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Newcastle disease virus (NDV) is a highly pathogenic avian infectious disease agent and also a promising oncolytic virus with broad application prospects. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery has been increasingly recognized for its crucial role in the life cycles of enveloped viruses, influencing processes such as viral entry, replication, and budding. In this study, we employed an RNA interference screening approach to identify key ESCRT components that regulate NDV replication in tumor cells. qPCR, immunofluorescence, and Western blot assays demonstrated that knockdown of HRS, CHMP4A, CHMP4B, and CHMP4C significantly impaired NDV replication in HeLa cells, with HRS exhibiting the most pronounced inhibitory effect. Additionally, HRS knockout significantly inhibited viral budding and suppressed NDV-induced cell death in HeLa cells. Notably, NDV infection was shown to significantly upregulate HRS gene and protein expression in a time-dependent manner. In conclusion, this study systematically identifies critical ESCRT components involved in NDV replication within tumor cells, with a particular focus on the role of HRS in promoting NDV’s replication by promoting viral budding, offering new insights for the development of NDV-based oncolytic therapies.

With the widespread adoption of next-generation sequencing technologies, the speed and convenience of genome sequencing have significantly improved, and many biological genomes have been sequenced. However, during the assembly of small genomes, we still face a series of challenges, including repetitive fragments, inverted repeats, low sequencing coverage, and the limitations of sequencing technologies. These challenges lead to unknown gaps in small genomes, hindering complete genome assembly. Although there are many existing assembly software options, they do not fully utilize the potential of artificial intelligence technologies, resulting in limited improvement in gap filling. Here, we propose a novel method, DLGapCloser, based on deep learning, aimed at assisting traditional tools in further filling gaps in small genomes. Firstly, we created four datasets based on the original genomes of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Neurospora crassa, and Micromonas pusilla. To further extract effective information from the gene sequences, we also added homologous genomes to enrich the datasets. Secondly, we proposed the DGCNet model, which effectively extracts features and learns context from sequences flanking gaps. Addressing issues with early pruning and high memory usage in the Beam Search algorithm, we developed a new prediction algorithm, Wave-Beam Search. This algorithm alternates between expansion and contraction phases, enhancing efficiency and accuracy. Experimental results showed that the Wave-Beam Search algorithm improved the gap-filling performance of assembly tools by 7.35%, 28.57%, 42.85%, and 8.33% on the original results. Finally, we established new gap-filling standards and created and implemented a novel evaluation method. Validation on the genomes of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Neurospora crassa, and Micromonas pusilla showed that DLGapCloser increased the number of filled gaps by 8.05%, 15.3%, 1.4%, and 7% compared to traditional assembly tools.

The unique structure of G4.0 PAMAM dendrimers allows a drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin hydrochloride (DOX) were optimized. The physicochemical properties of the system were monitored using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. The Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier’s surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the Isothermal calorimetry (ITC) isotherm. Fluorescence spectra and release curves identified the reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of the G4.0-DOX complex was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is essential from a therapeutic point of view.

π–π stacking are omnipresent interactions, crucial in many areas of chemistry, and often studied using quantum chemical methods. Here, we report a simple and computationally efficient method of estimating the binding energies of stacked polycyclic aromatic hydrocarbons based on steered molecular dynamics. This method leverages the force field parameters for accurate calculation. The presented results show good agreement with those obtained through DFT at the ωB97X-D3/cc-pVQZ level of theory. It is demonstrated that this force field-driven SMD method can be applied to other aromatic molecules, allowing insight into the complexity of the stacking interactions and, more importantly, reporting π–π stacking energy values with reasonable precision.

