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Abstract Single-cell RNA sequencing (scRNA-seq) has emerged as a pivotal tool for exploring cellular landscapes across diverse species and tissues. Precise annotation of cell types is essential for understanding these landscapes, relying heavily on empirical knowledge and curated cell marker databases. In this study, we introduce MarkerGeneBERT, a natural language processing (NLP) system designed to extract critical information from the literature regarding species, tissues, cell types, and cell marker genes in the context of single-cell sequencing studies. Leveraging MarkerGeneBERT, we systematically parsed full-text articles from 3702 single-cell sequencing-related studies, yielding a comprehensive collection of 7901 cell markers representing 1606 cell types across 425 human tissues/subtissues, and 8223 cell markers representing 1674 cell types across 482 mouse tissues/subtissues. Comparative analysis against manually curated databases demonstrated that our approach achieved 76% completeness and 75% accuracy, while also unveiling 89 cell types and 183 marker genes absent from existing databases. Furthermore, we successfully applied the compiled brain tissue marker gene list from MarkerGeneBERT to annotate scRNA-seq data, yielding results consistent with original studies. Conclusions: Our findings underscore the efficacy of NLP-based methods in expediting and augmenting the annotation and interpretation of scRNA-seq data, providing a systematic demonstration of the transformative potential of this approach. The 27323 manual reviewed sentences for training MarkerGeneBERT and the source code are hosted at https://github.com/chengpeng1116/MarkerGeneBERT .

Abstract This study examines tuberculosis (TB) incidence among students in Jilin Province, China, focusing on spatial, temporal, and demographic dynamics in areas of social inequality. Variation in incidence rate of TB was analyzed using the joinpoint regression method. Spatial analyses techniques included the global and local Moran indices and Getis-Ord Gi* analysis. Demographic changes in new cases were analyzed descriptively, and the Geodetector method measured the influence of risk factors on student TB incidence. The analysis revealed a declining trend in TB cases, particularly among male students. TB incidence showed geographical heterogeneity, with lower rates in underdeveloped rural areas compared to urban regions. Significant spatial correlations were observed, with high-high clusters forming in central Jilin Province. Hotspots of student TB transmission were primarily concentrated in the southwestern and central regions from 2008 to 2018. Socio-economic factors exhibited nonlinear enhancement effects on incidence rates, with a dominant bifactor effect. High-risk zones were predominantly located in urban centers, with university and high school students showing higher incidences than other educational stages. The study revealed economic determinants as being especially important in affecting TB incidence among students, with these factors having nonlinear interacting effects on student TB incidence.

Abstract Motor learning (ML), which plays a fundamental role in growth and physical rehabilitation, involves different stages of learning and memory processes through different brain regions. However, the neural mechanisms that underlie ML are not sufficiently understood. Here, a previously unreported neuronal projection from the dorsal hippocampus (dHPC) to the zona incerta (ZI) involved in the regulation of ML behaviors is identified. Using recombinant adeno‐associated virus, the projections to the ZI are surprisingly identified as originating from the dorsal dentate gyrus (DG) and CA1 subregions of the dHPC. Furthermore, projection‐specific chemogenetic and optogenetic manipulation reveals that the projections from the dorsal CA1 to the ZI play key roles in the acquisition and consolidation of ML behaviors, whereas the projections from the dorsal DG to the ZI mediate the retrieval/retention of ML behaviors. The results reveal new projections from the dorsal DG and dorsal CA1 to the ZI involved in the regulation of ML and provide insight into the stages over which this regulation occurs.

Abstract Indigenous animal genetic resources play a crucial role in preserving global genetic diversity and supporting the livelihoods of millions of people. In Ethiopia, the majority of the cattle population consists of indigenous breeds. Understanding the genetic architecture of these cattle breeds is essential for effective management and conservation efforts. In this study, we sequenced DNA samples from 70 animals from seven indigenous cattle breeds, generating about two terabytes of pair-end reads with an average coverage of 14X. The sequencing data were pre-processed and mapped to the cattle reference genome (ARS-UCD1.2) with an alignment rate of 99.2%. Finally, the variant calling process produced approximately 35 million high-quality SNPs. These data provide a deeper understanding of the genetic landscape, facilitate the identification of causal mutations, and enable the exploration of evolutionary patterns to assist cattle improvement and sustainable utilization, particularly in the face of unpredictable climate changes.

Abstract This study aims to refine clinical designs within clear aligner therapy, exploring the appropriate ratio of anterior tooth retraction to intrusion under maximum anchorage. Using a three-dimensional finite element model and evaluating 19 load scenarios with first premolar extraction, the research identifies the optimal force angle for anterior tooth retraction as 45 to 55°. For clinical planning, it is recommended to design a retraction of 0.19 mm combined with an intrusion of 0.16 mm to achieve anterior tooth retraction. This investigation is crucial for enhancing understanding of biomechanical principles in clear aligner orthodontics, offering significant insights for effective treatments.

