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Abstract Designing high‐performance and low‐cost electrocatalysts for oxygen evolution reaction (OER) is critical for the conversion and storage of sustainable energy technologies. Inspired by the biomineralization process, we utilized the phosphorylation sites of collagen molecules to combine with cobalt‐based mononuclear precursors at the molecular level and built a three‐dimensional (3D) porous hierarchical material through a bottom‐up biomimetic self‐assembly strategy to obtain single‐atom catalysts confined on carbonized biomimetic self‐assembled carriers (Co SACs/cBSC) after subsequent high‐temperature annealing. In this strategy, the biomolecule improved the anchoring efficiency of the metal precursor through precise functional groups; meanwhile, the binding‐then‐assembling strategy also effectively suppressed the nonspecific adsorption of metal ions, ultimately preventing atomic agglomeration and achieving strong electronic metal‐support interactions (EMSIs). Experimental characterizations confirm that binding forms between cobalt metal and carbonized self‐assembled substrate (Co–O4–P). Theoretical calculations disclose that the local environment changes significantly tailored the Co d‐band center, and optimized the binding energy of oxygenated intermediates and the energy barrier of oxygen release. As a result, the obtained Co SACs/cBSC catalyst can achieve remarkable OER activity and 24 h durability in 1 M KOH (η10 at 288 mV; Tafel slope of 44 mV dec−1), better than other transition metal‐based catalysts and commercial IrO2. Overall, we presented a self‐assembly strategy to prepare transition metal SACs with strong EMSIs, providing a new avenue for the preparation of efficient catalysts with fine atomic structures.

Abstract Triple‐negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%–80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c‐Myc, further promoting the stability of c‐Myc via deacetylation‐mediated inhibition of K48‐linked ubiquitylation. Stably expressed c‐Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p‐AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD‐L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c‐Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

Abstract Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.

Abstract There has been an upward trend in the incidence of glioma, with high recurrence and high mortality. The beta subunits of the 20S proteasome are encoded by the proteasome beta (PSMB) genes and may affect the proteasome’s function in glioma, assembly and inhibitor binding. This study attempted to reveal the function of the proliferation and invasion of glioma cells, which is affected by proteasome 20S subunit beta 2 (PSMB2). We subjected the data downloaded from the TCGA database to ROC, survival, and enrichment analyses. After establishing the stable PSMB2 knockdown glioma cell line. We detect the changes in the proliferation, invasion and migration of glioma cells by plate colony formation assay, transwell assay, wound healing assay and flow cytometry and PSMB2 expression was verified by quantitative PCR and Western blotting to identify the mRNA and protein levels. PSMB2 expression was higher in glioma tissues, and its expression positively correlated with poor prognosis and high tumor grade and after PSMB2 knockdown, the proliferation, invasion and migration of glioma cells were weakened.

Background: Yinqiaosan decoction (YQSD), a traditional Chinese medicinal recipe, has been employed to treat influenza in China for approximately 300 years. Objective: Our study aimed to explore the mechanisms of YQSD against influenza via in vivo and in vitro experimental studies. Study design: and methods UHPLC-Q-TOF-MS/MS was utilized to examine the substances of the YQSD. The chemical components of YQSD detected by UHPLC-Q-TOF-MS/MS were used for network pharmacology analysis. The antiviral effect of YQSD in vivo was investigated. The potential mechanisms of YQSD in combating influenza, which were predicted from network pharmacology analysis, were validated in vitro. Results: By use of UHPLC-Q-TOF-MS/MS, 97 compounds were identified from YQSD. Network pharmacology analysis revealed that the therapeutic effect of YQSD against influenza may be associated with the regulation of T cell receptors (TCR) and Phosphoinositide 3-Kinase (PI3K)- protein kinase B (Akt) signaling pathways. Treatment with YQSD significantly prolonged the mean survival time of the mice and reduced lung injury due to the influenza A virus in vivo. It was discovered that YQSD efficiently inhibited the expression of inflammation-related cytokines. Moreover, YQSD has been found to significantly reduce the expression levels of cluster of differentiation 3 (CD3), monocyte chemoattractant protein-1 (MCP-1), and H1N1 virus nucleoprotein (NP), and prevent the decrease of epithelial cadherin (E-cadherin) protein. In addition, YQSD can inhibit the phosphorylation of the zeta chain of T cell receptor-associated protein kinase 70 (ZAP70) and PI3K proteins in vitro. Conclusion: The capacity of YQSD to suppress viral multiplication and inflammatory response by modulating T cell immunity may explain its effect against influenza viral pneumonia, which may involve the regulation of TCR and PI3K signaling pathways.

Summary: Background: Since the initial identification of the Severe Fever with Thrombocytopenia Syndrome (SFTS) in ticks in rural areas of China in 2009, the virus has been increasingly isolated from a diverse array of hosts globally, exhibiting a rising trend in incidence. This study aims to conduct a systematic analysis of the temporal and spatial distribution of SFTS cases, alongside an examination of the infection rates across various hosts, with the objective of addressing public concerns regarding the spread and impact of the disease. Methods: In this systematic review and meta-analysis, an exhaustive search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Medline, CNKI, WanFang, and CQVIP. The literature search was confined to publications released between January 1, 2009, and May 29, 2023. The study focused on collating data pertaining to animal infections under natural conditions and human infection cases reported. Additionally, species names were unified using the National Center for Biotechnology Information (NCBI) database. The notification rate, notification death rate, case fatality rate, and infection rates (or MIR) were assessed for each study with available data. The proportions were pooled using a generalized linear mixed-effects model (GLMM). Meta-regressions were conducted for subgroup analysis. This research has been duly registered with PROSPERO, bearing the registration number CRD42023431010. Findings: We identified 5492 studies from database searches and assessed 238 full-text studies for eligibility, of which 234 studies were included in the meta-analysis. For human infection data, the overall pooled notification rate was 18.93 (95% CI 17.02–21.05) per ten million people, the overall pooled notification deaths rate was 3.49 (95% CI 2.97–4.10) per ten million people, and the overall pooled case fatality rate was 7.80% (95% CI 7.01%–8.69%). There was an increasing trend in notification rate and deaths rate, while the case fatality rate showed a significant decrease globally. Regarding animal infection data, among 94 species tested, 48 species were found to carry positive nucleic acid or antibodies. Out of these, 14 species were classified under Arthropoda, while 34 species fell under Chordata, comprising 27 Mammalia and 7 Aves. Interpretation: This systematic review and meta-analysis present the latest global report on SFTS. In terms of human infections, notification rates and notification deaths rates are on the rise, while the case fatality rate has significantly decreased. More SFTSV animal hosts have been discovered than before, particularly among birds, indicating a potentially broader transmission range for SFTSV. These findings provide crucial insights for the prevention and control of SFTS on a global scale. Funding: None.

