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ObjectiveThe aim of this study was to investigate the predictive value of systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV) in predicting intravenous immunoglobulin (IVIG) resistance in children diagnosed with Kawasaki disease (KD).MethodsThe clinical data of pediatric patients diagnosed with Kawasaki disease and admitted to our hospital between January 2006 and December 2022 were retrospectively analyzed.ResultsIn total, 771 children diagnosed with KD were included in this study, 86 (11.2%) of whom were diagnosed with IVIG resistance. The correlation between SII, SIRI, PIV and IVIG resistance was evaluated using univariate testing, binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. Our study found that the SII, SIRI, and PIV were independent risk factors (p=0.001, p

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates, particularly preterm infants. Many factors can lead to NEC, but microbial dysbiosis is one of the most important risk factors that can induce this disease. Given the major role of the gut virome in shaping bacterial homeostasis, virome research is a fledgling but rapidly evolving area in the field of microbiome that is increasingly connected to human diseases, including NEC. This review provides an overview of the development of the gut virome in newborns, discusses its emerging role in NEC, and explores promising therapeutic applications, including phage therapy and fecal virome transplantation.

Many efforts have been taken in recent years to push atomic gravimeters toward practical applications. We demonstrate an atomic gravimeter named NIM-AGRb2 that is transportable and suitable for high-precision gravity measurements. Constraint-structured active vibration isolation (CS-AVI) is used to reduce the ground vibration noise. The constraint structure in CS-AVI ensures that the isolation platform only has vertical translation, with all other degrees of freedom (DoFs) being constrained. Therefore, the stability of active vibration isolation is enhanced. With the implementation of CS-AVI, the sensitivity of NIM-AGRb2 reached as low as 20.5 μGal/Hz1/2. The short-term sensitivity could be further reduced to 10.8 μGal/Hz1/2 in a seismologic observation station. Moreover, we evaluated the system noise of the gravimeter, and the results were consistent with our observations.

Currently, 1060 aluminum alloy is widely applied in the electronics industry, construction, the aerospace field, traffic engineering, decorations, and the consumer goods market for its good chemical, physical, and mechanical properties. In general, excellent processing property is necessary and important for the manufacturing of complicated panels. In this paper, a special 2D ultrasonic vibration incremental forming method is designed to improve its plasticity and mechanical properties. Three kind of processing methods, including traditional single-point incremental forming, longitudinal ultrasonic vibration incremental forming, and 2D ultrasonic vibration incremental forming, are used for the flexible manufacturing of cones and cylindrical cups of 1060 aluminum alloy sheet. Then, micro-hardness tests, residual stress tests, and scanning electron microscopy tests are carried out to probe the changes in micro-structure and mechanical properties and to analyze the effects of different types of ultrasonic vibration on the plasticity and fracture characteristic of 1060 aluminum alloy. It is proven that 2D ultrasonic vibration facilitates the improvement of plasticity and surface qualities of 1060 aluminum alloy better than the other two processing methods. Therefore, the novel 2D ultrasonic vibration incremental forming process possesses substantial application value for the flexible and rapid manufacturing of complicated thin-walled component of aluminum alloy.

With the rapid development of Internet technologies, security issues have always been the hot topics.Continuous identity authentication based on mouse behavior plays a crucial role in protecting computer systems, but there are still some problems to be solved.Aiming at the problems of low authentication accuracy and long authentication latency in mouse behavior authentication method, a new continuous identity authentication method based on mouse behavior was proposed.The method divided the user’s mouse event sequence into corresponding mouse behaviors according to different types, and mined mouse behavior characteristics from various aspects based on mouse behaviors.Thereby, the differences in mouse behavior of different users can be better represented, and the authentication accuracy can be improved.Besides, the importance of mouse behavior features was obtained by the ReliefF algorithm, and on this basis, the irrelevant or redundant features of mouse behavior were removed by combining the neighborhood rough set to reduce model complexity and modeling time.Moreover binary classification was adopted.The algorithm performed the training of the authentication model.During identity authentication, the authentication model was used to obtain a classification score based on the mouse behavior collected each time, and then the user’s trust value was updated in combination with the trust model.When the user’s trust value fell below the threshold of the trust model, it might be judged as illegal user.The authentication effect of the proposed method was simulated on the Balabit and DFL datasets.The results show that, compared with the methods in other literatures, this method not only improves the authentication accuracy and reduces the authentication latency, but also has a certain robustness to the illegal intrusion of external users.