Abstract A fundamental understanding of the underlying mechanisms involved in biological invasions is crucial to developing effective risk assessment and control measures against invasive species. The fall armyworm (FAW), Spodoptera frugiperda, is a highly invasive pest that has rapidly spread from its native Americas into much of the Eastern Hemisphere, with a highly homogeneous nuclear genetic background. However, the exact mechanism behind its rapid introduction and propagation remains unclear. Here, a systematic investigation is conducted into the population dynamics of FAW in China from 2019 to 2021 and found that FAW individuals carrying “rice” mitochondria (FAW‐mR) are more prevalent (>98%) than that with “corn” mitochondria (FAW‐mC) at the initial stage of the invasion and in newly‐occupied non‐overwintering areas. Further fitness experiments show that the two hybrid‐strains of FAW exhibit different adaptions in the new environment in China, and this may have been facilitated by amino acid changes in mitochondrial‐encoded proteins. FAW‐mR used increases energy metabolism, faster wing‐beat frequencies, and lower wing loadings to drive greater flight performance and subsequent rapid colonization of new habitats. In contrast, FAW‐mC individuals adapt with more relaxed mitochondria and shuttle energetics into maternal investment, observed as faster development rate and higher fecundity. The presence of two different mitochondria types within FAW has the potential to significantly expand the range of damage and enhance competitive advantage. Overall, the study describes a novel invasion mechanism displayed by the FAW population that facilitates its expansion and establishment in new environments.

The white paper on China’s Arctic Policy, which proposed the joint construction of the Polar Silk Road (PSR), was officially published in January 2018. As a short and economically feasible sea route, the PSR will inevitably affect the carrier’s market choice behaviour, thereby affecting the foreland network structure and foreland pattern of China’s coastal container ports (CCCP). Grasping the evolution trend of CCCP foreland under the PSR will help predict the development trend of the port and shipping market in advance and enable measures to be taken to adapt to the changing market environment. This paper constructs the port foreland network evolution (PFNE) model and presents a complex network delineation method of port foreland to simulate the effects of PSR on CCCP foreland evolution in different scenarios. Results show that the PSR’s addition to the CCCP foreland network will improve shipping connectivity, increase the connection between long-distance ports, reshape the clustering groups, promote the orderliness of the network and help the development of small and medium-sized ports. China’s global maritime transport pattern will change, which is mainly reflected in the enhanced shipping links between CCCP and Asia, Europe and Africa, while the importance of the Americas for CCCP weaken. PSR has a more obvious role in promoting the establishment of maritime links between China’s northern ports and the world ports. In the discussion, we propose the development policy of CCCP under the PSR.

Abstract Centromere protein A (CENP‐A), a centromere‐specific histone H3 variant, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure‐activity relationship (SAR) study of the cell‐cycle‐arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)‐6‐Br‐JP18 and (+)‐6‐Cl‐JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X‐ray crystallography analysis reveals that both molecules bind to the colchicine‐binding site of β‐tubulin. Treatment of human cells with microtubule‐targeting agents (MTAs), including these two compounds, results in CENP‐A accumulation by destabilizing Cdh1, a co‐activator of the anaphase‐promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP‐A accumulation using small‐molecule tools and highlights the role of Cdh1 in CENP‐A proteolysis.

As a crucial exploration technique for unconventional reservoirs, hydraulic fracturing enables the formation of complex fracture networks, thereby facilitating the flow of oil and gas. The closure of natural fractures decreases stimulation performance. Microparticle proppants are used to fill natural fractures and effectively increase the stimulation area. The 100-mesh proppant conventionally used in field operations may be insufficiently small to effectively access natural fractures. In order to effectively overcome natural fractures closure, microparticle proppants (i.e., proppants with a diameter of 75 μm (200-mesh) or less) are required. The particle size threshold test of microparticle proppants placement is conducted to determine the size threshold of proppants flowing into natural fractures. The microparticle proppants placement experiment in multi-branch fractures is conducted to investigate the volume difference of proppants in different fractures. Numerical simulations are performed to model proppant transport within fractures of actual dimensions to facilitating the optimization of stimulation parameters. The main conclusions are as follows: (1) Effective inflow of microparticle proppants requires a size threshold of proppants. For the 200-mesh proppants, the size should be less than half of natural fractures width when microparticle proppants effectively flow into natural fractures. (2) Sand concentration affects the size threshold of microparticle proppants. The size threshold should appropriately increase to ensure the inflow of proppant. (3) Difference of multi-branch fracture width has a significant effect on volume of microparticle proppants inside fractures. When the width ratio of multi-branch fractures exceeds 2, this effect becomes obvious. (4) Particle size has an effect on proppant placement. 200-mesh proppants can obtain uniform distribution of proppants among natural fractures. 140-mesh proppants can obtain maximum proppant volume among natural fractures. Sand concentration significantly affects proppant placement performance. The optimal sand concentration is 60kg/m3. The pumping rate for a single cluster fracture should not be excessively low. The pumping rate should be larger than 0.5m3/min and the optimal pumping rate 2m3/min. In this paper, the particle size and concentration of particulate proppant are optimized and the geometric characteristics of fractures are considered. These conclusions provide important practical guidance and scientific basis for the optimization and application of hydraulic fracturing technology.

