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Abstract Waste oyster shells (WOS) have the potential to serve as a construction material, offering a sustainable alternative to traditional fine aggregates in the production of WOS concrete. This can play a critical role in reducing environmental issues resulting from the overexploitation of river sand and the haphazard disposal of WOS. Although existing research has predominantly focused on understanding the static mechanical characteristics of concrete when WOS is employed, the dynamic mechanical properties have still received less attention. To understand the impact of WOS as a substitute for fine aggregates on the dynamic mechanical properties of concrete, a series of tests employing Split Hopkinson Pressure Bar (SHPB) were carried out. The findings demonstrate that the peak stress and elastic modulus increase as the WOS substitution ratio (S r ) increases from 0 to 20% but exhibit an exponential decline as S r increases from 20 to 100%. This response can be explained by the joint effects of the pore-filling effect caused by WOS sand and the increasing air content caused by WOS sand. As S r increases from 0 to 20%, the pore-filling mechanism becomes predominant as the water absorption rate decreases slightly from 4.31 to 3.83%. However, for S r increasing from 20 to 100%, the negative influence of the air content becomes the primary contributing factor, where the water absorption rate increases from 3.83 to 14.68%. Furthermore, under the same impact pressure, the concrete with S r = 20% absorbed the most energy, providing the best dynamic mechanical performance. These findings highlight the potential use of WOS in concrete for improving its dynamic characteristics, promoting both sustainable construction and enhancing the material properties in impact-resistant structures.

The continual emergence of highly pathogenic novel coronaviruses and their variants has underscored the importance of neutralizing monoclonal antibodies (mAbs) as a pivotal therapeutic approach. In the present study, we report the specific neutralizing antibodies 13H7 and 9G11, which target the N-terminal domain (NTD) and receptor-binding domain (RBD) of the SARS-CoV-2, respectively. The comparative analysis observed that 13H7 not only neutralizes early variants of concern (VOCs) but also exhibits neutralizing activity against the Omicron sublineage, including BA.4, BA.5, BQ.1, and BQ.1.1. 9G11, as an RBD antibody, also demonstrated remarkable neutralizing efficacy. A cocktail antibody combining 13H7 and 9G11 with the previously reported 3E2 broaden the neutralization spectrum against new variants of the SARS-CoV-2. We elucidated the cryo-EM structure of the complex, clarifying the mechanism of action of the cocktail antibody combination. Additionally, we also emphasized the molecular mechanism between 13H7 and SARS-CoV-2 NTD, revealing the impact of Y144 and H146 residue deletions and mutations on the neutralizing efficacy of 13H7. Taken together, our findings not only offer novel insights into the combination therapy of NTD and RBD neutralizing mAbs but also lay a theoretical foundation for the development of vaccines targeting NTD antibodies, thus providing valuable understanding of alleviating the emergence of SARS-CoV-2 variants.

Abstract Background Nasopharyngeal carcinoma (NPC) poses a significant health burden in specific regions of Asia, and some of NPC patients have bone metastases at the time of initial diagnosis. Bone metastasis can cause pathologic fractures and pain, reducing patients' quality of life, and is associated with worse survival. This study aims to unravel the complex role of insulin-like growth factor 1 receptor (IGF-1R) in NPC bone metastasis, offering insights into potential therapeutic targets. Methods We assessed IGF-1R expression in NPC cells and explored its correlation with bone metastasis. Experiments investigated the impact of osteoclast-secreted IGF-1 on the IGF-1R/AKT/S6 pathway in promoting NPC cell proliferation within the bone marrow. Additionally, the reciprocal influence of tumor-secreted Granulocyte–macrophage colony-stimulating factor (GM-CSF) on osteoclast differentiation and bone resorption was examined. The effects of IGF-1 neutralizing antibody, IGF-1R specific inhibitor (NVP-AEW541) and mTORC inhibitor (rapamycin) on nasopharyngeal carcinoma bone metastasis were also explored in animal experiments. Results Elevated IGF-1R expression in NPC cells correlated with an increased tendency for bone metastasis. IGF-1, secreted by osteoclasts, activated the IGF-1R/AKT/S6 pathway, promoting NPC cell proliferation in the bone marrow. Tumor-secreted GM-CSF further stimulated osteoclast differentiation, exacerbating bone resorption. The IGF-1 neutralizing antibody, NVP-AEW541 and rapamycin were respectively effective in slowing down the rate of bone metastasis and reducing bone destruction. Conclusion The intricate interplay among IGF-1R, IGF-1, and GM-CSF highlights potential therapeutic targets for precise control of NPC bone metastasis, providing valuable insights for developing targeted interventions.

