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Bees, one of the most vital pollinators in the ecosystem and agriculture, are currently threatened by neonicotinoids. To explore the molecular mechanisms of neonicotinoid toxicity to bees, the different binding modes of imidacloprid, thiacloprid, and flupyradifurone with nicotinic acetylcholine receptor (nAChR) α1β1 and cytochrome P450 9Q3 (CYP9Q3) were studied using homology modeling and molecular dynamics simulations. These mechanisms provided a basis for the design of compounds with a potential low bee toxicity. Consequently, we designed and synthesized a series of triazinone derivatives and assessed their bioassays. Among them, compound 5anot only displayed substantially insecticidal activities against Aphis glycines(LC50= 4.40 mg/L) and Myzus persicae(LC50= 6.44 mg/L) but also had low toxicity to Apis mellifera. Two-electrode voltage clamp recordings further confirmed that compound 5ainteracted with the M. persicaenAChR α1 subunit but not with the A. melliferanAChR α1 subunit. This work provides a paradigm for applying molecular toxic mechanisms to the design of compounds with low bee toxicity, thereby aiding the future rational design of eco-friendly nicotinic insecticides.

Purpose: Describe and analyze the trends of thyroid cancer incidence and mortality in Guangzhou, explore the potential influencing factors, and provide evidence for the government to formulate prevention and treatment measures. Methods: Incident and death cases of thyroid cancer were retrieved from the Guangzhou cancer registry. The joinpoint regression models were used to estimate the incidence and mortality trends. Age-period-cohort models were used to estimate the age, period, and cohort effects on the time trends. Grey correlation analysis was performed to explore possible connections between thyroid cancer and social factors. Results: A total of 15,955 new cases of thyroid cancer were registered in Guangzhou during 2004–2018, the age-standardized incidence rate (ASIR) of thyroid cancer increased from 4.29/105in 2004 to 22.36/105in 2018, with the average annual percentage change (AAPC) of 13.40%. The overall increase can be attributed to the increase in the incidence of papillary thyroid carcinoma (PTC), which was dominated by tumors <2 cm. The ASIR was higher in women (16.12/105) compared to men (5.46/105), and young and middle-aged individuals had higher incidence rates than older people. The number of thyroid cancer deaths registered between 2010 and 2018 was 356, and the age-standardized mortality rates (ASMRs) were stable (approximately 0.42/105). Men’s ASMR (0.34/105) and women’s (0.49/105) were similar, and those 60 and older had greater mortality. The period and cohort relative risks showed an overall increasing trend. Furthermore, there was a strong positive correlation between the ASIRs and social determinants. Conclusions: During the study period, the incidence rate of thyroid cancer among young and middle-aged people in Guangzhou showed a rapidly increasing trend, and the mortality was relatively stable. In the future, more effective preventive measures should be taken for this age group to reduce the burden of disease and avoid overdiagnosis.

In this study, a spatial multi‐directional local calibration method is proposed for 3D displays, which is used to accurately measure and adjust the local parameter deviation of large‐sized 3D displays at various angles. The experiment shows this spatial multi directional local compensation can improve the yield of 3D displays, enhance imaging quality, and reduce crosstalk.

The eye tracking‐based autostereoscopic 3D display provides a large viewing angle, low crosstalk, and large depth perception 3D image experience without using any 3D eyeglasses. However, accurate and fast eye position detection and tracking are still challenging. This study presents an accurate and fast eye positioning algorithm by reducing the computational load of stereo matching and stereo rectification in stereo vision. The accuracy of distance measurement is up to 98.46%. The processing time needed to calculate the distance between the target and the cameras is less than 0.012s.

Oncolytic peptides represent promising novel candidates for anticancer treatments. In our efforts to develop oncolytic peptides possessing both high protease stability and durable anticancer efficiency, three rounds of optimization were conducted on the first-in-class oncolytic peptide LTX-315. The robust synthetic method, in vitro and in vivo anticancer activity, and anticancer mechanism were investigated. The D-type peptides represented by FXY-12 possessed significantly improved proteolytic stability and sustained anticancer efficiency. Strikingly, the novel hybrid peptide FXY-30, containing one FXY-12 and two camptothecin moieties, exhibited the most potent in vitro and in vivo anticancer activities. The mechanism explorations indicated that FXY-30 exhibited rapid membranolytic effects and induced severe DNA double-strand breaks to trigger cell apoptosis. Collectively, this study not only established robust strategies to improve the stability and anticancer potential of oncolytic peptides but also provided valuable references for the future development of D-type peptides-based hybrid anticancer chemotherapeutics.

Photocatalytic coupling technologies have emerged as popular strategies to increase the treatment efficiency of dye-containing wastewater. Herein, the Z-scheme Co3O4/BiOBr heterojunction (Z-CBH) was constructed and developed as a photocatalytic peroxydisulfate (PDS) activator for the degradation of high-concentration Rhodamine B (RhB). Multiple testing techniques were employed to confirm the formation of Z-CBHs. When 0.1 g·L–1of Z-CBH20 and 1.0 mmol·L–1of PDS were added simultaneously under simulated sunlight irradiation, the RhB degradation efficiency could approach 91.3%. Its reaction rate constant (0.01231 min–1) was much beyond the sum of those in the Z-CBH20/light system (0.00436 min–1) and the PDS/light system (0.0062 min–1). h+, •OH, •O2–, SO4•–, and 1O2were detected as the dominant reactive species for RhB degradation. The potential mechanism of photocatalytic PDS oxidation was proposed. The possible intermediates were determined by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry assisted with density functional theory and Fukui theory. The possible degradation pathways of RhB degradation were put forward. The toxicological properties of RhB and its intermediates were evaluated by quantitative structure–activity relationship prediction. This work will not only provide a reference for developing photocatalytic persulfate activators but also gain an insight into the degradation pathways of RhB and the toxicity of its intermediates.