Abstract The skin is intrinsically a cell-membrane-compartmentalized hydrogel with high mechanical strength, potent antimicrobial ability, and robust immunological competence, which provide multiple protective effects to the body. Methods capable of preparing hydrogels that can simultaneously mimic the structure and function of the skin are highly desirable but have been proven to be a challenge. Here, dual structurally and functionally skin-mimicking hydrogels are generated by crosslinking cell-membrane compartments. The crosslinked network is formed via free radical polymerization using olefinic double bond-functionalized extracellular vesicles as a crosslinker. Due to the dissipation of stretching energy mediated by vesicular deformation, the obtained compartment-crosslinked network shows enhanced mechanical strength compared to hydrogels crosslinked by regular divinyl monomers. Biomimetic hydrogels also exhibit specific antibacterial activity and adequate ability to promote the maturation and activation of dendritic cells given the existence of numerous extracellular vesicle-associated bioactive substances. In addition, the versatility of this approach to tune both the structure and function of the resulting hydrogels is demonstrated through introducing a second network by catalyst-free click reaction-mediated crosslinking between alkyne-double-ended polymers and azido-decorated extracellular vesicles. This study provides a platform to develop dual structure- and function-controllable skin-inspired biomaterials.

Abstract The pink stem borer, Sesamia inferens (Walker), is a significant polyphagous pest historically restricted to regions south of N34° latitude. However, with changes in global climate and farming practices, the distribution of this moth has progressively exceeded its traditional limit of 34° N and encompassed most regions in North China. The genetic adaptations of S. inferens remain incompletely understood due to the lack of high-quality genome resources. Here, we sequenced the genome of S. inferens using PacBio and Hi-C technology, yielding a genome assembly of 865.04 Mb with contig N50 of 1.23 Mb. BUSCO analysis demonstrated this genome assembly has a high-level completeness of 96.1% gene coverage. In total, 459.72 Mb repeat sequences (53.14% of the assembled genome) and 20858 protein-coding genes were identified. We used the Hi-C technique to anchor 1135 contigs to 31 chromosomes, yielding a chromosome-level genome assembly with a scaffold N50 of 29.99 Mb. In conclusion, our high-quality genome assembly provided valuable resource that exploring the genetic characteristics of local adaptation and developing an efficient control strategy.

Predicting the production amounts has great significance for exploitation of oil and gas resources. The flow–geomechanical coupling effect plays an important role in predicting production. Shale rocks and the stress-dependent permeability model are critical for representing this coupling effect. The pore network of shale rock is not abundant like that of coal rock, and the matrix blocks of shale rock are not completely separated by the pore network. There is stress concentration around the pores when shale rock is deformed. Based on previous studies, the stress-dependent permeability model considering the impact of stress concentration is used in this study to build a numerical simulation model for flow–geomechanical coupling in a shale gas reservoir and validation using field data. Sensitivity studies are conducted to discuss the difference in production prediction between the new and common models. The main conclusions of this study are as follows: 1) The new model can fit both the field and experimental data well; the average error in daily production rate between the numerical solution and field data is 8%, which indicates that the new model can be used to predict shale gas production. 2) Under the geomechanical condition of a real reservoir, the difference in predicted production between models with and without stress concentration can be large and increase with the ratio of a to b. If this ratio is less than 50, the impact of stress concentration is not significant. Otherwise, the impact of stress concentration on production increases sharply and can exceed 20%. 3) The adsorption-induced strain enhances the impact of stress concentration on production. When the Langmuir pressure exceeds 1 MPa and Langmuir strain exceeds 0.01, the impact magnitude of stress concentration can exceed 10%.

Lewis Fry Richardson proposed his famous picture of turbulent flows in 1922, where the kinetic energy is transferred from large-scale to small-scale structures until the viscosity converts it into heat. This cascade idea, also known as the forward energy cascade, is now widely accepted and is treated as the cornerstone of not only turbulent modeling, but also global circulation models of the ocean and atmosphere. In this work, the Filter-Space-Technique is applied to the oceanic flow field provided by the CMEMS reanalysis model to quantify the scale-to-scale energy flux. A rich dynamical pattern associated with different scales is observed. More precisely, either positive or negative fluxes are observed, indicating the direction of the energy cascade, where the energy is transferred from large-scale structures to small-scale ones or vice versa. High-intensity energy exchange is found mainly in the Western Boundary Current Systems and Equatorial Counter Currents. For the latter case, a wavelike pattern is observed on the westward travel. Moreover, strong seasonal variation is evident for some scales and regions. These results confirm the existence of forward and inverse cascades and rich regional dynamics.

Abstract The yellow peach moth, Conogethes punctiferalis, is a highly polyphagous pest widespread in eastern and southern Asia. It demonstrates a unique ability to adapt to rotten host fruits and displays resistance to pathogenic microorganisms, including fungi. However, the lack of available genomic resources presents a challenge in comprehensively understanding the evolution of its innate immune genes. Here, we report a high-quality chromosome-level reference genome for C. punctiferalis utilizing PacBio HiFi sequencing and Hi-C technology. The genome assembly was 494 Mb in length with a contig N50 of 3.25 Mb. We successfully anchored 1,226 contigs to 31 pseudochromosomes. Our BUSCO analysis further demonstrated a gene coverage completeness of 96.3% in the genome assembly. Approximately 43% repeat sequences and 21,663 protein-coding genes were identified. In addition, we resequenced 110 C. punctiferalis individuals from east China, achieving an average coverage of 18.4 × and identifying 5.8 million high-quality SNPs. This work provides a crucial resource for understanding the evolutionary mechanism of C. punctiferalis’ innate immune system and will help in developing new antibacterial drugs.

