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Abstract The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis. Graphical Abstract

Abstract Objectives A higher reperfusion grade after endovascular thrombectomy (EVT) is associated with a good prognosis. However, the effect of the number of retrievals has not yet been investigated in vertebrobasilar occlusion (VBAO). Therefore, the aim of this study was to investigate whether to continue retrieval after early modified thrombolysis in cerebral infarction (mTICI) 2b to achieve a better reperfusion grade. Methods We retrospectively analyzed the data of patients who underwent EVT caused by VBAO in a multicenter registry dataset. Patients who underwent successful reperfusion were included (mTICI 2b/3). Regression models were used to analyze the correlation of different reperfusion grades stratified by the number of retrieval attempts with clinical prognosis and hemorrhage transition. Results We included 432 patients: 34.5% (n = 149) had a final mTICI score of 2b and 65.5% (n = 283) had a final mTICI score of 3. Patients who obtained a mTICI of 3 after the first pass had significantly increased odds of having a good prognosis. As the number of passes increases, the chances of obtaining a good prognosis decreases. After three or more passes, the odds of achieving functional independence and favorable outcomes were comparable to those of the first mTICI 2b, regardless of the 90‐day (OR 1.132 95% CI 0.367–3.487 p = 0.829; OR 1.070 95% CI 0.375–3.047 p = 0.900) or 1‐year follow‐up (OR 1.217 95% CI 0.407–3.637 p = 0.725; OR 1.068 95% CI 0.359–3.173 p = 0.906). Interpretation Within two retrieval attempts, mTICI 3 was better than the first retrieval to mTICI 2b. After early mTICI 2b, each retrieval should be undertaken with caution to pursue a higher reperfusion grade.

Abstract O6‐methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the guanine O6 position (O6‐MG) and repairs DNA damage. High MGMT expression results in poor response to temozolomide (TMZ). However, the biological importance of MGMT and the mechanism underlying its high expression in pancreatic neuroendocrine tumors (PanNETs) remain elusive. Here, it is found that MGMT expression is highly elevated in PanNET tissues compared with paired normal tissues and negatively associated with progression‐free survival (PFS) time in patients with PanNETs. Knocking out MGMT inhibits cancer cell growth in vitro and in vivo. Ectopic MEN1 expression suppresses MGMT transcription in a manner that depends on β‐Catenin nuclear export and degradation. The Leucine 267 residue of MEN1 is crucial for regulating β‐Catenin‐MGMT axis activation and chemosensitivity to TMZ. Interference with β‐Catenin re‐sensitizes tumor cells to TMZ and significantly reduces the cytotoxic effects of high‐dose TMZ treatment, and MGMT overexpression counteracts the effects of β‐Catenin deficiency. This study reveals the biological importance of MGMT and a new mechanism by which MEN1 deficiency regulates its expression, thus providing a potential combinational strategy for treating patients with TMZ‐resistant PanNETs.

Dynamic searchable symmetric encryption(DSSE) combines dynamic update with searchable encryption, allowing users to not only achieve keyword retrieval, but also dynamically update encrypted data stored on semi-trusted cloud server, effectively protecting user’s privacy. However, the majority of existing DSSE schemes exhibit inefficiencies in practical applications because of their complex structure. In addition, to store the status of keywords, the storage requirements of the client increase proportionally with the number of keyword/document pairs. Therefore, the client storage will be overwhelmed when confronted with a substantial increase in the volume of keyword/document pairs. To solve these issues, we propose a practical efficient dynamic searchable symmetric encryption scheme with lightweight clients—CoD-DSSE. A novel index structure similar to a chest of drawers is proposed in CoD-DSSE, which allows users to efficiently search all document indexes through XOR operations and keeps the keyword status on the server to lightweight clients. Furthermore, we use a random number generator to construct new search tokens for forward security and achieve backward security by using a Bloom filter to store the deleted document index, which can significantly reduce communication costs. The experimental and security analyses show that CoD-DSSE is efficient and secure in practice.

Honey adulteration with exogenous syrup has become a common phenomenon, and current detection techniques that require large instruments are cumbersome and time-consuming. In this study, a simple and efficient method was developed by integrating the rapid extraction of nucleic acids (REMD) and recombinase polymerase amplification (RPA), known as REMD-RPA, for the rapid screening of syrup adulteration in honey. First, a rapid extraction method was developed to rapidly extract corn syrup DNA in five minutes to meet the requirements of PCR and RPA assays. Then, the RPA method for detecting endogenous maize genes (ZssIIb) was established, which could detect 12 copies/μL of the endogenous maize gene within 30 min without cross-reacting with other plant-derived genes. This indicated that the RPA technique exhibited high sensitivity and specificity. Finally, the REMD-RPA detection platform was used to detect different concentrations of corn syrup adulteration, and 1 % adulteration could be detected within 30 min. The 22 commercially available samples were tested to validate the efficacy of this method, and the established RPA was able to detect seven adulterated samples in less than 30 min. Overall, the developed method is rapid, sensitive, and specific, providing technical support for the rapid field detection of honey adulteration and can serve as a reference for developing other field test methods.

Background and objectives: Both myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) are demyelinating diseases of the central nervous system. They present similar clinical manifestations such as optica neuritis, myelitis and area postrema syndrome (APS). The distinctions of optica neuritis (ON) and myelitis between them have been elaborated to great length while their differences in APS remain to be elucidated. We aim to report the frequency of APS in patients with MOGAD as well as NNOSD patients, and to compare the characteristics of APS between patients with MOGAD and those with NMOSD. Methods: Seven MOG-IgG positive APS patients were retrospectively identified between 2017 and 2022. APS phenotypes have been previously described. The similarities and differences between MOGAD and NMOSD patients with APS was compared, including the frequency and duration of APS between the two diseases, and their incidences of accompanied subtentorial lesions have also been described and compared. Results: We reviewed a cohort of 218 MOG-IgG-positive patients, and 396 patients with NMOSD. 200 MOGAD patients and 332 NMOSD patients were included in this study. In the cohort, seven patients with MOG-IgG-positive antibody presented with APS were analyzed, four of whom had disease onset with APS. Of the 332 patients with NMOSD, 47 had APS attacks while 31 had APS at disease onset. In patients with MOGAD, 2 had nausea, 3 had vomiting, 5 had hiccups, and 1 patient presented with all three symptoms above. In patients with NMOSD, 70.2 % had nausea, vomiting and hiccups at the same time during APS attacks. Apart from the medulla oblongata, other subtentorial regions were also affected in 6/7 MOGAD patients while 14/47 NMOSD patients had other subtentorial regions involved. During an APS attack, the incidence of concomitant lesions in the brainstem and other regions was significantly greater in MOGAD than in the NMOSD cohort (P = 0.008*). Conclusion: APS is a rare, but not isolated clinical manifestation of MOGAD. APS happened more frequently with other supratentorial and subtentorial lesions in MOGAD. The symptoms of NVH (nausea, vomiting, hiccups) tended to happen respectively in MOGAD compared with NMOSD. The phenotype or mechanism of APS in MOGAD may differ from that in NMOSD.