This study investigated the effects of rumen bypass dandelion extract on the lactation performance, immune index, and mammary oxidative stress of lactating dairy cows fed a high-concentrate diet. This study used a complete randomized block design, and initial milk production, somatic cell counts, and parities were set as block factors. Sixty Holstein cows with similar health conditions and lactating periods (70 ± 15 d) were divided into three groups with 20 replicates per group. The treatments included the LCD group (low-concentrate diet, concentrate–forage = 4:6), HCD group (high-concentrate group, concentrate–forage = 6:4), and DAE group (dandelion aqueous extract group, HCD group with 0.5% DAE). The experimental period was 35 d, and cows were fed three times in the morning, afternoon, and night with free access to water. The results showed the following: (1) Milk production in the HCD and DAE groups was significantly higher (p < 0.05) than that in the LCD group from WK4, and the milk quality differed during the experimental period. (2) The HCD group’s pH values significantly differed (p < 0.01) from those of the LCD and DAE groups. (3) In WK2 and WK4 of the experimental period, the somatic cell counts of dairy cows in the HCD group were significantly higher (p < 0.05) than those in the DAE group. (4) The serum concentrations of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and protein carbonyl (PC) in the HCD group were significantly higher (p < 0.05) than those in the LCD group. The activity of catalase (CAT) in the LCD and DAE groups was stronger (p < 0.01) than that in the HCD group. (5) The correlation analysis revealed significantly positive correlations between the plasma LPS concentration and serum concentrations of 8-OHdG (p < 0.01), PC (p < 0.01), and malondialdehyde (MDA, p < 0.05) and significantly negative correlations (p < 0.01) between the plasma LPS concentration and activities of CAT and superoxide dismutase. (6) Compared with that in the HCD and DAE groups, the mRNA expression of α, β, and κ casein and acetyl CoA carboxylase in bovine mammary epithelial cells was significantly higher (p < 0.05) in the LCD group, and the mRNA expression of fatty acid synthetase and stearoyl CoA desaturase in the LCD group was significantly higher (p < 0.01) than that in the HCD group. (7) Compared with that in the LCD and HCD groups, the mRNA expression of Nrf2 was significantly higher (p < 0.01) in the DAE group, and the mRNA expression of cystine/glutamate transporter and NAD (P) H quinone oxidoreductase 1 in the DAE group was significantly higher (p < 0.05) than that in the HCD group. Overall, feeding a high-concentrate diet could increase the milk yield of dairy cows, but the milk quality, rumen homeostasis, and antioxidative capability were adversely affected. The supplementation of DAE in a high-concentrate diet enhanced antioxidative capability by activating the Nrf2 regulatory factor and improved rumen homeostasis and production performance.

As one of the largest and most diverse classes of specialized metabolites in plants, terpenoids (oprenoid compounds, a type of bio-based material) are widely used in the fields of medicine and light chemical products. They are the most important secondary metabolites in coniferous species and play an important role in the defense system of conifers. Terpene synthesis can be promoted by regulating the expressions of terpene synthase genes, and the terpene biosynthesis pathway has basically been clarified in Pinus massoniana, in which there are multiple rate-limiting enzymes and the rate-limiting steps are difficult to determine, so the terpene synthase gene regulation mechanism has become a hot spot in research. Herein, we amplified a PmDXR gene (GenBank accession no. MK969119.1) of the MEP pathway (methyl-erythritol 4-phosphate) from Pinus massoniana. The DXR enzyme activity and chlorophyll a, chlorophyll b and carotenoid contents of overexpressed Arabidopsis showed positive regulation. The PmDXR gene promoter was a tissue-specific promoter and can respond to ABA, MeJA and GA stresses to drive the expression of the GUS reporter gene in N. benthamiana. The DXR enzyme was identified as a key rate-limiting enzyme in the MEP pathway and an effective target for terpene synthesis regulation in coniferous species, which can further lay the theoretical foundation for the molecularly assisted selection of high-yielding lipid germplasm of P. massoniana, as well as provide help in the pathogenesis of pine wood nematode disease.

Insects heavily rely on the olfactory system for food, mating, and predator evasion. However, the caste-related olfactory differences in Apis cerana, a eusocial insect, remain unclear. To explore the peripheral and primary center of the olfactory system link to the caste dimorphism in A. cerana, transcriptome and immunohistochemistry studies on the odorant receptors (ORs) and architecture of antennal lobes (ALs) were performed on different castes. Through transcriptomesis, we found more olfactory receptor genes in queens and workers than in drones, which were further validated by RT-qPCR, indicating caste dimorphism. Meanwhile, ALs structure, including volume, surface area, and the number of glomeruli, demonstrated a close association with caste dimorphism. Particularly, drones had more macroglomeruli possibly for pheromone recognition. Interestingly, we found that the number of ORs and glomeruli ratio was nearly 1:1. Also, the ORs expression distribution pattern was very similar to the distribution of glomeruli volume. Our results suggest the existence of concurrent plasticity in both the peripheral olfactory system and ALs among different castes of A. cerana, highlighting the role of the olfactory system in labor division in insects.

