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This paper proposes an improved noniterative fault location method on untransposed transmission lines without utilizing line parameters. Two-end three phase voltage and current phasor measurements before and during the fault are typically required. First, the parameter-free fault location problem is formulated through multi-section transmission line models, and the necessary condition of noniterative solutions is carefully investigated to determine the maximum possible section number of the multi-section line model. Afterwards, with the determined section number, the analytical solution of the fault location is derived with full utilization of the inherent characteristics of the line parameter matrices. Instead of solving all the parameters, two key variables inside the parameter matrices are extracted and the fault location is obtained by analytically solving a polynomial equation. The method provides a closed-form analytical solution, and therefore avoids convergence issues of iterative algorithms. In addition, line asymmetry of untransposed transmission lines are fully considered to minimize fault location errors. Extensive numerical experiments show that the proposed method has improved fault location accuracy compared to the existing method, with different fault types, locations and impedances.

Recurrent proximal 16p11.2 deletion (16p11.2del) is a risk factor for diverse neurodevelopmental disorders with incomplete penetrance and variable expressivity. Although investigation with human induced pluripotent stem cell models has confirmed disruption of neuronal development in 16p11.2del neuronal cells, which genes are responsible for abnormal cellular phenotypes and what determines the penetrance of neurodevelopmental abnormalities are unknown. We performed haplotype phasing of the 16p11.2 region in a 16p11.2del neurodevelopmental disorders cohort and generated human induced pluripotent stem cells for two 16p11.2del families with distinct residual haplotypes and variable neurodevelopmental disorder phenotypes. Using transcriptomic profiles and cellular phenotypes of the human induced pluripotent stem cell-differentiated cortex neuronal cells, we revealed MAPK3 to be a contributor to dysfunction in multiple pathways related to early neuronal development, with altered soma and electrophysiological properties in mature neuronal cells. Notably, MAPK3 expression in 16p11.2del neuronal cells varied on the basis of a 132 kb 58 single nucleotide polymorphism (SNP) residual haplotype, with the version composed entirely of minor alleles associated with reduced MAPK3 expression. Ten SNPs on the residual haplotype were mapped to enhancers of MAPK3. We functionally validated six of these SNPs by luciferase assay, implicating them in the residual haplotype-specific differences in MAPK3 expression via cis-regulation. Finally, the analysis of three different cohorts of 16p11.2del subjects showed that this minor residual haplotype is associated with neurodevelopmental disorder phenotypes in 16p11.2del carriers. TOC summary Liu et al. provide a molecular explanation for the variable penetrance of the neurodevelopmental disorder phenotype in 16p11.2 deletion syndrome, by characterizing residual haplotype-specific transcriptomic profiles and neuronal phenotypes.

As a highly conserved and ubiquitously expressed serine/threonine kinase, p21-activated kinase 2 (Pak2) participates in diverse biologic events. However, its roles in mouse oocyte meiotic maturation remain unclear. The present study revealed that mouse oocytes depleted of Pak2 were unable to completely progress through meiosis and that a majority were arrested at metaphase I. Pak2 depletion thus prompted MI arrest and induced meiotic apparatus assembly defects in mouse oocytes, in part due to a reduction in polo-like kinase (Plk1). We demonstrated that Pak2’s interaction with Plk1 protected it from degradation by APC/CCdh1, and that it promoted meiotic progression and bipolar spindle formation. Our data collectively display critical functions for Pak2 in meiotic progression and meiotic apparatus assembly in mouse oocytes and may mediate the effects of maternal aging on female reproduction.

