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Abstract Background Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which represents application niches for lysosome-targeted fluorescent probes. Additionally, in view of the complexity of the autophagy pathway, it entails more stringent requirements for probes suitable for monitoring autophagy. Meanwhile, aggregation-induced emission (AIE) fluorescent probes have been impressively demonstrated in the biomedical field, which bring fascinating possibilities to the autophagy visualization. Methods We reported a generalizable de novo design of a novel pH-sensitive AIE probe ASMP-AP tailored to lysosome targeting for the interpretation of autophagy. Firstly, the theoretical calculation was carried out followed by the investigation of optical properties. Then, the performance of ASMP-AP in visualizing autophagy was corroborated by starvation or drugs treatments. Furthermore, the capability of ASMP-AP to monitor autophagy was demonstrated in ex vivo liver tissue and zebrafish in vivo. Results ASMP-AP displays a large stokes shift, great cell permeability and good biocompatibility. More importantly, ASMP-AP enables a good linear response to pH, which derives from the fact that its aggregation state can be manipulated by the acidity. It was successfully applied for imaging autophagy in living cells and was proved capable of monitoring mitophagy. Moreover, this novel molecular tool was validated by ex vivo visualization of activated autophagy in drug-induced liver injury model. Interestingly, it provided a meaningful pharmacological insight that the melanin inhibitor 1-phenyl-2-thiourea (PTU)-induced autophagy was clearly presented in wild-type zebrafish. Conclusions ASMP-AP offers a simple yet effective tool for studying lysosome and autophagy. This is the first instance to visualize autophagy in zebrafish using a small-molecule probe with AIE characters, accurate lysosome targeting and simultaneous pH sensitivity. Ultimately, this novel fluorescent system has great potential for in vivo translation to fuel autophagy research. Graphical Abstract

Abstract Background Anterior colporrhaphy (AC) is a conventional surgical repair technique for cystocele but with high recurrence rate. We present a novel technique: Cable-suspended structure (CSS) by non-absorbable suture combined with "bridge" formation in surgical treatment of cystocele. This study aimed to evaluate and compare the long-term outcome of CSS technique for anterior vaginal wall repair with AC. Methods A retrospective review was performed on patients who underwent anterior vaginal wall repair between January 2012 and March 2017 at our center. All the patients were under a follow-up survey. The primary outcomes were objective cure (anterior prolapse POP-Q ≤ stage 1) and subjective cure (no symptoms of bulge or retreatment for prolapse). Secondary outcomes included quality of life (QOL) and patients’ satisfaction, outcomes of site-specific POP-Q points Aa, Ba and C, as well as postoperative complications. Results Of 91 included participants, 43 underwent AC and 48 underwent CSS. The proportion of sarcrospinous ligament fixation in the CSS group was higher than in the AC group (81.4% vs. 77.1%, P

The deciduous tree hickory (Carya cathayensis) holds economic significance in China due to its high oil content, particularly in unsaturated fatty acids. Oil bodies are crucial for storing triacylglycerol (TAG), with caleosin serving as a predominant oil body protein that aids in oil body formation and stability maintenance. Our study utilized bioinformatics techniques to identify caleosin genes within Carya cathayensis, Carya illinoinensis, and Juglans regia. Three caleosin genes were discovered in the genomes of Carya cathayensis, Carya illi-noinensis, and Juglans regia. These genes encode hydrophilic proteins. Additionally, all caleosin proteins feature a single Ca2+-binding EF-hand, a conserved “proline knot” motif, and a C-terminal hydrophilic region with four potential phosphorylation sites. The caleosin proteins in Carya cathayensis consist of α-helix, β-corner, extended chain, and random curl structures. Cis-acting elements related to stress response and hormone signaling were identified in Carya cathayensis, Carya illinoinensis, and Juglans regia, with distinct cis-acting elements implicated in seed-specific regulation in Carya cathayensis. Additionally, subcellular localization analysis confirmed that CcaCLO1 and CcaCLO2 were localized within oil bodies. Transcriptome analysis and quantitative real-time polymerase chain reaction (qRT-PCR) data demonstrated a significant up-regulation of CcaCLO1 expression during the developmental stages of the Carya cathayensis embryo. Furthermore, qPCR findings indicated that caleosins from Carya cathayensis were responsive to salt stress, with a significant up-regulation of CcaCLO1 following exposure to salt stress treatment. Consequently, caleosin genes in Carya cathayensis, Carya illinoinensis, and Juglans regia share similar physicochemical characteristics and conserved motifs. Specifically, CcaCLO1 in Carya cathayensis primarily responds to embryo development and salt stress. These findings offer foundational insights for future investigations into the regulatory mechanisms of oil accumulation and response to salt stress in hickory.

Drought and poor soil quality are the main characteristics of extreme environments in arctic–alpine areas. Understanding how herbaceous plants in alpine grasslands maintain the normal supply and utilisation of nutrients under different rainfall conditions is key to maintaining population stability. In the present study, the native plants Poa crymophila and Stipa purpurea of the Qinghai–Tibet Plateau were used to conduct a controlled experiment involving water and fertiliser to analyse their physiological responses in terms of nutrient uptake and utilisation. The results showed that decreased soil moisture increased proline and non-structural carbohydrates in P. crymophila, mainly accumulating in the leaves and stems. Nitrogen (N) addition promoted proline accumulation, whereas nonstructural carbohydrate content decreased. However, the proline and non-structural carbohydrate contents of S. purpurea were less affected by water and fertiliser. Additionally, drought restricted rhizospheric and non-rhizospheric alkaline-hydrolysed N release, increased rapidly available phosphorus (RAP) content in rhizospheric soil, limited root growth, and reduced surface area, root length, and root volume. Both aboveground and underground N fertiliser utilisation rates decreased. Under well-hydrated conditions (WH), high N levels increased rhizospheric alkaline-hydrolysed N and urease activity while inhibiting RAP and activity of alkaline phosphatase contents, thereby limiting root growth and reducing N fertiliser utilisation. The results indicate that both plant species have relatively low overall nutrient requirements that are limited mainly by water availability. The addition of low amounts of fertiliser is beneficial for nutrient release and utilisation, improving their adaptability to arctic–alpine environments and their suitability and superiority in the community. This study has significant implications for nutrient management and ecological restoration measures in arctic–alpine grasslands.

Information about the distribution of coniferous forests holds significance for enhancing forestry efficiency and making informed policy decisions. Accurately identifying and mapping coniferous forests can expedite the achievement of Sustainable Development Goal (SDG) 15, aimed at managing forests sustainably, combating desertification, halting and reversing land degradation, and halting biodiversity loss. However, traditional methods employed to identify and map coniferous forests are costly and labor-intensive, particularly in dealing with large-scale regions. Consequently, a methodological framework is proposed to identify coniferous forests in northwestern Liaoning, China, in which there are semi-arid and barren environment areas. This framework leverages a multi-classifier fusion algorithm that combines deep learning (U2-Net and Resnet-50) and shallow learning (support vector machines and random forests) methods deployed in the Google Earth Engine. Freely available remote sensing images are integrated from multiple sources, including Gaofen-1 and Sentinel-1, to enhance the accuracy and reliability of the results. The overall accuracy of the coniferous forest identification results reached 97.6%, highlighting the effectiveness of the proposed methodology. Further calculations were conducted to determine the area of coniferous forests in each administrative region of northwestern Liaoning. It was found that the total area of coniferous forests in the study area is about 6013.67 km2, accounting for 9.59% of northwestern Liaoning. The proposed framework has the potential to offer timely and accurate information on coniferous forests and holds promise for informed decision making and the sustainable development of ecological environment.