Pilots use their senses and training to generate situational awareness (SA). They then use this SA to make sound aeronautical decisions. Autonomous vehicles, by contrast, cannot rely on pilot expertise in off‐nominal situations. They must rely on their onboard sensors to build SA of the environment. As these sensors degrade, it is hypothesized that a point exists where the SA generated by these sensors is inadequate to allow the autonomous vehicle to make sound aeronautical decisions. In previous work, a point was defined based on broad assumptions within a modeling and simulation environment (i.e., the error within each sensor was known and not random). This research used a larger data set that contained random errors within the sensors. The data was then used to build predictive equations through a Monte Carlo simulation in the same simulation environment as previous work. While the data showed there was a statistically significant relationship between the error values in each sensor and the fused distance value, the resulting predictive equations were not able to provide adequate SA to make sound aeronautical decisions. This research highlights multiple issues the test and evaluation community will face when trying to develop new techniques for the verification and validation of autonomous systems.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situform AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50= 3.5 μM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 μM, better than fluconazole (17.2% at 1 μM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

Endothelial dysfunction, a central hallmark of cardiovascular pathogenesis in diabetes mellitus, is characterized by impaired endothelial nitric oxide synthase (eNOS) and NO bioavailability. However, the underlying mechanisms remain unclear. Here in this study, we aimed to identify the role of calmodulin (CaM) in diabetic eNOS dysfunction. Human umbilical vein endothelial cells and murine endothelial progenitor cells (EPCs) treated with high glucose (HG) exhibited downregulated CaM mRNA/protein and vascular endothelial growth factor (VEGF) expression with impeded eNOS phosphorylation and cell migration/tube formation. These perturbations were reduplicated in CALM1-knockdown cells but prevented in CALM1-overexpressing cells. EPCs from type 2 diabetes animals behaved similarly to HG-treated normal EPCs, which could be rescued by CALM1-gene transduction. Consistently, diabetic animals displayed impaired eNOS phosphorylation, endothelium-dependent dilation, and CaM expression in the aorta, as well as deficient physical interaction of CaM and eNOS in the gastrocnemius. Local CALM1gene delivery into a diabetic mouse ischemic hindlimb improved the blunted limb blood perfusion and gastrocnemius angiogenesis, and foot injuries. Diabetic patients showed insufficient foot microvascular autoregulation, eNOS phosphorylation, and NO production with downregulated CaM expression in the arterial endothelium, and abnormal CALM1transcription in genome-wide sequencing analysis. Therefore, our findings demonstrated that downregulated CaM expression is responsible for endothelium dysfunction and angiogenesis impairment in diabetes, and provided a novel mechanism and target to protect against diabetic endothelial injury.

During hot environment work tasks with whole-body enclosed anti-bioaerosol suit, the combined effect of heavy sweating and exhaled hot humid air may cause the N95 medical respirator to saturate with water/sweat (i.e., water-blocking).

The concept of triboelectric nanogenerator (TENG)-based fibrous air filters, in which the electroactive fibers are ready to enhance the electrostatic adsorption by sustainable energy harvesting, is appealing for long-term respiratory protection and in vivo real-time monitoring. This effort discloses a self-reinforcing electroactivity strategy to confer extreme alignment and refinement of the electrospun poly(lactic acid) (PLA) nanofibers, significantly facilitating formation of electroactive phases (i.e., β-phase and highly aligned chains and dipoles) and promotion of polarization and electret properties. It endowed the PLA nanofibrous membranes (NFMs) with largely increased surface potential and filtration performance, as exemplified by efficient removal of PM0.3and PM2.5(90.68 and 99.82%, respectively) even at the highest airflow capacity of 85 L/min. With high electroactivity and a well-controlled morphology, the PLA NFMs exhibited superior TENG properties triggered by regular respiratory vibrations, enabling 9.21-fold increase of surface potential (−1.43 kV) and nearly 68% increase of PM0.3capturing (94.3%) compared to those of conventional PLA membranes. The remarkable TENG mechanisms were examined to elaborately monitor the personal respiration characteristics, particularly those triggered large and rapid variations of output voltages like coughing and tachypnea. Featuring desirable biocompatibility and degradability, the self-powered PLA NFMs permit promising applications in the fabrication of ecofriendly air filters toward high-performance purification and intelligent monitoring.

