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Metazoan animals rely on oxygen for survival, but during normal development and homeostasis, animals are often challenged by hypoxia (low oxygen). In metazoans, many of the critical hypoxia responses are mediated by the evolutionarily conserved hypoxia-inducible transcription factors (HIFs). The stability and activity of HIF complexes are strictly regulated. In the model organism C . elegans , HIF-1 stability and activity are negatively regulated by VHL-1, EGL-9, RHY-1 and SWAN-1. Importantly, C . elegans mutants carrying strong loss-of-function mutations in these genes are viable, and this provides opportunities to interrogate the molecular consequences of persistent HIF-1 over-activation. We find that the genome-wide gene expression patterns are compellingly similar in these mutants, supporting models in which RHY-1, VHL-1 and EGL-9 function in common pathway(s) to regulate HIF-1 activity. These studies illuminate the diversified biological roles played by HIF-1, including metabolism and stress response. Genes regulated by persistent HIF-1 over-activation overlap with genes responsive to pathogens, and they overlap with genes regulated by DAF-16. As crucial stress regulators, HIF-1 and DAF-16 converge on key stress-responsive genes and function synergistically to enable hypoxia survival.

Oxygen is essential to all the aerobic organisms. However, during normal development, disease and homeostasis, organisms are often challenged by hypoxia (oxygen deprivation). Hypoxia-inducible transcription factors (HIFs) are master regulators of hypoxia response and are evolutionarily conserved in metazoans. The homolog of HIF in the genetic model organism C . elegans is HIF-1. In this study, we aimed to understand short-term hypoxia response to identify HIF-1 downstream genes and identify HIF-1 direct targets in C . elegans . The central research questions were: (1) which genes are differentially expressed in response to short-term hypoxia? (2) Which of these changes in gene expression are dependent upon HIF-1 function? (3) Are any of these hif-1 -dependent genes essential to survival in hypoxia? (4) Which genes are the direct targets of HIF-1? We combine whole genome gene expression analyses and chromatin immunoprecipitation sequencing (ChIP-seq) experiments to address these questions. In agreement with other published studies, we report that HIF-1-dependent hypoxia-responsive genes are involved in metabolism and stress response. Some HIF-1-dependent hypoxia-responsive genes like efk-1 and phy-2 dramatically impact survival in hypoxic conditions. Genes regulated by HIF-1 and hypoxia overlap with genes responsive to hydrogen sulfide, also overlap with genes regulated by DAF-16. The genomic regions that co-immunoprecipitate with HIF-1 are strongly enriched for genes involved in stress response. Further, some of these potential HIF-1 direct targets are differentially expressed under short-term hypoxia or are differentially regulated by mutations that enhance HIF-1 activity.

Background Valine-glutamine motif-containing proteins (VQ proteins) play important roles in plant growth, development and response to stress. However, information on the VQ gene family in rubber tree ( Hevea brasiliensis Muell. Arg.) is limited. Results In this study, a total of 21 VQ protein genes (named HbVQ1 ~ HbVQ21) were identified in rubber trees and divided into six subfamilies. Gene structure analysis revealed that most of HbVQs had no introns except for HbVQ5 and HbVQ20 . Gene expression analysis revealed that HbVQ4 , 5 , and 21 were expressed at relatively high levels in latex. In addition, HbVQ4, 5, and 21 interact with the WRKY transcription factor HbWRKY14. Transient co-expression of HbVQ4 or HbVQ5 and HbWRKY14 resulted in relieved HbWRKY14-mediated transcription inhibition of the gene encoding small rubber particle protein ( HbSRPP ), whereas transient co-expression of HbVQ21 and HbWRKY14 resulted in increased HbWRKY14-mediated HbSRPP transcription inhibition. Conclusions In summary, HbVQ4, 5, and 21 interact with HbWRKY14 to regulate the expression of HbSRPP . This study provides insight into the functions of VQ proteins in regulating natural rubber biosynthesis.

Aims Excessive neuroinflammation mediated mainly by microglia plays a crucial role in ischemic stroke. AZD1390, an ataxia telangiectasia mutated (ATM) specific inhibitor, has been shown to promote radio‐sensitization and survival in central nervous system malignancies, while the role of AZD1390 in ischemic stroke remains unknown. Methods Real‐time PCR, western blot, immunofluorescence staining, flow cytometry and enzyme‐linked immunosorbent assays were used to assess the activation of microglia and the release of inflammatory cytokines. Behavioral tests were performed to measure neurological deficits. 2,3,5‐Triphenyltetrazolium chloride staining was conducted to assess the infarct volume. The activation of NF‐κB signaling pathway was explored through immunofluorescence staining, western blot, co‐immunoprecipitation and proximity ligation assay. Results The level of pro‐inflammation cytokines and activation of NF‐κB signaling pathway was suppressed by AZD1390 in vitro and in vivo. The behavior deficits and infarct size were partially restored with AZD1390 treatment in experimental stroke. AZD1390 restrict ubiquitylation and sumoylation of the essential regulatory subunit of NF‐κB (NEMO) in an ATM‐dependent and ATM‐independent way respectively, which reduced the activation of the NF‐κB pathway. Conclusion AZD1390 suppressed NF‐κB signaling pathway to alleviate ischemic brain injury in experimental stroke, and attenuated microglia activation and neuroinflammation, which indicated that AZD1390 might be an attractive agent for the treatment of ischemic stroke. AZD1390 suppressed NF‐κB signaling pathway through restricting ubiquitylation and sumoylation of NEMO, which alleviated ischemic brain injury in experimental stroke and attenuated the activation of microglia and neuroinflammation.

