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Abstract Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1β, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.

Abstract Highly integrated optoelectronic and photonic systems underpin the development of next-generation advanced optical and quantum communication technologies, which require compact, multiwavelength laser sources at the telecom band. Here, we report on-substrate vertical emitting lasing from ordered InGaAs/InP multi-quantum well core–shell nanowire array epitaxially grown on InP substrate by selective area epitaxy. To reduce optical loss and tailor the cavity mode, a new nanowire facet engineering approach has been developed to achieve controlled quantum well nanowire dimensions with uniform morphology and high crystal quality. Owing to the strong quantum confinement effect of InGaAs quantum wells and the successful formation of a vertical Fabry–Pérot cavity between the top nanowire facet and bottom nanowire/SiO2 mask interface, stimulated emissions of the EH11a/b mode from single vertical nanowires from an on-substrate nanowire array have been demonstrated with a lasing threshold of ~28.2 μJ cm−2 per pulse and a high characteristic temperature of ~128 K. By fine-tuning the In composition of the quantum wells, room temperature, single-mode lasing is achieved in the vertical direction across a broad near-infrared spectral range, spanning from 940 nm to the telecommunication O and C bands. Our research indicates that through a carefully designed facet engineering strategy, highly ordered, uniform nanowire arrays with precise dimension control can be achieved to simultaneously deliver thousands of nanolasers with multiple wavelengths on the same substrate, paving a promising and scalable pathway towards future advanced optoelectronic and photonic systems.

Abstract DNA polymerase theta (Polθ) is a DNA helicase-polymerase protein that facilitates DNA repair and is synthetic lethal with homology-directed repair (HDR) factors. Thus, Polθ is a promising precision oncology drug-target in HDR-deficient cancers. Here, we characterize the binding and mechanism of action of a Polθ helicase (Polθ-hel) small-molecule inhibitor (AB25583) using cryo-EM. AB25583 exhibits 6 nM IC50 against Polθ-hel, selectively kills BRCA1/2-deficient cells, and acts synergistically with olaparib in cancer cells harboring pathogenic BRCA1/2 mutations. Cryo-EM uncovers predominantly dimeric Polθ-hel:AB25583 complex structures at 3.0-3.2 Å. The structures reveal a binding-pocket deep inside the helicase central-channel, which underscores the high specificity and potency of AB25583. The cryo-EM structures in conjunction with biochemical data indicate that AB25583 inhibits the ATPase activity of Polθ-hel helicase via an allosteric mechanism. These detailed structural data and insights about AB25583 inhibition pave the way for accelerating drug development targeting Polθ-hel in HDR-deficient cancers.

Abstract Polymer-based circularly polarized luminescence (CPL) materials with the advantage of diversified structure, easy fabrication, high thermal stability, and tunable properties have garnered considerable attention. However, adequate and precise tuning over CPL in polymer-based materials remains challenging due to the difficulty in regulating chiral structures. Herein, visualized full-color CPL is achieved by doping red, green, and blue quantum dots (QDs) into reconfigurable blue phase liquid crystal elastomers (BPLCEs). In contrast to the CPL signal observed in cholesteric liquid crystal elastomers (CLCEs), the chiral 3D cubic superstructure of BPLCEs induces an opposite CPL signal. Notably, this effect is entirely independent of photonic bandgaps (PBGs) and results in a high g lum value, even without matching between PBGs and the emission bands of QDs. Meanwhile, the lattice structure of the BPLCEs can be reversibly switched via mechanical stretching force, inducing on-off switching of the CPL signals, and these variations can be further fixed using dynamic disulfide bonds in the BPLCEs. Moreover, the smart polymer-based CPL systems using the BPLCEs for anti-counterfeiting and information encryption have been demonstrated, suggesting the great potential of the BPLCEs-based CPL active materials.

BackgroundMultiple Chronic Diseases (MCD) are the co-occurrence of two or more chronic conditions within an individual. Compared to patients with a single chronic disease, those with MCD face challenges related to polypharmacy, which increases the risk of adverse drug events, side effects, and drug–drug interactions. Understanding the specific medication preferences of patients with MCD is crucial to optimize treatment plans and enhance treatment safety.ObjectiveThis study aims to evaluate the medication preferences among patients with multiple chronic diseases in rural areas of an eastern province of China.MethodsA discrete choice experiment (DCE) was used to measure patients’ medication preferences. According to literature research, expert panel discussions, and in-depth patient interviews, we identified six attributes: monthly out-of-pocket cost, onset speed of action, adverse effects, whether it is covered by health insurance, origin of medications, and types of medications. The conditional logit models (CLM) and mixed logit models (MIXL) were used to evaluate the choice data. Willingness to pay (WTP) was used to reflect the monetary value that patients were willing to pay or receive reimbursement after changes in different attribute levels.ResultsA total of 956 respondents were included in the analysis. Of which, 68.62% were female, with an average age of 68 years, and 65.89% had a Body Mass Index (BMI) greater than or equal to 24. Statistical significance was observed for all attributes (p

BackgroundThe study aimed to examine the association between the systemic immune-inflammation index (SII), a contemporary metric of systemic inflammatory response, and biological aging, which are closely interconnected processes.MethodsThis cross-sectional study utilized 10 cycles of data from the NHANES database spanning from 1990 to 2018. The study examined the relationship between the SII index, calculated as P * N/L, where P represents preoperative peripheral platelet count, N represents neutrophil count, and L represents lymphocyte count, and biological aging. Biological aging was assessed through various methods, such as phenotypic age, phenotypic age acceleration (PhenoAgeAccel), biological age, and biological age acceleration (BioAgeAccel). Correlations were analyzed using weighted linear regression and subgroup analysis.ResultsAmong the 7,491 participants analyzed, the average age was 45.26 ± 0.34 years, with 52.16% being female. The average phenotypic and biological ages were 40.06 ± 0.36 and 45.89 ± 0.32 years, respectively. Following adjustment for potential confounders, elevated SII scores were linked to increased phenotypic age, biological age, Phenotypic age acceleration, and Biological age acceleration. Positive correlations were observed between health behavior and health factor scores and biological aging, with stronger associations seen for health factors. In health factor-specific analyses, the β coefficient was notably higher for high BMI. The robust positive associations between SII scores and both phenotypic age and biological age in the stratified analyses were consistently observed across all strata.ConclusionThe evidence from the NHANES data indicate that SII may serve as a valuable marker for assessing different facets of aging and health outcomes, such as mortality and the aging process. Additional research is warranted to comprehensively elucidate the implications of SII in the aging process and its utility as a clinical instrument for evaluating and addressing age-related ailments.