ObjectiveTo examine the association of lactate-to-albumin ratio (LAR) with 30-day and 90-day mortality in patients with cerebral infarction admitted to the intensive care unit (ICU).MethodsIn this retrospective observational study, 1,089 patients with cerebral infarction were recruited. The concentration of blood lactate and serum albumin on the first day of ICU admission were recorded. The relationship between LAR levels and mortality was evaluated through univariate and multivariate Cox regression analyses, four-knot multivariate restricted cubic spline regression, and Kaplan–Meier (KM) curves.ResultsThe overall 30-day and 90-day mortality rates in the entire cohort were 27.3 and 35.8%, respectively. KM analysis revealed a significant relationship between high LAR index and the risk of all-cause mortality (log-rank p

Abstract Infected bone defects are a major challenge in orthopedic treatment. Native bone tissue possesses an endogenous electroactive interface that induces stem cell differentiation and inhibits bacterial adhesion and activity. However, traditional bone substitutes have difficulty in reconstructing the electrical environment of bone. In this study, we develop a self-promoted electroactive mineralized scaffold (sp-EMS) that generates weak currents via spontaneous electrochemical reactions to activate voltage-gated Ca2+ channels, enhance adenosine triphosphate-induced actin remodeling, and ultimately achieve osteogenic differentiation of mesenchymal stem cells by activating the BMP2/Smad5 pathway. Furthermore, we show that the electroactive interface provided by the sp-EMS inhibits bacterial adhesion and activity via electrochemical products and concomitantly generated reactive oxygen species. We find that the osteogenic and antibacterial dual functions of the sp-EMS depend on its self-promoting electrical stimulation. We demonstrate that in vivo, the sp-EMS achieves complete or nearly complete in situ infected bone healing, from a rat calvarial defect model with single bacterial infection, to a rabbit open alveolar bone defect model and a beagle dog vertical bone defect model with the complex oral bacterial microenvironment. This translational study demonstrates that the electroactive bone graft presents a promising therapeutic platform for complex defect repair.

Abstract Background Triple-negative breast cancer (TNBC) is a subtype of breast cancer with higher aggressiveness and poorer outcomes. Recently, long non-coding RNAs (lncRNAs) have become the crucial gene regulators in the progression of human cancers. However, the function and underlying mechanisms of lncRNAs in TNBC remains unclear. Methods Based on public databases and bioinformatics analyses, the low expression of lncRNA MIDEAS-AS1 in breast cancer tissues was detected and further validated in a cohort of TNBC tissues. The effects of MIDEAS-AS1 on proliferation, migration, invasion were determined by in vitro and in vivo experiments. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were carried out to reveal the interaction between MIDEAS-AS1 and MATR3. Luciferase reporter assay, Chromatin immunoprecipitation (ChIP) and qRT-PCR were used to evaluate the regulatory effect of MIDEAS-AS1/MATR3 complex on NCALD. Results LncRNA MIDEAS-AS1 was significantly downregulated in TNBC, which was correlated with poor overall survival (OS) and progression-free survival (PFS) in TNBC patients. MIDEAS-AS1 overexpression remarkably inhibited tumor growth and metastasis in vitro and in vivo. Mechanistically, MIDEAS-AS1 mainly located in the nucleus and interacted with the nuclear protein MATR3. Meanwhile, NCALD was selected as the downstream target, which was transcriptionally regulated by MIDEAS-AS1/MATR3 complex and further inactivated NF-κB signaling pathway. Furthermore, rescue experiment showed that the suppression of cell malignant phenotype caused by MIDEAS-AS1 overexpression could be reversed by inhibition of NCALD. Conclusions Collectively, our results demonstrate that MIDEAS-AS1 serves as a tumor-suppressor in TNBC through modulating MATR3/NCALD axis, and MIDEAS-AS1 may function as a prognostic biomarker for TNBC.

Abstract Background Studies have shown that microRNA-191 (miR-191) is involved in the development and progression of a variety of tumors. However, the function and mechanism of miR-191 in oral squamous cell carcinoma (OSCC) have not been clarified. Methods The expression level of miR-191 in tumor tissues of patients with primary OSCC and OSCC cell lines were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. OSCC cells were treated with miR-191 enhancers and inhibitors to investigate the effects of elevated or decreased miR-191 expression on OSCC cells proliferation, migration, cell cycle, and tumorigenesis. The target gene of miR-191 in OSCC cells were analyzed by dual-Luciferase assay, and the downstream signaling pathway of the target genes was detected using western blot assay. Results The expression of miR-191 was significantly upregulated in OSCC tissues and cell lines. Upregulation of miR-191 promoted proliferation, migration, invasion, and cell cycle progression of OSCC cells, as well as tumor growth in nude mice. Meanwhile, reduced expression of miR-191 inhibited these processes. Phospholipase C delta1 (PLCD1) expression was significantly downregulated, and negatively correlated with the expression of miR-191 in OSCC tissues. Dual-Luciferase assays showed that miR-191-5p could bind to PLCD1 mRNA and regulate PLCD1 protein expression. Western blot assay showed that the miR-191 regulated the expression of β-catenin and its downstream gene through targeting PLCD1. Conclusion MicroRNA-191 regulates oral squamous cell carcinoma cells growth by targeting PLCD1 via the Wnt/β-catenin signaling pathway. Thus, miR-191 may serve as a potential target for the treatment of OSCC.

Abstract Chemoresistance is one of the major causes of therapeutic failure and poor prognosis for breast cancer patients, especially for triple-negative breast cancer patients. However, the underlying mechanism remains elusive. Here, we identified novel functional roles of heat shock protein beta-1 (HSPB1), regulating chemoresistance and ferroptotic cell death in breast cancer. Based on TCGA and GEO databases, HSPB1 expression was upregulated in breast cancer tissues and associated with poor prognosis of breast cancer patients, which was considered an independent prognostic factor for breast cancer. Functional assays revealed that HSPB1 could promote cancer growth and metastasis in vitro and in vivo. Furthermore, HSPB1 facilitated doxorubicin (DOX) resistance through protecting breast cancer cells from drug-induced ferroptosis. Mechanistically, HSPB1 could bind with Ikβ-α and promote its ubiquitination-mediated degradation, leading to increased nuclear translocation and activation of NF-κB signaling. In addition, HSPB1 overexpression led to enhanced secretion of IL6, which further facilitated breast cancer progression. These findings revealed that HSPB1 upregulation might be a key driver to progression and chemoresistance through regulating ferroptosis in breast cancer while targeting HSPB1 could be an effective strategy against breast cancer.

Abstract Ocean mining activities have been ongoing for nearly 70 years, making great contributions to industrialization. Given the increasing demand for energy, along with the restructuring of the energy supply catalyzed by efforts to achieve a low-carbon economy, deep seabed mining will play an important role in addressing energy- and resource-related problems in the future. However, deep seabed mining remains in the exploratory stage, with many challenges presented by the high-pressure, low-temperature, and complex geologic and hydrodynamic environments in deep-sea mining areas, which are inaccessible to human activities. Thus, considerable efforts are required to ensure sustainable, economic, reliable, and safe deep seabed mining. This study reviews the latest advances in marine engineering geology and the environment related to deep-sea mining activities, presents a bibliometric analysis of the development of ocean mineral resources since the 1950s, summarizes the development, theory, and issues related to techniques for the three stages of ocean mining (i.e., exploration, extraction, and closure), and discusses the engineering geology environment, geological disasters, in-situ monitoring techniques, environmental protection requirements, and environmental effects in detail. Finally, this paper gives some key conclusions and future perspectives to provide insights for subsequent studies and commercial mining operations.

Abstract Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L‐arginine‐loaded selenium‐coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)‐induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI.