BackgroundKawasaki disease (KD) is an acute systemic vasculitis that can involve multiple organs. Few reports have been published about KD patients presenting with multiple complications such as acute abdomen, KD shock syndrome (KDSS), and macrophage activation syndrome (MAS).Case DescriptionWe present the cases of two males (9 and 12 years old) diagnosed with KD accompanied by rare manifestations. Case 1 is a 9-year-old male treated for acute appendicitis, KDSS, and MAS. Case 2 is a 12-year-old male who presented with KDSS, MAS, and an ileal perforation. They were treated with intravenous immunoglobulin, aspirin, high-dose corticosteroids, vasoactive drugs, and symptomatic treatment, with good outcomes.ConclusionsClinicians should be aware of the possibility of KD in the presence of fever and unusual manifestations, such as severe inflammatory indicators and acute abdomen that is nonresponsive to antibiotic therapy. Meanwhile, KD-related unusual complications should be recognized, such as KDSS and MAS.

Background: Re-Du-Ning injection (RDN) is a renowned heat-clearing traditional Chinese medicine for the treatment of respiratory diseases owing to its anti-inflammatory effects. However, very little is known about the pulmonary distribution and lung exposure–efficacy relationships. This study aimed to investigate the pulmonary distribution and biopharmaceutics concerning lung penetrability and affinity and the local anti-inflammatory effects after intravenous and pulmonary administration of RDN. Methods: Two iridoids and seven phenolic acid components were selected as the chemical markers in RDN. The in vitro pulmonary distribution and biopharmaceutics were conducted by evaluating the binding and disassociation kinetics of chemical markers in lung tissue explants whereas the in vivo evaluation was performed by determining the time-dependent concentrations of chemical markers in plasma, lung epithelial lining fluid (ELF), lung tissues and immune cells in the ELF after intratracheal and intravenous administrations of RDN. The inhibitory effects on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production were used to evaluate the anti-inflammatory effect of RDN on lung tissues in vitro and on mice with LPS-induced lung inflammation. Results: The chemical markers of RDN exhibited excellent lung penetrability but poor lung affinity in vitro and in vivo. After intravenous administration, the chemical markers appeared to rapidly penetrate through the lung tissue to reach the ELF, leading to markedly higher drug exposure to ELF and immune cells in the ELF than to lung tissues. Compared to intravenous injection, the intratracheal instillation of RDN increased drug exposure to lung tissue and immune cells in the ELF by up to > 80-fold, leading to improved anti-inflammatory potency and prolonged duration of action. Conclusion: The drug exposure to immune cells in the ELF was correlated with the lung-targeted anti-inflammatory effects of RDN and pulmonary delivery has the potential to replace intravenous injection of RDN for the treatment of respiratory diseases.

Background: Chuankezhi injection (CKZ) is a traditional Chinese medicine for the treatment of respiratory diseases and has been often used off-label as a nebulization therapy. However, little is known about the aerosolization performance and pulmonary fate of the inhaled CKZ. This study aimed to evaluate the aerodynamic characteristics of nebulizer generated aerosols and to compare the properties of pharmacokinetics, lung distribution and anti-inflammation effects of CKZ after intratracheal and intravenous administration. Methods: The nebulization performance was evaluated in vitro based on the aerodynamic particle size distribution and aerosol output. The concentrations of epimedins A, B, C and icariin, the main active ingredients of CKZ, in plasma, bronchoalveolar lavage fluids (BALF) and lung tissues were measured by LC-MS/MS analysis. The pulmonary anti-inflammatory efficacy were tested using LPS-induced pulmonary inflammation mice model as indicated by the total cells counts, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF. Results: The aerosols of CKZ generated by a commercial nebulizer showed excellent aerodynamic properties and delivery output. Following intratracheal instillation of CKZ, epidemins A, B and C, and icariin, were absorbed into the bloodstream with the mean absorption time varying from 101.8 min to 271.8 min, and their absolute bioavailabilities ranging from 26.4 % to 104 %. The instillation of CKZ increased the lung to plasma concentration ratios by 25.5–718 folds compared to intravenous administration, leading to improved and prolonged local anti-inflammatory effects. Conclusion: Nebulization therapy of CKZ could be a promising alternative to the injectable counterpart.

