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Abstract Deoxyhypusine synthase (DHPS) is an enzyme encoded by the DHPS gene, with high expression in various cancers, including ovarian cancer (OC). DHPS regulates the translation initiation factor EIF5A, and EIF5A2 knockout inhibits OC tumor growth and metastasis by blocking the epithelial-to-mesenchymal transition (EMT) and the TGFβ pathway. In this study, we show that DHPS is amplified in OC patients, and its elevated expression correlates with poor survival. Using lentiviral CRISPR/Cas9 vectors for DHPS knockout, we observed EMT inhibition in SKOV3 and OVCAR8 cells through suppressed hypusination and reduced EIF5A2 expression. Inhibition of DHPS activity with GC7 similarly blocked hypusination and EMT. Disrupting DHPS expression, either genetically or pharmacologically, inhibited primary tumor growth and metastasis in OC mouse models. These findings suggest that targeting DHPS and inhibiting hypusination could be promising strategies for OC treatment.

BackgroundIn recent years, extensive research has been conducted on endometrial receptivity (ER), with rapidly evolving research hotspots and trends. Our study aimed to explore the development of ER research from 2000 to the present and provide insights for future endeavors.Materials and methodsRelevant research publications on ER from 2000 to 2024 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace, VOSviewer and Excel tools were employed to conduct the bibliometric analysis.ResultsA total of 3,354 articles were analyzed, revealing an overall upward trend in annual publication numbers, signifying the increasing attractiveness and research value of this field. Globally, China led with a notable advantage of 1,030 publications, followed by the United States (650) and Spain (251), constituting the first tier of international research. Valencia University topped the list of institutions with 108 publications, closely followed by Shanghai Jiao Tong University with 87. Fertility and Sterility (IF6.6, Q1) is the one with the largest number of publications, accounting for 7.96% of the total publications. The three most co-cited journals were Fertility and Sterility, Biology of Reproduction, and Human Reproduction. A co-citation reference analysis revealed that ER research can be categorized into ten major subfields, including embryo implantation, frozen embryo transfer, integrins, recurrent implantation failure, intrauterine adhesions, etc. Since 2020, the keywords with the strongest citation bursts include repeated implantation failure and frozen.ConclusionThis study employs bibliometric analysis to offer researchers in the field of ER a comprehensive perspective. Since 2000, there has been a remarkable surge in the number of publications in the ER research field. These studies primarily concentrate on delving into the pathophysiological mechanisms of ER, with the primary objective of enhancing clinical pregnancy rates and live birth rates, benefiting more infertile patients. Currently, addressing the ER issues in patients with recurrent implantation failure represents the forefront of research. The primary treatment approaches currently in use involve optimizing embryo transfer timing and employing innovative strategies such as immunotherapy. These cutting-edge analyses not only provide new insights into the treatment of ER but also offer researchers fresh research directions, and staying abreast of the latest trends and advancements in the field.

Angelica sinensis polysaccharides are important active ingredients and biological resources in traditional Chinese medicine. Properly changing the fermentation conditions of microorganisms may alter the yield of fermentation products. Based on single factor test results, three factors with great influence on the yield of Angelica sinensis polysaccharides produced by Aspergillus niger were optimized: initial pH value, fermentation time, and culture temperature. According to the box Behnken central combination principle, a response surface analysis scheme with three factors and three levels was designed, and the yields of active polysaccharide of Angelica sinensis were taken as the response value to optimize the fermentation process. The results of response surface analysis showed that under the optimized fermentation temperature of 30 °C, cultivation time of 8 days, and initial pH value of 5, the predicted yield of active polysaccharides from Angelica sinensis was 15.5%, while the actual value was 15.35%, which was 0.11% lower than the predicted value. This indicated that using response surface analysis to optimize the fermentation conditions of Angelica sinensis polysaccharides was reasonable and feasible. This method can effectively improve the biological resource utilization rate of Angelica sinensis polysaccharides.

