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The operation condition of wind turbine is complex with frequent load disturbances. However, the traditional rigid connection wind turbine has shortcomings in rejecting impact load disturbance. In this paper, a novel double rotor wind turbine generation system is proposed. Firstly, the concept design of the new system is carried out by adopting the technical route of ”double rotor machine + electrically excited synchronous generator”, and the main components and structural forms of the system are given. Then, the balance equations of speed, torque and power are derived based on the principles of kinematics and electrotechnics. Finally, the characteristics of the double rotor wind turbine generation system under different wind conditions are analyzed through simulation, where the anti-impact load capacity is evaluated. The simulation results show the superiority of the proposed novel double rotor wind turbine generation system.

Arctigenin is a phenylpropanoid dibenzylbutyro lactone lignan compound with multiple biological functions. Previous studies have shown that arctigenin have neuroprotective effects in Alzheimer’s disease (AD) models both in vivo and in vitro; however, its metabolism in vivo has not been studied. Most traditional analytical methods only partially characterize drug metabolite prototypes, so there is an urgent need for a research strategy that can fully characterize drug metabolites. In the present study, ions fishing with a serial five-membered lactone ring as a fishhook strategy based on ultrahigh-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was utilised to characterise the metabolism of arctigenin, and the establishment of this strategy also solved the challenge of creating a comprehensive metabolic profile of neolignan. Based on the proposed strategy, a total of 105 metabolites were detected and characterised, 76 metabolites of which were found in rats and 49 metabolites in liver microsomes. These metabolites were postulated to be produced through oxidation, reduction, hydrolysis, and complex reactions. Subsequently, network pharmacology was utilized to elucidate the mechanism of arctigenin and its main metabolites against Alzheimer’s disease, screening 381 potential targets and 20 major signaling pathways. The study on the comprehensive metabolism of arctigenin provides a holistic metabolic profile, which will help to better understand the mechanism of arctigenin in the treatment of Alzheimer’s disease (AD) and also provide a basis for the safe administration of arctigenin.

Acorus calamus var. angustatus Besser (ATT) is a traditional herb with a long medicinal history. The volatile oil of ATT (VOA) does possess many pharmacological activities. It can restore the vitality of the brain, nervous system and myocardial cells. It is used to treat various central system, cardiovascular and cerebrovascular diseases. It also showed antibacterial and antioxidant activity. Many studies have explored the benefits of VOA scientifically. This paper reviews the extraction methods, chemical components, pharmacological activities and toxicology of VOA. The molecular mechanism of VOA was elucidated. This paper will serve as a comprehensive resource for further carrying the VOA on improving its medicinal value and clinical use.

Neomangiferin (NMF) is an extremely special xanthone that could be simultaneously attributed to C-glycoside and O-glycoside with a variety of biological activities, such as anti-inflammatory, antitumor, antipyretic, and so on. So far as we know, the metabolism profiling has been insufficient until now. Herein, Drug Metabolite Cluster Centers (DMCCs)-based Strategy has been developed to profile the NMF metabolites in vivo and in vitro. Firstly, the DMCCs was proposed depending on literature-related and preliminary analysis results. Secondly, the specific metabolic rule was implemented to screen the metabolites of candidate DMCCs from the acquired Ultra High Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS) data by extracted ion chromatography (EIC) method. Thirdly, candidate metabolites were accurately and tentatively identified according to the pyrolysis law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic product ions (DPIs) deduced preliminarily. Finally, network pharmacology was adopted to elucidate the anti-inflammatory action mechanism of NMF on the basis of DMCCs. As a result, 3 critical metabolites including NMF, Mangiferin (MF) and Norathyriol (NA) were proposed as DMCCs, and a total of 61 NMF metabolites (NMF included) were finally screened and characterized coupled with 3 different biological sample preparation methods including solid phase extraction (SPE), acetonitrile precipitation and methanol precipitation. Among them, 32 metabolites were discovered in rat urine, 30 in rat plasma, 12 in rat liver, 9 metabolites in liver microsomes and 8 in rat faeces, respectively. Our results also illustrated that NMF primarily underwent deglucosylation, glucuronidation, methylation, sulfation, dihydroxylation and their composite reactions in vivo and in vitro. Additionally, network pharmacology analysis based on DMCCs revealed 85 common targets of disease-metabolites, and the key targets were TNF, EGFR, ESR1, PTGS2, HIF1A, IL-2, PRKCA and PRKCB. They exerted anti-inflammatory effects mainly through the pathways of inflammatory response, calcium-dependent protein kinase C activity, nitrogen metabolism, pathways in cancer and so on. In general, our study constructed a novel strategy to comprehensive elucidate the biotransformation pathways of NMF in vivo and in vitro, and provided vital reference for further understanding its anti-inflammatory action mechanism. Moreover, the established strategy could be generalized to the metabolism and action mechanism study of other natural products.

Abstract In fuel cells, the generally low oxygen reduction reactions (ORR) rate at the cathode is a major factor limiting the overall performance of fuel cell, so the development of high‐performance, stable and inexpensive ORR electrocatalysts is a major researching direction. Nano‐electrocatalysts, especially one‐dimensional (1D) electrocatalysts, exhibit good catalytic behavior in fuel cell reactions due to their unique anisotropic structure, large specific surface area, high elasticity and excellent stability. To date, many advanced 1D electrocatalysts have been reported for optimizing the cathode ORR of fuel cells. Therefore, a comprehensive review of the structural design of 1D nano‐electrocatalysts and a systematic analysis of their enhanced performance still need further summarized and concluded. In this review, we firstly introduce the main synthetic methods of 1D electrocatalysts, and then discuss the recent advances and advantages of different structured 1D electrocatalysts involving nanofibers, nanotubes, nanorods, nanochains, nanowires, nanobelts, nanoneedles, nanowhiskers, and coaxial nanocables. In addition, we also introduce 1D electrocatalysts while highlighting advanced strategies and preparation methods for these different structured 1D electrocatalysts to improve ORR performance. Finally, we prospect the future development of 1D ORR electrocatalysts.

The elderly are particularly vulnerable to brain dysfunction after fracture surgery, but the mechanism underlying the cognitive decline due to anesthesia/surgery is not well understood. In this study, we observed hippocampus-dependent cognitive impairment in aged mice undergoing anesthesia and tibial fracture surgery, a common model of postoperative cognitive dysfunction in aged mice. We used Golgi staining and neuroelectrophysiological techniques to detect structurally and functionally impaired synaptic plasticity in hippocampal CA1 region of Postoperative cognitive dysfunction aged mice, respectively. Based on the ‘third party synapse’ hypothesis of astrocytes, we used glial fibrillary acidic protein to label astrocytes and found an increase in abnormal activation of astrocytes in the CA1 region of hippocampus. We hypothesize that abnormal astrocyte function is the driving force for impaired synaptic plasticity. So we used chemogenetic methods to intervene astrocytes. Injection of adeno-associated virus into the CA1 region of the hippocampus bilateral to aged mice resulted in the specific expression of the Gq receptor, a receptor specially designed to be activated only by certain drugs, within astrocytes. The results of novel object recognition and conditioned fear experiments showed that CNO activation of astrocyte Gq pathway could improve the learning and memory ability and the synaptic plasticity of Postoperative cognitive dysfunction aged mice was also improved. The results of this study suggest that activation of the Gq pathway in astrocytes alleviates Postoperative cognitive dysfunction induced by anesthesia and surgery in aged mice.