Recurrent proximal 16p11.2 deletion (16p11.2del) is risk factor of diverse neurodevelopmental disorders (NDDs) with variable penetrance. Although previous human induced pluripotent stem cell (hiPSC) models of 16p11.2del confirmed disrupted neuron development, it is not known which gene(s) at this interval are mainly responsible for the abnormal cellular phenotypes and how the NDD penetrance is regulated. After haplotype phasing of 16p11.2 region, we generated hiPSCs for two 16p11.2del families with distinct residual haplotypes and variable NDD phenotypes. We also differentiated the hiPSCs to cortical neural cells and demonstrated MAPK3 as a driver signal of 16p11.2 region contributing to the dysfunctions in multiple pathways related to neuron development, which leads to altered morphological or electrophysiological properties in neuron cells. Furthermore, residual haplotype-specific MAPK3 expression was identified in 16p11.2del neuron cells, associating MAPK3 down-expression with the minor allele of the residual haplotype. Ten SNPs of the residual haplotype are mapped as enhancer SNPs (enSNPs) of MAPK3, eight enSNPs were functionally validated by luciferase assays, implying enSNPs contribute to residual haplotype-specific MAPK3 expression via cis-regulation. Finally, the analyses of three different patient cohorts showed that the residual haplotype of 16p11.2del is associated with variable NDD phenotypes.

The Xe44+ 2.7203 Å line, which has been proposed as one of the diagnostic lines for the x-ray imaging crystal spectrometer on ITER, is observed on the EAST tokamak together with its several satellite lines. The observations are made under high electron temperature (T e ) conditions (core T e > 5 keV). Most of the observed xenon lines are identified by comparing the experiment results with the atomic simulation results. The first ion temperature measurements made by the xenon spectra on EAST are also reported in this article. These xenon spectra observations contribute to the justification for using xenon as the diagnostic impurity in x-ray crystal spectrometers in future reactor-scale high-temperature plasmas.

Hypoxia-induced decrease in cisplatin (CDDP) sensitivity in human osteosarcoma (OS) is a significant obstacle to effective chemotherapy. Recently, mitophagy has been shown to be associated with CDDP sensitivity. However, whether it regulates hypoxia-induced decreases in CDDP sensitivity in OS and the underlying mechanisms remain unknown. In this study, we found that hypoxia activated mitophagy and suppressed mitophagy with specific inhibitors, mitochondrial division inhibitor-1 (Mdivi-1) or lysosome inhibitor chloroquine (CQ), which inhibited CDDP-induced apoptosis in hypoxic U-2OS and MG-63 cells. In addition, hypoxia upregulated the phosphorylation level of FUN14 domain-containing protein 1 (FUNDC1), whereas the activation of mitophagy and decreased CDDP sensitivity were inhibited by transfection with FUNDC1 small interfering RNA (siRNA). Hypoxia treatment also led to the up-regulation of heat shock protein 90 (HSP90), whereas HSP90 siRNA inhibited FUNDC1-mediated activation of mitophagy and decreased CDDP sensitivity. Furthermore, activation of Unc-51 like autophagy activating kinase 1 (Ulk1) was found in U-2OS and MG-63 cells after induction of hypoxia. Overexpression of Ulk1 prevented the inhibitory effect of HSP90 siRNA on the activation of FUNDC1 and mitophagy and decreased CDDP sensitivity in hypoxic U-2OS and MG-63 cells. Finally, hypoxia induced the activation of forkhead box transcription factor 3a (FOXO3a), whereas FOXO3a siRNA inhibited hypoxia-induced HSP90 up-regulation, Ulk1 activation, and FUNDC1-mediated activation of mitophagy, and decreased CDDP sensitivity in U-2OS and MG-63 cells. Using a chromatin immunoprecipitation (ChIP) assay, we confirmed that FOXO3a binds to the HSP90 promoter region. In conclusion, our findings suggest that hypoxia alleviates CDDP-induced apoptosis by activating mitophagy through the FOXO3a/HSP90/Ulk1/FUNDC1 signaling pathway in OS cells.

