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Ground hydraulic fracturing plays a crucial role in controlling the far-field hard roof, making it imperative to identify the most suitable target stratum for effective control. Physical experiments are conducted based on engineering properties to simulate the gradual collapse of the roof during longwall top coal caving (LTCC). A numerical model is established using the material point method (MPM) and the strain-softening damage constitutive model according to the structure of the physical model. Numerical simulations are conducted to analyze the LTCC process under different hard roofs for ground hydraulic fracturing. The results show that ground hydraulic fracturing releases the energy and stress of the target stratum, resulting in a substantial lag in the fracturing of the overburden before collapse occurs in the hydraulic fracturing stratum. Ground hydraulic fracturing of a low hard roof reduces the lag effect of hydraulic fractures, dissipates the energy consumed by the fracture of the hard roof, and reduces the abutment stress. Therefore, it is advisable to prioritize the selection of the lower hard roof as the target stratum.

Multi-stage fracturing in Horizontal well increases the permeability of coalbed methane by generating multiple fractures. However, the heterogeneity of coal reservoirs is a crucial factor that cannot be ignored in the study of multiple hydraulic fracture propagation. Therefore, we established a two-dimensional model for multiple hydraulic fracture propagation based on the combined finite-discrete element method (FDEM) and assigned a Weibull distribution function to the heterogeneity of the physical parameters of the cohesive elements in the model. The objective was to simulate and study the fracture propagation law of multi-cluster fracturing in horizontal wells in heterogeneous coal reservoirs. The research results indicated that: 1) as the heterogeneity of the coal reservoir weakened, the deflection angle of the main fracture increased. More secondary fractures were generated in the coal reservoir, leading to significant discontinuity. 2) The fracturing disturbance area was always concentrated at the tip of the main fracture, with a double wing shape. However, the fracturing disturbance areas at the tips of multiple main fractures could easily converge, with a square shape; 3) It is recommended to use a moderate injection rate and increase the perforation spacing appropriately when hydraulic fracturing is carried out in coal reservoirs with a heterogeneity coefficient m=5.

Abstract The induction of type-I interferons (IFN-Is) is important for the efficacy of chemotherapy. By investigating the role of amino acids in regulation of IFN-I production under chemo-drug treatment in bladder cancer (BC) cells, we find an inherent AhR-dependent negative feedback to restrain STING signaling and IFN-I production. Mechanistically, in a ligand dependent manner, AhR bridges STING and CUL4B/RBX1 E3 ligase complex, facilitating STING degradation through ubiquitin-proteasome pathway. Inhibition of AhR increases STING levels and reduces tumor growth under cisplatin or STING agonist treatment. Endogenous AhR ligands are mainly consisted of tryptophan (Trp) metabolites; dietary Trp restriction, blocking the key Trp metabolism rate-limiting enzyme IDO1 or inhibition of cellular Trp importation also show similar effect as AhR inhibition. Clinically, BC patients with higher intratumoral expression of AhR or stronger intratumoral Trp metabolism (higher IDO1 or Kyn levels) that lead to higher AhR activation show worse response rate to neoadjuvant chemotherapy (NAC).

Summary: Dysregulation of transcription is a hallmark of cancer, including bladder cancer (BLCA). CRISPR-Cas9 screening using a lentivirus library with single guide RNAs (sgRNAs) targeting human transcription factors and chromatin modifiers is used to reveal genes critical for the proliferation and survival of BLCA cells. As a result, the nuclear transcription factor Y subunit gamma (NFYC)-37, but not NFYC-50, is observed to promote cell proliferation and tumor growth in BLCA. Mechanistically, NFYC-37 interacts with CBP and SREBP2 to activate mevalonate pathway transcription, promoting cholesterol biosynthesis. However, NFYC-50 recruits more of the arginine methyltransferase CARM1 than NFYC-37 to methylate CBP, which prevents the CBP-SREBP2 interaction and subsequently inhibits the mevalonate pathway. Importantly, statins targeting the mevalonate pathway can suppress NFYC-37-induced cell proliferation and tumor growth, indicating the need for conducting a clinical trial with statins for treating patients with BLCA and high NFYC-37 levels, as most patients with BLCA have high NFYC-37 levels.

