Enhancing Water Resistance and Mechanical Properties of Cemented Soil with Graphene Oxide.

Although cemented soil as a subgrade fill material can meet certain performance requirements, it is susceptible to capillary erosion caused by groundwater. In order to eliminate the hazards caused by capillary water rise and to summarize the relevant laws of water transport properties, graphene oxide (GO) was used to improve cemented soil. This paper conducted capillary water absorption tests, unconfined compressive strength (UCS) tests, softening coefficient tests, and scanning electron microscope (SEM) tests on cemented soil using various contents of GO. The results showed that the capillary water absorption capacity and capillary water absorption rate exhibited a decreasing and then increasing trend with increasing GO content, while the UCS demonstrated an increasing and then decreasing trend. The improvement effect is most obvious when the content is 0.09%. At this content, the capillary absorption and capillary water absorption rate were reduced by 25.8% and 33.9%, respectively, and the UCS at 7d, 14d, and 28d was increased by 70.32%, 57.94%, and 61.97%, respectively. SEM testing results demonstrated that GO reduces the apparent void ratio of cemented soil by stimulating cement hydration and promoting ion exchange, thereby optimizing the microstructure and improving water resistance and mechanical properties. This research serves as a foundation for further investigating water migration and the appropriate treatment of GO-modified cemented soil subgrade.

Comparative transcriptome and metabolome profiles of the leaf and fruits of a Xianjinfeng litchi budding mutant and its mother plant.

Background: Litchi (Litchi chinensis) is an important sub-tropical fruit in the horticulture market in China. Breeding for improved fruit characteristics is needed for satisfying consumer demands. Budding is a sustainable method for its propagation. During our ongoing breeding program, we observed a litchi mutant with flat leaves and sharp fruit peel cracking in comparison to the curled leaves and blunt fruit peel cracking fruits of the mother plant. Methods: To understand the possible molecular pathways involved, we performed a combined metabolome and transcriptome analysis. Results: We identified 1,060 metabolites in litchi leaves and fruits, of which 106 and 101 were differentially accumulated between the leaves and fruits, respectively. The mutant leaves were richer in carbohydrates, nucleotides, and phenolic acids, while the mother plant was rich in most of the amino acids and derivatives, flavonoids, lipids and organic acids and derivatives, and vitamins. Contrastingly, mutant fruits had higher levels of amino acids and derivatives, carbohydrates and derivatives, and organic acids and derivatives. However, the mother plant's fruits contained higher levels of flavonoids, scopoletin, amines, some amino acids and derivatives, benzamidine, carbohydrates and derivatives, and some organic acids and derivatives. The number of differentially expressed genes was consistent with the metabolome profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enriched gene expressions showed consistent profiles as of metabolome analysis. Conclusion: These results provide the groundwork for breeding litchi for fruit and leaf traits that are useful for its taste and yield.

A Fanca knockout mouse model reveals novel Fancd2 function.

Fanconi anemia (FA) is a genetically and clinically heterogenous inherited disorder. Clinically, Fanca subtype patients exhibited milder phenotypes compared to Fancd2 subtypes. Increasing evidence suggests that Fancd2 perform independent functions, but the detailed mechanisms are not well characterized. In this study, we developed a Fanca KO mice model in C57BL/6 background with ATG region deletion, then performed a detailed FA phenotypes characterization and analysis with Fanca KO mice and Fancd2 KO mice in the same congenic background. We found that both the Fanca KO and Fancd2 KO cause severe FA phenotypes in mice. However, Fanca KO mice exhibited milder FA phenotypes comparing to Fancd2 KO mice. Fanca KO mice showed higher embryonic and postnatal survival rate, less congenital eye defects in early development. At adult stage, Fanca KO mice showed increased HSC number and reconstitution function. Furthermore, we did RNA-seq study and identified differential expression of Dlk1 and Dlk1 pathway genes in Fanca KO and Fancd2 KO embryonic cells and adult HSCs. Finally, we revealed that Fancd2 was expressed and physically interact with Dlk1 in Fanca KO cells. Collectively, our findings suggested that Fancd2 has distinct functions in the absence of Fanca.