Abstract The cryptocurrency market is a complex and rapidly evolving financial landscape in which understanding the inter- and intra-asset dependencies among key financial variables, such as return and liquidity, is crucial. In this study, we analyze daily return and liquidity data for six major cryptocurrencies, namely Bitcoin, Ethereum, Ripple, Binance Coin, Litecoin, and Dogecoin, spanning the period from June 3, 2020, to November 30, 2022. Liquidity is estimated using three low-frequency proxies: the Amihud ratio and the Abdi and Ranaldo (AR) and Corwin and Schultz (CS) estimators. To account for autoregressive and persistent effects, we apply the autoregressive integrated moving average-generalized autoregressive conditional heteroscedasticity (ARIMA-GARCH) model and subsequently utilize the copula method to examine the interdependent relationships between the return on and liquidity of the six cryptocurrencies. Our analysis reveals strong cross-asset lower-tail dependence in return and significant cross-asset upper-tail dependence in illiquidity measures, with more pronounced dependence observed in specific cryptocurrency pairs, primarily involving Bitcoin, Ethereum, and Litecoin. We also observe that returns tend to be higher when liquidity is lower in the cryptocurrency market. Our findings have significant implications for portfolio diversification, asset allocation, risk management, and trading strategy development for investors and traders, as well as regulatory policy-making for regulators. This study contributes to a deeper understanding of the cryptocurrency marketplace and can help inform investment decision making and regulatory policies in this emerging financial domain.

This paper concentrates on the secure consensus control problem for a class of second-order connected vehicle systems (CVSs) in the presence of denial-of-service (DoS) attacks. First, the necessary and sufficient conditions for the consensus of CVSs are derived in the attack-free case. Second, in order to defend against DoS attacks, we design a novel secure consensus control protocol where resilient predictors are used to estimate the states of other vehicles during DoS attacks. Then, by using Lyapunov stability theory, matrix analysis tool, and algebraic graph theory, the convergence of CVSs with the resilient predictors against DoS attacks is achieved in the attack case. It is proved that under the designed secure consensus control protocol with resilient predictors, not only the prediction errors can be converged to a bounded range, but also the system errors can be converged. Finally, the effectiveness of the proposed novel secure consensus control protocol with resilient predictors is illustrated by some simulation results.

Abstract Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process, and ovarian aging is shown by a decrease in the number and quality of oocytes. However, little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging, especially in goats. Therefore, the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution. Results For the first time, we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn, young and aging goats, and identified nine ovarian cell types with distinct gene-expression signatures. Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes, such as Wnt beta-catenin signalling was enriched in germ cells, whereas ovarian steroidogenesis was enriched in granulosa cells (GCs). Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system, oxidative phosphorylation, and apoptosis. Subsequently, we identified a series of dynamic genes, such as AMH, CRABP2, THBS1 and TIMP1, which determined the fate of GCs. Additionally, FOXO1, SOX4, and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging. Conclusions This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell type-specific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.

Ore collection devices are important for the collection of deep-sea polymetallic nodules. Based on the CFD-DEM solid–liquid two-phase flow coupling calculation method, this paper simulated the rise and transport phases of polymetallic nodules using the Coanda effect ore collection device. The validity of the numerical simulation method was confirmed through experimental testing. On this basis, the effects of different working and structural parameters on the collection rate were studied. The results indicate that the flow rate of the collection jet and the bottom clearance were the primary factors affecting the collection rate of the polymetallic nodules. An increase in the collection jet flow rate leads to a substantial rise in the collection rate of polymetallic nodules. Conversely, an increase in bottom clearance results in a decrease in the collection rate. A collection rate exceeding 90% can be achieved in both scenarios: a 10 mm bottom clearance with an 8 m/s collection jet flow rate, and a 30 mm bottom clearance with a 10 m/s collection jet flow rate. The collection nozzle slant angle has no substantial impact on the collection rate, and the recommended collection nozzle slant angle is 35° to reduce energy loss.

Abstract Diabetic ketoacidosis (DKA) is a life‐threatening acute complication of diabetes characterized by the accumulation of ketone bodies in the blood. Breath acetone, a ketone, directly correlates with blood ketones. Therefore, monitoring breath acetone can significantly enhance the safety and efficacy of diabetes care. In this work, the design and fabrication of an InP/Pt/chitosan nanowire array‐based chemiresistive acetone sensor is reported. By incorporation of chitosan as a surface‐functional layer and a Pt Schottky contact for efficient charge transfer processes and photovoltaic effect, self‐powered, highly selective acetone sensing is achieved. The sensor has exhibited an ultra‐wide acetone detection range from sub‐ppb to >100 000 ppm level at room temperature, covering those in the exhaled breath from healthy individuals (300–800 ppb) to people at high risk of DKA (>75 ppm). The nanowire sensor has also been successfully integrated into a handheld breath testing prototype, the Ketowhistle, which can successfully detect different ranges of acetone concentrations in simulated breath samples. The Ketowhistle demonstrates the immediate potential for non‐invasive ketone monitoring for people living with diabetes, in particular for DKA prevention.

