Mobility census for monitoring rapid urban development.

Monitoring urban structure and development requires high-quality data at high spatio-temporal resolution. While traditional censuses have provided foundational insights into demographic and socio-economic aspects of urban life, their pace may not always align with the pace of urban development. To complement these traditional methods, we explore the potential of analysing alternative big-data sources, such as human mobility data. However, these often noisy and unstructured big data pose new challenges. Here, we propose a method to extract meaningful explanatory variables and classifications from such data. Using movement data from Beijing, which are produced as a by-product of mobile communication, we show that meaningful features can be extracted, revealing, for example, the emergence and absorption of subcentres. This method allows the analysis of urban dynamics at a high-spatial resolution (here 500 m) and near real-time frequency, and high computational efficiency, which is especially suitable for tracing event-driven mobility changes and their impact on urban structures.

Magnetic Microrobot Swarms with Polymeric Hands Catching Bacteria and Microplastics in Water.

The forefront of micro- and nanorobot research involves the development of smart swimming micromachines emulating the complexity of natural systems, such as the swarming and collective behaviors typically observed in animals and microorganisms, for efficient task execution. This study introduces magnetically controlled microrobots that possess polymeric sequestrant "hands" decorating a magnetic core. Under the influence of external magnetic fields, the functionalized magnetic beads dynamically self-assemble from individual microparticles into well-defined rotating planes of diverse dimensions, allowing modulation of their propulsion speed, and exhibiting a collective motion. These mobile microrobotic swarms can actively capture free-swimming bacteria and dispersed microplastics "on-the-fly", thereby cleaning aquatic environments. Unlike conventional methods, these microrobots can be collected from the complex media and can release the captured contaminants in a second vessel in a controllable manner, that is, using ultrasound, offering a sustainable solution for repeated use in decontamination processes. Additionally, the residual water is subjected to UV irradiation to eliminate any remaining bacteria, providing a comprehensive cleaning solution. In summary, this study shows a swarming microrobot design for water decontamination processes.

Retrospective analysis of laboratory results in 18 cases of severe asthma treated with omalizumab.

OBJECTIVE: The aim of this study was to explore the laboratory results in severe as asthma patients with omalizumab therapy and provide evidence for estimating omalizumab efficacy. METHODS: Retrospective study of 18 patients with severe asthma received omalizumab therapy in Shanghai General Hospital from 2020 to 2022 was performed. The basic data of patients were collected. The absolute number and the percentage of basophil and eosinophil in peripheral blood, total IgE level in serum, and as pulmonary function were detected at the beginning of treatment and 4 months after treatment. Differences between two groups were analyzed using Paired T test. RESULTS: The most common allergens collected from patients with moderate to severe asthma were dust mite (positive ratio 55.56%), mixed mold (16.67%), cat and dog dander, and Aspergillus fumigatus (11.11%). There was no significant difference in eosinophil and basophil counts in peripheral blood between the two groups. However, serum total IgE levels increased from (437.55±279.35) KU/L to (1071.42±721.28) KU/L (P=0.004), and FEV1/FVC ratio increased from (65.53±14.15)% to (73.91±13.63)% (P=0.005) after 4 months of treatment. CONCLUSIONS: The existing laboratory indicators for evaluation of omalizumab efficacy are still very limited, and new biomarkers need to be further developed. Elevated serum IgE levels at four weeks of treatment and FEV1/FVC may be potential indicators for omalizumab monitoring.

Prenatal dexamethasone exposure impairs rat blood-testis barrier function and sperm quality in adult offspring via GR/KDM1B/FSTL3/TGFß signaling.