Abstract The dysregulation of Hippo signaling is a crucial factor driving the progression of gastric cancer, making the targeting of the Hippo pathway a promising therapeutic strategy. However, effective drugs targeting the Hippo/YAP axis remain unavailable. Thus, identifying potential therapeutic targets and mechanisms that inhibit the activity of the Hippo/YAP axis in gastric cancer is of paramount importance. The ubiquitination modification of the Hippo/YAP pathway plays a significant role in signaling transduction and cancer progression. In an effort to shed light on effective therapeutic targets, we conducted a screening using a deubiquitinase small interfering RNA library, leading to the identification of USP12 as an important deubiquitinase in the context of Hippo/YAP axis and the progression of gastric cancer. Our bioinformatic analysis further demonstrated a correlation between USP12 and poor survival, as well as a positive association with classical YAP target genes in gastric cancer samples. Notably, USP12 depletion was found to inhibit gastric cancer progression via the Hippo/YAP axis, whereas USP12 overexpression exhibited the opposite effect, promoting gastric cancer growth and enhancing YAP activity. Further studies through immuno-staining and immuno-precipitation assays indicated the nuclear localization of USP12 and its association with YAP to enhance YAP stability. Specifically, our findings revealed that USP12 could inhibit K48-linked poly-ubiquitination of YAP, predominantly at the K315 site. As a result, we have identified a novel regulatory mechanism involving USP12 and Hippo signaling in the progression of gastric cancer, with the potential for blockade of USP12 to materialize as a promising strategy for combating gastric cancer.

Abstract Background The Hippo pathway is crucial in organ size control and tumorigenesis. Dysregulation of the Hippo/YAP axis is commonly observed in gastric cancer, while effective therapeutic targets for the Hippo/YAP axis are lacking. Identification of reliable drug targets and the underlying mechanisms that could inhibit the activity of the Hippo/YAP axis and gastric cancer progression is urgently needed. Methods We used several gastric cancer cell lines and xenograft models and performed immunoblotting, qPCR, and in vivo studies to investigate the function of CXCR7 in gastric cancer progression. Results In our current study, we demonstrate that the membrane receptor CXCR7 (C-X-C chemokine receptor 7) is an important modulator of the Hippo/YAP axis. The activation of CXCR7 could stimulate gastric cancer cell progression through the Hippo/YAP axis in vitro and in vivo, while pharmaceutical inhibition of CXCR7 via ACT-1004–1239 could block tumorigenesis in gastric cancer. Molecular studies revealed that the activation of CXCR7 could dephosphorylate YAP and facilitate YAP nuclear accumulation and transcriptional activation in gastric cancer. CXCR7 functions via G-protein Gαq/11 and Rho GTPase to activate YAP activity. Interestingly, ChIP assays showed that YAP could bind to the promoter region of CXCR7 and facilitate its gene transcription, which indicates that CXCR7 is both the upstream signalling and downstream target of the Hippo/YAP axis in gastric cancer. Conclusion In general, we identified a novel positive feedback loop between CXCR7 and the Hippo/YAP axis, and blockade of CXCR7 could be a plausible strategy for gastric cancer.

Honeycomb structures serve as the core of sandwich structures in various industries, such as aerospace and rail transit. In this study, a novel design was introduced where hexagonal honeycomb cores were flattened in specific areas to form S-shaped reinforced cores. Compression tests were conducted on S-shaped reinforced honeycomb cores with different rotational structures – left-hand, right-hand, and mixed rotation. The deformation process of these cores was thoroughly investigated. Additionally, a theoretical prediction model was proposed to determine the Young's modulus and peak load of S-shaped reinforced honeycomb cores. The experimental data was compared with the theoretical model to validate its accuracy. Moreover, the study examined the effects of changing the relative density and cell wall angle of S-shaped reinforced honeycomb cores on the peak and specific peak loads. The results demonstrated that the use of S-shaped reinforced structures successfully altered the deformation mode of the honeycomb cores. In particular, the peak loads of S-LL and S-LR specimens were 29.14% and 86.12% higher than that of plain honeycomb, respectively. In summary, increasing the relative density of S-shaped reinforced honeycomb cores proved to enhance the peak load and specific peak load, thereby augmenting the design capabilities of these cores.

Highlights 1. DUB1 is an important modulator of Hippo signaling in gastric cancer. 2. DUB1 expression is elevated in human gastric cancer samples and correlates with poor survival in gastric cancer. 3. DUB1 facilitates gastric cancer progression via the Hippo/TAZ axis. 4. DUB1 associates with TAZ and directly inhibits YAP polyubiquitination and degradation.