Abstract Few studies have provided data on the metabolomics characteristics of metabolic diseases such as hyperuricemia and hyperbilirubinemia in the Tibetan plateau. In the current study, we sought to investigate the serum metabolomics characteristics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau, with the aim to provide a basis for further research on their pathogenesis, prevention, and treatment. The study participants were born in low-altitude areas below 1000 m and had no prior experience living in a high-altitude area before entering Golmud, Tibet (average elevation: 3000 m) and Yushu, Qinghai (average elevation: 4200 m). Thirty-four participants with hyperbilirubinemia (18 in Golmud and 16 in Yushu), 24 participants with hyperuricemia, and 22 healthy controls were enrolled. The serum samples of subjects were separated and then sent to a local tertiary hospital for biochemical examination. Serum widely targeted technology, based on the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) platform, was used to detect serum metabolites and differential metabolites. Compared to the healthy controls, hyperbilirubinemia patients from Golmud showed 19 differential metabolites, hyperbilirubinemia patients from Yushu showed 12 differential metabolites, and hyperuricemia patients from Yushu showed 23 differential metabolites. Compared to the hyperbilirubinemia patients from Golmud that is at a low altitude, the Yushu groups had 33 different metabolites. Differential metabolites are primarily classified into amino acids and their derivatives, nucleotides and their derivatives, organic acids and their derivatives, and lipids/fatty acids. These are related to metabolic pathways such as caffeine metabolism, arachidonic acid metabolism, and tyrosine metabolism. Hyperbilirubinemia and hyperuricemia in the Tibetan plateau have unique serum metabolomics characteristics. Glycine derivatives and arachidonic acid and its derivatives were associated with plateau hyperbilirubinemia, and vanillic acid and pentadecafluorooctanoic acid were associated with plateau hyperuricemia.

Heat treatment is important for optimizing the strength performance and improving the toughness of titanium alloys. In this study, we investigated the impact of three heat treatment methods (β-annealing, double annealing, and solid-solution and aging treatment) on the mechanical properties and fracture morphology of Ti555211 titanium alloy. The results show that after β-annealing treatment, the alloy retains a high strength, while showing almost no ductility, and no yield strength. The alloy after double annealing has a high elongation rate (~54%) and lower strength. After solid-solution and aging heat treatment, the alloy was able to retain both high strength and a certain degree of ductility. The optimal heat-treatment process is solid-solution treatment at 820 °C/2 h and aging at 560 °C/12 h, which results in a maximum tensile strength of 1404 MPa and an elongation rate of 11%.

Accurate monitoring of leaf phenology, from individual trees to entire ecosystems, is vital for understanding and modeling forest carbon and water cycles, as well as assessing climate change impact. However, the accuracy of many remote-sensing phenological products remains difficult to directly corroborate using ground-based monitoring, owing to variations in the observed indicators and the scales used. This limitation hampers the practical implementation of remote-sensing phenological metrics. In our study, the start of growing season (SOS) from 2016 to 2021 was estimated for the continental USA using Sentinel-2 images. The results were then matched with several ground-based spring vegetation phenology metrics obtained by the USA National Phenology Network (USA-NPN). In this study, we focused on the relationships between the leaf-unfolding degree (LUD), the SOS, and the factors that drive these measures. Our results revealed that: (1) the ground-based leaves and increasing leaf size stages were significantly correlated with the SOS; (2) with the closest match being observed for a leaf spread of 13%; (2) the relationship between the SOS and LUD varied according to the species and ecoregion, and the pre-season cumulative radiation was found to be the main factor affecting the degree of matching between the ground observations and the metrics derived from the Sentinel-2 data. Our investigations provide a ground-based spring phenology metric that can be used to verify or evaluate remote-sensing spring phenology products and will help to improve the accuracy of remote-sensing phenology metrics.

In this paper, a comprehensive study combined multiple characterizations and SPH numerical simulation was conducted to investigate the microstructure evolution, extreme thermomechanical behavior and consequences of the explosive welded CLAM/316L interface. The interfaces of the two welding materials underwent remarkable temperature rise and rapid cooling under high-speed collision conditions, forming a tight bond that presents a wavy structure with vortices. The SPH simulation adequately reproduced the heating and cooling process of the interface during explosive welding, revealing the high heterogeneity of the thermodynamic behavior during the impact process. Furthermore, the EBSD analyses showed the perplexing evolution of crystal structure at the bonding interface with vortex, including ultra-fine grains, columnar grains, equiaxed grains, deformed grains and serious lattice distortion. By correlating the temperature histories and grain characteristics at different positions of the interface, the formation mechanism of diverse grains was revealed, referring to crystallization from liquid, recrystallization from the solid and plastic deformation. The recrystallization at the interface was closely related to the material properties, and the significant variations in dislocation density and plastic strain values at the interface, as well as the thermal softening of the material, could be explained by different degrees of dynamic recovery and recrystallization.

This study proposed a dynamic self-constrained explosive welding method to fabricate the copper-steel bimetallic tube without external mold. The mechanical balance of the self-constrained process was carefully revealed by three-dimensional (3D) numerical simulations. Besides, the microstructure evolution, element distribution, and mechanical properties of the copper-steel interface were systematically investigated. Results showed that the dynamic self-constrained system could effectively strike a balance between the inner and outer tubes in terms of stress, velocity, and displacement. The max hoop tensile stress near the outer surface of the base tube was significantly reduced from 535 MPa (in the unconstrained experiment) to 387 MPa avoiding the appearance of radial cracks. The welding interface varied from a nearly straight one via a large wave to an irregularly small wave. Meanwhile, the microhardness test showed a significant increase in the region near the welding interface.

Abstract Transgenic soybean is one of the most planted crops for human food and animal feed. The channel catfish (Ictalurus punctatus) is an important aquatic organism cultured worldwide. In this study, the effect of six different soybean diets containing: two transgenic soybeans expressing different types of cp4-epsps, Vip3Aa and pat genes (DBN9004 and DBN8002), their non-transgenic parent JACK, and three conventional soybean varieties (Dongsheng3, Dongsheng7, and Dongsheng9) was investigated in juvenile channel catfish for eight weeks, and a safety assessment was performed. During the experiment, no difference in survival rate was observed in six groups. The hepatosomatic index (HSI) and condition factor (CF) showed no significant difference. Moreover, comparable feed conversion (FC), feeding rate (FR), and feed conversion ratio (FCR) were found between transgenic soybean and JACK groups. Assessment of growth performance showed that the weight gain rate (WGR) and specific growth rate (SGR) of channel catfish were consistent. In addition, there were no changes in enzyme activity indexes (lactate dehydrogenase (LDH), total antioxidant capacity (T-AOC), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) in channel catfish among treatments. The research provided an experimental basis for the aquaculture feed industry to employ transgenic soybean DBN9004 and DBN8002 for commercial purposes.

