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Abstract Background 1P36 deletion syndrome is recognized as the most common terminal microdeletion syndrome in humans, characterized by early developmental delay and consequent intellectual disability, seizure disorder, and distinctive facial features. Variable deletion locations may attributed to phenotypic variability. However, the abnormal phenotypes of hematology are rarely reported in 1P36 deletion syndrome patients. Case presentation We present a case of postnatal intellectual disability accompanied by pancytopenia. Copy number variation analysis revealed a pathogenic deletion in 1p36.331p36.32 with a deletion size of 2.21 Mb. Following successful treatment with glucocorticoids, the patient was diagnosed with immuno-related hemocytopenia (IRH). Discussion The patient experienced IRH, an uncommon characteristic of 1p36 deletion syndrome. The deletion fragment of 1p36.33-p36.32, particularly the loss of GNB1 gene, has been associated with the development of pancytopenia. Genotype-phenotype correlations are valuable in identifying the genes responsible for various clinical characteristics of the syndrome by associating phenotypic variation with specific genes located within the chromosome deletion region. Genome sequencing is recommended in cases where clinical manifestations indicate the presence of a genetic disorder but pose diagnostic challenges.

Abstract Background Coat color, as a distinct phenotypic characteristic of pigs, is often subject to preference and selection, such as in the breeding process of new breed. Shanxia long black pig was derived from an intercross between Berkshire boars and Licha black pig sows, and it was bred as a paternal strain with high-quality meat and black coat color. Although the coat color was black in the F1 generation of the intercross, it segregated in the subsequent generations. This study aims to decode the genetic basis of coat color segregation and develop a method to distinct black pigs from the spotted in Shanxia long black pig. Results Only a QTL was mapped at the proximal end of chromosome 6, and MC1R gene was picked out as functional candidate gene. A total of 11 polymorphic loci were identified in MC1R gene, and only the c.67_68insCC variant was co-segregating with coat color. This locus isn’t recognized by any restriction endonuclease, so it can’t be genotyped by PCR-RFLP. The c.370G > A polymorphic locus was also significantly associated with coat color, and has been in tightly linkage disequilibrium with the c.67_68insCC. Furthermore, it is recognized by BspHI. Therefore, a PCR-RFLP method was set up to genotype this locus. Besides the 175 sequenced individuals, another more 1,391 pigs were genotyped with PCR-RFLP, and all of pigs with GG (one band) were black. Conclusion MC1R gene (c.67_68insCC) is the causative gene (mutation) for the coat color segregation, and the PCR-RFLP of c.370G > A could be used in the breeding program of Shanxia long black pig.

Abstract Eusocial pollinators are crucial elements in global agriculture. The honeybees and bumblebees are associated with a simple yet host-restricted gut community, which protect the hosts against pathogen infections. Recent genome mining has led to the discovery of biosynthesis pathways of bioactive natural products mediating microbe-microbe interactions from the gut microbiota. Here, we investigate the diversity of biosynthetic gene clusters in the bee gut microbiota by analyzing 477 genomes from cultivated bacteria and metagenome-assembled genomes. We identify 744 biosynthetic gene clusters (BGCs) covering multiple chemical classes. While gene clusters for the post-translationally modified peptides are widely distributed in the bee guts, the distribution of the BGC classes varies significantly in different bee species among geographic locations, which is attributed to the strain-level variation of bee gut members in the chemical repertoire. Interestingly, we find that Gilliamella strains possessing a thiopeptide-like BGC show potent activity against the pathogenic Melissococcus plutonius. The spectrometry-guided genome mining reveals a RiPP-encoding BGC from Gilliamella with a 10 amino acid-long core peptide exhibiting antibacterial potentials. This study illustrates the widespread small-molecule-encoding BGCs in the bee gut symbionts and provides insights into the bacteria-derived natural products as potential antimicrobial agents against pathogenic infections.

Introduction: Extracellular vesicles (EVs)-mediated cell-to-cell communication is crucial for hypoxia-induced cell proliferation and tissue repair, but its function in endogenous cardiac regeneration is still unknown. Objectives: Herein, we aimed to determine whether hypoxia-inducible circWhsc1 in endothelial EVs promoted cardiomyocyte (CM) proliferation and cardiac regeneration. Methods: RNA-sequence data was used to identify EV circRNAs that were involved into endogenous cardiac regeneration. Quantitative polymerase chain reactions were conducted to determine circRNA expression in tissue, cells and EVs. Gain- and loss-of-function assays were performed to explore the function of EV-derived circWhsc1 during cardiac regeneration. Western blotting and RNA pulldown assays were used to investigate its underlying mechanism. Results: We found that circWhsc1 was enriched in neonatal mouse hearts, particularly in cardiac ECs, and was further upregulated both in ECs and EC-derived EVs under hypoxic conditions. When cocultured with hypoxia-preconditioned neonatal ECs or their secreted EVs, both neonatal and adult CMs exhibited an increased proliferation rate and G2/M ratio, which could be attenuated by knockdown of circWhsc1 in ECs. In vivo, EC-restricted overexpression of circWhsc1 and EV-mediated delivery of circWhsc1 induced CM proliferation, alleviated cardiac fibrosis and restored cardiac function following myocardial infarction in adult mice. Mechanistic studies revealed that EV-derived circWhsc1 activated TRIM59 by enhancing its phosphorylation, thereby reinforcing the binding of TRIM59 to STAT3, phosphorylating STAT3 and inducing CM proliferation. Conclusion: The current study demonstrated that hypoxia-inducible circWhsc1 in EC-derived EVs induces CM proliferation and heart regeneration. EC-CM communication mediated by EV-derived circWhsc1 might represent a prospective therapeutic target for inducing cardiac repair post-myocardial infarction.

Abstract With the increasing attention to the state and role of people in intelligent manufacturing, there is a strong demand for human-cyber-physical systems (HCPS) that focus on human-robot interaction. The existing intelligent manufacturing system cannot satisfy efficient human-robot collaborative work. However, unlike machines equipped with sensors, human characteristic information is difficult to be perceived and digitized instantly. In view of the high complexity and uncertainty of the human body, this paper proposes a framework for building a human digital twin (HDT) model based on multimodal data and expounds on the key technologies. Data acquisition system is built to dynamically acquire and update the body state data and physiological data of the human body and realize the digital expression of multi-source heterogeneous human body information. A bidirectional long short-term memory and convolutional neural network (BiLSTM-CNN) based network is devised to fuse multimodal human data and extract the spatiotemporal features, and the human locomotion mode identification is taken as an application case. A series of optimization experiments are carried out to improve the performance of the proposed BiLSTM-CNN-based network model. The proposed model is compared with traditional locomotion mode identification models. The experimental results proved the superiority of the HDT framework for human locomotion mode identification.

Abstract Background Human hydatid disease typically occurs in organs such as the liver and kidney. Primary solitary intramuscular hydatid disease, however, is rare. Case Presentation We report a case of a giant muscle hydatid in the lower extremity, with neurological symptoms as the first manifestation. The symptoms specifically manifested as intermittent pain in the right lower extremity and numbness in the sole of the right foot. However, there were no obvious abnormalities detected in electromyography and lumbar MRI. Subsequent ultrasonography and calf MRI showed that the patient had cystic lesions in the calf. The patient was initially diagnosed with a muscle hydatid cyst. Treatment involved complete surgical excision of the lesion, and the diagnosis of a hydatid cyst was confirmed through macroscopic and microscopic histopathological examination after the mass was excised. The patient was given oral albendazole, and no recurrence was observed during the 12 months of follow-up. Conclusions This case underscores the need to consider hydatid disease when diagnosing soft tissue masses in muscles, particularly in endemic areas. Patients may initially present with atypical symptoms like peripheral nerve issues.