Abstract Objective This study aimed to explore the optimal time of laparoscopic cystectomy for unilateral ovarian endometrioma patients and evaluate the influence on ovarian reserve. Materials and methods This prospective randomized controlled study included 88 women with unilateral ovarian endometrioma at a tertiary teaching hospital. All patients received their first identified diagnosis of ovarian endometrioma by ultrasound (> 4 cm and ≤ 10 cm) and were administered an oral contraceptive pill (OC) for one cycle before laparoscopy. They were randomly divided into two groups: laparoscopy at the late luteal phase (group LLP) (n = 44) (termination of OC for two days) and laparoscopy at the early follicular phase (group EFP) (n = 44) (day 3 after menstruation). Basic clinical characteristics were recorded. Serum Anti-Müllerian hormone (AMH) levels were measured at various times to predict ovarian reserve. Serum levels of Anti-Müllerian hormone (AMH) were measured at several time sites to predict the ovarian reserve; AMH and leukocyte esterase (LE) levels of the endometrioma wall were measured. Results Before surgery, serum AMH levels decreased in both groups from preoperative to one week and six months postoperatively. In contrast, the difference values of group EFP were larger than those of group LLP at postoperative one week and postoperative six months (1.87 ± 0.97 vs. 1.31 ± 0.93, P = 0.07; 1.91 ± 1.06 vs. 1.54 ± 0.93, P = 0.001). The mean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP, significantly higher than those in group LLP (25.83% vs. 31.43%, P

Abstract Background Salpingotomy may change the anatomical structure and patency of the fallopian tube, which may affect the fallopian function. This study is to investigate the clinical efficacy of preliminary hysteroscopic tubal hydrotubation (HTH) after laparoscopic salpingotomy for tubal ampullary pregnancy. Methods A retrospective study was carried out, 140 women underwent laparoscopic salpingotomy for ampullary pregnancy from March 2013 to March 2017. Some patients received HTH in the 1st month and hysterosalpingography (HSG) in the 3rd month after salpingotomy (HTH group; n = 95), and some patients only received HSG in the 3rd month after salpingotomy (control group; n = 45). Clinical data, tubal patency and fertility outcome were evaluated after follow-up of 15 months. Results The tubal patency rate of the operated side was significantly higher in the HTH group than that in the control group (89.47% vs 68.89%, P

This paper proposes a voltage stability constrained optimal power flow (VSC-OPF) for an unbalanced distribution system with distributed generators (DGs) based on semidefinite programming (SDP). The AC optimal power flow (ACOPF) for unbalanced distribution systems is formulated as a chordal relaxation-based SDP model. The minimal singular value (MSV) of the power flow Jacobian matrix is adopted to indicate the voltage stability margin. The Jacobian matrix can be explicitly expressed by ACOPF state variables. The nonlinear constraint on the Jacobian MSV is then replaced with its maximal convex subset using linear matrix inequality (LMI), which can be incorporated in the SDP-based ACOPF formulation. A penalty technique is leveraged to improve the exactness of the SDP relaxation. Case studies performed on several IEEE test systems validate the effectiveness of the proposed method.

Abstract The purpose of this study was to develop a dynamic model to predict the risk of spontaneous preterm birth at

Abstract Here, we develop k -mer substring space decomposition (Kssd), a sketching technique which is significantly faster and more accurate than current sketching methods. We show that it is the only method that can be used for large-scale dataset comparisons at population resolution on simulated and real data. Using Kssd, we prioritize references for all 1,019,179 bacteria whole genome sequencing (WGS) runs from NCBI Sequence Read Archive and find misidentification or contamination in 6164 of these. Additionally, we analyze WGS and exome runs of samples from the 1000 Genomes Project.