Streptococcus equi subsp. zooepidemicus (SEZ) is a significant zoonotic pathogen that causes septicemia, meningitis, and mastitis in domestic animals. Recent reports have highlighted high-mortality outbreaks among swine in the United States. Traditionally recognized for its adaptive immune functions, the CRISPR-Cas system has also been implicated in gene regulation, bacterial pathophysiology, virulence, and evolution. The Type I-C CRISPR-Cas system, which is prevalent in SEZ isolates, appears to play a pivotal role in regulating the pathogenicity of SEZ. By constructing a Cas3 mutant strain (ΔCas3) and a CRISPR-deficient strain (ΔCRISPR), we demonstrated that this system significantly promotes biofilm formation and cell adhesion. However, the deficiency in the CRISPR-Cas system did not affect bacterial morphology or capsule production. In vitro studies showed that the CRISPR-Cas system enhances pro-inflammatory responses in RAW264.7 cells. The ΔCas3 and ΔCRISPR mutant strains exhibited reduced mortality rates in mice, accompanied by a decreased bacterial load in specific organs. RNA-seq analysis revealed distinct expression patterns in both mutant strains, with ΔCas3 displaying a broader range of differentially expressed genes, which accounted for over 70% of the differential genes observed in ΔCRISPR. These genes were predominantly linked to lipid metabolism, the ABC transport system, signal transduction, and quorum sensing. These findings enhance our understanding of the complex role of the CRISPR-Cas system in SEZ pathogenesis and provide valuable insights for developing innovative therapeutic strategies to combat infections.

ABSTRACT: Metal foam and fins are two popular structures that are employed to enhance the heat transfer of phase change materials in shell-and-tube heat storage units. However, it remains unclear which structure is better in terms of energy storage performance. In this study, the heat transfer enhancement performances of metal foam and fins are compared to provide guidance on the optimal structure to be chosen for practical applications. Three fin structures (four fins, two vertical fins, and two horizontal fins) are considered. Under the full configuration (volume fraction of metal = 3%), the unit with four fins was found to have a faster melting rate than those with vertical or horizontal fins. In other words, increasing the number of fins helps to accelerate the melting process. Nevertheless, the unit with metal foam enhancement has the highest melting rate. Under the half configuration (volume fraction of metal = 1.5%), the melting rate of the unit enhanced by metal foam is significantly decreased, whereas there is no remarkable changes in the units enhanced by fins. However, metal foam is still shown to be the best thermal enhancer. The energy storage rate of the unit enhanced by metal foam can be up to 10 times higher than that of the unit enhanced by fins.

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is a global economic pest that poses a serious threat to the fruit industry. In the southwest of China, Yunnan Province sustains a severe infestation of B. dorsalis. An automated monitoring system designed for B. dorsalis was employed in this study to elucidate the annual population dynamics of B. dorsalis in four counties: Yuanjiang, Huaping, Guangnan, and Ludian in Yunnan. The system utilizes sex parapheromone and image recognition technology. The data uploaded by the device are used to analyze the annual population dynamics of B. dorsalis in different regions. The results showed that the populations of adult B. dorsalis in all four counties peaked twice annually, with Yuanjiang experiencing the earliest peak periods, followed by Huaping, Guangnan, and Ludian. Adult B. dorsalis occurred in Yuanjiang throughout the year, and Yuanjiang had the highest number of B. dorsalis monitored. In Huaping, adult B. dorsalis occurred in March–December and was highly active, with a high population density in 2019. Bactrocera dorsalis did not occur in December in Guangnan but only in May–October in Ludian. Bactrocera dorsalis abundance was correlated with temperature in all four areas. The outcomes of this experiment provide a practical foundation for developing control strategies targeting B. dorsalis in various orchards across each county.

The current deep learning methods for copy–move forgery detection (CMFD) are mostly based on deep convolutional neural networks, which frequently discard a large amount of detail information throughout convolutional feature extraction and have poor long-range information extraction capabilities. The Transformer structure is adept at modeling global context information, but the patch-wise self-attention calculation still neglects the extraction of details in local regions that have been tampered with. A local-information-refined dual-branch network, LBRT (Local Branch Refinement Transformer), is designed in this study. It performs Transformer encoding on the global patches segmented from the image and local patches re-segmented from the global patches using a global modeling branch and a local refinement branch, respectively. The self-attention features from both branches are precisely fused, and the fused feature map is then up-sampled and decoded. Therefore, LBRT considers both global semantic information modeling and local detail information refinement. The experimental results show that LBRT outperforms several state-of-the-art CMFD methods on the USCISI dataset, CASIA CMFD dataset, and DEFACTO CMFD dataset.

Miniaturized light sources at telecommunication wavelengths are essential components for on-chip optical communication systems. Here, we report the growth and fabrication of highly uniform p-i-n core-shell InGaAs/InP single quantum well (QW) nanowire array light emitting diodes (LEDs) with multi-wavelength and high-speed operations. Two-dimensional cathodoluminescence mapping reveals that axial and radial QWs in the nanowire structure contribute to strong emission at the wavelength of ~1.35 and ~1.55 μm, respectively, ideal for low-loss optical communications. As a result of simultaneous contributions from both axial and radial QWs, broadband electroluminescence emission with a linewidth of 286 nm is achieved with a peak power of ~17 μW. A large spectral blueshift is observed with the increase of applied bias, which is ascribed to the band-filling effect based on device simulation, and enables voltage tunable multi-wavelength operation at the telecommunication wavelength range. Multi-wavelength operation is also achieved by fabricating nanowire array LEDs with different pitch sizes on the same substrate, leading to QW formation with different emission wavelengths. Furthermore, high-speed GHz-level modulation and small pixel size LED are demonstrated, showing the promise for ultrafast operation and ultracompact integration. The voltage and pitch size controlled multi-wavelength high-speed nanowire array LED presents a compact and efficient scheme for developing high-performance nanoscale light sources for future optical communication applications.

