Design, synthesis and evaluation of thieno[3,2-d]pyrimidine derivatives as novel potent CDK7 inhibitors.

The targeting of cyclin-dependent kinase 7 (CDK7) has become a highly desirable therapeutic approach in the field of oncology due to its dual role in regulating essential biological processes, encompassing cell cycle progression and transcriptional control. We have previously identified a highly selective thieno[3,2-d]pyrimidine-based CDK7 inhibitor with demonstrated efficacy and safety in animal model. In this study, we sought to optimize the thieno[3,2-d]pyrimidine core to discover a novel series of CDK7 inhibitors with improved potency and pharmacokinetic (PK) properties. Through extensive structure-activity relationship (SAR) studies, compound 20 has emerged as the lead candidate due to its potent inhibitory activity against CDK7 and remarkable efficacy on MDA-MB-453 cells, a representative triple negative breast cancer (TNBC) cell line. Furthermore, 20 has demonstrated favorable oral bioavailability and exhibited highly desirable pharmacokinetic (PK) properties, making it a promising lead candidate for further structural optimization.

Risk of heavy metal(loid) compositions in fine particulate matter on acute cardiovascular mortality: a poisson analysis in Anyang, China.

Fine particulate matter (PM2.5) is a risk factor of cardiovascular disease. Associations between PM2.5 compositions and cardiovascular disease are a point of special interest but inconsistent. This study aimed to explore the cardiovascular effects of heavy metal(loid) compositions in PM2.5. Data for mortality, air pollutants and meteorological factors in Anyang, China from 2017 to 2021 were collected. Heavy metal(loid) in PM2.5 were monitored and examined monthly. A Case-crossover design was applied to the estimated data set. The interquartile range increase in cadmium (Cd), antimony (Sb) and arsenic (As) at lag 1 was associated with increment of 8.1% (95% CI: 3.3, 13.2), 4.8% (95% CI: 0.2, 9.5) and 3.5% (95% CI: 1.1, 6.0) cardiovascular mortality. Selenium in lag 2 was inversely associated with cerebrovascular mortality (RR = 0.920 95% CI: 0.862, 0.983). Current-day exposure of aluminum was positively associated with mortality from ischemic heart disease (RR = 1.083 95% CI: 1.001, 1.172). Stratified analysis indicated sex, age and season modified the cardiovascular effects of As (P < 0.05). Our study reveals that heavy metal(loid) play key roles in adverse effects of PM2.5. Cd, Sb and As were significant risk factors of cardiovascular mortality. These findings have potential implications for accurate air pollutants control and management to improve public health benefits.

Grassland degradation amplifies the negative effect of nitrogen enrichment on soil microbial community stability.

Although nitrogen (N) enrichment is known to threaten the temporal stability of aboveground net primary productivity, it remains unclear how it alters that of belowground microbial abundance and whether its impact can be regulated by grassland degradation. Using data from N enrichment experiments at temperate grasslands with no, moderate, severe, and extreme degradation degrees, we quantified the temporal stability of soil microbial abundance (hereafter 'microbial community stability') using the ratio of the mean quantitative PCR to its standard deviation over 4 years. Both bacterial and fungal community stability sharply decreased when N input exceeded 30 g N m-2 year-1 in non-degraded grasslands, whereas a reduction in this threshold occurred in degraded grasslands. Microbial species diversity, species asynchrony, and species associations jointly altered microbial community stability. Interestingly, the linkages between plant and microbial community stability were strengthened in degraded grasslands, suggesting that plants and soil microbes might depend on each other to keep stable communities in harsh environments. Our findings highlighted the importance of grassland degradation in regulating the responses of microbial community stability to N enrichment and provided experimental evidence for understanding the relationships between plant and microbial community stability.

Sensitive dual-signal detection and effective removal of tetracycline antibiotics in honey based on a hollow triple-metal organic framework nanozymes.

In this work, a colorimetric/fluorescent dual-signal mode sensor is proposed for the sensitive, selective and accurate detection and removal of tetracycline antibiotics (TCs). A triple-metal MOF of NiCoFe is successfully synthesized and controllable adjusted the shape of the hollow structure for the first time, and then modified with TCs aptamer. The as-prepared triple-atom MOF (apt-NiCoFe-MOF-74) exhibits well-defined hollow morphology, high crystallinity, and high surface areas endow their alluring adsorption and removal performances for TCs. More attractively, this triple-metal MOF show a good peroxidase-like activity and strong fluorescence property at 540 nm of apt-NiCoFe-MOF-74 when excitation wavelength was 370 nm. Inspire by this, a dual-signal output biosensor is constructed and the linear absorbance response is well correlated with wide range and low LOD for TCs. The biosensor provided an universal method with satisfactory sensitivity and accuracy for TCs analysis in real food samples.

Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis.

Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway.

The impact of superselective adrenal artery embolization on renal function in patients with primary aldosteronism: a prospective cohort study.

Superselective adrenal artery embolization (SAAE) is an effective treatment for patients with primary aldosteronism (PA). However, the impact of SAAE on renal function in the PA population remains uncertain. We investigated the estimated glomerular filtration rate (eGFR) and age, sex, body mass index, and diabetes-specific percentiles of eGFR residuals in 182 PA patients treated with SAAE in a prospective cohort from Nanchang SAAE in treating PA registry study. Data suggest that SAAE caused a significant decrease in eGFR from 91.9 ± 26.1 to 88.7 ± 24.1 ml/min/1.73 m2 (p < 0.05) after a median follow-up of 8 months in PA patients. Patients experienced a significant decrease in eGFR from 110.6 ± 18.9 to 103.8 ± 18.2 ml/min/1.73 m2 (p < 0.001) and a very slight increase from 71.1 ± 14.8 to 71.8 ± 17.8 ml/min/1.73 m2 (p = 0.770) with baseline eGFR ≥90 and <90 ml/min/1.73 m2, respectively. Patients with high eGFR residuals (glomerular hyperfiltration) experienced a significant decrease in their eGFR levels from 123.1 ± 22.6 to 105.0 ± 18.6 ml/min/1.73 m2 (p < 0.001). In contrast, there was no significant impact of SAAE on the eGFR of patients with normal or low eGFR residuals. The very early eGFR changes (24 h after SAAE) best predicted the effect of SAAE on eGFR changes after median of eight months in PA patients. On the whole, SAAE seems to have a beneficial impact on renal function in patients with PA, the results of which vary depending on the patient's baseline eGFR and glomerular hyperfiltration status.

Dispel the Clouds and See the Sun: Influencing Factors and Multiple Paths of User Retention Intention Formation.

To achieve user retention through multifactor synergy, Internet enterprises must reduce costs and increase efficiency and sustainable development. In response to the dilemma that Internet companies are experiencing increasingly high user acquisition costs and serious user churn, this paper investigates a sample of 46,695 user reviews of nine product series from Xiaomi Ecological Chain. Case studies and qualitative comparative analysis are used to explore the influence mechanisms of quality of experience, brand trust, and brand attachment on users' retention intentions. Our findings are as follows. (1) Brand attachment alone is not necessary for high user retention intention, but user perception, cognition, and brand trust are necessary. (2) Quality of experience positively impacts brand trust, attachment, and user retention intention. Therefore, improving user perception and cognition is critical in generating high user retention intention. (3) Five configuration paths can achieve high user retention intention, while three configuration paths lead to low user retention intention, and there is an asymmetric relationship between these paths. Among them, the role of quality of experience-driven configuration paths in generating user retention intention is the most prominent. (4) User perception and cognition can substitute with brand trust and attachment in the substitution relationship between configuration paths. Our findings have important theoretical and practical implications for revealing the realization paths of high user retention intention in Internet companies and provide a new perspective for future research.

LiBF4-Promoted Aromatic Fluorodetriazenation under Mild Conditions.

An efficient and mild fluorination method through LiBF4-promoted aromatic fluorodetriazenation of 3,3-dimethyl-1-aryltriazenes is developed. The reaction proceeds smoothly and tends to complete within 2 h in the absence of a protic acid or strong Lewis acid. This method tolerates a wide range of functional groups and affords the aryl fluoride products in moderate to excellent yields.

The protective effects of sophocarpine on sepsis-induced cardiomyopathy.