ABSTRACT Ethylene regulates mycelial growth, primordium formation, and postharvest mushroom maturation and senescence in the white button mushroom, Agaricus bisporus. However, it remains unknown how ethylene is detected by the mushroom. In this study, we found that two hybrid histidine kinases in the mushroom, designated AbETR1 and AbETR2, showed domain structures similar to those of plant ethylene receptors. The transmembrane helices of AbETR1 and AbETR2 were expressed in yeast cells and showed ethylene-binding activities. Mushroom strains with downregulated expressions of AbETR1 and AbETR2 showed reduced sensitivity to the ethylene inhibition of mycelial growth, ethylene regulation of their own synthesis, postharvest mushroom maturation, and senescence and expression of maturation- and senescence-related genes. Therefore, AbETR1 and AbETR2 are expected to be biologically functional ethylene receptors and exhibit a different mode of action from that of the receptors of plants. Here, we fill gaps in the knowledge pertaining to higher fungus ethylene receptors, discover a novel mode of action of ethylene receptors, confirm ethylene as a novel fungal hormone, and provide a facilitated approach for preventing the maturation and senescence of postharvest button mushrooms. IMPORTANCE Ethylene regulates diverse physiological activities in bacteria, cyanobacteria, fungi, and plants, but how to perceive ethylene by fungi only remains unknown. In this study, we identify two biologically functional ethylene receptors in the basidiomycete fungus Agaricus bisporus, which fills the gaps of deficient fungal ethylene receptors. Furthermore, we found that decreased expression of the ethylene receptors facilitates preventing the maturation and senescence of postharvest button mushrooms, indicating that the two fungal ethylene receptors positively regulate the ethylene response, in contrast to that in plants.

ABSTRACT Pyolysin (PLO) is secreted by Trueperella pyogenes as a water-soluble monomer after forming transmembrane β-barrel channels in the cell membrane by binding cholesterol. Two significantly conserved residues at domain 1 of PLO are mutated, which provides novel evidence of a relationship between conformational change and interaction with the cell membrane and uncovers the pore formation mechanism of the cholesterol-dependent cytolysin (CDC) family. Moreover, PLO is a special member of the CDCs, which the percentage of sequence identities between PLO and other CDC members is from 31% to 45%, while others are usually from 40% to 70%. It is important to understand that at very low sequence identities, models can be different in the pathogenic mechanisms of these CDC members, which are dedicated to a large number of Gram-positive bacterial pathogens. Our studies, for the first time, located and mutated two different highly conserved structural sites in the primary structure critical for PLO structure and function that proved the importance of these sites. Together, novel and repeatable observations into the pore formation mechanism of CDCs are provided by our findings. IMPORTANCE Postpartum disease of dairy cows caused by persistent bacterial infection is a global disease, which has a serious impact on the development of the dairy industry and brings huge economic losses. As one of the most relevant pathogenic bacteria for postpartum diseases in dairy cows, Trueperella pyogenes can secrete pyolysin (PLO), a member of the cholesterol-dependent cytolysin (CDC) family and recognized as the most important toxin of T. pyogenes. However, the current research work on PLO is still insufficient. The pathogenic mechanism of this toxin can be fully explored by changing the local structure and overall function of the toxin by a previously unidentified single point mutation. These studies lay the groundwork for future studies that will explore the contribution of this large family of CDC proteins to microbial survival and human disease.

The role of the inositol 1, 4, 5-trisphosphate receptor (IP3R) in hippocampal neuronal apoptosis and cognitive dysfunction induced by sevoflurane is currently unclear. Therefore, in this study, we investigated the role of the IP3R in endoplasmic reticulum (ER) stress and hippocampal neuronal apoptosis induced by sevoflurane in aged rats and isolated hippocampal neurons using both in vivo and in vitro experiments, including bioinformatics, functional enrichment analysis, gene set enrichment analysis, hematoxylin, and eosin staining, TUNEL assay, flow cytometry, western blot analysis and transmission electron microscopy. Furthermore, behavioral assessment was performed with the Morris water maze test. We identified 232 differentially expressed genes induced by sevoflurane exposure, including 126 upregulated genes and 106 downregulated genes. Sevoflurane exposure caused cognitive impairment and neuronal injury, and increased p-IP3R levels and ER stress. An IP3R inhibitor, 2-APB, suppressed these changes, while an IP3R agonist, FK-506, aggravated these changes. Together, these findings suggest that sevoflurane exposure causes marked cognitive dysfunction in aged rats and neuronal injury in isolated hippocampal neurons by activating the IP3R and inducing cytoplasmic calcium overload, thereby resulting in ER stress and hippocampal neuronal apoptosis.GRAPHICAL ABSTRACT

It is widely documented that social capital can benefit individual and social development. However, research on the roles of internet technologies in cultivating social capital has not arrived at a consensus. This article aims to understand the effects of online social interactions (OSIs) on generalized trust and prosocial civic engagement, two essential forms of social capital, with a longitudinal study and structural equation model. Fixed-effect model estimations consistently show that OSIs can effectively increase levels of generalized trust in China. Also, trust in parents is used as an alternative dependent variable to provide a comparative analysis. The mechanisms of these two sources of trust are different, and insignificant effects of OSIs on trust in parents are found to implicitly support the causal link between OSIs and trust in strangers. In this study, we implemented a series of robustness checks, for example, examinations using only the netizens as a sample and cross-sectional methods. Furthermore, we explored the relationship between OSIs and prosocial civic engagement (charitable donation), a behavior form of social capital. The SEM results suggested that charitable behaviors were positively affected by OSIs and generalized trust played a positive mediating role. Additionally, significant positive direct and indirect effects through the generalized trust in OSIs were found on prosocial behaviors.

Owing to their autonomous movement characteristics, micromotors can perform various tasks that traditional drug‐delivery carriers fail to perform. The development of adaptable, highly efficient, functional micromotors has become the primary research goal in biomedical field. Micromotors modified with polymers can exhibit strong propulsion ability and unique performance in a complex biological environment, facilitating their application to various complex environments. Herein, different micromotor designs based on natural and synthetic polymers are discussed and the role of polymers in the structure and performance of micromotors is focused on. Overall, the polymer‐modified micromotors can facilitate new developments, particularly in biomedical applications, such as drug delivery and biological detection.

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disease of the intestine. Dysbiosis, especially the expansion of facultative anaerobic Enterobacteriaceae, maybe the main pathogenesis of UC. Gegen Qinlian decoction (GD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun, is commonly used to treat UC and has shown an excellent effect on inducing disease remission. However, the role of GD in regulating gut microbiota has not been fully clarified. Herein, we investigated the potential effect of GD on inhibiting the expansion of Enterobacteriaceae and further explored the potential mechanism of this action. Our study demonstrated that GD remarkably reduced body weight loss of colitis mice, shortening of colon length, and inflammation of the colon. Peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling was inactivated in colitis colon tissue, and the abundance of Escherichia coli (E. coli, family of Enterobacteriaceae) in colonic contents and the concentration of lipopolysaccharide (LPS) in colonic tissue were significantly upregulated after DSS-treatment. Notably, GD administration can result in the activation of PPAR-γ and inactivation of iNOS, which lead to the reduction of nitrate, the inhibition of E. coli, and less production of LPS. Combined GD with PPAR-γ antagonist, the effect of GD on the treatment of UC was weakened, and effectless in inhibiting the expansion of Enterobacteriaceae. Therefore, GD ameliorates UC by preventing a dysbiotic expansion of potentially pathogenic E. coli by reducing nitrate levels in the lumen through activating PPAR-γ signaling.