Both epidemiological and animal studies suggest that adverse environment during pregnancy can change the offspring development programming, but it is difficult to achieve prenatal early warning. In this study we investigated the impact of prenatal dexamethasone exposure (PDE) on sperm quality and function of blood-testis barrier (BTB) in adult offspring and the underlying mechanisms. Pregnant rats were injected with dexamethasone (0.1, 0.2 and 0.4 mg·kg-1·d-1, s.c.) from GD9 to GD20. After weaning (PW4), the pups were fed with lab chow. At PW12 and PW28, the male offspring were euthanized to collect blood and testes samples. We showed that PDE significantly decreased sperm quality (including quantity and motility) in male offspring, which was associated with impaired BTB and decreased CX43/E-cadherin expression in the testis. We demonstrated that PDE induced morphological abnormalities of fetal testicle and Sertoli cell development originated from intrauterine. By tracing to fetal testicular Sertoli cells, we found that PDE dose-dependently increased expression of histone lysine demethylases (KDM1B), decreasing histone 3 lysine 9 dimethylation (H3K9me2) levels of follistatin-like-3 (FSTL3) promoter region and increased FSTL3 expression, and inhibited TGFß signaling and CX43/E-cadherin expression in offspring before and after birth. These results were validated in TM4 Sertoli cells following dexamethasone treatment. Meanwhile, the H3K9me2 levels of FSTL3 promoter in maternal peripheral blood mononuclear cell (PBMC) and placenta were decreased and its expression increased, which was positively correlated with the changes in offspring testis. Based on analysis of human samples, we found that the H3K9me2 levels of FSTL3 promoter in maternal blood PBMC and placenta were positively correlated with fetal blood testosterone levels after prenatal dexamethasone exposure. We conclude that PDE can reduce sperm quality in adult offspring rats, which is related to the damage of testis BTB via epigenetic modification and change of FSTL3 expression in Sertoli cells. The H3K9me2 levels of the FSTL3 promoter and its expression in the maternal blood PBMC can be used as a prenatal warning marker for fetal testicular dysplasia.

Distinct toxic effects, gene expression profiles, and phytohormone responses of Polygonatum cyrtonema exposed to two different antibiotics.

The excessive usage of veterinary antibiotics has raised significant concerns regarding their environmental hazard and agricultural impact when entering surface water and soil. Animal waste serves as a primary source of organic fertilizer for intensive large-scale agricultural cultivation, including the widely utilized medicinal and edible plant, Polygonatum cyrtonem. In this study, we employed a novel plant stress tissue culture technology to investigate the toxic effects of tetracycline hydrochloride (TCH) and sulfadiazine (SDZ) on P. cyrtonema. TCH and SDZ exhibited varying degrees of influence on plant growth, photosynthesis, and the reactive oxygen species (ROS) scavenging system. Flavonoid levels increased following exposure to TCH and SDZ. The biosynthesis and signaling pathways of the growth hormones auxin and gibberellic acid were suppressed by both antibiotics, while the salicylic acid-mediated plant stress response was specifically induced in the case of SDZ. Overall, the study unveiled both common and unique responses at physiological, biochemical, and molecular levels in P. cyrtonema following exposure to two distinct types of antibiotics, providing a foundational framework for comprehensively elucidating the precise toxic effects of antibiotics and the versatile adaptive mechanisms in plants.

Discovery, Optimization, and Evaluation of Novel Pyridin-2(1H)-one Analogues as Potent TRK Inhibitors for Cancer Treatment.

Tropomyosin receptor kinase (TRK) fusion, an oncogenic form of kinase with pan-tumor occurrence, is a clinically validated important antitumor target. In this study, we screened our in-house kinase inhibitor library against TRK and identified a promising hit compound 4 with a novel pyridin-2(1H)-one scaffold. Through a combination of structure-based drug design and structure-activity relationship (SAR) study, compound 14q was identified as a potent TRK inhibitor with good kinase selectivity. It also blocked cellular TRK signaling, thereby inhibiting TRK-dependent cell viability. Additionally, 14q displayed acceptable pharmacokinetic properties with 37.8% oral bioavailability in mice. Strong in vivo tumor growth inhibition of 14q was observed in subcutaneous M091 and KM12 tumor xenograft models with TRK fusion, causing significant tumor inhibition or even complete tumor regression.