Abstract Serine proteases (SPs) and their homologs (SPHs) are among the best-characterized gene families. They are involved in several physiological processes, including digestion, embryonic development and immunity. In the current study, a total of 177 SPs-related genes were characterized in the genome of Ostrinia furnacalis. The activation site of SPs/SPHs and enzyme specificity of SPs were identified, and the findings showed that most of the SPs analyzed possessed trypsin substrate specificity. Several SPs/SPHs with similar simple gene structures had tandem repeat-like distributions on the scaffold, indicated that gene expansion has occurred in this large family. Furthermore, we constructed 30 RNA sequencing libraries including four with developmental stage and four middle larval stage tissues to study the transcript levels of these genes. Differentially upregulated and downregulated genes were obtained via data analysis. More than one-quarter of the genes were specifically identified as highly expressed in the midgut in compared to the other three tissues evaluated. In the current study, the domain structure, gene location and phylogenetic relationship of genes in O. furnacalis were explored. Orthologous comparisons of SPs/SPHs between model insects and O. furnacalis indicated their possible functions. This information provides a basis for understanding the functional roles of this large family.

Letting f be a transcendental meromorphic function, we consider the value distribution of the differential polynomials φfl(f(k))n−a, where φ(≢0) is a small function of f, l(≥2), n(≥1), k(≥1) are integers and a is a non-zero constant, and obtain an important inequality concerning the reduced counting function of φfl(f(k))n−a. Our results improve and generalize the results obtained by Xu and Ye, Karmakar and Sahoo, Chakraborty et.al, and Chen and Huang.

Nucleic acid quantification, allowing us to accurately know the copy number of target nucleic acids, is significant for diagnosis, food safety, agricultural production, and environmental protection. However, current digital quantification methods require expensive instruments or complicated microfluidic chips, making it difficult to popularize in the point-of-care detection. Paper is an inexpensive and readily available material. In this study, we propose a simple and cost-effective paper membrane-based digital loop-mediated isothermal amplification (LAMP) method for nucleic acid quantification. In the presence of DNA fluorescence dyes, the high background signals will cover up the amplicons-formed bright spots. To reduce the background fluorescence signals, a quencher-fluorophore duplex was introduced in LAMP primers to replace non-specific fluorescence dyes. After that, the amplicons-formed spots on the paper membrane can be observed; thus, the target DNA can be quantified by counting the spots. Take Vibrio parahaemolyticus DNA detection as an instance, a good linear relationship is obtained between the light spots and the copy numbers of DNA. The paper membrane-based digital LAMP detection can detect 100 copies target DNA per reaction within 30 min. Overall, the proposed nucleic acid quantification method has the advantages of a simple workflow, short sample-in and answer-out time, low cost, and high signal-to-noise, which is promising for application in resourced limited areas.

Microplastics (MPs) and the heavy metal cadmium (Cd) have attracted global attention for their toxicological interactions in aquatic organisms. The purpose of this investigation was evaluating the effect of MPs (1 mg L−1) and Cd (5 mg L−1) on the liver function, immune response of crucian carp (Carassius carassius) after 96 h exposure, and intestinal microbiota after 21 days, respectively. Co-exposure to MPs and Cd significantly enhanced MP accumulation in the liver of the crucian carp compared to the accumulation with exposure to MPs alone. Co-exposure to MPs and Cd triggered notable histopathological alterations accompanied by increased hepatic cell necrosis and inflammation, and was associated with higher aspartate aminotransferase and alanine aminotransferase levels, lower superoxide dismutase and catalase activity levels, but higher malondialdehyde content and total antioxidant capacity in the liver. Moreover, the combined treatment of MPs and Cd led to the up-regulated transcription of genes related to immune response, such as interleukin 8 (il-8), il-10, il-1β, tumor necrosis factor-α, and heat shock protein 70, both in the liver and spleen. Co-exposure to MPs and Cd reduced the variety and abundance of the intestinal microbiota in the crucian carp. Our research indicates that the combined exposure to MPs and Cd may exert synergistic toxic effects on crucian carp, which could impede the sustainable growth of the aquaculture industry and pose potential risks to food safety.

Abstract Background Colorectal cancer (CRC), a commonly diagnosed cancer often develops slowly from benign polyps called adenoma to carcinoma. Altered gut microbiota is implicated in colorectal carcinogenesis. It is warranted to find non-invasive progressive microbiota biomarkers that can reflect the dynamic changes of the disease. This study aimed to identify and evaluate potential progressive fecal microbiota gene markers for diagnosing advanced adenoma (AA) and CRC. Results Metagenome-wide association was performed on fecal samples from different cohorts of 871 subjects (247 CRC, 234 AA, and 390 controls). We characterized the gut microbiome, identified microbiota markers, and further constructed a colorectal neoplasms classifier in 99 CRC, 94 AA, and 62 controls, and validated the results in 185 CRC, 140 AA, and 291 controls from 3 independent cohorts. 21 species and 277 gene markers were identified whose abundance was significantly increased or decreased from normal to AA and CRC. The progressive gene markers were distributed in metabolic pathways including amino acid and sulfur metabolism. A diagnosis model consisting of four effect indexes was constructed based on the markers, the sensitivities of the Adenoma Effect Index 1 for AA, Adenoma Effect Index 2 for high-grade dysplasia (HGD) adenoma were 71.3% and 76.5%, the specificities were 90.5% and 90.3%, respectively. CRC Effect Index 1 for all stages of CRC and CRC Effect Index 2 for stage III–IV CRC to predict CRC yielded an area under the curve (AUC) of 0.839 (95% CI 0.804–0.873) and 0.857 (95% CI 0.793–0.921), respectively. Combining with fecal immunochemical test (FIT) significantly improved the sensitivity of CRC Effect Index 1 and CRC Effect Index 2 to 96.7% and 100%. Conclusions This study reports the successful diagnosis model establishment and cross-region validation for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene markers. The results suggested that the novel diagnosis model can significantly improve the diagnostic performance for advanced adenoma.