Enhancement of dissolution rate and oral bioavailability of poorly soluble drug florfenicol by using solid dispersion and effervescent disintegration technology.

OBJECTIVE: Florfenicol(FF) is an excellent veterinary antibiotic, limited by poor solubility and poor bioavailability. SIGNIFICANCE: Here in, we aimed to explore the applicability of fast disintegrating tablets compressed from Florfenicol-loaded solid dispersions (FF-SD-FDTs) to improve the dissolution rate and oral bioavailability of Florfenicol. METHODS: Utilizing selecting appropriate preparation methods and carriers, the solid dispersions of Florfenicol (FF-SDs) were prepared by solvent evaporation and the fast disintegrating tablets (FF-SD-FDTs) were prepared by the direct compression (DC) method. RESULTS: The tablet properties including hardness, friability, disintegration time, weight variation, etc. all met the specifications of Chinese Veterinary Pharmacopeia(CVP). FF-SD-FDTs significantly improved drug dissolution and dispersion of FF in vitro compared to florfenicol conventional tablets (FF-CTs). A pharmacokinetics study in German shepherd dogs proved the AUC0-∞ and Cmax values of FF-SD-FDTs are 1.38 and 1.38 times more than FF-CTs, respectively. CONCLUSIONS: Overall, it can be concluded that FF-SD-FDTs with excellent disintegration and dissolution properties were successfully produced, which greatly improved the oral bioavailability of the poorly soluble drug FF, and the study provided a new idea for a broader role of FF in pet clinics.

Degradation of thermal stability and micromechanical properties of the C-S-H phase induced by ultra-confined water at elevated temperatures.

Water in the nanometer to micrometer-sized pores of calcium silicate hydrate (C-S-H) is essential for the binding process of cementitious materials. The quantity, location, and physical state of water in C-S-H pores under extreme conditions significantly influence the strength and durability of cementitious materials. The present study employed ReaxFF and molecular dynamics (MD) simulation to evaluate the effects of water ultra-confined in the nanopores on the structure, bonds, dynamics, and tensile mechanism of the C-S-H grains at elevated temperatures. The results indicate that the temperature elevation may interfere with the water molecule's hydrogen-bond network between the C-S-H grains, causing a notable nanometer-scale pore expansion. Simultaneously, the diffusion coefficient of water molecules confined in nanopores gradually increased, and their dynamic characteristics shifted from a glassy nature to free water. Additionally, high temperatures promoted hydrolysis reactions and the breakage of chemical bonds in the C-S-H framework, causing disintegration of the silicate skeleton and a decrease in the mechanical attributes of C-S-H. Moreover, the uniaxial tensile test at high temperatures revealed that the silicate chain groups in the C-S-H substrates underwent thermal curling. In contrast to interlayer-bound water, under the action of tension, water molecules in nanopores are viscous, forming water layers.

Collagen-Based Hydrogels for Cartilage Regeneration.

Cartilage regeneration remains difficult due to a lack of blood vessels. Degradation of the extracellular matrix (ECM) causes cartilage defects, and the ECM provides the natural environment and nutrition for cartilage regeneration. Until now, collagen hydrogels are considered to be excellent material for cartilage regeneration due to the similar structure to ECM and good biocompatibility. However, collagen hydrogels also have several drawbacks, such as low mechanical strength, limited ability to induce stem cell differentiation, and rapid degradation. Thus, there is a demanding need to optimize collagen hydrogels for cartilage regeneration. In this review, we will first briefly introduce the structure of articular cartilage and cartilage defect classification and collagen, then provide an overview of the progress made in research on collagen hydrogels with chondrocytes or stem cells, comprehensively expound the research progress and clinical applications of collagen-based hydrogels that integrate inorganic or organic materials, and finally present challenges for further clinical translation.