Abstract Background To report a case in which silicone oil accidentally entered Berger’s space (BS) after vitrectomy and to explore the effective treatments and possible etiological mechanisms. Case presentation A 68-year-old male underwent vitrectomy and silicone oil injection for the treatment of retinal detachment (RD) in the right eye. Six months later, we noticed an unexpected lens-like round translucent substance located behind the posterior lens capsule and diagnosed it as BS filled by silicone oil. Subsequently, we conducted vitrectomy and the drainage of the silicone oil in BS in the second surgery. A 3-month follow-up showed significant anatomic recovery and visual recovery. Conclusions Our case report presents a patient with silicone oil entering BS after vitrectomy and provides photographs of BS from a relatively unique perspective. Furthermore, we illustrate the surgical treatment procedure and reveal the possible etiology and prevention method of silicon oil entering BS, which will provide good insights for clinical diagnosis and treatment.

Identifying the potential factors associated with the impact of long-term drip irrigation (DI) on soil ecosystems is essential for responding to the environmental changes induced by extensive application of DI technology in arid regions. Herein, we examined the effects of the length of time that DI lasts in years (NDI) on soil bacterial diversity as well as the soil bacterial community assembly process and the factors influencing it. The results showed that long-term DI substantially reduced soil salinity and increased soil bacterial diversity while affecting the soil bacterial community structure distinctly. Null model results showed that the soil bacterial community assembly transitioned from stochastic processes to deterministic processes, as NDI increased. Homogeneous selection, a deterministic process, emerged as the dominant process when NDI exceeded 15 years. Both random forest and structural equation models showed that soil salinity was the primary factor affecting the bacterial community assembly process. In summary, this study suggested that soil bacteria respond differently to long-term DI and depends on the NDI, influencing the soil bacterial community assembly process under long-term DI.

BackgroundLeukodystrophies are hereditary white matter diseases characterized by genetic polymorphisms and considerable phenotypic variability. They can be classified into myelin and non-myelin malformations. These diseases are rare, affecting 1 out of 250,000–500,000 individuals and can manifest at any age. A subtype of leukodystrophy, associated with missense mutations in the RNA polymerase subunit III (POLR3A) gene, is inherited in an autosomal recessive manner.Case reportWe report and analyse a case of a 34-year-old female who presented with ataxia. Magnetic Resonance Imaging (MRI) of the brain revealed demyelinating lesions in the white matter. Genetic testing identified the c.4044C > G and c.1186-2A > G variants in the POLR3A gene. The patient was diagnosed with hypomyelinating leukodystrophy type 7 and received neurotrophic and symptomatic supportive therapy. However, after 1 month of follow-up, there was no improvement in her symptoms.ConclusionPOLR3A-induced leukodystrophy is relatively rare and not well understood, making it challenging to diagnose and easy to overlook. The prognosis for this disease is generally poor, significantly impacting the quality of life of affected individuals. Currently, no cure is available for this condition, and treatment is limited to managing symptoms. Further research into new treatment methods for POLR3A-induced leukodystrophy is imperative to improve the quality of life and potentially extend the life expectancy of patients.

Research on vacancy analysis and spatial layout of protected natural areas has been carried out for many years around the world, but most of the research objects are land-type protected natural areas, while studies on Marine protected natural areas are relatively rare, and there are few cases to carry out integrated optimization research on spatial layout of protected natural areas. This study will take Changdao in Yantai, Shandong Province, China as an example, from the protection of how much? How representative? Where is it protected? Starting from the three problems, the vacancy analysis is carried out, and the integrated optimization research is carried out based on the existing spatial layout, aiming at the rescue protection, coordinated protection and forward-looking protection. The results show that the integrated and optimized Changdao protected area eliminates the protection vacancy, integrates the overlapping protected areas, optimizes the unreasonable protected space, alleviates the contradiction between protection and development, promotes the coordinated development of ecology and economy and society, and can provide a scientific reference for the integrated and optimized spatial layout of Marine protected areas.

Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body’s primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.

In recent years, coronavirus disease 2019 (COVID-19) has plagued the world, causing huge losses to the lives and property of people worldwide. How to simulate the spread of an epidemic with a reasonable mathematical model and then use it to analyze and to predict its development trend has attracted the attention of scholars from different fields. Based on the susceptible–infected–recovered (SIR) propagation model, this work proposes the susceptible–exposed–infected–recovered–dead (SEIRD) model by introducing a specific medium having many changes such as the self-healing rate, lethality rate, and re-positive rate, considering the possibility of virus propagation through objects. Finally, this work simulates and analyzes the propagation process of nodes in different states within this model, and compares the model prediction results optimized by the adaptive genetic algorithm with the real data. The experimental results show that the susceptible–exposed–infected–recovered–dead model can effectively reflect the real epidemic spreading process and provide theoretical support for the relevant prevention and control departments.

The validity of local thermodynamic equilibrium (LTE) in plasma is a long-term concern for laser-induced breakdown spectroscopy applications. In this paper, the spatial and temporal dependence of LTE deviation in picosecond laser-induced plasmas has been proved. A picosecond (∼20 ps) laser operated at 532 nm was used to ablate a silicon target to produce plasma at a pressure of 10−5 mbar. A general electron energy distribution function was used to provide access to the insight into population ratios of different energy levels for the spatially and temporally resolved optical emission intensity of laser-induced plasma. A precise temporal and spatial LTE boundary of plasma generated in picosecond laser ablation was obtained, and the results showed that only at delay times of 180–300 ns, the plasma away from the surface (>4 mm) is in LTE.

The growth of Li dendrites in a solid electrolyte is commonly idealized by a pressure‐filled crack. Recent observations in both garnet and sulfide electrolytes show that sparsely filled cracks exist prior to shorting of the cell, thereby invalidating this assumption. Herein, a variational principle that uses the Onsager formalism to couple Li deposition into the crack, elastic deformation of the electrolyte, and cracking of the electrolyte with the electrochemical driving forces and dissipation within the electrolyte and interfaces is developed. Consistent with observations, it is shown that Li ingress and cracking occur together for garnet electrolytes, but the cracks are sparsely filled. This sparse filling is a direct consequence of the mismatch between the elastic opening of the cracks and the deposition of Li into the cracks across the crack flanks. An increase in the resistance of Li ingress into the tips of Li filaments results in crack propagating ahead of the Li filaments, as observed for sulfide electrolytes. In such cases, the cracks are largely dry. The results provide a framework to model Li ingress into solid electrolytes and explain why the observations are qualitatively so different from dendrites in liquid electrolytes.

