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ABSTRACT Arthropods harbor complex microbiota that play a pivotal role in host fitness. While multiple factors, like host species and diet, shape microbiota in arthropods, their impact on community assembly in wild insects remains largely unknown. In this study, we surveyed bacterial and fungal community assembly in nine sympatric wild insect species that share a common citrus fruit diet. Source tracking analysis suggested that these insects acquire some bacteria and fungi from the citrus fruit with varying degrees. Although sharing a common diet led to microbiota convergence, the diversity, composition, and network of both bacterial and fungal communities varied significantly among surveyed insect groups. Null model analysis indicated that stochastic processes, particularly dispersal limitation and drift, are primary drivers of structuring insect bacterial and fungal communities. Importantly, the influence of each community assembly process varied strongly depending on the host species. Thus, we proposed a speculative view that the host specificity of the microbiome and mycobiome assembly is widespread in wild insects despite sharing the same regional species pool. Overall, this research solidifies the importance of host species in shaping microbiomes and mycobiomes, providing novel insights into their assembly mechanisms in wild insects.IMPORTANCESince the microbiome has been shown to impact insect fitness, a mechanistic understanding of community assembly has potentially significant applications but remains largely unexplored. In this paper, we investigate bacterial and fungal community assembly in nine sympatric wild insect species that share a common diet. The main findings indicate that stochastic processes drive the divergence of microbiomes and mycobiomes in nine sympatric wild insect species. These findings offer novel insights into the assembly mechanisms of microbiomes and mycobiomes in wild insects.

Aiming at the problem of waveform distortion of the secondary traveling wave obtained from the primary traveling wave signal transmitted by the voltage traveling wave sensor, an accurate detection method of voltage traveling wave based on ensemble empirical mode decomposition (EEMD) and L1 norm least squares regularization is proposed in this paper. Firstly, the forward transfer function model of the specialized voltage traveling wave sensor is established, and the inversion model is derived to analyze the phase frequency and amplitude frequency characteristics of the secondary traveling wave after transmission. EEMD is used to decompose the secondary traveling wave into the intrinsic modal function (IMF) components of different frequency bands. The L1 norm least square regularization inversion algorithm was used to invert each IMF component. Finally, the IMF' components after inversion are synthesized to obtain the primary traveling wave. Simulation and experimental results demonstrate that the proposed method is not affected by noise, mode aliasing effect and regularization parameter accuracy, and the obtained waveform has high similarity to the simulated waveform, which enables precise identification of fault traveling wave.

Abstract Two‐dimensional (2D) non‐layered materials, along with their unique surface properties, offer intriguing prospects for sensing applications. Introducing mechanical degrees of freedom is expected to enrich the sensing performances of 2D non‐layered devices, such as high frequency, high tunability, and large dynamic range, which could lead to new types of high performance nanosensors. Here, we demonstrate 2D non‐layered nanomechanical resonant sensors based on β‐In2S3, where the devices exhibit robust nanomechanical vibrations up to the very high frequency (VHF) band. We show that such device can operate as pressure sensor with broad range (from 10−3 Torr to atmospheric pressure), high linearity (with a nonlinearity factor as low as 0.0071), and fast response (with an intrinsic response time less than 1 μs). We further unveil the frequency scaling law in these β‐In2S3 nanomechanical sensors and successfully extract both the Young's modulus and pretension for the crystal. Our work paves the way towards future wafer‐scale design and integrated sensors based on 2D non‐layered materials.