IntroductionOptimizing the management of dairy cattle reproduction can reduce postpartum ovarian disease in high-yielding dairy cows and thus enhance ranch economic benefit. The hypothesis of this study was that the Double-Ovsynch (DO) protocol in high-producing dairy cows would result in a lower incidence of follicular cysts but a higher incidence of luteal cysts compared to those undergoing the Presynch-Ovsynch (PS) protocol.MethodsIn this experiment, 384 cows (204 primiparous and 180 multiparous) were allocated to the DO group, which followed the protocol: GnRH-7d-PGF2α-3d-GnRH-7d-Ovsynch-56 h (GnRH-7d-PGF2α-56 h-GnRH-16hTAI), starting on 39 ± 3 days in milk (DIM). Additionally, 359 cows (176 primiparous and 183 multiparous) were assigned to the PS group, which followed the protocol: PGF2α-14d-PGF2α-12d-Ovsynch-56 h, starting on 31 ± 3 DIM. In DO, B-mode ultrasound examinations were conducted 1 day after the GnRH-7d-PGF2α-3d-GnRH protocol to diagnose the presence of ovarian diseases followed by reexamination after 7 days of suspected cases. In PS, B-mode ultrasound examinations were conducted 1 day after the PGF2α-14d-PGF2α protocol to diagnose the presence of ovarian diseases followed by reexamination after 7 days. For all cows confirmed to having ovarian diseases, a second B-mode ultrasound examination was conducted at the time of the second GnRH and timed artificial insemination (TAI). If the ovary showed a normal developing follicle in combination with normal ovulation, the ovarian disease was considered to be cured.ResultsThe current study revealed no significant difference in the overall incidence and cure rate of postpartum ovarian diseases between DO and PS (incidence rate: 3.9% vs. 6.7%, cure rate: 50% vs. 41.7%, DO vs. PS). Also, there was no significant difference in the incidence and cure rate of luteal cysts between DO and PS (incidence rate: 2.9% vs. 2.2%, cure rate: 50.0% vs. 50.0%). The incidence of follicular cysts was significantly lower in the DO group than in the PS group (0.8% vs. 2.8%, DO vs. PS, p = 0.037), but there was no significant difference in the cure rates (66.7% vs. 50%). The occurrence of inactive ovary was lower in DO compared to PS (0.2% vs. 1.7%, p = 0.047). There was no significant difference in the pregnancy rate between the DO and PS groups (48.2% vs. 41.8%), although the DO group had a higher rate. What is different from our assumption is that PS did not effectively reduce the incidence of postpartum luteal cysts.

Silica nanoparticles (SiNPs) have been widely used in electronics, chemistry, and biomedicine. Human exposure to SiNPs and possible health effects have attracted much attention. The potential cardiovascular toxicity of SiNPs and their related mechanisms are still unclear. Therefore, in this study, we investigated the toxic effects of SiNPs on human umbilical vein endothelial cells (HUVECs). We found that SiNPs could induce HUVECs ferroptosis. The results showed that the level of intracellular divalent iron and lipid peroxidation increased, and mitochondrial cristae decreased. In addition, the pretreatment of the iron chelator deferoxamine mesylate (DFO) could alleviate the ferroptosis of cells. Interestingly, pretreatment of 3-methyladenine (3-MA), an autophagy/PI3K inhibitor could partially inhibit autophagy and reduce ferroptosis, which indicated that autophagy played an important role in cell ferroptosis. Additionally, after knocking down nuclear receptor coactivator 4 (NCOA4), Ferritin Heavy Chain 1 (FTH1) expression was up-regulated, and the levels of divalent iron and lipid peroxidation decreased, which suggested that NCOA4 mediated the ferroptosis of HUVECs induced by SiNPs. In conclusion, this study shows that SiNPs can induce cardiovascular toxicity in which there is ferroptosis. NCOA4-mediated ferritinophagy and resultant ferroptosis by SiNPs may play an important role. This study provides a new theoretical strategy for the treatment and prevention of cardiovascular diseases in the future.

AbstractAs a landmark in China’s hydraulic engineering history, the Central Route of the South–North Water Diversion Project (SNWD-CR) plays a major role in alleviating severe water shortages in Northern China. Existing InSAR monitoring of the SNWD-CR based on one-dimensional viewing geometry and Sentinel-1 imaging is insufficient for a comprehensive assessment of deformation causes. Moreover, the poor geocoding accuracy hampers the previous interpretation of the estimated deformations. Here we carry out comprehensive two-dimensional deformation analyses over the head of the SNWD-CR by integrating the multitemporal PS/DS InSAR and the stress–strain model, where the well-designed topography and geocoded error correction can help to identify the causes of deformation. We apply our strategy to ascending and descending TerraSAR-X meter-resolution datasets acquired from June 2020 to February 2021. Geocoding errors in both ascending and descending orbits are corrected, and the relationship between topography error and horizontal positioning error is discussed. The multi-data fusion results reveal insignificant deformations in the east–west direction except for a makeshift rigid-frame bridge, whereas the vertical deformation field shows two uplifts and a subsidence area in the narrow canal with a maximum rate of 23 mm/y, which are likely to be related to rainfall and water diversion pressure. Furthermore, the combination of the external DEM and topographic residual offers the chance to reconstruct the high-accuracy DEM.