Corridor quality buffers extinction under extreme droughts in experimental metapopulations.

Corridors with good-quality habitats maintain the spatial dynamics of metapopulations by promoting dispersal between habitat patches, potentially buffering populations, and communities against continued global change. However, this function is threatened by habitats becoming increasingly fragmented, and habitat matrices becoming increasingly inhospitable, potentially reducing the resilience and persistence of populations. Yet, we lack a clear understanding of how reduced corridor quality interacts with rates of environmental change to destabilize populations. Using laboratory microcosms containing metapopulations of the Collembola Folsomia candida, we investigate the impact of corridor quality on metapopulation persistence under a range of simulated droughts, a key stressor for this species. We manipulated both drought severity and the number of patches affected by drought across landscapes connected by either good- or poor-quality corridors. We measured the time of metapopulation extinction, the maximum rate of metapopulation decline, and the variability of abundance among patches as criteria to evaluate the persistence ability of metapopulations. We show that while drought severity negatively influenced the time of metapopulation extinction and the increase in drought patches caused metapopulation decline, these results were mitigated by good-quality corridors, which increased metapopulation persistence time and decreased both how fast metapopulations declined and the interpatch variability in abundances. Our results suggest that enhancing corridor quality can increase the persistence of metapopulations, increasing the time available for conservation actions to take effect, and/or for species to adapt or move in the face of continued stress. Given that fragmentation increases the isolation of habitats, improving the quality of habitat corridors may provide a useful strategy to enhance the resistance of spatially structured populations.

B, N, and Si Single-Doping at Graphene/Cu (111) Interfaces to Adjust Electrical Properties.

We investigated the structural and electrical properties of B-, N-, and Si-doped graphene/Cu interfaces through density functional theory. B-doping enhances the interfacial bonding strength, N-doping has little effect on the interfacial interaction, and Si-Cu bonds are formed in the Si-doped interface. The energy bands and density of states show that the pristine and N-doped graphene/Cu interfaces exhibit n-type semiconductor properties, and the B-doped and Si-doped graphene/Cu interfaces exhibit p-type semiconductor properties. According to the Mulliken charge populations and charge properties, B-doping and Si-doping improve the ability of charge transport and orbital hybridization at the interface. Graphene doping has a significant effect on the interfacial work function. This result will help to understand the contact between B-, N-, and Si-doped graphene and Cu surfaces and to predict the performance of related micro-nano electronic devices.

Prognostic significance of perihematomal edema in basal ganglia hemorrhage after minimally invasive endoscopic evacuation.

OBJECTIVE: Spontaneous basal ganglia hemorrhage is a common type of intracerebral hemorrhage (ICH) with no definitive treatment. Minimally invasive endoscopic evacuation is a promising therapeutic approach for ICH. In this study the authors examined prognostic factors associated with long-term functional dependence (modified Rankin Scale [mRS] score ≥ 4) in patients who had undergone endoscopic evacuation of basal ganglia hemorrhage. METHODS: In total, 222 consecutive patients who underwent endoscopic evacuation between July 2019 and April 2022 at four neurosurgical centers were enrolled prospectively. Patients were dichotomized into functionally independent (mRS score ≤ 3) and functionally dependent (mRS score ≥ 4) groups. Hematoma and perihematomal edema (PHE) volumes were calculated using 3D Slicer software. Predictors of functional dependence were assessed using logistic regression models. RESULTS: Among the enrolled patients, the functional dependence rate was 45.50%. Factors independently associated with long-term functional dependence included female sex, older age (≥ 60 years), Glasgow Coma Scale score ≤ 8, larger preoperative hematoma volume (OR 1.02), and larger postoperative PHE volume (OR 1.03, 95% CI 1.01-1.05). A subsequent analysis evaluated the effect of stratified postoperative PHE volume on functional dependence. Specifically, patients with large (≥ 50 to < 75 ml) and extra-large (≥ 75 to 100 ml) postoperative PHE volumes had 4.61 (95% CI 0.99-21.53) and 6.75 (95% CI 1.20-37.85) times greater likelihood of long-term dependence, respectively, than patients with a small postoperative PHE volume (≥ 10 to < 25 ml). CONCLUSIONS: A large postoperative PHE volume is an independent risk factor for functional dependence among basal ganglia hemorrhage patients after endoscopic evacuation, especially with postoperative PHE volume ≥ 50 ml.