Background: Despite rapid advances in the treatment of prostate cancer (PCa), the optimal treatment for elderly patients with PCa remains unclear due to a lack of high-quality evidence. This study aimed to evaluate whether surgical procedures are beneficial for PCa patients aged 75 years and older and compare the effects of focal ablation and prostatectomy. Methods: Male patients aged 75 years and older who were diagnosed with Tis-T2/N0/M0 PCa between 2000 and 2017 were retrospectively identified from the Surveillance, Epidemiology, and End Results program database. Cox regression models were used to test for statistical differences between the overall survival (OS) and disease-specific survival (DSS). Results: A total of 114,506 patients aged 75 years and older with PCa were included in this study, among which 60,131 died during the study period. The most prevalent surgical procedure for these patients was focal ablation. The local excision rate increased with advancing age, while the prostatectomy rate decreased sharply with age. The proportion of the elderly patients who underwent a focal ablation also increased with the age at diagnosis. The survival rate of patients aged 75 years and older who underwent a focal ablation was significantly worse than that for those who did not undergo any surgical procedures (OS: HR, 1.32, P

Aims: To develop, optimize, and validate a novel model using alanine aminotransferase (ALT) and total bilirubin (TB) dynamic evolution patterns in predicting acute liver failure (ALF) in drug-induced liver injury (DILI) patients.Methods: The demographics, clinical data, liver biopsy, and outcomes of DILI patients were collected from two hospitals. According to the dynamic evolution of ALT and TB after DILI onset, the enrolled patients were divided into ALT-mono-peak, TB-mono-peak, double-overlap-peak, and double-separate-peak (DSP) patterns and compared. Logistic regression was used to develop this predictive model in both discovery and validation cohorts.Results: The proportion of ALF was significantly higher in patients with the DSP pattern than in the ALT-mono-peak pattern and DOP pattern (10.0 vs. 0.0% vs. 1.8%,p < 0.05). The area under receiver operating characteristic curve (AUROC) of the DSP pattern model was 0.720 (95% CI: 0.682–0.756) in the discovery cohort and 0.828 (95% CI: 0.788–0.864) in the validation cohort in predicting ALF, being further improved by combining with international normalized ratio (INR) and alkaline phosphatase (ALP) (AUROC in the discovery cohort: 0.899; validation cohort: 0.958). Histopathologically, patients with the DSP pattern exhibited a predominantly cholestatic hepatitis pattern (75.0%, p < 0.05) with a higher degree of necrosis (29.2%, p = 0.084).Conclusion: DILI patients with the DSP pattern are more likely to progress to ALF. The predictive potency of the model for ALF can be improved by incorporating INR and ALP. This novel model allows for better identification of high-risk DILI patients, enabling timely measures to be instituted for better outcome.

Abstract Background To assess the correlation between lumbar disc degeneration (LDD), multifidus muscle atrophy (LMA), and facet joints degeneration in patients with L4-L5 lumbar disc herniation (LDH). Methods Sixty patients with L4-L5 LDH diagnosed by a 1.5 T MRI scanner were enrolled in the study group and another 60 patients with non-specific back pain were enrolled in the control group. LDD, LMA, and facet joints degeneration were examined and analyzed independently by two independent orthopedic surgeons using T2-weighted images. Wilcoxon test was used for analyzing the difference of LDD and facet joints degeneration between L3-L4 and L5-S1 and difference of LMA between the herniated and control groups. Correlation analysis of the three degeneration grades at the same level was determined by Spearman rank correlation test. Results In the herniated group, most LMA at L3-L4 level was grade 1 (42, 70.0%); grade 2 (33, 55.0%) at L4-L5 level; and grade 3 (27, 45.0%) at L5-S1 level. LMA and LDD grading were significantly different between L3-L4 and L5-S1 levels (P 0.05) at the L5-S1 level. The differences in LMA between the herniated and control groups at the three levels were significant (P

Herbaceous plants contribute greatly to plant diversity and play an important role in regulating the structure and functioning of forest ecosystems. Comparing with woody species, herbs exhibit higher sensitivity to seasonal changes from spring-growth to autumn-mortality. Despite extensive research on understory herb diversity (e.g., abundance and richness) in forests, how the underlying mechanisms change across seasons remain unclear, especially in temperate forests. We explored the seasonal dynamics of herb diversity (here abundance and richness) by surveying herbs of 174 quadrats (1 m × 1 m) in a 25-ha (500 m × 500 m) temperate forest in spring, summer, and autumn of 2022, respectively. We examined the effects of overstory trees (diversity, composition, and three-dimensional (3D) structural complexity detected by LiDAR), topography (elevation, slope, and aspect), and microsite conditions (light availability, soil nutrients, and soil water content) on herb diversity in different seasons. We found a similar seasonal pattern for herb abundance and richness, i.e., both decreased from spring to summer and then to autumn, but the driving mechanisms differed remarkably across seasons. Specifically, the importance of overstory trees, topography, and microsite conditions on herb abundance vs. richness varied inversely across seasons. For herb abundance, the importance of overstory trees (primarily 3D structural complexity) increased from spring to autumn, while the importance of topography decreased. Conversely, for herb richness, the importance of overstory trees decreased from spring to autumn, while the importance of topography increased. Microsite conditions governed spatial variations of herb abundance in all seasons but only in autumn for herb richness, with importance of soil nutrients remaining relatively constant while that of soil water content and light availability changed greatly across seasons. Our results demonstrate substantial seasonal variations in driving mechanisms of herb diversity in the temperate forest. These differentiated responses of herb abundance and richness to different drivers across seasons further highlight the significance of considering seasonal variations of the mechanisms underlying understory plant diversity in forest biodiversity conservation.