Abstract Background Emerging evidence suggests that gut microbiota plays a predominant role in Crohn’s disease (CD). However, the microbiome alterations in the early stage of CD patients still remain unclear. The present study aimed to identify dysbacteriosis in patients with early CD and explore specific gut bacteria related to the progression of CD. Methods This study was nested within a longitudinal prospective Chinese CD cohort, and it included 18 early CD patients, 22 advanced CD patients and 30 healthy controls. The microbiota communities were investigated using high-throughput Illumina HiSeq sequencing targeting the V3–V4 region of 16S ribosomal DNA (rDNA) gene. The relationship between the gut microbiota and clinical characteristics of CD was analyzed. Results Differential microbiota compositions were observed in CD samples (including early and advanced CD samples) and healthy controls samples. Notably, Lachnospiracea_incertae_sedis and Parabacteroides were enriched in the early CD patients, Escherichia/Shigella, Enterococcus and Proteus were enriched in the advanced CD patients, and Roseburia, Gemmiger, Coprococcus, Ruminococcus 2, Butyricicoccus, Dorea, Fusicatenibacter, Anaerostipes, Clostridium IV were enriched in the healthy controls [LDA score (log10) > 2]. Furthermore, Kruskal–Wallis Rank sum test results showed that Blautia, Clostridium IV, Coprococcus, Dorea, Fusicatenibacter continued to significantly decrease in early and advanced CD patients, and Escherichia/Shigella and Proteus continued to significantly increase compared with healthy controls (P 2]. Some genera were significantly correlated with various clinical parameters, such as fecal calprotectin, erythrocyte sedimentation rate, C-reactive protein, gland reduce, goblet cells decreased, clinical symptoms (P

The Invar alloy has excellent properties, such as a low coefficient of thermal expansion, but there are few reports about the rapid solidification of this alloy. In this study, Invar alloy solidification at different undercooling (ΔT) was investigated via glass melt-flux techniques. The sample with the highest undercooling of ΔT = 231 K (recalescence height 140 K) was obtained. The thermal history curve, microstructure, hardness, grain number, and sample density of the alloy were analyzed. The results show that with the increase in solidification undercooling, the XRD peak of the sample shifted to the left, indicating that the lattice constant increased and the solid solubility increased. As the solidification of undercooling increases, the microstructure changes from large dendrites to small columnar grains and then to fine equiaxed grains. At the same time, the number of grains also increases with the increase in the undercooling. The hardness of the sample increases with increasing undercooling. If ΔT ≥ 181 K (128 K), the grain number and the hardness do not increase with undercooling.

Both parasitoids and entomopathogenic fungi are becoming increasingly crucial for managing pest populations. Therefore, it is essential to carefully consider the potential impact of entomopathogenic fungi on parasitoids due to their widespread pathogenicity and the possible overlap between these biological control tools during field applications. However, despite their importance, little research has been conducted on the pathogenicity of entomopathogenic fungi on parasitoids. In our study, we aimed to address this knowledge gap by investigating the interaction between the well-known entomopathogenic fungus Beauveria bassiana, and the pupal endoparasitoid Pteromalus puparum. Our results demonstrated that the presence of B. bassiana significantly affected the survival rates of P. puparum under laboratory conditions. The pathogenicity of B. bassiana on P. puparum was dose- and time-dependent, as determined via through surface spraying or oral ingestion. RNA-Seq analysis revealed that the immune system plays a primary and crucial role in defending against B. bassiana. Notably, several upregulated differentially expressed genes (DEGs) involved in the Toll and IMD pathways, which are key components of the insect immune system, and antimicrobial peptides were rapidly induced during both the early and late stages of infection. In contrast, a majority of genes involved in the activation of prophenoloxidase and antioxidant mechanisms were downregulated. Additionally, we identified downregulated DEGs related to cuticle formation, olfactory mechanisms, and detoxification processes. In summary, our study provides valuable insights into the interactions between P. puparum and B. bassiana, shedding light on the changes in gene expression during fungal infection. These findings have significant implications for the development of more effective and sustainable strategies for pest management in agriculture.

In addition to increasing grain yield, improving rice (Oryza sativa L.) quality has received increasing attention recently. The cooking and eating quality (CEQ) is an important indicator of rice quality. Chalkiness and floury endosperm have a significant impact on the CEQ of rice, resulting in noticeable changes. Due to the easily observable phenotype of floury endosperm, cloning single gene mutations that cause floury endosperm and indirectly evaluating changes in CEQs facilitates the exploration of minor genes controlling CEQ. In this study, a stable genetic allele variant of flo4, named flo4-7, was obtained through EMS mutagenesis. The flo4-7 allele variant carries the cyOsPPDKB mutation. flo4-7 showed a significant reduction in compound starch granules and a significant increase in single starch granules in endosperm cells, indicating the involvement of cyOsPPDKB in the synthesis of endosperm starch. Additionally, flo4-7 exhibited a significant decrease in gel consistency (GC) compared to the wild type. Through the analysis of GC data from 166 rice germplasm resources, a C-T variation in the 18th exon of cyOsPPDKB was found to be a crucial site, causing a significant difference in GC between indica and japonica rice. This locus can be used in the future to develop molecular markers for molecular marker-assisted breeding. This study provides a good research foundation for improving the CEQ of rice.

Besides increasing grain yield, improving rice (Oryza sativa L.) quality has been paid more and more attention recently. Cooking and eating quality (CEQ) is an important indicator of rice quality. Since CEQs are quantitative traits and challenging for measurement, efforts have mainly focused on two major genes, Wx and SSIIa. Chalkiness and floury endosperm significantly affect the eating quality of rice, leading to noticeable changes in CEQ. Due to the easily observable phenotype of floury endosperm, cloning single gene mutations that cause floury endosperm and evaluating changes in CEQs indirectly facilitate the exploration of the minor genes controlling CEQ. In this study, eight mutants with different degrees of floury endosperm, generated through ethylmethane sulfonate (EMS) mutagenesis, were analyzed. These mutants exhibited wide variation in starch morphology and CEQs. Particularly, the z2 mutant showed spherical starch granules significantly increased rapid visco analyzer (RVA) indexes and urea swelling, while the z4 mutant displayed extremely sharp starch granules and significantly decreased RVA indexes and urea swelling compared to the wild type. Additionally, these mutants still maintained correlations with certain RVA profiles, suggesting that the genes PUL, which affect these indexes, may not undergo mutation. Cloning these mutated genes in the future, especially in z2 and z4, will enhance the genetic network of rice eating quality and hold significant importance for molecular marker-assisted breeding to improve rice quality.

There are numerous methods used for measuring the coefficient of thermal expansion of alloys and density change at low temperatures, but it is difficult to accurately measure the volume and density of high-temperature melts, particularly during the process of rapid volume change during material phase transformation. This article proposes a method for measuring and analysing the volume and density changes in high-temperature alloy melts using high-speed photography and computer MATLAB program image analysis technology, which includes the ordinary image threshold segmentation method, the elliptical fitting method, and the local dynamic threshold segmentation method. The ordinary image threshold segmentation method is best suited to samples with clear boundaries; the elliptical fitting method is the simplest and can be used to analyse samples with unclear boundaries; and the local dynamic threshold segmentation method is the most accurate and best suited to samples with unclear boundaries. These techniques will aid in understanding the variations in the volume and density of high-temperature melt samples during the phase transition process.