Attitude is an essential parameter in autonomous navigation. Existing high-precision navigation sensors are expensive and large. Therefore, miniaturized and low-cost autonomous navigation technologies have become the research focus. Inspired by biomimetics, an inversion estimation model of autonomous undersea vehicle(AUV) attitude based on a pressure sensor array was constructed. The model takes known pressure and attitude data as input and trains the model parameters to use the pressure data to invert attitude information. The effectiveness of the proposed method was verified through multiple experiments with different trajectories, depths, speeds, and other factors. The experimental results show that using the proposed method, the estimated pitch angle error is below 2.069 9°, and the estimated roll angle error is below 2.990 8°. Furthermore, there are no cumulative attitude errors; this, implies that the proposed method has strong potential for applications in autonomous navigation systems.

Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-β signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.

One of the most significant pieces of linear infrastructure in China is the Middle Route of the South-to-North Water Diversion Project (MR-SNWDP), a large section of which consists of an expansive soil slope (ESS) that threatens the safety of the canal. Here, we prepared 144 Sentinel-1 data from May 2017 to July 2022 to study the behavior of the ESS in the canal section in Huixian City in the MR-SNWDP. Then, the Elastoplastic Deformation model under Wetting and Heating Effects (EDWHE) was employed to accurately characterize the displacement of the ESS. The InSAR results illustrate that the unstable zones tend to be small and are distributed along the canal slope, with the magnitude of deformations generally no more than 20 mm/year. Additionally, their deformation time series generally accumulate exponentially and evolve in a significant pattern of seasonal swelling and shrinkage. We observed that the slope movements significantly accelerated during the period when extreme rainfall occurred around 22 July 2021. Affected by satellite imagery and the geometric structure of the slope, the magnitudes and evolving trends of LOS deformation vary with different aspects of the slope sections. Then, the elastic swelling-shrinkage deformations were derived through the EDWHE model, of which the uplift or settlement was mainly dependent on geological and meteorological conditions. Moreover, the active zone depths of the ESS were retrieved using an InSAR-based lag-time approach and clearly reflected their distribution pattern. In this investigation, the behavior of the ESS in the study area was quantitatively analyzed using InSAR, and the results provide support for designing protective slope treatments and keeping the canal safe in the MR-SNWDP.

Both oxyhydrogen and butanol are renewable alternative fuels. Based on gasoline/butanol compound injection mode, although the introduction of oxyhydrogen can effectually enhance the optimal BDIr (butanol direct injection ratio), it also leads to an increase in NO emission. Therefore, this paper further studies the influence of lean-burn on the combustion and emission of ternary-fuel combined supply engine with oxyhydrogen/butanol/gasoline. In this paper, three variables are set, namely five BDIr (0–80%), five ONPIv (oxyhydrogen negative pressure inhalation volume) (0–16 L/min) and five λ (1.0–1.4). The results show that the larger the λ, the more significant the impact of oxyhydrogen on improving combustion and thermal transfer inside the cylinder. With the increase of ONPIv, CoVIMEP, CA 10–90 and CA 0-10 decrease, IMEP increases. Under all lean-burn conditions, ONPI can reduce CO and HC emissions. Under the condition of λ = 1.4, when ONPIv = 16 L/min, NO emission is 49.98% lower than the value of the original engine. Moreover, based on BDIr = 40%, 16 L/min ONPIv can elevate the λ limit from 1.41 to 1.83. In summary, “1.1 = λ ≤ 1.2+ONPIv = 16 L/min+60%≤BDIr≤80%” is the excellent control strategy of ONPI + BDI + GPI engine. The synergistic influence of lean-burn and larger BDIr can greatly reduce gasoline consumption and NOx emission caused by oxyhydrogen, but also worsen the mixture combustion atmosphere. ONPI can effectively improve this problem, and further increase energy efficiency. The coupling technology of ternary-fuel combined supply and lean-burn has a positive impact on improving thermal transfer efficiency, optimizing mixture combustion and decreasing gaseous emission.

Abstract Background Premature ovarian insufficiency (POI) is one of the common women reproductive endocrine diseases which adversely impacts female fertility, but the etiology and pathogenesis still remain elusive. Recently increasing researches focus on the roles of lncRNA in POI. LncRNA DANCR was involved in cell differentiation and multiple cancers. It’s highly expressed in ovary while the role of DANCR in POI is still unknown. Results Here, we identify a new POI related lncRNA DANCR, which negatively contributes to ovarian granulosa cells aging and follicular atresia. DANCR is proved to be decreasingly expressed in POI patients’ granulosa cells. Additionally, Dancr knockout (Dancr −/− ) mice were constructed and characterized with POI phenotypes and fertility decline, compared with Dancr +/+ mice. Further, in vitro experiments indicated that DANCR knockdown in granulosa cells led to cell aging and series of aging-related changes including proliferation inhibition, cell cycle G1 arrest and DNA damage. Mechanism research revealed DANCR binds with hNRNPC and p53, while DANCR knockdown attenuates the binding of hNRNPC and p53, thus enhancing protein level of p53 and promoting granulosa cells aging significantly. Conclusion The newly identified lncRNA DANCR inhibits p53-dependent granulosa cells aging by regulating hNRNPC-p53 interaction, and eventually counteracting POI. This provides new insights into the pathogenesis of POI and provides a potential target for future diagnosis and treatment.

Silicon carbide (SiC) is widely used in abrasives, heating devices, light emitting diodes and high-power electronics, because of its unique physical-chemical properties including high hardness, high melting point, excellent thermal conductivity, and wide bandgap. In recent years, its color centers have also been used as potential sources of single photons. Given that borides and carbides are refractory materials, we decided to study a heterostructure formed by an n-doped silicon carbide substrate and a layer of tantalum monoboride (TaB) for near ultraviolet (UV) photodetection. It is shown that the addition of TaB creates a rectifying device that can handle currents higher than 300 mA, showing its potential for high-power optoelectronic devices. The detector also has a high responsivity of 2.9 A/W at the free-space wavelength of 405 nm and a fast frequency response of 610 kHz. The high performance of the detector is attributed to the high thermal and electrical conductivity, large bandgap of SiC, and its moderately close match in atomic arrangement with TaB. Such heterostructure offers a simple method to produce high-performance near UV photodetectors operating under hard conditions such as high power, high temperature and corrosive or oxidizing environments.