Skin cutaneous melanoma (SKCM) is a highly malignant and aggressive cancer. Previous studies have shown that cellular senescence is a promising therapeutic strategy to limit melanoma cell progression. However, models to predict the prognosis of melanoma based on senescence-related lncRNAs and the efficacy of immune checkpoint therapy remain undefined. In this study, we developed a predictive signature consisting of four senescence-related lncRNAs (AC009495.2, U62317.1, AATBC, MIR205HG), and we then classified patients into high- and low-risk groups. GSEA (Gene set enrichment analysis) showed different activation of immune-related pathways in two groups. In addition, there were significant differences between the scores of tumor immune microenvironment, tumor burden mutation, immune checkpoint expression, and chemotherapeutic drug sensitivity between the two groups of patients. It provides new insights to guide more personalized treatment for patients with SKCM.

Chelerythrine (CHE) is a majorly harmful isoquinoline alkaloid ingredient in Chelidonium majus that could trigger potential hepatotoxicity, but the pivotal molecular mechanisms remain largely unknown. In the present study, CHE-induced cytotoxicity and the underlying toxic mechanisms were investigated using human HepG2 cells in vitro. Data showed that CHE treatment (at 1.25–10 μM)-induced cytotoxicity in HepG2 cells is dose-dependent. CHE treatment increased the production of ROS and induced oxidative stress in HepG2 cells. Additionally, CHE treatment triggered the loss of mitochondrial membrane potential, decreased the expression of mitochondrial complexes, upregulated the expression of Bax, CytC, and cleaved-PARP1 proteins and the activities of caspase-9 and caspase-3, and downregulated the expression of Bcl-XL, and HO-1 proteins, finally resulting in cell apoptosis. N-acetylcysteine supplementation significantly inhibited CHE-induced ROS production and apoptosis. Furthermore, CHE treatment significantly downregulated the expression of phosphorylation (p)-Akt (Ser473), p-mTOR (Ser2448), and p-AMPK (Thr172) proteins in HepG2 cells. Pharmacology inhibition of Akt promoted CHE-induced the downregulation of HO-1 protein, caspase activation, and apoptosis. In conclusion, CHE-induced cytotoxicity may involve the inhibition of Akt pathway and the activation of oxidative stress-mediated mitochondrial apoptotic pathway in HepG2 cells. This study sheds new insights into understanding the toxic mechanisms and health risks of CHE.

Porphyrin derivatives are popular photodynamic therapy (PDT) agents; however, their typical insolubility in water has made it challenging to separate cells of organisms in a liquid water environment. Herein, a novel water-soluble 5,10,15,20-tetrakis(4-methoxyphenyl-3-sulfonatophenyl) porphyrin (TMPPS) was synthesized with 95% yield by modifying the traditional sulfonation route. The reaction of TMPPS with AgNO3 afforded AgTMPPS an unusual Ag(II) oxidation state (97% yield). The free base and Ag(II) complex were characterized by matrix-assisted laser desorption ionization-mass spectroscopy, and 1H nuclear magnetic resonance, Fourier-transform infrared, UV-vis, fluorescence, and X-ray photolectron spectroscopies. Upon 460 nm laser irradiation, AgTMPPS generated a large amount of 1O2, whereas no ⦁OH was detected. Antibacterial experiments on methicillin-resistant Staphylococcus aureus (MRSA) revealed that the combined action of AgⅡ ions and PDT could endow AgTMPPS with a 100% bactericidal ratio for highly concentrated MRSA (108 CFU/mL) at a very low dosage (4 μM) under laser irradiation at 360 J/cm2. Another PDT response was demonstrated by photocatalytically oxidizing 1,4-dihydronicotinamide adenine dinucleotide to NAD+ with AgTMPPS. The structural features of the TMPPS and AgTMPPS molecules were investigated by density functional theory quantum chemical calculations to demonstrate the efficient chemical and photodynamical effects of AgTMPPS for non-invasive antibacterial therapy.