IntroductionLactococcus lactis (L.L) is safe and can be used as vehicle. In this study, the immunoregulatory effect of L.L on dendritic cell (DC) activation and mechanism were investigated. The immune responses and antigen cross-presentation mechanism of DC-based vaccine prepared with OVA recombinant L.L were explored.MethodsConfocal microscopy and flow cytometry were used to analyze the mechanism of L.L promoting DC maturation, phagosome membrane rupture and antigen presentation. The antitumor effect of DC vaccine prepared with L.L-OVA was assessed in the B16-OVA tumor mouse model.ResultsL.L significantly promoted DC maturation, which was partially dependent on TLR2 and downstream MAPK and NF-κB signaling pathways. L.L was internalized into DCs by endocytosis and did not co-localized with lysosome. OVA recombinant L.L enhanced antigen cross-presentation of DCs through the phagosome-to-cytosol pathway in a reactive oxygen species (ROS)- and proteasome-dependent manner. In mouse experiments, L.L increased the migration of DCs to draining lymph node and DC vaccine prepared with OVA recombinant L.L induced strong antigen-specific Th1 and cytotoxic T lymphocyte responses, which significantly inhibited B16-OVA tumor growth.ConclusionThis study demonstrated that recombinant L.L as an antigen delivery system prepared DC vaccine can enhance the antigen cross-presentation and antitumor efficacy.

Introduction:Bacillus species are known for their ability to produce nanoparticles with various potential applications.Methods: In this study, we present a facile approach for the green synthesis of selenium nanoparticles (Se NPs) using the biogenic selenate-reducing bacterium Bacillus paramycoides 24522. We optimized the growth conditions and sodium selenite reduction efficiency (SSRE) of B. paramycoides 24522 using a response surface approach.Results: Se NPs were synthesized by reducing selenite ions with B. paramycoides 24522 at 37 °C, pH 6, and 140 r/min, resulting in stable red-colored Se NPs and maximal SSRE (99.12%). The synthesized Se NPs demonstrated lethality against Staphylococcus aureus and Escherichia coli with MICs of 400 and 600 μg/mL, and MBCs of 600 and 800 μg/mL, respectively, indicating the potential of Se NPs as antibacterial agents. Furthermore, the Se NPs showed promising antioxidant capabilities through scavenging DPPH radicals and reducing power.Discussion: This study highlights the environmentally friendly production of Se NPs using B. paramycoides 24522 and their possible applications in addressing selenium pollution, as well as in the fields of environment and biotechnology.

Summary: Supramolecular prodrug self-assembly is a cost-effective and powerful approach for creating injectable anticancer nanoassemblies. Herein, we describe the self-assembly of small-molecule prodrug nanotherapeutics for tumor-restricted pharmacology that can be self-activated and independent of the exogenous stimuli. Covalent dimerization of the anticancer agent cabazitaxel via reactive oxygen species (ROS)- and esterase-activatable linkages produced the homodimeric prodrug diCTX, which was further coassembled with an ROS generator, dimeric dihydroartemisinin (diDHA). The coassembled nanoparticles were further refined in an amphiphilic matrix, making them suitable for in vivo administration. The ROS obtained from the coassembled diDHA synergized with intracellular esterase to activate the neighboring diCTX, which in turn induced potent cytotoxicity. In a preclinical orthotopic model of human osteosarcomas, nanoparticle administration exhibited durable antitumor efficacy. Furthermore, this smart, dual-responsive nanotherapeutic exhibited lower toxicity in animals than those of free drug combinations. We predict that this platform has great potential for further clinical translation.

Abstract Background A subset of patients with hypertrophic cardiomyopathy (HCM) will experience adverse clinical events such as heart failure (HF), cardiovascular death, and new-onset atrial fibrillation (AF). Current risk stratification methods are imperfect and limit the identification of patients at high risk for HCM. This study aimed to evaluate the role of cardiac magnetic resonance (CMR)-derived left atrial strain parameters in the occurrence of adverse clinical events in patients with HCM. Methods Left atrial (LA) structural, functional, and strain parameters were evaluated in 99 patients with HCM and compared with 89 age-, sex-, and BMI-matched control subjects. LA strain parameters were derived from CMR two- and four-chamber cine images by a semiautomatic method. LA strain parameters include global longitudinal strain (GLS) and global circumferential strain (GCS). The LA GLS includes reservoir strain (GLS reservoir), conduit strain (GLS conduit), and booster strain (GLS booster). Three LA GLS strain rate (SR) parameters were derived: SR reservoir, SR conduit, and SR booster. The primary endpoint was set as a composite of adverse clinical events, including SCD, new-onset or worsening to hospitalized HF, new-onset AF, thromboembolic events, and fatal ventricular arrhythmias. Results LA GLS, GLS SR and GCS were impaired in HCM patients compared to control subjects (all p

Abstract Solid oxide cells (SOCs) are all solid ceramic devices with the dual functionality of solid oxide fuel cells (SOFCs) to convert the chemical energy of fuels like H2, natural gas and other hydrocarbons to electricity and of solid oxide electrolysis cells (SOECs) to store renewable electric energy of sun and wind in hydrogen fuel. Among the electrochemical energy conversion and storage devices, SOCs are the most clean and efficient technology with unique dual functionality. Due to the high operation temperature (typically 600–800°C), SOCs exhibit many advantages over other energy conversion devices, such as low material cost, high efficiency and fuel flexibility. There has been rapid development of SOC technologies over the last decade with significant advantages and progress in key materials and a fundamental understanding of key issues such as an electrode, electrolyte, performance degradation, poisoning, and stack design. The reversible polarization also has a critical effect on the surface segregation and stability of the electrode and electrode/electrolyte interface. This critical review starts with a brief introduction, working principles and thermodynamics of SOC technology to readers with interests in this rapidly developing and emerging field. Then the key materials currently used in SOCs are summarized, followed by the discussion of the most advanced electrode modification methods and critical issues of SOCs, including the surface chemistry, segregation, electrode/electrolyte interface and varying material degradation mechanisms under reversible operations. The challenges and prospects of SOC technology for future developments are discussed.

Abstract Background Suanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the “drug-active ingredient-disease-target-pathway” was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice. Results The results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment. Conclusions The anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.

Abstract The mechanism of reduction and dephosphorization of phosphorus-containing magnetite was studied using SiC as reducing agent. The thermodynamic conditions for the reduction of Ca3(PO4)2 and Fe3O4 by SiC were simulated by FactSage7.1 thermodynamics software, respectively, indicating that the reduction of Ca3(PO4)2 by SiC is thermodynamically feasible, but the kinetic conditions of the system are not good when no liquid phase is formed. The Fe2SiO4 liquid phase can be formed by reducing Fe3O4 by SiC at 1200 ℃. When the SiC ratio is 10 wt.%, the liquid phase content is the largest, which can reach more than 60 wt.%. Therefore, in this paper, the Fe2SiO4 liquid phase generated by the reduction of Fe3O4 by SiC is used to improve the kinetic conditions of the reduction of Ca3(PO4)2 by SiC at high temperature, and relevant experiments were carried out. The research results show that the system generates a suitable amount of liquid phase at 1250 °C, and the gasification dephosphorization rate is the highest, which is 39.89 wt.%, at 1200 °C, the reduction reaction was not fully carried out, and the dephosphorization rate by gasification was only 23.79 wt.%. At 1300 °C, Fe3O4 was completely reduced to metallic Fe, which combined with the reduced P4 gas to form Fe2P. Gasification dephosphorization rate is only 28.25 wt.%.