Water scarcity is a key limitation to winter wheat production in the North China Plain, and it is essential to explore the optimal timing of spring irrigation to optimize N and Si uptake as well as to safeguard yields. The aim of this study was to systematically study the effect mechanism of nitrogen and silicon absorption of winter wheat on yield under spring irrigation and to provide a scientific basis for optimizing irrigation strategy during the growth period of winter wheat. In this experiment, the winter wheat ‘Heng 4399’ was used. Five irrigation periods, i.e., 0 d (CK), 5 d (AJ5), 10 d (AJ10), 15 d (AJ15), and 20 d (AJ20) after the jointing stage, were set up to evaluate the nitrogen (N) and silicon (Si) absorption and grain yield (GY). The results showed that delayed irrigation for 5–10 days at the jointing stage had increased the GY. With the delay of irrigation time, the N/Si content of the entire plant at the maturity period increased first and then decreased; among that, the maximum N contents appeared in AJ15 and AJ5 in 2015 and 2020, respectively, while the Si concentrations appeared in AJ5 and AJ10 in sequence. Compared with AJ15 and AJ20, the N accumulation of vegetative organs in AJ5 increased by 3.05~23.13% at the flowering stage, 14.12~40.12% after the flowering stage, and a 1.76~6.45% increase in the N distribution rate at maturity stage. A correlation analysis revealed that the GY was significantly and positively correlated with the N/Si accumulation at the anthesis and N translocation after the anthesis stage. In conclusion, under limited irrigation conditions, delaying watering for 5 to 10 days at the jointing stage can improve the nitrogen and silicon absorption and nutrient status of wheat plants and increase wheat yield.

In this paper, a fast method to generate a constant-modulus (CM) waveform for a multiple-input, multiple-output, (MIMO) radar is proposed. To simplify the optimization process, the design of the transmit waveform is decoupled from the design of transmit beamformers (TBs) and subpulses. To further improve the computational efficiency, the TBs’ optimization is conducted in parallel, and a linear programming model is proposed to match the desired beampattern. Additionally, we incorporate the perturbation vectors into the TBs’ optimization so that the TBs can be adjusted to satisfy the CM constraint. To quickly generate the CM subpulses with the desired range-compression (RC) performance, the classical linear frequency modulation (LFM) signal and non-LFM (NLFM) are adopted as subpulses. Meanwhile, to guarantee the RC performance of the final angular waveform, the selection of LFM signal parameters is analyzed to achieve a low cross-correlation between subpulses. Numerical simulations verify the transmit beampattern performance, RC performance, and computational efficiency of the proposed method.

Alternariol (AOH), an emerging mycotoxin, inevitably exists widely in various food and feed commodities with cereals and fruits being particularly susceptible, raising global concerns over its harm to human and livestock health. The development of eco-friendly and efficient strategies to decontaminate AOH has been an urgent task. This study provided insight into the utilization of crude soybean hull peroxidase as a powerful biocatalyst for degrading AOH. The results confirmed that crude soybean hull peroxidase (SHP) could catalyze the oxidation of AOH by use of H2O2 as a co-substrate. The optimum reaction conditions for SHP-catalyzed AOH degradation were recorded at pH 4.0–8.0, at 42–57 °C, and at H2O2 concentration of 100–500 μM. Mass analysis elucidated the degradation of AOH through hydroxylation and methylation by crude SHP. Moreover, toxicological analysis indicated that crude SHP-catalyzed AOH degradation detoxified the hepatotoxicity of this mycotoxin. The performance of crude SHP to degrade AOH in food matrices was further evaluated, and it was found that the enzyme agent could achieve AOH degradation by 77% in wheat flour, 84% in corn flour, 34% in grape juice, and 26% in apple juice. Collectively, these findings establish crude SHP as a promising candidate for effective AOH degradation, with potential applications in the food and feed industry.

This study integrates genetic algorithms with simulation programs, applying the genetic algorithm’s (GA) fitness calculation within the simulation to reduce complexity and significantly improve the efficiency of the optimization process. Additionally, the simulation introduces the concept of “Field Leveling” (FL), utilizing a push–pull strategy to explore more space for absorbing and utilizing unnecessary spillage for energy generation, thereby maximizing electricity production and ensuring optimal reservoir scheduling. Two methods are provided, namely the field-leveling genetic algorithms GAFL1 and GAFL2. GAFL1 involves only pushing and does not include a push–pull process; thus, it cannot optimize spillage. On the other hand, GAFL2 implements a complete push–pull strategy, continuously exploring additional space to absorb and utilize unnecessary spillage. Both GAFL1 and GAFL2 achieved reasonable results; specifically, compared to SQP, GAFL1 improved firm yield by 8.3%, spillage increased by 2.2 times, and total energy decreased by 1.2%. GAFL2, building on the basis of GAFL1, effectively reduces spillage under all hydrological conditions without affecting the highest priority of stable output. However, the impact of reducing spillage on energy generation is not consistent; in wet and dry years, reducing spillage increases energy generation. However, in normal years, a reduction in spillage corresponds with decreased energy generation.

Abstract Large earthquakes not only directly damage buildings but also trigger debris flows, which cause secondary damage to buildings, forming a more destructive earthquake-debris flow disaster chain. A quantitative assessment of building vulnerability is essential for damage assessment after a disaster and for pre-disaster prevention. Using mechanical analysis based on pushover, a physical vulnerability assessment model of buildings in the earthquake-debris flow disaster chain is proposed to assess the vulnerability of buildings in Beichuan County, China. Based on the specific sequence of events in the earthquake-debris flow disaster chain, the seismic vulnerability of buildings is 79%, the flow impact and burial vulnerabilities of damaged buildings to debris flow are 92% and 28% respectively, and the holistic vulnerability of buildings under the disaster chain is 57%. By comparing different vulnerability assessment methods, we observed that the physical vulnerability of buildings under the disaster chain process is not equal to the statistical summation of the vulnerabilities to independent hazards, which implies that the structural properties and vulnerability of buildings have changed during the disaster chain process. Our results provide an integrated explanation of building vulnerability, which is essential for understanding building vulnerability in earthquake-debris flow disaster chain and building vulnerability under other disaster chains.

Abstract Introducing superconductivity into two-dimensional (2D) films with nontrivial topology has been intensively pursued as one of the feasible scenarios to realize 1D topological superconductor. Prevailing endeavors mostly exploit the external gating or proximity effect of a traditional superconductor, by which the critical temperatures ( T c $T_{\mathrm{c}}$ ) are limited to several Kelvin range. Here, we report on the discovery of interface-enhanced superconductivity in monolayer 1T′-MoTe2 film. A thermally driven phase transition from Mo6Te6 nanowires to 1T′-MoTe2 films, grown on SrTiO3(001) surface by the molecular beam epitaxial methods, is demonstrated. A combined study of scanning tunneling microscopy/spectroscopy, electrical transport and magnetization measurements indicates the T c $T_{\mathrm{c}}$ of MoTe2 film is around 30 K, two orders of magnitude larger than its 3D counterpart crystal. This study shows that interfacial engineering is an efficient way to tune monolayer 1T′-MoTe2 film into superconducting states, and thus may pave the way toward higher- T c $T_{\mathrm{c}}$ 1D intrinsic topological superconductivity.

This is an essay in the field of mineral analysis. After the samples were roasted and digested in 50% aqua regia by sealed dissolution,the gold in ore samples were adsorbed by 0.25g polyurethane foam during the oscillating, the polyurethane foam was washed to removing the slurry and acid, and gold was eluted out from polyurethane foam with 1% thiourea. Thus, a determination method of gold in ore samples by flame atomic absorption spectrometry of sealed dissolution after adsorption with polyurethane foam was established.The roasting method of some special gold ore samples was discussed.The conditions of sealed dissolution time, foam pretreatment, adsorption temperature and solution temperature were optimized, the results showed that when the sealed dissolution for 2 h, the gold was completely decomposed. After the polyurethane foam was treated with 5%HCl, the adsorption recoveries of gold could reach 95% at room temperature, the temperature of solution and standard solution shall be consistent with room temperature during determination. The calibration curve was prepared by foam adsorption and desorption process. Under the selected experimental conditions, the limit of detection was 0.13 μg/g, the limit of quantification was 0.43 μg/g, and the upper limit of determination was 80 μg/g. The standard recoveries were between 98.7% and 101%, the relative standard deviations(RSD, n=5) were between 1.10% and 2.07%. Verified by the determination of gold ore certified reference materials, the results were basically consistent with the certified value.