This investigation elucidates the impact of sophocarpine treatment on lipopolysaccharide (LPS) stimulated sepsis-induced cardiomyopathy (SIC) via in vivo and in vitro experiments. Echocardiography, ELISA, TUNEL, Western blotting experiments, and Hematoxylin/Eosin, Dihydroethidium, and Immunohistochemistry staining assays, were carried out to identify associated indicators. The echocardiography revealed that sophocarpine treatment alleviated LPS-induced cardiac dysfunction as indicated by fractional shortening shortened and improved ejection fraction. Heart injury biomarkers, such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, were assessed, and indicated that sophocarpine treatment could alleviate LPS-induced upregulation of these indices. Furthermore, different experimental protocols revealed that sophocarpine treatment inhibits LPS-induced pathological alterations and decreases LPS-stimulated inflammatory cytokines, IL-1ß, monocyte chemoattractant protein-1, IL-6, NOD-like receptor protein-3, and TNF-α, increase. Apoptotic proteins such as cytochrome-c, Bax, and cleaved-caspase-3 were increased, and Bcl-2 was alleviated after LPS stimulation; however, these effects were inhibited by sophocarpine treatment. Decreased antioxidant proteins [superoxide dismutase-1 (SOD-1) and SOD-2] induced by LPS stimulation were upregulated by sophocarpine treatment. LPS upregulated autophagic proteins such as Beclin-1 and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I and downregulated sequestosome 1 (SQSTM1, or P62), sophocarpine therapy reversed these effects. Moreover, it was indicated that sophocarpine treatment inhibited the Toll-like receptor-4 (TLR-4)/nuclear transcription factor-kappa B (NF-κB) signaling pathway and activated nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In conclusion, sophocarpine treatment could alleviate LPS-trigger SIC by repressing oxidative stress, autophagy, inflammation, and apoptosis via TLR-4/NF-κB inhibition and Nrf2/HO-1 signaling pathway activation, implicating the potential of sophocarpine as a new therapeutic approach against SIC.

Superselective adrenal arterial embolization for primary aldosteronism without lateralized aldosterone secretion: an efficacy and safety, proof-of-principle study.

Superselective adrenal arterial embolization (SAAE) appears to be beneficial in primary aldosteronism (PA) patients with lateralized aldosterone secretion (unilateral PA). As confirmed by adrenal vein sampling (AVS), nearly 40% of PA patients would be PA without lateralized aldosterone secretion (bilateral PA). We aimed to investigate the efficacy and safety of SAAE on bilateral PA. We identified 171 bilateral PA patients from 503 PA patients who completed AVS. Thirty-eight bilateral PA patients received SAAE, and 31 completed a median 12-month clinical follow-up. The blood pressure and biochemical improvements of these patients were carefully analyzed. 34% of patients were identified as bilateral PA. Plasma aldosterone concentration, plasma renin activity, and aldosterone/renin ratio (ARR) were significantly improved 24-h after SAAE. SAAE was associated with 38.7% and 58.6% of complete/partial clinical and biochemical success within a median 12-month follow-up. A significant reduction in left ventricular hypertrophy was shown in patients who obtained complete biochemical success compared with partial/absent biochemical success. SAAE was associated with a more apparent nighttime blood pressure reduction than daytime blood pressure reduction in patients with complete biochemical success. No major adverse safety events related to SAAE were reported during the intraoperative, postoperative, and follow-up periods. SAAE was associated with blood pressure and biochemical improvements in part of bilateral PA and appeared safe. The biochemistry success was accompanied by improved cardiac remodeling and a more prominent decrease in nocturnal blood pressure. This study was part of a trial registered with the Chinese Clinical Trial Registry, number ChiCTR2100047689.

Amelioration of metabolic disorders in H9C2 cardiomyocytes induced by PM2.5 treated with vitamin C.

OBJECTIVE: Particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) is a public health risk. We investigate PM2.5 on metabolites in cardiomyocytes and the influence of vitamin C on PM2.5 toxicity. MATERIALS AND METHODS: For 24 hours, H9C2 were exposed to various concentrations of PM2.5 (0, 100, 200, 400, 800 µg/ml), after which the levels of reactive oxygen species (ROS) and cell viability were measured using the cell counting kit-8 (CCK-8) and 2',7'-dichlorofluoresceindiacetate (DCFH2-DA), respectively. H9C2 were treated with PM2.5 (200 µg/ml) in the presence or absence of vitamin C (40 µmol/L). mRNA levels of interleukin 6(IL-6), caspase-3, fatty acid-binding protein 3 (FABP3), and hemeoxygenase-1 (HO-1) were investigated by quantitative reverse-transcription polymerase chain reaction. Non-targeted metabolomics by LC-MS/MS was applied to evaluate the metabolic profile in the cell. RESULTS: Results revealed a concentration-dependent reduction in cell viability, death, ROS, and increased expression of caspase-3, FABP3, and IL-6. In total, 15 metabolites exhibited significant differential expression (FC > 2, p < 0.05) between the control and PM2.5 group. In the PM2.5 group, lysophosphatidylcholines (LysoPC,3/3) were upregulated, whereas amino acids (5/5), amino acid analogues (3/3), and other acids and derivatives (4/4) were downregulated. PM2.5 toxicity was lessened by vitamin C. It reduced PM2.5-induced elevation of LysoPC (16:0), LysoPC (16:1), and LysoPC (18:1). DISCUSSION AND CONCLUSIONS: PM2.5 induces metabolic disorders in H9C2 cardiomyocytes that can be ameliorated by treatment with vitamin C.