Abstract Short‐term traffic flow prediction is particularly important for urban traffic control and congestion management. To improve the accuracy of traffic flow prediction, a new traffic flow prediction approach is proposed from the perspective of vehicle functions by using Radio Frequency Identification (RFID) electronic license plate (ELP) data. First, the improved Wavelet Neural Network (WNN) is introduced by adding three momentum terms to avoid local minimum and overfitting. The Long Short‐Term Memory Neural Network (LSTM) is constructed to train the time series with long time lags. Second, a novel short‐term traffic flow prediction method is developed by combining the improved WNN and LSTM in an urban road section. The proposed method performs a weighted combination to obtain a new prediction value according to whether the difference between the prediction values of the two methods satisfy the defined threshold, and then selects the one with the smallest error among the three prediction values as the final prediction result. Third, the experiments explore the prediction performance of the weekdays and weekends with 5 min‐interval, 15 min‐interval and 30 min‐interval via using RFID‐ELP data from Chongqing, China. Compared with existing prediction methods, the proposed approach can promote prediction performance and meet real‐time requirements.

【Objective】The study was carried out to investigate the prevalence of porcine circovirus Type 2 (PCV2) in pigs and cattle in Yunnan Province, and to identify the genetic variation and molecular evolution trend of PCV2 strains in Yunnan Province.【Method】PCR method was used to detect the etiology of PCV2 in 783 blood and manure samples of pigs and cattle from 11 regions of Yunnan Province. The whole genome amplification, cloning and sequencing of 6 PCV2 positive samples were carried out. The whole gene and ORF2 amino acid sequences were compared and analyzed by DNAStar software, and the genetic evolution tree was drawn by MEGA software.【Result】The positive rate of PCV2 of detected samples was 48.73%. A total of 6 strain PCV2 genome sequences were measured, of which 5 strain were 1 767 bp and 1 strain was 1 768 bp. The genetic development analysis showed that there were 2 strains of PCV2a subtype, 2 strains of PCV2b subtype and 2 strains of PCV2d subtype. The homology of 6 strains PCV2 was 94.6%-99.9%, and the homology with 20 national reference strains in GenBank database was 91.4 %-99.8 %. The ORF2 of 6 strains PCV2 had their typical amino acid sites. The amino acid site of PCV2a strain was mutated to be consistent with PCV2 (b/d) at the 80th (V80L) amino acid site, and the amino acid site of PCV2b strain was mutated to be consistent with PCV2d at the 59th (R59K), 63rd (K63R), 190th (A190T) and other amino acid sites.【Conclusion】PCV2 commonly exists in pigs in Yunnan, and the three gene subtypes of PCV2a, PCV2b and PCV2d coexist, and PCV2 (a/b) has a tendency to mutate to PCV2d. Holstein cows have not been infected with PCV2.

Abstract Ischemia/reperfusion (I/R)-induced liver injury with severe cell death is a major complication of liver transplantation. Transmembrane member 16A (TMEM16A), a component of hepatocyte Ca2+-activated chloride channel, has been implicated in a variety of liver diseases. However, its role in hepatic I/R injury remains unknown. Here, mice with hepatocyte-specific TMEM16A knockout or overexpression were generated to examine the effect of TMEM16A on hepatic I/R injury. TMEM16A expression increased in liver samples from patients and mice with I/R injury, which was correlated with liver damage progression. Hepatocyte-specific TMEM16A knockout alleviated I/R-induced liver damage in mice, ameliorating inflammation and ferroptotic cell death. However, mice with hepatic TMEM16A overexpression showed the opposite phenotype. In addition, TMEM16A ablation decreased inflammatory responses and ferroptosis in hepatocytes upon hypoxia/reoxygenation insult in vitro, whereas TMEM16A overexpression promoted the opposite effects. The ameliorating effects of TMEM16A knockout on hepatocyte inflammation and cell death were abolished by chemically induced ferroptosis, whereas chemical inhibition of ferroptosis reversed the potentiated role of TMEM16A in hepatocyte injury. Mechanistically, TMEM16A interacted with glutathione peroxidase 4 (GPX4) to induce its ubiquitination and degradation, thereby enhancing ferroptosis. Disruption of TMEM16A–GPX4 interaction abrogated the effects of TMEM16A on GPX4 ubiquitination, ferroptosis, and hepatic I/R injury. Our results demonstrate that TMEM16A exacerbates hepatic I/R injury by promoting GPX4-dependent ferroptosis. TMEM16A–GPX4 interaction and GPX4 ubiquitination are therefore indispensable for TMEM16A-regulated hepatic I/R injury, suggesting that blockades of TMEM16A–GPX4 interaction or TMEM16A inhibition in hepatocytes may represent promising therapeutic strategies for acute liver injury.

Abstract Background β-Secretase (BACE1) is the vital enzyme in the pathogenic processes of Alzheimer's disease (AD). However, the development of a powerful tool with sensitivity for BACE1 determination in vivo is a challenge. Methods A novel NIR fluorescent probe HBAE was synthetized from 2-hydroxy-3-methylbenzaldehyde and 2-amino-benzenethiol by 5 steps. The fluorescence mechanism in the ESIPT systems of HBAE probe was insighted with time-dependent density functional theory (TD-DFT) at the TDPBE0 level with the def2-TZVP approach. The corresponding docking between HBAE and BACE1 (PDB: 5I3Y) was performed through the ducking method by DOCK6.8. Then the BBB permeability of HBAE is verified by transwell orifice plate. 22-month-old male AD-model (5XFAD) mice and age-matched wild-type mice were employed to observe the brain kinetics by intravenous injection. Finally, Immunohistochemistry was performed on the AD brain section to reveal the levels of BACE1 in hippocampus and cortex areas and other regions in AD mice through the brain tissue slices by HBAE. Results The NIR fluorescent probe HBAE was successfully applied in imaging BACE1 in AD model mice. The capability of HBAE in reflecting different level of BACE1 was performed by the specific imaging of the hippocampus region. Conclusions We reported the first ESIPT near-infrared fluorescence probe HBAE for monitoring endogenous BACE1 in the AD live model mice, thus offering a versatile chemical tool for visualizing in the pathological processes of AD live brains. Remarkably, high resolution images showed the localization of red fluorescence stains in hippocampus of the AD brain. This study provides a promising way for functional insights from protein BACE1 in vivo.

This study investigates the effect of aspect ratios (Ra*) on the wake bi-stability behind the GTS model using improved delayed-detached eddy simulation (IDDES) at a Reynolds number of 2.7×104. Eight cases with Ra* in the range of Ra*∈[0.5, 2.0] have been considered to investigate the asymmetric wake flow and the corresponding aerodynamic response. The primary objective of this study is to reveal the mechanism of the Ra* effects on the GTS’s flow topology, asymmetric wake flow and the bi-stable flow switching process. The accuracy of the numerical method has been validated by comparing the recirculation bubble, vortex core and aerodynamic drag with those obtained from the previous large-eddy simulation study and the water channel experiment. The results show that three typical flow topologies (FT-I, FT-II and FT-III) are classified according to the drag coefficient and the length relation between the vertical and horizontal recirculation region. The vertical and horizontal asymmetric characteristics can be transformed between two adjacent flow topologies. Moreover, a switching process of the bi-stable wake flow is also observed as Ra* is equal to 0.71. Additionally, the ground motion can reverse the dominated flow state and inhibiting the corresponding switching process.