Abstract Enterococcus faecalis is one of the main pathogens that causes hospital-acquired infections because it is intrinsically resistant to some antibiotics and often is capable of biofilm formation, which plays a critical role in resisting the external environment. Therefore, attacking biofilms is a potential therapeutic strategy for infections caused by E. faecalis. Current research indicates that diacerein used in the treatment of osteoarthritis showed antimicrobial activity on strains of gram-positive cocci in vitro. In this study, we tested the MICs of diacerein using the broth microdilution method, and successive susceptibility testing verified that E. faecalis is unlikely to develop resistance to diacerein. In addition, we obtained a strain of E. faecalis HE01 with strong biofilm-forming ability from an eye hospital environment and demonstrated that diacerein affected the biofilm development of HE01 in a dose-dependent manner. Then, we explored the mechanism by which diacerein inhibits biofilm formation through qRT-PCR, extracellular protein assays, hydrophobicity assays and transcriptomic analysis. The results showed that biofilm formation was inhibited at the initial adhesion stage by inhibition of the expression of the esp gene, synthesis of bacterial surface proteins and reduction in cell hydrophobicity. In addition, transcriptome analysis showed that diacerein not only inhibited bacterial growth by affecting the oxidative phosphorylation process and substance transport but also inhibited biofilm formation by affecting secondary metabolism, biosynthesis, the ribosome pathway and luxS expression. Thus, our findings provide compelling evidence for the substantial therapeutic potential of diacerein against E. faecalis biofilms.

Abstract Deep learning (DL) based detection models are powerful tools for large-scale analysis of dynamic biological behaviors in video data. Supervised training of a DL detection model often requires a large amount of manually-labeled training data which are time-consuming and labor-intensive to acquire. In this paper, we propose LFAGPA (Learn From Algorithm-Generated Pseudo-Annotations) that utilizes (noisy) annotations which are automatically generated by algorithms to train DL models for ant detection in videos. Our method consists of two main steps: (1) generate foreground objects using a (set of) state-of-the-art foreground extraction algorithm(s); (2) treat the results from step (1) as pseudo-annotations and use them to train deep neural networks for ant detection. We tackle several challenges on how to make use of automatically generated noisy annotations, how to learn from multiple annotation resources, and how to combine algorithm-generated annotations with human-labeled annotations (when available) for this learning framework. In experiments, we evaluate our method using 82 videos (totally 20,348 image frames) captured under natural conditions in a tropical rain-forest for dynamic ant behavior study. Without any manual annotation cost but only algorithm-generated annotations, our method can achieve a decent detection performance (77% in $$F_1$$ F 1 score). Moreover, when using only 10% manual annotations, our method can train a DL model to perform as well as using the full human annotations (81% in $$F_1$$ F 1 score).

Abstract Salt-affected soils urgently need to be remediated to achieve the goals of carbon neutrality and food security. Limited reviews are available on biochar performance in remediating salt-affected soils in the context of carbon neutrality and climate change mitigation. This work summarized the two pathways to achieve carbon neutrality during remediating salt-affected soils using biochars, i.e., biochar production from sustainable feedstock using thermal technologies, application for promoting plant productivity and mitigating greenhouse gas (GHG) emission. Converting biomass wastes into biochars can reduce GHG emission and promote carbon dioxide removal (CDR), and collection of halophyte biomass as biochar feedstocks, development of biochar poly-generation production systems with carbon neutrality or negativity could be promising strategies. Biochar can effectively improve plant growth in salt-affected soils, showing that the grand mean of plant productivity response was 29.3%, via improving physicochemical characteristics, shifting microbial communities, and enhancing plant halotolerance. Moreover, biochar can mitigate GHG emission via inducing negative priming effect, improving soil properties, changing microbial communities associated with carbon and nitrogen cycle, direct adsorption of GHG. However, biochar also may pose negative effects on plant growth because of stress of toxic compounds and free radicals, and deterioration of soil properties. The promoted GHG emission is mainly ascribed to positive priming effect, and provision of labile carbon and inorganic nitrogen fractions as microbial substrates. Finally, this review pointed out the gaps in the current studies and the future perspectives. Particularly, the development of “carbon neutral” or “carbon negative” biochar production system, balancing the relationship of biochar effectiveness and functionality with its environmental risks and costs, and designing biochar-based GHG adsorbents would be important directions for remediating salt-affected soils to achieve carbon neutrality and abate climate change. Graphical Abstract

The role of acoustic cavitation in various surface cleaning disciplines is important. However, the physical mechanisms underlying acoustic cavitation-induced surface cleansing are poorly understood. This is due to the combination of microscopic and ultrashort timescales associated with the dynamics of acoustic cavitation bubbles. Here, we have precisely controlled single-bubble cavitation in both space and time. Ultrasonic excitation leads to the cavitation of generated single bubbles. A synchronous ultrafast photomicrographic system simultaneously records the dynamics of single acoustic cavitation bubbles (SACBs) and the cleaning process of the nearby surface in liquids with varying viscosities. Finally, we analysed the correlation between bubble dynamics and surface cleaning situations. The differences in the typical dynamic characteristics of the bubbles during collapse in liquids with varying viscosities reveal two main mechanisms underlying surface cleaning by acoustic cavitation, which are respective the Laplace pressure during the bubble’s movement and liquid jets during bubble collapse. Our study provides a better physical understanding of the ultrasonic cleaning process based on acoustic cavitation, and will help to optimize and facilitate the applications of surface cleaning, especially for the cleaning of substrates with tightly attached dirt.

ABSTRACTThis study aims to summarize the clinical characteristics and prognosis of Listeria monocytogenes (LM) meningitis in children in Chongqing, China. A retrospective analysis of the clinical data and follow-up results of 20 LM meningitis patients admitted to the Children’s Hospital of Chongqing Medical University (CHCMU) from January 2012 to December 2022 was performed. The LM meningitis incidence rate was between 0 and 14.3 per 100,000 persons. The median age at onset was 8.98 months. There were five neonate cases, which all had perinatal abnormalities. Seven non-neonatal cases (7/15, 46.7%) had a documented history of contaminated food intake. One case had primary immunodeficiency. The most common symptoms were fever (20/20), altered consciousness (19/20), and vomiting (15/20). Seven cases had seizures, eight cases had cranial nerve involvement, eight cases had positive Babinski sign, and 10 cases had positive meningeal signs. The most common complications were hyponatremia (6/20), hypokalemia (6/20), respiratory failure (5/20), subdural effusion (3/20), and hydrocephalus (2/20). Treatment primarily involved monotherapy or combination therapy with meropenem (15/20) and ampicillin (10/20). Fifteen cases were treated with monotherapy or combination therapy using vancomycin. Twelve cases were successfully followed up from 10 months to 9 years and 6 months, and all had favorable long-term outcomes. LM meningitis incidence in children is low and with nonspecific clinical manifestations. Strengthening food hygiene and safety education, and avoiding infections during pregnancy are important to prevent LM infection in neonates and high-risk individuals. Meropenem and ampicillin are the preferred treatments. Early diagnosis and treatment can improve prognosis.IMPORTANCEThe incidence of LM meningitis is extremely low, and there is currently no standardized treatment. We conducted a retrospective analysis of ten years of data from CHCMU regarding diagnosed LM meningitis cases, aiming to provide clinical evidence for the diagnosis and treatment.

Based on the self-developed high permeability water pressure loading system, the physical and mechanical properties and pore structure evolution under various high permeability water pressures were studied. This study aims to reveal the microscopic damage mechanism of concrete when subjected to high permeability water pressures. The results indicate that the internal water content increases with the rising of water pressure under various high permeability conditions. Furthermore, the higher the water pressure, the greater the reduction in strength, particularly evident in low-strength-grade concrete. High permeability water pressure causes to the expansion of gelatinized pores with small sizes into transition pores. Moreover, there is a concurrent alteration in both pore size and pore number under high permeability water pressure.