Due to the coupled transformations between metal ions with variable valence states, manganese ferrite (MnFe2O4) is regarded as an efficient catalyst in a heterogeneous Fenton-like system for the degradation of organic contaminants. In this work, the magnetic nanoscale MnFe2O4was synthesized via a simple hydrothermal method and characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and vibrating sample magnetometer (VSM). Results on the degradation tests indicated a high catalytic ability of MnFe2O4nanocrystals to activate hydrogen dioxide (H2O2) to degrade active dye rhodamine B (RhB). Moreover, the RhB degradation process in the MnFe2O4-H2O2Fenton-like system followed a Behnajady–Modirshahla–Ghanbery (BMG) kinetic model. The catalytic conditions, including catalyst dosage, RhB concentration, H2O2dosage, solution pH and reaction temperature, had essential effects on RhB degradation efficiency and BMG kinetic parameters. The process optimization of RhB degradation was designed by central composite design (CCD) under response surface methodology (RSM). A mathematic model of the quadratic polynomial was established for the fitting analysis of RhB degradation, which was significant and reliable by the analysis of variance (ANOVA). Based on the programmed prediction, the optimum parameters for RhB degradation in the MnFe2O4–H2O2system were determined as 2 of solution pH, 19.6 mmol·L−1of H2O2dosage, 2.0 g·L−1of catalyst dosage and 180 min of reaction time. Under these optimum conditions, the predicted and experimental values of RhB degradation efficiency were 99.42% and 98.17%, respectively.

To discover fungicides with novel targets, a series of N-acyl-1,2,3,4-tetrahydroquinoline (NATHQ) derivatives were designed and synthesized by linking the active substructure NATHQ moiety in aspernigerin with the O-benzyl oxime-ether scaffold in commercial agrochemicals. Target compound structures were identified using proton and carbon-13 nuclear magnetic resonance spectroscopies and high-resolution mass spectrometry. Preliminary bioassays indicated that at 40 mg/L, some target compounds exhibited moderate to considerable in vitro fungicidal activities against Rhizoctonia solaniand Botrytis cinerea. In particular, compound 3jexhibited higher fungicidal activities both in vitro (EC50= 0.733 mg/L) and in vivo (EC50= 15.2 mg/L) against R. solanithan the commercial fungicide prochloraz; therefore, it should be a promising fungicide candidate against rice sheath blight. Additionally, compound 3jexhibited good laccase inhibitory activity (73.2% at 200 mg/L). Molecular docking revealed that the bis-cyano-oxime-ether moiety of compound 3jexhibited an excellent binding mode with the laccase target protein and could be used as a lead compound for developing laccase inhibitors. The structural features of these NATHQ derivatives will provide inspiration for developing laccase inhibitors and discovering more effective fungicides to control agricultural diseases.

Poly(lactic acid) (PLA)-based nanofibrous membranes (NFMs) hold great potential in the field of biodegradable filters for air purification but are largely limited by the relatively low electret properties and high susceptibility to bacteria. Herein, we disclosed a facile approach to the fabrication of electroactive and antibacterial PLA NFMs impregnated with a highly dielectric photocatalyst. In particular, the microwave-assisted doping (MAD) protocol was employed to yield Zn-doped titanium dioxide (Zn-TIO), featuring the well-defined anatase phase, a uniform size of ∼65 nm, and decreased band gap (3.0 eV). The incorporation of Zn-TIO (2, 6, and 10 wt %) into PLA gave rise to a significant refinement of the electrospun nanofibers, decreasing from the highest diameter of 581 nm for pure PLA to the lowest value of 264 nm. More importantly, dramatical improvements in the dielectric constants, surface potential, and electret properties were simultaneously achieved for the composite NFMs, as exemplified by a nearly 94% increase in surface potential for 3-day-aged PLA/Zn-TIO (90/10) compared with that of pure PLA. The well regulation of morphological features and promotion of electroactivity contributed to a distinct increase in the air filtration performance, as demonstrated by 98.7% filtration of PM0.3with the highest quality factor of 0.032 Pa–1at the airflow velocity of 32 L/min for PLA/Zn-TIO (94/6), largely surpassing pure PLA (89.4%, 0.011 Pa–1). Benefiting from the effective generation of reactive radicals and gradual release of Zn2+by Zn-TIO, the electroactive PLA NFMs were ready to profoundly inactivate Escherichia coliand Staphylococcus epidermidis. The exceptional combination of remarkable electret properties and excellent antibacterial performance makes the PLA membrane filters promising for healthcare.

The methods and procedures within United States naval aviation to certify an aircraft safe for flight are well established. However, these methods and procedures are based on clearing a system that is operated or monitored by a human. A fully autonomous system will not have a human in or on the loop and will therefore require a new method for certifying it safe for flight. This paper details how to use run time assurance as the framework for a safety of flight certification of autonomous behavior within United States naval aviation. We present an aerial refueling task with run time assurance as use case for the framework for certification. Within the use case we then give more details on the mechanics of using RTA to enable autonomous functionality within naval aviation.

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n= 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed seven associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n= 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.

We consider optimization problems whose parameters are known only approximately, based on noisy samples. In large-scale applications, the number of samples one can collect is typically of the same order [...]