Abstract Objective The objectives of this study were to analyze the difference between the preoperative radiological and postoperative pathological stages of colorectal cancer (CRC) and explore the feasibility of elastic lamina invasion (ELI) as a prognostic marker for patients with stage III colon cancer. Methods A total of 105 consecutive patients underwent radical surgery (R0 resection) for stage III colon cancer at the Cancer Hospital of China Medical University between January 2015 and December 2017. Clinicopathological features, including radiological stage and elastic lamina staining, were analyzed for prognostic significance in stage III colon cancer. Results A total of 105 patients with stage III colon cancer who met the criteria and had complete data available were included. The median follow-up period of survivors was 41 months. During the follow-up period, 33 (31.4%) patients experienced recurrence after radical resection, and the 3-year disease-free survival (DFS) rate was 64.8%. The consistency between preoperative radiological and postoperative pathological staging was poor (κ = 0.232, P < 0.001). The accuracy of ≤ T2 stage diagnoses was 97.1% (102/105), that of T3 stage was 60.9% (64/105), that of T4a stage was 68.6% (72/105) and that of T4b stage was 91.4% (96/105). The DFS rate of T3 ELI (+) patients was significantly lower than that of both T3 ELI (−) patients (P = 0.000) and pT4a patients (P = 0.013). The DFS rate of T3 ELI (−) patients was significantly higher than that of pT4b patients (P=0.018). T3 ELI (+) (HR (Hazard ratio), 8.444 [95% CI, 1.736–41.067]; P = 0.008), T4b (HR, 57.727[95% CI, 5.547-600.754]; P = 0.001), N2 stage (HR, 10.629 [95% CI, 3.858–29.286]; P < 0.001), stage III (HR, 0.136 [95% CI, 0.31–0.589]; P = 0.008) and perineural invasion (PNI) (HR, 8.393 [95% CI, 2.094–33.637]; P = 0.003) were independent risk factors for postoperative recurrence of stage III colon cancer. Conclusions The consistency between preoperative radiological and postoperative pathological staging was poor, especially for tumors located in the ascending colon and descending colon. Elastic lamina staining is expected to become a stratified indicator of recurrence risk for patients with stage III colon cancer and a guide for individualized adjuvant chemotherapy, thus improving patient prognosis.

Abstract Numerous studies have shown that circRNAs are aberrantly expressed in various cancers and play a significant role in tumor progression. However, the molecular mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain ambiguous. By intersecting throughput data and qRT-PCR results from tissues and cell lines, circ-TRIO was identified as a potential oncogenic regulator of TNBC. Moreover, circ-TRIO expression was detected in TNBC tissues and was correlated with the recurrence and prognosis of TNBC patients. The circular characteristics of circ-TRIO were verified by RNase R and CHX assays. Functionally, the knockdown of circ-TRIO inhibited the proliferation, migration and invasion of TNBC cells, while the overexpression of circ-TRIO resulted in the opposite impacts. Mechanistically, a dual luciferase reporter assay and RNA immunoprecipitation were performed and indicated that circ-TRIO could combine with miR-432-5p to regulate the expression of coiled-coil domain containing 58 (CCDC58). In summary, our study illustrates that circ-TRIO plays an important role in the progression of TNBC by regulating the miR-432-5p/CCDC58 axis, which could broaden our insight into the underlying mechanisms and provide a novel prognostic marker of TNBC in the clinic.

This study characterizes the fractography of ferritic ductile iron under various loads, including tensile, fatigue and bending, and impact conditions. The results indicate that ductile fracture is the primary mechanism observed during tensile testing at room temperature. The fractography resulting from fatigue testing exhibits characteristics similar to cleavage fracture, and explains the formation of fatigue striations caused by the joint effects of dislocation slip and oxidation under crack tip stress. Under impact testing, the main fracture mechanism transitions from ductile to brittle with decreasing temperature. At high temperatures, fractography is mainly characterized by elliptical dimples with graphite nodules at the center that deform along the stress direction. In the ductile-brittle transition temperature range, a mixed fracture mechanism involving both dimples and cleavage patterns is observed. At low temperatures, the fracture mechanism is cleavage fracture, cleavage fracture is mainly caused by the deformation twin, inducing crack nucleation. These findings further validate D.O.Frenandino’s quantitative analysis method for determining the main crack propagation direction of ductile fracture and brittle fracture. By employing larger statistical datasets, it is shown that this method yields high accuracy in determining the main crack propagation direction of ferritic ductile iron, thereby promoting its application as a general method for impact fractography analysis.

With the drastic change in global climate, the wide distribution of natural lakes over the Qinghai-Tibet Plateau (TP) has attracted extensive attention due to their high climate sensitivity. In this paper, we investigated the dynamics of Paiku Co, the largest inland lake in the Qomolangma Natural Reserve, with the associated response to climate change in the past three decades. The methods used contain the water index method, the spatial and temporal fusion model, the statistical mono-window algorithm, and multi-variable linear regression. Lake area fluctuated greatly in 1990–2000, followed by a continuous shrinkage in 2000–2010, and it stabilized after that (2010–2020). We forecasted that Paiku Co would enter a slow expansion period. Conjoint analysis with climate factors showed that the area variation of Paiku Co was not significantly related to precipitation change, but negatively related to the change of air temperature and lake temperature. We found that the lake change was not dominated by a single factor but showed different climate sensitivity in each period. Especially, there was a common inflection point around 2013 that might herald the occurrence of a new trend of climate change. This article provides new ideas and solutions for the research of lakes in the Qinghai-Tibet Plateau and offers a reference for water resource management. HIGHLIGHTS The lake area has experienced a process of sharp shrink – recovery – continuous retreat – stabilization.; Paiku Co is mainly affected by temperature and exhibits variable climate sensitivity.; The area of Paiku Co stabilized in 2013 and may have a slow upward trend in the future.;

Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality. Although increasing lines of evidence suggest that both the placenta and the decidua likely play roles in the pathogenesis of PE, the molecular mechanism of PE remains elusive partly because of the heterogeneity nature of the maternal-fetal interface. In this study, we perform single-cell RNA-seq on the placenta and the decidual from patients with late-onset PE (LOPE) and women in normal pregnancy. Analyses of single-cell transcriptomes reveal that in LOPE, there are likely a global development deficiency of trophoblasts with impaired invasion of extravillous trophoblasts (EVT) and increased maternal immune rejection and inflammation in the placenta, while there are likely insufficient decidualization of decidual stromal cells (DSC), increased inflammation, and suppressed regulatory functions of decidual immune cells. These findings improve our understanding of the molecular mechanisms of PE.