Abstract Cement sheath is an annular structure situated between casing and formation, which is designed to seal the formation and reinforce the borehole. However, owing to the surface irregularity and drilling mud residue, the interface between the cement sheath and the formation is one of the weakest parts for fluid leakage causing well integrity issues, which would also affect the reliability of the cement bond logs. To evaluate the cementation state and tensile properties of the cement-formation interface, rock-cement composite disc specimens are prepared, considering key factors such as lithology, interface irregularity, treatment of oil-based drilling mud contamination, and flushing fluid washing. Flushing efficiency of the drilling mud contaminated rock surface, interface cementation characteristic, referenced tensile strength, and tensile fracture morphology are acquired and analysed comparatively. Results show that (1) the flushing efficiencies of shale and sandstone are 74.1 ~ 61.9% and 52.4 ~ 28.4%, respectively, decreasing with the increase in surface irregularity. (2) The rock-cement interface gradually becomes poorly cemented as the surface cleanliness decreasing and the irregularity increasing. (3) Under the condition of drilling fluid contamination, there exists a transitional area at the cemented interface, where microcracks and pores are developed. (4) With the influence of drilling mud contamination, the referenced tensile strengths of shale-cement and sandstone-cement interfaces drop from 2.716 to 0.586 MPa and from 2.840 to 0.007 MPa, respectively. The effects of underground temperature and pressure environment are not particularly considered in this study and would be investigated systematically in future research.

Abstract Owing to superior comprehensive performance than conventional superalloys at high temperature, refractory high entropy alloy (RHEA) is becoming a promising candidate for the next generation high-temperature material. Herein, contemporary aspects of corresponding development of RHEAs are reviewed to discuss various factors affecting the organization structure and service performance. It mainly covers alloying system and strengthening mechanism, the preparation method, plastic deformation and the related mechanism, as well as microstructure control by heat treatment. Firstly, the alloy systems and strengthening mechanism are introduced. This is followed by different preparation methods and the comparison of strengths and shortcomings based on different RHEAs. Then, hot deformation behavior and plastic deformation under different loadings are analyzed. Based on this, the influence of heat treatment on microstructures prior to and after the deformation is further summarized. Finally, some important research areas to be carried out in future are pointed out. This review will give a deep understanding of the effects of different factors on the service performance and provide scientific guide in designing RHEAs with improved performance.

Abstract Background Diabetic retinopathy (DR), a specific neuron-vascular complication of diabetes, is a major cause of vision loss among middle-aged people worldwide, and the number of DR patients will increase with the increasing incidence of diabetes. At present, it is limited in difficult detection in the early stages, limited treatment and unsatisfactory treatment effects in the advanced stages. Main body The pathogenesis of DR is complicated and involves epigenetic modifications, oxidative stress, inflammation and neovascularization. These factors influence each other and jointly promote the development of DR. DNA methylation is the most studied epigenetic modification, which has been a key role in the regulation of gene expression and the occurrence and development of DR. Thus, this review investigates the relationship between DNA methylation and other complex pathological processes in the development of DR. From the perspective of DNA methylation, this review provides basic insights into potential biomarkers for diagnosis, preventable risk factors, and novel targets for treatment. Conclusion DNA methylation plays an indispensable role in DR and may serve as a prospective biomarker of this blinding disease in its relatively early stages. In combination with inhibitors of DNA methyltransferases can be a potential approach to delay or even prevent patients from getting advanced stages of DR.

Abstract The ternary RMn2Ge2 (R = rare earth) intermetallic compounds have attracted great attention due to their interesting magnetic behaviors and magnetotransport responses. Here, we reported our observation of anisotropic magnetic property, magnetostriction, and magnetocaloric effect (MCE) in TbMn2Ge2 single crystal. Below the transition temperature of Tb magnetic sublattices ( $$T_{{\text{C}}}^{{{\text{Tb}}}}$$ T C Tb ~ 95 K), strong Ising-like magnetocrystalline anisotropy is observed with an out-of-plane ferromagnetic moments 5.98 μ B/f.u. along the easy c axis, which is two orders of magnitude larger than that of field along a axis. Above $$T_{{\text{C}}}^{{{\text{Tb}}}}$$ T C Tb , a field-induced metamagnetic transition is observed from the spin-flip of Mn sublattices. During this transition, remarkable magnetostriction effect is observed, indicating of strong spin–lattice coupling. The responses of Tb and Mn sublattices to the magnetic field generate a giant magnetic entropy change ( $$- \Delta S_{M}$$ - Δ S M ) and large values of relative cooling power (RCP) and temperature-averaged entropy change (TEC). The calculated maximum magnetic entropy change ( $$- \Delta S_{M}^{\max }$$ - Δ S M max ), RCP, and TEC(10) with magnetic field change of 7 T along c axis reach 24.02 J kg−1 K−1, 378.4 J kg−1, and 21.39 J kg−1 K−1 near $$T_{{\text{C}}}^{{{\text{Tb}}}}$$ T C Tb , which is the largest among RMn2Ge2 families. More importantly, this giant MCE shows plateau behavior with wide window temperatures from 93 to 108 K, making it be an attractive candidate for magnetic refrigeration applications.

Measurement(s) Robot and human trajectories, human full-body motion capture, and eye gaze directions. Technology Type(s) Mobile robot, inertial measurement unit-based motion capture system, and eye tracker.

Abstract Gas has become the main fuel for electricity production as a result of the significant growth in gas‐fired units (GFU), which can lead to a shortage of supply gas for power generation. Meanwhile, there is a higher chance of power mismatch due to the rising penetration of renewable energy in the power system. Considering that power system and gas natural network are increasingly interdependent under more coupling elements, such as power‐to‐gas (PtG) and GFU, cascading failures will occur more often if demand mismatch is not dealt with efficiently. To explore the potential of PtG and GFU to enhance the flexibility of the integrated power and gas system (IPGS), the collaborative load shifting effect (LSE) of them is researched. Therefore, this article contributes a two‐stage robust energy scheduling model that considers the LSE of PtG and GFU on the electric and gas demand side. Simplifying the dual process in the max–min optimization, this article applies a modified Benders decomposition methodology introducing virtual balance to solve the model. Also, the LSE of PtG and GFU is demonstrated in the form of security region (SR) in the case study. Based on the proposed load uniformity level (LUL) index, the results show that GFU and PtG are mainly involved in the load shifting in the power system, and PtG prefers to work when load shifting level is high. As a result, the equipment of PtG and GFU increases the SR by 40.9% and 14.3%, respectively. Moreover, the impact of the fluctuation of wind power on the IPGS, especially on the natural gas network (NGN), is validated through the reduction of the load shifting range by 5%.

The present study investigated the role of stromal cell-derived factor-1 in the progression of renal injury in type 2 diabetic nephropathy. The 8-week old male db/db mice were used as the model of diabetic nephropathy and aged-matched male C57BL/6 mice constituted the control group. Fasting blood glucose, 24 hour urinary albumin and the creatinine clearance rate were measured. The expressions of stromal cell-derived factor-1, CXC chemokine receptor 4 and F4/80 were detected. Normal rat kidney epithelial cells were exposed to stromal cell-derived factor-1α, high glucose, tumour growth factor-β1, valsartan and LY294002, respectively. The extracellular matrix expression was evaluated. It was found that creatinine clearance rate was significantly decreased in 28-week db/db mice compared to the age-matched C57BL/6 mice and valsartan could significantly increase creatinine clearance rate. The expression of stromal cell-derived factor-1, CXC chemokine receptor 4 and F4/80 was significantly increased in the kidney of db/db mice but not in C57BL/6 mice, which was improved with valsartan treatment. In vitro, the expression of CXC chemokine receptor 4 was detected in the rat kidney epithelial cells. Tumour growth factor-β1 increased the expressions of type IV collagen and fibronectin in rat kidney epithelial cells under low glucose and high glucose condition. Stromal cell-derived factor-1α inhibited the harmful effect of tumour growth factor-β1 on extracellular matrix expression, and valsartan exerted synergistic effect on stromal cell-derived factor-1α. Stromal cell-derived factor-1α decreased tumour growth factor-β1expression and increased p-AKT expression, which were inhibited by LY294002 treatment. Stromal cell-derived factor-1 improved renal fibrosis which might partly involve TGF-β-mediated extracellular matrix via PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Abstract Biomolecular condensates assembled through phase transitions regulate diverse aspects of plant growth, development, and stress responses. How biomolecular condensates control plant immunity is poorly understood. In Nature Plants, a new study (Zhou et al., Nat Plants 9:289–301, 2023) reveals how plants assemble translational condensates to balance tissue health and disease resistance.