Biodiversity, large trees, and environmental conditions such as climate and soil have important effects on forest carbon stocks. However, recent studies in temperate forests suggest that the relative importance of these factors depends on tree mycorrhizal associations, whereby large-tree effects may be driven by ectomycorrhizal (EM) trees, diversity effects may be driven by arbuscular mycorrhizal (AM) trees, and environment effects may depend on differential climate and soil preferences of AM and EM trees. To test this hypothesis, we used forest-inventory data consisting of over 80,000 trees from 631 temperate-forest plots (30 m ​× ​30 ​m) across Northeast China to examine how biodiversity (species diversity and ecological uniqueness), large trees (top 1% of tree diameters), and environmental factors (climate and soil nutrients) differently regulate aboveground carbon stocks of AM trees, EM trees, and AM and EM trees combined (i.e. total aboveground carbon stock). We found that large trees had a positive effect on both AM and EM tree carbon stocks. However, biodiversity and environmental factors had opposite effects on AM vs. EM tree carbon stocks. Specifically, the two components of biodiversity had positive effects on AM tree carbon stocks, but negative effects on EM tree carbon stocks. Environmental heterogeneity (mean annual temperature and soil nutrients) also exhibited contrasting effects on AM and EM tree carbon stocks. Consequently, for the total carbon stock, the positive large-tree effect far surpasses the diversity and environment effect. This is mainly because when integrating AM and EM tree carbon stock into total carbon stock, the opposite diversity-effect (also environment-effect) on AM vs. EM tree carbon stock counteracts each other while the consistent positive large-tree effect on AM and EM tree carbon stock is amplified. In summary, this study emphasized a mycorrhizal viewpoint to better understand the determinants of overarching aboveground carbon profile across regional forests.

As a vital component of biodiversity, phyllosphere bacteria in forest canopy play a critical role in maintaining plant health and influencing the global biogeochemical cycle. There is limited research on the community structure of phyllosphere bacteria in natural forests, which creates a gap in our understanding of whether and/or how phyllosphere bacteria are connected to leaf traits of their host. In this study, we investigated the bacterial diversity and composition of the canopy leaves of six dominant tree species in deciduous broad-leaved forests in northeastern China, using high-throughput sequencing. We then compare the differences in phyllosphere bacterial community structure and functional genes of dominant tree species. Fourteen key leaf functional traits of their host trees were also measured according to standard protocols to investigate the relationships between bacterial community composition and leaf functional traits. Our result suggested that tree species with closer evolutionary distances had similar phyllosphere microbial alpha diversity. The dominant phyla of phyllosphere bacteria were Proteobacteria, Actinobacteria, and Firmicutes. For these six tree species, the functional genes of phyllosphere bacteria were mainly involved in amino acid metabolism and carbohydrate metabolism processes. The redundancy and envfit analysis results showed that the functional traits relating to plant nutrient acquisition and resistance to diseases and pests (such as leaf area, isotope carbon content, and copper content) were the main factors influencing the community structure of phyllosphere bacteria. This study highlights the key role of plant interspecific genetic relationships and plant attributes in shaping phyllosphere bacterial diversity.

Soil respiration in forests contributes to significant carbon dioxide emissions from terrestrial ecosystems but it varies both spatially and seasonally. Both abiotic and biotic factors influence soil respiration but their relative contribution to spatial and seasonal variability remains poorly understood, which leads to uncertainty in models of global C cycling and predictions of future climate change. Here, we hypothesize that tree diversity, soil diversity, and soil properties contribute to local-scale variability of soil respiration but their relative importance changes in different seasons. To test our hypothesis, we conducted seasonal soil respiration measurements along a local-scale environmental gradient in a temperate forest in Northeast China, analyzed spatial variability of soil respiration and tested the relationships between soil respiration and a variety of abiotic and biotic factors including topography, soil chemical properties, and plant and soil diversity. We found that soil respiration varied substantially across the study site, with spatial coefficients of variation (CV) of 29.1%, 27.3% and 30.8% in spring, summer, and autumn, respectively. Soil respiration was consistently lower at high soil water content, but the influence of other factors was seasonal. In spring, soil respiration increased with tree diversity and biomass but decreased with soil fungal diversity. In summer, soil respiration increased with soil temperature, whereas in autumn, soil respiration increased with tree diversity but decreased with increasing soil nutrient content. However, soil nutrient content indirectly enhanced soil respiration via its effect on tree diversity across seasons, and forest stand structure indirectly enhanced soil respiration via tree diversity in spring. Our results highlight that substantial differences in soil respiration at local scales was jointly explained by soil properties (soil water content and soil nutrients), tree diversity, and soil fungal diversity but the relative importance of these drivers varied seasonally in our temperate forest.