β‐thalassaemia is a prevalent hereditary haematological disease caused by mutations in the human haemoglobin β (HBB) gene. Among them, the HBB IVS2‐654 (C > T) mutation, which is in the intron, creates an aberrant splicing site. Bone marrow transplantation for curing β‐thalassaemia is limited due to the lack of matched donors. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9), as a widely used tool for gene editing, is able to target specific sequence and create double‐strand break (DSB), which can be combined with the single‐stranded oligodeoxynucleotide (ssODN) to correct mutations. In this study, according to two different strategies, the HBB IVS2‐654 mutation was seamlessly corrected in iPSCs by CRISPR/Cas9 system and ssODN. To reduce the occurrence of secondary cleavage, a more efficient strategy was adopted. The corrected iPSCs kept pluripotency and genome stability. Moreover, they could differentiate normally. Through CRISPR/Cas9 system and ssODN, our study provides improved strategies for gene correction of β‐Thalassaemia, and the expression of the HBB gene can be restored, which can be used for gene therapy in the future.

Experiments on pellet fueling have been carried out in edge localized mode (ELM)-free high-confinement mode (H-mode) plasmas with q 95 ∼ 6 in the EAST tokamak. Cryogenic deuterium pellets were injected into the ELM-free plasmas at a frequency of 10 or 5 Hz from ∼45 cm above the mid-plane on the low-field side. It is found that the ELM-free H-mode plasmas are still sustained even if both the edge and core plasma are impacted by the pellet injections (PIs). Several small ELMs would appear and the edge coherent mode accompanying the ELM-free phase fades or even disappears just after the pellet events, but the plasma would rapidly recover to the ELM-free state. Although the ELMing phase is very short, it may be an issue that still needs to be resolved in the future. Meanwhile, the 3/2 tearing mode often appearing in ELM-free discharges would be stabilized by the PIs, and the high-Z impurity concentration would be reduced during the PIs. All these results will be meaningful to International Thermonuclear Experimental Reactor and future fusion reactors.

Lu M, Liu D, Li Y. Onco Targets Ther. 2020;13:10607–10619. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised regarding the duplication of images in Figure 2E. Specifically, Figure 2E, Invasion, NC appears to have been duplicated with Figure 2E, Invasion, LINC01436. The authors did not respond to our queries and were unable to provide original data for their study. The decision was made to retract the article. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Background Obesity is a serious social and public health problem in the world, especially in children and adolescents. For school-age children with obesity, this stage is in the transition from childhood to adolescence, and both physical, psychological, and external environments will be full of challenges. Studies have showed that school-age children are the largest proportion of people who continue to be obese in adulthood. Physical exercise is considered as an effective way to control weight. Therefore, we focus on this point to study which factors will be improved to reduce childhood obesity. Objective To assess the effects of aerobic and resistance exercise on physical indexes, such as body mass index (BMI) and body fat percentage, and cardiovascular risk factors such as VO2peak, triglycerides (TG) and low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), insulin and insulin resistance in school-age children who are overweight or obese. Method PubMed, SPORTDiscus, Medline, Cochrane-Library, Scopus, Ovid and Web of Science were searched to locate studies published between 2000 and 2021 in obese and overweight school-age children between 6–12 years old. The articles are all randomized controlled trials (RCTs) and in English. Data were synthesized using a random-effect or a fixed-effect model to analyze the effects of aerobic and resistance exercise on six elements in in school-age children with overweight or obese. The primary outcome measures were set for BMI. Results A total of 13 RCTs (504 participants) were identified. Analysis of the between-group showed that aerobic and resistance exercise were effective in improving BMI (MD = -0.66; p < 0.00001), body fat percentage (MD = -1.29; p = 0.02), TG (std.MD = -1.14; p = 0.005), LDL (std.MD = -1.38; p = 0.003), TC (std.MD = -0.77; p = 0.002), VO2peak (std.MD = 1.25; p = 0.001). However, aerobic and resistance exercise were not significant in improving HDL (std.MD = 0.13; p = 0.27). Conclusions Aerobic exercise and resistance exercise are associated with improvement in BMI, body fat percentage, VO2peak, TG, LDL, TC, while not in HDL in school-age children with obesity or overweight. Insulin and insulin resistance were not able to be analyzed in our review. However, there are only two articles related to resistance exercise in children with obesity and overweight at school age, which is far less than the number of 12 articles about aerobic exercise, so we cannot compare the effects of the two types of exercises.