Essentially, wound healing is a complicated physiological process in which there exists an interaction between the organism’s immune regulation and antimicrobial therapy. However, multiple drug-resistant bacteria implicated in chronic non-healing wound are not merely impeding the cure process, but more than a burden on economic and social development. Due to the inefficiency of conventional antibiotics, nanomedicine in the biomedical field is emerging as a prospective anti-infective therapy method. Herein, a novel nano-drug with antibacterial and anti-inflammatory characteristics was synthesized by loading Rutin into zeolitic imidazolate framework-8 (ZIF-8), abided by the principle of electrostatic adsorption. The synthetic ZIF-8 loaded Rutin (ZIF-8@Rutin) was affirmed by testing the changes in the diameter and chemical functional group. Interestingly, the ladened Rutin afforded nanocomposite with anti-inflammatory activity by its antioxidant capacity for the polarization of macrophages. Further, the prepared ZIF-8@Rutin exhibited highly effective antibacterial activity against Escherichia coli and Staphylococcus aureus in vitro. More importantly, it could shorten the infected wound healing process and alleviate the inflammation around the wound in vivo. Also, ZIF-8@Rutin had acceptable cytocompatibility. Thus, ZIF-8@Rutin may become a multifunctional nanomedicine with anti-inflammatory and bactericidal properties to promote infected wound healing.

Herein, a controlled synthesis route with precise growth tunability of perovskite Cs4PbBr6 micro‐flakes and micro‐flowers with embedded CsPbBr3 nanocrystals (Cs4PbBr6@CsPbBr3) is elaborated. This room‐temperature synthesis scheme initiates the nucleation and growth process of the majority crystalline phase of Cs4PbBr6 with a few CsPbBr3 impurities as confirmed by the X‐ray diffraction studies. The microstructures and shape control are further investigated by scanning electron microscopy (SEM) and the high‐resolution transmission electron microscopy (HRTEM). The results depict hexagonal Cs4PbBr6 micro‐flakes with embedded CsPbBr3 that can spontaneously self‐assemble into micro‐flowers with varying external conditions. This approach gives access to perovskite semiconductors with both structural and excellent optical properties by correlating the dimensionality with quantum confinement effects. The photoluminescence, absorption, and time‐resolved photoluminescence spectroscopy confirm that such as‐synthesized materials exhibit bright green emission with an optical bandgap of 2.3 eV. Lasing action is obtained under an excitation wavelength of 400 nm at 10 K where the light intensity and lifetime are examined at different pump fluences. There exist two linear regions corresponding to spontaneous emission and lasing, respectively. The lower lasing threshold of 27 μJ cm−2 per pulse is obtained and the corresponding Q factor is estimated to be 1090.

Summary: Utilization of naturally occurring resources to construct functional catalytic materials is significantly important, and facile and environmental-benign strategies are highly desired to afford the materials having a specific structure and good catalytic activity. Herein, we reported an innovative deep eutectic solvent (DES)-assisted strategy to synthesize zirconium phytate with a thin nanosheet structure (denoted as Zr-Phy-DES) using plant-originated phytic acid (PhyA) as the renewable building block. This strategy was eco-friendly and adjustable owing to the designability of DESs. The Zr-Phy-DES as an acidic catalyst showed high activity on two important biomass transformations, i.e., dehydration of carbohydrates and Meerwein-Ponndorf-Verley reduction of ethyl levulinate. Interestingly, Zr-Phy-DES showed higher catalytic performance than the zirconium phytates prepared in ethylene glycol and N,N-dimethylformamide, confirming the advantage of DESs for preparing functional materials. Notably, the unique feature of this proposed strategy is that renewable catalysts are prepared in an environmental-benign solvent for efficiently catalyzing biomass transformation.

Abstract Objective Iron and steel industry workers are exposed to high levels of inhalable dust particles that contain various elements, including metals, and cause occupational lung diseases. We aim to assess the relationship between occupational dust exposure, systemic inflammation, and spirometric decline in a cohort of Chinese iron and steel workers. Methods We studied 7513 workers who participated in a Health Surveillance program at Wugang Institute for Occupational Health between 2008 and 2017. Time-weighted exposure intensity (TWEI) of dust was quantified based on self-reported dust exposure history, the experience of occupational hygienists, and historical data of dust exposure for workers with certain job titles. A linear mixed-effects model was used for association analyses. Results The average annual change of lung function was − 50.78 ml/year in forced expiratory volume in 1 s (FEV1) and − 34.36 ml/year in forced vital capacity (FVC) in males, and − 39.06 ml/year in FEV1 and − 26.66 ml/year in FVC in females. Higher TWEI prior to baseline was associated with lower longitudinal measurements of FEV1 and FVC but not with their decline rates. Higher WBC and its differential at baseline were associated with lower longitudinal measurements and a more rapid decline of FEV1 and FVC in a dose-dependent monotonically increasing manner. Moreover, the increase of WBC and its differential post-baseline was also associated with a more rapid decline of FEV1 and FVC. Conclusions Our findings support the important role of systemic inflammation in affecting the temporal change of lung function in iron and steel industry workers.

Abstract The acquisition of 2–50 Hz low-frequency vibration signals is of great significance for the monitoring researches on engineering seismology, bridges & dams, oil & gas exploration, etc. A multi-cantilever beam low-frequency FBG acceleration sensor is proposed against the low sensitivity that predominates in the low-frequency vibration measurement by FBG acceleration sensors. Structural parameters of the sensor is subjected to simulation analysis and optimization design using the ANSYS software; the real sensor is developed based on the simulation results in the following manner: Three rectangular of the cantilever beams are evenly arranged around the mass block at 120°to improve the sensitivity and alleviate the transverse crosstalk of sensor; in the end, a performance test is performed on the sensor. According to the research findings, the sensor, whose natural frequency is approximately 64 Hz, is applicable for monitoring the low-frequency vibration signals within the range 16–54 Hz. The sensor sensitivity is approximately $$87.955\,{\text{pm/m}}\;{\text{s}}^{ - 2}$$ 87.955 pm/m s - 2 , the linearity being greater than 99%, the transverse interference immunity being lower than 2.58%, and the dynamic range being up to 86 dB. The findings offer a reference for developing sensor of the same type and further improving the sensitivity of fiber optic acceleration sensor.

Abstract Background Breast cancer is the fastest-growing cancer among females and the second leading cause of female death. At present, targeted antibodies combined with hyperthermia locally in tumor has been identified as a potential combination therapy to combat tumors. But in fact, the uniformly deep distribution of photosensitizer in tumor sites is still an urgent problem, which limited the clinical application. We reported an HER2-modified thermosensitive liposome (immunoliposome)-assisted complex by reducing gold nanocluster on the surface (GTSL-CYC-HER2) to obtain a new type of bioplasma resonance structured carrier. The HER2 decoration on the surface enhanced targeting to the breast cancer tumor site and forming irregular, dense, "petal-like" shells of gold nanoclusters. Due to the good photothermal conversion ability under near-infrared light (NIR) irradiation, the thermosensitive liposome released the antitumor Chinese traditional medicine, cyclopamine, accompanied with the degradation of gold clusters into 3–5 nm nanoparticles which can accelerate renal metabolism of the gold clusters. With the help of cyclopamine to degrade the tumor associated matrix, this size-tunable gold wrapped immunoliposome was more likely to penetrate the deeper layers of the tumor, while the presence of gold nanoparticles makes GTSL-CYC-HER2 multimodal imaging feasible. Results The prepared GTSL-CYC-HER2 had a size of 113.5 nm and displayed excellent colloidal stability, photo-thermal conversion ability and NIR-sensitive drug release. These GTSL-CYC-HER2 were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. As for the in vivo experiments, compared to the other groups, under near-infrared laser irradiation, the temperature of GTSL-CYC-HER2 rises rapidly to the phase transition temperature, and released the cyclopamine locally in the tumor. Then, the released cyclopamine destroyed the stroma of the tumor tissue while killing the tumor cells, which in turn increased the penetration of the liposomes in deep tumor tissues. Moreover, the GTSL-CYC-HER2 enhanced the performance of multimodal computed tomography (CT) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. Conclusions This optically controlled biodegradable plasmonic resonance structures not only improves the safety of the inorganic carrier application in vivo, but also greatly improves the anti-tumor efficiency through the visibility of in vivo CT and PT imaging, as well as chemotherapy combined with hyperthermia, and provides a synergistic treatment strategy that can broaden the conventional treatment alone. Graphic Abstract