Microplastics (MPs) weather after entering the environment gradually, and the interaction with metal ions in the aqueous environment has received extensive attention. However, there are few studies on Hg(Ⅱ), especially the effect of MPs on the release of Hg0(DEM) in water after entering the aqueous environment. In this study, four types of MPs (PP, PE, PET, PVC) were selected to study the adsorption and desorption behavior of Hg(Ⅱ) after photoaging and to explore the influence of MPs on the release of DEM in seawater under different lighting conditions. The results showed that the specific surface area, negative charges, and oxygen-containing functional group of MPs increased after aging. The adsorption capacity of aged MPs for Hg(Ⅱ) was significantly improved, which was consistent with the pseudo-first-order and pseudo-second-order model, indicating that the adsorption process was a chemical and physical adsorption. The fitting results of the in-particle diffusion model indicated that the adsorption was controlled by multiple steps. Hg(Ⅱ) was easier to desorb in the simulated gastric fluid environment. Because the aged MPs had the stronger binding force to Hg(Ⅱ), their desorption rate is lower than new MPs. Under visible light and UVA irradiation, MPs inhibited the release of Hg0. Under UVA, the mass of DEM produced in seawater with aged PE and PVC was higher than that of new PE and PVC. The aged PE and PVC could produce more ·O2-, which was conducive to the reduction of mercury. However, in UVB irradiation, the addition of MPs promoted the release of DEM, and ·O2- also played an important contribution in affecting the photochemical reaction of mercury. Therefore, the presence of aged MPs will significantly affect the water-air exchange of Hg in water. Compared with new MPs, aged MPs improved the contribution of free radicals in Hg transformation by releasing reactive oxygen species. This study extends the understanding of the effects of MPs on the geochemical cycle of Hg(Ⅱ) in seawater, better assesses the potential combined ecological risks of MPs and Hg(Ⅱ), and provides certain guidance for the pollution prevention and control of MPs.

Variable flux memory machines (VFMMs) have become a research hotspot due to their adjustable air-gap flux with the employment of low coercive force (LCF) permanent magnets (PMs). Series hybrid magnet VFMMs (SHM-VFMMs) utilizing series-magnetic-circuit high coercive force (HCF) and LCF PMs are extensively investigated due to their excellent unintentional demagnetization (UD) withstand capability. Nevertheless, the existing researches still focus on the UD of LCF PMs under heavy load operation, and the remagnetization issue remains unreported. Therefore, in this paper, the over-load unintentional remagnetization (UR) effect of the a dual-layer-SHM-VFMM (DLSHM-VFMM) is first revealed, and its mechanism is investigated and analyzed in depth based on finite element (FE) analyses. A DLSHM-VFMM prototype is manufactured and tested to verify the effectiveness of the theoretical analyses.

Abstract Data mining from computational materials database has become a popular strategy to identify unexplored catalysts. Herein, the opportunities and challenges of this strategy are analyzed by investigating a discrepancy between data mining and experiments in identifying low‐cost metal oxide (MO) electrocatalysts. Based on a search engine capable of identifying stable MOs at the pH and potentials of interest, a series of MO electrocatalysts is identified as potential candidates for various reactions. Sb2WO6 attracted the attention among the identified stable MOs in acid. Based on the aqueous stability diagram, Sb2WO6 is stable under oxygen reduction reaction (ORR) in acidic media but rather unstable under high‐pH ORR conditions. However, this contradicts to the subsequent experimental observation in alkaline ORR conditions. Based on the post‐catalysis characterizations, surface state analysis, and an advanced pH‐field coupled microkinetic modeling, it is found that the Sb2WO6 surface will undergo electrochemical passivation under ORR potentials and form a stable and 4e‐ORR active surface. The results presented here suggest that though data mining is promising for exploring electrocatalysts, a refined strategy needs to be further developed by considering the electrochemistry‐induced surface stability and activity.

Background: Pulmonary hypertension (PH) is characterized with vascular remodeling, which is intiated by vascular endothelial dysfunction. N6-methyladenosine (m6A) modification mediates gene expression in many ways including mediating RNA degradation, splicing, nuclear export et al. m6A modification have been found to be associated with the development of PH. However, the role of m6A regulators in pulmonary artery endothelial cells (PAECs) dysfunction of PH is still under research. Methods: The expression levels of m6A regulators in PAECs were analyzed with the single-cell sequencing Data(scRNA). Next, the target differentially expressed genes (DEGs) of m6A regulators in PAECs were functionally annotated. The analysis of cellular interactions included the examination of receptor—ligand pairs regulated by m6A regulators. Pseudo-time trajectory analyses and a ceRNA network involving lncRNAs, miRNAs, and mRNAs were conducted in PAECs. Furthermore, microarray data (GSE180169) for Sugen Hypoxia PH (SuHx PH) mouse models was screened for DEGs and m6A regulators in PAECs. Moreover, the expression of YTHDC1 in the lung samples of SuHx PH models was determined using immunofluorescence. In vitro, the mRNA expression of YTHDC1 in HPAECs under hypoxia conditions was detected. The effect of YTHDC1 recombinant protein on HPAEC proliferation was detected by Cell Counting Kit-8 (CCK8). Results: Dysregulation of m6A regulators was observed in mouse PAECs. The m6A reader of YTHDC1 was decreased in PAECs in scRNA data and RNAseq data of isolated PAECs of SuHx PH models. Downregulation of YTHDC1 was caused by hypoxia in PAECs in vitro and similar results was observed in PAECs of SuHx PH mouse models. Next, YTHDC1 recombinant protein was found to inhibit HPAECs proliferation. The DEGs targeted by YTHDC1 were enriched in angiogenesis, endothelial cell migration, fluid shear stress, and stem cell maintenance. Analysis indicates that interactions among endothelial cells, smooth muscle cells, fibroblasts, and immune cells, mediated by specific YTHDC1 target genes (e.g., PTPRC-MRC1, ITBG2-ICAM1, COL4A1-CD44), contribute to PH development. Also, the YTHDC1 expression were consistent with Thioredoxin interacting protein (TXNIP). What's more, the predicted transcription factors showed that NFKB1, Foxd3 may be involved in the regulation of YTHDC1. Lastly, our data suggest that YTHDC1 may be involved in regulating PAECs dysfunction through lncRNA/miRNA/mRNA network. Conclusion: For the first time, we analyzed changes in the expression and biological functions of m6A regulators in SuHx PH mouse models. We causatively linked YTHDC1 to PAECs dysfunction, providing novel insight into and opportunities to diagnose and treat PH.

Background: The incidence of renal clear cell carcinoma (ccRCC) is steadily growing, and cellular metastasis and extensive infiltration of CD8+ T cells are the primary factors contributing to its undesirable prognosis. GLIPR2 (GLI pathogenesis related 2) belongs to the PR-1 family, and it was upregulated in hepatocellular carcinoma, playing a role in the regulation of epithelial cell to mesenchymal transition (EMT). However, its involvement in ccRCC remains unknown. Methods: Genes associated with tumor metastasis and CD8+ T cell levels were identified through weighted gene coexpression network analysis (WGCNA) leveraging the TCGA and GEO databases. Afterwards we follow survival, univariate Cox regression, receiver operating characteristic (ROC) and drug susceptibility analyses confirmed the most influential gene. Further exploration of its molecular, metastatic, and immune properties was carried out through bioinformatics analysis and experimental validation. Results: Initially, GLIPR2 was identified as the most influential gene via WGCNA. Our findings indicated that GLIPR2 exhibited high expression levels in ccRCC and metastatic ccRCC, and its over-expression is significantly correlated with an unfavorable prognosis. Competing endogenous RNAs (CeRNA) network analysis offered insights into the potential regulatory mechanisms governing its expression. Pathway enrichment analysis revealed the involvement of GLIPR2 in multiple pathways intertwined with immune and cellular metastasis. Meanwhile, experiments provided confirmation that GLIPR2 may facilitate the metastasis of ccRCC through EMT. However, the specific mechanisms by which GLIPR2 regulated EMT to promote invasion and migration in ccRCC required in-depth exploration. Single-cell sequencing, immune infiltration, immune survival, and immunotherapy analysis demonstrated the close association between GLIPR2 and CD8+ T cells in ccRCC, as well as its potential for immunotherapeutic intervention. Conclusions: The upregulation of GLIPR2 in ccRCC is associated with cellular metastasis and enrichment of CD8+ T cells. Herein, it may hold promising potential as a predictive independent biomarker for ccRCC metastasis, immune infiltration, and prognosis.