Wheat is one of the major food crops in the world. Functional validation of the genes in increasing the grain yield of wheat by genetic engineering is essential for feeding the ever-growing global population. This study investigated the role of ABP7, a bHLH transcription factor from maize involved in kernel development, in regulating grain yield-related traits in transgenic wheat. Molecular characterization showed that transgenic lines HB123 and HB287 contained multicopy integration of ABP7in the genome with higher transgene expression. At the same time, QB205 was a transgenic event of single copy insertion with no significant difference in ABP7expression compared to wild-type (WT) plants. Phenotyping under field conditions showed that ABP7over-expressing transgenic lines HB123 and HB287 exhibited improved grain yield-related traits (e.g., grain number per spike, grain weight per spike, thousand-grain weight, grain length, and grain width) and increased grain yield per plot, compared to WT plants, whereas line QB205 did not. In addition, total chlorophyll, chlorophyll a, chlorophyll b, and total soluble sugars were largely increased in the flag leaves of both HB123 and HB287 transgenic lines compared to the WT. These results strongly suggest that ABP7 positively regulates yield-related traits and plot grain yield in transgenic wheat. Consequently, ABP7can be utilized in wheat breeding for grain yield improvement.

Background: To evaluate the methodological and reporting quality of published meta-analyses (MAs) in four major gastrointestinal endoscopic journals, and identify the predicted factors for high quality. Methods: A systematic search was performed in PubMed to identify MAs from 1, January, 2016 to 31, December, 2020 in four major gastrointestinal endoscopic journals (including Digestive Endoscopy, Gastrointestinal Endoscopy, Surgical Endoscopy,and Endoscopy). We collected the characteristics of MAs after filtering unqualified articles, and assessed methodological and reporting qualities for eligible articles by AMSTAR tool and PRISMA checklist, respectively. Logistic regression was used for identifying predictive factors for high quality. Results: A total of 289 MAs were identified after screening by predefined inclusion and exclusion criteria. The scores (mean ± SD) of AMSTAR and PRISMA were 7.73 ± 1.11 and 22.90 ± 1.85, respectively. In PRISMA checklist, some items had less than 50% complete adherence, including item 2 (structured summary), items 5 (protocol and registration), items 12 and 19 (risk of bias in studies), item 27 (funding support). Item 1 (a priori design), item 4 (gray literature research), item 5 (list of included and excluded) were inferior to 50% adherence in AMSTAR tool. We found the predictive factors for high quality through logistic regression analysis: a priori design and funding support were associated with methodological quality. Protocol and registration influenced the methodological and reporting quality closely. Conclusion: In general, qualities on the methodology and the reporting of MAs published in the gastrointestinal endoscopic journals are good, but both of which still potentially need further improvement.

Objective: This study aims to construct and validate a predictable deep learning model associated with clinical data and multi-sequence magnetic resonance imaging (MRI) for short-term postoperative facial nerve function in patients with acoustic neuroma. Methods: A total of 110 patients with acoustic neuroma who underwent surgery through the retrosigmoid sinus approach were included. Clinical data and raw features from four MRI sequences (T1-weighted, T2-weighted, T1-weighted contrast enhancement, and T2-weighted-Flair images) were analyzed. Spearman correlation analysis along with least absolute shrinkage and selection operator regression were used to screen combined clinical and radiomic features. Nomogram, machine learning, and convolutional neural network (CNN) models were constructed to predict the prognosis of facial nerve function on the seventh day after surgery. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate model performance. A total of 1050 radiomic parameters were extracted, from which 13 radiomic and 3 clinical features were selected. Results: The CNN model performed best among all prediction models in the test set with an area under the curve (AUC) of 0.89 (95% CI, 0.84–0.91). Conclusion: CNN modeling that combines clinical and multi-sequence MRI radiomic features provides excellent performance for predicting short-term facial nerve function after surgery in patients with acoustic neuroma. As such, CNN modeling may serve as a potential decision-making tool for neurosurgery.

AbstractControlled incorporation of bioactive hydroxyapatite (HA) into poly(lactic acid) (PLA) signifies a promising approach to design and development of biomedical-adaptive materials. Here we unravel a microwave-assisted biomineralization approach to synthesis of HA nanowhiskers (HANWs), which were characterized by well-controlled diameter (∼30 nm) and length (80 − 120 nm), combined with a desirable calcium − phosphorus ratio (Ca/P) of 1.67. A high-shear liquid dispersion (HSLD) method that provided a combination of high pressure (up to 50 kPa) and high shear rate approaching 10000 s−1was established to fabricate homogeneous PLA/HANWs composites. In particular, upon incorporation of 30 wt % HANWs the tensile strength and elastic modulus of PLA-HA30 (76.7 MPa and 3.3 GPa) were elevated by 48% and 84% compared to those of pure PLA, respectively, as accompanied by a nearly 2-fold increase in the cell viability. This work paves a facile yet effective roadway to strong and osteoconductive PLA composites appealing for bone tissue repairing.

Increasing the planting density is one way to enhance grain production in maize. However, high planting density brings about growth and developmental defects such as barrenness, which is the major factor limiting grain yield. In this study, the barrenness was characterized in an association panel comprising 280 inbred lines under normal (67 500 plants ha–1, ND) and high (120 000 plants ha–1, HD) planting densities in 2017 and 2018. The population was genotyped using 776 254 single nucleotide polymorphism (SNP) markers with criteria of minor allele frequency >5% and <20% missing data. A genome-wide association study (GWAS) was conducted for barrenness under ND and HD, as well as the barrenness ratio (HD/ND), by applying a Mixed Linear Model that controls both population structure and relative kinship (Q+K). In total, 20 SNPs located in nine genes were significantly (P<6.44×10–8) associated with barrenness under the different planting densities. Among them, seven SNPs for barrenness at ND and HD were located in two genes, four of which were common under both ND and HD. In addition, 13 SNPs for the barrenness ratio were located in seven genes. A complementary pathway analysis indicated that the metabolic pathways of amino acids, such as glutamate and arginine, and the mitogen-activated protein kinase (MAPK) signaling pathway might play important roles in tolerance to high planting density. These results provide insights into the genetic basis of high planting density tolerance and will facilitate high yield maize breeding.