Effective regulation of gene-edited products and resolution of public concerns are the prerequisites for the industrialization of gene-edited crops and their derived foods. CRISPR-associated protein, the core element of the CRISPR system, requires to be regulated. Thus, there is an urgent need to establish qualitative and quantitative detection methods for the Cas gene. In the present study, the primers and probes were designed and screened for Cas12a (Cpf1), which is the most commonly used target site in gene editing; we performed PCR system optimization, determined the optimal primer concentration and annealing temperature, and established qualitative PCR and quantitative PCR (qPCR) assays for detecting Cpf1 in gene editing by specificity and sensitivity tests. In specificity testing, qualitative PCR and qPCR methods could 100% detect samples containing Cpf1 DNA, while the detection rate of other samples without Cpf1 was 0%. In the assay sensitivity test, the limit of detection of qualitative PCR was 0.1% (approximately 44 copies), and the limit of detection of the qPCR method was 14 copies. In the stability test, both the qualitative PCR and qPCR methods were repeated 60 times at their corresponding lowest detection limit concentrations, and the results were positive. Thus, the qualitative and quantitative assays for Cpf1 are specific, sensitive, and stable. The method provides technical support for the effective monitoring of gene-edited products and their derived foods in the future.

Classical eutectic growth models are based on the use of eutectic composition. These models neglect the effect of primary phase formation, and their direct use in the rapid solidification process of off-eutectic (hypoeutectic and hypereutectic) alloys is absent. Combining the effect of the primary phase in the eutectic transformation and an off-eutectic composition, the solidification growth model is derived in the present work. The effect of the model and material parameters on solidification kinetics is discussed in comparison with experimental data. Computational results on the off-eutectic growth model show that the model agrees well with experimental data on the solidification kinetics of Ni–B and Ti–Si alloys.

Insects employ multifaceted strategies to combat invading fungi, with immunity being a promising mechanism. Immune pathways function in signal transduction and amplification, ultimately leading to the activation of antimicrobial peptides (AMPs). Although several studies have shown that immune pathways are responsible for defending against fungi, the roles of parasitoid immune pathways involved in antifungal responses remain unknown. In this study, we evaluated the roles of the Toll and IMD pathways of a pupal parasitoid, Pteromalus puparum (Hymenoptera: Pteromalidae), in fighting against Beauveria bassiana (Hypocreales: Cordycipitaceae). Successful colonization of B. bassiana on P. puparum adults was confirmed by scanning electron microscopy (SEM). AMPs were induced upon B. bassiana infection. The knockdown of key genes, PpTollA and PpIMD, in Toll and IMD signaling pathways, respectively, significantly compromised insect defense against fungal infection. The knockdown of either PpTollA or PpIMD in P. puparum dramatically promoted the proliferation of B. bassiana, resulting in a decreased survival rate and downregulated expression levels of AMPs against B. bassiana compared to controls. These data indicated that PpTollA and PpIMD participate in Toll and IMD-mediated activation of antifungal responses, respectively. In summary, this study has greatly broadened our knowledge of the parasitoid antifungal immunity against fungi.

Characterized by complicated backgrounds, various types, large size variations, and arbitrary orientations, the detection and recognition of arbitrary-oriented objects in remote sensing images are challenging. To address the aforementioned problem, an anchor-free arbitrary-oriented object detector using box boundary-aware vectors is proposed. With the idea of CenterNet to detect objects as points, oriented object detection is achieved by predicting the center, the box boundary-aware vectors, the size, and the type of the bounding box. In the feature extraction stage of the designed architecture, Res2Net, a multiscale convolutional neural network, is used to extract feature maps of different scales and adaptively spatial feature fusion is adopted to improve the detector's adaptability to objects of different sizes. In the detector, a context enhancement module with a multibranch network is designed to enhance the contextual information of the objects and improve the detector's robustness to the complicated backgrounds. Experiments are carried on three challenging benchmarks (i.e., HRSC2016, UCAS-AOD, and DOTA) and our method achieves state-of-the-art performance with 90.30%, 89.70%, and 77.18% mAP, respectively.

This work presents a systematic study of microstructure and mechanical property of TiNi Alloy/Q235 steel explosive-welded interface. The structure evolution as well as the thermodynamic state during the welding process was simulated using Smoothed Particle Hydrodynamic (SPH) numerical method. The interface is featured by regular wave structure with a period of ∼400 μm and an amplitude of ∼120 μm, resulting from the periodic interaction process of jets and colliding plates. Furthermore, it was found that the waves do not form in the initial collision zone, but undergo an evolutionary process of straight-irregular small wave-steady wave transformation. Intermetallic compounds like Fe2Ti and Ni3Ti were found in melting zones, which are the source of the microscopic cracks. Even so, the interface exhibits good bonding strength of 291 MPa that is higher than the Q235 steel of 180 MPa. The nanoindentation results show the hardness values decrease at first and then increase to the initial value with increasing distance from the bonding interface. The melting zone exhibits an ultrahigh hardness of 11.06 GPa, which confirms the formation of brittle intermetallic in the melting zone.

Background: Achieving rapid and complete vascular recanalization in patients with acute large vessel occlusion can significantly improve patients’ prognosis. Objective: We aimed to investigate the potential contribution of the first-pass effect (FPE) to the clinical outcome of patients with acute vertebrobasilar artery occlusion (VBAO). Methods: We retrospectively analyzed the data of patients who underwent endovascular thrombectomy (EVT) caused by VBAO in a multicentered retrospective registry dataset. FPE was defined as successful recanalization [modified thrombolysis in cerebral infarction (mTICI) 2b/3 as modified FPE (mFPE); mTICI 3 as true FPE (tFPE)] after one pass of the device without rescue therapy. The baseline characteristics and procedural and clinical outcomes were analyzed. Multivariate analysis was used to explore the predictors of FPE and the relationship between FPE and 90-day prognosis. Results: A total of 508 patients (age, 63.7 ± 13.1 years, male, 71.6%) were finally included, 29.9% (152/508) of whom achieved mFPE, and 21.1% (107/508) of whom achieved tFPE. FPE was significantly associated with improved clinical outcomes, regardless of mFPE [odds ratio (OR): 0.601, 95% confidence interval (CI): 0.370–0.977, p = 0.040] and tFPE (OR: 0.547, 95% CI: 0.318–0.940, p = 0.029). The use of contact aspiration, favorable collateral status, cardioembolic etiology, and basilar artery occlusion were statistically significant predictors of mFPE and tFPE, whereas hypertension was a negative predictor. Intravenous (IV) recombinant tissue plasminogen activator (rt-PA) prior to EVT was a positive predictor of mFPE but not of tFPE. Conclusion: FPE was associated with significantly favorable outcomes in EVT patients with VBAO. The predictors of FPE include infarct etiology, the site of occlusion, collateral status, EVT strategies, and IV rt-PA bridging strategies. Trial registration number: URL: http://www.chictr.org.cn/ ; Unique identifier: ChiCTR2000033211.