Unveiling the toxic effects, physiological responses and molecular mechanisms of tobacco (Nicotiana tabacum) in exposure to organic ultraviolet filters.

Exposure to organic ultraviolet (UV) filters has raised concerns due to their potential adverse effects on environments. However, their toxic mechanisms on plants remain elusive. In this study, using integrative physiological and transcriptomic approaches we investigated the physiological and molecular responses to three representative UV filters, namely oxybenzone (OBZ), avobenzone (AVB), and octinoxate (OMC), in an agricultural model plant tobacco. The exposure to UV filters disrupts the functionality of photosystem reaction centers and the light-harvesting apparatus. Concurrently, UV filters exert a suppressive effect on the expression of genes encoding Rubisco and Calvin-Benson cycle enzymes, resulting in a decreased efficiency of the Calvin-Benson cycle and consequently hampering the process of photosynthesis. Exposure to UV filters leads to significant generation of reactive oxygen species within tobacco leaves and downregulation of oxidoreductase activities. Moreover, UV filters promote abscisic acid (ABA) accumulation by inducing the expression of ABA biosynthesis genes whereas repress indole-3-acetic acid (IAA) biosynthesis gene expression, which induce leaf yellowing and slow plant growth. In summary, the organic UV filters exert toxic effects on tobacco growth by inhibiting chlorophyll synthesis, photosynthesis, and the Calvin-Benson cycle, while generating excessive reactive oxygen species. This study sheds light on the toxic and tolerance mechanisms of UV filters in agricultural crops.

Discovery of a 1,6-naphthyridin-4-one-based AXL inhibitor with improved pharmacokinetics and enhanced in vivo antitumor efficacy.

The receptor tyrosine kinase AXL has emerged as an attractive target in anticancer drug discovery. Herein, we described the discovery of a new series of 1,6-naphthyridin-4-one derivatives as potent AXL inhibitors. Starting from a low in vivo potency compound 9 which was previously reported by our group, we utilized structure-based drug design and scaffold hopping strategies to discover potent AXL inhibitors. The privileged compound 13c was a highly potent and orally bioavailable AXL inhibitor with an IC50 value of 3.2 ± 0.3 nM. Compound 13c exhibited significantly improved in vivo antitumor efficacy in AXL-driven tumor xenograft mice, causing tumor regression at well-tolerated dose, and demonstrated favorable pharmacokinetic properties (MRT = 16.5 h, AUC0-∞ = 59,815 ng h/mL) in Sprague-Dawley rats. These results suggest that 13c is a promising therapeutic candidate for AXL-targeting cancer treatment.

Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Effect of acupuncture on mild cognitive impairment in the elderly: A randomized controlled trial.

Background and objective: Mild cognitive impairment (MCI) is a cognitive dysfunction syndrome defined mostly by memory or other cognitive impairments, and may serve as a precursor to Alzheimer's disease (AD). In recent years, acupuncture has gained recognition as a potential intervention for MCI, attracting significant attention as a promising and well-established therapy. In this study, we critically evaluate the clinical efficacy and safety of an innovative acupuncture approach, termed "Kidney Nourishment and Spirit Regulation", as a therapeutic modality for MCI in geriatric populations. Methods: A prospective, randomized, single-blind, placebo-controlled, single-center clinical trial design where patients will be allocated in acupuncture, placebo (sham acupuncture sessions), or blank for eight weeks. The blank group will receive health education over the same eight-week period and will be offered compensatory acupuncture therapy after this period. The selected acupoints for this investigation include GV20, EX-HN1, GV24, GV29, CV6, CV4, PC6, KI3, LI4, LR3, HT7 and SP6. The primary outcome measure will be the Montreal Cognitive Assessment (MoCA), while secondary outcomes include the Mini Mental State Examination (MMSE), Activity of Daily Living (ADL), and Electroencephalogram (EEG). Discussion: This study seeks to provide an optimum regimen for acupuncture therapy in elderly MCI patients and to provide considerable theoretical evidence for its popularization and future broad adoption. We thus postulate that the current trial data might enlighten and potentially guide future research in terms of study design refinement.