Abstract Main goal of the JUNO experiment is to determine the neutrino mass ordering using a 20 kt liquid-scintillator detector. Its key feature is an excellent energy resolution of at least 3% at 1 MeV, for which its instruments need to meet a certain quality and thus have to be fully characterized. More than 20,000 20-inch PMTs have been received and assessed by JUNO after a detailed testing program which began in 2017 and elapsed for about four years. Based on this mass characterization and a set of specific requirements, a good quality of all accepted PMTs could be ascertained. This paper presents the performed testing procedure with the designed testing systems as well as the statistical characteristics of all 20-inch PMTs intended to be used in the JUNO experiment, covering more than fifteen performance parameters including the photocathode uniformity. This constitutes the largest sample of 20-inch PMTs ever produced and studied in detail to date, i.e. 15,000 of the newly developed 20-inch MCP-PMTs from Northern Night Vision Technology Co. (NNVT) and 5000 of dynode PMTs from Hamamatsu Photonics K. K.(HPK).

Abstract Narrowband red, green, blue self-filtering perovskite photodetectors and a broadband white photodetector are incorporated into a single pixel imaging camera to mimic the long-, medium-, and short-wavelength cone cells and rod cells in human visual system, leading to the demonstration of high-resolution color images in diffuse mode.

Blockchain technology is considered to be a disruptive technology that has real potential for change after steam engines, electricity, and the Internet. However, in terms of power generation, the current level of hydropower development in my country is only 39%. Compared with developed countries, there is still a big gap and a high development space. This article proposes a research on the application of blockchain technology in smart sustainable energy business models, studies the conversion path of sustainable energy systems, introduces integrated energy service blockchain technology, and builds a sustainable energy transition model. The selection of practical dimensions requires both Quantitative indicators also require cultural and behavioral qualitative indicators; finally, through the analysis of social development trends and government policies, the external variable landscape signals are parameterized. Sustainable energy rather than fossil energy is the energy of the future. Weak landscape signals have significantly weakened the development of the sustainable energy niche: the proportion of coal consumption has declined slowly. Although it has transformed from a system to a niche, it has always been higher than that of other energy types. Only with long-term landscape pressure, positive changes to sustainable energy technologies and infrastructure, and continuous changes in consumer preferences, can sustainable energy ultimately dominate.

The physics potential of detecting ^8 B solar neutrinos will be exploited at the Jiangmen Underground Neutrino Observatory (JUNO), in a model-independent manner by using three distinct channels of the charged current (CC), neutral current (NC), and elastic scattering (ES) interactions. Due to the largest-ever mass of ^13 C nuclei in the liquid scintillator detectors and the expected low background level, ^8 B solar neutrinos are observable in the CC and NC interactions on ^13 C for the first time. By virtue of optimized event selections and muon veto strategies, backgrounds from the accidental coincidence, muon-induced isotopes, and external backgrounds can be greatly suppressed. Excellent signal-to-background ratios can be achieved in the CC, NC, and ES channels to guarantee the observation of the ^8 B solar neutrinos. From the sensitivity studies performed in this work, we show that JUNO, with 10 yr of data, can reach the 1 σ precision levels of 5%, 8%, and 20% for the ^8 B neutrino flux, ${\sin }^{2}{\theta }_{12}$ , and ${\rm{\Delta }}{m}_{21}^{2}$ , respectively. Probing the details of both solar physics and neutrino physics would be unique and helpful. In addition, when combined with the Sudbury Neutrino Observatory measurement, the world's best precision of 3% is expected for the measurement of the ^8 B neutrino flux.

In order to improve the chitinase production performance of an endophytic bacterium Bacillus thuringiensis Bt028 isolated from sour orange fruit, the effects of medium composition and fermentation conditions on chitinase production were investigated by single factor test and the shaking flask fermentation conditions of chitinase production were optimized by response surface methodology. The results of single factor test showed that concentration of colloidal chitin, temperature and initial pH had obvious effects on chitinase production. The results of response surface test showed that the optimum fermentation conditions were as follows: Colloidal chitin concentration was 0.8%, yeast powder concentration was 1%, the initial pH was 6.9, inoculation amount was 3%, liquid volume was 100 mL/250 mL, cultured temperature was 30 ℃ and culture time was 48 h. Under these conditions, the highest enzyme activity of the strain fermentation broth was 10.48 U/mL. The studied results laid a foundation for the further development and application of the chitinase produced by Bacillus thuringiensis Bt028.

In order to reveal the basic enzymatic properties of the chitinase produced by an endophytic bacterium Bacillus thuringiensis Bt028 isolated from sour orange fruit, the chitinase in the strain fermentation broth were purified by centrifugation, ammonium sulfate precipitation, dextran gel G-100 chromatography and SDS-polyacrylamide gel electrophoresis and the optimum temperature, optimum pH and catalytic kinetic parameters of the chitinase were also investigated. The results showed that electrophoretic pure chitinase was obtained by centrifugation, ammonium sulfate precipitation and dextran G-100 gel chromatography from fermentation broth of the strain Bt028, with the specific activity of 681.78 U/mg, the purification factor of 3.21 and enzymatic activity recovery of 15.52%, and the molecular mass of the chitinase was determined to be 65 kDa by SDS-polyacrylamide gel electrophoresis. The enzymatic characteristics study results showed that the optimum reaction temperature of the chitinase was 60 ℃ with good stability when temperature lower than 60 ℃; and the optimum reaction pH was 6.5 with good stability at pH5.5~7.5. Mg2+, Ca2+, Hg2+ and Co2+ had inhibitory effect on the enzyme activity, while Cu2+ and Fe3+ had a certain promotion effect. Low concentrations of methanol, ethanol, n-propanol and dimethyl sulfoxide increased the enzymatic activity, however, the chitinase would be inhibited when the concentration of these organic solvents were increased to a certain level. The chitinase could be activated by acetone but inhibited by formaldehyde. Under the optimal catalytic conditions, the value of Km, Vmax and Kcat of the chitinase-catalyzed reaction were 29.533 mg/mL, 108.696 μmoL/(L·min) and 0.527/min, respectively. Research results provide technical parameters for the practical application of the chitinase.

