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Neonatal hypoxic-ischemic encephalopathy (HIE) is a severe disease with a poor prognosis, whose clinical treatment is still limited to therapeutic hypothermia with limited efficacy. Perillyl alcohol (POH), a natural monoterpene found in various plant essential oils, has shown neuroprotective properties, though its effects on HIE are not well understood. This study investigates the neuroprotective effects of POH on HIE both in vitro and in vivo. We established an in vitro model using glucose deprivation and hypoxia/reperfusion (OGD/R) in PC12 cells, alongside an in vivo model via the modified Rice-Vannucci method. Results indicated that POH acted as an indirect antioxidant, reducing inducible nitric oxide synthase and malondialdehyde production, maintaining content of antioxidant molecules and enzymes in OGD/R-induced PC12 cells. In vivo, POH remarkably lessened infarct volume, reduced cerebral edema, accelerated tissue regeneration, and blocked reactive astrogliosis after hypoxic-ischemic brain injury. POH exerted antiapoptotic activities through both the intrinsic and extrinsic apoptotic pathways. Mechanistically, POH activated Nrf2 and inactivated its negative regulator Keap1. The use of ML385, a Nrf2 inhibitor, reversed these effects. Overall, POH mitigates neuronal damage in HIE by combating oxidative stress, reducing inflammation, and inhibiting apoptosis via the Nrf2/Keap1 pathway, suggesting its potential for HIE treatment. [ABSTRACT FROM AUTHOR]

Background: Abnormal pulmonary vascular development poses significant clinical challenges for infants with bronchopulmonary dysplasia (BPD). Although numerous factors have been suggested to control the development of pulmonary blood vessels, the mechanisms underlying the role of long noncoding RNAs (lncRNAs) in this process remain unclear. Methods: A lncRNA array was used to measure the differential expression of lncRNAs in premature infants with and without BPD. The expression of lncRNA-VSIG2-1:1 in patients with BPD and hyperoxia-induced human pulmonary microvascular endothelial cells (HPMECs) was assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) assay was performed to detect the subcellular localization of lncRNA-VSIG2-1:1. Pulmonary microvascular endothelial cells were stably transfected with adenoviral vectors to silence or overexpress lncRNA-VSIG2-1:1. The effects of lncRNA-VSIG2-1:1 on the proliferation, migration, and tube formation abilities of HPMECs subjected to hyperoxia were examined by performing Cell Counting Kit‐8 (CCK-8), cell migration, and tubule formation assays. RNA sequencing (RNA-seq) was performed to determine the correlation between lncRNA-VSIG2-1:1 and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT). The protein levels of vascular endothelial growth factor (VEGF), p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting. Results: The expression of lncRNA-VSIG2-1:1 was upregulated in patients with BPD and hyperoxia-treated HPMECs. Inhibiting lncRNA-VSIG2-1:1 expression promoted the proliferation, migration, and tube-formation abilities of HPMECs, while significantly increasing VEGF, p-PI3K, and p-AKT levels. Conclusion: Our findings reveal that the suppression of lncRNA-VSIG2-1:1 expression stimulates angiogenesis in vitro by inducing the initiation of the VEGF/PI3K/AKT signaling pathway. This observation may aid the development of novel therapeutic targets for treating BPD. [ABSTRACT FROM AUTHOR]