Laccase is a potential target for novel agricultural fungicide discovery. PMDD-5Ywas the first agent reported with high activity against laccase to control phytopathogenic fungi. Thirty-two novel agents containing cinnamaldehyde thiosemicarbazide were synthesized with PMDD-5Yas the lead compound, with most of the target compounds exhibiting excellent activity in vitro. Compound a2(EC50= 9.71 μg/mL) exhibited greater potency against Magnaporthe oryzaethan the commercial fungicide isoprothiolane (EC50= 18.62 μg/mL). The curative and protective effects of a2against M. oryzaeon rice were more than those of PMDD-5Y. Scanning electron microscopy indicated that a2could cause mycelial growth atrophy and malformation. Furthermore, a2(IC50= 0.18 mmol/L) showed higher activity against laccase than PMDD-5Y(IC50= 0.33 mmol/L) and cysteine (IC50= 0.30 mmol/L). Molecular docking analysis revealed the nature of interaction between these compounds and laccase. This research identified a novel laccase inhibitor a2as a fungicide candidate to control rice blast in agriculture.

Social behaviors and immunity can help termites defend against pathogenic infections, which require the consumption of plenty of energy. Phosphofructokinase (PFK) is a key rate-limiting enzyme in glycolysis (a carbohydrate metabolic pathway) that generates energy. However, how PFK-mediated energy metabolism influences social behaviors and immunity against pathogens in termites is unknown. Here, we investigated the impacts of the pfk gene and entomopathogenic fungus Metarhizium anisopliae (Metschnikoff) on social behaviors (locomotion and allogrooming) and immunity in the termite Reticulitermes chinensis Snyder. Our results showed that pfk gene silencing and fungal infection decreased the production of energy (ATP and NADH), impaired locomotion, weakened immunity (decreased immune gene expression and reduced antifungal activity) and reduced survival at the individual level in termites. Silencing of the pfk gene in nestmates caused lower allogrooming frequencies toward fungus-exposed termites. Downregulation of pfk significantly disrupted locomotion and decreased the survival of fungus-exposed termites placed with pfk-silenced nestmates compared to fungus-treated termites placed with gfp-silenced nestmates. Our findings illustrated that pfk-mediated dysfunctional energy metabolism disturbed social behaviors and immunity to defend against fungal infections in termites, which provides new insights into understanding the mechanisms of social behaviors and immunity in social insects.

Hammerstein structure is commonly used for describing nonlinear dynamic characteristics, and its identification is a basic premise of nonlinear system analysis and control. This paper investigates online identification methods for a class of Hammerstein nonlinear systems, which consists of a nonlinear memoryless element followed by a linear output-error subsystem. The unmeasurable noise-free output of the linear subsystem makes the model parameters cannot be directly estimated by traditional identification methods. To address this difficulty, by using a series of weighted particles to adaptively approximate the posterior probability density function of the unmeasurable noise-free output, this paper proposes a particle filter-based stochastic gradient algorithm. Moreover, to enhance the data utilization and estimation accuracy, a particle filter-based multi-innovation stochastic gradient algorithm is developed through the innovation expansion technique. The simulation results demonstrate that compared with the existing benchmark algorithms, the proposed algorithms need a little more computational time due to the introduction of the adaptive particle filter, but they have the improved identification accuracies. [ABSTRACT FROM AUTHOR]

•The feasibility of classification of husbandry pattern of yak meat is investigated by visible and near-infrared spectroscopy combined with chemometrics.•Meat from grazing or feedlot yaks were captured as unique fingerprints by Vis-NIR spectroscopy.•The partial least squares discriminant analysis performed better than the soft independent modeling of class analogies.•PLS-DA modeling in 400–2500 nm verified the feeding pattern of yak meat with the accuracy of 100%.

When subjected to a vessel collision in the presence of scour induced by wave-current or flood, a bridge can sustain more severe damage compared to the pristine bridge undergoing the same impact. Scouring diminishes the ultimate capacity of pile foundations and can result in local damage to piers and pile foundations post-collision. This study aimed to mitigate impact damage on a scoured steel reinforced concrete (RC) bridge by employing a concrete-filled steel tubular pier and increasing the pile foundation section area. Pendulum impact tests were conducted on four concrete-filled steel-tubular pier-pile foundation systems to study their impact behaviors with scour depth effects. Experimental results show that while the displacement at the top of the pier increases with scour depth, there is no observed local damage to the impacted pier, even at deep scour depths. Subsequently, an FE model of the steel RC bridge was developed to assess the local dynamic behavior and damage based on the validated model. The impact performance of the scoured bridge, reinforced with a concrete-filled steel tubular pier and an increased pile section area, was then evaluated. Compared to the pristine bridge, the pile foundation with scour is prone to yield under the same impact condition, especially at deep scour depths. The increased section area method significantly enhances impact performance and reduces potential local damage to pile foundations, even under deep scour conditions. Additionally, a concrete-filled steel tubular pier markedly improves impact behavior compared to a conventional RC bridge pier. These findings underscore the efficacy of structural enhancements in bolstering the resilience of bridges against vessel collisions in scour-prone environments.