Linking trait network to growth performance of submerged macrophytes in response to ammonium pulse.

Extreme precipitation events caused by climate change leads to large variation of nitrogen input to aquatic ecosystems. Our previous study demonstrated the significant effect of different ammonium pulse patterns (differing in magnitude and frequency) on submersed macrophyte growth based on six plant morphological traits. However, how connectivity among plant traits responds to nitrogen pulse changes, which in turn affects plant performance, has not yet been fully elucidated. The response of three common submersed macrophytes (Myriophyllum spicatum, Vallisneria natans and Potamogeton maackianus) to three ammonium pulse patterns was tested using plant trait network (PTN) analysis based on 18 measured physiological and morphological traits. We found that ammonium pulses enhanced trait connectivity in PTN, which may enable plants to assimilate ammonium and/or mitigate ammonium toxicity. Large input pulses with low frequency had stronger effects on PTNs compared to low input pulses with high frequency. Due to the cumulative and time-lagged effect of the plant response to the ammonium pulse, there was a profound and prolonged effect on plant performance after the release of the pulse. The highly connected traits in PTN were those related to biomass allocation (e.g., plant biomass, stem ratio, leaf ratio and ramet number) rather than physiological traits, while phenotype-related traits (e.g., plant height, root length and AB ratio) and energy storage-related traits (e.g., stem starch) were least connected. V. natans showed clear functional divergence among traits, making it more flexible to cope with unfavorable habitats (i.e., high input pulses with low frequencies). M. spicatum with high RGR revealed strong correlations among traits and thus supported nitrogen accumulation from favourable environments (i.e., low input pulses with high frequencies). Our study highlights the responses of PTN for submerged macrophytes to ammonium pulses depends on their intrinsic metabolic rates, the magnitude, frequency and duration of the pulses, and our results contribute to the understanding of the impact of resource pulses on the population dynamics of submersed macrophytes within the context of global climate change.

Modified Sijunzi granule decreases post-weaning diarrhea in Rex rabbits via promoting intestinal development.

Traditional Chinese medicine (TCM) formulas can be adjusted on the basis of TCM basic theory to achieve the best curative effect, especially for diseases with complex pathogenesis, such as post-weaning diarrhea (PWD). Shugan Jianwei Sijunzi decoction (SJ-SJZD) can be recognized as modified Sijunzi Decoction (SJZD) supplemented with Astragalus mongholicus Bunge, Bupleurum chinense DC, Citrus × aurantium L., and Crataegus pinnatifida Bunge (fruit) in a fixed dosage ratio. The inactive ingredients were subsequently added to make granule, which was Shugan Jianwei Sijunzi granule (SJ-SJZG). Previous studies have confirmed the antagonism of SJ-SJZG to PWD. However, the mechanism of SJ-SJZG protective effects on small intestine in weaned Rex rabbits remained unclear. Animals were randomly divided into negative control (NC), low dose (LD), medium dose (MD), high dose (HD), and positive control (PC). SJ-SJZG significantly increased the intestinal length and the jejunum villi length. The SIgA level was statistically increased in duodenum and jejunum with the ELISA. Immunohistochemical detection showed that SIgA protein expression was also increased significantly in jejunum. Meanwhile, the relative expression of Zo1 in duodenum and jejunum of SJ-SJZG group increased significantly. SJ-SJZG significantly increased the relative expression of occludin in duodenum and jejunum as well. Moreover, real-time PCR results showed a significant increase in GLUT2 and SGLT1 relative expression in ileum. SJ-SJZG could also obviously enhance the expression of GLUT2 in jejunum and the expression of SGLT1 in duodenum. In conclusion, SJ-SJZG had been proven to be effective in promoting the development of small intestine and improving the immunity of small intestine. Moreover, SJ-SJZG could ensure the integrity of mucosal barrier and increase the ability of intestine to absorb glucose in small intestine.

