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Objective·To explore the epidemiological characteristics of severe asthma in children and analyze the risk factors.Methods·A single-center prospective cohort study was conducted. Six hundred and seventy four children with difficult-to-treat asthma who visited the Children´s Hospital of Fudan University from January 1 to December 31, 2021 were included to establish a dynamic cohort. Basic information (including gender, age, gestational age at birth, birth weight, etc.) and comorbidity of the cohort members were collected. The asthma control status, drug inhalation technique level, medication compliance, pulmonary function parameters [forced expiratory volume in one second (FEV1) as a percent-age of the predicted value (FEV1%pred), FEV1/ forced vital capacity (FVC), and the rate of estimated values of forced expiratory flow at 50% of FVC exhaled (FEF50), FEF75, and FEF25-75 in percent-predicted value, respectively], airway inflammation index [fraction exhaled nitric oxide (FeNO)], and allergy status parameters [eosinophil (EOS) and immunoglobulin E (IgE)] of all cohort members were evaluated. All cohort members underwent re-evaluation respectively at the specialist asthma clinic of the hospital at 3, 6, 9, and 12 months.Results·At the endpoint of the cohort, 52 children were diagnosed with severe asthma, accounting for 7.7%. A high proportion of severe asthma was found in children who were exposed to secondhand smoke, used air conditioning at home all year round, or had coexisting rhinitis/nasosinusitis, FEV1%pred300/μL, IgE>200 IU/L, or FeNO>20/25 ppb [FeNO>20 ppb (≤12 years old) or >25 ppb (>12 years old), 1 ppb=1×10-9 mol/L]. A high proportion of non-severe asthma was found in children who were breastfed for 6 months or longer, or had good medication compliance. The differences were statistically significant (all P

Sports performance is one of the important indicators to evaluate athletes, which reflects the level of physical exercise. In recent years, our national physical quality has been declining and the physical health of young people is unsatisfactory. In order to improve the quality of national health, promote the harmonious development of society and cultivate students' awareness of lifelong fitness, it is necessary and far-reaching to study the most important factors affecting human physical fitness. Sports performance is an important indicator to evaluate athletes, and sports performance is closely related to the level of physical fitness, so the most basic and valuable thing for sportsmen and women is to ensure their body fat and physical fitness. In recent years, with the rapid economic development, social progress and improvement of people's quality of life in China, fitness in such a fiercely competitive environment has become more and more important. Therefore, in order to better promote the national physical health problem to be solved as soon as possible we must do a good job of national fitness program, which can provide more talent support and intellectual support for the national sports career and improve the national physical fitness. In this paper, through the statistics and analysis of athletes' physical health test data, we can provide more talent support for sports programs.

Password guessing is an important research direction in password security.Password guessing based on generative adversarial network(GAN) is a new method proposed in recent years,which guides the update of the generator according to evaluation results on passwords generated by the discriminator.Consequently,password guessing sets can be generated with trained GANs.However,the existing GAN-based password guessing models have low efficiency due to inadequate guidance of the discriminator to the generator.To solve this problem,an improved GAN password guessing model AC-Pass based on reinforcement learning Actor-Critic algorithm is proposed.The AC-Pass model guides the update of the generation strategy of the Actor network at each time step through the output rewards of the discriminator and the Critic network,and realizes the reinforce guidance of password sequence generation process.The proposed AC-Pass model is implemented on RockYou,LinkedIn and CSDN data sets and compared with PCFG model and the existing GANs-based password guessing models such as PassGAN and seqGAN.Results on homologous testing sets and heterologous testing sets indicate that password cracking rate of AC-Pass model on the guessing set is higher than that of PassGAN and seqGAN.Moreover,AC-Pass shows better guessing performance than PCFG when the password spatial distribution between the testing set and the training set is significant.In addition,the AC-Pass model has a large password output space.As the size of password guessing set increases,the cracking rate continues to rise.