Abstract Background Programmed cell death ligand 1 (PD-L1) is an important immune-inhibitory protein expressed on cancer cells to mediate cancer escape through interaction with PD-1 expressed on activated T lymphocytes (T cells). Previously, we reported that colon and breast cancer stem cells (CSCs) expressed much higher levels of PD-L1 than their parental cells, suggesting they will be more resistant to immune attack. Methods We investigated the underlining mechanism of PD-L1 increase in colon CSCs, with a special focus on the effect of insulin and epithelial growth factor (EGF), the two fundamental components to sustain the metabolism and stemness in the culture of CSCs. Results We found that insulin increased the total and surface PD-L1 levels through PI3K/Akt/mTOR pathway as the increase could be inhibited by the dual inhibitor of the pathway, BEZ235. EGF didn’t affect the total PD-L1 levels of CSCs but increased the cell surface protein levels by flow cytometry analysis, indicating EGF promotes the transport of PD-L1 to the cell surface. Blocking cell surface PD-L1 with a specific antibody resulted in a significant reduction of tumour sphere formation but didn’t interfere with the sphere growth, suggesting that cell surface PD-L1 may act as an adhering molecule for CSCs. Conclusions Apart from the essential roles in metabolism and stemness, insulin and EGF involve in up-regulation of PD-L1 expression in colon CSCs, therefore the inhibition of insulin and EGF/EGFR pathways can be considered for cancer immunotherapy or combined with PD-1/PD-L1 antibody-based cancer immunotherapy to eliminate CSCs.

Increasingly frequent natural disasters and man-made malicious attacks threaten the power systems. Improving the resilience has become an inevitable requirement for the development of power systems. The importance assessment of components is of significance for resilience improvement, since it plays a crucial role in strengthening grid structure, designing restoration strategy, and improving resource allocation efficiency for disaster prevention and mitigation. This paper proposes a component importance assessment approach of power systems for improving resilience under wind storms. Firstly, the component failure rate model under wind storms is established. According to the model, system states under wind storms can be sampled by the non-sequential Monte Carlo simulation method. For each system state, an optimal restoration model is then figured out by solving a component repair sequence optimization model considering crew dispatching. The distribution functions of component repair moment can be obtained after a sufficient system state sampling. And Copeland ranking method is adopted to rank the component importance. Finally, the feasibility of the proposed approach is validated by extensive case studies.

Ivermectin (IVM) could cause potential neurotoxicity; however, the precise molecular mechanisms remain unclear. This study explores the cytotoxicity of IVM in human neuroblastoma (SH-SY5Y) cells and the underlying molecular mechanisms. The results show that IVM treatment (2.5–15 μM) for 24 h could induce dose-dependent cell death in SH-SY5Y cells. Compared to the control, IVM treatment significantly promoted the production of ROS, mitochondrial dysfunction, and cell apoptosis. IVM treatment also promoted mitophagy and autophagy, which were charactered by the decreased expression of phosphorylation (p)-Akt and p-mTOR proteins, increased expression of LC3II, Beclin1, ATG5, PINK, and Pakin1 proteins and autophagosome formation. N-acetylcysteine treatment significantly inhibited the IVM-induced production of ROS and cell death in SH-SY5Y cells. Autophagy inhibitor (e.g., 3-methyladenine) treatment significantly inhibited IVM-induced autophagy, oxidative stress, and cell apoptosis. Taken together, our results reveal that IVM could induce autophagy and apoptotic cell death in SH-SY5Y cells, which involved the production of ROS, activation of mitochondrial pathway, and inhibition of Akt/mTOR pathway. Autophagy inhibition improved IVM-induced oxidative stress and apoptotic cell death in SH-SY5Y cells. This current study provides new insights into understanding the molecular mechanism of IVM-induced neurotoxicity and facilitates the discovery of potential neuroprotective agents.

Advanced oxidation protein products (AOPPs) are a family of oxidized protein compounds and could induce oxidative stress and inflammatory lesion in various cells. The accumulation of AOPPs was associated with female reproductive diseases such as polycystic ovary syndrome (PCOS), leiomyoma and endometriosis. However, the relationship between AOPPs and endometrial cells is unclear. To explore the effects of accumulated AOPPs on endometrial cells, we treated normal rat endometrial epithelial cells (rEECs) and endometriosis model rats with AOPPs. Primary rEECs were collected from 8-week-old female Wistar rats. Increasing the amount of AOPPs in the media of rEECs enhanced rEEC proliferation and migration, and inhibited apoptosis. Moreover, AOPPs triggered the production of reactive oxygen species and nitrite along with activated ERK and P38 signal and this, in turn, led to an upregulation of proliferation and migration. With the treatment of antioxidants or the inhibitors of ERK and P38, the above effects of AOPPs on rEECs were attenuated. Additionally, in an endometriosis rat model, a similar phenomenon was observed in that the growth of endometriotic implants were promoted by AOPPs and EECs were significantly increased. This study indicated that the accumulation of AOPPs could promote rEEC proliferation and migration through ERK and P38 signal both in vivo and in vitro. This article has an associated First Person interview with the first author of the paper.