Abstract The sudden spread of COVID-19 infections in a region can catch its healthcare system by surprise. Can one anticipate such a spread and allow healthcare administrators to prepare for a surge a priori? We posit that the answer lies in distinguishing between two types of waves in epidemic dynamics. The first kind resembles a spatio-temporal diffusion pattern. Its gradual spread allows administrators to marshal resources to combat the epidemic. The second kind is caused by super-spreader events, which provide shocks to the disease propagation dynamics. Such shocks simultaneously affect a large geographical region and leave little time for the healthcare system to respond. We use time-series analysis and epidemiological model estimation to detect and react to such simultaneous waves using COVID-19 data from the time when the B.1.617.2 (Delta) variant of the SARS-CoV-2 virus dominated the spread. We first analyze India’s second wave from April to May 2021 that overwhelmed the Indian healthcare system. Then, we analyze data of COVID-19 infections in the United States (US) and countries with a high and low Indian diaspora. We identify the Kumbh Mela festival as the likely super-spreader event, the exogenous shock, behind India’s second wave. We show that a multi-area compartmental epidemiological model does not fit such shock-induced disease dynamics well, in contrast to its performance with diffusion-type spread. The insufficient fit to infection data can be detected in the early stages of a shock-wave propagation and can be used as an early warning sign, providing valuable time for a planned healthcare response. Our analysis of COVID-19 infections in the US reveals that simultaneous waves due to super-spreader events in one country (India) can lead to simultaneous waves in other places. The US wave in the summer of 2021 does not fit a diffusion pattern either. We postulate that international travels from India may have caused this wave. To support that hypothesis, we demonstrate that countries with a high Indian diaspora exhibit infection growth soon after India’s second wave, compared to countries with a low Indian diaspora. Based on our data analysis, we provide concrete policy recommendations at various stages of a simultaneous wave, including how to avoid it, how to detect it quickly after a potential super-spreader event occurs, and how to proactively contain its spread.

Abstract Background: Antibodies and derivative drugs targeting immune checkpoints have been approved for the treatment of several malignancies, but there are fewer responses in patients with pancreatic cancer. Here, we designed a nanobody molecule with bi-targeting on PD-L1 and CXCR4, as both targets are overexpressed in many cancer cells and play important roles in tumorigenesis. We characterized the biochemical and anti-tumour activities of the bispecific nanobodies in vitro and in vivo. Methods: A nanobody molecule was designed and constructed. The nanobody sequences targeting PD-L1 and CXCR4 were linked by the (G4S)3 flexible peptide to construct the anti-PD-L1/CXCR4 bispecific nanobody. The bispecific nanobody was expressed in E. coli cells and purified by affinity chromatography. The purified nanobody was biochemically characterized by mass spectrometry, Western blotting and flow cytometry to confirm the molecule and its association with both PD-L1 and CXCR4. The biological function of the nanobody and its anti-tumour effects were examined by an in vitro tumour cell-killing assay and in vivo tumour inhibition in mouse xenograft models. Results: A novel anti-PD-L1/CXCR4 bispecific nanobody was designed, constructed and characterized. The molecule specifically bound to two targets on the surface of human cancer cells and inhibited CXCL12-induced Jurkat cell migration. The bispecific nanobody increased the level of IFN-γ secreted by T-cell activation. The cytotoxicity of human peripheral blood mononuclear cells (hPBMCs) against pancreatic cancer cells was enhanced by the molecule in combination with IL-2. In a human pancreatic cancer xenograft model, the anti-PD-L1/CXCR4 nanobody markedly inhibited tumour growth and was superior to the combo-treatment by anti-PD-L1 nanobody and anti-CXCR4 nanobody or treatment with atezolizumab as a positive control. Immunofluorescence and immunohistochemical staining of xenograft tumours showed that the anti-tumour effects were associated with the inhibition of angiogenesis and the infiltration of immune cells. Conclusion: These results clearly revealed that the anti-PD-L1/CXCR4 bispecific nanobody exerted anti-tumour efficacy in vitro and inhibited tumour growth in vivo. This agent can be further developed as a therapeutic reagent to treat human pancreatic cancer by simultaneously blocking two critical targets.

Objective Tan lambs (n = 36, 3 mo old, 19.1±0.53 kg) were used to assess effects of dietary guanidinoacetic acid (GAA) and rumen-protected methionine (RPM) on growth performance, carcass traits, meat quality, and serum parameters. Methods Lambs were randomly assigned to three treatment groups, with 6 pens per group and 2 lambs per pen. Dietary treatments were: basal diet alone (I); basal diet supplemented with 0.08% GAA+0.06% RPM (II); and basal diet supplemented with 0.08% GAA+0.08% RPM (III). Diets were provided three times a day for 90 d. Intake per pen was recorded daily and individual lamb body weight (BW) was measured monthly. Carcass traits were measured after slaughter and meat quality at the end of the experiment, blood samples were taken on a subgroup of lambs for analysis of indicators mostly related to protein metabolism. Results Final BW and average daily gain for the first and second month, and for the entire experiment were greater in Treatment II compared to Treatment I (p

Objective To report the outcomes and feasibility of a new technique to change K‐line (−) to K‐line (+) via only a posterior approach to treat multilevel non‐continuous cervical ossification of the posterior longitudinal ligament (C‐OPLL) with kyphotic deformity. Methods In this study, 17 consecutive cases of patients who underwent vertical pressure procedure (VP) combined with posterior cervical single‐open‐door laminoplasty and instrumented fusion from January 1, 2017 to December 31, 2019 were enrolled. The following radiographic parameters: C2‐C7 Cobb angle, local Cobb angle, extent of OPLL, and the distance from OPLL to the K‐line(DK) were measured and analyzed. Clinically, the JOA score, VAS‐N and VAS‐A, NDI, and complications were collected from medical records to evaluate the clinical outcomes. Results All 17 cases shifted from K‐line (−) to K‐line (+).Comparing the preoperative images to the final follow‐up images, the mean C2‐7 Cobb angle changed from −6.94° ± 8.30° to 8.18° ± 4.43°, and the local Cobb angle altered from −9.12° ± 8.68° to 6.65° ± 6.11°. The mean DK increased from −2.64 ± 1.52 mm to 3.09 ± 2.19 mm. One patient showed C5 palsy and recovered within 3 months. The mean JOA score increased from 8.88 ± 2.11 to 14.71 ± 1.36. The average NDI decreased from 20.65 ± 7.80 to 8.94 ± 4.93. The mean VAS‐N and VAS‐A decreased from 3.44 ± 1.80 and 4.69 ± 1.97 to 1.25 ± 0.86 and 1.38 ± 1.16. All patients were followed up for at least 1 year. Conclusion A new technique added to posterior decompression and fusion (PDF), the vertical pressure procedure effectively corrects K‐line (−) to K‐line (+) and avoids the shortcomings of conventional anterior decompression and fusion (ADF) as well as PDF to provide a relatively safe and adequate decompression, cervical realignment. It pronounced satisfactory clinical outcome for extensive non‐continuous OPLL with kyphotic deformity even though OPLL remains ventral to the spinal cord.