Abstract Studying language evolution brings a crucial perspective to bear on questions of human prehistory. As the most linguistically diverse region on earth, East and Southeast Asia have witnessed extensive sociocultural and ethnic contacts among different language communities. Especially, the Kra-Dai language family exhibits tremendous socio-cultural importance in these regions. Due to limited historical accounts, however, there are several controversies on their linguistic relatedness, ambiguities regarding the divergence time, and uncertainties on the dispersal patterns. To address these issues, here we apply Bayesian phylogenetic methods to analyze the largest lexical dataset containing 646 cognate sets compiled for 100 Kra-Dai languages. Our dated phylogenetic tree showed their initial divergence occurring approximately 4000 years BP. Phylogeographic results supported the early Kra-Dai language dispersal from the Guangxi-Guangdong area of South China towards Mainland Southeast Asia. Coupled with genetic, archaeological, paleoecologic, and paleoclimatic data, we demonstrated that the Kra-Dai language diversification could have coincided with their demic diffusion and agricultural spread shaped by the global climate change in the late Holocene. The interdisciplinary alignments shed light on reconstructing the prehistory of Kra-Dai languages and provide an indispensable piece of the puzzle for further studying prehistoric human activities in East and Southeast Asia.

Systemic toxicity is a major challenge in the development of therapeutics. Consequently, cell-type-specific targeting is needed to improve on-target efficacy while reducing off-target toxicity. Here, we describe a cell-targeting system we have termed BRAID (BRidged Activation by Intra/intermolecular Division) whereby an active molecule is divided into two inactive or less active parts that are subsequently brought together via a so-called ‘bridging receptor’ on the target cell. This concept was validated using the WNT/β-catenin signaling system, demonstrating that a multivalent WNT agonist molecule divided into two inactive components assembled from different epitopes via the hepatocyte receptor βKlotho induces signaling specifically on hepatocytes. These data provide proof of concept for this cell-specific targeting strategy, and in principle, this may also allow activation of multiple signaling pathways where desirable. This approach has broad application potential for other receptor systems.

Abstract Chemotherapy prior to immune checkpoint blockade (ICB) treatment appears to improve ICB efficacy but resistance to ICB remains a clinical challenge and is attributed to highly plastic myeloid cells associating with the tumor immune microenvironment (TIME). Here we show by CITE-seq single-cell transcriptomic and trajectory analyses that neoadjuvant low-dose metronomic chemotherapy (MCT) leads to a characteristic co-evolution of divergent myeloid cell subsets in female triple-negative breast cancer (TNBC). Specifically, we identify that the proportion of CXCL16 + myeloid cells increase and a high STAT1 regulon activity distinguishes Programmed Death Ligand 1 (PD-L1) expressing immature myeloid cells. Chemical inhibition of STAT1 signaling in MCT-primed breast cancer sensitizes TNBC to ICB treatment, which underscores the STAT1’s role in modulating TIME. In summary, we leverage single-cell analyses to dissect the cellular dynamics in the tumor microenvironment (TME) following neoadjuvant chemotherapy and provide a pre-clinical rationale for modulating STAT1 in combination with anti-PD-1 for TNBC patients.

In East Asian archaeology, initial domestication and early dispersal of rice have continuously attracted scholarly interest in the recent decade, which has generated abundant new materials and revised opinions. This paper starts with a refreshed understanding of the domestication concept that emphasizes the dominant role of human behavior in the mutualistic relationship. A thorough review of the approaches to and data on reconstructing the rice story during 10,000–7,000 BP demonstrates the causally chained changes in phenotype, genotype, and human behavior in the establishment of domestication. Future studies will benefit from the revised paradigm, which has great potential to extract archaeological information to explain multiple mechanisms in rice domestication.

Abstract The accomplishment of condition monitoring and intelligent maintenance for cantilever structure‐based energy harvesting devices remains a challenge. Here, to tackle the problems, a novel cantilever‐structure freestanding triboelectric nanogenerator (CSF‐TENG) is proposed, which can capture ambient energy or transmit sensory information. First, with and without a crack in cantilevers, the simulations are carried out. According to simulation results, the maximum change ratios of natural frequency and amplitude are 1.1% and 2.2%, causing difficulties in identifying defects by these variations. Thus, based on Gramian angular field and convolutional neural network, a defect detection model is established to achieve the condition monitoring of the CSF‐TENG, and the experimental result manifests that the accuracy of the model is 99.2%. Besides, the relation between the deflection of cantilevers and the output voltages of the CSF‐TENG is first built, and then the defect identification digital twin system is successfully created. Consequently, the system is capable of duplicating the operation of the CSF‐TENG in a real environment, and displaying defect recognition results, so the intelligent maintenance of the CSF‐TENG can be realized.

Pathogenic fungi of the genus Cryptococcus can undergo bisexual and unisexual reproduction. Here, the authors construct a gene-deletion library for over 100 transcription factor genes in Cryptococcus deneoformans and provide insights into regulatory cascades that are specific for each reproductive mode.

Mechanisms for cellular detoxification of drug compounds are of significant interest in human health. Cyclosporine A (CsA) and tacrolimus (FK506) are widely known antifungal and immunosuppressive microbial natural products. However, both compounds can result in significant side effects when used as immunosuppressants. The insect pathogenic fungus Beauveria bassiana shows resistance to CsA and FK506. However, the mechanisms underlying the resistance have remained unknown. Here, we identify a P4-ATPase gene, BbCRPA, from the fungus, which confers resistance via a unique vesicle mediated transport pathway that targets the compounds into detoxifying vacuoles. Interestingly, the expression of BbCRPA in plants promotes resistance to the phytopathogenic fungus Verticillium dahliae via detoxification of the mycotoxin cinnamyl acetate using a similar pathway. Our data reveal a new function for a subclass of P4-ATPases in cell detoxification. The P4-ATPases conferred cross-species resistance can be exploited for plant disease control and human health protection.