Background: The treatment of oral leukoplakia (OLK) with aminolaevulinic acid photodynamic therapy (ALA-PDT) is widespread. Nonetheless, there is variation in efficacy. Therefore, this study constructed a model for predicting the short-term efficacy and recurrence of OLK after ALA-PDT. Methods: The short-term efficacy and recurrence of ALA-PDT were calculated by statistical analysis, and the relevant influencing factors were analyzed by Logistic regression and COX regression model. Finally, prediction models for total response (TR) rate, complete response (CR) rate and recurrence in OLK patients after ALA-PDT treatment were established. Features from pathology sections were extracted using deep learning autoencoder and combined with clinical variables to improve prediction performance of the model. Results: The logistic regression analysis showed that the non-homogeneous (OR: 4.911, P: 0.023) OLK and lesions with moderate to severe epithelial dysplasia (OR: 4.288, P: 0.042) had better short-term efficacy. The area under receiver operating characteristic curve (AUC) of CR, TR and recurrence predict models after the ALA-PDT treatment of OLK patients is 0.872, 0.718, and 0.564, respectively. Feature extraction revealed an association between inflammatory cell infiltration in the lamina propria and recurrence after PDT. Combining clinical variables and deep learning improved the performance of recurrence model by more than 30 %. Conclusions: ALA-PDT has excellent short-term efficacy in the management of OLK but the recurrence rate was high. Prediction model based on clinicopathological characteristics has excellent predictive effect for short-term efficacy but limited effect for recurrence. The use of deep learning and pathology images greatly improves predictive value of the models.

ABSTRACT Cyclic purine nucleotides are important signal transduction molecules across all domains of life. 3′,5′-cyclic di-adenosine monophosphate (c-di-AMP) has roles in both prokaryotes and eukaryotes, while the signals that adjust intracellular c-di-AMP and the molecular machinery enabling a network-wide homeostatic response remain largely unknown. Here, we present evidence for an acetyl phosphate (AcP)-governed network responsible for c-di-AMP homeostasis through two distinct substrates, the diadenylate cyclase DNA integrity scanning protein (DisA) and its newly identified transcriptional repressor, DasR. Correspondingly, we found that AcP-induced acetylation exerts these regulatory actions by disrupting protein multimerization, thus impairing c-di-AMP synthesis via K66 acetylation of DisA. Conversely, the transcriptional inhibition of disA was relieved during DasR acetylation at K78. These findings establish a pivotal physiological role for AcP as a mediator to balance c-di-AMP homeostasis. Further studies revealed that acetylated DisA and DasR undergo conformational changes that play crucial roles in differentiation. Considering the broad distribution of AcP-induced acetylation in response to environmental stress, as well as the high conservation of the identified key sites, we propose that this unique regulation of c-di-AMP homeostasis may constitute a fundamental property of central circuits in Actinobacteria and thus the global control of cellular physiology.IMPORTANCESince the identification of c-di-AMP is required for bacterial growth and cellular physiology, a major challenge is the cell signals and stimuli that feed into the decision-making process of c-di-AMP concentration and how that information is integrated into the regulatory pathways. Using the bacterium Saccharopolyspora erythraea as a model, we established that AcP-dependent acetylation of the diadenylate cyclase DisA and its newly identified transcriptional repressor DasR is involved in coordinating environmental and intracellular signals, which are crucial for c-di-AMP homeostasis. Specifically, DisA acetylated at K66 directly inactivates its diadenylate cyclase activity, hence the production of c-di-AMP, whereas DasR acetylation at K78 leads to increased disA expression and c-di-AMP levels. Thus, AcP represents an essential molecular switch in c-di-AMP maintenance, responding to environmental changes and possibly hampering efficient development. Therefore, AcP-mediated posttranslational processes constitute a network beyond the usual and well-characterized synthetase/hydrolase governing c-di-AMP homeostasis.

Aims: Cerebral ischemic preconditioning is a neuroprotective therapy against cerebral ischemia and ischemia-reperfusion injury. This study aims to demonstrate the alternation of gene expression in exosomes from brain tissue of mice after ischemic preconditioning and their potential functions. Methods: Ten mice were divided into the sham and the cerebral ischemic preconditioning groups. Their brain tissues were harvested, from which the exosomes were extracted. The characteristics and protective effects of exosomes were evaluated. Whole transcriptome sequencing was used to demonstrate the gene expression discrepancy between the exosomes from the two groups of mice brains. Volcano graphs and heatmaps were used to picture the difference in expression quantity of mRNA, lncRNA, and circRNA. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to demonstrate the functions of differentially expressed RNAs. Results: Exosomes were successfully extracted, and those from the cerebral ischemic preconditioning group had better protective effects on cells that received oxygen-glucose deprivation and restoration injury. A total of 306 mRNAs and 374 lncRNAs were significantly upregulated, and 320 mRNAs and 405 lncRNAs were significantly downregulated in the preconditioning group. No circRNAs were differentially expressed between the two groups. GO and KEGG pathway analysis indicated that the functions of differentially expressed RNAs were related to both neural protective and injurious effects. Conclusion: The brain-derived exosomes may participate in the neuroprotective effect of cerebral ischemic preconditioning. Thorough research is necessary to investigate exosome functions derived from the ischemic preconditioned brain.