Remote cerebellar hemorrhage after supratentorial craniotomy: illustrative cases.

BACKGROUND: Remote cerebellar hemorrhage (RCH) is an extremely rare and potentially fatal complication after supratentorial craniotomy. However, the exact pathophysiological mechanism of RCH remains unclear, so clinicians often lack clinical experience in prevention, early diagnosis, and standardized treatment. OBSERVATIONS: The authors retrospectively analyzed data of patients who underwent surgery for supratentorial lesions at their center between 2012 and 2021. They identified 4 patients who developed RCH among 4,075 patients who underwent supratentorial craniotomy. All 4 patients were male, with an average age of 57.5 years. One RCH occurred after tumor resection, and the other 3 occurred after aneurysm clipping. One patient was asymptomatic and received conservative treatment with a favorable outcome. The remaining 3 patients underwent lateral ventricular drainage and/or suboccipital decompression; 2 died, and 1 recovered well. LESSONS: The authors believe that RCH should be considered as a multifactorial cause, and massive cerebrospinal fluid loss plays a key role in the development and progression of RCH. Asymptomatic RCH can be treated conservatively. However, in the case of conscious disturbance, hydrocephalus, and brain stem compression, surgery should be performed immediately. Early detection and individualized treatment would be helpful to avoid potentially fatal outcomes caused by RCH.

Multi-Scenario Simulation and Trade-Off Analysis of Ecological Service Value in the Manas River Basin Based on Land Use Optimization in China.

Rapid socio-economic development has had a significant impact on land use/cover (LULC) changes, which bring great pressure to the ecological environment. LULC changes affect ecosystem services by altering the structure and function of ecosystems. It is of great significance to reveal the internal relationship between LULC changes and ecosystem service value (ESV) for the protection and restoration of ecological environments. In this study, based on the spatial and temporal evolution of ecological service values in the Manas River basin from 1980 to 2020 and considering ecological and economic benefits, we coupled the gray multi-objective optimization model (GMOP) and patch-generating land-use simulation (PLUS) model (GMOP-PLUS model) to optimize the LULC structure under three scenarios (a natural development scenario, ND; ecological priority development scenario, (EPD); and balanced ecological and economic development scenario, EED) in 2030, and analyzed the trade-offs and synergies in the relationships among the four services. We found that from 1980 to 2020, farmland and construction land expanded 2017.90 km2 and 254.27 km2, respectively, whereas the areas of grassland and unused land decreased by 1617.38 km2 and 755.86 km2, respectively. By 2030, the trend of LULC changes will be stable under the ND scenario, the area of ecological land will increase by 327.42 km2 under the EPD scenario, and the area of construction land will increase most under the EED scenario, reaching 65.01 km2. From 1980 to 2020, the ESV exhibited an upward trend in the basin. In 2030, the ESV will increase by 7.18%, 6.54%, and 6.04% under the EPD, EED, and ND scenarios, respectively. The clustering of the four services is obvious in the desert area and around the water system with "low-low synergy" and "high-high synergy"; the plain area and mountainous area are mainly "high-low trade-off" and "low-high trade-off" relationships. This paper provides a scientific reference for coordinating economic development and ecological protection in the basin. It also provides a new technical approach to address the planning of land resources in the basin.

Near-Interface Defects in Graphene/H-BN In-Plane Heterostructures: Insights into the Interfacial Thermal Transport.