Brain activity is intrinsically organised into spatiotemporal patterns, but it is still not clear whether the intrinsic dynamical patterns are functional or epiphenomenal. Using a simultaneous fMRI-EEG implementation of a well-known bi-stable visual task, we showed that the latent transient states (~100-ms) in the intrinsic EEG oscillations can predict the upcoming involuntarily perceptual transitions. The critical state predicting a dominant perceptual transition was characterised by the phase coupling between the precuneus (PCU), a key node of the Default Mode Network (DMN), and the primary visual cortex (V1). The interaction between the lifetime of this state and the PCU->V1 causal effect is correlated with the rate of perceptual fluctuation. Our study suggests that the brain’s endogenous dynamics are phenomenologically relevant, as they can trigger a diversion between potential visual processing pathways, while external stimuli remain the same. In this sense, the intrinsic DMN dynamics pre-empt the content of consciousness.

Background. Endocrinopathies are common in patients withβ-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism inβ-thalassemia major based on a meta-analysis.Methods. PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) inβ-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients withβ-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted.Results. A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM inβ-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders inβ-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias.Conclusion. High prevalence of endocrine disorders involving abnormal glucose metabolism was detected inβ-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

During the combustion of polymeric materials, plenty of heat, smoke, and toxic gases are produced that may cause serious harm to human health. Although the flame retardants such as halogen- and phosphorus-containing compounds can inhibit combustion, they cannot effectively reduce the release of toxic fumes. Zinc hydroxystannate (ZHS, ZnSn(OH)6) is an environmentally friendly flame retardant that has attracted extensive interest because of its high efficiency, safety, and smoke suppression properties. However, using ZHS itself may not contribute to the optimal flame retardant effect, which is commonly combined with other flame retardants to achieve more significant efficiency. Few articles systematically review the recent development of ZHS in the fire safety field. This review aims to deliver an insight towards further direction and advancement of ZHS in flame retardant and smoke suppression for multiple polymer blends. In addition, the fire retarded and smoke suppression mechanism of ZHS will be demonstrated and discussed in depth.

Background The timing of laparoscopic cholecystectomy (LC) performed after the mild acute biliary pancreatitis (MABP) is still controversial. We conducted a review to compare same-admission laparoscopic cholecystectomy (SA-LC) and delayed laparoscopic cholecystectomy (DLC) after mild acute biliary pancreatitis (MABP). Methods We systematically searched several databases (PubMed, EMBASE, Web of Science, and the Cochrane Library) for relevant trials published from 1 January 1992 to 1 June 2018. Human prospective or retrospective studies that compared SA-LC and DLC after MABP were included. The measured outcomes were the rate of conversion to open cholecystectomy (COC), rate of postoperative complications, rate of biliary-related complications, operative time (OT), and length of stay (LOS). The meta-analysis was performed using Review Manager 5.3 software (The Cochrane Collaboration, Oxford, United Kingdom). Results This meta-analysis involved 1833 patients from 4 randomized controlled trials and 7 retrospective studies. No significant differences were found in the rate of COC (risk ratio [RR] = 1.24; 95% confidence interval [CI], 0.78–1.97; p = 0.36), rate of postoperative complications (RR = 1.06; 95% CI, 0.67–1.69; p = 0.80), rate of biliary-related complications (RR = 1.28; 95% CI, 0.42–3.86; p = 0.66), or OT (RR = 1.57; 95% CI, − 1.58–4.72; p = 0.33) between the SA-LC and DLC groups. The LOS was significantly longer in the DLC group (RR = − 2.08; 95% CI, − 3.17 to − 0.99; p = 0.0002). Unexpectedly, the subgroup analysis showed no significant difference in LOS according to the Atlanta classification (RR = − 0.40; 95% CI, − 0.80–0.01; p = 0.05). The gallstone-related complications during the waiting time in the DLC group included gall colic, recurrent pancreatitis, acute cholecystitis, jaundice, and acute cholangitis (total, 25.39%). Conclusion This study confirms the safety of SA-LC, which could shorten the LOS. However, the study findings have a number of important implications for future practice.