BackgroundStandard-dose intravenous alteplase for acute ischemic stroke (AIS) in the unknown or extended time window beyond 4.5 h after symptom onset is both effective and safe for certain patients who were selected based on multimodal neuroimaging. However, uncertainty exists regarding the potential benefit of using low-dose alteplase among the Asian population outside the 4.5-h time window.MethodsConsecutive AIS patients who received intravenous alteplase between 4.5 and 9 h after symptom onset or with an unknown time of onset guided by multimodal computed tomography (CT) imaging were identified from our prospectively maintained database. The primary outcome was excellent functional recovery, defined as having a modified Rankin scale (mRS) score of 0–1 at 90 days. Secondary outcomes included functional independence (an mRS score of 0–2 at 90 days), early major neurologic improvement (ENI), early neurologic deterioration (END), any intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Propensity score matching (PSM) and multivariable logistic regression models were used to adjust for confounding factors and compare the clinical outcomes between the low- and standard-dose groups.ResultsFrom June 2019 to June 2022, a total of 206 patients were included in the final analysis, of which 143 were treated with low-dose alteplase and 63 were treated with standard-dose alteplase. After accounting for confounding factors, we observed that there were no statistically significant differences between the standard- and low-dose groups with respect to excellent functional recovery [adjusted odds ratio = 1.22 (aOR), 95% confidence interval (CI): 0.62–2.39; adjusted rate difference (aRD) = 4.6%, and 95% CI: −11.2 to 20.3%]. Patients of both groups had similar rates of functional independence, ENI, END, any ICH, sICH, and 90-day mortality. In the subgroup analysis, patients aged ≥70 years were more likely to achieve excellent functional recovery when receiving standard-dose rather than low-dose alteplase.ConclusionThe effectiveness of low-dose alteplase might be comparable to that of standard-dose alteplase in AIS patients aged

With the development of society and the advancement of technology, the emergence of the Internet of Things (IoT) has changed people’s lifestyles and raised the demand for energy to a new level. However, there are some drawbacks in terms of energy supply for IoT sensors, such as limited battery capacity and limitations in replacement and maintenance. Therefore, it has become urgent to develop a sustainable green energy source (wind energy) using the surrounding environment. Meanwhile, triboelectric nanogenerators (TENGs) with advantages such as flexible structure, low manufacturing cost, and environmental friendliness provide enormous potential for constructing self-powered sensing systems. In this work, we present a novel coaxial rolling charge pump TENG (CR-TENG) based on wind energy to enhance the output performance and durability. The rolling friction charge pump TENG directly injects positive and negative charges into the main TENG, which is more wear-resistant compared to sliding friction, and greatly increases the charge density and output power. In addition, the charge pumping part and the main TENG adopt the coaxial design, reducing the complexity of the structural design. On comparing the output performance of the CR-TENG under the initial state, rectifier bridge supplemental charge strategy, and charge pump supplemental charge strategy, results shown that the output voltage performance of the CR-TENG can be improved by 5800% under the charge pump supplemental charge strategy. Moreover, the output performance of the CR-TENG remains stable after 72,000 cycles. The output power of the CR-TENG can reach 1.21 mW with a load resistance of 3 × 107 Ω. And the CR-TENG can charge a 0.1 μF capacitor to 5 V in just 1.6 s. This work provides new insights for the rotary durable high output charge pump compensating a triboelectric nanogenerator and demonstrates the important potential of harvesting environmental energy to supply intelligent IoT nodes.

Abstract Purpose To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients. Patients and methods From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis. Results The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p = 0.248) and progression-free survival (p = 0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301–23.547; p = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine. Conclusion In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.

BackgroundAs one of the major constituents of the cannabis sativa plant, cannabidiol (CBD) is approved for use in medical treatment and cosmetics because of its potential health benefits. With the rapid growth of the CBD market, customers purchase these products, and relevant discussions are becoming more active on social media. ObjectiveIn this study, we aimed to understand the users’ attitudes toward CBD products in various countries by conducting text mining on social media in countries with different substance management policies. MethodsWe collected posts from Reddit and Xiaohongshu, conducted topic mining using the latent Dirichlet allocation model, and analyzed the characteristics of topics on different social media. Subsequently, a co-occurrence network of high-frequency keywords was constructed to explore potential relationships among topics. Moreover, we conducted sentiment analysis on the posts’ comments and compared users’ attitudes toward CBD products on Reddit and Xiaohongshu using chi-square test. ResultsCBD-related posts on social media have been rapidly increasing, especially on Xiaohongshu since 2019. A total of 1790 posts from Reddit and 1951 posts from Xiaohongshu were included in the final analysis. The posts on the 2 social media platforms, Reddit and Xiaohongshu, were categorized into 7 and 8 topics, respectively, by the latent Dirichlet allocation model, and these topics on the 2 social media were grouped into 5 themes. Our study showed that the themes on Reddit were mainly related to the therapeutic effects of CBD, whereas the themes on Xiaohongshu concentrated on cosmetics, such as facial masks. Theme 2 (CBD market information) and theme 3 (attitudes toward CBD) on Reddit had more connections with other themes in the co-occurrence network, and theme 3 and theme 1 (CBD therapeutic effects) had a high co-occurrence frequency (22,803/73,865, 30.87%). Meanwhile, theme 1 (CBD cosmetics) on Xiaohongshu had various connections with others (169,961/384,575, 44.19%), and the co-occurrence frequency of theme 4 (CBD ingredients) and theme 1 was relatively prominent (27,128/49,312, 55.01%). Overall, users’ comments tended to be positive for CBD-related information on both Reddit and Xiaohongshu, but the percentage was higher on Xiaohongshu (82.25% vs 86.18%; P

Background: Glioma is the most common primary tumor of the central nervous system. The conventional glioma treatment strategies include surgical excision and chemo- and radiation-therapy. Interferon Gamma (IFN-γ) is a soluble dimer cytokine involved in immune escape of gliomas. In this study, we sought to identify IFN-γ-related genes to construct a glioma prognostic model to guide its clinical treatment.Methods: RNA sequences and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) and the China Glioma Genome Atlas (CGGA). Using univariate Cox analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm, IFN-γ-related prognostic genes were selected to construct a risk scoring model, and analyze its correlation with the clinical features. A high-precision nomogram was drawn to predict prognosis, and its performance was evaluated using calibration curve. Finally, immune cell infiltration and immune checkpoint molecule expression were analyzed to explore the tumor microenvironment characteristics associated with the risk scoring model.Results: Four out of 198 IFN-γ-related genes were selected to construct a risk score model with good predictive performance. The expression of four IFN-γ-related genes in glioma tissues was significantly increased compared to normal brain tissue (p < 0.001). Based on ROC analysis, the risk score model accurately predicted the overall survival rate of glioma patients at 1 year (AUC: The Cancer Genome Atlas 0.89, CGGA 0.59), 3 years (AUC: TCGA 0.89, CGGA 0.68), and 5 years (AUC: TCGA 0.88, CGGA 0.70). Kaplan-Meier analysis showed that the overall survival rate of the high-risk group was significantly lower than that of the low-risk group (p < 0.0001). Moreover, high-risk scores were associated with wild-type IDH1, wild-type ATRX, and 1P/19Q non-co-deletion. The nomogram predicted the survival rate of glioma patients based on the risk score and multiple clinicopathological factors such as age, sex, pathological grade, and IDH Status, among others. Risk score and infiltrating immune cells including CD8 T-cell, resting CD4 memory T-cell, regulatory T-cell (Tregs), M2 macrophages, resting NK cells, activated mast cells, and neutrophils were positively correlated (p < 0.05). In addition, risk scores closely associated with expression of immune checkpoint molecules such as PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, TIGIT, CD48, CD226, and CD96.Conclusion: Our risk score model reveals that IFN-γ -associated genes are an independent prognostic factor for predicting overall survival in glioma, which is closely associated with immune cell infiltration and immune checkpoint molecule expression. This model will be helpful in predicting the effectiveness of immunotherapy and survival rate in patients with glioma.