Climate warming rates in the Arctic are far greater than the global average, exerting stronger impacts on permafrost degradation and thermokarst landform development. Thermokarst lakes and ponds (TLPs), which are widely distributed in the Lena Basin in the Russian Arctic, play a vital role in altering local ecosystem. However, the detailed distribution of TLPs in the Lena Basin still remains poorly known. In this study, we built the first 10 m resolution TLP dataset for the Lena Basin in the 2020 thawing season by utilizing 4902 Sentinel-2 images. A robust mapping workflow was developed and implemented in the Google Earth Engine (GEE) platform. The accuracy assessment demonstrates a satisfactory accuracy (93.63%), and our results exhibit a better consistency with real TLPs than global water body products. A total of 380,477 TLPs (~0.53% of the total surface area of the Lena Basin) were identified, showing an uneven distribution in the five sub-basins. The TLPs were found to be mainly located within plain areas, with an active layer thickness in the range of 80–100 cm. The higher ground ice content and mean annual ground temperature were favorable for TLP development. This dataset will be valuable for investigating the complex interaction between TLPs and permafrost. It will also serve as a baseline product for better incorporating thermokarst processes into permafrost-climate models.

Abstract Coix lacryma-jobi L. is one of the most economically and medicinally important corns. This study constructed a high-density genetic linkage map of C. lacryma-jobi based on a cross between the parents 'Qianyi No. 2' × 'Wenyi No. 2' and their F2 progeny through high-throughput sequencing and the construction of a specific-locus amplified fragment (SLAF) library. After pre-processing, 325.49 GB of raw data containing 1628 M reads were obtained. A total of 22,944 high-quality SLAFs were identified, among which 3952 SLAFs and 3646 polymorphic markers met the requirements for the construction of a genetic linkage map. The integrated map contained 3605 high-quality SLAFs, which were grouped into ten genetic linkage groups. The total length of the map was 1620.39 cM, with an average distance of 0.45 cM and an average of 360.5 markers per linkage group. This report presents the first high-density genetic map of C. lacryma-jobi. This map was constructed using an F2 population and SLAF-seq approach, which allows the development of a large number of polymorphic markers in a short period. These results provide a platform for precise gene/quantitative trait locus (QTL) mapping, map-based gene separation, and molecular breeding in C. lacryma-jobi. They also help identify a target gene for tracking, splitting quantitative traits, and estimating the phenotypic effects of each QTL for QTL mapping. They are of great significance for improving the efficiency of discovering and utilizing excellent gene resources of C. lacryma-jobi.

Abstract Background Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood. Results Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level. Conclusions Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.

This study aimed to develop a method based on hyperspectral imaging (400–1 000 nm) combined with chemometrics to identify the diverse geographical origins of Lycium barbarum fruit. Hyperspectral images of L. barbarum fruit from Ningxia, Gansu, Inner Mongolia, Qinghai and Xinjiang were acquired, and spectral data was extracted from the region of interest (ROI) by threshold segmentation method. Multiple preprocessing methods were employed to eliminate the interference information from the spectra, and the results showed that the discriminant model based on normalized reflectance spectrum (NR) exhibited better performance. Furthermore, the successive projection algorithm (SPA), competitive adaptive reweighted sampling (CARS), particle swarm optimization (PSO), iteratively retaining informative variables (IRIV), and CARS + IRIV were used to select characteristic wavelengths. The results showed that the simplified model based on the wavelengths selected by CARS + IRIV had the best performance. In the models ranging from binary to quintuple classifications, the selected characteristic wavelengths accounted for only 15.6% to 27.7% of the full spectra. The prediction accuracy was 97.7%, 90.9%, 89.2%, and 87.1%, respectively. In addition, a confusion matrix was employed to visualize the optimal simplified classification model in order to intuitively distinguish the classification categories. Satisfactory sensitivity, specificity and Kappa coefficients were obtained in classifying L. barbarum. The results illustrated that hyperspectral imaging technology combined with chemometric methods could effectively identify the geographical origin of L. barbarum and provide crucial technical support for the development of the L. barbarum industry.