An innovative explosive welding method for the fabrication of multiple plates (EWMP) was proposed to further improve the energy efficiency of explosive welding explosive charges and reduce the impact on the surrounding environment. In this method, six metal plates were placed in parallel and three composite plates were obtained through one explosion in this paper. The microstructure of the joint was analyzed by optical microscopy (OM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron backscattering diffraction (EBSD). Compared to traditional explosive welding (TEW), the EWMP dramatically reduced the noise and vibration and increased the energy efficiency of explosives. The results showed the vibration data of EWMP were reduced by 16.7, 16.4, 2.8, and 1.5%, respectively, and at places of 3, 4, 5, and 6 m away from the explosion center, and explosive consumption of EWMP was reduced by at least half, compared to the traditional method when obtaining the same amount of welded plates. Through numerical simulation, the collision speeds of the composite plate are 610, 516, and 471 m/s, respectively, and the waveform of the composite plate is basically in coincidence with the result of the experiment.

Bacterial lipopolysaccharide (LPS) in the aquatic environment has been reported to cause diseases in red swamp crayfish (Procambarus clarkii). In addition, deoxynivalenol (DON) is one of the primary mycotoxins found in aquaculture. However, the potential synergistic toxic effects of LPS and DON on crayfish are yet to be fully elucidated. In this study, crayfish were exposed to LPS (1 mg kg−1), DON (3 mg kg−1), and their combination (1 mg kg−1 LPS + 3 mg kg−1 DON, L+D) for a duration of six days. Co-exposure to LPS and DON exhibited the lowest survival rate compared to the control or individual treatments with LPS or DON alone. In the initial stage of the experiment, the combined treatment of LPS and DON showed a more pronounced up-regulation of antioxidant and immune-related enzymes in the sera compared to the other treatment groups, with a fold change ranging from 1.3 to 15. In addition, the (L+D) treatment group showed a down-regulation of immune-related genes, as well as Toll pathway-related genes in the hepatopancreas compared to LPS or DON. Moreover, the (L+D) treatment group demonstrated a 100% incidence of histopathological changes in the hepatopancreas, which were significantly more severe compared to the other three groups. In conclusion, our study provides physiological and histopathological evidence that the co-exposure to LPS and DON exerted synergistic toxic effects on crayfish. The observed effects could potentially hinder the development of the crayfish aquaculture industry in China.

Abstract Background and purpose The purpose of our study was to analyse endovascular treatment (EVT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) during the pandemic and post-epidemic periods. Methods Patients with AIS-LVO of the anterior circulation who underwent EVT were enrolled. According to the times of Wuhan closure and reopening, patients were divided into a pre-pandemic group (from November 8, 2019, to January 22, 2020), pandemic group (from January 23, 2020, to April 8, 2020) and post-epidemic group (from April 9, 2020, to June 24, 2020). The primary endpoints were the time delay among symptom onset to arriving hospital door, to groining puncture and to vascular reperfusion. Secondary endpoints were the functional outcomes evaluated by 90-day modified Rankin scale (mRS) score. Results In total, the times from onset to reperfusion (OTR, median 356 min vs. 310 min, p = 0.041) and onset to door (OTD, median 238 min vs. 167 min, p = 0.017) were prolonged in the pandemic group compared to the pre-pandemic group, and the delay continue in the post-epidemic period. In the subgroup analysis, the time from door to imaging (DTI) was significantly prolonged during the pandemic period. Interestingly, the prolonged DTI was corrected in the directly admitted subgroup during post-epidemic period. In addition, the functional outcomes showed no significant differences across the three periods. Conclusions Total time and prehospital time were prolonged during the pandemic and post-epidemic periods. Urgent public education and improved in-hospital screening processes are necessary to decrease time delays.

Polyethylene glycol (PEG) has previously been reported to improve outcomes of peripheral nerve microsuturing. However, recent studies have challenged this finding. Given its clinical importance, we investigated the potential of PEG as a facilitator of peripheral nerve restoration. The sciatic nerve of 144 rats was transected and submitted either to simple suturing (Group A), PEG-enhanced suturing (Group B), and insertion in an arterial sleeve conduit without PEG (Group C), or with PEG (Group D) in equal numbers. Behavioral recovery was assessed with the sciatic function index (SFI). Nerve impulse conduction was assessed with compound muscle action potentials (CMAPs). Histology comprised standard hematoxylin/eosin staining, electron microscopy and glial cell line-derived neurotrophic factor (GDNF) immunohistochemistry. Expression of GDNF was also assessed with western blotting. Results were evaluated at weeks 1, 4, and 8. PEG treatment significantly improved behavioral recovery and morphology of nerve restoration, particularly in the sleeve conduit group, relative to that of controls. In conclusion, PEG may improve outcomes of peripheral nerve reconstruction.

Digital green innovation (DGI) is the core factor that affects the digitalization and decarbonization strategy of agricultural high-end equipment manufacturing (AHEM) system. Although AHEM enterprises actively cooperate with academic research institutes to develop agricultural high-end equipment, there are many obstacles in the process of DGI. Moreover, the integration of digital technology and green innovation from the perspective of partner matching for the AHEM system has not been fully introduced in current literature. Hence, this study aimed to (i) establish a suitable framework system for the AHEM system in general, (ii) quantify the selection of DGI by academic research institutions based on niche theory, and (iii) propose an extended niche field model combined with fuzzy VIKOR model. First, a theoretical framework consisting of three core elements of technology superposition, mutual benefit, and mutual trust, and technological complementarity was constructed based on niche intensity and niche overlap degree. DGI ability superposition of technology, mutual trust, and technical complementarity are beneficial for transferring DGI knowledge from academic research institutes to the AHEM industry. Second, triangle fuzzy number and prospect theory combined with the VIKOR method were introduced into the field theory to construct the complementary field model of DGI resources. The niche field model has been successfully applied to practical cases to illustrate how the model can be implemented to solve the problem of DGI partner selection. Third, the results of a case study show that the criteria framework and the niche field model can be applied to real-world partner selection for AHEM enterprises. This study not only puts forward the standard framework of niche fitness evaluation based on niche theory but also establishes the niche domain model of innovation partner selection management based on niche theory. The standard framework and novel niche field model can help enterprises to carry out digital green innovation in the development of high-end agricultural equipment. The study has the following theoretical and practical implications: (i) constructing a criteria framework based on niche theory; (ii) developing a novel niche field model for DGI partner selection of AHEM enterprises; and (iii) assisting AHEM enterprises to perform DGI practice.