MicroRNAs in Small Extracellular Vesicles from Amniotic Fluid and Maternal Plasma Associated with Fetal Palate Development in Mice.

Cleft palate (CP) is a common congenital birth defect. Cellular and morphological processes change dynamically during palatogenesis, and any disturbance in this process could result in CP. However, the molecular mechanisms steering this fundamental phase remain unclear. One study suggesting a role for miRNAs in palate development via maternal small extracellular vesicles (SEVs) drew our attention to their potential involvement in palatogenesis. In this study, we used an in vitro model to determine how SEVs derived from amniotic fluid (ASVs) and maternal plasma (MSVs) influence the biological behaviors of mouse embryonic palatal mesenchyme (MEPM) cells and medial edge epithelial (MEE) cells; we also compared time-dependent differential expression (DE) miRNAs in ASVs and MSVs with the DE mRNAs in palate tissue from E13.5 to E15.5 to study the dynamic co-regulation of miRNAs and mRNAs during palatogenesis in vivo. Our results demonstrate that some pivotal biological activities, such as MEPM proliferation, migration, osteogenesis, and MEE apoptosis, might be directed, in part, by stage-specific MSVs and ASVs. We further identified interconnected networks and key miRNAs such as miR-744-5p, miR-323-5p, and miR-3102-5p, offering a roadmap for mechanistic investigations and the identification of early CP biomarkers.

The recent advances in cell delivery approaches, biochemical and engineering procedures of cell therapy applied to coronary heart disease.

Cell therapy is an important topic in the field of regeneration medicine that is gaining attention within the scientific community. However, its potential for treatment in coronary heart disease (CHD) has yet to be established. Several various strategies, types of cells, routes of distribution, and supporting procedures have been tried and refined to trigger heart rejuvenation in CHD. However, only a few of them result in a real considerable promise for clinical usage. In this review, we give an update on techniques and clinical studies of cell treatment as used to cure CHD that are now ongoing or have been completed in the previous five years. We also highlight the emerging efficacy of stem cell treatment for CHD. We specifically examine and comment on current breakthroughs in cell treatment applied to CHD, including the most effective types of cells, transport modalities, engineering, and biochemical approaches used in this context. We believe the current review will be helpful for the researcher to distill this information and design future studies to overcome the challenges faced by this revolutionary approach for CHD.

Reconfigurable self-assembly of photocatalytic magnetic microrobots for water purification.

The development of artificial small-scale robotic swarms with nature-mimicking collective behaviors represents the frontier of research in robotics. While microrobot swarming under magnetic manipulation has been extensively explored, light-induced self-organization of micro- and nanorobots is still challenging. This study demonstrates the interaction-controlled, reconfigurable, reversible, and active self-assembly of TiO2/α-Fe2O3 microrobots, consisting of peanut-shaped α-Fe2O3 (hematite) microparticles synthesized by a hydrothermal method and covered with a thin layer of TiO2 by atomic layer deposition (ALD). Due to their photocatalytic and ferromagnetic properties, microrobots autonomously move in water under light irradiation, while a magnetic field precisely controls their direction. In the presence of H2O2 fuel, concentration gradients around the illuminated microrobots result in mutual attraction by phoretic interactions, inducing their spontaneous organization into self-propelled clusters. In the dark, clusters reversibly reconfigure into microchains where microrobots are aligned due to magnetic dipole-dipole interactions. Microrobots' active motion and photocatalytic properties were investigated for water remediation from pesticides, obtaining the rapid degradation of the extensively used, persistent, and hazardous herbicide 2,4-Dichlorophenoxyacetic acid (2,4D). This study potentially impacts the realization of future intelligent adaptive metamachines and the application of light-powered self-propelled micro- and nanomotors toward the degradation of persistent organic pollutants (POPs) or micro- and nanoplastics.