Breast cancer is one of the most lethal malignancies among women; however, the underlying molecular mechanism involved in the progression and metastasis of breast cancer remains unclear. Numerous studies have confirmed that long noncoding RNAs are abnormally expressed in breast cancer and play crucial roles in cell proliferation and metastasis. In the study, we evaluated the functional role and detailed mechanism of DGUOK-AS1 in breast cancer progression and metastasis. DGUOK-AS1 knockdown suppressed proliferation, migration, and invasion of breast cancer cells in vitro and in vivo. Mechanistically, miR-204-5p was identified as an inhibitory target of DGUOK-AS1, which served as a tumor suppressor in breast cancer. Significantly, we found that the ectopic expression of miR-204-5p could counteract DGUOK-AS1-mediated promotion of cell proliferation and metastasis in breast cancer. Moreover, IL-11 was found to be the downstream target of miR-204-5p, and DGUOK-AS1 could protect IL-11 from miR-204-5p-mediated degradation. DGUOK-AS1 overexpression promoted breast cancer cell migration, angiogenesis, and macrophage migration, mediating by the increased secretion of IL-11, which was extremely important for cancer progression. Collectively, our studies reveal that DGUOK-AS1/miR-204-5p/IL-11 axis plays a significant role in the progression and metastasis of breast cancer, and DGUOK-AS1 might be a novel biomarker and therapeutic target for breast cancer.

Mining cities are clusters of communities that specialized in mining and extractive industries. The extensive mining activities in these cities have stimulated widespread and substantial ecological stresses to the surrounding environment, that significantly jeopardize the health condition of vegetation and human. Given the recent recognition of remote sensing in monitoring large-scale environmental change, we incorporated Ziyuan #1-02D, a recently released hyperspectral remote sensing data, into the ecological vulnerability assessment framework, using Panzhihua city as a case study, which is recognized as one of the most representative mining cities in China. The multi-spectral imaging data was widely applied in previous research. However, with the wide bands, multi-spectral imaging data cannot depict detailed characteristics of spectral targeted. As a result, we introduce indexes from the hyperspectral imaging to ecological vulnerability assessment proposed in this study, which can depict and monitor the growth and restoration of vegetation more accurately. We used the optimum index factor method to select bands from the satellite-based Ziyuan #1-02D data for quantifying vegetation indexes and red edge. Besides, we obtained inventory data, land-use, soil type, and typography of Panzhihua city to reconstruct its ecological vulnerability index (EVI) for 2020 and 2021. Comparing to the multi-spectral data, the ecological vulnerability results from hyperspectral imaging performed better in precision and concentration in EVI values, reaching the conclusions more directly. Specifically, the mining area and the relevant hazard types and impact areas were delineated through intensive fieldwork. Results suggested that the east and west districts, and north of Renhe district suffer great ecological stress, in which we observed intensive coal and metal-related mining industry. The central region, which occupies vanadium titanomagnetite mines, also shows substantial ecological issues, while the other mining industries, such as granite ore did not significantly influence the local environment. Although the newly released satellite-based data only have two-year periods, we still observed improving ecological conditions, with the southeast and west regions showing much lower ecological vulnerability values. The spatial autocorrelation analysis suggested that the high-high clustering region of EVI is located in the east, west, and Renhe districts, primarily due to the mining industries of variations scales. We also found that the clustering of low ecological vulnerable regions, mostly surrounds the vanadium titanomagnetite excavation industry, thanks to the local restoration projects.

BackgroundForeign imported patients and within-household transmission have been the focus and difficulty of coronavirus disease 2019 (COVID-19) prevention and control, which has also posed challenges to border areas' management. However, household transmission caused by foreign imported cases has not been reported in China's border areas. This study aimed to reveal a clear family clustering transmission chain of COVID-19 caused by contact with Myanmar refugees along the China–Myanmar border during an outbreak in October to November 2021.MethodsDuring the outbreak, detailed epidemiological investigations were conducted on confirmed patients with COVID-19 and their close contacts in daily activities. Patients were immediately transported to a designated hospital for treatment and quarantine, and their close contacts were quarantined at designated sites. Regular nucleic acid testing and SARS-CoV-2 antibody testing were provided to them.ResultsA clear four-generation family clustering transmission involving five patients with COVID-19 was found along the China–Myanmar border. The index case (Patient A) was infected by brief conversations with Myanmar refugees across border fences during work. His wife (Patient B) and 9-month-old daughter (Patient C) were second-generation cases infected by daily contact with him. His 2-year-old daughter (Patient D) was the third-generation case infected by her mother and sister during quarantine in the same room and then transmitted the virus to her grandmother (Patient E, the fourth-generation case) who looked after her after Patients B and C were diagnosed and transported to the hospital. The household secondary attack rate was 80.0%, the average latent period was 4 days, and the generation time was 3 days. Ten of 942 close contacts (1.1%) of this family had positive IgM antibody during the medical observation period. In total 73.9% (696/942) of them were positive for IgG antibody and 8.3% (58/696) had IgG levels over 20 S/CO (optical density of the sample/cut-off value of the reagent).ConclusionThis typical transmission chain indicated that it is essential to strengthen COVID-19 prevention and control in border areas, and explore more effective children care approaches in quarantine sites.

This paper explores the potential for communication-efficient federated learning (FL) in modern distributed systems. FL is an emerging distributed machine learning technique that allows for the distributed training of a single machine learning model across multiple geographically distributed clients. This paper surveys the various approaches to communication-efficient FL, including model updates, compression techniques, resource management for the edge and cloud, and client selection. We also review the various optimization techniques associated with communication-efficient FL, such as compression schemes and structured updates. Finally, we highlight the current research challenges and discuss the potential future directions for communication-efficient FL.

Abstract Hybrid precoding achieves a compromise between the sum rate and hardware complexity of millimeter wave (mmWave) massive multiple-input multiple-output (MIMO) systems. However, most prior works on multi-user hybrid precoding only consider the full-connected structure. In this paper, a novel multi-user hybrid precoding algorithm is proposed for the sub-connected structure. Based on the improved successive interference cancellation (SIC), the analog precoding matrix optimization problem is decomposed into multiple analog precoding sub-matrix optimization problems. Further, a near-optimal analog precoder is designed through factorizing the precoding sub-matrix for each sub-array. Furthermore, digital precoding is designed according to the block diagonalization (BD) technology. Finally, the water-filling power allocation method is used to further improve the communication quality. The extensive simulation results demonstrate that the sum rate of the proposed algorithm is higher than the existing hybrid precoding methods with the sub-connected structure, and has higher energy efficiency compared with existing approaches. Moreover, the proposed algorithm is closer to the state-of-the-art optimization approach with the full-connected structure. In addition, the simulation results also verify the effectiveness of the proposed hybrid precoding design of the uniform planar array (UPA).