The microstructural characteristics of the explosive welded niobium-steel interface were systematically investigated by various characterizations and a two-step numerical simulation. A coupled Lagrange-Eulerian simulation was firstly developed to compute the impact velocity, this model allows to establish an accurate impact condition. Microstructure observations show that the niobium-steel interface is featured by a wave structure with two vortices located at the wave front and back, and micro defects like voids and cracks were detected inside the vortex. Grains of the niobium and steel matrix near the interface were characterized by elongated and fine equiaxed structures, respectively, while that in vortex area was fine columnar grains. Then, the interfacial thermokinetics was investigated by a smoothed particles hydrodynamics simulation to reveal the formation of the observed defects and diverse grains. The ultimate strength of the composite exceeds 350 MPa with disparate heat-treated temperatures obtained by the tensile tests. Meanwhile, tensile-shear test shows a robust bonding strength of 220 MPa. The strong mechanical properties of the composite guarantee a great prospect of its application in the nuclear industry.

IntroductionAntidepressants are the front-line treatments for major depressive disorder (MDD), but remain unsatisfactory in outcome. An increasing number of patients are interested in acupuncture and moxibustion treatment as complementary therapies. This study aims to evaluate the efficacy and safety of integrative acupuncture and moxibustion (iAM) treatment in patients with MDD.Methods and AnalysisThis multicenter, single-blind, 2 × 2 factorial randomized trial will enroll 592 patients with MDD of moderate severity from nine hospitals. All patients will be randomized, in a ratio of 2:2:2:1, through a computerized central randomization system, into four groups (the combined, iAM-only, sertraline-only, and placebo groups). Participants will undergo a 12-week intervention with either 50 mg of sertraline or a placebo once a day and active/sham iAM treatment three times per week. The primary outcome is depression severity, assessed using the Hamilton Depression Scale-17. The secondary outcomes include self-rated depression severity, anxiety, and sleep quality. The primary and secondary outcomes will be measured at weeks 0, 4, 8, 12, and the 8th week posttreatment. Safety will be evaluated through liver and kidney function tests conducted before and after treatment and through monitoring of daily adverse events. An intent-to-treat principle will be followed for the outcome analyses.ConclusionThis trial will provide sufficient evidence to ascertain whether iAM is effective and safe for treating MDD and provides a suitable combination strategy for treating MDD.Clinical Trial Registration[www.chictr.org.cn], identifier [ChiCTR2100042841].

CRISPR/Cas12a technology is used for nucleic acid detection due to its specific recognition function and non-specific single-stranded DNA cleavage activity. Here, we developed a fluorescence visualisation detection method based on PCR and CRISPR/Cas12a approaches. The method was used to detect the nopaline synthase terminator (T-nos) of genetically modified (GM) crops, circumventing the need for expensive instruments and technicians. For enhanced sensitivity and stability of PCR-CRISPR/Cas12a detection, we separately optimised the reaction systems for PCR amplification and CRISPR/Cas12a detection. Eleven samples of soybean samples were assessed to determine the applicability of the PCR-CRISPR/Cas12a method. The method could specifically detect target gene levels as low as 60 copies in the reaction within 50 min. In addition, accurate detection of all 11 samples confirmed the applicability. The method is not limited by large-scale instruments, making it suitable for mass detection of transgenic components in plants in the field. In conclusion, we developed a new, accurate, rapid, and cost-effective method for GM detection.

In this study, a uniform anomalous eutectic is formed in a slow cooling process of undercooled hypoeutectic Ni-B alloy. The longer the cooling time, the higher the hardness of the Ni3B phase. This is a result of higher concentration of boron being arrested by the Ni3B phase.

Background and PurposeSuccessful recanalization after the first pass of the device in endovascular thrombectomy (EVT) can significantly improve patients' prognosis. We aimed to investigate the possible factors that influence achieving the first-pass effect (FPE).MethodsWe retrospectively analyzed the patients who underwent EVT caused by anterior circulation large vessel occlusion stroke (ALVOS) in our center. The FPE was defined as a successful recanalization [modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 defined as modified FPE (mFPE); mTICI 3 as true FPE (tFPE)] after one pass of the device without rescue therapy. Univariate and multivariate regression analyses were used to explore the predictors of FPE and the relationship between FPE and prognosis.ResultsThere were 278 patients (age, 69.3 ± 10.9 years, male, 51.1%) included, 30.2% of them achieved mFPE, while 21.2% achieved tFPE. We found the higher clot burden score (CBS), the truncal-type occlusion, and the favorable anatomy of both extracranial and intracranial segments of the internal carotid artery (ICA) were associated with achieving mFPE. The higher CBS and truncal-type occlusion were statistically significant predictors of tFPE. Moreover, FPE was significantly associated with improved clinical outcomes, regardless of mFPE and tFPE.ConclusionsThe CBS, tortuosity of ICA, and angiographic occlusion type were independent predictors of achieving FPE. The rate of improved clinical and safety outcomes was higher in patients with FPE, which has important clinical significance.

Abstract Background Determining the risk factors for brachial-ankle pulse wave velocity (baPWV) may help to identify people susceptible to diabetic atherosclerosis and could prevent diabetic macrovascular complications in the early stages. We aim to comprehensively investigate risk factors contributing to arterial stiffness in patients with and without diabetes. Methods BaPWV was measured in 5651 individuals who attended health check-ups at baseline and follow-up. Lasso regression was used to screen for risk factors. Mixed models and multiple linear regressions were subsequently established to evaluate the effect size of the potential risk factors on baPWV and PWV change rates. All analyses were stratified by diabetes. Mediation analysis was also conducted to demonstrate the mechanisms of arterial stiffness in patients with diabetes. Results In lasso regression, postprandial 2-h glucose (P2hG), systolic blood pressure (SBP) and age were associated with baPWV regardless of diabetes. Platelet counts (PLT), mean corpuscular volume (MCV) and coronary heart disease (CHD) were associated with baPWV in patients with diabetes. In the mixed models, PLT were positively associated with baPWV in patients with diabetes (β platelet, perSD = 25.80; 18.26–33.33). Elevated PLTs could also significantly increase the PWV change rate in patients with diabetes (β platelet, perSD = 54.05; 10.00–107.10). In mediation analysis, diabetes had a significant average direct effect on baPWV. The average causal mediation effect (ACME) of PLTs was 1.76, with a range of 0.17 to 3.70. Conclusions Elevated PLT counts can increase baPWV in diabetes and are a potential mediator between diabetes and atherosclerosis.