Influenza pandemic with H1N1 (H1N1pdms) causes severe lung damage and “cytokine storm,” leading to higher mortality and global health emergencies in humans and animals. Explaining host antiviral molecular mechanisms in response to H1N1pdms is important for the development of novel therapies. In this study, we organised and analysed multimicroarray data for mouse lungs infected with different H1N1pdm and nonpandemic H1N1 strains. We found that H1N1pdms infection resulted in a large proportion of differentially expressed genes (DEGs) in the infected lungs compared with normal lungs, and the number of DEGs increased markedly with the time of infection. In addition, we found that different H1N1pdm strains induced similarly innate immune responses and the identified DEGs during H1N1pdms infection were functionally concentrated in defence response to virus, cytokine-mediated signalling pathway, regulation of innate immune response, and response to interferon. Moreover, comparing with nonpandemic H1N1, we identified ten distinct DEGs (AREG, CXCL13, GATM, GPR171, IFI35, IFI47, IFIT3, ORM1, RETNLA, and UBD), which were enriched in immune response and cell surface receptor signalling pathway as well as interacted with immune response-related dysregulated genes during H1N1pdms. Our discoveries will provide comprehensive insights into host responding to pandemic with influenza H1N1 and find broad-spectrum effective treatment.

Abstract Nosema ceranae is an intracellular parasite invading the midgut of honeybees, which causes serious nosemosis implicated in honeybee colony losses worldwide. The core gut microbiota is involved in protecting against parasitism, and the genetically engineering of the native gut symbionts provides a novel and efficient way to fight pathogens. Here, using laboratory-generated bees mono-associated with gut members, we find that Snodgrassella alvi inhibit microsporidia proliferation, potentially via the stimulation of host oxidant-mediated immune response. Accordingly, N. ceranae employs the thioredoxin and glutathione systems to defend against oxidative stress and maintain a balanced redox equilibrium, which is essential for the infection process. We knock down the gene expression using nanoparticle-mediated RNA interference, which targets the γ-glutamyl-cysteine synthetase and thioredoxin reductase genes of microsporidia. It significantly reduces the spore load, confirming the importance of the antioxidant mechanism for the intracellular invasion of the N. ceranae parasite. Finally, we genetically modify the symbiotic S. alvi to deliver dsRNA corresponding to the genes involved in the redox system of the microsporidia. The engineered S. alvi induces RNA interference and represses parasite gene expression, thereby inhibits the parasitism significantly. Specifically, N. ceranae is most suppressed by the recombinant strain corresponding to the glutathione synthetase or by a mixture of bacteria expressing variable dsRNA. Our findings extend our previous understanding of the protection of gut symbionts against N. ceranae and provide a symbiont-mediated RNAi system for inhibiting microsporidia infection in honeybees.

Climate change is causing permafrost in the Qinghai–Tibet Plateau to degrade, triggering thermokarst hazards and impacting the environment. Despite their ecological importance, the distribution and risks of thermokarst lakes are not well understood due to complex influencing factors. In this study, we introduced a new interpretable ensemble learning method designed to improve the global and local interpretation of susceptibility assessments for thermokarst lakes. Our primary aim was to offer scientific support for precisely evaluating areas prone to thermokarst lake formation. In the thermokarst lake susceptibility assessment, we identified ten conditioning factors related to the formation and distribution of thermokarst lakes. In this highly accurate stacking model, the primary learning units were the random forest (RF), extremely randomized trees (EXTs), extreme gradient boosting (XGBoost), and categorical boosting (CatBoost) algorithms. Meanwhile, gradient boosted decision trees (GBDTs) were employed as the secondary learning unit. Based on the stacking model, we assessed thermokarst lake susceptibility and validated accuracy through six evaluation indices. We examined the interpretability of the stacking model using three interpretation methods: accumulated local effects (ALE), local interpretable model-agnostic explanations (LIME), and Shapley additive explanations (SHAP). The results showed that the ensemble learning stacking model demonstrated superior performance and the highest prediction accuracy. Approximately 91.20% of the total thermokarst hazard points fell within the high and very high susceptible areas, encompassing 20.08% of the permafrost expanse in the QTP. The conclusive findings revealed that slope, elevation, the topographic wetness index (TWI), and precipitation were the primary factors influencing the assessment of thermokarst lake susceptibility. This comprehensive analysis extends to the broader impacts of thermokarst hazards, with the identified high and very high susceptibility zones affecting significant stretches of railway and highway infrastructure, substantial soil organic carbon reserves, and vast alpine grasslands. This interpretable ensemble learning model, which exhibits high accuracy, offers substantial practical significance for project route selection, construction, and operation in the QTP.

Partially encased composite beams (PECBs) have advantages over conventional steel–concrete composite beams in load-carrying capacity, flexural stiffness and fire resistance. In order to determine whether the shearing force is sufficient to ensure the yield of the tensile reinforcement in the case of a large tensile reinforcement ratio, as well as the influence of encasing concrete strength and the addition of studs on the steel web, three PECB specimens were tested under bending. The results show that, in the case of a 5% tensile reinforcement ratio, natural bonding and friction forces ensure the yield of tensile reinforcement whether studs are added on the steel web or not. The encasing concrete strength and the addition of studs on the steel web have no obvious effect on both the elastic and plastic bending resistance of PECBs. The addition of studs on the steel web significantly slows down the stiffness deterioration of PECBs within the elastoplastic stage, while the flexural stiffness is not obviously affected by the strength of encasing concrete. The simplified plastic theory is proved to be applicable to predict the flexural capacity of PECBs with a large tensile reinforcement ratio. It is also indicated by calculation that, by increasing the tensile reinforcement ratio from 2% to 5%, the flexural capacity of PECBs has a significant increase, by about 32%.

As the quality of public space has become significant for urban development, the creation of high-quality public spaces is becoming increasingly important. Since the implementation of urban renewal policies, an increasing number of buildings have emerged, creating new types of public spaces. Compared to original public spaces, new public spaces are more open, flexible, and diverse. The design of public spaces is closely related to users and the flâneur can precisely serve as a user and observer to conduct in-depth research. So, our study was conducted under the identity of the flâneur, focusing on two cases in Guangzhou. The flâneur completes the data collection through two methods. Static research involves observing and taking photos, whereas dynamic research involves interviews and questionnaires. This study analysed three aspects: the group category, behavioural diversity, and activity time and evaluated the public space using the NPS scale. The study found that the recommendation rate of new urban public spaces is higher than that of original public spaces. The study also found that original public spaces need to be improved in four ways: equipping furniture facilities, improving traffic congestion, increasing blue-green spaces, and establishing artistic spaces. New urban public spaces need to make efforts to create more interactive spaces and increase stagnation points.

RNA interference inhibitors were initially discovered in plant viruses, representing a unique mechanism employed by these viruses to counteract host RNA interference. This mechanism has found extensive applications in plant disease resistance breeding and other fields; however, the impact of such interference inhibitors on insect cell RNA interference remains largely unknown. In this study, we screened three distinct interference inhibitors from plant and mammal viruses that act through different mechanisms and systematically investigated their effects on the insect cell cycle and baculovirus infection period at various time intervals. Our findings demonstrated that the viral suppressors of RNA silencing (VSRs) derived from plant and mammal viruses significantly attenuated the RNA interference effect in insect cells, as evidenced by reduced apoptosis rates, altered gene regulation patterns in cells, enhanced expression of exogenous proteins, and improved production efficiency of recombinant virus progeny. Further investigations revealed that the early expression of VSRs yielded superior results compared with late expression during RNA interference processes. Additionally, our results indicated that dsRNA-binding inhibition exhibited more pronounced effects than other modes of action employed by these interference inhibitors. The outcomes presented herein provide novel insights into enhancing defense mechanisms within insect cells using plant and mammal single-stranded RNA virus-derived interference inhibitors and have potential implications for expanding the scope of transformation within insect cell expression systems.