A different regioselective three-component reaction of alkenes, oxygen sources, and hydroperoxides mediated by ammonium iodine to α-oxyperoxidates has been developed. Mechanistic studies demonstrated that regioselective radical addition and subsequent SN2 nucleophilic substitution were possible for the formation of products. In addition to the traditional pathway of SN2 reaction, that is, where nucleophiles attack the α-C atoms at the back side, an additional unusual transition configuration with the H2O molecule attacking the α-C atom at the front side was obtained.

The introduction of active groups of natural products into the framework of pesticide molecules is an effective approach for discovering active lead compounds, and thus has been widely used in the development of new agrochemicals. In this work, a novel series of 1,2,3,4-tetrahydroquinoline derivatives containing a pyrimidine ether scaffold were designed and synthesized by the active substructure splicing method. The new compounds showed good antifungal activities against several fungi. Especially, compound 4fhdisplayed excellent in vitroactivity against Valsa maliand Sclerotinia sclerotiorumwith EC50values of 0.71 and 2.47 μg/mL, respectively. 4fhhad slightly stronger inhibitory activity (68.08% at 50 μM) against chitin synthase (CHS) than that of polyoxin D (63.84% at 50 μM) and exhibited obvious curative and protective effects on S. sclerotiorumin vivo.Thus, 4fhcan be considered as a new candidate fungicide as a chitin synthase inhibitor. An accurate and reliable three-dimensional quantitative structure–activity relationship (3D-QSAR) model presented a useful direction for the further excogitation of more highly active fungicides. Molecular docking revealed that the conventional hydrogen bond mainly affected the binding affinity of 4fhwith chitin synthase. The present results will provide a guidance to discover potential CHS-based fungicides for plant disease control in agriculture.

Allergic rhinitis (AR) is a chronic inflammatory reaction by immunoglobulin E (IgE) mediators after individual contact with allergens. It affects 10–40% of the world’s population and reduces the quality of life. Long-term symptoms of rhinitis can cause inflammation to spread and trigger asthma, which can harm human health. Herein, we develop a Smart PeptIde defeNse (SPIN) web technique, which in situ constructs a peptide web, trapping IgE against AR. Two candidate SPINs, SPIN-1 and SPIN-2, are designed with different IgE-binding sequences. The SPIN-1 or SPIN-2 is able to bind to IgE and transform from nanoparticles into entangled nanofibers. In turn, the web of SPIN-1 or SPIN-2 acts as a long-term trap of IgE to prevent the IgE from binding to mast cells. SPIN-1 or SPIN-2 (10 mg/kg) is able to treat AR model Balb/c mice with high efficiency and reduced symptoms of rhinitis and inflammatory factors, even better than a first-line clinical drug, cetirizine (10 mg/kg). For example, the amount of IL-4 released in the AR group (185.5 ± 6.8 pg/mL) is significantly reduced after the treatment with SPIN-1 (70.4 ± 14.1 pg/mL), SPIN-2 (86.0 ± 9.3 pg/mL), or cetirizine (112.8 ± 19.3 pg/mL). More importantly, compared with the cetirizine group (1 day), the SPIN-1 or SPIN-2 group shows long-term therapeutic effects (1 week). The SPIN web technique shows the great potential for blocking IgE binding to mast cells in vivo, attenuating AR or other allergic reactions.

Chance constraints are an important modeling tool in stochastic optimization, providing probabilistic guarantees that a solution 'succeeds' in satisfying a given constraint. Although they control the probability of 'success,' they [...]

Graphical abstract:

In order to improve the anticorrosive performance of waterborne epoxy (WEP) coating, small amounts of polyaniline (PANI) were blended under ultrasonic irradiation to obtain PANI/WEP composite coatings with high dispersibility of PANI particles. The PANI/WEP composite coatings were characterized by Fourier transform infrared spectroscopy and field emission scanning electron microscopy. Their adhesive force level and hardness grade were tested based on the Chinese National Standard GB/T9286-1998 and GB/T6739-1996, respectively. These results indicated that, compared to the pristine WEP coating, the addition of PANI with suitable content could completely fill the micropores or microcracks and remarkably improve the hardness grade of composite coatings. The electrochemical impedance spectra and Tafel polarization curves revealed that the addition of PANI not only could increase the impedance arc, but also could increase the impedance modulus at low frequency. Then, the salt spray tests were employed to observe the anticorrosive performance of PANI/WEP composite coatings. Finally, the enhanced anticorrosive mechanism of WEP coating by the addition of small amounts of PANI was proposed and discussed. The addition of PANI with suitable content could play an important role of physical and chemical barriers to improve the anticorrosive performance of waterborne epoxy coating.