Unprecedented sesterterpenoids, orientanoids A-C: discovery, bioinspired total synthesis and antitumor immunity.

Sesterterpenoids are a very rare class of important natural products. Three new skeletal spiro sesterterpenoids, named orientanoids A-C (1-3), were isolated from Hedyosmum orientale. Their structures were determined by a combination of spectroscopic data, X-ray crystallography, and total synthesis. To obtain adequate materials for biological research, the bioinspired total syntheses of 1-3 were effectively achieved in 7-8 steps in overall yields of 2.3-6.4% from the commercially available santonin without using any protecting groups. In addition, this work also revised the stereochemistry of hedyosumins B (6) and C (10) as 11R-configuration. Tumor-associated macrophages (TAMs) have emerged as important therapeutic targets in cancer therapy. The in-depth biological evaluation revealed that these sesterterpenoids antagonized the protumoral and immunosuppressive functional phenotype of macrophages in vitro. Among them, the most potent and major compound 1 inhibited protumoral M2-like macrophages and activated cytotoxic CD8+ T cells, and consequently inhibited tumor growth in vivo.

Transcriptome profiling and ceRNA network of small extracellular vesicles from resting and degranulated mast cells.

Aim: This study aimed to investigate the transcriptomic characteristics and interactions between competitive endogenous RNAs (ceRNAs) within small extracellular vesicles (sEVs) derived from mast cells (MCs). Methods: Transcriptome sequencing analyzed lncRNA, circRNA and mRNA expression in resting and degranulated MC-derived sEVs. Constructed ceRNA regulatory network through correlation analysis and target gene prediction. Results: Differentially expressed 1673 mRNAs, 173 lncRNAs and 531 circRNAs were observed between resting and degranulated MCs-derived sEVs. Enrichment analysis revealed involvement of neurodegeneration, infection and tumor pathways. CeRNA networks included interactions between lncRNA-miRNA, circRNA-miRNA and miRNA-mRNA, targeting genes in the hippo and wnt signaling pathways linked to tumor immune regulation. Conclusion: This study provides valuable insights into MC-sEV molecular mechanisms, offering significant data resources for further investigations.

Mast cells (MCs) are important for various health conditions, including allergies, infections, tumors and brain disorders. MCs release tiny structures called small extracellular vesicles (sEVs) that carry different molecules, such as genetic material, to communicate with other cells in the body's immune system. However, we still do not know much about how these sEVs work. In this study, we examined the sEVs from MCs and found specific genetic molecules that change when MCs become activated. We discovered that these molecules are involved in important processes related to diseases like neurodegeneration and infection. We also identified networks of molecules that interact with each other, influencing immune regulation of tumor. By studying this, we gain new knowledge about how MCs use sEVs to communicate with other cells in our body during immune responses.

Molecular evaluation of Cryptosporidium spp. in sheep in southern Xinjiang, China.