AGIs (agricultural geographical indicators) are effective quality signals that can improve market welfare, but few studies have investigated the impact of AGIs on economic development. To fill this gap, this paper explores the impact of AGIs on per capita GDP and its mechanisms, according to country-level data in China from 2000 to 2018. For every additional AGI in the country, GDP per capita increased by 0.2–0.4%. Our conclusion remained reliable after various robustness tests. These effects were more salient in western areas, the main grain-producing areas, and settled areas. AGIs related to aquatic environments, animal husbandry, and planting products promoted economic development most significantly. For these effects, encouraging an increase in agricultural value (improving the quantity and quality of products) and promoting the agglomeration of populations, capital, and enterprises in the agricultural sector were the main mechanisms.

The geometrical structures, relative stabilities, and electronic and magnetic properties of niobium carbon clusters, Nb7Cn (n = 1–7), are investigated in this study. Density functional theory (DFT) calculations, coupled with the Saunders Kick global search, are conducted to explore the structural properties of Nb7Cn (n = 1–7). The results regarding the average binding energy, second-order difference energy, dissociation energy, HOMO-LUMO gap, and chemical hardness highlight the robust stability of Nb7C3. Analysis of the density of states suggests that the molecular orbitals of Nb7Cn primarily consist of orbitals from the transition metal Nb, with minimal involvement of C atoms. Spin density and natural population analysis reveal that the total magnetic moment of Nb7Cn predominantly resides on the Nb atoms. The contribution of Nb atoms to the total magnetic moment stems mainly from the 4d orbital, followed by the 5p, 5s, and 6s orbitals.

Honeybees play a major role in crop pollination, which supports the agricultural economy and international food supply. The colony health of honeybees is threatened by the parasitic mite Varroa destructor, which inflicts physical injury on the hosts and serves as the vector for variable viruses. Recently, it shows that V. destructor may also transmit bacteria through the feeding wound, yet it remains unclear whether the invading bacteria can exhibit pathogenicity to the honeybees. Here, we incidentally isolate Enterococcus faecalis, one of the most abundant bacteria in Varroa mites, from dead bees during our routine generation of microbiota-free bees in the lab. In vivo tests show that E. faecalis is only pathogenic in Apis mellifera but not in Apis cerana. The expression of antimicrobial peptide genes is elevated following infection in A. cerana. The gene-based molecular evolution analysis identifies positive selection of genes encoding Späetzle 4 (Spz4) in A. cerana, a signaling protein in the Toll pathway. The amino acid sites under positive selection are related to structural changes in Spz4 protein, suggesting improvement of immunity in A. cerana. The knock-down of Spz4 in A. cerana significantly reduces the survival rates under E. faecalis challenge and the expression of antimicrobial peptide genes. Our results indicate that bacteria associated with Varroa mites are pathogenic to adult bees, and the positively selected gene Spz4 in A. cerana is crucial in response to this mite-related pathogen.

Unmanned surface vessel (USV) target detection algorithms often face challenges such as misdetection and omission of small targets due to significant variations in target scales and susceptibility to interference from complex environments. To address these issues, we propose a small target enhanced YOLOv7 (STE-YOLO) approach. Firstly, we introduce a specialized detection branch designed to identify tiny targets. This enhancement aims to improve the multi-scale target detection capabilities and address difficulties in recognizing targets of different sizes. Secondly, we present the lite visual center (LVC) module, which effectively fuses data from different levels to give more attention to small targets. Additionally, we integrate the lite efficient layer aggregation networks (L-ELAN) into the backbone network to reduce redundant computations and enhance computational efficiency. Lastly, we use Wise-IOU to optimize the loss function definition, thereby improving the model robustness by dynamically optimizing gradient contributions from samples of varying quality. We conducted experiments on the WSODD dataset and the FIOW-Img dataset. The results on the comprehensive WSODD dataset demonstrate that STE-YOLO, when compared to YOLOv7, reduces network parameters by 14% while improving AP50 and APs scores by 2.1% and 1.6%, respectively. Furthermore, when compared to five other leading target detection algorithms, STE-YOLO demonstrates superior accuracy and efficiency.

AbstractGastrointestinal tumors are the most common cancers with the highest morbidity and mortality worldwide. Surgery accompanied by chemotherapy, radiotherapy and targeted therapy remains the first option for gastrointestinal tumors. However, poor specificity for tumor cells of these postoperative treatments often leads to severe side effects and poor prognosis. Tumor immunotherapy, including checkpoint blockade and tumor vaccines, has developed rapidly in recent years, showing good curative effects and minimal side effects in the treatment of gastrointestinal tumors. National Comprehensive Cancer Network guidelines recommend tumor immunotherapy as part of the treatment of gastrointestinal tumors. However, the heterogeneity of tumor cells, complicacy of the tumor microenvironment and poor tumor immunogenicity hamper the effectiveness of tumor immunotherapy. Hydrogels, defined as three-dimensional, hydrophilic, and water-insoluble polymeric networks, could significantly improve the overall response rate of immunotherapy due to their superior drug loading efficacy, controlled release and drug codelivery ability. In this article, we briefly describe the research progress made in recent years on hydrogel delivery systems in immunotherapy for gastrointestinal tumors and discuss the potential future application prospects and challenges to provide a reference for the clinical application of hydrogels in tumor immunotherapy.

ABSTRACTIn recent years, an increasing number of emerging and remerging virus outbreaks have occurred and the rapid development of vaccines against these viruses has been crucial. Controlling the replication of premature termination codon (PTC)-containing viruses is a promising approach to generate live but replication-defective viruses that can be used for potent vaccines. Here, we used anticodon-engineered transfer RNAs (ACE-tRNAs) as powerful precision switches to control the replication of PTC-containing viruses. We showed that ACE-tRNAs display higher potency of reading through PTCs than genetic code expansion (GCE) technology. Interestingly, ACE-tRNA has a site preference that may influence its read-through efficacy. We further attempted to use ACE-tRNAs as a novel viral vaccine platform. Using a human immunodeficiency virus type 1 (HIV-1) pseudotyped virus as an RNA virus model, we found that ACE-tRNAs display high potency for read-through viral PTCs and precisely control their production. Pseudorabies virus (PRV), a herpesvirus, was used as a DNA virus model. We found that ACE-tRNAs display high potency for reading through viral PTCs and precisely controlling PTC-containing virus replication. In addition, PTC-engineered PRV completely attenuated and lost virulence in mice in vivo, and immunization with PRV containing a PTC elicited a robust immune response and provided complete protection against wild-type PRV challenge. Overall, replication-controllable PTC-containing viruses based on ACE-tRNAs provide a new strategy to rapidly attenuate virus infection and prime robust immune responses. This technology can be used as a platform for rapidly developing viral vaccines in the future.

Abstract Metallocenes are privileged backbones in the fields of synthetic chemistry, catalysis, polymer science, etc. Direct C–H functionalization is undoubtedly the simplest approach for tuning the properties of metallocenes. However, owing to the presence of multiple identical C(sp2)‐H sites, this protocol often suffers from low reactivity and selectivity issues, especially for the regioselective synthesis of 1,3‐difunctionalized metallocenes. Herein, an efficient iridium‐catalyzed meta‐selective C–H borylation of metallocenes is reported. With no need of preinstalled directing groups, this approach enables a rapid synthesis of various boronic esters based on benzoferrocenes, ferrocenes, ruthenocene, and related half sandwich complex. A broad range of electron‐deficient and ‐rich functional groups are all compatible with the process. Notably, C–H borylation of benzoferrocenes takes place exclusively at the benzene ring, which is likely ascribed to the shielding effect of pentamethylcyclopentadiene. The synthetic utility is further demonstrated by easy scalability to gram quantities, the conversion of boron to heteroatoms including N3, SePh, and OAc, as well as diverse cross‐coupling reactions.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders, with an increasing incidence. Gastrointestinal symptoms are common comorbidities of ASD. The gut microbiota composition of children with autism is distinct from that of typical developmental (TD) children, suggesting that the gut microbiota probably influences on hosts via the microbiota-gut-brain axis. However, the relationship between intestinal dysbiosis and host brain function remains unclear. In this study, we creatively developed a honeybee model and investigated the potential effects of fecal microbiota on hosts. Fecal microbiota from children with autism and TD children were transplanted into microbiota-free honeybees (Apis mellifera), resulting in induced ASD-fecal microbiota transplantation (FMT) honeybees (A-BEE group) and TD-FMT honeybees (T-BEE group), respectively. We found that cognitive abilities of honeybees in the A-BEE group were significantly impaired in olfactory proboscis extension response conditioning. Metagenomics was used to evaluate fecal microbiota colonization, revealing several differential species responsible for altered tryptophan metabolism and taurine metabolism within the bee gut, including Bacteroides dorei, Bacteroides fragilis, Lactobacillus gasseri, and Lactobacillus paragasseri. Furthermore, fecal microbiota from children with autism downregulated brain genes involved in neural signaling and synaptic transmission within honeybees. Notably, differentially spliced genes observed within brains of honeybees from the A-BEE group largely overlapped with those identified in human diagnosed with autism via SFARI and SPARK gene sets. These differentially spliced genes were also enriched within pathways related to neural synaptic transmission. Our findings provide novel insights into the pivotal role of the human gut microbiota, which may contribute to neurological processes in honeybees. Additionally, we present a few research sources on gut-brain connections in ASD.