This study systematically investigated the microstructural evolution and mechanical properties of GH4780 superalloy under various solution treatment conditions. Experimental results reveal a strong temperature dependence of grain growth kinetics, with the average grain diameter increasing from approximately 20 μm to 194 μm as the solution temperature rises from 1020 °C to 1110 °C. Mechanical testing demonstrates that grain coarsening reduces the yield strength by 19% at room temperature (from 920 MPa to 743 MPa) and by 9.5% at 760 °C (from 707 MPa to 640 MPa), primarily due to decreased grain boundary density and enhanced dislocation mobility. High-temperature deformation mechanisms were characterized, showing that the reduced grain boundary area facilitates dislocation motion while compromising strength. Furthermore, a grain growth kinetic model was developed, providing a quantitative prediction of microstructural evolution. These findings offer significant guidance for improving the high-temperature performance of GH4780 superalloy by optimizing heat treatment processes.

Objective To investigate the clinical significance of the detection of bone mineral density (BMD) and bone turnover markers (BTM) in older women with osteoporosis, and to compare their predictive power for osteoporotic fractures (OF). Methods In this retrospective study, 96 patients with OF and 107 patients with osteoporosis who were hospitalized in the Department of Orthopedics at the First Affiliated Hospital of Chengdu Medical College were examined from October 2017 to February 2019. All selected patients were divided into either the fracture group (96 cases, 47.3%) or the non‐fracture group (107 cases, 52.7%). BMD was measured by dual‐energy X‐ray absorptiometry (DXA). BTM were detected by electrochemical luminescence: aminoterminal propeptide of type I procollagen (PINP), β‐cross‐linked C‐telopeptide of type I collagen (β‐CTX), and molecular fragment of osteocalcin N terminal (N‐MID). Bone metabolism‐related indicators were detected, including alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P). Independent‐samples t‐tests were used to compare the measurement data between the two groups, one‐way ANOVA to compare the gaps between groups, and binary logistic regression to analyze the correlation of BMD and BTM with OF. Results There were no significant differences in age, weight, height, body mass index, age, and time of menopause between the two groups. There were a total of 71 cases (35.0%) in group A (60–70 years), 80 cases (39.4%) in group B (71–80 years), and 52 cases (25.6%) in group C (81–90 years). The fracture group was compared with the non‐fracture group for BMD in the lumbar (0.75 ± 0.05 vs 0.88 ± 0.13, 0.75 ± 0.16 vs 0.87 ± 0.09, 0.74 ± 0.21 vs 0.87 ± 0.12 g/cm2; P < 0.05), BMD in the hip (0.62 ± 0.16 vs 0.74 ± 0.14, 0.61 ± 0.15 vs 0.73 ± 0.0, 0.58 ± 0.13 vs 0.73 ± 0.08 g/cm2; P < 0.05), PINP (83.7 ± 5.7 vs 74.8 ± 5.0, 80.7 ± 4.1 vs 72.1 ± 5.1, 81.2 ± 7.0 vs 68.7 ± 6.3 ng/mL, P < 0.05), and β‐CTX (829.7 ± 91.5 vs 798.8 ± 52.2, 848.1 ± 71.2 vs 812.4 ± 79.0, 867.3 ± 53.1 vs 849.1 ± 67.2 pg./mL, P < 0.05). N‐MID (19.0 ± 6.7 vs 21.3 ± 9.7, 16.2 ± 7.0 vs 18.0 ± 5.3 ng/mL, P < 0.05) in the fracture cases was lower than in the non‐fracture cases for groups B and C, and there was statistical significance. Among the fracture cases, PINP in group A was higher than in group B and C, and β‐CTX in group C was higher than in group A and B (P < 0.05). There was no significant difference in the ALP, P, and Ca between the two groups (P > 0.05). Binary logistic regression analysis showed that for BMD in the lumbar and hip, β‐CTX and OF were significantly correlated (respectively, odds ratio [OR] = −4.182, 95% confidence interval [CI] 1.672–3.448; OR = 6.929, 95% CI 2.586–12.106; OR = 7.572, 95% CI 1.441–3.059), and the differences were statistically significant. PINP and N‐MID were correlated with OF (respectively, OR = 4.213, 95% CI 0.978–1.005; OR = 2.510, 95% CI 1.070–1.134, P > 0.05), the difference was not statistically significant. Conclusion Osteoporotic older women, with lower bone density and higher β‐CTX, are more likely to incur OF. β‐CTX is better than BMD at predicting OF and can help in its management and in implementing interventions in high‐risk populations.