Purpose: Neonatal bacterial meningitis (NBM) is a serious disease with high morbidity and mortality. This study aimed to establish a foundation for the selection of empirical antibiotics for NBM through an analysis of pathogen distribution and shift in antimicrobial resistant pattern. Patients and Methods: A retrospective cohort study on culture confirmed NBM from 2005 to 2022. Results: A total of 191 cases were enrolled, 48 for premature infants and 70 for early-onset meningitis. The incidence of NBM in first half and last half period was 0.2‰ and 0.24‰, while the mortality was 12.0% and 5.6% respectively. The top two pathogens were Escherichia coli (E. coli) (40.3%) and Group B Streptococcus (GBS) (29.8%). E. coli was the most common pathogen in both periods, Enterococcus (13.3% vs 0.9%, P < 0.05) and Staphylococcus aureus (8.4% vs 1.9%, P < 0.05) decreased, while GBS increased significantly in the periods [16.9% vs 39.8%, P < 0.001]. Gram-positive bacteria were more common in full term infants (53.8% vs 27.1%, P = 0.001), while gram-negative bacteria were more common in preterm infants (72.9% vs 46.2%, P = 0.001). All isolated GBS strains were susceptible to penicillin. On the other hand, less than 60% of E. coli were susceptible to third generation of cephalosporins, and were only susceptible to carbapenem or amikacin. This was mainly due to production of extended-spectrum beta-lactamase (ESBLs) which was higher in late-onset group than that in early-onset group (45.1% vs 19.2%, P = 0.026). Conclusion: Incidence of NBM has not changed significantly over the last 2 decades. E. coli remains as the most common pathogen of NBM despite that GBS has increased in recent 9 years, especially in full-term infants. While all isolated GBS are susceptible to penicillin, over a third of E. coli strains are multidrug resistant due to production of ESBLs. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cell level can provide valuable insights for the development of more effective treatment strategies for CRC. Methods: We conducted single-cell RNA sequencing (scRNA-seq) analysis on tumor and adjacent normal colorectal samples from 15 overweight/obese and 15 normal-weight CRC patients. Immunological and metabolic differences between overweight/obese CRC and non-obese CRC were characterized. Results: We obtained single-cell transcriptomics data from a total of 192,785 cells across all samples. By evaluating marker gene expression patterns, we annotated nine main cell types in the CRC ecosystem. Specifically, we found that the cytotoxic function of effector T cells and NK cells was impaired in overweight/obese CRC compared with non-obese CRC, relating to its metabolic dysregulation. CD4+T cells in overweight/obese CRC exhibited higher expression of immune checkpoint molecules. The antigen-presenting ability of DCs and B cells is down-regulated in overweight/obese CRC, which may further aggravate the immunosuppression of overweight/obese CRC. Additionally, dysfunctional stromal cells were identified, potentially promoting invasion and metastasis in overweight/obese CRC. Furthermore, we discovered the up-regulated metabolism of glycolysis and lipids of tumor cells in overweight/obese CRC, which may impact the metabolism and function of immune cells. We also identified inhibitory interactions between tumor cells and T cells in overweight/obese CRC. Conclusions: The study demonstrated that overweight/obese CRC has a more immunosuppressive microenvironment and distinct metabolic reprogramming characterized by increased of glycolysis and lipid metabolism. These findings may have implications for the development of novel therapeutic strategies for overweight/obese CRC patients. [ABSTRACT FROM AUTHOR]

Objective: An increasing number of cases of neonatal sepsis due to extended-spectrum beta-lactamase (ESBL)-producing multi-drug resistant (MDR) Escherichia coli (E. coli) have been reported worldwide. The aim of this study was to explore the risk factors associated with ESBL-producing MDR E. coli among neonates with culture-confirmed E. coli sepsis and thereby to help selection of appropriate empirical antibiotics. Patients and Methods: All newborn infants with a confirmed pathogen isolated from blood or cerebrospinal fluid (CSF) from 2016 to 2021 were identified and those with E. coli infection were included in this analysis. We compared a group of neonatal patients with ESBL-producing MDR E. coli sepsis (n=69) to a group with ESBL-negative E. coli (n=70) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors associated with ESBL-producing MDR E. coli strains among the neonates with culture-confirmed E. coli sepsis. Results: ESBL-producing MDR E. coli sepsis was more common in premature infants and newborns with hospital-acquired late-onset sepsis (HALOS). The mortality rate of neonatal sepsis caused by ESBL-producing E. coli was about twice as that of sepsis caused by ESBL-negative E. coli. Antepartum exposure to cephalosporins (OR=25.191, 95% CI: 3.184– 199.326, P< 0.01) and parenteral nutrition for more than 1 week (OR=4.495, 95% CI: 2.009– 10.055, P< 0.01) were independent risk factors for neonatal infection with ESBL-producing stains among infants with E. coli sepsis. Conclusion: E. coli remains the most common Gram-negative bacterial pathogen causing neonatal sepsis. A higher proportion of ESBL-producing MDR E. coli is seen in premature infants and those newborns with HALOS and is associated with higher mortality. Antepartum use of cephalosporins and prolonged use of parenteral nutrition may be important factors to consider in the selection of empirical antibiotics for use in neonatal sepsis caused by gram-negative rods prior to the availability of the results of antimicrobial susceptibility. [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoxic-ischemic brain injury (HIE) is caused by perinatal asphyxia, which is associated with various confounding factors. Although studies on the pathogenesis and treatment of HIE have matured, sub-hypothermia is the only clinical treatment available for HIE. Previous evidence indicates that chlorogenic acid (CGA) exerts a potential neuroprotective effect on brain injury. However, the role of CGA on neonatal HI brain damage and the exact mechanism remains elusive. Here, we investigate the effects of CGA on HI models in vivo and in vitro and explore the underlying mechanism. Methods: In the in vivo experiment, we ligated the left common carotid artery of 7-day-old rats and placed the rats in a hypoxic box for 2 h. We did not ligate the common carotid artery of the pups in the sham group since they did not have hypoxia. Brain atrophy and infarct size were evaluated by Nissl staining, HE staining and 2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining. Morris Water Maze test (MWM) was used to evaluate neurobehavioral disorders. Western-blotting and immunofluorescence were used to detect the cell signaling pathway. Malondialdehyde (MDA) content test, catalase (CAT) activity detection and Elisa Assay was used to detect levels of inflammation and oxidative stress. in vitro experiments were performed on isolated primary neurons. Result: In our study, pretreatment with CGA significantly decreased the infarct volume of neonatal rats after HI, alleviated brain edema, and improved tissue structure in vivo. Moreover, we used the Morris water maze to verify CGA's effects on enhancing the learning and cognitive ability and helping to maintain the long-term spatial memory after HI injury. However, Sirt1 inhibitor EX-527 partially reversed these therapeutic effects. CGA pretreatment inhibited neuronal apoptosis induced by HI by reducing inflammation and oxidative stress. The findings suggest that CGA potentially activates Sirt1 to regulate the Nrf2-NF-κB signaling pathway by forming complexes thereby protecting primary neurons from oxygen-glucose deprivation (OGD) damage. Also, CGA treatment significantly suppresses HI-induced proliferation of glial. Conclusion: Collectively, this study uncovered the underlying mechanism of CGA on neonatal HI brain damage. CGA holds promise as an effective neuroprotective agent to promote neonatal brain recovery from HI-induced injury. 8NePktn-RrRjrUAHAHCXyY Video Abstract [ABSTRACT FROM AUTHOR]