BackgroundImported COVID-19 patients posed great challenges to border areas' COVID-19 control. However, research was scarce to reveal epidemiological characteristics of COVID-19 in border areas. This study aimed to explore the detailed transmission chains, and reveal epidemiological and clinical characteristics of the largest COVID-19 outbreak caused by Delta variant of concern (VOC) occurred in the China-Myanmar border area.MethodsDuring the outbreak from July to September, 2021 in Ruili City, Yunnan Province, China, epidemiological investigation data and clinical-related data pertaining to confirmed COVID-19 patients were collected. Patients' contact history data and viral gene sequencing were used for inference of transmission chains. Sociodemographic and epidemiological characteristics, cycle threshold (Ct) value, and antibodies level were compared between patients who were vaccinated against COVID-19 or not.ResultsA total of 117 COVID-19 patients were confirmed during the outbreak, among which 86 (73.5%) were breakthrough infections. These patients evenly split between Chinese and Myanmar people (50.4% vs. 49.6%). Most of these patients were mild (45.3%) or moderate (48.7%) infections with no death reported. Multi-source of infection led to 16 transmission chains with a maximum of 45 patients in one chain. Patients vaccinated against COVID-19 before infection had relatively higher antibodies (IgM and IgG) levels and more rapid response to infection than non-vaccinated patients (p < 0.05).ConclusionLand border areas have greater risks of imported COVID-19 and more complicated epidemics. It should be cautious in formulating entry and exit requirements for border areas. The immune effect of COVID-19 vaccines and related mechanism should be further explored.

Amoxicillin appears to be clinically drug-resistant due to the presence of β-lactamase in bacteria. Here, we designed and prepared a hollow Prussian Blue (HPB)-based therapeutic nanoplatform that was constructed by encapsulating amoxicillin into polyethyleneimine with β-lactamase inhibitor 4-carboxyphenylboronic acid (4-Cpba) decorated HPB nanoparticles (CPA NPs). The antibacterial effect of the CPA NPs on drug-resistant bacteria was observed by in vitro colony-forming unit, minimum inhibitory concentration, scanning electron microscopy, and fluorescence tests. The results show that amoxicillin effectively inhibited Escherichia coli and Staphylococcus aureus-resistant bacteria in the presence of 4-Cpba. The in vivo experimental results show that the CPA NPs exhibited a synergistic anti-infective effect in vivo, which inhibited the inflammatory response and apoptosis induced by the drug-resistant bacterial infection, and promoted wound healing in mice. The hematoxylin and eosin staining and blood biochemical experiments revealed that the acute toxicity of the material was negligible and it had good biocompatibility. Our results verify our design that CPA NPs can restore the antibacterial activity of amoxicillin.

Human bocavirus 1 (HBoV1), a member of the genus Bocaparvovirus of the family Parvoviridae, causes acute respiratory tract infections in young children. Well-differentiated pseudostratified human airway epithelium cultured at an air-liquid interface (HAE-ALI) is an ideal in vitro culture model to study HBoV1 infection. Unique to other parvoviruses, bocaparvoviruses express a small nonstructured protein NP1 of ~25 kDa from an open reading frame (ORF) in the center of the viral genome. NP1 plays an important role in viral DNA replication and pre-mRNA processing. In this study, we performed an affinity purification assay to identify HBoV1 NP1-inteacting proteins. We identified that Ku70 and RPA70 directly interact with the NP1 at a high binding affinity, characterized with an equilibrium dissociation constant (KD) of 95 nM and 122 nM, respectively. Furthermore, we mapped the key NP1-interacting domains of Ku70 at aa266-439 and of RPA70 at aa181-422. Following a dominant negative strategy, we revealed that the interactions of Ku70 and RPA70 with NP1 play a significant role in HBoV1 DNA replication not only in an in vitro viral DNA replication assay but also in HBoV1-infected HAE-ALI cultures. Collectively, our study revealed a novel mechanism by which HBoV1 NP1 enhances viral DNA replication through its direct interactions with Ku70 and RPA70.

Abstract Background Nano-Fenton reactors as novel strategy to selectively convert hydrogen peroxide (H2O2) into active hydroxyl radicals in tumor microenvironment for cancer therapy had attracted much attention. However, side effects and low efficiency remain the main drawbacks for cancer precise therapy. Results Here, ruthenium-loaded palmitoyl ascorbate (PA)-modified mesoporous silica (Ru@SiO2-PA) was successfully fabricated and characterized. The results indicated that Ru@SiO2-PA under pH6.0 environment displayed enhanced growth inhibition against human cancer cells than that of pH7.4, which indicated the super selectivity between cancer cells and normal cells. Ru@SiO2-PA also induced enhanced cancer cells apoptosis, followed by caspase-3 activation and cytochrome-c release. Mechanism investigation revealed that Ru@SiO2-PA caused enhanced generation of superoxide anion, which subsequently triggered DNA damage and dysfunction of MAPKs and PI3K/AKT pathways. Moreover, Ru@SiO2-PA effectively inhibited tumor spheroids and tumor xenografts growth in vivo by induction of apoptosis. The real-time imaging by monitoring Ru fluorescence in vitro and in vivo revealed that Ru@SiO2-PA mainly accumulated in cell nucleus and tumor xenografts. Importantly, Ru@SiO2-PA showed no side effects in vivo, predicting the safety and potential application in clinic. Conclusions Our findings validated the rational design that Ru@SiO2-PA can act as novel tumor microenvironment-response nano-Fenton reactors for cancer precise therapy. Graphic Abstract

With the increasing installed capacity of wind turbines, ensuring the safe operation of wind turbines is of great significance. However, the failure of wind turbines is still a severe problem, especially as blade damage can cause serious harm. To detect blade damage in time and prevent the accumulation of microdamage of blades evolving into severe injury, a damage dataset based on GH Bladed simulation of blade damage is proposed. Then, based on the wavelet packet analysis theory method, the MATLAB software can automatically analyze and extract the energy characteristics of the signal to identify the damage. Finally, the GH Bladed simulation software and MATLAB software are combined for fault diagnosis analysis. The results show that the proposed method based on GH Bladed to simulate blade damage and wavelet packet analysis can extract damage characteristics and identify single-unit damage, multiple-unit damage, and different degrees of damage. This method can quickly and effectively judge the damage to wind turbine blades; it provides a basis for further research on wind turbine blade damage fault diagnosis.

In modern large-scale wind farms, power loss caused by the wake effect is more than 30%, and active yaw control can greatly reduce the influence of the wake effect by deflecting the wind turbine’s wake. The yawed wind turbine’s wake characteristics are complex, and a deep comprehension of a yawed turbine’s wake is necessary. The actuator line method combined with URANS (unsteady Reynold-averaged Navier–Stokes equations) is used to study the yawed wind turbine’s wake characteristics in this paper. Compared with an un-yawed wind turbine, a yawed one has two main characteristics, deflection and deformation. With an increasing yaw angle, turbine wake shows an increasing deflection. The results indicated that deflection at different height was different, the wake profile showed the biggest deflection at about the hub height, while the smallest deflection existed at the top and bottom of the yawed turbine’s wake. This can be visually demonstrated by the evolution of a kidney-shape velocity distribution at the vertical cross-section. Two-dimensional and three-dimensional presentations of velocity deficit distributions are presented in this paper. The evolution of an irregular kidney-shape distribution is discussed in this paper. It is formed by the momentum exchange caused by the counter-rotating vortex pair. The results indicated that the counter-rotating vortex pair was composed of the streamwise vortex flux brought by the tip vortex. Furthermore, when the wind turbine rotated clockwise and yawed clockwise, the negative vorticity of counter-rotating vortex first appeared in the upper left position.