To evaluate the geotechnical properties of coarse-grained soil affected by cyclic freeze-thaw, the electrical resistivity and mechanical tests are conducted. The soil specimens are prepared under different water contents, dry densities and exposed to 0-20 freeze-thaw cycles. As a result, the stress-strain behavior of the specimen (w =14.0% and ρd=1.90 g/cm3) changes from strain-hardening into strain-softening due to the freeze-thaw effect. The electrical resistivity of test specimen increases with the freeze-thaw cycles change, but the mechanical parameters (the unconfined compressive strength qu and the deformation modulus E) and brittleness index decrease considerably at the same conditions. All of them tend to be stable after 7−9 cycles. Moreover, both the dry density and the water content have reciprocal effects on the freeze-thaw actions. The failure and pore characteristics of specimens affected by freeze-thaw cycles are discussed by using the image analysis method. Then, an exponential function equation is developed to assess the electrical resistivity of specimens affected by the cyclic freeze-thaw. Linear relations between the mechanical parameters and the electrical resistivity of specimens are established to evaluate the geotechnical properties of the soil exposed to freeze-thaw actions through the corresponding electrical resistivity.

Freeze-thaw cycles are closely related to the slope instability in high-altitude mountain regions. In this study, cohesive coarse-grained soils were collected from a high-altitude slope in the Qinghai-Tibet Plateau to study the effect of cyclic freeze-thaw on their uniaxial mechanical properties. The soil specimens were remolded with three dry densities and three moisture contents. Then, after performing a series of freeze-thaw tests in a closed system without water supply, the soil specimens were subjected to a uniaxial compression test. The results showed that the stress-strain curves of the tested soils mainly performed as strain-softening. The softening feature intensified with the increasing dry density but weakened with an increase in freeze-thaw cycles and moisture content. The uniaxial compressive strength, resilient modulus, residual strength and softening modulus decreased considerably with the increase of freeze-thaw cycles. After more than nine freeze-thaw cycles, these four parameters tended to be stable. These parameters increased with the increase of dry density and decreased with the increasing moisture content, except for the residual strength which did not exhibit any clear variation with an increase in moisture content. The residual strength, however, generally increased with an increase in dry density. The soil structural damage caused by frozen water expansion during the freeze-thaw is the major cause for the changes in mechanical behaviors of cohesive coarse-grained soils. With results in this study, the deterioration effect of freeze-thaw cycles on the mechanical properties of soils should be considered during the slope stability analysis in high-altitude mountain regions.

A novel fluorescent and electron-deficient hybrid, N -methylated [Eu (pddb)phen(ox) 0.5 ] n (Eu-MOF-Me) has been prepared via post-synthetic modification. Considering its special luminescent properties and cationic framework, Eu-MOF-Me is developed as a visualized fluorescent probe. Notably, water-stable Eu-MOF-Me exhibits advantages like good structural and fluorescent stability in a wide range of pH value (3.39–10.86), excellent identification ability for F − , I − , and S 2− (it can easily distinguish F − and I − from other halogen ions and can realize naked eye identification of F − , I − , and S 2− ), relatively low detection limits (6.61 μM for S 2− , 7.57 μM for F − ), and reusability. More importantly, it has been utilized for the construction of a Boolean logic gate system. In this system, Eu-MOF-Me serves as the gate, by taking F − , I − , and S 2− as the inputs and fluorescence emission bands (UV380, B437, and R612) as the outputs; some primary logic gates (NOR, IMP, YES, NOT) and the combination of them have been realized. Moreover, we achieved a cascaded logic gate (NOR+OR). For further application, a molecular computing keypad-lock security system has been obtained. Graphical abstract A novel fluorescent and electron-deficient hybrid named Eu-MOF-Me has been prepared via post-synthetic methylation. Considering its special luminescent properties and cationic framework, Eu-MOF-Me was developed as a fluorescent probe for the visual monitoring of important anions. In addition, it was used for the construction of Boolean logic library and a keypad-lock system was achieved

Aiming at the shortcomings of the BP neural network in practical applications, such as easy to fall into local extremum and slow convergence speed, we optimized the initial weights and thresholds of the BP neural network using the particle swarm optimization (PSO). Additionally, cloud computing service, web technology, cloud database and numerical simulation were integrated to construct an intelligent feedback analysis cloud program for underground engineering safety monitoring based on the PSO-BP algorithm. The program could conveniently, quickly, and intelligently carry out numerical analysis of underground engineering and dynamic feedback analysis of surrounding rock parameters. The program was applied to the cloud inversion analysis of the surrounding rock parameters for the underground powerhouse of the Shuangjiangkou Hydropower Station. The calculated displacement simulated with the back-analyzed parameters matches the measured displacement very well. The posterior variance evaluation shows that the posterior error ratio is 0.045 and the small error probability is 0.999. The evaluation results indicate that the intelligent feedback analysis cloud program has high accuracy and can be applied to engineering practice.