To study the development trend of embedded platforms in home appliances Internet of Things (IoT), an application of embedded Linux in the design of IoT gateway is designed. ARM microprocessor S3C2410, EM310 radio frequency (RF) module, and Ethernet DM9000A module are used to realize the home network information-processing platform. The platform utilizes existing network facilities, RF modules, and network interface modules to realize the interconnection of the home perception network through wireless or wired links. For experimental analysis, Ping the central server (gateway) from the IoT node B is set to twice: The first time ttl = 255 time = 1.9 ms, the second time: ttl = 255 time = 2.4 ms. After application verification, the system has the characteristics of low cost, small size, low power consumption, and vital ease of use. It can not only integrate the home Internet and the IoT gateway but also directly run application-layer communication protocols such as HTTP/MQTT between IoT nodes and Internet terminals. The design supports multi-hop communication and significantly increases the deployment range of IoT nodes without signal relay equipment, hence reducing the cost of IoT networking and the complexity of the network architecture.

Abstract Most of the smallest flying insects use bristled wings. It was observed that during the second half of their upstroke, the left and right wings become parallel and close to each other at the back, and move upward at zero angle of attack. In this period, the wings may produce drag (negative vertical force) and side forces which tend to push two wings apart. Here we study the aerodynamic forces and flows of two simplified bristled wings experiencing such a motion, compared with the case of membrane wings (flat-plate wings), to see if there is any advantage in using the bristled wings. The method of computational fluid dynamics is used in the study. The results are as follows. In the motion of two bristled wings, the drag acting on each wing is 40% smaller than the case of a single bristled wing conducting the same motion, and only a very small side force is produced. But in the case of the flat-plate wings, although there is similar drag reduction, the side force on each wing is larger than that of the bristled wing by an order of magnitude (the underlying physical reason is discussed in the paper). Thus, if the smallest insects use membrane wings, their flight muscles need to overcome large side forces in order to maintain the intended motion for less negative lift, whereas using bristled wings do not have this problem. Therefore, the adoption of bristled wings can be beneficial during upward movement of the wings near the end of the upstroke, which may be one reason why most of the smallest insects adopt them.

Side-scan sonar (SSS) is an important underwater imaging method that has high resolutions and is convenient to use. However, due to the restriction of conventional pulse compression technology, the side-scan sonar beam sidelobe in the range direction is relatively high, which affects the definition and contrast of images. When working in a shallow-water environment, image quality is especially influenced by strong bottom reverberation or other targets on the seabed. To solve this problem, a method for image-quality improvement based on deconvolution is proposed herein. In this method, to increase the range resolution and lower the sidelobe, a deconvolution algorithm is employed to improve the conventional pulse compression. In our simulation, the tolerance of the algorithm to different signal-to-noise ratios (SNRs) and the resolution ability of multi-target conditions were analyzed. Furthermore, the proposed method was applied to actual underwater data. The experimental results showed that the quality of underwater acoustic imaging could be effectively improved. The ratios of improvement for the SNR and contrast ratio (CR) were 32 and 12.5%, respectively. The target segmentation results based on this method are also shown. The accuracy of segmentation was effectively improved.

Toxic metabolites produced by phytopathogens can subvert host immunity. Here the authors show that the Arabidopsis P4-ATPases, AtALA1 and AtALA7 mediate mycotoxin detoxification by promoting vesicle transport and their subsequent sequestration and degradation in vacuoles.

Milk production in the Andean highlands is variable over space and time. This variability is related to fluctuating environmental factors such as rainfall season which directly influence the availability of livestock feeding resources. The main aim of this study was to develop a time-series model to forecast milk production in a mountainous geographical area by analysing the dynamics of milk records thorough the year. The study was carried out in the Andean highlands, using time-series models of monthly milk records collected routinely from dairy cows maintained in a controlled experimental farm over a 9-year period (2008-2016). Several statistical forecasting models were compared. The Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and Mean Absolute Percent Error (MAPE) were used as selection criteria to compare models. A relation between monthly milk records and the season of the year was modelled using seasonal autoregressive integrated moving average (SARIMA) methods to explore temporal redundancy (trends and periodicity). According to white noise residual test (Q = 13.951 and p = 0.052), Akaike Information Criterion and MAE, MAPE, and RMSE values, the SARIMA (1, 0, 0) x (2, 0, 0)12 time-series model resulted slightly better forecasting model compared to others. In conclusion, time-series models were promising, simple and useful tools for producing reasonably reliable forecasts of milk production thorough the year in the Andean highlands. The forecasting potential of the different models were similar and they could be used indistinctly to forecast the milk production seasonal fluctuations. However, the SARIMA model performed the best good predictive capacity minimizing the prediction interval error. Thus, a useful effective strategy has been developed by using time-series models to monitor milk production and alleviate production drops due to seasonal factors in the Andean highlands.