The world is witnessing increasing frequency of extreme events. The power system is the backbone critical infrastructure of our economy and is under treat of such events. The resilient power system is intended to cope with low probability, high risk extreme events including extreme natural disasters and man-made attacks. Realizing resilience in the power system has been an unprecedented mission. Equipped with today’s smart grid technologies, power system can be rendered more resilient by the strategies taken before, during and after a disruptive event erupts. Based on a thorough review of existing works, we present the most-investigated problems and solving measures according to their application stage. In the preparation stage, innovative planning frameworks considering disaster scenarios are discussed; after the event, the system can alter the topology and integrate resource allocation to alleviate load shedding. The characteristics of different disasters are investigated to facilitate enhancing resilience. The review provides a summary of resilience strategies in the power system and can shed light to future research and application. Keywords: Power system, Resilience, Critical infrastructure, Extreme event, Natural disaster

This research is based on an approach that looks at cross-cultural research design as a "lens" for a deeper understanding of what goes on in the classroom. The research question is how a cross-cultural study like this one can lead to identifying the cultural script of teaching and help educators reflect on their practice. In this context, Chinese lessons could be described as a case-based study of pedagogical reasoning that drives a shift from focusing on "content" to "competence". This article draws on qualitative data collected by the researchers and a cross-cultural analysis of a science lesson in an elementary school in Beijing, China. Using the Japanese educators' critiques and Chinese reviews, the article determines the cultural script of teaching science (the first research question) and the way Chinese teachers reflect on their practice through the Japanese lens (the second research question). This study exposes the importance of teachers' understanding and reflecting on their practice, "technically," "practically," and "critically." The analysis results show how teachers learn to change their lenses, to reflect on their teaching and reconstruct their understanding about teacher professionalism through at least four basic elements: "didactics," "praxis," "pedagogy," and "theory."

Cancer stem-like cells, possessing “stemness” properties, play crucial roles in progression, metastasis, and drug resistance in various cancers. Viral microRNAs (such as EBV-miR-BART7-3p), as exogenous regulators, have been discovered to regulate malignant progression of nasopharyngeal carcinoma (NPC), suggesting a possible role of viral microRNAs in imposing stemness. In this study, we found that EBV-miR-BART7-3p induce stemness of NPC cells. We firstly reported that EBV-miR-BART7-3p increased the percentage of side population cells, the development of tumor spheres, and the expression level of stemness markers in vitro. This viral microRNA also enhanced stem-like or cancer-initiating properties of NPC cells in vivo. Besides, we identified SMAD7 as a novel target gene of EBV-miR-BART7-3p in addition to PTEN gene we previously reported; this viral microRNA suppressed SMAD7, led to activation of TGF-β signaling, and eventually enhanced the stemness of NPC cells. Silencing of SMAD7 resembled the effects generated by EBV-miR-BART7-3p in NPC cells. After reconstitution of SMAD7, EBV-miR-BART7-3p-expressing cells underwent a phenotypic reversion. EBV-positive NPC cells were used to enable experimental validation. Finally, we further discovered that EBV-miR-BART7-3p increased chemo-resistance of NPC in vitro and in vivo, supporting that EBV-miR-BART7-3 resulted in increased stemness of NPC cells and lead to drug resistance and cancer recurrence. Overall, this study uncovered a novel mechanism underlying viral microRNA-associated stemness of NPC cells. This viral microRNA and its associated cellular genes may be potential therapeutic targets for restraining chemo-resistance and recurrence of NPC.