NK cells-based cancer therapy combined with chemotherapeutic drugs for the treatment of tumors can enhance the immunosensitivity of NK cells, increase the expression of NK cell receptors, and eventually boost the killing effect of NK cells on cancer cells. Selenium (Se) with different chemical structures can be metabolized into selenoproteins to regulate tumor and immune cells’ fate and functions. Herein, we found that, functionalized Se nanoparticles (SeNPs) combining with metformin (met) could amply the immunotherapeutic effects of NK92 cells against osteosarcoma cancer. The results revealed that TW80-SeNPs combined with met had the optimum performance on NK92 cells for HepG2 cells, owing to the increased ROS in HepG2 cells and the augmented expression of cell surface receptor proteins ULBP-3/4, PD-L1, MICA, and NK92 cell surface receptor proteins PD-1 and FasL. Additionally, TW80-SeNPs were gradually metabolized into selenoproteins (Gpx4 and TR1) into human osteosarcoma MG63 cells to reinforce the anticancer effect of NK92 cells by regulating the redox balance in the tumor microenvironment. This study provides a therapeutic approach in treating cancer itself or diabetes coupled with cancer. Moreover, it provides a multidrug strategy to improve immune cell function in practical applications, especially for synergistic immunotherapy of osteosarcoma.

ObjectiveTo discuss the family environment characteristics of senior high school students with psychological problems， and to provide references for realizing management of senior high school students' mental health.MethodsA total of 1 917 senior high school students in Foshan No. 2 Middle School were enrolled， and assessed using Middle School Student Mental Health Scale （MSSMHS-60） and a self-compiled family environment questionnaire. Then the family environment characteristics of senior high school students with psychological problems were analyzed.ResultsThe total score of MSSMHS-60 was （1.83±0.49） in 1 917 senior high school students， and was （2.40±0.36） in 602 （31.40%） students with psychological problems. The detection rate of psychological problems demonstrated significant difference among senior high school students with different status of companionship， household finance， parental rearing style and kinship （χ2=16.951， 38.142， 90.545， 59.448， P

Background: At present lacking of effective and safe anti-obesity drugs available leads to initiate obesity worldwide that promotes several diseases like cardiovascular diseases, liver diseases, and NASH. The development of new therapeutics is an emergency demand to cure obesity-related diseases. Mitochondrial uncoupling protein 1 (UCP1) gene could be a potential target to develop new drug moieties that can treat obesity-related diseases. Methods: We used a GFP reporter cell line to screen epigenetic drug libraries to identify UCP1 regulators that could be effective drug candidates to treat obesity-related diseases. In this study, we employed an in-silico study that revealed drug-protein interaction and stability of drugs with protein. Results: Screening epigenetic drug libraries, we identified XL019 significant TYK2, JAK2, and JAK3, inhibitors that can significantly promote UCP1 gene expression in brown adipocytes. Here, we found that XL019 plays a vital role to modulates mitochondrial function and could be beneficial against obesity. Further analysis shows that XL019 significantly improved mitochondrial ATP production and mitochondrial DNA copy number of adipocytes compared with the control group. The in-silico study demonstrated drug-protein interaction and binding side with UCP1 gene. Thus XL019 improves mitochondrial function that would be effective drug candidate to treat metabolic diseases and obesity-related diseases. Conclusion: In this study, we confirm the potential effect of the XL019 epigenetic drug that modulates mitochondrial function and in-silico study on drug-likeness, stability, and safety profile. Further investigation will reveal the new insight into the mechanism of action against obesity, metabolic diseases ( NASH, Fibrosis, cardiac diseases and so on), by modulation of the mitochondrial UCP1 gene and mitochondrial function.