The influence of a mechanical structure’s volume increment on the volume power density (VPD) of triboelectric nanogenerators (TENGs) is often neglected when considering surface charge density and surface power density. This paper aims to address this gap by introducing a standardized VPD metric for a more comprehensive evaluation of TENG performance. The study specifically focuses on 2 frequency-up mechanisms, namely, the integration of planetary gears (PG-TENG) and the implementation of a double-cantilever structure (DC-TENG), to investigate their impact on VPD. The study reveals that the PG-TENG achieves the highest volume average power density, measuring at 0.92 W/m3. This value surpasses the DC-TENG by 1.26 times and the counterpart TENG by a magnitude of 69.9 times. Additionally, the PG-TENG demonstrates superior average power output. These findings introduce a new approach for enhancing TENGs by incorporating frequency-up mechanisms, and highlight the importance of VPD as a key performance metric for evaluating TENGs.

BackgroundOur study aimed to construct and validate prognostic nomograms for predicting survival for patients with Nonfunctional Pancreatic neuroendocrine tumor (NF-pNET).MethodsThis retrospective study included 1824 patients diagnosed with NF-pNET in the Surveillance, Epidemiology and End Results database between 2004 and 2016. Randomization divided the patients into training (n = 1278) and validation (n = 546) cohorts. Prognostic factors were determined using Cox regression analyses, nomograms based on AJCC 7th and 8th staging system were constructed separately. The prediction models were validated using internal validation and external validation.ResultsAge, year of diagnosis, primary tumor site, grade, 7th or 8th TNM stage, surgery, tumor size were determined as prognostic indicator to construct two nomograms. Harrell's concordance index (C-index) of two nomograms exhibited a clinical predictive ability of 0.828 (95%CI, 0.808~0.849) vs 0.828 (95% CI, 0.808~0.849) in the internal verification. The c-index in the external validation was 0.812 (95%CI, 0.778~0.864) vs 0.814 (95% CI, 0.779~0.848). The predictive power of the two nomograms is comparable.ConclusionsOur nomogram may be a effective tool for predicting overall survival in patients with NF-pNET. The AJCC 8th-edition system provides discrimination similar to that of the 7th-edition system.

Introcution: Water-flooding is an effective way to develop the extra-low permeability oil reservoirs and the water-flooding induced fracture (WIF) can improve waterflooding efficiency. However, geomechanical properties of rocks may alter due to the water-rock interactions, which usually increases the heterogeneity of reservoir properties and affects the WIF propagation.Methods: In this study, a method to calculate the WIF propagation length was proposed and numerical models were established considering the effect of water-rock interactions on geomechanical properties. In addition, the numerical model of stress distribution of the WIF propagation was validated by theoretical solutions based on the fracture mechanics. Moreover, the WIF propagation mechanism and the effect of water-rock interactions on the WIF propagation was analyzed.Results: Results indicate that the numerical model is valid to calculate the stress distribution induced by the WIF with an error under 5%. In addition, the WIF propagation can be affected by several factors, including the injection pressure, the damage variable and the initial fracture length. Noteworthy, the injection pressure should be strictly controlled because the WIF propagation is highly sensitive to the injection pressure. An increase of 2 MPa in the injection pressure can result in 90 m WIF propagation length, accounting for 64% of initial fracture length in the case studied in this work.Discussion: Moreover, water-rock interactions aggravate the heterogeneity of the reservoir and promote the WIF propagation due to the alteration of the geomechanical properties such as Young’s modulus. Therefore, the WIF can propagate even if the injection pressure is less than the minimum horizontal stress. Furthermore, the stress intensity factor (KIA) and WIF propagation length increase with the initial fracture length, which may lead to sudden water flux and reduce the efficiency of waterflooding.

Abstract An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications.

Jumping is an important locomotion function to extend navigation range, overcome obstacles, and adapt to unstructured environments. Here, authors demonstrate legless soft robot capable of rapid, continuous, and steered jumping based on a soft electrohydrostatic bending actuator.

Abstract The combination of biological neurology and memristive theory has greatly promoted the development of neuromorphic computing. To build a large-scale artificial intelligence alert system, the exploration of bionic synapses compatible with standard processes has become an urgent problem to be solved in the next step. In response to the above application requirements, this paper proposes a volatile avalanche diode threshold switching (VADTS) that is fully compatible with standard semiconductor technology to simulate the various functions of the synapse. Technology computer-aided design device-level simulation can verify the bionic principle of VADTS. The function of VADTS's bionic synapse was verified by the experimental test platform. The results show that under the action of the excitation signal (11.25 V), the device can continuously change from a high-resistance state to a low-resistance state. When the excitation signal is lower than the threshold, VADTS presents a “no adaptation” state of nerve synapses. When the excitation signal is higher than the threshold and changes continuously, the current changes along with the amplitude of the excitation signal, similar to the “sensitization” state of the nerve synapse.

Stand age is a significant factor when investigating forest resource management. How to obtain age data at a sub-compartment level on a large regional scale conveniently and in real time has become an urgent scientific challenge in forestry research. In this study, we established two strategies for stand-age estimation at sub-compartment and pixel levels, specifically object-based and pixel-based approaches. First, the relationship between canopy height and stand age was established based on field measurement data, which was achieved at the Mao’er Mountain Experimental Forest Farm in 2020 and 2021. The stand age was estimated using the relationship between the canopy height, the stand age, and the canopy-height map, which was generated from multi-resource remote sensing data. The results showed that the validation accuracy of the object-based estimation results of the stand age and the canopy height was better than that of the pixel-based estimation results, with a root mean squared error (RMSE) increase of 40.17% and 33.47%, respectively. Then, the estimated stand age was divided into different age classes and compared with the forest inventory data (FID). As a comparison, the object-based estimation results had better consistency with the FID in the region of the broad-leaved forests and the coniferous forests. In addition, the pixel-based estimation results had better accuracy in the mixed forest regions. This study provided a reference for estimating stand age and met the requirements for stand-age data at the pixel and sub-compartment levels for studies involving different forestry applications.