Based on nonequilibrium molecular dynamics (NEMD) and nonequilibrium Green's function simulations, the interfacial thermal conductance (ITC) of graphene/h-BN in-plane heterostructures with near-interface defects (monovacancy defects, 585 and f5f7 double-vacancy defects) is studied. Compared to pristine graphene/h-BN, all near-interface defects reduce the ITC of graphene/h-BN. However, differences in defective structures and the wrinkles induced by the defects cause significant discrepancies in heat transfer for defective graphene/h-BN. The stronger phonon scattering and phonon localization caused by the wider cross-section in defects and the larger wrinkles result in the double-vacancy defects having stronger energy hindrance effects than the monovacancy defects. In addition, the approximate cross-sections and wrinkles induced by the 585 and f5f7 double-vacancy defects provide approximate heat hindrance capability. The phonon transmission and vibrational density of states (VDOS) further confirm the above results. The double-vacancy defects in the near-interface region have lower low-frequency phonon transmission and VDOS values than the monovacancy defects, while the 585 and f5f7 double-vacancy defects have similar low-frequency phonon transmission and VDOS values at the near-interface region. This study provides physical insight into the thermal transport mechanisms in graphene/h-BN in-plane heterostructures with near-interface defects and provides design guidelines for related devices.

[Intervention effects of erythropoietin derived peptide (HBSP) on renal injury induced by acute skeletal muscle strain in rats].

Objective: To investigate the protective effects of erythropoietin derived peptide, also known as spiral B surface peptide (HBSP), on kidney and aggregated proteins (Agrin) levels in acute skeletal muscle strain rats. Methods: Forty SPF grade SD male rats were randomly divided into control group, injury group, HBSP group and EPO group, with 10 rats in each group. Acute skeletal muscle strain animal models were established except the control group. After successful modeling, the rats in HBSP group and EPO group were intraperitoneally injected with 60 µg/kg HBSP and 5 000 U/kg recombinant human erythropoietin (rhEPO), and the rats in the control group and the injured group were intraperitoneally injected with 0.9% normal saline. Renal function was monitored with relevant kits; Hematoxylin-eosin staining was used to observe the pathological morphology of kidney tissue and skeletal muscle strain tissue. The apoptosis rate of renal tissue cells was detected by in situ terminal transferase labeling (TUNEL). Western blot and quantitative polymerase chain reaction (Q-PCR) were used to determine the expressions of Agrin and muscular-specific kinase (MuSK) in the injured skeletal muscle of rats in each group. Results: Compared with the control group, the renal function indexes serum creatinine (Cr), urea nitrogen (BUN) and 24 h urinary protein (UP24) levels of rats in injured group were increased (P＜ 0.05), but the levels of BUN, Cr and UP24 of rats in HBSP group were decreased (P＜0.05). Compared with HBSP group, there were no significant differences in the above indexes in EPO group (P＞0.05). In the control group, the muscle fiber structure was intact, the shape and structure of the fiber bundles were normal, and there was no infiltration of red blood cells and inflammatory cells in the interstitium, and no fibrohyperplasia. In the injured group, the muscle tissue showed sparse and irregular arrangement, and the interstitial widened with a large number of inflammatory cells and red blood cell infiltration. Erythrocytes and inflammatory cells were reduced in HBSP group and EPO group, and the transverse and longitudinal lines of muscle were clear. The glomerular structure of the rats in the fibrohyperplasia control group was intact and no lesions were observed. In the injured group, glomerular hypertrophy and significant matrix hyperplasia were observed, as well as the expansion of renal cysts with vacuolar and significant inflammatory infiltration were observed, and the inflammatory infiltration was reduced in the HBSP and EPO groups. Glomerular hypertrophy and hyperplasia were alleviated. The apoptosis rates of kidney cells in control group, injured group, HBSP group and EPO group were (4.05±0.51) %, (26.30±2.05) %, (14.28±1.62) % and (16.03±1.77) %, respectively, and there were significant differences among these groups (P＜0.05). Compared with control group, the levels of Agrin and MuSK in skeletal muscle pulled tissue were significantly decreased (P＜0.05), and those of HBSP group and EPO group were significantly increased compared with injured group (P＜0.05), but there was no significant difference between HBSP group and EPO group (P＞0.05). Conclusion: Erythropoietin derived peptide (HBSP) has obvious intervention effects on renal function injury in rats with acute skeletal muscle strain, and its mechanisms may be related to reducing the apoptosis rate of renal tissue cells and activating Agrin and MuSK expression.