Sodium-ion batteries (SIBs) have shown great promise as an alternative to lithium-ion batteries (LIBs) due to abundant sodium resources. Accurate and universal state of charge (SOC) estimation is essential for building an effective battery management system (BMS) for these emerging batteries. However, traditional SOC estimation methods for LIBs cannot be directly applied to SIBs due to significant differences in charge–discharge mechanisms and electrochemical characteristics. To address challenges with SIBs, this study proposes a novel framework integrating deep learning models. The BiLSTM is implemented to learn patterns from current and voltage time series. Additionally, the N-BEATS network extracts high-level features without manual feature engineering to mitigate the low sensitivity of SOC to voltage. By combining strengths of both networks, the fused model enhances SOC prediction robustness. Specifically, the proposed model is trained under various operating conditions and evaluated on both training and untrained datasets. Experiments demonstrate the fused model reduces root mean square error (RMSE) by 11.24% and 74.44% compared to individual N-BEATS and BiLSTM networks. The SOC estimation achieves mean absolute error (MAE) and RMSE below 0.30% and 0.39%, respectively. This research can inform the development of effective BMS for practical applications of SIBs, paving the way to the application of the new battery type.

Advanced and aggressive prostate cancer (PCa) depends on glutamine for survival and proliferation. We have previously shown that inhibition of glutaminase 1, which catalyzes the rate-limiting step of glutamine catabolism, achieves significant therapeutic effect; however, therapy resistance is inevitable. Here we report that while the glutamine carbon is critical to PCa survival, a parallel pathway of glutamine nitrogen catabolism that actively contributes to pyrimidine assembly is equally important for PCa cells. Importantly, we demonstrate a reciprocal feedback mechanism between glutamine carbon and nitrogen pathways which leads to therapy resistance when one of the two pathways is inhibited. Combination treatment to inhibit both pathways simultaneously yields better clinical outcome for advanced PCa patients.

Laccase is a novel target for fungicides. We previously developed a new fungicide, 4-chlorocinnamaldehyde thiosemicarbazide (PMDD-5Y), as a laccase inhibitor. The introduction of active groups of natural products into the framework of a pesticide molecular structure is an effective method for discovering active lead compounds, and it has applications in the discovery of new pesticides. In this work, PMDD-5Y was selected as a lead compound, and we designed and synthesized a series of novel sulfonyl hydrazide derivatives containing the natural product scaffold 1,2,3,4-tetrahydroquinoline. The new compounds had antifungal activities against several fungi, especially Valsa maliand Sclerotinia sclerotiorum. One compound (4bl) displayed very good in vitroactivity against S. sclerotiorumand V. mali, with EC50values of 3.32 and 2.78 μg/mL, respectively. The results of an enzyme activity assay showed that 4bhhad the best inhibitory activity against laccase, with an EC50value of 14.85 μg/mL. This was more active than the lead compound PMDD-5Y and the positive control cysteine. Using a molecular docking method, we studied the binding mode of the title compounds with laccase. The structural features of these new laccase inhibitors as fungicides will advance research and impact the field of discovering more potent fungicides to control diseases in agriculture.

Objective: Smooth muscle cell (SMC) phenotypic switching is associated with development of a variety of occlusive vascular diseases. Paeonol has been reported to be involved in suppressing SMC proliferation. However, it is still unknown whether paeonol can regulate SMC phenotypic switching, and which eventually result in suppressing vasculogenesis.Methods: Murine left common carotid artery was injured by completely ligation, and paeonol was administrated by intraperitoneal injection. Hematoxylin and eosin (H&E) staining was performed to visualize vascular neointima formation. Rat aortic SMCs were used to determine whether paeonol suppresses cell proliferation and migration. And murine hind limb ischemia model was performed to confirm the function role of paeonol in suppressing vasculogenesis.Results: Complete ligation of murine common carotid artery successfully induced neointima formation. Paeonol treatment dramatically reduced the size of injury-induced neointima. Using rat aortic primary SMC, we identified that paeonol strongly suppressed cell proliferation, migration, and decreased extracellular matrix deposition. And paeonol treatment dramatically suppressed vasculogenesis after hind limb ischemia injury.Conclusion: Paeonol could regulate SMC phenotypic switching through inhibiting proliferation and migration of SMC, which results in inhibiting ischemia-induced vasculogenesis.

Cardia neuroendocrine cancer is a rare malignant tumor. The treatment regimens mainly refer to the small-cell lung cancer diagnosis and treatment guidelines and there is no standard treatment guideline specifically for neuroendocrine cancer. The use of albumin paclitaxel plus carboplatin combined with sintilimab for refractory cardia neuroendocrine carcinoma (NEC) has never been reported. This article reported a case that a 68-year-old man presented with belching without obvious reasons who was diagnosed with refractory cardia NEC by gastroscopy and pathological results. After failure of multi-line therapy including etoposide plus cisplatin as the first-line therapy, surufatinib plus toripalimab as the second-line therapy, FOLFIRI combined with bevacizumab as the third-line therapy, he received three cycles of albumin paclitaxel plus carboplatin combined with sintilimab as the fourth-line therapy and still obtained partial response of good efficiency. After the patient received this treatment regimen, the symptoms of dysphagia disappeared and the change trends of neuron-specific enolase were decreased. The computed tomography (CT) examination after three cycles of treatment was performed to show that the measured lesions have shrunk by more than 30% compared to the baseline CT. Additionally, there were no other adverse events such as nausea, vomiting, and diarrhea, except for grade III bone marrow suppression. At present, the patient is still being treated. This is the first case report that the albumin paclitaxel plus carboplatin combined with sintilimab has achieved good efficacy after failure of multi-line treatment of cardia NEC. It is very necessary to further explore the effectiveness and safety of this regimen in the treatment of NEC.