Objective Through a pain study of buccal gingival mucosa sensitivity of the mandible, the corresponding sensitive area of pain was determined, which provided the basis for reducing the pain and discomfort of oral diagnosis and treatment. Methods 400 patients with mandibular tooth extraction in the outpatient department of stomatology were selected. During tooth extraction, articaine epinephrine injection was used for infiltration anesthesia. The injection needle size was 0.3 mm × 21 mm, and the injection site was about 5 mm away from the buccal gingival margin. The pain degree of the patients was recorded. The data were statistically analyzed using the modified International pain classification method. Results Among the 400 patients who underwent mandible extraction, 75% (300 patients) graded their pain from painless to moderate, and 25% (100 patients) reported moderate to severe and severe pain. Of those in the moderate to severe and severe groups, 50% and 42% reported pain in the central and lateral incisors, respectively, and 38% were in the canine group. When comparing the moderate to severe and the severe groups, 16% and 10% were in the bicuspid group, 16% and 12% and 16% were in the molar group, respectively . There were significant differences in the pain sensitivity of different teeth positions (χ2=54.203, P < 0.001). The proportion of moderate to severe and severe pain in the anterior teeth group was higher than it was in the posterior teeth group (χ2=55.555, P < 0.001). There were significant differences in the pain sensitivity of different ages (χ2=96.501, P=0.000), and there was a positive correlation between pain and age (r=0.465, P < 0.001). The proportion of women with at least a moderate degree of pain was higher than that of men (χ2=12.298, P=0.031). Conclusion The sensitivity of the buccal gingival mucosa to pain is different in different positions of the mandible. The sensitivity of the anterior gingiva is higher than that of the posterior gingiva. Age is positively correlated with the degree of pain. Further, compared with men, women are more sensitive to pain.

With the rapid development of computer networks, more hosts are connected to the Internet where they could communicate with each other. The need for network service has exceeded the service capacity of the network, and the Quality of Service (QoS) is gradually declining. Based on existing Shortest Path First (SPF) algorithm, this paper proposes a new QoS required transmission path approach by considering the overhead balance of network resources. This paper uses the entropy granularity as the main line in the application of routing protocols. Firstly, it researches the optimization of routing algorithms for network load balancing resources, routing algorithms based on link traffic distributing weights, link weight optimization based on adaptive genetic algorithm and computational intelligence based on entropy granularity theory. This research proposes a method to apply entropy granularity to Open Shortest Path First (OSPF) routing, including the implementation of the method. After that, a case study is presented by using some examples.

Objective(s): The aim of this study is to explore the potential neuroprotective effects of Ginkgolide B (GB), a main terpene lactone and active component in Ginkgo biloba, in hypoxia-induced neuronal damage, and to further investigate its possible mechanisms.Materials and Methods: 54 Sprague-Dawley rats were randomly divided into three groups: the untreated control group (n=18); the hypoxia group (n=18; exposed to 6000 m simulated plateau altitude for six days); and the GB group (n=18; intragastric administration of 12 mg/kg GB three days prior to rapid adaption to 6000 m and on the first two days of hypoxia). After hypoxia exposure for six days, we dissected out the brain hippocampi and performed hematoxylin and eosin staining, Nissl staining, and TUNEL staining. Homogenates of the hippocampi were used to test the oxidative stress indices including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase. Bax and caspase-3 expression in the hippocampal tissue was measured using qRT-PCR.Results: Treatment with GB before exposure to hypoxia could protect neural cells and increase the number of Nissl bodies. TUNEL and qRT-PCR results demonstrated that GB treatment could decrease apoptotic cells in different areas of the hippocampus. Antioxidant defense systems such as SOD, GSH, and catalase were decreased (P

Compared to silicon devices, silicon carbide (SiC) devices have much lower C(oss) and Q(g); they can switch at much higher speed, SiC power modules are thus more sensitive to stray parameters. Large stray inductance may result in high voltage spikes and cause severe electro-magnetic interference (EMI) issues; unbalanced stray inductance may contribute to uneven current sharing between parallel devices. Low and symmetrical inductance is a necessity to fully utilise the superior characteristics of SiC devices. This paper first studies the current sharing and voltage spike mechanisms of multichip power modules (MCPMs). Stray inductance distribution, current sharing as well as voltage spikes under different direct bonded copper (DBC) layout conditions are investigated using finite element modelling software. A round symmetrical DBC layout is then proposed. Compared with conventional ones, the proposed structure is symmetrical in stray inductance distribution; thus improving the consistency among chips. To reduce the total equivalent stray inductance and tackle the voltage spike problem, this study further presents an improved 3D structure on the basis of the round symmetrical DBC. The stray inductance extraction and double pulse simulation results verify the effectiveness of the improved 3D structure in current sharing as well as voltage spike reduction.