Abstract Background Although high serum cholesterol is widely recognized as a major risk factor for heart disease, the health effects of low cholesterol are less clear. Several studies have found a correlation between low cholesterol and depression, but the results are inconsistent. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were utilized in this cross-sectional study. The analysis of the relationship between cholesterol and depression was performed at three levels: low total cholesterol, low high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. The inclusion criteria were as follows: (1) people with low (

Promoting cropland carbon (C) sequestration through straw return has always been the focus of numerous studies. However, there is still a lack of comprehensive understanding of the straw return effects on soil organic carbon (SOC) and soil inorganic carbon (SIC) sequestration. Therefore, the present study aims to investigate the effects of long-term straw return on SOC and SIC sequestration across the 0–100 cm soil profile in the maize planting cropland in Northeastern China. The results showed an increasing trend in SOC contents in the 0–100 cm soil profile following long-term straw return, while significant decreases in SIC contents were observed in the surface (0–20 cm) and subsoil (20–60 cm) layers, respectively. In addition, the SOC stock increased significantly in the subsoil layer following long-term straw return, by an average value of 44%, which is higher than those observed in other soil layers. On the other hand, the SIC stock in the subsoil layer increased by an average value of 24% and decreased in the surface and under-subsoil layers by average values of 53% and 33%, respectively. Moreover, the exchangeable calcium contents were positively correlated with SOC and SIC stock, demonstrating the soil calcium contributes to SOC and SIC sequestration. The present study highlighted the importance of the subsoil layer for effective straw return strategies in cropland to promote SOC and SIC sequestration in croplands.

The tight gas reservoirs of the Xujiahe Formation in western Sichuan Depression have become an important field for expanding oil and gas exploration and discovering new reserves.The development characteristics of tight gas reservoirs and their accumulation mechanism have become one of the key scientific problems that need to be solved urgently. Applied geochemistry, geophysics and sedimentology analysis methods, systematic analysis of the source and reservoir characteristics and accumulation model of the Xu-3 Member was conducted, and the high-efficiency source rocks and high-quality reservoirs were identified and predicted. The accumulation period and accumulation mode were determined.The following conclusions were drawn: ①The lacustrine source rocks in the mature and highly mature stage of the Xu-3 Member in western Sichuan Depression are dominated by type Ⅲ kerogen, and occasionally type Ⅱ2 kerogen.It is developed as a high-efficiency source rock when it is developed near the largest lake flooding surface in the lower sub-segment of Xu-3, with shale content above 65% or a single layer with a large thickness and requiring 1.50% ≤ TOC ≤ 10%.②According to the median value of sandstone grain size, the 4th stage (S1, S2, S3 and S4) high-quality reservoirs were identified, which belonged to low-porosity and ultra-low-permeability-ultra-low-porosity and ultra-low-permeability tight reservoirs. Reservoir space is dominated by secondary pores, micropores and microfractures.Most developed in the front edge of the delta and a small amount developed in the front delta.The particle size distribution range is 0.5-0.062 5 mm, the thickness is generally 5-10 m.③The hydrocarbon generation and expulsion time of the Xu-3 Member source rock in western Sichuan Depression lasted longer, and the Middle Jurassic began to generate hydrocarbons until the end of the Early Cretaceous; the Late Jurassic began to expel hydrocarbons and reached a peak at the end of the Early Cretaceous.High-quality reservoirs experience early natural gas continuous charging and late condensate gas charging.The natural gas charging time is earlier than the condensate gas charging time.The accumulation mode of tight gas reservoirs in the Xu-3 Member is "vertical fault transmission, first gathering and then dense, and later transformation and adjustment".