Abstract Objectives The aim of this study was to evaluate the postoperative analgesia effect of ultrasound-guided single popliteal sciatic nerve block for calcaneal fracture. Methods A total of 120 patients scheduled for unilateral open reduction and internal fixation of calcaneal fracture were enrolled in this prospective randomized study. Patients in group B received ultrasound-guided single popliteal sciatic nerve block after operation, but Patients in group A did not. All patients received patient-controlled intravenous analgesia (PCIA) after operation. The time to initiation of PCIA, the time of first pressing the analgesia pump, duration of analgesia pump use and the total number of times the patient pressed the analgesia pump were recorded. The time of rescue analgesia and the adverse reactions were recorded. Pain magnitude of the patients immediately after discharge from operating room (T1), and at 4th (T2), 8th (T3), 12th (T4), 16th (T5), 24th (T6) and 48th (T7) h after the operation were assessed with visual analog scale (VAS). In addition, patient, surgeon and nurse satisfaction were recorded. Results The VAS scores at T2 ~ T5, the time of rescue analgesia and the adverse reactions, the total number of times the patient pressed the analgesia pump were significantly declined in group B (p

Proteases have a fundamental role in maintaining physiological homeostasis, but their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis. This striking importance plus superior biological recognition and catalytic performance of proteases, combining with the excellent physicochemical characteristics of nanomaterials, results in enzyme-activated nano-drug delivery systems (nanoDDS) that perform theranostic functions in highly specific response to the tumor phenotype stimulus. In the tutorial review, the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types, on the premise of summarizing the structure and function of each protease. Subsequently, the incomplete matching and recognition between enzyme and substrate, structural design complexity, volume production, and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics. This will facilitate the promotion of nanotechnology in the management of malignant tumors.

Abiotic–biotic hybrid systems are promising to trap light for fuel and chemical transformation with high efficacy and selectivity. This study reports a coenzyme-mediated supramolecular host-guest semibiological system combining supramolecular catalyst and enzymes for solar alcohol splitting.

Meningococcal meningitis caused by Neisseria meningitidis is a reportable infectious disease in China, due to the high incidence of meningitis in the era before the availability of vaccines. The disease incidence was markedly reduced after meningococcal vaccination was introduced in the 1980s. Currently, there are polysaccharide, conjugate, and combined vaccine formulations against meningococcal meningitis in the Chinese market, almost all of which are produced by domestic manufacturers. It is necessary to further enhance national meningococcal surveillance to improve the level of prevention and control of meningococcus. However, the immune efficacy and persistence of immunity of vaccines should be monitored. More importantly, additional investments should be made to develop serogroup B meningococcal vaccines.

The dysbiosis of gut flora and its metabolites plays important roles in the progression of hyperlipidemia (HL), and some bioactive peptides are available for HL treatment. In this study, we aimed to isolate an active peptide (AR-9) from active peptides of E. sinensis (APE) and determine whether AR-9 could improve many symptoms of a HL rat induced by a high-fat diet (HFD) by modulating gut flora and its metabolites. Above all, AR-9 was derived from APE using ion-exchange chromatography, and its structure was deconstructed by Fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectroscopy, and UHPLC-Q-Exactive-Orbitrap MS. Then, an HFD-induced HL model in SD rats was established and used to clarify the regulatory effects of AR-9 (dose of 3 mg/kg) on HL. Normal diet–fed rats were taken as the control. The plasma samples and liver were harvested for biochemical and histopathological examinations. 16S rRNA gene sequencing and untargeted metabolomics were sequenced to assess changes in gut flora and its metabolites from rat fecal samples. Finally, Spearman’s correlation analysis was used to assess the relationship between lipid-related factors, gut flora, and its metabolites so as to evaluate the mechanism of AR-9 against HL. The results of the separation experiments showed that the amino acid sequence of AR-9 was AVFPSIVGR, which was a fragment of the actin protein from Blattaria insects. Moreover, HFD rats developed exaltation of index factors, liver lipid accumulation, and simple fibrosis for 8 weeks, and the profiles of gut flora and its metabolites were significantly altered. After treatment, AR-9 decreased the levels of lipid factors in plasma and the extent of liver damage. 16S rRNA gene sequencing results indicated that AR-9 significantly increased the relative abundance of beneficial bacteria Bacteroidetes and reduced the relative abundance of the obesity-associated bacteria Firmicutes. Furthermore, AR-9 changed gut microbiota composition and increased the relative abundance of beneficial bacteria: Lactobacillus, Clostridium, Dehalobacterium, and Candidatus arthromitus. Fecal metabolomics showed that the pathway regulated by AR-9 was “arginine biosynthesis”, in which the contents were citrulline and ornithine. Spearman’s correlation analysis revealed that two metabolites (ornithine and citrulline) showed significantly negative correlations with obesity-related parameters and positive correlations with the gut genera (Clostridium) enriched by AR-9. Overall, our results suggested interactions between gut microbial shifts and fecal amino acid/lipid metabolism and revealed the mechanisms underlying the anti-HL effect of AR-9. The abovementioned results not only reveal the initial anti-HL mechanism of AR-9 but also provide a theoretical basis for the continued development of AR-9.

PurposeTo identify the most important factors affecting physician decision-making regarding antiplatelet therapy.MethodsWe retrospectively gathered data from minor ischemic stroke patients with NIHSS scores ≤ 5 within 72 h of onset from 2010 to 2018. The population was divided into four groups by initial antiplatelet therapy: aspirin monotherapy (AM), dual antiplatelet therapy with aspirin and a loading dose of clopidogrel (clopidogrel loading dose of 300 mg on the first day; DAPT-ALC), dual antiplatelet therapy with aspirin and no loading dose of clopidogrel (clopidogrel 75 mg daily, no loading dose; DAPT-AUC), and clopidogrel monotherapy (CM).ResultsIn total, 1,377 patients were included in the analysis (excluding patients who accepted thrombolytic drugs, participated in other clinical trials, or had not used antiplatelet drugs). The mean ± S.D. age was 62.0 ± 12.7 years; 973 (70.7%) patients were male. The four groups were AM (n = 541, 39.3%), DAPT-ALC (n = 474, 34.4%), DAPT- AUC (n = 301, 21.9%), and CM (n = 61, 4.4%). Patients receiving antiplatelet monotherapy were older than those receiving dual antiplatelet therapy (63.7–65.7 vs. 59.6–61.4 years), and the median initial systolic blood pressure level was higher in the DAPT-ALC group than in the other groups (all P < 0.05). Patients under 75 years old with an admission SBP lower than 180 mmHg, a history of AM, coronary heart disease, no history of intracerebral hemorrhage, stroke onset occurring after guideline recommendations were updated (the year of 2015), onset-to-arrival time within 24 h, and initial NIHSS score ≤ 3 were more likely to take DAPT-ALC than AM. Compared with DAPT-ALC, DAPT-AUC was associated with an initial SBP level lower than 180 mmHg, a history of smoking, hypertension, no history of ICH, previous treatment with antihypertensives, and onset year after the recommendations were updated.ConclusionsMany factors affect doctors' decisions regarding antiplatelet therapy, especially guidelines, age, admission SBP level, and hypertensive disease.