Fragility modeling and real-time risk assessment can be widely applied to evaluate and enhances the resilience of the power system to High-Impact and Low Probability events. In previous studies, fragility modeling generally targets extreme weather conditions other than thunderstorm. This paper proposes a fragility model to describe the relationship between the duration of a thunderstorm and the probability of lightning related trip-out. The duration of thunderstorms, which can usually be forecasted from the meteorological department, together with the fragility function expression can help a power company to predict the possibility of lightning related trip-out. Furthermore, this paper proposes a real-time risk assessment model that can dynamically adjust the risk value based on the update of the location, peak current, and subsequent stroke of real-time thunderstorm. A case study conducted on the lightning related trip-out data in Southwest China demonstrates that the average risk of transmission line trip-out in high risk group is about ten times that in low risk group. It clearly demonstrates that real-time risk assessment can efficiently distinguish the trip-out risks of different real-time thunderstorms. [ABSTRACT FROM AUTHOR]

Lightning performance evaluation is aimed at classifying transmission lines into different risk levels of thunderstorm-induced trip-out. Its applications range from better lightning protection guidance, arrester installation design, transmission line retrofits, and line corridor design. Previous studies fail to consider the real-time lightning intensity, which is an essential factor of lightning trip-out that must not be ignored. This article proposes a novel lightning performance evaluation model based on the idea that the tower, which has a record of lightning trip-out with weaker real-time lightning intensity, is more susceptible to trip out, which means low lightning performance. In order to quantify the lightning intensity, this article puts forward a new definition of lightning intensity which includes three kinds of real-time characteristics, that is the location, the current of lightning strike, and the number of times the lightning movement track crosses the transmission line. More specifically, with the rapid development of lightning location system, a novel Lightning Identification, Tracking, and Analysis algorithm is proposed to search lightning movement track based on a database of 17 million lightning records. When lightning trip-out happens, the lightning performance level is graded according to the real-time lightning intensity. By comparing the similarity of static characteristics, the lightning performance level is extended to the tower, which has no record of lightning trip-out. By comparison with the traditional model, the proposed model is closer to the actual situation and can significantly improve the accuracy of lightning performance evaluation, which is improved by 66.7%. [ABSTRACT FROM AUTHOR]