How to restore the load of power system after disasters, especially to guarantee the power supply of the important load, is a significant segment of the research on power system resilience. Nowadays, quantities of research existing has been done to reduce the load loss after disasters. However, there is no clear methodologies or metrics available to evaluate the effects of restoration strategies. Here, a method for evaluating the recovery and economic efficiency of the power system post-disaster recovery strategy is explored, and assessment metrics related are defined. The method considers the repair and recovery process of transmission lines, generators, and the distributed generation at load nodes. After given the repair strategies, components state sampling and system power flow calculation will be conducted to analyse the running state of the system, then simulate the component repair and the load recovery procedure, and finally calculate corresponding metrics. This novel method can obtain and compare the expected effects of different restoration strategies in advance, providing more reliable reference information for system decision makers. Finally, the proposed method is applied to IEEE 14-bus system and verifies its effectiveness and application value.

The frequent occurrence of natural disasters and malicious attacks has exerted unprecedented disturbances on power systems, accounting for the extensive attention paid to power system resilience. Combined with the evolving nature of general disasters, this paper proposes resilience assessment approaches for power systems under a tri-stage framework. The pre-disaster toughness is proposed to quantify the robustness of power systems against potential disasters, where the thinking of area division and partitioned multi-objective risk method (PMRM) is introduced. In the case of information deficiency caused by disasters, the during-disaster resistance to disturbance is calculated to reflect the real-time system running state by state estimation (SE). The post-disaster restoration ability consists of response ability, restoration efficiency and restoration economy, which is evaluated by Sequential Monte-Carlo Simulation to simulate the system restoration process. Further, a synthetic metric system is presented to quantify the resilience performance of power systems from the above three aspects. The proposed approaches and framework are validated on the IEEE RTS 79 system, and helpful conclusions are drawn from extensive case studies.

High-voltage direct current (HVDC) grids are emerging, and their reliability has been an increasing concern for the utilities. HVDC grids are different from typical two-terminal HVDC transmission systems due to the loops in their topology, which makes it difficult to evaluate the reliability by conventional analytical methods. This paper proposes an innovative hybrid method to evaluate the reliability of meshed HVDC grids. First, steady-state models and reliability models are established for the components in HVDC grids, especially for converters and power flow controllers. In the models, virtual buses are introduced to represent the external AC connections to the HVDC grid. Then a hybrid reliability evaluation method is proposed based on an analytical approach and Monte Carlo simulation. One innovation of the paper is the application of an analytical analysis method to accelerate state evaluation in Monte Carlo simulation by skipping unnecessary optimization. The proposed models and methods are verified on two HVDC grids. Test results show that HVDC grids under most failure states (approximately 70%) tend to shed no load except on buses connected to faulted converters, and the application of the analytical method could promote evaluation efficiency significantly.

In order to consider the uncertainty and correlation of wind power in multiobjective transmission network expansion planning (TNEP), this paper presents an extended point-estimation method to calculate the probabilistic power flow, based on which the correlative power outputs of wind farm are sampled and the uncertain multiobjective transmission network planning model is transformed into a solvable deterministic model. A modified epsilon multiobjective evolutionary algorithm is used to solve the above model and a well-distributed Pareto front is achieved, and then the final planning scheme can be obtained from the set of nondominated solutions by a fuzzy satisfied method. The proposed method only needs the first four statistical moments and correlation coefficients of the output power of wind farms as input information; the modeling of wind power is more precise by considering the correlation between wind farms, and it can be easily combined with the multiobjective transmission network planning model. Besides, as the self-adaptive probabilities of crossover and mutation are adopted, the global search capabilities of the proposed algorithm can be significantly improved while the probability of being stuck in the local optimum is effectively reduced. The accuracy and efficiency of the proposed method are validated by IEEE 24 as well as a real system.

Identification of pathogen-inducible promoters largely lags behind cloning of the genes for disease resistance. Here, we cloned the soybean GmaPPO12 gene and found that it was rapidly and strongly induced by Phytophthorasojae infection. Computational analysis revealed that its promoter contained many known cis-elements, including several defense related transcriptional factor-binding boxes. We showed that the promoter could mediate induction of GUS expression upon infection in both transient expression assays in Nicotianabenthamiana and stable transgenic soybean hairy roots. Importantly, we demonstrated that pathogen-induced expression of the GmaPPO12 promoter was higher than that of the soybean GmaPR1a promoter. A progressive 5' and 3' deletion analysis revealed two fragments that were essential for promoter activity. Thus, the cloned promoter could be used in transgenic plants to enhance resistance to phytophthora pathogens, and the identified fragment could serve as a candidate to produce synthetic pathogen-induced promoters.