Pyroptosis is a relatively newly discovered programmed cell death accompanied by an inflammatory response. In the classical view, pyroptosis is mediated by caspases-1,-4,-5,-11 and executed by GSDMD, however, recently it was demonstrated that caspase-3 and-8 also participate in the process of pyroptosis, by cleaving GSDMD/E and GSDMD respectively. Different from autophagy and apoptosis, many pores are formed on the cell membrane during pyroptosis, which makes the cell membrane lose its integrity, eventually leading to the release of cytokines interleukin(IL)-1β and IL-18. When the body is infected with pathogens or exposed to some stimulations, pyroptosis could play an immune defense role. It is found that pyroptosis exists widely in infectious and inflammatory respiratory diseases such as acute lung injury, bronchial dysplasia, chronic obstructive pulmonary disease, and asthma. Excessive pyroptosis may accompany airway inflammation, tissue injury, and airway damage, and induce an inflammatory reaction, leading to more serious damage and poor prognosis of respiratory diseases. This review summarizes the relationship between pyroptosis and related respiratory diseases.

We investigated the protective effect of young plasma on anesthesia- and surgery-induced cognitive impairment and the potential underlying mechanism using bioinformatics, functional enrichment analysis, gene set enrichment analysis, Golgi-Cox staining, dendritic spine analysis, immunofluorescence assay, western blot analysis, and transmission electron microscopy. Furthermore, we performed behavioral assessments using the open field test, the novel object recognition test, and the Morris water maze test. We identified 1969 differentially expressed genes induced by young plasma treatment, including 800 upregulated genes and 1169 downregulated genes, highlighting several enriched biological processes (signal release from synapse, postsynaptic density and neuron to neuron synapse). Anesthesia- and surgery-induced cognitive impairment in aged rats was comparatively less severe following young plasma preinfusion. In addition, the decreased levels of synapse-related and tyrosine kinase B/extracellular signal-regulated protein kinase/cyclic adenosine monophosphate response element-binding protein (TrkB/ERK/CREB) signaling pathway-related proteins, dendritic and spine deficits, and ultrastructural changes were ameliorated in aged mice following young plasma preinfusion. Together, these findings suggest that young plasma reverses anesthesia- and surgery-induced cognitive impairment in aged rats and that the mechanism is associated with the activation of the TrkB/ERK/CREB signaling pathway and improvement in hippocampal synaptic plasticity.

BackgroundPrevious prediction models of osteosarcoma have not focused on survival in patients undergoing surgery, nor have they distinguished and compared prognostic differences among amputation, radical and local resection. This study aimed to establish and validate the first reliable prognostic nomogram to accurately predict overall survival (OS) after surgical resection in patients with osteosarcoma. On this basis, we constructed a risk stratification system and a web-based nomogram.MethodsWe enrolled all patients with primary osteosarcoma who underwent surgery between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. In patients with primary osteosarcoma after surgical resection, univariate and multivariate cox proportional hazards regression analyses were utilized to identify independent prognostic factors and construct a novel nomogram for the 1-, 3-, and 5-year OS. Then the nomogram's predictive performance and clinical utility were evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultThis study recruited 1,396 patients in all, with 837 serving as the training set (60%) and 559 as the validation set (40%). After COX regression analysis, we identified seven independent prognostic factors to develop the nomogram, including age, primary site, histological type, disease stage, AJCC stage, tumor size, and surgical method. The C-index indicated that this nomogram is considerably more accurate than the AJCC stage in predicting OS [Training set (HR: 0.741, 95% CI: 0.726–0.755) vs. (HR: 0.632, 95% CI: 0.619–0.645); Validation set (HR: 0.735, 95% CI: 0.718–0.753) vs. (HR: 0.635, 95% CI: 0.619–0.652)]. Moreover, the area under ROC curves, the calibration curves, and DCA demonstrated that this nomogram was significantly superior to the AJCC stage, with better predictive performance and more net clinical benefits.ConclusionThis study highlighted that radical surgery was the first choice for patients with primary osteosarcoma since it provided the best survival prognosis. We have established and validated a novel nomogram that could objectively predict the overall survival of patients with primary osteosarcoma after surgical resection. Furthermore, a risk stratification system and a web-based nomogram could be applied in clinical practice to assist in therapeutic decision-making.

Cotton is an important source of fiber. The precise and intelligent management of cotton fields is the top priority of cotton production. Many intelligent management methods of cotton fields are inseparable from cotton boll localization, such as automated cotton picking, sustainable boll pest control, boll maturity analysis, and yield estimation. At present, object detection methods are widely used for crop localization. However, object detection methods require relatively expensive bounding box annotations for supervised learning, and some non-object regions are inevitably included in the annotated bounding boxes. The features of these non-object regions may cause misjudgment by the network model. Unlike bounding box annotations, point annotations are less expensive to label and the annotated points are only likely to belong to the object. Considering these advantages of point annotation, a point annotation-based multi-scale cotton boll localization method is proposed, called MCBLNet. It is mainly composed of scene encoding for feature extraction, location decoding for localization prediction and localization map fusion for multi-scale information association. To evaluate the robustness and accuracy of MCBLNet, we conduct experiments on our constructed cotton boll localization (CBL) dataset (300 in-field cotton boll images). Experimental results demonstrate that MCBLNet method improves by 49.4% average precision on CBL dataset compared with typically point-based localization state-of-the-arts. Additionally, MCBLNet method outperforms or at least comparable with common object detection methods.

Bifacial dye-sensitized solar cells (DSCs), harvesting light from both front and rear sides, are potential high-efficiency photovoltaic devices with broad application environments. The electrocatalytic counter electrodes (CEs) of bifacial DSCs could determine the light-harvesting from the rear side and the charge collection of solar cells through electrocatalytic processes. As a result, high-activity and high-transparency CEs are essential for bifacial DSCs. Recently, novel CEs based on strong metal-support interaction (SMSI) have been proven to improve the catalysis and stability of the metal catalytic sites and induce great efficiency increase of bifacial DSCs. However, the contradiction between the transparency and conductivity of support is still a major challenge for the application of SMSI-based CEs on bifacial DSCs. Herein, we utilized a solution plasma (SP) method to introduce oxygen vacancies into a transparent MoOx support film. These SP-induced oxygen vacancies improved the conductivity of MoOx and the interaction between the metal Pt catalytic sites and support, thereby enhancing the catalytic activity and transparency of MoOx/Pt CEs. Consequently, the bifacial DSCs with MoOx/Pt CEs yielded a high efficiency of 7.56% and 6.41% with the front- and rear-side illumination, respectively. This impressive front-to-rear efficiency ratio of 85% indicates that the SP method has a positive effect in constructing high-performance CEs and other electrocatalytic materials based on the SMSI.