The single-factor evaluation method, improved Nemerow index method, fuzzy mathematical synthesis evaluation method and comprehensive nutrient status index method were used to evaluate the water quality of the Zijiang River in summer, and to analyze the applicability of the evaluation methods. The results show that: (1) The Zijiang River is heavily polluted with nitrogen and TN is the main pollutant in the summer. The overall nutrient status index is 34.33, which is not eutrophic. (2) The single-factor evaluation method is simple and suitable for rapid identification of excessive pollutants, but cannot reflect the water quality. the Nemerow index method takes into account the weight of each evaluation factor in the river water quality, and is suitable for making a comprehensive evaluation of the river water quality, but has a certain degree of subjectivity when classifying the water quality. The fuzzy comprehensive evaluation method is suitable for reflecting the influence of different evaluation factors on water quality by calculating the weight and membership degree of each evaluation factor, but the calculation is complicated.The Integrated Nutrient Status Index method is suitable for determining whether eutrophication is occurring in a water body and cannot determine the water quality category.

This paper takes each province and region as the research object and 2017 as the research period, and the water consumption of power production was analyzed. The results showed that China’s electricity production consumed 6.57 billion m³ of water, accounting for 2% of the total social water consumption in 2017. Thermal power is the most water-consuming power source in China, accounting for 78% of the total water consumption in the country’s electric power development. Based on the calculated results, this study also puts forward relevant suggestions for realizing energy-water coordinated security.

This paper takes each province and region as the research object and 2017 as the research period, and the energy consumption of China’s social water cycle process was analyzed. The results showed that the total power consumption of China’s social water cycle process was 1082.81 billion kWh, accounting for 17.2% of the total power consumption of China’s society in 2017. Terminal water consumption is the biggest energy consumption. Based on the calculated results, this study puts forward relevant suggestions for realizing energy-water coordinated security.

Sirtuin 1 (SIRT1) is a histone/protein deacetylase in the cellular response to inflammatory, metabolic, and oxidative stressors. We previously reported that myeloid SIRT1 regulates the inflamed livers canonical pyroptosis cell death pathway. However, whether/how hepatocyte SIRT1 is engaged in programmed cell death in the cold-stressed liver remains uncertain. Here, we undertook translational studies in human and mouse orthotopic liver transplantation (OLT) to interrogate the significance of hepatocyte-specific SIRT1 in cold-stored donor livers and liver grafts after reperfusion. In the clinical arm of sixty human OLT patients, hepatic SIRT1 levels in cold-preserved donor livers correlated with the anti-apoptotic Bcl-2 expression. After reperfusion, improved OLT function was accompanied by hepatic SIRT1 levels negatively associated with cleaved caspase-3 expression. In the experimental arm, we compared FLOX-control with hepatocyte-specific SIRT1-KO livers after orthotopic transplantation into WT mouse recipients, parallel with primary murine hepatocyte cultures subjected to cold activation with/without knockdown of SIRT1, GSDME, and IL18Rβ. Indeed, hepatocyte SIRT1 deficiency upregulated apoptosis and GSDME-mediated programmed cell death, deteriorating hepatocellular function and shortening OLT survival. Augmented GSDME processing, accompanied by increased secretion of IL18 by stressed hepatocytes, was prominent in SIRT1-deficient, cold-stored livers. Hepatocyte SIRT1 expression regulated anti-apoptotic Bcl-2/XIAP proteins, suppressed cold stress-triggered apoptosis, and mitigated GSDME licensing to release IL18. Notably, consistent with the ability of IL18 to depress hepatocyte SIRT1 and Bcl-2/XIAP in vitro, IL18 neutralization in vivo prevented hepatocellular damage and restored the anti-apoptotic phenotype in otherwise injury-prone SIRT1-deficient OLTs. In conclusion, this translational study identifies a novel hepatocyte SIRT1-IL18 molecular circuit as a therapeutic target in the mechanism underpinning hepatocyte death pathways in human and mouse liver transplantation.