Objective: To investigate the associations between dietary intakes, eating habits, socioeconomic determinants and malnutrition in children under 5 years old in south China. Method: A case-control study with 182 malnourished (case) and 254 normal (control) children was conducted in four towns using anthropometric measurements and questionnaires. Results: The dietary intakes of calory, protein, vitamin and minerals of malnourished children were lower than their normal counterparts. Overall, 37.9% children ‘monthly or never’ ate egg and egg products, 61.5% ‘monthly or never’ ate beans and soy products, but 76.7% had candies or cakes ‘daily or weekly’. Four identified determinants of malnutrition were: 1) low education level of mother (OR 1.65; 95% CI 1.02-2.67); 2) more children in one family (OR 1.86; 95% CI 1.14-3.03); 3) absence of independent eating habit (OR 1.75; 95% CI 1.13-2.72); and 4) long dining time (≥20 min) (OR 1.91; 95% CI 1.12-3.24). Conclusions: Inadequate dietary intake, lower socioeconomic status and inappropriate eating habits were the major determinants of childhood malnutrition in south China. Nutritional intervention focusing on education and behavior change are warranted to help reduce the rate of malnourishment among the children of rural families in the future.

Previous work suggests that mitophagy in neurons is could be therapeutic in Alzheimer’s disease (AD). Here, the authors screen a library of drugs and identify UMI-77, a mitophagy inducer with beneficial effects in an AD mouse model, by binding MCL-1, which they identify as a mitophagy receptor.

Mitochondria are key cellular organelles and play vital roles in energy metabolism, apoptosis regulation and cellular homeostasis. Mitochondrial dynamics refers to the varying balance between mitochondrial fission and mitochondrial fusion that plays an important part in maintaining mitochondrial homeostasis and quality. Mitochondrial malfunction is involved in aging, metabolic disease, neurodegenerative disorders, and cancers. Mitophagy, a selective autophagy of mitochondria, can efficiently degrade, remove and recycle the malfunctioning or damaged mitochondria, and is crucial for quality control. In past decades, numerous studies have identified a series of factors that regulate mitophagy and are also involved in carcinogenesis, cancer cell migration and death. Therefore, it has become critically important to analyze signal pathways that regulate mitophagy to identify potential therapeutic targets. Here, we review recent progresses in mitochondrial dynamics, the mechanisms of mitophagy regulation, and the implications for understanding carcinogenesis, metastasis, treatment, and drug resistance.

Mitochondria are highly dynamic organelles, which can form a network in cells through fusion, fission, and tubulation. Its morphology is closely related to the function of mitochondria. The damaged mitochondria can be removed by mitophagy. However, the relationship between mitochondrial morphology and non-selective autophagy is not fully understood. We found that mitochondrial fusion machinery, not fission or tubulation machinery, is essential for energy deprivation-induced autophagy. In response to glucose starvation, deletion of mitochondrial fusion proteins severely impaired the association of Atg1/ULK1 with Atg13, and then affected the recruitment of Atg1 and other autophagic proteins to PAS (phagophore assembly site). Furthermore, the deletion of fusion proteins blocks mitochondrial respiration, the binding of Snf1-Mec1, the phosphorylation of Mec1 by Snf1, and the dissociation of Mec1 from mitochondria under prolonged starvation. We propose that mitochondrial fusion machinery regulates energy deprivation-induced autophagy through maintaining mitochondrial respiration.

The acetyltransferase Tip60 mediates signaling pathways by acetylating non-histone proteins. Here the authors show that fatty acids induce Tip60–dependent acetylation of phosphatidic acid phosphatase lipin1 which, then, translocates to the ER and generates diacylglycerols for triglyceride synthesis.