ObjectiveThe study was designed to explore the evolution of non-small cell lung cancer (NSCLC) management in the last 20 years.MethodsThe top 100 most-cited papers on NSCLC treatment were retrieved from the Web of Science Core Collection database. R and VOSviewer were used to extract bibliographic information, including the year of publication, countries/regions, institutions, authors, journals, keywords, impact factor, and total citations. The topic and type of papers were checked independently by authors. Bibliometric analysis was conducted and visualized with R, CiteSpace, Excel and VOSviewer to identify output dynamics, research forces, topics, hotspots, and frontiers in the field.ResultsThe average citation of each retrieved top 100 most-cited NSCLC management papers was 1,725 (range: 615-7,340). Fifty-seven corresponding authors were from the United States. This country contributed the most papers (n=76), followed by Germany (n=34), France (n=33), and South Korea (n=32). The top contributors were Paz-Ares L. (n=12) and Reck M. (n=12). The Memorial Sloan Kettering Cancer Center published the largest number of papers (n=20). There were two significant citation paths, indicating publications in medicine/medical/clinical journals primarily cited journals in molecular/biology/genetics fields, partly cited health/nursing/medicine fields. Top-cited papers mainly came from the New England Journal of Medicine (n=33, citations=80,427), followed closely by the Journal of Clinical Oncology (n=28, citations=32,408). “Chemotherapy” (n=36) was the keyword with the greatest frequency of co-occurrence. “Open-label” was the keyword with the strongest burst strength (=4.01), followed by “nivolumab” (=3.85), “blockade” (=2.86), and “efficacy” (=2.85).ConclusionsThe United States as a nation and the Memorial Sloan Kettering Cancer Center as an institute contributed the most to this field. The New England Journal of Medicine is the most eye-catching journal. Hotspots of NSCLC management have almost undergone an evolution from chemotherapy and radiotherapy to targeted therapy to immunotherapy. Molecular/biological/genetic fields become the main research base for NSCLC treatment. Immunotherapy and combination therapy are research frontiers.

Gut microbiota play a vital role in fish health homeostasis. Antibiotics are known to alter microbial community composition and diversity; however, the substantial effects of antibiotics upon the gut microbiome with respect to immune-related pathways in healthy fish remain unclear. Accordingly, here we explored the impact of two antibiotics on the intestinal health, immune response, microbiome dynamics, and transcriptome profiles of grass carp. A two-week feeding trial was carried out in which the basal diet was complemented with enrofloxacin (10 mg/kg) or florfenicol (10 mg/kg). The results showed that: (1) Enrofloxacin and florfenicol both induced intestinal oxidative stress and reduced the digestive enzyme activity of grass carp. (2) High-throughput sequencing of 16S rDNA revealed that enrofloxacin but not the florfenicol treatment influenced gut microbiota diversity in grass carp by shifting α/β-diversity with more abundant pathogens detected. (3) Transcriptome profiling demonstrated that florfenicol down-regulated the immune-related pathways of grass carp, and the network analysis revealed that IgA was negatively correlated with certain pathogens, such as Shewanella and Aeromonas. (4) Antibiotic-induced alternations of gut core microbes were revealed via immune-related transcripts, as were lower mRNA expression levels of mucosal-related genes. (5) Apoptosis and histopathological changes were detected in the enrofloxacin- and florfenicol-treated groups compared with the control group. Overall, administering antibiotics will promote oxidative stress, cause intestinal flora dysbiosis, inhibit the mucosal immune system, and induce apoptosis in grass carp.

Both moist heatwaves (HWs) and heavy precipitation events (HP) have increased in both frequency and magnitude over China in recent decades. However, the relationship between HW and HP and changes in the lagged coincidence of events (i.e., the occurrence of an HP event several days after an HW event, noted HWHP) remain unknown. We show here that HWHP events account for nearly one-third of HP events over China in summer, with high values in North China, Northeast China, and the East arid zone. HWHP events assessed using the heat index and the wet-bulb temperature methods increased by 45.25 and 23.97% from 1961 to 2019, respectively. These concurrent HWHP events tend to be spatially clustered, and the areas affected simultaneously have grown significantly. The increase in HW is the major driver of these changes in HWHP events, except in the western arid zone and North China. Our findings provide an understanding of the spatiotemporal changes in HWHP events over China and their implications for disaster mitigation.

BackgroundThe capacity to distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on morphological features obtained by conventional echocardiography is limited. We investigated the global myocardial work of the left ventricle in two types of hypertrophies using the non-invasive myocardial work index (NMWI).MethodsConventional echocardiography was performed on 107 subjects with preserved left ventricular ejection fraction (LVEF ≥ 50%), who comprised patients with HCM (n = 40), H-LVH (n = 35), and healthy people with normal blood pressure and left ventricular structure (n = 32). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters based on pressure-strain loops, including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were evaluated in three groups. Multivariate discriminant analysis and receiver operating characteristic (ROC) curve were used to evaluate the incremental value of NMWI for distinguishing HCM from H-LVH.ResultsCompared to the control group, GWI and GCW were significantly lower in HCM patients (P < 0.05), whereas GWI was significantly higher in H-LVH patients. GWW was higher and GWE was significantly decreased in both HCM and H-LVH patients than in the control group (P < 0.05). Multivariate discriminant analysis and ROC curve revealed that the inter-ventricular septum thickness (IVST)/left ventricular posterior wall thickness (LVPWT) and GCW were each able to distinguish HCM from H-LVH. The combination of IVST/LVPWT and GCW discriminated HCM and H-LVH with a higher predictive accuracy of 94.7%.ConclusionNMWI may provide additional information in evaluating the myocardial function in patients with HCM and H-LVH. Myocardial work combined with conventional echocardiography could improve the clinical diagnostic accuracy of distinguishing HCM and H-LVH.

The dried fruit of Amomum tsao-ko is well-known as a spice as well as a Chinese traditional herb. This study aimed to identify the bioactive constituents in the powder of methanol extract from Amomum tsao-ko (PMEAT) and to evaluate the hypoglycemic and antioxidant effects of PMEAT, in vitro and in vivo. We identified 36 phytochemicals in PMEAT by employing HPLC-MS/MS. PMEAT solution was found to have potent α-glucosidase-inhibiting activity (IC50, 0.145 mg/mL) in vitro, twice as strong as that of acarbose (IC50, 0.273 mg/mL). To investigate the hypoglycemic activity of PMEAT in vivo, we studied the impact of low-dose PMEAT (the addition of 100 mg/kg PMEAT to the mice diet) and high-dose PMEAT (200 mg/kg PMEAT addition) treatments in STZ-induced diabetic mice. After 6 weeks of intervention, significantly decreased fasting blood glucose (FBG) (p < 0.05), significantly decreased area under the curve (AUC) of the oral glucose tolerance test (p < 0.05), significantly decreased HOMA-IR (p < 0.05), and significantly increased HOMA-β (p < 0.05) were observed in the high-dose PMEAT group. Moreover, we performed an antioxidant activity experiment in vitro. The results showed that PMEAT had a strong ability to scavenge DPPH (IC50, 0.044 mg/mL) as well as ABTS free radicals (IC50, 0.040 mg/mL). In an animal experiment conducted on oxidative damage mice model which was induced by D-glucose and a high-fat diet, we observed significantly increased dismutase (SOD) (p < 0.01), glutathione (GSH) (p < 0.01), and glutathione peroxidase (GSH-Px) (p < 0.01) and significantly reduced malondialdehyde (MDA) and 8-ISO-prostaglandin-PGF2α (8-ISO-PGF2α), after treatment with PMEAT for 90 days. In conclusion, this study reveals the therapeutic potential of Amomum tsao-ko for the treatment of diabetes and helps us discover new antioxidant candidates from natural sources.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle paralysis, which is followed by degeneration of motor neurons in the motor cortex of the brainstem and spinal cord. The etiology of sporadic ALS (sALS) is still unknown, limiting the exploration of potential treatments. Ferroptosis is a new form of cell death and is reported to be closely associated with Alzheimer’s disease (AD), Parkinson’s disease (PD), and ALS. In this study, we used datasets (autopsy data and blood data) from Gene Expression Omnibus (GEO) to explore the role of ferroptosis and ferroptosis-related gene (FRG) alterations in ALS. Gene set enrichment analysis (GSEA) found that the activated ferroptosis pathway displayed a higher enrichment score, and the expression of 26 ferroptosis genes showed obvious group differences between ALS and controls. Using weighted gene correlation network analysis (WGCNA), we identified FRGs associated with ALS, of which the Gene Ontology (GO) analysis displayed that the biological process of oxidative stress was the most to be involved in. KEGG pathway analysis revealed that the FRGs were enriched not only in ferroptosis pathways but also in autophagy, FoxO, and mTOR signaling pathways. Twenty-one FRGs (NR4A1, CYBB, DRD4, SETD1B, LAMP2, ACSL4, MYB, PROM2, CHMP5, ULK1, AKR1C2, TGFBR1, TMBIM4, MLLT1, PSAT1, HIF1A, LINC00336, AMN, SLC38A1, CISD1, and GABARAPL2) in the autopsy data and 16 FRGs (NR4A1, DRD4, SETD1B, MYB, PROM2, CHMP5, ULK1, AKR1C2, TGFBR1, TMBIM4, MLLT1, HIF1A, LINC00336, IL33, SLC38A1, and CISD1) in the blood data were identified as target genes by least absolute shrinkage and selection operator analysis (LASSO), in which gene signature could differentiate ALS patients from controls. Finally, the higher the expression of CHMP5 and SLC38A1 in whole blood, the shorter the lifespan of ALS patients will be. In summary, our study presents potential biomarkers for the diagnosis and prognosis of ALS.