Research into next-generation propellants with green fuel–oxidizer pairs to replace the currently used highly toxic hydrazine–N2O4 system has attracted widespread attention. Ionic liquids (ILs) and hydrogen peroxide have demonstrated their feasibility as a green fuel and an oxidizer, respectively. However, the realisation of effective auto-ignition is the key problem. In this study, a new strategy to trigger the auto-ignition of ILs fuels with hydrogen peroxide by using a unique copper-containing liquid as the promoter is developed. The copper-containing promoter is designed such that its cationic structure is similar to that of the ILs fuels. Based on the principle of “like dissolves like,” the fuel and promoter can be miscible at any ratio to eventually form a catalytic fuel. In addition, the physicochemical properties (e.g. density, viscosity and decomposition temperature) and performance parameters (e.g. ignition delay time and specific impulse) of the as-prepared catalytic fuel are completely characterised. Owing to their excellent hypergolic performance with a short ignition delay time of 16 ms, in combination with the advantages of simple preparation, perfect solubility and green characteristics, the catalytic fuel–oxidizer pair demonstrates promise as bipropellants for rocket applications.

Abstract Background A temporal network of generalized anxiety disorder (GAD) symptoms could provide valuable understanding of the occurrence and maintenance of GAD. We aim to obtain an exploratory conceptualization of temporal GAD network and identify the central symptom. Methods A sample of participants (n = 115) with elevated GAD-7 scores (Generalized Anxiety Disorder 7-Item Questionnaire [GAD-7] ≥ 10) participated in an online daily diary study in which they reported their GAD symptoms based on DSM-5 diagnostic criteria (eight symptoms in total) for 50 consecutive days. We used a multilevel VAR model to obtain the temporal network. Results In temporal network, a lot of lagged relationships exist among GAD symptoms and these lagged relationships are all positive. All symptoms have autocorrelations and there are also some interesting feedback loops in temporal network. Sleep disturbance has the highest Out-strength centrality. Conclusions This study indicates how GAD symptoms interact with each other and strengthen themselves over time, and particularly highlights the relationships between sleep disturbance and other GAD symptoms. Sleep disturbance may play an important role in the dynamic development and maintenance process of GAD. The present study may develop the knowledge of the theoretical model, diagnosis, prevention and intervention of GAD from a temporal symptoms network perspective.

Abstract With the continuous transformation of the global power system, ensuring the flexibility and stability of the power system has become a direction that the global energy industry has been striving for. This puts forward higher requirements for load forecasting, especially high‐precision short‐term residential load forecasting. However, the high volatility and uncertainty of electric consumption make this problem challenging. Existing methods usually focus on capturing temporal correlations and ignore the underlying spatial correlations in historical loads, which is crucial for accurate forecasting. In this paper, we propose a novel spatial–temporal gated fusion network (STGNet) for short‐term residential load forecasting including not only individual residential load but also aggregated load. By seeking both adaptive neighbors and temporal similarity neighbors, we construct a dynamic graph based on a data‐driven method. On this basis, we provide an adaptive graph gated fusion mechanism to capture fine‐grained node‐specific spatial dependence more accurately and comprehensively. Finally, a bidirectional gated recurrent unit (BiGRU) is utilized to learn the temporal dependence of load data. Extensive experiments on real‐world datasets are conducted and demonstrate the superiority of STGNet over the existing approaches.