The integration of energy storage facilities into existing structures will result in increased costs. Therefore, it is of great significance to optimize the configuration of integrated power systems with multienergy flows to reduce the cost of the comprehensive utilization of energy. This study established a wind-solar-battery-fuel cell integrated power supply system to optimize the grid-connected regional power supply. First, the load is given with a known daily energy demand. The optimization goal is to minimize the average annual cost and the loss of power supply probability. The cost model includes the constraints of transportation costs and the benefits of selling hydrogen and oxygen. Then, an improved genetic algorithm is developed to optimize the structure of the wind-solar-battery-fuel cell integrated power supply system. The basic idea of the improved genetic algorithm is to change the coordination mode of the crossover operator and the mutation operator according to the size of the initial population fitness. Finally, according to the calculation results of the improved genetic algorithm, the optimal configuration of the capacity of devices in the system is obtained, verifying the effectiveness of the improved genetic algorithm. The cost calculation result of the genetic algorithm is 18.7% higher than that of the improved genetic algorithm, and it completely converges at approximately 70 steps. The cost calculation result of the particle swarm optimization is 17.1% higher than that of the improved genetic algorithm, and it completely converges at approximately 75 steps. The cost calculation result of the nondominated sorting genetic algorithm is 9.6% higher than that of the improved genetic algorithm, and it completely converges at approximately 58 steps. The system established in this research can fully meet the power demands for a given area and effectively reduce the local curtailment of wind energy and solar energy.

The low-strain integrity testing of large-diameter piles has attracted more and more attention because of its wide application in offshore engineering, such as for wind turbines, etc. Body and Rayleigh waves generate on the top surface of large-diameter piles after the excitation load. The multi-reflections of these waves from the pile side result in the obvious three-dimensional effect at the pile top. Therefore, one-dimensional wave theory is no longer suitable for interpreting the wave propagation in the pile body under vertical excitation. In this paper, based on the “pile in pile” conception, both the pile and soil were simulated using a three-dimensional continuum model, considering the vertical displacement, to investigate the influence of the three-dimensional effect of the pile-soil system on the vertical dynamic response of large-diameter piles in low-strain integrity testing. The axisymmetric solution to the three-dimensional pile-soil system was obtained, and the rationality of the proposed solution was verified by comparing it with the results of the finite element method and the results of other existing solutions. Arithmetic examples were used to describe the influence of the three-dimensional effect of the pile-soil system on the vertical dynamic response of large-diameter piles.

The traditional ampere-hour (Ah) integration method ignores the influence of battery health (SOH) and considers that the battery capacity will not change over time. To solve the above problem, we proposed a joint SOH-SOC estimation model based on the GWO-BP neural network to optimize the Ah integration method. The method completed SOH estimation through the GWO-BP neural network and introduced SOH into the Ah integration method to correct battery capacity and improve the accuracy of state of charge (SOC) estimation. In addition, the method also predicted the SOH of the battery, so the driver could have a clearer understanding of the battery aging level. In this paper, the stability of the joint SOH-SOC estimation model was verified by using different battery data from different sources. Comparative experimental results showed that the estimation error of the joint SOH-SOC estimation model could be stabilized within 5%, which was smaller compared with the traditional ampere integration method.

Hantavirus nucleocapsid protein (NP) inhibits protein kinase R (PKR) dimerization by an unknown mechanism to counteract its antiviral responses during virus infection. Here we demonstrate that NP exploits an endogenous PKR inhibitor P58IPK to inhibit PKR. The activity of P58IPK is normally restricted in cells by the formation of an inactive complex with its negative regulator Hsp40. On the other hand, PKR remains associated with the 40S ribosomal subunit, a unique strategic location that facilitates its free access to the downstream target eIF2α. Although both NP and Hsp40 bind to P58IPK, the binding affinity of NP is much stronger compared to Hsp40. P58IPK harbors an NP binding site, spanning to N-terminal TPR subdomains I and II. The Hsp40 binding site on P58IPK was mapped to the TPR subdomain II. The high affinity binding of NP to P58IPK and the overlap between NP and Hsp40 binding sites releases the P58IPK from its negative regulator by competitive inhibition. The NP-P58IPK complex is selectively recruited to the 40S ribosomal subunit by direct interaction between NP and the ribosomal protein S19 (RPS19), a structural component of the 40S ribosomal subunit. NP has distinct binding sites for P58IPK and RPS19, enabling it to serve as bridge between P58IPK and the 40S ribosomal subunit. NP mutants deficient in binding to either P58IPK or RPS19 fail to inhibit PKR, demonstrating that selective engagement of P58IPK to the 40S ribosomal subunit is required for PKR inhibition. Cells deficient in P58IPK mount a rapid PKR antiviral response and establish an antiviral state, observed by global translational shutdown and rapid decline in viral load. These studies reveal a novel viral strategy in which NP releases P58IPK from its negative regulator and selectively engages it on the 40S ribosomal subunit to promptly combat the PKR antiviral responses.

In this paper, an extended separation-of-variable (SOV) method is developed to achieve the closed-form solutions for free vibration of rectangular nonlocal Mindlin plates with arbitrary homogeneous boundary conditions. With the weighted residual notion, the amplitude of the potential energy functional and the kinetic energy coefficient are derived, then the Rayleigh's principle is formulated for the nonlocal Mindlin plates. In accordance with the principle, the extended SOV method is realized. In the present method, the mode functions are in a separation-of-variable form and the natural frequencies corresponding to two-direction mode functions are considered to be independent in a mathematical sense. Numerical comparison results verify the correctness and accuracy of the present method. Moreover, the effects of nonlocal parameter, boundary conditions and thickness ratio on the free vibration are discussed comprehensively.

The estimation of the state of charge (SOC) of a battery’s power is one of the key technologies in a battery management system (BMS). As a common SOC estimation method, the traditional ampere-hour integral method regards the actual capacity of the battery, which is constantly changed by the usage conditions and environment, as a constant for calculation, which may cause errors in the results of SOC estimation. Considering the above problems, this paper proposes an improved ampere-hour integral method based on the Long Short-Term Memory (LSTM) network model. The LSTM network model is used to obtain the actual battery capacity variation, replacing the fixed value of battery capacity in the traditional ampere-hour integral method and optimizing the traditional ampere-hour integral method to improve the accuracy of the SOC estimation method. The experimental results show that the errors of the results obtained by the improved ampere-hour integral method for the SOC estimation are all less than 10%, which proves that the proposed design method is feasible and effective.

In recent years, wind turbines have shown a maximization trend. However, most of the wind turbine blades operate in areas with a relatively poor natural environment. The stability, safety, and reliability of blade operation are facing many challenges. Therefore, it is of great significance to monitor the structural health of wind turbine blades to avoid the failure of wind turbine outages and reduce maintenance costs. This paper reviews the commonly observed types of damage and damage detection methods of wind turbine blades. First of all, a comprehensive summary of the common embryonic damage, leading edge erosion, micro-cracking, fiber defects, and coating defects damage. Secondly, three fault diagnosis methods of wind turbine blades, including nondestructive testing (NDT), supervisory control and data acquisition (SCADA), and vibration signal-based fault diagnosis, are introduced. The working principles, advantages, disadvantages, and development status of nondestructive testing methods are analyzed and summarized. Finally, the future development trend of wind turbine blade detection and diagnosis technology is discussed. This paper can guide the use of technical means in the actual detection of wind turbine blades. In addition, the research prospect of fault diagnosis technology can be understood.