Based on ship navigational requirements and safety in foggy conditions and with a particular emphasis on avoiding ship collisions and improving navigational abilities, we constructed a fog navigation dataset along with a new method for enhancing foggy images and perceived visibility using a discriminant deep learning architecture and the EfficientNet neural network by replacing the SE module and incorporating a convolution block attention module and focal loss function. The accuracy of our model exceeded 95%, which meets the needs of an intelligent ship navigation environment in foggy conditions. As part of our research, we also determined the best enhancement algorithm for each type of fog according to its classification.

Although the use of detergents in thermal proteome profiling (TPP) has become a common practice to identify membrane protein targets in complex biological samples, surprisingly, there is no proteome-wide investigation into the impacts of detergent introduction on the target identification performance of TPP. In this study, we assessed the target identification performance of TPP in the presence of a commonly used non-ionic detergent or a zwitterionic detergent using a pan-kinase inhibitor staurosporine, our results showed that the addition of either of these detergents significantly impaired the identification performance of TPP at the optimal temperature for soluble target protein identification. Further investigation showed that detergents destabilized the proteome and increased protein precipitation. By lowering the applied temperature point, the target identification performance of TPP with detergents is significantly improved and is comparable to that in the absence of detergents. Our findings provide valuable insight into how to select the appropriate temperature range when detergents are used in TPP. In addition, our results also suggest that the combination of detergent and heat may serve as a novel precipitation-inducing force that can be applied for target protein identification.

At present, deep-sea enzymes are a research hotspot. In this study, a novel copper–zinc superoxide dismutase (CuZnSOD) was successfully cloned and characterized from a new species of sea cucumber Psychropotes verruciaudatus (PVCuZnSOD). The relative molecular weight of the PVCuZnSOD monomer is 15 kDa. The optimum temperature of PVCuZnSOD is 20 °C, and it maintains high activity in the range of 0–60 °C. It also has high thermal stability when incubated at 37 °C. PVCuZnSOD has a maximum activity of more than 50% in the pH range of 4–11 and a high activity at pH 11. In addition, PVCuZnSOD has strong tolerance to Ni2+, Mg2+, Ba2+, and Ca2+, and it can withstand chemical reagents, such as Tween20, TritonX-100, ethanol, glycerol, isopropanol, DMSO, urea, and GuHCl. PVCuZnSOD also shows great stability to gastrointestinal fluid compared with bovine SOD. These characteristics show that PVCuZnSOD has great application potential in medicine, food, and other products.

Coffee (Coffea arabica L.) is one of the most consumed non-alcoholic beverages. To expand the coffee market and attract consumers to a diversity of coffee types, data on the nutritional potential of different coffee varieties are needed. The present study assessed the phytochemical constituents, i.e., total flavonoid content (TFC), total anthocyanin content (TAC), and total phenolic content (TPC), and the antioxidant activities of extracts from Bourbon coffee berries differing in color. Furthermore, the metabolome profiles of the four Bourbon berries, i.e., purple (PF), red (RF), orange (ORF), and yellow (YF), were explored. The results indicated that the TFC and TPC were significantly higher in RF (7.12 ± 0.96 and 9.01 ± 1.36 mg/g), followed by YF (6.54 ± 0.38 and 7.80 ± 0.10 mg/g), ORF (6.31 ± 0.15 and 7.20 ± 0.40 mg/g), and PF (4.66 ± 0.53 and 6.60 ± 1.10 mg/g). A UPLC-MS/MS analysis resulted in the identification of 579 metabolites belonging to 11 different compound classes. Of these, 317 metabolites were differentially accumulated in the four varieties. These differentially accumulated metabolites were majorly classified as flavonoids, organic acids, phenolics, and amino acids and derivatives. Based on the metabolome profiles, we discuss the major compounds in each Bourbon coffee variety and highlight their nutritional and health potentials. These findings will serve as a foundation for the promotion of each variety and provide useful information for coffee improvement programs.

Underwater video object detection is a challenging task due to the poor quality of underwater videos, including blurriness and low contrast. In recent years, Yolo series models have been widely applied to underwater video object detection. However, these models perform poorly for blurry and low-contrast underwater videos. Additionally, they fail to account for the contextual relationships between the frame-level results. To address these challenges, we propose a video object detection model named UWV-Yolox. First, the Contrast Limited Adaptive Histogram Equalization method is used to augment the underwater videos. Then, a new CSP_CA module is proposed by adding Coordinate Attention to the backbone of the model to augment the representations of objects of interest. Next, a new loss function is proposed, including regression and jitter loss. Finally, a frame-level optimization module is proposed to optimize the detection results by utilizing the relationship between neighboring frames in videos, improving the video detection performance. To evaluate the performance of our model, We construct experiments on the UVODD dataset built in the paper, and select mAP@0.5 as the evaluation metric. The mAP@0.5 of the UWV-Yolox model reaches 89.0%, which is 3.2% better than the original Yolox model. Furthermore, compared with other object detection models, the UWV-Yolox model has more stable predictions for objects, and our improvements can be flexibly applied to other models.

Leaf traits can reflect plant photosynthetic capacity, resource utilization strategy and adaptability to the environment. However, whether species’ leaf traits are tightly related to the functioning of their community and how that relationship varies with environmental gradients remain largely unexplored. We measured 6 leaf traits, including petiole fineness (PF), specific leaf area (SLA), leaf area (LA), leaf length–width ratio (LLWR), leaf nitrogen content (LN) and leaf phosphorus content (LP), of 733 populations (415 species) of 19 woody angiosperm communities in the eastern Qinghai–Tibetan Plateau across multiple climatic zones or vegetation types. Through meta-analysis and relative importance analysis, the relationship between leaf traits of species and their community dominance and its change with environments were analyzed. The results showed that species dominance was correlated positively with their LA and LP, suggesting that species with high light interception and resource utilization capacity can easily become dominant species in woody angiosperm communities. Along the altitudinal gradient, the effect of PF and SLA on species dominance increased and changed significantly in their pattern, from positive or nonsignificant in temperate forests to negative in alpine and subalpine shrubs, suggesting that increasing petiole mechanical support and lamina protection cost is a dominant leaf growth strategy in stressful high-altitude environments. Our findings demonstrate that the demand for efficient light acquisition and/or utilization and species adaptability or tolerance to specific environmental stress are key mechanisms by which leaf traits govern community composition and functioning.