With the rapid development of shale gas exploration and development in China, casing deformation in shale gas horizontal wells happens frequently, which directly impacts the development efficiency and benefits of shale gas. In order to explore casing deformation prediction, prevention and treatment methods, this paper analyzes the geological and engineering causes of casing deformation in shale-gas horizontal wells through laboratory work, such as the casing resistance to internal pressure alternating test, the ground simulation test and systematical casing deformation characteristic analysis of MIT24 caliper logging, and the large-scale physical simulation test and numerical simulation of casing deformation. Then, combined with the generalized shear activity criterion, a new method for evaluating casing deformation risk points and some technical measures for preventing casing deformation were formulated. And the following research results were obtained. First, the deformation characteristics of 119 casing deformation points in 23 wells interpreted by MIT24 caliper logging are consistent with the mechanical behaviors of shear compression deformation test. Second, the large-scale physical simulation test shows that natural fault-fractures slip obviously under the state of strike-slip stress. Third, numerical simulation shows that the compression stress on casing increases with the increase of fault-fracture slip. When the fault-fracture slip is between 7.5 mm and 9.0 mm, the casing reaches the critical yield strength and begins to undergo plastic deformation. The “temporary fracture plugging + long segment and multi-cluster” and other technologies are field tested in 28 wells in Weiyuan area of southern Sichuan Basin. The casing deformation rate decreases from 54% (before this research) to 14.3%, and the segment loss rate decreases from 7.8% to 0, which reveals remarkable achievements in casing deformation treatment. In conclusion, the shear slip of fault and macro fractures (referred to as fault-fracture) is the main cause of casing deformation in shale gas horizontal wells, and some measures (e.g. “temporary fracture plugging + long segment and multi-cluster”, reducing fracturing scale and releasing wellbore pressure properly) shall be taken in advance to reduce the fault-fracture activity before the risk point of casing deformation is fractured, so as to reach the goal of casing deformation prevention.

Atmospheric deposition of nitrogen (N) and phosphorus (P) far exceeding the pre-industrial levels have the potential to change carbon (C) dynamics in northern peatlands. However, the responses of soil C concentration and organo-chemical composition to different rates and durations of nutrient enrichment are still unclear. Here, we compared the short- (3 years) and long-term (10 years) effects of N and P fertilizations on the physicochemical properties of peat and porewater in a bog-fen complex in northern China. Our results showed that the short-term fertilization increased Sphagnum moss cover, while the expansion of vascular plants was observed owing to the long-term fertilization. The preserved soil C did not vary considerably after the short- and long-term fertilizations. The harsh soil conditions may impede the decomposition of organic matters by soil microorganisms during the short-term fertilization. For the long-term fertilization, the input of high-phenolic litters owing to vascular plant expansion likely exerted an important control on soil C dynamics. These processes constrained the variation in soil C concentrations when the addition rate and cumulative amount of external N and P increased, which will advance our understanding and prediction of the resilience of soil C storage to imbalanced nutrient enrichment of N and P in northern peatlands.

Soil fungal communities are key players in biogeochemical processes of peatlands, which are important carbon stocks globally. Although it has been elucidated that fungi are susceptible to environmental changes, little is known about the intricate and interactive effect of long-term nitrogen (N) and phosphorus (P) enrichment on fungal community structure in northern peatlands. In this study, we compared a short- (2 years) with a long-term (10 years) fertilization experiment in a peatland complex in northeastern China to assess how N and/or P additions influence fungal community structure. The results showed that fungal community composition and diversity were altered by N addition, without a significant interactive effect with P addition. Not only the long-term but also the short-term nutrient addition could change the abundance of different plant functional types. However, there were no strong cascading effects on the fungal community in any of the fertilization experiments. Long-term nutrient addition showed a stronger effect on the relative abundance of different fungal functional guilds; an increase in the relative abundance of saprotrophs after fertilization did not jeopardize mycorrhizal fungi. Moreover, the decline in Sphagnum cover after long-term N addition did not parallel changes in the relative abundance of Sphagnum-associated fungi (Clavaria sphagnicola, Galerina tibiicystis, G. sphagnicola, and G. paludosa). Given that short- and long-term fertilization showed strongly contrasting effects on fungal community structure, our study highlights the necessity of assessing the long-term effects of nutrient enrichment on the association between vegetation and fungal community in peatland ecosystems. Future research priorities should emphasize the connection between the community structure of fungal functional guilds and their functionality, which is of paramount importance to better understand their influences on C storage in the face of uncertain N and P deposition regimes.