Introduction: Electro-acupuncture (EA) can significantly improve inflammatory response, but the specific mechanism is not clear. Limb ischemia-reperfusion (I/R) first produces inflammatory reactions in the lungs. In this study, EA on Zusanli (ST36) and Sanyinjiao (SP6) were used to explore the mechanism of improving tissue inflammation by sciatic nerve disconnection. Material and Methods: A total of 56 male Sprague-Dawley rats were randomly divided into sham group, model group, EA group, SEA group, SNC+EA group, TNC+EA group and PNC+EA group. The sham groups were not given any treatment. Rats in the model group were treated with limb I/R without acupuncture intervention. In the EA group, ST36 and SP6 were given EA treatment for 30min before modeling. No electric current was given in the SEA group, and other operations were the same as those in the EA group. The SNC+EA group, TNC+EA group and PNC+EA group were respectively given sciatic nerve, tibial nerve or peroneal nerve amputation 72h before modeling, and the others were the same as the model group. Results: Compared with the sham group, PaO2 and a/A ratios decreased significantly in the model group (P < 0.05), while PA-aO2, RI, the ratio of wet to dry, lung injury value and inflammatory factor TNF-α, IL-1, IL-6, and MPO increased significantly (P < 0.05). Compared with the model group, PaO2, a/A ratios increased significantly in the EA group (P < 0.05), while PA-aO2, RI, the ratio of wet to dry lung, lung injury value, and TNF-α, IL-1, IL-6, and MPO decreased significantly (P < 0.05). After transection of the sciatic nerve, the protective effect of EA disappeared. However, when the peroneal or tibial nerve was severed, EA continued to maintain the protective effect. Conclusion: EA on ST36 and SP6 can alleviate lung injury caused by limb I/R through the sciatic nerve. [ABSTRACT FROM AUTHOR]

The characteristic impedance value of the overhead line is different from that of the underground cable. Existing traveling wave‐based fault location methods for mixed power transmission systems have setbacks including location error caused by wave velocity and difficulty in detecting wave arrival time. In order to solve these problems, the increase of available information from different locations by installing wire‐based sensors along the power line is a feasible solution. In this paper, a traveling wave‐based fault location system, which is based on the current data measured at the midpoint of the overhead line and the joint point, is introduced. The data at these two locations are measured by the wire‐based current sensor we designed. The whole transmission line system is divided by these two sensors into three segments. The first step of this proposed method is to record the postfault current data at the two measuring devices. Second, by comparing the amplitudes and polarities of the current at these two measurement points, the faulty segment can be identified. Finally, postfault wave propagation paths are ascertained; the accurate velocity values of the waves in the overhead line and underground cable are obtained; and then, the fault point is located without the need of time synchronization. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

Summary: With the increasing interdependency of electricity and gas, it is necessary to simultaneously investigate electric power system and natural gas system from the perspective of an electricity‐gas integrated energy system (EGIES). As an extension and integration of both optimal power flow (OPF) and optimal gas flow (OGF), optimal energy flow (OEF) is regarded as the cornerstone of the EGIES and lays an essential foundation for further research on the EGIES's operation and analysis considering stochastic conditions and contingency states. The objective of this paper is to develop a generalized mathematical model and a universally applicable simulation tool for the OEF problem. First, natural gas system is modeled in a way similar to electric power system according to electricity‐gas analogy analysis, where gas admittance, gas nodal admittance matrix, and the nodal equation of gas flow conservation are derived. Then, a generalized accurate OEF model is formulated by simultaneously integrating the OPF model and the OGF model as well as their coupling constraints in a unified modeling framework. Furthermore, an available hybrid optimization approach consisting of whale optimization algorithm, MATPOWER, hydraulic calculation iterative program, and nonstationary penalty function method is put forward to solve the OEF problem. The accuracy, feasibility, and applicability of the proposed modeling and solution method is finally demonstrated by analyzing Belgian 20‐node gas system combined with IEEE 30‐bus test system. Gas nodal admittance matrix is formulated to describe natural gas system with electricity‐gas analogy analysis. A nodal admittance matrix‐based mathematical model for optimal energy flow of electricity‐gas integrated energy system is presented by combining optimal power flow and optimal gas flow as well as their coupling constraints in a unified modeling framework. An effective hybrid optimization approach is developed to solve optimal energy flow by integrating whale optimization algorithm, MATPOWER, hydraulic calculation iterative program, and nonstationary penalty function. [ABSTRACT FROM AUTHOR]

A novel traveling-wave-based fault-location algorithm for multiterminal transmission lines is introduced in this paper. Existing traveling-wave fault-location methods that based on the data measured at line terminals lack reliability and accuracy because time synchronization is needed, which brings error. To solve this problem, the complex structure of multiterminal power system is divided into several fault identification branches, current at the midpoint of each branched is measured, a novel fault-location algorithm is proposed, and the time synchronization error is eliminated. A line-based device is designed to measure the current at the midpoint of each branch. An accurate value of the traveling wave speed can be obtained by merely applying the data record in one measuring device. Thus, the fault-location accuracy is improved. The system model applied in this paper comprises one transmission line and two tapped lines, and the proposed method applies to networks with more terminals. Performance of this method is tested by different cases by PSCAD. The hardware platform has been tested in Sichuan Province, China. [ABSTRACT FROM AUTHOR]