Metabolite profiling and transcriptome analyses provide insight into the regulatory network of graft incompatibility in litchi.

Litchi is an important commercial fruit crop widely grown in the world. Graft incompatibility between rootstocks and scions is a major constraint for large-scale cultivation of litchi orchards, popularization of new and excellent litchi varieties, and associated industrial development. Further, the genetic mechanism of graft incompatibility is still unclear in litchi. To reduce the incompatibility problems, this study investigated metabolic and transcriptomic differences between graft compatible and incompatible rootstock-scion combinations of litchi. The result of metabolomics analysis showed that incompatible rootstock-scion interaction modified the profiles of several metabolic substances. However, various compounds of flavonoids, phenolic acids, and lignin predominantly exhibited significantly altered abundance in graft incompatible combinations. Transcriptome analysis identified that graft incompatibility induces dynamic gene differences. The majority of these differentially expressed genes were enriched in biosynthetic pathways of phenylpropanoids. The differential expressions of genes in these pathways could be linked to the differential abundance levels of flavonoids, phenolic acids, and lignin compounds. Integrated metabolomic and transcriptomic analyses revealed a strong relationship between differential genes and differential metabolites identified in this study. In addition, identified hub genes and metabolites were closely associated with graft incompatibility of litchi. This study characterized the abundance of metabolites and genes in graft incompatible combinations and further discussed the genetic mechanism of graft incompatibility in litchi. Our results provide a platform to dissect the molecular mechanisms of graft incompatibility in the litchi fruit.

Deciphering the bacterial microbiome in response to long-term mercury contaminated soil.

Hg contaminated soils are of concern due to the toxic effects on soil microbes. Currently, the adaptation of bacterial community to long-term Hg contamination remains largely unknown. Here, we assessed the effects of Hg contaminated soils on the bacterial communities under controlled conditions using 16S rRNA gene amplicon sequencing. The results showed that the bacterial α-diversity and richness were significant positively correlated with total Hg (p < 0.05). Land-use type, pH, EC, TK, and nitrate-N played important roles in shaping the bacterial communities. Long-term Hg-contaminated soils can be divided into three types based on land use types: slag type, farmland type, and mining area type. The dominant phyla include Proteobacteria, Actinobacteriota, Acidobacteriota, Chloroflexi, and Firmicutes. The dominant genera identified were Pseudomonas, Gaiella, Sphingomonas, Bacillus, Arthrobacter, Nocardioides. Network analysis showed that dominant taxa had non-random co-occurrence patterns and module 1 had an important role in responding Hg stress. Keystone genera identified were Bauldia, Phycicoccus, Sphingomonas, Gaiella, Nitrospira. The above results further our understanding of the adaptation of the bacterial community in long-term Hg-contaminated soil. This study has important guiding significance for the use of bacterial consortia to remediate Hg-contaminated soil.

Tumor-associated macrophages increase COX-2 expression promoting endocrine resistance in breast cancer via the PI3K/Akt/mTOR pathway.

Breast cancer is the most common malignancy in females. The emergence of endocrine resistance is frustrating for estrogen receptor (ER)-positive breast cancer patients even the efficacy of endocrine therapy is acceptable. Our previous study has shown that tumor-associated macrophages (TAMs) are associated with endocrine resistance, yet the mechanism remains unclear. This article is dedicated to discuss the role of TAMs in the endocrine resistance of breast cancer. It was found that tamoxifen-resistant MCF-7 cells induced more macrophages polarized into TAMs. Conversely, TAMs increased the expression of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), which promoted tamoxifen resistance through the activation of the PI3K/Akt/mTOR signaling pathway in MCF-7 cells. Furthermore, clinical analysis supported that five-year progression-free survival (PFS) of breast cancer patients with abundant COX-2 expression in TAMs was shorter (p<0.05). Therefore, these results show a positive feedback loop between TAMs and breast cancer cells, suggesting that TAMs and COX-2 may be new therapeutic targets for breast cancer patients suffering from endocrine resistance.