At present, the research on detection of lung cancer includes the sample image segmentation, extracting visual features of lung cancer and generating the classification model by training learning, then according to the classification model generated to classify the inspected images. But this kind of method usually needs a large amount of calculation and speed is slow. In order to find the region of interest as soon as possible and improve the detection speed, this paper attempts to introduce the current popular Itti visual attention model into the lung cancer detection. However, because medical images usually have low contrast, the Itti method is not directly applied to extract the region of interest in medical image. Therefore the selective visual attention mechanism combined with shape feature of target is proposed. Firstly some primary features are chosen, such as gray scale, direction, corner point and edge to generate saliency map, and then the significant regions are segmented and judged. Compared to popular lung cancer detection method, this method can improve the detection rate of suspected lung cancer and has great significance for the early detection, early diagnosis and treatment of lung cancer.

Background & aimsAlthough Ikaros (IKZF1) is a well-established transcriptional regulator in leukocyte lymphopoiesis and differentiation, its role in myeloid innate immune responses remains unclear. Sirtuin 1 (SIRT1) is a histone/protein deacetylase involved in cellular senescence, inflammation, and stress resistance. Whether SIRT1 signaling is essential in myeloid cell activation remains uncertain, while the molecular communication between Ikaros and SIRT1, two major transcriptional regulators, has not been studied.MethodsWe undertook molecular and functional studies to interrogate the significance of the myeloid Ikaros-SIRT1 axis in innate immune activation and whether it may serve as a homeostatic sentinel in human liver transplant recipients (hepatic biopsies) and murine models of sterile hepatic inflammation (liver warm ischemia-reperfusion injury in wild-type, myeloid-specific Sirt1-knockout, and CD11b-DTR mice) as well as primary bone marrow-derived macrophage (BMM) cultures (Ikaros silencing vs. overexpression).ResultsIn our clinical study, we identified increased post-reperfusion hepatic Ikaros levels, accompanied by augmented inflammasome signaling yet depressed SIRT1, as a mechanism of hepatocellular damage in liver transplant recipients. In our experimental studies, we identified infiltrating macrophages as the major source of Ikaros in IR-stressed mouse livers. Then, we demonstrated that Ikaros-regulated pyroptosis - induced by canonical inflammasome signaling in BMM cultures - was SIRT1 dependent. Consistent with the latter, myeloid-specific Ikaros signaling augmented hepatic pyroptosis to aggravate pro-inflammatory responses in vivo by negatively regulating SIRT1 in an AMPK-dependent manner. Finally, myeloid-specific SIRT1 was required to suppress pyroptosis, pro-inflammatory phenotype, and ultimately mitigate hepatocellular injury in ischemia-stressed murine livers.ConclusionThese findings identify the Ikaros-SIRT1 axis as a novel mechanistic biomarker of pyroptosis and a putative checkpoint regulator of homeostasis in response to acute hepatic stress/injury in mouse and human livers.Lay summaryThis report describes how crosstalk between Ikaros and SIRT1, two major transcriptional regulators, influence acute hepatic inflammation in murine models of liver ischemia-reperfusion injury and liver transplant recipients. We show that the myeloid Ikaros-SIRT1 axis regulates inflammasome-pyroptotic cell death and hepatocellular damage in stressed livers. Thus, the Ikaros-SIRT1 axis may serve as a novel checkpoint regulator that is required for homeostasis in response to acute liver injury in mice and humans.

Original citation: J Clin Invest. 2024;134(4):e170490. https://doi.org/10.n72/JCI170490. Citation for this corrigendum: J Clin Invest. 2024;134(8):e181374. https://doi.org/10.1172/JCI181374. The authors recently became aware that in Figure 7F, an incorrect image was shown [...]