Graphene oxide (GO) featuring a two-dimensional (2D) sheetlike structure and extensive oxygen functionalities occupies indispensable research branches in polymer composites. Key to the property translation from GO nanosheets to host polymers is the proper exfoliation and controlled dispersion that are profoundly governed by the competitive evolution between GO–GO intersheet attractions and GO–polymer interfacial interactions. Here, a microwave-assisted synthetic approach was proposed to enable direct in situgrowth of carbon nanotubes (CNTs) at GO templates, engendering a minute-level and one-pot route to create three-dimensional (3D) hierarchical nanohybrids (GO@CNT). Featuring a unique 3D structure, the nanohybrids were homogeneously dispersed and properly exfoliated in racemic polylactide (PLA) blends, in clear contrast to microscale local aggregation of GO due to extensive intersheet attractions. Albeit present at an extremely low amount (0.05 wt %), GO@CNT significantly outperformed GO in terms of boosting PLA stereocomplexation, achieving distinct overall improvements in gas barrier performance (oxygen permeability coefficient as low as 0.25 × 10–15cm3cm cm–2s–1Pa–1) and mechanical properties (tensile strength of ∼70 MPa and Young’s modulus of ∼2 GPa) for stereocomplexed PLAs. This work affords elucidation of direct covalent functionalization of 2D nanosheets and property-by-morphology understanding in polymer composites, which may motivate further extension to other 2D/one-dimensional (1D) hierarchical hybrids in need for the fabrication of multifunctional polymer composites.

When ordinary wounds are infected, the skin's self-healing capacity declines; thus appropriate dressings with both antibacterial ability and healing ability for bacteria-associated wounds are indispensable. In this work, multifunctional chitin/ZnO composite hydrogels have been designed as an infected full-thickness skin wound-healing material. The hydrogels are fabricated by a facile one-pot strategy through the sequential addition of commercial ZnO powders into aqueous alkaline chitin solutions, crosslinking and regeneration. The regenerated nanoscale ZnO particles aggregate into microscale particles and are embedded in the chitin matrix with tight interactions, including hydrogen bonding and coordination interactions. The decoration of ZnO endows the chitin/ZnO composite hydrogels with excellent antibacterial activity against Escherichia coli(E. coli) and Staphylococcus aureus(S. aureus), with acceptable biocompatibility. More importantly, the chitin/ZnO composite hydrogels show an outstanding accelerated infectious full-thickness wound-healing performance with more fibroblast proliferation, more collagen deposition, and more neogenesis of the epithelium and granulation tissue. Therefore, it is expected that the chitin/ZnO composite hydrogels can serve as competitive skin wound dressings for the prevention and control of infections.

Uncontrolled hemorrhage is a major problem both in surgical intervention and after trauma. Herein, we design an in situconstructable peptide network, mimicking and participating in the native coagulation process for enhanced hemostasis and wound healing. The network consists of two peptides including C6KL, mimicking platelets and C6KG, mimicking fibrin. The C6KL nanoparticles could bind to the collagen at the wound site and transform into C6KL nanofibers. The C6KG nanoparticles could bind to GPIIb/IIIa receptors on the surface of activated platelets and transform into C6KG nanofibers. The in situformed peptide network could interwind platelets, fibrin and red blood cells, causing embolism at the wound site. In a lethal femoral artery, vein, and nerve cut model of rats, the amount of bleeding was reduced to 32.8% by C6KL and C6KG with chitosan/alginate. The biomimetic peptides show great clinical potential as trauma hemostatic agents.

Selective detection of multiple analytes in a compact design with dual-modality and theranostic features presents great challenges. Herein, we wish to report a coumarin-thiazolidine masked d-penicillamine based dual-modality fluorescent probe COU-DPA-1for selective detection, differentiation, and detoxification of multiple heavy metal ions (Ag+, Hg2+, Cu2+). The probe shows divergent fluorescence (FL) /circular dichroism (CD) responses viadivergent bond-cleavage cascade reactions (metal ion promoted C-S cleavage and hydrolysis at two distinctive cleavage sites): FL “turn-off” and CD “turn-on” for Ag+(no hydrolysis), FL “turn-on” and CD “turn-off” for Hg2+(imine hydrolysis), and FL “self-threshold ratiometric” and CD “turn-off” for excess Cu2+(lactone and imine hydrolysis), providing the first example of a fluorescence/CD dual-modality probe for multiple species with complimentary responses. Moreover, the bond-cleavage cascade reactions also lead to the formation of d-penicillamine heavy metal ion complexes for potential detoxification treatments.

To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN).A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 μmol/L (n= 98); Q2 group: 358.23 ± 14.03 μmol/L (n= 99); Q3 group: 405.50 ± 14.59 μmol/L (n= 98) and Q4 group: 499.14 ± 56.97μmol/L (n= 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan–Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes.During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN (P= 0.747) was shown in the Kaplan–Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621–2.992; P= 0.439), 1.518 (0.768–3.002; P= 0.230) and 1.411 (0.706–2.821; P= 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P= 0.652).No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.