The gas reservoir of Upper Triassic Xujiahe Fm in the Sichuan Basin is characterized by “accumulation in the early stage, entrapment in the middle stage and activation in the late stage”. In order to provide guidance for the prediction of hydrocarbon enrichment zone of Xujiahe Fm, we first plotted the regional structure map based on the 2D and 3D seismic merging data of the basin. Then, we displayed and described the structural characteristics by means of the 3D visualization technology of low-angle vertical backlight irradiation. In addition, the structural system was classified according to the dynamic direction of regional structure and the structural interrelationship, and the formation stages of the structure were confirmed. Finally, based on drilling and testing data, the hydrocarbon enrichment zone of Xujiahe Fm was predicted. And the following research results were obtained. First, five structural systems are developed in Xujiahe Fm in the Sichuan Basin, including EW-oriented arc structure, NE-oriented linear structure, NE-oriented arc structure, SN-oriented to NW-oriented brush structure and NW-oriented arc structure. Second, the EW-oriented arc structure is formed due to the uplift and extrusion of the northern section of Longmenshan thrust belt in the Indosinian period, successively developed in the Yanshanian and stabilized in the Himalayan period. And it is widely distributed in the basin. Third, the NE-oriented linear structure in the north of Western Sichuan Depression is resulted from the Anxian movement of Longmenshan thrust belt in the Indosinian period. Fourth, the NW-oriented arc structure before the Dabashan and the NE-oriented linear structure before the Huaying Mountain are stabilized in the Yanshanian and successively developed in the Himalayan period. Fifth, the SN-oriented structure in the Western Sichuan Depression is formed due to the extrusion of the southern section of Longmenshan thrust belt in the Himalayan period. Sixth, the combination of SN structure to the east of Longquanshan fold belt and NW-oriented linear structure in the basin is a brush structure belt with Jiangyou paleo-uplift as the mainstay, which is resulted from the extrusion of the southern section of Longmenshan thrust belt in the Himalayan period. Seventh, the high-yield wells are usually distributed in the arc anticlines of Indosinian–Yanshanian superimposed with the faults of Himalayan period. The structures of the Himalayan period are usually dry traps, and their fracture development zones are mostly water producing layers. The Indosinian synclines are also ineffective traps even though they are uplifted to anticlines in the Himalayan period. In conclusion, the confirmation of structural system stages can provide a technical support for the prediction and description of hydrocarbon enrichment zone of Xujiahe Fm in the Sichuan Basin. Keywords: Sichuan Basin, Western Sichuan depression, Late Triassic, Xujiahe Fm, Structural characteristics, Structural system, Formation stage, Prediction of hydrocarbon enrichment zone

The modification of protein cysteine residues underlies some of the diverse biological functions of nitric oxide (NO) in physiology and disease. The formation of stable nitrosothiols occurs under biologically relevant conditions and time scales. However, the factors that determine the selective nature of this modification remain poorly understood, making it difficult to predict thiol targets and thus construct informatics networks. In this review, the biological chemistry of NO will be considered within the context of nitrosothiol formation and degradation whilst considering how specificity is achieved in this important post-translational modification. Since nitrosothiol formation requires a formal one-electron oxidation, a classification of reaction mechanisms is proposed regarding which species undergoes electron abstraction: NO, thiol or S-NO radical intermediate. Relevant kinetic, thermodynamic and mechanistic considerations will be examined and the impact of sources of NO and the chemical nature of potential reaction targets is also discussed.

Nuclear thermal propulsion (NTP) is regarded as the preferred option for the upcoming crewed interstellar exploration due to its excellent performance compared to the current most advanced chemical propulsion systems. Over the past several decades, many novel concepts have been proposed, among which the particle bed reactor (PBR) is the most efficient, compact, and lightweight method. Its unique features, such as the extremely high power density and the radial flow path of coolant in the fuel region, introduce many challengeable issues to the thermal hydraulic design of PBR, with the flow distribution being representative. In this work, the flow distribution process within the core is analyzed based on the understanding of the axial pressure profile in a dummy PBR. A “flow shift” phenomenon leading to the hot spot in the core is introduced first, and three methods, i.e., decreasing the pressure drop within the hot gas channel, increasing the flow resistance on the cold frit or hot frit, and changing the flow pattern from “Z” to “U”, are proposed to reduce the “flow shift” and the consequent temperature mal-distribution. The pros and cons of using cold frit or hot frit to distribute the coolant are also discussed. Finally, by using three numerical examples, these analyses are demonstrated. The findings here may provide technical support for PBR design.