The Chinese CubeSat Mission, Gamma Ray Integrated Detectors (GRID), recently detected its first gamma-ray burst, GRB 210121A, which was jointly observed by the Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM). This burst is confirmed by several other missions, including \fermi and \textit{Insight}-HXMT. We combined multi-mission observational data and performed a comprehensive analysis of the burst's temporal and spectral properties. Our results show that the burst is relatively special in its high peak energy, thermal-like low energy indices, and large fluence. By putting it to the $E_{\rm p}$-$E_{\rm\gamma, iso}$ relation diagram with assumed distance, we found this burst can be constrained at the redshift range of [0.3,3.0]. The thermal spectral component is also confirmed by the direct fit of the physical models to the observed spectra. Interestingly, the physical photosphere model also constrained a redshift of $z\sim$ 0.3 for this burst, which help us to identify a host galaxy candidate at such a distance within the location error box. Assuming the host galaxy is real, we found the burst can be best explained by the photosphere emission of a typical fireball with an initial radius of $r_0\sim$ 3.2 $\times 10^7$ cm., Comment: ApJ accpeted; 12 pages, 11 figures, 3 tables

This paper proposes an unsynchronized two-terminal fault location method on three phase untransposed transmission lines considering line parameter uncertainties. The method utilizes three phase voltage and current phasor measurements before and during the fault, without requirement of synchronization between two terminals. The proposed method first formulates the fault location problem considering line parameter uncertainties in a standard syntax, where the distributed parameters as well as the asymmetry of untransposed transmission lines are carefully considered to ensure accurate representation of physical laws before and during the fault. The location of the fault and unknown parameters of the untransposed transmission line are introduced as states of the system. Afterwards, the states of the system, including the location of the fault, are systematically solved using the state estimation algorithm. Extensive numerical experiments validate that the proposed method has higher accuracy compared to the existing fault location methods considering line parameter uncertainties, regardless of fault types, locations and impedances.

Background: Engineered nuclease-mediated gene targeting through homology-directed repair (HDR) in autologous hematopoietic stem and progenitor cells (HSPCs) has the potential to cure β-thalassemia (β-thal). Although previous studies have precisely corrected site-specific HBB mutations by HDR in vitro and in vivo, targeting the various HBB mutations in β-thal is still challenging. Here, we devised a universal strategy to achieve repaired most types of HBB mutations through the CRISPR/Cas9 and the rAAV6 donor.Methods: Using cord blood-derived HSPCs from health donors, we tested the strategy to achieved highly efficient targeted integration by optimizing design and delivery parameters of a ribonucleoprotein (RNP) complex comprising Cas9 protein and modified single guide RNA, together with a rAAV6 donor. We assessed the edited HSPCs function in vitro by methylcellulose colonies assay, CFU assay, differentiation experiment and Wright-Giemsa staining. Edited HSPCs transplanted into NSI mice to assess the long-term reconstitution in vivo. Whole-genome sequencing was used to analysis the off-target mutagenesis of edited HSPCs.Results: Edited HSPCs exhibited normal multilineage formation and erythroid differentiation abilities without off-target mutagenesis and retained the ability to engraft. Moreover, we used the strategy to efficiently correct the β-CD41/42 mutation of patient-derived HSPCs, erythrocytes differentiation from which expressed more HBB mRNA than uncorrected cells.Conclusion: This strategy demonstrated a universal approach to correct most types of HBB gene mutations in β-thal.