Cryptosporidium spp. are diarrheagenic intestinal parasites with multiple hosts worldwide. A total of 1252 fresh fecal samples of sheep were collected from 10 large-scale farms in southern Xinjiang. Based on the small subunit ribosomal (SSU rRNA) gene of Cryptosporidium, 100 Cryptosporidium-positive samples (8.0%, 100/1252) were detected by PCR. Nine out of 10 farms were positive for Cryptosporidium, with the highest infection rate being 18.4% (23/125) on farm 9 in Qira. The infection rates of Cryptosporidium in pre-weaned lambs, weaned lambs, fattening sheep, and adult sheep were 20.3% (61/301), 10.3% (34/329), 0.9% (3/327), and 0.7% (2/295), respectively. Three Cryptosporidium species were identified, namely, C. xiaoi (n = 61), C. parvum (n = 22), and C. ubiquitum (n = 17). Of them, C. xiaoi was detected on all positive farms and in different age groups of sheep. The subtypes of C. parvum and C. ubiquitum were identified by PCR at the 60 kDa glycoprotein (gp60) gene. Two C. parvum subtypes were identified: IIdA19G1 (n = 21) and IIdA15G1 (n = 1). One C. ubiquitum subtype was identified with XIIa (n = 17). These results indicated the common transmission and genetic diversity of Cryptosporidium in sheep in southern Xinjiang, and further investigations are needed on the zoonotic potential of C. parvum and C. ubiquitum in this region.

Nitrogen addition stimulates N2O emissions via changes in denitrification community composition in a subtropical nitrogen-rich forest.

Microbially driven nitrification and denitrification play important roles in regulating soil N availability and N2O emissions. However, how the composition of nitrifying and denitrifying prokaryotic communities respond to long-term N additions and regulate soil N2O emissions in subtropical forests remains unclear. Seven years of field experiment which included three N treatments (+0, +50, +150 kg N ha-1 yr-1; CK, LN, HN) was conducted in a subtropical forest. Soil available nutrients, N2O emissions, net N mineralization, denitrification potential and enzyme activities, and the composition and diversity of nitrifying and denitrifying communities were measured. Soil N2O emissions from the LN and HN treatments increased by 42.37% and 243.32%, respectively, as compared to the CK. Nitrogen addition significantly inhibited nitrification (N mineralization) and significantly increased denitrification potentials and enzymes. Nitrification and denitrification abundances (except nirK) were significantly lower in the HN, than CK treatment and were not significantly correlated with N2O emissions. Nitrogen addition significantly increased nirK abundance while maintaining the positive effects of denitrification and N2O emissions to N deposition, challenging the conventional wisdom that long-term N addition reduces N2O emissions by inhibiting microbial growth. Structural equation modeling showed that the composition, diversity, and abundance of nirS- and nirK-type denitrifying prokaryotic communities had direct effects on N2O emissions. Mechanistic investigations have revealed that denitrifier keystone taxa transitioned from N2O-reducing (complete denitrification) to N2O-producing (incomplete denitrification) with increasing N addition, increasing structural complexity and diversity of the denitrifier co-occurrence network. These results significantly advance current understanding of the relationship between denitrifying community composition and N2O emissions, and highlight the importance of incorporating denitrifying community dynamics and soil environmental factors together in models to accurately predict key ecosystem processes under global change.

LncRNA-Anrel promotes the proliferation and migration of synovial fibroblasts through regulating miR-146a-mediated annexin A1 expression.

OBJECTIVE: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) are closely related to multiple human autoimmune diseases, and their dysregulation is tightly linked to inflammation and disease progression. Nonetheless, little is known about the consequences of aberrant expression of lncRNAs during rheumatoid arthritis (RA) development. In this study, we screened for the expressions of lncRNAs in RA synovial fibroblasts (RA-SF) and investigated their functions in RA-SF proliferation and migration, and the relevant underlying mechanisms. METHODS: The lncRNAs expression profiles were interrogated with microarrays. The expressions of key lncRNAs were confirmed in synovial fibroblasts from RA patients and MH7A cells using qRT-PCR. Proliferations and migrations of MH7A and HFL-1 cells were evaluated using CCK-8 assay and cell migration assay kits, respectively. The expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and cell migration related proteins (MMP-1 and MMP-3) were evaluated using qRT-PCR and western blotting. Collagen type II-induced arthritis (CIA) in mice was used as an animal model of RA. RESULTS: Nine lncRNAs were significantly altered in RA-SF, of which lncRNA-000239 showing the most significant upregulation. Overexpression of lncRNA-000239 significantly enhanced the proliferation and migration of human RS-SF cells (MH7A), while the opposite effect was observed with lncRNA-000239 silencing. Importantly, lncRNA-000239 enhanced annexin A1 expression by upregulating the expression of miR-146a. Moreover, locally enhanced expression of lncRNA-000239 promoted the onset of arthritis in CIA. CONCLUSION: These data indicate that lncRNA-000239 upregulates annexin A1 expression via miR-146a and thus, promotes the proliferation and migration of RA-SF. This highlights a potential role of lncRNA-000239 as an inflammatory factor of RA.