Soil fertility shifts the relative importance of saprotrophic and mycorrhizal fungi for maintaining ecosystem stability.

Soil microbial communities are essential for regulating the dynamics of plant productivity. However, how soil microbes mediate temporal stability of plant productivity at large scales across various soil fertility conditions remains unclear. Here, we combined a regional survey of 51 sites in the temperate grasslands of northern China with a global grassland survey of 120 sites to assess the potential roles of soil microbial diversity in regulating ecosystem stability. The temporal stability of plant productivity was quantified as the ratio of the mean normalized difference vegetation index to its standard deviation. Soil fungal diversity, but not bacterial diversity, was positively associated with ecosystem stability, and particular fungal functional groups determined ecosystem stability under contrasting conditions of soil fertility. The richness of soil fungal saprobes was positively correlated with ecosystem stability under high-fertility conditions, while a positive relationship was observed with the richness of mycorrhizal fungi under low-fertility conditions. These relationships were maintained after accounting for plant diversity and environmental factors. Our findings highlight the essential role of fungal diversity in maintaining stable grassland productivity, and suggest that future studies incorporating fungal functional groups into biodiversity-stability relationships will advance our understanding of their linkages under different fertility conditions.

Remodeling nanodroplets into hierarchical mesoporous silica nanoreactors with multiple chambers.

Multi-chambered architectures have attracted much attention due to the ability to establish multifunctional partitions in different chambers, but manipulating the chamber numbers and coupling multi-functionality within the multi-chambered mesoporous nanoparticle remains a challenge. Herein, we propose a nanodroplet remodeling strategy for the synthesis of hierarchical multi-chambered mesoporous silica nanoparticles with tunable architectures. Typically, the dual-chambered nanoparticles with a high surface area of ~469 m2 g-1 present two interconnected cavities like a calabash. Furthermore, based on this nanodroplet remodeling strategy, multiple species (magnetic, catalytic, optic, etc.) can be separately anchored in different chamber without obvious mutual-crosstalk. We design a dual-chambered mesoporous nanoreactors with spatial isolation of Au and Pd active-sites for the cascade synthesis of 2-phenylindole from 1-nitro-2-(phenylethynyl)benzene. Due to the efficient mass transfer of reactants and intermediates in the dual-chambered structure, the selectivity of the target product reaches to ~76.5%, far exceeding that of single-chambered nanoreactors (~41.3%).

Critical transition of multifunctional stability induced by nitrogen enrichment in grasslands differing in degradation severity.

Nitrogen (N) enrichment poses a severe threat to ecosystem multifunctionality. Given increasing variability of ecosystem functioning and uncertainty under global change, a pressing question is how N enrichment affects temporal stability of multiple functions (i.e., 'multifunctional stability'). Whether the responses of multifunctional stability to N enrichment change with external disturbance, such as grasslands with different degradation statuses, remains unclear. We conducted multi-level N enrichment experiments at four grassland sites with no, moderate, severe, and extreme degradation statuses in Inner Mongolia, China. We measured temporal stability of five functions, comprising aboveground net primary productivity, soil total carbon (C) and N storage, and soil microbial biomass C and N storage, to explore how multifunctional stability responded to N enrichment. The temporal stability of most individual functions and multifunctional stability decreased sharply when N input exceeded 20 g N m-2 y-1 in the non-, moderately, and severely degraded grasslands, whereas the threshold declined to 10 g N m-2 y-1 in the extremely degraded grassland. The relative importance of plant and soil microbes in regulating multifunctional stability varied along the degradation gradient. In particular, plant species asynchrony and species richness showed strong positive relationships with multifunctional stability in the non- and moderately degraded grasslands, whereas soil microbial diversity, especially bacterial diversity, was positively associated with multifunctional stability in the severely and extremely degraded grasslands. Overall, our findings identified a critical threshold for N-induced multifunctional stability and called for context-specific biodiversity conservation strategies to buffer the negative effect of N enrichment on grassland ecosystem stability.

Nitrogen deficiency in soil mediates multifunctionality responses to global climatic drivers.