Coal is the most prevalent energy source in China and plays an important role in ensuring energy security. The continuous monitoring of coal mining activities is helpful to clarify the incremental space of coal production and establish a rational framework for future coal production capacity. In this study, a multi-source remote sensing approach utilizing SPOT 4, GF, and Landsat data is employed to monitor land cover and vegetation changes in the Juhugeng mining area of the Muli coalfield over a span of nearly 20 years. The analysis incorporates an object-oriented classification method and a vegetation parameter to derive insights. The findings reveal that the mining operations can be divided into two periods, since their initiation in 2003 until their cessation in 2021, with a dividing point around 2013/2014. The initial phase witnessed rapid and even accelerated expansion of the mine, while the subsequent phase was characterized by more stable development and the implementation of some restorative measures for the mine environment. Although the vegetation parameter, Fractional Vegetation Cover (FVC), indicates some reclamation efforts within the mining area, the extent of the reclaimed land remains limited. This study demonstrates the effective application of object-oriented classification in conjunction with the vegetation parameter FVC for monitoring coal mining areas.

COVID-19 pandemic is a global health risk, but our understanding on the induced durable immunity remains scarce. Here the authors assess antibody responses in 869 convalescent COVID-19 patients to find that specific antibody titers reduce with time, and the RBD-IgG positive rate exceed 70% at 12 month post diagnosis, with male and older patients showing stronger responses.

Abstract Influenza is an infectious disease that leads to an estimated 5 million cases of severe illness and 650,000 respiratory deaths worldwide each year. The early detection and prediction of influenza outbreaks are crucial for efficient resource planning to save patient’s lives and healthcare costs. We propose a new data-driven methodology for influenza outbreak detection and prediction at very local levels. A doctor’s diagnostic dataset of influenza-like illness from more than 3000 clinics in Malaysia is used in this study because these diagnostic data are reliable and can be captured promptly. A new region index (RI) of the influenza outbreak is proposed based on the diagnostic dataset. By analysing the anomalies in the weekly RI value, potential outbreaks are identified using statistical methods. An ensemble learning method is developed to predict potential influenza outbreaks. Cross-validation is conducted to optimize the hyperparameters of the ensemble model. A testing data set is used to provide an unbiased evaluation of the model. The proposed methodology is shown to be sensitive and accurate at influenza outbreak prediction, with average of 75% recall, 74% precision, and 83% accuracy scores across five regions in Malaysia. The results are also validated by Google Flu Trends data, news reports, and surveillance data released by World Health Organization.

Abstract Ethylene metabolism is very important for climacteric fruit, and apricots are typical climacteric fruit. The activity of pectinase is closely related to fruit firmness, which further affects fruit quality. To better understand ethylene metabolism, pectinase activity and their molecular regulation mechanisms during the development and ripening of apricot fruit, ethylene metabolism, pectinase activity and the “Luntaibaixing” apricot fruit transcriptome were analyzed at different developmental stages. Ethylene metabolic precursors, enzyme activities and ethylene release increased during fruit development and ripening, with significant differences between the ripening stage and other stages (P

Abstract Coronavirus disease 2019 (COVID‐19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID‐19 hyperimmune globulin (COVID‐HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP‐CorV (Sinopharm COVID‐19 vaccine). COVID‐HIG shows high‐affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike (S) protein, the receptor‐binding domain (RBD), the N‐terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin‐converting enzyme 2 (hACE2). Pseudotyped and authentic virus‐based assays show that COVID‐HIG displays broad‐spectrum neutralization effects on a wide variety of SARS‐CoV‐2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID‐HIG in an Adv5‐hACE2‐transduced IFNAR−/− mouse model of SARS‐CoV‐2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID‐HIG exhibits neutralization potency similar to that of anti‐SARS‐CoV‐2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID‐HIG against SARS‐CoV‐2 infection and provide reference for subsequent clinical trials.

Summary: Radiotherapy combined with immune checkpoint blockade has gradually revealed the superiority in the antitumor therapy; however, the contribution of host PD-L1 remains elusive. In this study, we found that the activation of CD8+ T cells was strikingly increased in both irradiated PD-L1-expressing primary tumor and distant non-irradiated syngeneic tumor in PD-L1-deficient mouse host, and thus enhanced radiation-induced antitumor abscopal effect (ATAE) by activating cGAS-STING pathway. Notably, the autophagy inhibitors distinctively promoted dsDNA aggregation in the cytoplasm and increased the release of cGAS-STING-regulated IFN-β from irradiated cells, which further activated bystander CD8+ T cells to release IFN-γ and contributed to ATAE. These findings revealed a signaling cascade loop that the cytokines released from irradiated tumor recruit CD8+ T cells that in turn act on the tumor cells with amplified immune responses in PD-L1-deficient host, indicating a potential sandwich therapy strategy of RT combined with PD-L1 blockage and autophagy inhibition.