Parental presence during induction of anesthesia in children undergoing tonsillectomy and adenoidectomy.

OBJECTIVE: To investigate the effect of parental presence during induction of anesthesia (PPIA) in relieving preoperative anxiety of children undergoing tonsillectomy and adenoidectomy. METHODS: One hundred and sixty children undergoing tonsillectomy and adenoidectomy were divided into the control group and the trial group. The control group received routine nursing in the operation room, while anesthesia was induced in the trial group children in the presence of their parents as part of the routine nursing. The differences in heart rate and mean dynamic pressure during pre-operative visit and anesthesia induction between the two groups were observed and recorded. The Modified Yale Preoperative Anxiety Scale (m-YPAS) and the Induction Compliance Checklist (ICC) were scored. The anxiety status of the children and their family members in the two groups was scored at different times, and the psychological stress of anesthesiologists during anesthesia induction was scored by a visual analogue scale. The differences in each index between the two groups were compared. Operation time and costs in-hospital were also compared. RESULTS: Compared with the control group, the heart rate and blood pressure scores as well as the ICC in the trial group were lower than those in the control group (P < 0.01). On comparing the scores of m-YPAS between the two groups, we observed that the scores of the children in the trial group were lower than those in the control group before entering the induction room and anesthesia induction (P < 0.01). There was no statistical difference between the scores of the children in the trial group and the control group on the day of operation and on the way to the operating room (P > 0.05). The nursing satisfaction scores of the family members in the trial group were significantly superior to those in the control group (P < 0.01). The scores of the visual analogue scale for psychological pressure of anesthesiologists during anesthesia induction were higher in the trial group than in the control group (P < 0.05). The operation time and costs in study group were both significantly higher than those of control group (P < 0.05). CONCLUSION: PPIA can significantly reduce preoperative anxiety and surgical physiological stress response in children undergoing tonsillectomy and adenoidectomy, and it is worth being encouraged.

ELK4 exerts opposite roles in cytokine/chemokine production and degranulation in activated mast cells.

The proliferative potential of mast cells after activation for 3-4h was found to be decreased, which suggests that mast cell degranulation and cell proliferation are differentially regulated. ELK4, a member of the ternary complex factor (TCF) subfamily of Ets transcription factors, is one of the downstream effectors of MAPK signaling that is critical for cell proliferation. And Elk4 has been identified to be vital for macrophage activation in response to zymosan and the transcriptional response to 12-O-tetrade canoyl phorbol-13-acetate (TPA) stimulation in fibroblast. However, the effect of ELK4 on the mast cell transcriptional response to FcϵRI and GPCR mediated activation and its potential functional significance in mast cells remain unclear. Here, we showed that ELK4 expression is downregulated in activated mast cells. Elk4 knockout suppresses cell proliferation and impedes the cell cycle in bone marrow-derived mast cells (BMMCs), which is associated with decreased transcription of cell cycle genes. Additionally, the transcriptional activation of cytokines and chemokines is diminished while mast cell degranulation is enhanced in Elk4 knockout BMMCs. Mechanistically, ELK4 might positively modulate Hdc, Ccl3 and Ccl4 transcription by interacting with MITF and negatively regulate the transcription of degranulation-related genes by complexing with SIRT6. Overall, our study identifies a new physiological role of the transcription factor ELK4 in mast cell proliferation and activation.