Objective Thoracic myelopathy caused by severe anterior ossification is often progressive and fails to respond to conservative treatment. Removal of the compressing ossification is the most effective method but is hard to operate. In this study, we describe a novel one‐stage posterior circumferential decompressive procedure assisted by an angled ultrasonic bone curette (UBC) for thoracic myelopathy caused by severe anterior ossification and evaluate its safety and efficacy. Methods The current study enrolled 15 consecutive patients (five men and 10 women) with thoracic myelopathy caused by severely anterior ossification between January 2017 and December 2019. All patients underwent posterior circumferential decompression assisted by angled UBC and segmental instrumentation with interbody fusion. At the time of surgery, the average age was 58.6 ± 6.3 years (47–70 years). Before and after surgery, the patient data, clinical manifestation, operative levels, blood loss, operative time, perioperative complications, Japanese Orthopaedic Association (JOA) score were recorded and analyzed retrospectively. Results All patients had successful one‐stage posterior circumferential decompression to remove anterior ossifications directly. There were 12 cases of OPLL, two cases of a calcified giant herniated disc, and one case of osteophyte. The average operation time was 153.4 ± 53.4 min (77–242 min), with a mean blood loss of 463.5 ± 155.8 mL (240–780 mL). The average length of stay in the hospital was 14.3 ± 4.7 days (9–25 days) and the mean follow‐up duration was 20.8 ± 8.8 months (12–39 months). Almost all patients had subjective improvement in motor power and gait. The average preoperative JOA score was 4.5 ± 1.6, which improved to 9.0 ± 1.8 at the final follow‐up. Postoperative differences in the overall JOA scores showed significant improvement (F = 105.446, p

Abstract Unrestricted reproduction and spread of pest had caused great damage to the quality and yield of crops in recent years. Besides the use of traditional chemical pesticides, natural products also make a huge contribution against pests. Chasmanthinine, a diterpenoid alkaloid isolated from Aconitum franchetii var. villosulum, shown extremely antifeedant activity against Spodoptera exigua. Therefore, a series of novel Chasmanthinine derivatives were synthesized and their biological activity was studied in this work. Compound 33 showed the strongest antifeedant activity (EC50 = 0.10 mg/cm2) among all the test compounds. The mechanism research of 33 revealed that its antifeedant effect was related to the inhibition of carboxylesterase (CES), and proved the thiophene acyl group could form a strong binding effect with CES by molecular docking. Moreover, compound 10 exhibited the strongest cytotoxicity (IC50 = 12.87 μM) against Sf9 cell line and moderate contact toxicity. The mechanism research indicated that compound 10 could induce Sf9 cells apoptosis. In summary, the results lay a foundation for the application of diterpene alkaloids in plant protection.

ABSTRACT Importance There are a variety of musculoskeletal malformations and injuries that can occur in newborns. These can be a significant cause of perinatal death or a reason for miscarriage and can lead to long‐term functional issues if not managed appropriately. There is no systematic and well‐established screening program for neonatal musculoskeletal malformations and injuries in China now. Objective To report the incidence and types of congenital musculoskeletal malformations in two hospitals in Shenzhen City, to explore and discuss the details of the screening procedure and improve future prevention and treatment. Methods From October 2013 to May 2014, 2564 one‐day‐old newborns were screened by a pediatric orthopedic physical examination, in combination with ultrasonography when required, and the incidence and variety of diseases were recorded statistically. Results Among 2564 screened newborns, the following musculoskeletal conditions were identified: congenital muscular torticollis (CMT) (seven cases, 0.27%), hip subluxation (four cases, 0.16%), hip dysplasia (47 cases, 1.83%), congenital talipes equinovarus (CTEV) (two cases, 0.08%), congenital talipes calcaneovalgus (15 cases, 0.58%), polydactyly (nine cases, 0.35%), syndactyly (one case, 0.04%), and spinal hemivertebra (one case, 0.04%). Additionally, there were five (0.19%) neonates with birth injuries. Interpretation It is feasible to carry out neonatal screening and identification of musculoskeletal malformations and birth injuries in China. This is helpful as timely detection and early intervention for many of these conditions can avoid permanent functional impairment in these children.

Low temperature inhibits the regeneration of amputated tails of Gekko japonicus by influencing the energy sensory Akt/mTOR pathway, which is also modulated by injury-induced Wnt signal.

Taste perception is an important factor in determining people's food intake. Understanding the relationship between taste sensitivity and food consumption behavior is one of the most innovative strategies for solving health problems caused by diet, and measuring the taste sensitivity of human subjects is the key to establish this relationship. In this paper, from the aspects of working principle, operation process and application of taste sensitivity determination, the methods of measuring human taste sensitivity at home and abroad are summarized, including psychophysical method, biopotential method, bacterial papilla counting method and genotyping method. Psychophysical measurement method is simple to operate and easy to implement, but subjective and error are large; biopotential measurement method reduces subjective errors, but the subjects need to remain relatively static during the measurement process, otherwise it will affect the stability of the electrode; fungal papilla counting method and genotyping method need to be carried out in conjunction with other methods. In addition, the genotyping method requires high technical content and cost. Through the analysis and evaluation of the above methods, it provides a theoretical basis and guidance for selecting different taste sensitivity determination methods.

Spin-orbit torques driven by the conventional spin Hall effect are widely used to switch magnetization, but this approach is nondeterministic and inefficient for magnets with perpendicular magnetic anisotropy. Here, the authors demonstrate deterministic, field-free switching in a Ni/Co multilayer by exploiting the magnetic spin Hall effect in adjacent Mn3Sn.

With the frequent occurrences of high-impact-low-probability (HILP) events such as typhoons, lightning strikes, and cyber attacks, people have the increasingly need of raising distribution network’s (DN) resilience. Deploying backup sources into the system can effectively improve the resilience of DNs. With the development of transportation electrification, the number of electric taxis (ETs) in urban transit is now growing. Besides, Vehicle-to-Grid (V2G) technology has also developed vigorously. Therefore, ETs can be dispatched to charging stations under unified command to feed power back to the grid when HILP events happen. To this end, we establish an optimization model for the post-event recovery of the DN using ETs. In this model, we combine the energy provided by V2G stations with the existing distributed generators and energy storage in the grid to restore the outage areas jointly. Topology reconfiguration technique and power flow balance of DN have also been fully considered in the modeling process. The whole grid is divided into several microgrids and powered by different sources. The multi-source multi-region power restoration method improves the stability of the DN restoration. It is easier to control the voltage and power quality. The method we proposed is tested on the modified IEEE 33-bus system. The simulation results verify the effectiveness and efficiency of our work.