Natural and anthropogenic processes that decrease the availability of nitrogen (N) frequently occur in soil. Losses of N may limit the multiple functions linked to carbon, N and phosphorous cycling of soil (soil multifunctionality, SMF). Microbial communities and SMF are intimately linked. However, the relationship between soil microbial communities and SMF in response to global changes under N deficiency has never been examined in natural ecosystems. Here, soil samples from nine temperate arid grassland sites were used to assess the importance of microbial communities as driver of SMF to climate change and N deficiency. SMF was significantly decreased by drought and drought-wetting cycles, independent of the availability of soil N. Interestingly, temperature changes (variable temperature and warming) significantly increased SMF in N-poor conditions. However, this was at the expense of decreased SMF resistance. Deterministic assembly-driven microbial α-diversity and particularly fungal α-diversity, but not ß-diversity, were generally found to play key roles in maintaining SMF in N-poor soil, irrespective of the climate. The results have two important implications. First, the absence of the stability offered by ß-diversity means N-poor ecosystems will be particularly sensitive to global climate changes. Second, fungi are more important than bacteria for maintaining SMF in N-poor soil under climate changes.

Effect of dexmedetomidine on oxytocin-induced uterine contraction during optimal caesarean section anaesthesia.

Numerous drugs are used during caesarean sections to provide regional and general anaesthesia. Dexmedetomidine has been used in some recent obstetric trials, but there are concerns about postpartum changes in uterine contractions. This study evaluated the effect of dexmedetomidine on oxytocin-induced uterine contractions in women undergoing caesarean section. Sixty women undergoing caesarean section in Lianyungang Second People's Hospital were randomly assigned to dexmedetomidine (group D, n = 30) or saline (group C, n = 30) groups. Equal volumes of saline or dexmedetomidine were administered intravenously (IV). During the intraoperative delivery of the foetus and placenta, oxytocin was administered to promote contractions. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were compared. The Ramsay scale was used to assess sedation, while the Tsai and Chu methods assessed shivering. Adverse intraoperative events were observed. All variables fluctuated significantly after anaesthesia onset in both groups but were most pronounced in group D. The VAS, Ramsay and shivering scores were significantly lower in group D compared to group C. During rapid IV infusion of oxytocin after foetal delivery, the incidence of nausea, vomiting, chest tightness and hypotension was significantly lower in group D than in group C.

Inhibition of semaphorin-3a alleviates lipopolysaccharide-induced vascular injury.

Alleviating vascular injury improves the prognosis of atherosclerosis. Semaphorin-3a (Sema3A) is a special membrane-associated secreted protein with various biological properties, like pro-inflammation, anti-tumor and et al. This study aims to investigate the effects of inhibition of Sema3A on lipopolysaccharide (LPS)-induced vascular injury in mice. The mice were randomized into three groups: control, LPS, and LPS + siRNA. Mice in the combined group were given siRNA through fast tail vein injection, then LPS was injected intraperitoneally 7 days later, finally the mice were euthanized 24 h later. Vascular function and structure were assessed by vascular injury biomarkers and relevant stainings. LPS-induced vascular dysfunction and pathological injury were substantially improved by inhibition of Sema3A. Western blot and quantitative real-time polymerase chain reaction assays were used for investigating molecular pathways. The relevant proteins of vascular endothelial cells activation, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), increased after LPS stimulation, while these effects were reversed by inhibition of Sema3A. The levels of inflammatory cytokines (IL-1ß, IL-6 and NLRP3) were upregulated after LPS stimulation, however, inhibition of Sema3A reversed it through NF-κB and MAPKs signaling pathways involvement. Moreover, inhibition of Sema3A alleviated LPS-induced oxidative stress, evidenced by a decrease in total reactive oxygen species and an increase in antioxidant protein of SOD-1. The results showed that inhibition of Sema3A protects against LPS-induced vascular injury by suppressing vascular endothelial cells activation, vascular inflammation, and vascular oxidative stress, implying that inhibition of Sema3A might be used as a therapeutic strategy for septic vascular injury or atherosclerosis.

Identification of potential pathways associated with indole-3-butyric acid in citrus bud germination via transcriptomic analysis.