Summary: This paper presents a distributed energy system (DES) for a local district and formulates a constrained nonlinear multiobjective optimization model for the daily operation of the system. The main objective of the study is to increase the efficiency by minimizing energy cost, energy consumption, and energy losses. It is implemented through the integration and complementation of renewable energies and fossil fuels as well as the recycling utilization of waste heat in the DES. The consideration of network topology and energy losses of water heating network could also contribute to the improvement of energy efficiency. To solve the optimization problem, a novel Whale Optimization Algorithm is employed. Furthermore, the economic and energy performance of the DES are evaluated and compared with that of conventional centralized energy systems, ie, the EG and MG energy‐supply modes. After simulation studies, the hourly optimal energy (both natural gas and electricity) purchasing schedule as well as the hourly optimal set points of mass water flow rates and supply/return water temperatures could be determined. The results show that the DES saves more than 50% of energy costs/energy consumption than the MG mode and over 22% than the EG mode for a whole day, verifying the competitive advantage and great potential of both energy saving and cost reduction of the DES. [ABSTRACT FROM AUTHOR]

Existing single‐ and double‐terminal travelling‐wave fault‐location approaches have some disadvantages including difficulty in distinguishing the sources of reflect and refract waves, system error in time synchronisation and wave propagation velocity. In this study, a distributed travelling‐wave‐based fault‐location system, which eliminates the time synchronisation and wave propagation velocity error, is introduced. This novel system is consisted of three measurement points, which are located at both ends and the mid‐point of the line. At first, the measurement points, installed at both line ends, record the post‐fault current data for a time interval. The measurement point, located at the mid‐point, records the time tags of the three sequential wavefronts as t1, t2 and t3 separately including the initial wave and following waves reflected at both the ends. Second, by comparing fault current recorded by the three measurement points, the fault interval can be determined based on current deviation theorem. Finally, travelling‐wave propagation velocity is calculated according to mathematic equation in terms of t1,2,3. Then, the fault point is located without the need of time synchronisation. The simulation and hardware tests match the theoretical analysis well, showing that the proposed location method provides not only high accuracy, but also good reliability. [ABSTRACT FROM AUTHOR]

In this paper, a multivariable direct adaptive controller using multiple models without minimum phase assumption is presented to improve the transient response when the parameters of the system jump abruptly. The controller is composed of multiple fixed controller models, a free-running adaptive controller model and a re-initialized adaptive controller model. The fixed controller models are derived from the corresponding fixed system models directly. The adaptive controller models adopt the direct adaptive algorithm to reduce the design calculation. At every instant, the optimal controller is chosen out according to the switching index. The interaction of the system is viewed as the measured disturbance which is eliminated by the choice of the weighing polynomial matrix. The global convergence is obtained. Finally, several simulation examples in a wind tunnel experiment are given to show both effectiveness and practicality of the proposed method. The significance of the proposed method is that it is applicable to a non-minimum phase system, adopting direct adaptive algorithm to overcome the singularity problem during the matrix calculation and realizing decoupling control for a multivariable system. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by perinatal asphyxia and is the main cause of neonatal death and chronic neurological diseases. Protection of neuron after hypoxic-ischemic (HI) brain injury is considered as a potential therapeutic target of HI brain injury. To date, there are no effective medicines for neonatal HI brain injury. Lycopene (Lyc), a member of the carotenoids family, has been reported to have anti-oxidative and anti-inflammatory effects. However, its effects and potential mechanisms in HI brain injury have not yet to be systematically evaluated. In this study, we investigated whether Lyc could ameliorate HI brain injury and explored the associated mechanism both in vivo and in vitro experiments. In vivo study, Lyc significantly reduced infarct volume and ameliorated cerebral edema, decreased inflammatory response, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. In vitro study, results showed that Lyc reduced expression of apoptosis mediators in oxygen-glucose deprivation (OGD)-induced primary cortical neurons. Mechanistically, we found that Lyc-induced Nrf2/NF-κB pathway could partially reversed by Brusatol (an Nrf2 inhibitor), indicated that the Nrf2/NF-κB pathway was involved in the therapy of Lyc. In summary, our findings indicate that Lyc can attenuated HI brain injury in vivo and OGD-induced apoptosis of primary cortical neurons in vitro through the Nrf2/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]