ABSTRACT: It is desirable to obtain high levels of viable Lacticaseibacillus paracasei, a widely used food probiotic whose antibacterial activity and potential application in milk remain largely uninvestigated. Here, we isolated and purified the L. paracasei strain XLK 401 from food-grade blueberry ferments and found that it exhibited strong antibacterial activity against both gram-positive and gram-negative foodborne pathogens, including Staphylococcus aureus, Salmonella paratyphi B, Escherichia coli O157, and Shigella flexneri. Then, we applied alternating tangential flow (ATF) technology to produce viable L. paracasei XLK 401 cells and its cell-free supernatant (CFS). Compared with the conventional fed-batch method, 22 h of ATF-based processing markedly increased the number of viable cells of L. paracasei XLK 401 to 12.14 ± 0.13 log cfu/mL. Additionally, the CFS exhibited good thermal stability and pH tolerance, inhibiting biofilm formation in the abovementioned foodborne pathogens. According to liquid chromatography-mass spectrometry analysis, organic acids were the main antibacterial components of XLK 401 CFS, accounting for its inhibition activity. Moreover, the CFS of L. paracasei XLK 401 effectively inhibited the growth of multidrug-resistant gram-positive Staph. aureus and gram-negative E. coli O157 pathogens in milk, and caused a reduction in the pathogenic cell counts by 6 to 7 log cfu/mL compared with untreated control, thus considerably maintaining the safety of milk samples. For the first time to our knowledge, ATF-based technology was employed to obtain viable L. paracasei on a large scale, and its CFS could serve as a broad-spectrum biopreservative for potential application against foodborne pathogens in milk products.

Abstract Background Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. Methods The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. Results We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 μM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 μM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in “ribosome biogenesis (GO:0042254)” and “ribosome (GO:0005840)” were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. Conclusions Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis. Graphical Abstract

Abstract Background Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. Methods In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. Results GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913–0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831–0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841–0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838–0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810–0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710–0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. Conclusion Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.

Abstract TRF2 is a component of shelterin, a telomere-specific protein complex that protects the ends of mammalian chromosomes from DNA damage signaling and improper repair. TRF2 functions as a homodimer and its interaction with telomeric DNA has been studied, but its full-length DNA-binding properties are unknown. This study examines TRF2’s interaction with single-DNA strands and focuses on the conformation of the TRF2-DNA complex and TRF2’s preference for DNA chirality. The results show that TRF2-DNA can switch between extended and compact conformations, indicating multiple DNA-binding modes, and TRF2’s binding does not have a strong preference for DNA supercoiling chirality when DNA is under low tension. Instead, TRF2 induces DNA bending under tension. Furthermore, both the N-terminal domain of TRF2 and the Myb domain enhance its affinity for the telomere sequence, highlighting the crucial role of multivalent DNA binding in enhancing its affinity and specificity for telomere sequence. These discoveries offer unique insights into TRF2’s interaction with telomeric DNA.

Abstract Oxidative stress dysfunction has recently been found to be involved in the pathogenesis of premature ovarian insufficiency (POI). Previously, we found that advanced oxidation protein products (AOPPs) in plasma were elevated in women with POI and had an adverse effect on granulosa cell proliferation. However, the mechanism underlying the effects of AOPPs on autophagy-lysosome pathway regulation in granulosa cells remains unclear. In this study, the effect of AOPPs on autophagy and lysosomal biogenesis and the underlying mechanisms were explored by a series of in vitro experiments in KGN and COV434 cell lines. AOPP-treated rat models were employed to determine the negative effect of AOPPs on the autophagy-lysosome systems in vivo. We found that increased AOPP levels activated the mammalian target of rapamycin (mTOR) pathway, and inhibited the autophagic response and lysosomal biogenesis in KGN and COV434 cells. Furthermore, scavenging of reactive oxygen species (ROS) with N-acetylcysteine and blockade of the mTOR pathway with rapamycin or via starvation alleviated the AOPP-induced inhibitory effects on autophagy and lysosomal biogenesis, suggesting that these effects of AOPPs are ROS-mTOR dependent. The protein expression and nuclear translocation of transcription factor EB (TFEB), the key regulator of lysosomal and autophagic function, were also impaired by the AOPP-activated ROS-mTOR pathway. In addition, TFEB overexpression attenuated the AOPP-induced impairment of autophagic flux and lysosomal biogenesis in KGN and COV434 cells. Chronic AOPP stimulation in vivo also impaired autophagy and lysosomal biogenesis in granulosa cells of rat ovaries. The results highlight that AOPPs lead to impairment of autophagic flux and lysosomal biogenesis via ROS-mTOR-TFEB signaling in granulosa cells and participate in the pathogenesis of POI.