Summary: Emerging threats of rapid spread highly lethal infectious diseases highlight the urgent need of vaccine development. Here, we describe the preparation of envelope virus-mimetic nanovaccines by hybridizing bioengineered cell membranes with bacterial vesicles. Membranes acquired from bioengineered cells overexpressing viral antigens are fused with bacterial outer membrane vesicles to develop hybrid nanovesicles. Because of the presence of intact viral antigenic proteins with natural conformation bound to lipid bilayer and pathogen-associated molecular patterns, hybrid nanovesicles can strikingly promote antigen uptake, processing and presentation by dendritic cells. Immunization with envelope virus-mimetic nanovaccines shows significantly enhanced maturation and activation of dendritic cells, which elicit robust humoral and cellular immune responses in mice. By virtue of their artificial characteristic and absence of loaded adjuvants, these biomimetic nanovaccines exhibit favorable biosafety. Our work demonstrates the effectiveness of envelope virus-mimetic nanovaccines to boost antigen-specific immunity and proposes a simple yet versatile platform to prepare antiviral vaccines.

Accurate and efficient large-scale mapping of P. euphratica distribution is of great importance for managing and protecting P. euphratica forests, policy making, and realizing sustainable development goals in the ecological environments of desert areas. In large regions, numerous types of vegetation exhibit spectral characteristics that closely resemble those of P. euphratica, such as Tamarix, artificial forests, and allée trees, posing challenges for the accurate identification of P. euphratica. To solve this issue, this paper presents a method for large-scale P. euphratica distribution mapping. The geographical distribution characteristics of P. euphratica were first utilized to rapidly locate the appropriate region of interest and to further reduce background complexity and interference from other similar objects. Spectral features, indices, phenological features, and backscattering features extracted from all the available Sentinel-2 MSI and Sentinel-1 SAR data from 2021 were regarded as the input for a random forest model used to classify P. euphratica in the GEE platform. The results were then compared with the results from the method using only spectral features and index features, the results from the method that only added phenological features, and the results from the method that added phenological features and backscattering features by visually and quantitatively referencing field-surveyed samples, UAV data, and high-spatial-resolution data from Google Earth Data and Map World. The comparison indicated that the proposed method, which adds both phenological and time-series backscattering features, could correctly distinguish P. euphratica from other types of vegetation that have spectral information similar to P. euphratica. The rates of omission errors (OEs), commission errors (CEs), and overall accuracy (OA) for the proposed method were 12.53%, 11.01%, and 89.32%, respectively, representing increases of approximately 9%, 17%, and 13% in comparison with the method using only spectral and index features. The proposed method significantly improved the accuracy of P. euphratica classification in terms of both omission and, especially, commission.

Mechanisms underlying gene repression and silencers remain poorly understood. Here the authors investigate the role of H3K27me3-rich regions in the genome, as defined from clusters of H3K27me3 peaks, in regulating gene expression via looping.

Two epigenetic pathways of transcriptional repression, DNA methylation and polycomb repressive complex 2 (PRC2), are known to regulate neuronal development and function. However, their respective contributions to brain maturation are unknown. We found that conditional loss of the de novo DNA methyltransferase Dnmt3a in mouse excitatory neurons altered expression of synapse-related genes, stunted synapse maturation, and impaired working memory and social interest. At the genomic level, loss of Dnmt3a abolished postnatal accumulation of CG and non-CG DNA methylation, leaving adult neurons with an unmethylated, fetal-like epigenomic pattern at ~222,000 genomic regions. The PRC2-associated histone modification, H3K27me3, increased at many of these sites. Our data support a dynamic interaction between two fundamental modes of epigenetic repression during postnatal maturation of excitatory neurons, which together confer robustness on neuronal regulation.

Abstract Sacha inchi (Plukenetia volubilis L.) is a shrub native to Amazon rainforests that’s of commercial interest as its seeds contain 35–60% edible oil (dry weight). This oil is one of the healthiest vegetable oils due to its high polyunsaturated fatty acid content and favourable ratio of omega-6 to omega-3 fatty acids. De novo transcriptome assembly and comparative analyses were performed on sacha inchi seeds from five stages of seed development in order to identifying genes associated with oil accumulation and fatty acid production. Of 30,189 unigenes that could be annotated in public databases, 20,446 were differentially expressed unigenes. A total of 14 KEGG pathways related to lipid metabolism were found, and 86 unigenes encoding enzymes involved in α-linolenic acid (ALA) biosynthesis were obtained including five unigenes encoding FATA (Unigene0008403), SAD (Unigene0012943), DHLAT (Unigene0014324), α-CT (Unigene0022151) and KAS II (Unigene0024371) that were significantly up-regulated in the final stage of seed development. A total of 66 unigenes encoding key enzymes involved in the synthesis of triacylglycerols (TAGs) were found, along with seven unigenes encoding PDCT (Unigene0000909), LPCAT (Unigene0007846), Oleosin3 (Unigene0010027), PDAT1 (Unigene0016056), GPDH (Unigene0022660), FAD2 (Unigene0037808) and FAD3 (Unigene0044238); these also proved to be up-regulated in the final stage of seed development.

The swelling-weakening behaviour of synthetic hydrogels is a major limitation to many applications. Here, the authors report on the covalent linkage of precursor loaded liposomes which are deformed upon hydrogel swelling and release precursor to form a secondary network strengthening the hydrogel.