Abstract Mitochondrial bioenergetic deficits and their resulting glucose hypometabolism are the key pathophysiological modulators that promote neurodegeneration. However, there are no specific potential molecules that have been identified to treat neurological diseases by regulating energy metabolism and repairing mitochondrial damage. Pyruvate dehydrogenase (PDH) complex (PDC), which can be phosphorylated by pyruvate dehydrogenase kinase (PDK), is the gate‐keeping enzyme for mitochondrial glucose oxidation. In this study, a small‐molecule scutellarin (SG) is discovered that can significantly alleviate the neuropathological changes in hippocampal CA1 of cerebral hypoperfusion model rats, rescued the morphological changes of abnormal mitochondria, and restored mitochondrial homeostasis. Mitochondrial proteomics, energy metabolism monitoring, and 13C‐metabolic flux analysis targeted SG activity on PDK2, thus regulating PDK‐PDC‐mediated glycolytic metabolism to TCA cycle during mitochondrial OXPHOS damage. The knockdown of PDK2 in the SK‐N‐SH cells validated that SG could rescue mitochondrial damage via the PDK‐PDC axis, promote the MMP level and reduce the mitochondria‐dependent apoptosis. Collectively, this study explored the novel therapeutic approach: the PDK‐PDC axis for neurological injury and cognitive impairment and uncovered the effect of SG on mitochondrial protection via the PDK‐PDC axis and mitochondrial glucose oxidation. The findings indicate that active components ameliorating mitochondrial bioenergetic deficits could be of significant value for neurological disease therapy.

Energy flux in food webs is a fundamental feature of ecosystems and an important link between biodiversity and ecosystem function. Studies of energy flow through the soil nematode food web have emerged in recent year; however, it is not clear whether and how the nematode food web structure affects the energy flow. In this study, the structures and carbon flux of soil nematode food webs in four different ecosystems, namely, forageland, cropland, secondary forest, and grass-shrubland, were assessed. The food web structure was represented by nematode community indices such as maturity index, structure index, genus and trophic group diversity, and slope of size spectra. The results showed that carbon flux through the nematode food webs was the highest and lowest in the secondary forest and forageland, respectively. The total carbon flux of nematode food web was higher in the cropland than that in the grass-shrubland. The magnitudes of bacterial and fungal energy channels were basically equal in the forageland and secondary forest. The energy flow through the bacterial channel was greater than that through the fungal channel in the grass-shrubland, whereas the pattern was reversed in the cropland. The total carbon flux through the nematode food web, the carbon fluxes through the bacterial or fungal channel, and the energy flow uniformity were positively correlated with the nematode structure index, maturity index, and genus diversity index. The trophic group diversity and size spectra slope of nematode communities were not significantly correlated with the carbon flux. The results indicate that mature and complex soil communities support high energy flux across soil food webs.

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

Background Ociperlimab, a novel, humanized monoclonal antibody (mAb), binds to T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) with high affinity and specificity. Tislelizumab is an anti-programmed cell death protein 1 mAb. We report results from a phase I, first-in-human, dose escalation study evaluating the safety, pharmacokinetics (PK), and preliminary antitumor activity of ociperlimab plus tislelizumab in patients with advanced solid tumors.Methods Eligible patients previously treated with standard systemic therapy, or for whom treatment was not available or tolerated, received ociperlimab intravenously on Cycle (C) 1 Day (D) 1 and tislelizumab 200 mg intravenously on C1 D8. If tolerated, patients received ociperlimab plus tislelizumab 200 mg sequentially on D29 and every 3 weeks (Q3W) thereafter until discontinuation. Dose escalation for ociperlimab was planned with four dose levels (50 mg, 150 mg, 450 mg, and 900 mg) according to a 3+3 design. An additional dose level of ociperlimab 1800 mg was also assessed. Primary endpoints were safety, determination of the maximum tolerated (or administered) dose, and the recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), duration of response (DoR), disease control rate (DCR) (Response Evaluation Criteria in Solid Tumors version 1.1), PK, and biomarker analysis.Results At data cut-off (September 29, 2022), 32 patients had received ≥1 dose of ociperlimab plus tislelizumab 200 mg Q3W. The maximum administered dose was ociperlimab 1800 mg plus tislelizumab 200 mg Q3W. The median age of enrolled patients was 59.5 years (range: 31–79). Most patients (96.9%) experienced ≥1 treatment-emergent adverse event (TEAE); 62.5% of patients experienced ≥grade 3 TEAEs and 50.0% of patients experienced serious TEAEs. No dose limiting toxicity events were reported. The maximum tolerated dose was not reached. The RP2D was ociperlimab 900 mg plus tislelizumab 200 mg Q3W. Overall, ORR was 10.0%, median DoR was 3.6 months, and DCR was 50.0%.Conclusions Ociperlimab plus tislelizumab was well tolerated in patients with advanced solid tumors, and preliminary antitumor activity was observed with 450 mg, 900 mg, and 1800 mg ociperlimab. Phase II/III trials of ociperlimab 900 mg plus tislelizumab 200 mg Q3W are underway in a range of solid tumors.Trial registration number NCT04047862.

In the context of the digital information era, consumers’ information capability plays a crucial role in shaping their green consumption intention. To delve deeper into the dynamics of how information capability influences consumers’ green consumption intention, this study constructs a theoretical model grounded in information asymmetry theory and cognitive bias theory. Additionally, the mediating role of green trust and the moderating role of media publicity are incorporated to comprehensively investigate the influence mechanism of information capability on consumers’ green consumption intention. Empirical analysis is conducted based on data collected through a questionnaire survey. The findings of this study reveal that information capability exerts a partially mediating effect on consumers’ green consumption intention. Specifically, information capability directly influences consumers’ green consumption intention, and it also indirectly impacts their green consumption intention through its influence on green trust. Furthermore, media publicity positively moderates the relationship between information capability and consumers’ green consumption intention. This research contributes to the existing literature by enhancing our understanding of the influence pathway leading to green consumption intention. Its insights offer valuable implications for promoting green consumption and advancing sustainable development initiatives.

Cipher-block chaining (CBC) is a widely used encryption mode for smart grid data, however, the chain structure leads to low encryption and decryption efficiency. To overcome this issue, this paper proposes a novel tree-CBC (TCBC) block encryption method. First, the smart grid plaintext is preprocessed according to the security level of the data. Second, the chain structure of the CBC mode is converted into a tree structure, and for the data block with a higher security level, its location is deeper in the encryption tree. Third, since the overall security and encryption time of data encrypted by TCBC depend on the number of forks of the encryption tree, this paper proposes a method to determine the optimal number of forks of TCBC based on the weights of the encryption time and security of the data blocks. The experiment shows that the encryption efficiency of the TCBC mode is improved by nearly 50% compared to the original CBC mode. And as the data size increases, the efficiency improvement becomes more obvious. Furthermore, compared with widely used encryption modes such as CFB, OFB, CTR, and PCBC, the proposed TCBC mode has higher encryption and decryption efficiency.