Human bocavirus 1 (HBoV1), an autonomous parvovirus, is a helper virus supporting replication of wild-type adeno-associated virus 2 (AAV2). In this study, we compared the helper functions from HBoV1 with those from adenovirus (Ad) for the production of recombinant AAV (rAAV) vector in HEK293 cells. We demonstrated that triple plasmids transfection of (1) a cloned HBoV1 helper minigenome (pBocaHelper) that expresses HBoV1 genes NP1, NS2, and BocaSR, (2) pAAV transfer plasmid, and (3) pAAVRepCap supports rAAV production in HEK293 cells. Despite a production yield of 1–2 log lower than that using pAdHelper (expressing Ad genes E2A, E4, and VA), rAAV vector produced using pBocaHelper transduced cells as efficiently as that produced using pAdHelper. The low vector production is largely due to the inefficient expression of the AAV Rep52 and capsid proteins, as well as reduced rAAV genome replication. When the AAV capsid proteins and Rep52 were ectopically expressed under strong promoters, the enhanced protein expression significantly improved the rAAV production using pBocaHelper, approaching a level of 50%–70% of that produced using pAdHelper. Through further dissection of the helper functions from pAdHelper in a five-plasmid transfection system, we found that the addition of the Ad E2A gene to the above HBoV1 helper system significantly increased rAAV DNA replication, which increased the rAAV vector production to a level of 3–7 times higher than that using pAdHelper. We finally combined HBoV1 NP1 and NS2 genes with Ad helper genes to create a novel dual helper plasmid (pABHelper) for rAAV vector production in the conventional three-plasmid transfection system. The pABHelper facilitated rAAV production at a yield ∼2 times higher than that using the pAdHelper. Keywords: rAAV, HBoV1, helper gene, DNA replication, gene expression

Abstract Leukemia inhibitory factor (LIF), an indispensable bioactive protein that sustains self‐renewal and pluripotency in stem cells, is vital for mouse embryonic stem cell (mESC) culture. Extensive research is conducted on reliable alternatives for LIF as its clinical application in stable culture and large‐scale expansion of ESCs is limited by its instability and high cost. However, few studies have sought to replace LIF with nanoparticles to provide a xeno‐free culture condition. MgAl‐LDH (layered double hydroxide) nanoparticles can partially replace LIF in maintaining pluripotency of mESCs; however, the requirement and tolerance for aluminum ions in mice are far lesser than those of iron ions. Hence, MgFe‐LDH nanoparticles are selected for this study. MgFe‐LDH is superior to MgAl‐LDH in maintaining self‐renewal and pluripotency of mESCs, in the absence of LIF and mouse embryonic fibroblast. Furthermore, combined transcriptomic and proteomic analysis confirms that MgFe‐LDH can activate the LIF receptor (LIFR)/phosphatidylinositol 3‐kinase (PI3K)/protein kinase B(AKT), LIFR/JAK/janus kinase (JAK)/signal transducer and activator of transcription 3(STAT3), and phospho‐signal transducer and activator of transcription 3(p‐STAT3)/ten‐eleven translocation (TET) signaling pathways, while the extra Fe2+ provided by MgFe‐LDH would also enhance TET1/2 abundance thus affecting the TET1/2 regulated pluripotency related marker expression and TET1/2 meditated DNA demethylation. These results suggest that MgFe‐LDH nanoparticles can thus be used as an affordable and efficient replacement for LIF in mESC cultivation.

Long non-coding RNAs(lncRNAs) play an important role in cancer initiation and progression. However, hub lncRNAs involved in breast cancer still remain underexplored. In this study, integrated bioinformatics analysis was used to define LINC01977 as a key oncogenic driver in breast cancer. Subsequently, in vitro assays showed that LINC01977 could significantly promote breast cancer progression and chemoresistance to doxorubicin. To further investigate its biological mechanism, we performed dual-luciferase reporter assay, real-time PCR, RNA immunoprecipitation (RIP), and rescue assay. Our results indicated that LINC01977 may function as ceRNA to prevent GOLM1 gene from miRNA-mediated repression by sponging miR-212-3p. Overall, LINC01977 can serve as a novel prognostic indicator, and help develop more effective therapeutic approaches for breast cancer patients.

BackgroundPrimary squamous cell carcinoma of parotid gland (parotid SCC) is a high malignant histologic subtype of parotid cancers with aggressive clinical presentation. However, the clinical features and survival benefit of postoperative radiotherapy (PORT) for primary parotid SCC are not well known.MethodsA retrospective population-based study was performed to identify the role of PORT in parotid SCC patients diagnosed between 1975 and 2016 from SEER database. A prognostic risk model was established based on patient clinical features, including age, tumor stage, and node involvement status. Patients were stratified into high, intermediate, and low risk according to this model. The survival benefit of radiotherapy was compared in the whole cohort and different risk groups.ResultsNine hundred thirty-one parotid SCC patients were extracted from SEER database, 634 (68.1%) in the RT group and 286 (30.7%) in the non-RT group. Overall, 503 (54.0%) deaths occurred, with a median follow-up of 84 months, the 5-year OS was 43.6% in the whole cohort, 47.7 vs 35.9% in patients with/without PORT (P = 0.005), and 58.9 vs. 38.8 vs. 27.1% in low-, intermediate-, and high-risk group (P < 0.001). Compared with surgery alone, PORT significantly improved the OS of patients with medium risk (47.5 vs. 20.6, P < 0.001), whereas not in the low risk (61 vs. 54%, P = 0.710) and high (25.6 vs. 28.7%, P = 0.524).ConclusionThis prognostic model can separate the patients with parotid squamous cell carcinoma into different risk. PORT significantly improved the OS of patients with intermediate risk, whereas high-risk group may need more intensive treatment strategies.

The free vibrations of nonlocal Euler and Timoshenko beams have been studied extensively, but there still remain some problems concerning boundary conditions and constitutive relations. For cantilever beams, a counterintuitive stiffening phenomenon is widely observed. And to the best of the authors’ knowledge, there is no work concerning about the Timoshenko beam with nonlocal shear force and local bending moment. This work reconsiders and explains these problems based on nonlocal differential theory. After obtaining the governing equation for nonlocal Euler beam, it is observed that the governing equation has the same form as that for the vibration of local beam with axial compressive force. Thus by comparing the nonlocal effects to the effects of end axial force, the stiffening phenomenon of cantilever beams is found to be caused by a meaningless term in boundary bending moment. This explanation is also suitable for nonlocal Timoshenko cantilever beams. Besides, for Timoshenko beams, the nonlocal effects on tensile and shear stress constitutive relations are considered separately. Three kinds of nonlocal Timoshenko beam models are solved. Numerical comparison shows that the effects of nonlocal tensile are bigger than that of nonlocal shear stress. Especially, for Timoshenko beams with nonlocal shear force only, the nonlocal effects lower the natural frequency for all boundary conditions. This finding can verify our explanation for the stiffening phenomenon of cantilever beams. In addition, it is also observed that, for both nonlocal beam theories, if all nonlocal internal forces are included in the governing equations, the eigenvalue equations and natural frequencies corresponding to local and nonlocal boundary conditions are the same.