Abstract We study damping signatures at the Jiangmen Underground Neutrino Observatory (JUNO), a medium-baseline reactor neutrino oscillation experiment. These damping signatures are motivated by various new physics models, including quantum decoherence, ν 3 decay, neutrino absorption, and wave packet decoherence. The phenomenological effects of these models can be characterized by exponential damping factors at the probability level. We assess how well JUNO can constrain these damping parameters and how to disentangle these different damping signatures at JUNO. Compared to current experimental limits, JUNO can significantly improve the limits on τ 3/m 3 in the ν 3 decay model, the width of the neutrino wave packet σ x , and the intrinsic relative dispersion of neutrino momentum σ rel.

Abstract Semiconductor nanowires (NWs) could simultaneously provide gain medium and optical cavity for performing nanoscale lasers with easy integration, ultracompact footprint, and low energy consumption. Here, we report III–V semiconductor NW lasers can also be used for self-frequency conversion to extend their output wavelengths, as a result of their non-centrosymmetric crystal structure and strongly localized optical field in the NWs. From a GaAs/In0.16Ga0.84As core/shell NW lasing at 1016 nm, an extra visible laser output at 508 nm is obtained via the process of second-harmonic generation, as confirmed by the far-field polarization dependence measurements and numerical modeling. From another NW laser with a larger diameter which supports multiple fundamental lasing wavelengths, multiple self-frequency-conversion lasing modes are observed due to second-harmonic generation and sum-frequency generation. The demonstrated self-frequency conversion of NW lasers opens an avenue for extending the working wavelengths of nanoscale lasers, even to the deep ultraviolet and THz range.

In alcohol-containing systems, the association of polar molecules significantly influences the calculation of water activity, leading to substantial deviations from ideal solution behavior. This makes it challenging for traditional hydrate formation condition models to accurately predict hydrate formation temperatures and pressures. To address this issue, we propose a novel unified thermodynamic framework based on the Parrish-Prausnitz (P-P) model and the Cubic-Plus-Association (CPA) equation of state (EoS) for calculating the hydrate formation condition in systems containing gas/water/alcohol, by using the advantages of the CPA EoS to characterize the association interaction of polar molecules. In addition, we utilize experimental data to model the molecular association in alcohol-containing systems and conduct regression analysis for binary interaction coefficients among alcohol, water, and gas. Multiple sets of experimental data on component fractions and hydrate formation conditions for methane-alcohol-water systems are used for validation. The proposed model shows an average relative error of 1.17–6.42% for predicting alcohol/methane component fractions in the liquid phase and 1.93–4.78% for predicting hydrate formation conditions in alcohol-containing systems. Compared to traditional models, this model demonstrates a significant improvement in accuracy and performs well in predicting hydrate formation conditions in alcohol-containing systems.

ADP-ribosylation is a post-translational modification of proteins that plays a key role in various cellular processes, including DNA repair. Recently, significant progress has been made in understanding the mechanism and function of ADP-ribosylation in DNA repair. ADP-ribosylation can regulate the recruitment and activity of DNA repair proteins by facilitating protein–protein interactions and regulating protein conformations. Moreover, ADP-ribosylation can influence additional post-translational modifications (PTMs) of proteins involved in DNA repair, such as ubiquitination, methylation, acetylation, phosphorylation, and SUMOylation. The interaction between ADP-ribosylation and these additional PTMs can fine-tune the activity of DNA repair proteins and ensure the proper execution of the DNA repair process. In addition, PARP inhibitors have been developed as a promising cancer therapeutic strategy by exploiting the dependence of certain cancer types on the PARP-mediated DNA repair pathway. In this paper, we review the progress of ADP-ribosylation in DNA repair, discuss the crosstalk of ADP-ribosylation with additional PTMs in DNA repair, and summarize the progress of PARP inhibitors in cancer therapy.

This study investigated the associations between diet and frailty in lung cancer patients and the potential role of the gut microbiota involved. We assessed dietary intake and frailty status in 231 lung cancer patients by 3-day, 24-h dietary recalls and Fried frailty criteria, respectively, and collected 50 fecal samples for next-generation sequencing. A total of 75 (32.5%) patients were frail, which might be related to significantly lower intake of energy, protein, carbohydrate, dietary fiber, niacin, leucine, some minerals, and a poorer dietary quality as indicated by the Chinese Healthy Eating Index (p < 0.05). Among these, carbohydrate (OR = 0.98; 95% CI 0.96–0.99; p = 0.010), calcium (OR = 0.99; 95% CI 0.99–1.00; p = 0.025), and selenium (OR = 1.03; 95% CI 1.00–1.06; p = 0.022) were all significantly associated with frailty. A multivariate logistic regression analysis showed that the mean risk of frailty was 0.94 times lower (95% CI 0.90–0.99; p = 0.009) among participants with higher CHEI scores. Additionally, the frail patients demonstrated significantly lower gut microbiota β diversity (p = 0.001) and higher relative abundance of Actinobacteriota (p = 0.033). Frailty in lung cancer patients might be associated with insufficient nutrients intake and a poor dietary quality through gut microbiota regulation.