In order to obtain high-quality CuCrZr/316L clad plates prepared by explosive welding (EW), theoretical analysis and numerical simulation were introduced to optimize welding parameters. The bonding properties of the achieved joints were systematically studied through multiscale interface analyses, mechanical performance tests, and evaluation of sealing properties. It was concluded that the theoretical analysis in collaboration with numerical calculations is an effective way to design parameters, because its predicted result was in good agreement with the ultrasonic test (UT) one. In both microstructure observations and mechanical tests, an excellent bonding quality of the CuCrZr/316L bimetallic plate was confirmed, where a uniform wavy morphology without defects such as voids and cracks was found at the bonding interface. The bonding strength was higher than the CuCrZr alloy. Moreover, a self-designed hydraulically pressed mold method was developed to manufacture a U-shaped CuCrZr/316L component, and the resulting sample matches well with the designed dimensions. Finally, the helium-leak test results demonstrate that the sealing property of the CuCrZr/316L bimetallic plate meets the practical requirements, indicating that the welded specimens were sound.

As one of the regions with intensive agriculture and rapid economic development in China, North China also has a high nitrogen (N) deposition. This study characterized the spatial pattern of N deposition in North China, combining the tropospheric columns from satellite measurements and the simulated profiles from an atmospheric chemistry transport model. The total N deposition fluxes ranged from 16.3 to 106.5 kg N ha−1 yr−1, with an average of 54.5 ± 17.2 kg N ha−1 yr−1. The high values were concentrated in urban and farmland areas, while low values were found in forests and grasslands with less human activities. Of the total N deposition, 36% was deposited via precipitation, 12% was deposited through dry particulate deposition, and the remaining 52% was comprised of dry gaseous deposition. For the seasonal variation of dry deposition, gaseous HNO3 and particulate NO3− were higher in winter and autumn, but lower in spring and summer. In contrast, gaseous NH3 and particulate NH4+ were higher in spring and summer, but lower in winter and autumn. This is possibly caused by the seasonal differences in emission intensity between NOx and NH3 emission sources. The gaseous NO2 deposition did not show strong seasonal variation. The wet deposition was mainly affected by precipitation, with high values in summer and low values in winter. This research provides an objective spatial perspective and insight into the total N deposition in North China.

BackgroundThe neddylation pathway is aberrantly overactivated in multiple human cancers and has been indicated as an effective target for anticancer therapy in clinical trials. We aimed to study whether the neddylation pathway is upregulated in pancreatic cancer and whether pevonedistat, a first-in-class anticancer agent specifically targeting this pathway, will suppress cancer tumorigenesis and progression.MethodsWe evaluated the expression pattern of neddylation pathway components in 179 pancreatic adenocarcinoma (PAAD) compared with 171 normal tissues from The Cancer Genome Atlas (TCGA) dataset and further assessed PAAD patient prognosis with high neddylation pathway expression via Gene Expression Profiling Interactive Analysis (GEPIA). We then analyzed malignant cancer phenotypes both in vitro and in vivo, as well as intrinsic molecular mechanisms upon pevonedistat treatment.ResultsWe found that the neddylation pathway was hyperactivated in pancreatic cancer. Patients with high neddylation pathway expression exhibited worse prognoses. Pevonedistat significantly inhibited the cancer cell cycle, cell growth, and proliferation; increased cell apoptosis; and decreased cancer cell xenografts in a mouse model. Mechanistically, pevonedistat treatment and the siRNA knockdown neddylation pathway were able to remarkably induce the accumulation of Wee1, p27, and p21. Further mechanistic studies revealed that pevonedistat mainly impaired the ubiquitination level and delayed the protein degradation of Wee1, p27, and p21.ConclusionsOur results showed that pevonedistat targeted the overexpression of the neddylation pathway in pancreatic cancer to induce cell growth suppression by inducing the accumulation of the cell cycle regulators Wee1, p27, and p21, which provides sound evidence for the clinical trial of pevonedistat for pancreatic cancer therapy.

Mesenchymal stem cells (MSCs) have been documented to be effective for the therapy of inflammation-related diseases but raised concerns on possible tumorigenic effects. Since most of the tumors are induced or promoted by chronic inflammation, one could expect that MSCs might be beneficial for the cancer therapy because of their potent roles on inhibiting inflammation. This study is aimed at performing a safety evaluation and evaluating the role of human umbilical cord mesenchymal stem cells (HUC-MSCs) on tumorigenesis. We found that HUC-MSCs cultured within 20 generations had no significant changes in proliferation, cell cycle, cellular senescence, apoptosis, and expression of mesenchymal stem cell markers. HUC-MSCs were unable to form any tumor in immunodeficiency or normal mice with or without inflammatory stimulation. Intriguingly, we observed that HUC-MSCs inhibited tumorigenesis in B16-derived or AOM/DSS-induced colon cancer models. We reasoned that the effect of HUC-MSCs on tumorigenesis might be through regulating the inflammatory response. Indeed, HUC-MSCs dramatically ameliorated the disease symptoms and pathological changes of DSS-induced colitis mice. We deciphered the mechanism that HUC-MSCs inhibited tumorigenesis through reducing the proportion of macrophages, which were decreased in the mice suffered from AOM/DSS-induced colon cancer. Correspondingly, the expression levels of TNF-α and IL-6, which were secreted by macrophages, were significantly decreased in the plasma of colon cancer and colitis mice after injection of HUC-MSCs. This study revealed the role of inhibiting macrophages and shed light on the therapeutic application of HUC-MSCs in inflammation-induced tumorigenesis.

Given the possibility that food contaminated with SARS-CoV-2 might become an infection source, there is an urgent need for us to develop a rapid and accurate nucleic acid detection method for SARS-CoV-2 in food to ensure food safety. Here, we propose a sensitive, specific, and reliable molecular detection method for SARS-CoV-2. It has a mechanism to control amplicon contamination. Swabs from spiked frozen shrimps were used as detection samples, which were processed by heating at 95 °C for 30 s. These preprocessed samples served as the templates for subsequent amplification. A colorimetric LAMP reaction was carried out to amplify both the SARS-CoV-2 target and the MS2 phage simultaneously in one tube. MS2 phage was detected by colorimetric LAMP as the internal control, while SARS-CoV-2 was detected with a CRISPR/Cas12a system. The fluorescence results could be visually detected with an ultraviolet lamp. Meanwhile, uracil was incorporated during the LAMP reaction to provide an amplicon contamination proof mechanism. This test could detect as low as 20 copies of SARS-CoV-2 in one reaction. Additionally, the detection could be finished in 45 min. The test only needs a heating block and an ultraviolet lamp, which shows the potential for field detection.