not been used in hydraulic engineering by previous researchers. This research used the sedimentation basin of the Yellow River Diversion Project as the research object, and a simulation model of the sedimentation basin channel #1 was developed using Mike 21 software to analyze its water and sediment characteristics and conditions in different periods. Using numerical simulation methods, three types of sedimentation basin operation schemes were targeted, the sedimentation changes and sedimentation law of channel #1 were evaluated in each scheme, and the sedimentation effects were compared. The results show that in conditions of different incoming water and sediment and diversion timings during the flood and non-flood seasons, the sedimentation basin adopts an operation scheme to lower the outlet water level, and the siltation volumes are 180,000 and 150,000 m3 lower than the high-outlet water levels, respectively. Moreover, its siltation status is significantly improved, which can effectively extend the service life of the sedimentation basin, prolong the period of silting removal by about 3.5 months, and provide a scientific basis and reference for the optimization of the operation mode of the sedimentation basin in other types of hydraulic engineering

PLXNC1 interference alleviates the inflammatory injury, apoptosis and extracellular matrix degradation of IL-1β-exposed chondrocytes via suppressing GRP78 expression

Abstract Background Osteoarthritis (OA) is a frequently encountered debilitating joint disorder. Whether plexin C1 (PLXNC1) is implicated in OA is far from being investigated despite its well-documented pro-inflammatory property in human diseases. The goal of this study is to expound the specific role of PLXNC1 in OA and elaborate the probable action mechanism. Methods Firstly, PLXNC1 expression in the cartilage tissues of patients with OA was examined with GEO database. In interleukin-1beta (IL-1β)-induced OA cell model, RT-qPCR and western blotting tested the expression of PLXNC1, glucose-regulating protein 78 (GRP78) and extracellular matrix (ECM) degradation-related factors. Cell viability and inflammation were respectively judged by CCK-8 assay and RT-qPCR. TUNEL and western blotting estimated cell apoptosis. The potential binding between PLXNC1 and GRP78 was corroborated by Co-IP assay. Western blotting also tested the expression of endoplasmic reticulum stress (ERS)-associated proteins. Results As it turned out, PLXNC1 expression was elevated in the cartilage tissues of patients with OA and IL-1β-treated chondrocytes. When PLXNC1 was depleted, the viability injury, inflammation, apoptosis and ECM degradation of chondrocytes exposed to IL-1β were obstructed. Besides, GRP78 bond to PLXNC1 in IL-1β-treated chondrocytes. The ascending GRP78 expression in the chondrocytes exposed to IL-1β was depleted after PLXNC1 was silenced. Meanwhile, the impacts of PLXNC1 deficiency on the viability, inflammatory response, apoptosis, ECM degradation as well as ERS in IL-1β-exposed chondrocytes were abolished by GRP78 up-regulation. Conclusion In summary, PLXNC1 silencing might interact with and down-regulate GRP78 to mitigate the apoptosis, inflammation, and ECM degradation of IL-1β-insulted chondrocytes in OA