Thermoset powder coatings exhibit distinctive characteristics such as remarkable hardness and exceptional resistance to corrosion. In contrast to conventional paints, powder coatings are environmentally friendly due to the absence of volatile organic compounds (VOCs). However, their irreversible cross-linking structures limit their chain segment mobility, preventing polymers from autonomously repairing cracks. Dynamic cross-linking networks have garnered attention for their remarkable self-healing capabilities, facilitated by rapid internal bond exchange. Herein, we introduce an innovative method for synthesizing thermoset epoxy containing boronic ester moieties which could prolong the life of the powder coating. The epoxy resin system relies on the incorporation of two curing agents: one featuring small-molecule diamines with boronic bonds and the other a modified polyurethane prepolymer. A state of equilibrium in mechanical properties was achieved via precise manipulation of the proportions of these agents, with the epoxy composite exhibiting a fracture stress of 67.95 MPa while maintaining a stable glass transition temperature (Tg) of 51.39 °C. This imparts remarkable self-healing ability to the coating surface, capable of returning to its original state even after undergoing 1000 cycles of rubbing (using 1200-grit abrasive paper). Furthermore, the introduction of carbon nanotube nanoparticles enabled non-contact sequential self-healing. Subsequently, we introduce this method into powder coatings of different materials. Therefore, this work provides a strategy to develop functional interior decoration and ensure its potential for broad-ranging applications, such as aerospace, transportation, and other fields.

The geomagnetic field constitutes a massive fingerprint database, and its unique structure provides potential position correction information. In recent years, particle filter technology has received more attention in the context of robot navigation. However, particle degradation and impoverishment have constrained navigation systems’ performance. This paper transforms particle filtering into a particle-matching positioning problem and proposes a geomagnetic localization method based on an adaptive fission particle filter. This method employs particle-filtering technology to construct a geomagnetic matching positioning model. Through adaptive particle fission and sampling, the problem of particle degradation and impoverishment in traditional particle filtering is solved, resulting in improved geomagnetic matching positioning accuracy. Finally, the proposed method was tested in a sea trial, and the results show that the proposed method has a lower positioning error than traditional particle-filtering and intelligent particle-filtering algorithms. Under geomagnetic map conditions, an average positioning accuracy of about 546.44 m is achieved.

Abstract Background The role of circular RNAs (circRNAs) and microRNAs (miRNAs) in osteosarcoma (OS) development has not been fully elucidated. Further, the contribution of the immune response to OS progression is not well defined. However, it is known that circRNAs and miRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of many cancers. Thus, the aim of this study was to identify novel key serum biomarkers for the diagnosis and metastatic prediction of OS by analysis of immune cell infiltration and associated RNA molecules. Methods Human OS differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified by analysis of microarray data downloaded from Gene Expression Omnibus (GEO) datasets. Further, characteristic patterns of OS-infiltrating immune cells were analyzed. On this basis, we identified statistically significant transcription factors. Moreover we performed pathway enrichment analysis, constructed protein–protein interaction networks, and devised competitive endogenous RNA (ceRNA) networks. Biological targets of the ceRNA networks were evaluated and potential OS biomarkers confirmed by RT-qPCR analysis of the patients’ serum. Results Seven differentially expressed circRNAs, 166 differentially expressed miRNAs, and 175 differentially expressed mRNAs were identified. An evaluation of cellular OS infiltration identified the highest level of infiltration by M0 macrophages, M2 macrophages, and CD8+ T cells, with M0 macrophages and CD8+ T cells as the most prominent. Significant patterns of tumor-infiltrating immune cells were identified by principal component analysis. Moreover, 185 statistically significant transcription factors were associated with OS. Further, in association with immune cell infiltration, hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A were identified as potential novel biomarkers for OS diagnosis. Of these, FAM98A had the most promise as a diagnostic marker for OS and OS metastasis. Most importantly, a novel diagnostic model consisting of these four biomarkers (hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A) was established with a 0.928 AUC value. Conclusions In summary, potential serum biomarkers for OS diagnosis and metastatic prediction were identified based on an analysis of immune cell infiltration. A novel diagnostic model consisting of these four promising serum biomarkers was established. Taken together, the results of this study provide a new perspective by which to understand immunotherapy of OS.

Research into cavitation phenomena in various fields shows that the elastic modulus of a boundary has a potential impact on cavitation erosion. To obtain the direct relationship between the elastic modulus of the boundary and cavitiation erosion, single-layer samples with different chemical composition and moduli, and double-layer samples with different elastic moduli and the same surface layer material, were prepared with silicone rubber. The results of cavitation experiments on single-layer samples, show that the coating chemical composition and mechanical properties together affect the cavitation morphology of the coating, and dominant factors vary with erosion stage. Through the cavitation test of double-layer samples, it was found that there is a positive correlation between the elastic modulus of the coating and the degree of cavitation. This study helps us to understand the relationship between coating elastic modulus and cavitation more directly, and provides theoretical and technical guidance for the application of anti-cavitation for elastic coating in engineering.

Abstract The OSIRIS detector is a subsystem of the liquid scintillator filling chain of the JUNO reactor neutrino experiment. Its purpose is to validate the radiopurity of the scintillator to assure that all components of the JUNO scintillator system work to specifications and only neutrino-grade scintillator is filled into the JUNO Central Detector. The aspired sensitivity level of $$10^{-16}\hbox { g/g}$$ 10 - 16 g/g of $$^{238}\hbox {U}$$ 238 U and $$^{232}\hbox {Th}$$ 232 Th requires a large ( $$\sim 20\,\hbox {m}^3$$ ∼ 20 m 3 ) detection volume and ultralow background levels. The present paper reports on the design and major components of the OSIRIS detector, the detector simulation as well as the measuring strategies foreseen and the sensitivity levels to U/Th that can be reached in this setup.