Tumors are among the leading causes of death worldwide. Cell-derived biomimetic functional materials have shown great promise in the treatment of tumors. These materials are derived from cell membranes, extracellular vesicles and bacterial outer membrane vesicles and may evade immune recognition, improve drug targeting and activate antitumor immunity. However, their use is limited owing to their low drug-loading capacity and complex preparation methods. Liposomes are artificial bionic membranes that have high drug-loading capacity and can be prepared and modified easily. Although they can overcome the disadvantages of cell-derived biomimetic functional materials, they lack natural active targeting ability. Lipids can be hybridized with cell membranes, extracellular vesicles or bacterial outer membrane vesicles to form lipid-hybrid cell-derived biomimetic functional materials. These materials negate the disadvantages of both liposomes and cell-derived components and represent a promising delivery platform in the treatment of tumors. This review focuses on the design strategies, applications and mechanisms of action of lipid-hybrid cell-derived biomimetic functional materials and summarizes the prospects of their further development and the challenges associated with it.

Background: Allergic dermatitis (AD) is an inflammatory skin disease that arises from abnormal T lymphocyte activation. A recombinant fusion protein comprising Helicobacter pylori neutrophil-activating protein and maltose binding protein, rMBP-NAP, has been documented as a novel immunomodulatory TLR agonist.Objective: To explore the effect of the rMBP-NAP on the OXA-induced AD in a mouse model and clarify the possible action mechanism.Methods: The AD animal model was induced by repeated administration of oxazolone (OXA) in BALB/c mice. H&E staining was used to analyze the ear epidermis thickness and the number of infiltrating inflammatory cells. TB staining was used to detect mast cell infiltration in the ear tissue. ELISA was used to analyze the secretion of cytokines IL-4 and IFN-γ in peripheral blood. qRT-PCR was used to determine the expression levels of IL-4, IFN-γ, and IL-13 in ear tissue.Results: OXA induced the establishment of an AD model. After the rMBP-NAP treatment, the thickness of the ear tissue and the number of mast cells infiltrated in AD mice reduced, and the serum and ear tissue levels of IL-4 and IFN-γ increased, but the ratio of IFN-γ (rMBP-NAP group)/IL-4 (rMBP-NAP group) was greater than the ratio of IFN-γ (sensitized group)/IL-4 (sensitized group).Conclusion: The rMBP-NAP improved the disease symptoms including skin lesions in AD, alleviated the inflammation in ear tissue, and restored the Th1/2 balance by inducing a shift from the Th2 to the Th1 response. The results of our work support the use of rMBP-NAP as an immunomodulator for AD treatment in future investigations.

Abstract Objectives This study aimed to compare the incidence, clinicopathological characteristics and survival results of pancreatic signet ring cell carcinoma (PSRCC) and pancreatic adenocarcinomas (PDAC), as well as to analyze the clinical characteristics related to the overall survival (OS) of PSRCC, and to establish an effective prognostic nomogram to predict the risks associated with patient outcomes. Methods A total of 85,288 eligible patients including 425 PSRCC and 84,863 PDAC cases were retrieved from the Surveillance, Epidemiology, and End Results database. The survival curve was calculated using the Kaplan–Meier method and differences in them were measured by Log-rank tests. The Cox proportional hazards regression model was used to identify independent predictors of OS in patients with PSRCC. A nomogram was constructed to predict 1-, 3-, and 5-year OS. The performance of the nomogram was measured by C-index, receiver operating characteristic (ROC) curve, decision curve analysis (DCA). Results The incidence of PSRCC is much lower than that of PDAC (10.798 V.S. 0.349 per millions). PSRCC is an independent predictor of pancreatic cancer with a poorer histological grade, a higher rate of lymph node and distant metastasis, and a poorer prognosis. We identified four independent prognostic factors including grade, American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) stage, surgery and chemotherapy based on the Cox regression model. The C-index and DCA curves showed better performance of the nomogram than TNM stage. ROC curve analysis also showed that the nomogram had good discrimination, with an area under the curve of 0.840, 0.896, and 0.923 for 1-, 3-, and 5-year survival. The calibration curves showed good agreement between the prediction by the nomogram and actual observations. Conclusion PSRCC is a rare but fatal subtype of pancreatic cancer. The constructed nomogram in this study accurately predicted the prognosis of PSRCC, performed better than the TNM stage.

Abstracts Background Preclinical studies suggest that glucocorticoids (GCs) promote the proliferation and development of colorectal cancer. Because GCs are broadly prescribed for treatment-related adverse events in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (NCRT), it’s essential to assess the effect of GCs on clinical outcomes. Methods LARC cases treated with NCRT followed by surgery were assessed retrospectively. Evaluation of the relationship between GCs use (GCs vs. non-GCs) and neoadjuvant rectal (NAR) score (as a three-level categorical dependent variable) was performed using multivariable multinomial logistic regression (MLR). We also examined the relationship between the accumulated dose of GCs and NAR using multivariate MLR. Survival analysis of disease-free survival (DFS) and overall survival (OS) was performed using the Kaplan–Meier method. Multivariate Cox regression was used to assess confounding factors that could influence OS and DFS. Results This retrospective cohort study included 790 patients with newly diagnosed non-metastatic LARC (T3-4/N + M0) who received NCRT followed by surgery between January 2012 and April 2017. The end of the follow-up period was May 11, 2022. Among the 790 patients with LARC, 342 (43.2%) received GCs treatment and 448 (56.8%) did not during the NCRT-to-surgery period. GCs medication was significantly different between mid-NAR (8–16) and low-NAR ( 16) and low-NAR (0.563; 0.352–0.900; 0.016). Patients exposed to GCs, had a decreased 5-year OS (GCs vs. non-GCs = 80.01% (95% CI, 75.87%–84.37%) vs. 85.30% (82.06%–88.67%), P = 0.023) and poorer 5-year DFS (73.99% (69.45%–78.82%) vs. 78.7% (75.14%–82.78%), P = 0.045). The accumulated dose of GCs was an independent risk factor for OS (hazard ratio [HR], 1.007 [1.001–1.014], 0.036) and DFS (1.010 [1.004–1.017], 0.001). Conclusions and relevance Our study revealed that GCs were associated with reduced efficacy of NCRT and worse clinical outcomes in patients with LARC during the NCRT-to-surgery period.

Abstract Hepatocellular carcinoma (HCC) is a global health problem. Its incidence and mortality are increasing. Exploring novel therapeutic targets against HCC is important and urgent. We here explored the expression and potential function of Gαi2 (G protein subunit alpha i2) in HCC. The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database shows that the number of Gαi2 transcripts in HCC tissues is significantly higher than that in the normal liver tissues. Moreover, Gαi2 overexpression in HCC correlates with poor prognosis of the patients. Gαi2 mRNA and protein expression are also elevated in local HCC tissues and different human HCC cells. In patient-derived primary HCC cells and immortalized HepG2 cells, Gαi2 silencing (by targeted shRNA) or knockout (KO, by the dCas9-sgRNA method) largely suppressed cell proliferation and motility, while inducing cell cycle arrest and caspase-apoptosis activation. Moreover, Gαi2 silencing or KO-induced reactive oxygen species (ROS) production and oxidative injury in primary and HepG2 HCC cells. Whereas different antioxidants ameliorated Gαi2-shRNA-induced anti-HCC cell activity. Using a lentiviral construct, Gαi2 overexpression further augmented proliferation and motility of primary and immortalized HCC cells. Further studies revealed that the binding between the transcription factor early growth response zinc finger transcription factor 1 (EGR1) and Gαi2 DNA promoter was significantly increased in HCC tissues and cells. In vivo, intratumoral injection of Gαi2 shRNA adeno-associated virus significantly hindered HCC xenograft growth in nude mice. Moreover, the growth of Gαi2-KO HCC xenografts in the nude mice was remarkably slow. Gαi2 depletion, oxidative injury, and apoptosis induction were detected in Gαi2-silenced or Gαi2-KO HCC xenografts. Together, overexpressed Gαi2 is required for HCC cell growth in vitro and in vivo, representing as a novel and promising diagnosis marker and therapeutic target of HCC.

Controlling molecular motion is challenging. Here, the authors report the effect of counter cations on the rotational barriers of hydroquinone rings in a molecular rotor based on anionic pillar[5]arenes.