This paper proposes an iterative parameter-free fault location algorithm on three-terminal untransposed transmission lines. Three phase voltage and current synchrophasor measurements at three terminals of the line before and during the fault are typically required. The proposed method considers the lumped shunt capacitance and does not require any assumption on the tower structure. The method first builds the transmission line models before and during faults, which describe all the physical laws that the line should obey. Meanwhile, the parameters of transmission line as well as the location of the fault are introduced as unknown variables. Afterwards, the fault location is obtained using the NewtonRaphson iterative method. Numerical experiments in PSCAD/EMTDC validate the fault location accuracy of the proposed method, which is independent of fault locations, fault types and fault impedances.

Background Triple‐negative breast cancer (TNBC) is one subtype of breast cancer, which is characterized by an aggressive disease. It is commonly accompanied with extremely poor prognosis because of no available molecularly targeted therapy. Thus, understanding the detailed molecular mechanisms of TNBC is urgently needed. Methods The levels of Axis inhibition protein 1 (Axin1), Cyclin D1, c‐Myc, and miR‐124‐3p.1 were measured by quantitative real‐time PCR (qRT‐PCR). Furthermore, the breast cancer cell proliferation was measured by CCK‐8 assay, colony formation assays, and EdU staining. Xenograft model was used to show the tumor genesis of breast cancer cells. The regulatory function of miR‐124‐3p.1 on Wnt/β‐catenin signaling activation through directly targeting Axin1 was proven using qRT‐PCR, Western blot analysis, and dual‐luciferase reporter assay. To further assess the clinical significance of miR‐124‐3p.1 in the prognosis of breast cancer patients, we performed Kaplan‐Meier survival analysis and log‐rank tests. Results miR‐124‐3p.1 expression was elevated in advanced TNBC patients, and high miR‐124‐3p.1 predicts poor overall survival in TNBC patients. Further data showed that miR‐124‐3p.1 downregulation diminished, while miR‐124‐3p.1 upregulation increased the growth of TNBC cells in vitro and in vivo. Finally, we proved that miR‐124‐3p.1 exerted its function via targeting tumor suppressor gene Axin1 and activating the Wnt signaling pathway. Conclusion In summary, all the results demonstrate that miR‐124‐3p.1 promotes TNBC cell growth by controlling Axin1, suggesting that targeting miR‐124‐3p.1 might offer an effective therapeutic strategy for TNBC in the future.

Despite significant progress in the treatment of breast cancer due to advances in surgery, cytotoxic agents, and endocrine therapy, the prognosis for patients has not improved much. Accumulated evidence indicates that heterogeneous nuclear ribonucleoprotein M (hnRNPM) and Wnt/β-catenin function as tumor oncogenes in the progression of many cancers. The present study aimed to explore whether HnRNPM/β-catenin signaling molecules might serve as a genetic target for breast cancer treatment. To shed light on this issue, quantitative real-time polymerase chain reaction (qRT-PCR) detection, Western blotting, and immunohistochemical staining were performed. The hnRNPM is expressed at a much higher level in breast cancer tissues and cell lines than in noncancerous tissues and cell lines. In vitro studies revealed that overexpressed hnRNPM promoted cell proliferation and colony formation but inhibited cell apoptosis. In vivo results demonstrated that upregulation of hnRNPM dramatically increased breast cancer xenograft tumor growth. Western blotting and immunofluorescence studies revealed that hnRNPM markedly activated the Wnt/β-catenin pathway and catalyzed its translocation from the cytoplasm to the nucleus by targeting axin, a negative regulator of Wnt/β-catenin signaling in MCF-7 and KPL-4 cells. Elevated levels of c-Myc and cyclin D1 were observed when MCF-7 and KPL-4 cells were transfected with a hnRNPM vector. These findings indicate that the hnRNPM/axin/β-catenin signaling pathway acts as an oncogenic promoter in the progression of breast cancer, suggesting that hnRNPM may be a potential target for the treatment of this disease.