BackgroundColon cancer (CC) is a highly heterogeneous malignancy associated with high morbidity and mortality. Pyroptosis is a type of programmed cell death characterized by an inflammatory response that can affect the tumor immune microenvironment and has potential prognostic and therapeutic value. The aim of this study was to evaluate the association between pyroptosis-related gene (PRG) expression and CC.MethodsBased on the expression profiles of PRGs, we classified CC samples from The Cancer Gene Atlas and Gene Expression Omnibus databases into different clusters by unsupervised clustering analysis. The best prognostic signature was screened and established using least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. Subsequently, a nomogram was established based on multivariate COX regression analysis. Next, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential molecular mechanisms between the high- and low-risk groups and to explore the differences in clinicopathological characteristics, gene mutation characteristics, abundance of infiltrating immune cells, and immune microenvironment between the two groups. We also evaluated the association between common immune checkpoints and drug sensitivity using risk scores. The immunohistochemistry staining was utilized to confirm the expression of the selected genes in the prognostic model in CC.ResultsThe 1163 CC samples were divided into two clusters (clusters A and B) based on the expression profiles of the 33 PRGs. Genes with prognostic value were screened from the DEGs between the two clusters, and an eight PRGs prognostic model was constructed. GSEA and GSVA of the high- and low-risk groups revealed that they were mainly enriched in inflammatory response-related pathways. Compared to those in the low-risk group, patients in the high-risk group had worse overall survival, an immunosuppressive microenvironment, and worse sensitivity to immunotherapy and drug treatment.ConclusionOur findings provide a foundation for future research targeting pyroptosis and new insights into prognosis and immunotherapy from the perspective of pyroptosis in CC.

Phycocyanin has been reported to exert antineoplastic function in non-small cell lung cancer (NSCLC), while the underlying molecular mechanism is still largely unclear. In this study, a whole transcriptome resequencing was employed. Results showed that lncRNA LINC00852 was inhibited by phycocyanin in NSCLC cells. Knockdown LINC00852 expression resulted in the attenuated proliferation, viability and migration ability of NSCLC cells. Meanwhile, dual-luciferase reporter assay indicated that LINC00852 acted as a ceRNA of miR-29a-3p which further targets regulator complex protein LAMTOR1 (LAMTOR1). Overexpression miR-29a-3p or knockdown LAMTOR1 expression decreased the activity of NSCLC cells, respectively. Moreover, AMPK signaling was activated upon LINC00852 knockdown, miR-29a-3p enhancement or LAMTOR1 inhibition, which was in consistent with the phycocyanin exposure results. In summary, we demonstrated that LINC00852 played a key role in phycocyanin-mediated NSCLC regulation process, and the epigenetic signaling LINC00852/miR-29a-3p/LAMTOR1 may be considered as novel molecular targets for fighting NSCLC base on marine functional foods.

BackgroundOwing to the complex pathophysiological features and heterogeneity of sepsis, current diagnostic methods are not sufficiently precise or timely, causing a delay in treatment. It has been suggested that mitochondrial dysfunction plays a critical role in sepsis. However, the role and mechanism of mitochondria-related genes in the diagnostic and immune microenvironment of sepsis have not been sufficiently investigated.MethodsMitochondria-related differentially expressed genes (DEGs) were identified between human sepsis and normal samples from GSE65682 dataset. Least absolute shrinkage and selection operator (LASSO) regression and the Support Vector Machine (SVM) analyses were carried out to locate potential diagnostic biomarkers. Gene ontology and gene set enrichment analyses were conducted to identify the key signaling pathways associated with these biomarker genes. Furthermore, correlation of these genes with the proportion of infiltrating immune cells was estimated using CIBERSORT. The expression and diagnostic value of the diagnostic genes were evaluated using GSE9960 and GSE134347 datasets and septic patients. Furthermore, we established an in vitro sepsis model using lipopolysaccharide (1 µg/mL)-stimulated CP-M191 cells. Mitochondrial morphology and function were evaluated in PBMCs from septic patients and CP-M191 cells, respectively.ResultsIn this study, 647 mitochondrion-related DEGs were obtained. Machine learning confirmed six critical mitochondrion-related DEGs, including PID1, CS, CYP1B1, FLVCR1, IFIT2, and MAPK14. We then developed a diagnostic model using the six genes, and receiver operating characteristic (ROC) curves indicated that the novel diagnostic model based on the above six critical genes screened sepsis samples from normal samples with area under the curve (AUC) = 1.000, which was further demonstrated in the GSE9960 and GSE134347 datasets and our cohort. Importantly, we also found that the expression of these genes was associated with different kinds of immune cells. In addition, mitochondrial dysfunction was mainly manifested by the promotion of mitochondrial fragmentation (p

The stability and dynamics of soil organic carbon (SOC) pools in forest soils are crucial for assessing and predicting the effectiveness of forest carbon sequestration. Various factors such as soil depth, nutrients availability, crustal elements, pH, and stand characteristics (tree type, tree age) influence the stability of SOC pools. To better understand SOC stability of cold temperate forest soil, soil samples were collected from 0–10 cm, 10–20 cm, 20–40 cm, and 40–60 cm depths in a Larix gmelinii forest. Then, the distribution characteristics of SOC pools under different protection mechanisms and their influencing factors were examined. Our results showed that the unprotected SOC pool was the highest, while the physical–chemical protected SOC pool was the lowest. Total organic carbon (TOC) had a linear positive relationship with unprotected and physical-protected SOC pools, and a logarithmic positive relationship with physical–chemical protected and chemical-protected SOC pools. Soil depth was the predominant factor affecting the SOC pools of each protection mechanism. The physical–chemical protected SOC pool significantly differed from forest types and forest ages, and the chemical-protected SOC pool was associated with the synergistic effects of forest age and type. Furthermore, soil moisture and acidity, and the crustal elements may play prominent role in the variation of SOC pools in the Larix gmelinii forests. Our findings suggested that the silt- and clay-associated SOC pools in the Larix gmelinii forest soils had approached or achieved saturation, while more organic C was fixed in the relatively active unprotected SOC pool. This unprotected pool was more sensitive to ecosystem change, indicating its importance in assessing forest carbon sequestration. Our study provided insights into the active and dynamic SOC pools in forest soils and their responses to different environmental factors. These findings can be utilized to accurately assess the carbon sink potential of cold temperate forest soils and inform the management of forest ecosystems.

Abstract Radiative transfer models are widely applied in climate models to simulate vertical temperature perturbations caused by external radiative forcings. A large part of radiative transfer models is the infrared gaseous spectral transmittance scheme, which quantifies the longwave atmospheric absorption. A rapid infrared gaseous spectral transmittance scheme, called the Optimized alternate Mapping Correlated K‐Distribution model (OMCKD), is introduced in this paper. To improve the accuracy of our scheme without increasing pseudo‐monochromatic calculations, we introduce the optimal iteration method to automatically tune the equivalent absorption coefficients in the cumulative probability subspace. In addition, a new expression weighted by black‐body radiation is introduced to calculate the equivalent absorption coefficient. The OMCKD simulates heating rate and radiation flux with errors of less than 0.12 K d−1 and 0.35 W m−2, respectively, below stratopause for standard atmospheric profiles. The OMCKD is also evaluated and compared with the rapid radiative transfer model for general circulation models (RRTMG) in realistic atmospheric profiles. We found that OMCKD can accurately produce heating rates and generally captures radiative forcings associated with large perturbations to the concentrations of main greenhouse gases. Furthermore, the number of pseudo‐monochromatic calculations in OMCKD is 11.4% less than that in RRTMG, which indicates less computational cost.