Tumor-promoting function of PIMREG in glioma by activating the ß-catenin pathway.

Glioma is the most common primary brain tumor in adults with an adverse prognosis and obscure pathogenesis. PICALM interacting mitotic regulator protein (PIMREG) functions as an oncogene in multiple types of cancer, but its function in glioma remains unknown. The Gene Expression Profiling Interactive Analysis 2 (GEPIA2, http://gepia2.cancer-pku.cn/#index) showed that PIMREG expression in the glioma tissues was higher than that in normal brain tissues. Herein, cell counting kit-8 assay and flow cytometry analysis exhibited that overexpression of PIMREG significantly promoted the proliferation of glioma cells and the transition from G1 phase of the cell cycle to S phase. Wound-healing and transwell assays showed that overexpression of PIMREG markedly enhanced the migration and invasion of glioma cells. Western blot analysis revealed that overexpression of PIMREG increased the expression of cyclin D1, cyclin E, Vimentin, matrix metalloproteinase (MMP)-2, and MMP-9, but reduced the expression of E-cadherin. In addition, overexpression of PIMREG activated the ß-catenin signaling pathway, as evidenced by the increased total and nuclear expression of ß-catenin and the up-regulated expression of its downstream target c-myc. Furthermore, immunofluorescence staining further indicated the increased nuclear translocation of ß-catenin in PIMREG-overexpressing cells. However, knockdown of PIMREG exerted opposite effects on glioma cells. Blockade of the ß-catenin signaling by ICG-001 markedly impeded the promoting effects of PIMREG on glioma cell proliferation and invasion. In conclusion, PIMREG acts as a tumor promoter in glioma at least partly via activating the ß-catenin signaling pathway. This study provides new insights into the molecular mechanism for glioma pathogenesis and treatment.

Caspase-3-mediated GSDME induced Pyroptosis in breast cancer cells through the ROS/JNK signalling pathway.

Pyroptosis is a new form of programmed cell death generated by some inflammasomes, piloting the cleavage of gasdermin (GSDM) and stimulation of dormant cytokines like IL-18 and IL-1ß; these reactions are narrowly linked to certain diseases like diabetic nephropathy and atherosclerosis. Doxorubicin, a typical anthracycline, and famous anticancer drug has emerged as a prominent medication in several cancer chemotherapies, although its application is accompanied with expending of dose-dependent, increasing, irreversible and continuing cardiotoxic side effects. However, the exact path that links the induced pyroptosis to the mechanism by which Doxorubicin (DOX) acts against breast cancer cells is still puzzling. The present study seeks to elucidate the potential link between DOX-induced cell death and pyroptosis in two human breast cancer cell lines (MDA-MB-231 and T47D). We proved that treatment with DOX reduced the cell viability in a dose-dependent way and induced pyroptosis morphology in MDA-MB-231 and T47D cells. Also, protein expression analyses revealed GSDME as a key regulator in DOX-induced pyroptosis and highlighted the related role of Caspase-3 activation. Furthermore, DOX treatments induced intracellular accumulation of ROS, stimulated the phosphorylation of JNK, and Caspase-3 activation, subsequently. In conclusion, the study suggests that GSDME triggered DOX-induced pyroptosis in the caspase-3 dependent reactions through the ROS/JNK signalling pathway. Additionally, it showed that the DOX-induced cardiotoxicity and pyroptosis in breast cancer cells can be minimized by reducing the protein level of GSDME; thus, these outcomes provide a new research target and implications for the anticancer investigations and therapeutic applications.