For solving the operation problems of floating liquefied natural gas (FLNG) vessels in harsh sea areas, especially in the areas where typhoon happens frequently, the characteristics of cyclone (typhoon) in China sea areas were analyzed based on the environmental conditions of the South China Sea. Then, the FLNG vessel connection operation and the FLNG vessel disconnection and evacuation plans in the situation of cyclones were compared. And finally, a series of research was carried out on the technical difficulties related to the FLNG vessel connection operation plan, such as the temperature field of LNG cofferdam, the vapor treatment and diffusion during a cyclone, such as a typhoon, and the typhoon generator at the shallow-water platform. Based on these analysis and research, the following recommendations were proposed. First, it is recommended to adopt the FLNG vessel connection operation plan during a typhoon to guarantee convenient and safe operation and to improve oil and gas field benefits. Second, a ballast cabin can be set inside the vessel to ensure the safety of Grade E steel in FLNG vessel, especially during a typhoon. Third, BOG diffusion can be still safe in the most dangerous working condition when the vent pipe reaches a certain height during a typhoon. Fourth, four groups of mooring systems (five pieces in each group) can be designed to guarantee the mooring strength of FLNG vessel connection operation during a typhoon. And fifth, when a typhoon arrives, it is necessary to stop FLNG production, release the pressure and organize personnel evacuation in a planned way. After the typhoon leaves, personnel return and FLNG production starts again. In this way, efficiency can be increased effectively, and the operational convenience and safety of FLNG vessels can be ensured.

Acetylation of Atg3 regulates lipidation of Atg8 and therefore autophagy, but the molecular mechanisms remain unclear. Here, Liet al. semi-synthesize diacetylated Atg3, allowing them to show that acetylated Atg3 enhances Atg8 lipidation by promoting interaction of Atg3 with liposomes containing physiological levels of phosphatidylethanolamine.

AIM: To conduct a Meta-analysis pooling randomized controlled trials (RCTs) to compare hydrophobic with hydrophilic acrylic intraocular lenses in terms of posterior capsule opacification (PCO) development. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library were queried from their starting till January 2020. RCTs investigating the impact of hydrophobic versus hydrophilic acrylic intraocular lenses on PCO were considered eligible in this study. The pooled effect estimates were calculated using the random-effects model. RESULTS: Thirteen RCTs comprising of 939 patients (1263 eyes) were covered in this study. Patients with hydrophobic acrylic intraocular lenses had a lower PCO score than those with a hydrophilic acrylic intraocular lenses [standard mean difference: -1.80; 95% confidence interval (CI): -2.62 to -0.98; P

The role of tumor-associated macrophages (TAMs), along with the regulatory mechanisms underlying distinct macrophage activation states, remains poorly understood in prostate cancer (PCa). Herein, we report that PCa growth in mice with macrophage-specific Ubc9 deficiency is substantially suppressed compared with that in wild-type littermates, an effect partially ascribed to the augmented [CD8.sup.+] T cell response. Biochemical and molecular analyses revealed that signal transducer and activator of transcription 4 (STAT4) is a crucial UBC9-mediated SUMOylation target, with lysine residue 350 (K350) as the major modification site. Site-directed mutation of STAT4 (K350R) enhanced its nuclear translocation and stability, thereby facilitating the proinflammatory activation of macrophages. Importantly, administration of the UBC9 inhibitor 2-D08 promoted the antitumor effect of TAMs and increased the expression of PD-1 on [CD8.sup.+] T cells, supporting a synergistic antitumor efficacy once it combined with the immune checkpoint blockade therapy. Together, our results demonstrate that ablation of UBC9 could reverse the immunosuppressive phenotype of TAMs by promoting STAT4-mediated macrophage activation and macrophage [CD8.sup.+] T cell crosstalk, which provides valuable insights to halt the pathogenic process of tumorigenesis., Introduction Prostate cancer (PCa) progression is regulated by multiple cell types existing within the tumor microenvironment (TME) (1). [CD8.sup.+] T cells, the predominant tumoricidal effector population, are commonly present in [...]