Indole-3-butyric acid (IBA) is widely used to encourage root development in cuttings of general field crops, vegetables, forest trees, fruit trees, and flowers. However, previous studies reported that IBA inhibited the germination of citrus buds via an unknown molecular mechanism. This study aimed to unravel the regulatory mechanisms underlying this inhibition. Citrus apical buds were sprayed with 100 mg ⋅ L-1 IBA. Subsequently, the plant hormone levels were analyzed, and transcriptomic analysis was performed. The results identified 3325 upregulated genes and 2926 downregulated genes in the citrus apical buds. The gene set enrichment analysis method was used to determine the Gene Ontology related to the treatment. Genes were enriched into 157 sets, including 17 upregulated sets and 140 downregulated sets, after indole butyric acid treatment. The upregulated gene sets were related to glucose import, sugar transmembrane transporter activity, and photosynthesis. The downregulated genes were mainly related to the ribosomal subunit and cell cycle process under butyric acid treatment. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed the enrichment of 11 pathways. Of note, genes related to the ribosome and proteasome pathways were significantly downregulated. Only one pathway was significantly upregulated: the autophagy pathway. Overall, these results provided insights into the molecular mechanisms underpinning the IBA-mediated inhibition of citrus bud germination inhibition. Also, the study provided a large transcriptomics dataset that could be used for further research.

The effect of soil depth on temperature sensitivity of extracellular enzyme activity decreased with elevation: Evidence from mountain grassland belts.

Temperature sensitivity of soil extracellular enzyme activity (EEA), indicated by the temperature coefficient Q10, is used to predict the effect of temperature on soil carbon (C), nitrogen (N), and phosphorus (P) cycling. At present, we lack understanding of elevation and soil depth variations in Q10 of EEA. Here, we measured the Q10 of three enzymes participating in C- (ß-1,4-glucosidase, BG), N- (leucine aminopeptidase, LAP), and P- (acid phosphatase, AP) cycling along a vertical grassland belt of China. Soils from five depths (0-10, 10-20, 20-40, 40-60, and 60-100 cm) were sampled from three elevations (low, <1000 m; middle, 1000-2000 m; high, 2000-3000 m) and incubated at four temperatures (5, 15, 25, 35 °C). The average Q10 of soil EEA ranged from 0.97 to 1.11 and the Q10 of LAP was higher than that of BG and AP. Generally, the Q10 of BG and LAP both increased from low to middle elevation and then decreased, while the Q10 of AP was stable. Moreover, the effect of soil depth on Q10 of EEA was weakened from low elevation to high elevation, and the factors driving Q10 of soil EEA changed with elevation. This study improved the understanding of the vertical pattern of Q10 of soil EEA in water-limited ecosystems, and highlighted that elevation could regulate the effect of soil depth on Q10 of EEA.

HAGLR aggravates neuropathic pain and promotes inflammatory response and apoptosis of lipopolysaccharide-treated SH-SY5Y cells by sequestering miR-182-5p from ATAT1 and activating NLRP3 inflammasome.

BACKGROUND: Chronic neuropathic pain is characterized by neuroinflammation. Previously, long noncoding RNA (lncRNA) HAGLR was reported to regulate the inflammatory response of SH-SY5Y cells. However, neither the specific function nor the potential mechanism of HAGLR in neuropathic pain has been explored. AIM OF THE STUDY: Our study is aimed to figure out the role of HAGLR in neuropathic pain. METHODS: SH-SY5Y cells were treated with lipopolysaccharide (LPS) to mimic neuron injury in vitro. The chronic constriction injury (CCI) rat models were established by ligation of sciatic nerve to mimic neuropathic pain in vivo. Behavioral assessment assays were performed to determine the effects of HAGLR on hypersensitivity in neuropathic pain. Enzyme-linked immunosorbent assay kits were used for detection of inflammatory cytokines. Flow cytometry analysis and Western blot were applied to detect apoptosis. RESULTS: HAGLR displayed high levels in spinal cords of CCI rats and in LPS treated SH-SY5Y cells. Knockdown of HAGLR inhibited inflammation and neuron apoptosis of LPS treated SH-SY5Y cells. Mechanistically, HAGLR bound with miR-182-5p in SH-SY5Y cells. ATAT1 served as a target of miR-182-5p. HAGLR activated the NLRP3 inflammasome by ATAT1. Rescue assays demonstrated that overexpression of ATAT1 or NLRP3 reversed the suppressive effects of HAGLR silencing on apoptosis and inflammatory response in SH-SY5Y cells and in spinal cords of CCI rats. The inhibitory effects of silenced HAGLR on hypersensitivity in neuropathic pain were also rescued by ATAT1 or NLRP3. CONCLUSIONS: HAGLR aggravates neuropathic pain by sequestering miR-182-5p from ATAT1 and activating NLRP3 inflammasome, which may provide a potential therapeutic target for neuropathic pain treatment.