Uterine myomas affect 70% of women of reproductive age, potentially impacting their fertility and health. Manual film reading is commonly used to identify uterine myomas, but it is time-consuming, laborious, and subjective. Clinical treatment requires the consideration of the positional relationship among the uterine wall, uterine cavity, and uterine myomas. However, due to their complex and variable shapes, the low contrast of adjacent tissues or organs, and indistinguishable edges, accurately identifying them in MRI is difficult. Our work addresses these challenges by proposing an instance segmentation network capable of automatically outputting the location, category, and masks of each organ and lesion. Specifically, we designed a new backbone that facilitates learning the shape features of object diversity, and filters out background noise interference. We optimized the anchor box generation strategy to provide better priors in order to enhance the process of bounding box prediction and regression. An adaptive iterative subdivision strategy ensures that the mask boundary details of objects are more realistic and accurate. We conducted extensive experiments to validate our network, which achieved better average precision (AP) results than those of state-of-the-art instance segmentation models. Compared to the baseline network, our model improved AP on the uterine wall, uterine cavity, and myomas by 8.8%, 8.4%, and 3.2%, respectively. Our work is the first to realize multiclass instance segmentation in uterine MRI, providing a convenient and objective reference for the clinical development of appropriate surgical plans, and has significant value in improving diagnostic efficiency and realizing the automatic auxiliary diagnosis of uterine myomas.

The trade-offs between key functional traits in plants have a decisive impact on biomass production. However, how precipitation and nutrient deposition affect the trade-offs in traits and, ultimately, productivity is still unclear. In the present study, a mesocosm experiment was conducted to explore the relationships between biomass production and the aboveground and belowground key functional traits and their trade-offs under changes in precipitation and nutrient depositions in Leymus chinensis, a monodominant perennial rhizome grass widespread in the eastern Eurasian steppe. Our results showed that moisture is the key factor regulating the effect of nitrogen (N) and phosphorus (P) deposition on increased biomass production. Under conditions of average precipitation, water use efficiency (WUE) was the key trait determining the biomass of L. chinensis. There were obvious trade-offs between WUE and leaf area, specific leaf area, leaf thickness, and leaf dry matter. Conversely, under increasing precipitation, the effect of restricted soil water on leaf traits was relieved; the key limiting trait changed from WUE to plant height. These findings indicate that the shift of fundamental traits of photosynthetic carbon gain induced by precipitation under N and P deposition is the key ecological driving mechanism for the biomass production of typical dominant species in semi-arid grassland.

The space cable-driven continuous manipulator (SCCM) has a slender structure, ultra-high degrees of freedom, and a low mass, which make it suitable for equipment inspection and maintenance operations in an unstructured and limited space environment. In this paper, the SCCM including the cable network and plenty of joint links was deeply modeled. Firstly, the mapping relationship between the cable-driving space, joint space, and task space of the SCCM was studied, and the complete kinematic relationship of the SCCM was established. Secondly, the stiffness components of the SCCM are discussed, and the stiffness modeling method of each part is given. Finally, the Cartesian space equivalent stiffness model of the end was established. Then, a dynamic co-modeling method of Matlab + Adams is proposed, which greatly improved the modeling efficiency while ensuring the modeling accuracy. Finally, based on the stiffness model, the end stiffness characteristics of a specific configuration were analyzed, and the influence of the cable tension on the stiffness and frequency of the manipulator was analyzed. Based on the dynamic co-modeling, the task trajectory dynamics’ simulation analysis and space slit crossing experiment were carried out, which verified that the designed SCCM can meet the needs of slit crossing.

The 2195 aluminum alloy is widely used in cryogenic storage tanks for space vehicles, where it can reach a temperature of 20 K. In order to explore the reasons for the increased strength of 2195 aluminum alloys at cryogenic temperatures, uniaxial tensile tests were conducted in the range of 20 K–298 K. Tensile fracture was observed. In addition, the microstructures under different temperatures were observed using EBSD (electron back-scattered diffraction) and TEM (transmission electron microscopy) techniques, and the dislocation density of the material was quantitatively characterized using the modified Williamsone–Hall method based on XRD (X-ray diffraction) analysis. The results indicated that the ultimate strength increased at an increasing rate with the temperature decrease, while the elongation increase was insignificant. The fracture’s surface exhibited that dimple characteristics seemed to be unapparent while the quantity of tearing ridges was enhanced by the temperature decrease. Meanwhile, the fracture mode changed from ductile to brittle fracture. The microdeformation degree revealed by KAM images showed an aggravating trend, and the deformation tended to be more uniform. The increasingly enhanced dislocation density quantitatively revealed by the modified Williamsone–Hall method also proved this and that the increase in dislocations had a similar trend to that of tensile strength, which was furtherly revealed by TEM images. This indicated that the more regions are involved in deformation, the more dislocations are generated in the material during deformation, resulting in an increase in strength at cryogenic temperatures.

Phenols are important readily available synthetic building blocks and starting materials for organic synthetic transformations, which are widely found in agrochemicals, pharmaceuticals, and functional materials. The C–H functionalization of free phenols has proven to be an extremely useful tool in organic synthesis, which provides efficient increases in phenol molecular complexity. Therefore, approaches to functionalizing existing C–H bonds of free phenols have continuously attracted the attention of organic chemists. In this review, we summarize the current knowledge and recent advances in ortho-, meta-, and para-selective C–H functionalization of free phenols in the last five years.

Abstract The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients. Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising, yet greatly challenging, to reverse postoperative immunosuppression. Here, an injectable hierarchical gel matrix, composed of dual lipid gel (DLG) layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios, was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy. The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide (GO) nanoparticles. GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages (TAMs) and promote an immunogenic tumor microenvironment. The inner layer, loaded with anti-CD47 antibody (aCD47), could maintain the gel state for a much longer time, enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory protein α (SIRPα) pathway for a long-term antitumor effect. In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape, thereby boosting the systemic immune responses.

Abstract Background Aroma is one the most crucial inherent quality attributes of fruit. ‘Ruixue’ apples were selected from a cross between ‘Pink Lady’ and ‘Fuji’, a later ripening yellow new cultivar. However, there is little known about the content and composition of aroma compounds in ‘Ruixue’ apples or the genetic characters of ‘Ruixue’ and its parents. In addition, the metabolic pathways for biosynthesis of aroma volatiles and aroma-related genes remain poorly understood. Results Volatile aroma compounds were putatively identified using gas chromatography-mass spectrometry (GC–MS). Our results show that the profile of volatile compounds changes with ripening. Aldehydes were the dominant volatile compounds in early fruit development, with alcohols and esters increasing dramatically during maturation. On the basis of a heatmap dendrogram, these aroma compounds clustered into seven groups. In ripe fruit, esters and terpenoids were the main aroma volatiles in ripening fruit of ‘Pink Lady’ and ‘Fuji’ apples, and they included butyl 2-methylbutanoate; propanoic acid, hexyl ester; propanoic acid, hexyl ester; hexanoic acid, hexyl ester; acetic acid, hexyl ester and (Z, E)-α-farnesene. Interestingly, aldehydes and terpenoids were the dominant volatile aroma compounds in ripening fruit of ‘Ruixue’, and they mainly included hexanal; 2-hexenal; octanal; (E)-2-octenal; nonanal and (Z, E)-α-farnesene. By comparing the transcriptome profiles of ‘Ruixue’ and its parents fruits during development, we identified a large number of aroma-related genes related to the fatty acid, isoleucine and sesquiterpenoid metabolism pathways and transcription factors that may volatile regulate biosynthesis. Conclusions Our initial study facilitates a better understanding of the volatile compounds that affect fruit flavour as well as the mechanisms underlying differences in flavour between ‘Ruixue’ and its parents.