Flavonoids are ubiquitous polyphenolic compounds that play a vital role in plants’ defense response and medicinal efficacy. UV-B radiation is a vital environmental regulator governing flavonoid biosynthesis in plants. Many plants rapidly biosynthesize flavonoids as a response to UV-B stress conditions. Here, we investigated the effects of flavonoid biosynthesis via UV-B irradiation in Euphorbia lathyris. We found that exposure of the E. lathyris callus to UV-B radiation sharply increased the level of one O-methyltransferase (ElOMT1) transcript and led to the biosynthesis of several methylated flavonoids. The methyltransferase ElOMT1 was expressed heterologously in E. coli, and we tested the catalytic activity of recombinant ElOMT1 with possible substrates, including caffeic acid, baicalin, and luteolin, in vitro. ElOMT1 could efficiently methylate when the hydroxyl groups were contained in the core nucleus of the flavonoid. This molecular characterization identifies a methyltransferase responsible for the chemical modification of the core flavonoid structure through methylation and helps reveal the mechanism of methylated flavonoid biosynthesis in Euphorbiaceae. This study identifies the O-methyltransferase that responds to UV-B irradiation and helps shed light on the mechanism of flavonoid biosynthesis in Euphorbia lathyris.

Due to the specificity of their structure, protein systems are adapted to carry various ligands. The structure of many proteins potentially allows for two types of immobilization of a therapeutic agent, either on the outer surface of the protein or within the protein structure. The existence of two active sites in BSA’s structure, the so-called Sudlow I and II, was confirmed. The conducted research involved determining the effectiveness of BSA as a potential carrier of 5-fluorouracil (5FU). 5-fluorouracil is a broad-spectrum anticancer drug targeting solid tumors. The research was carried out to estimate the physicochemical properties of the system using complementary measurement techniques. The optimization of the complex formation conditions made it possible to obtain significant correlations between the form of the drug and the effective localization of the active substance in the structure of the protein molecule. The presence of two amino groups in the 5FU structure contributes to the deprotonation of the molecule at high pH values (pH > 8) and the transition to the anionic form (AN1 and AN3). To investigate the binding affinity of the tautomeric form with BSA, UV-vis absorption, fluorescence quenching, zeta potential, QCM-D, and CD spectroscopic studies were performed. The experimental research was supported by molecular dynamics (MD) simulations and molecular docking. The simulations confirm the potential location of 5FU tautomers inside the BSA structure and on its surface.

Autophagy plays a critical role in nutrient recycling/re-utilizing under nutrient deprivation conditions. However, the role of autophagy in soybeans has not been intensively investigated. In this study, the Autophay-related gene 7 (ATG7) gene in soybeans (referred to as GmATG7) was silenced using a virus-induced gene silencing approach mediated by Bean pod mottle virus (BPMV). Our results showed that ATG8 proteins were highly accumulated in the dark-treated leaves of the GmATG7-silenced plants relative to the vector control leaves (BPMV-0), which is indicative of an impaired autophagy pathway. Consistent with the impaired autophagy, the dark-treated GmATG7-silenced leaves displayed an accelerated senescence phenotype, which was not seen on the dark-treated BPMV-0 leaves. In addition, the accumulation levels of both H2O2 and salicylic acid (SA) were significantly induced in the GmATG7-silenced plants compared with the BPMV-0 plants, indicating an activated immunity. Consistently, the GmATG7-silenced plants were more resistant against both Pseudomonas syringae pv. glycinea (Psg) and Soybean mosaic virus (SMV) compared with the BPMV-0 plants. However, the activated immunity in the GmATG7-silenced plant was not dependent upon the activation of MPK3/MPK6. Collectively, our results demonstrated that the function of GmATG7 is indispensable for autophagy in soybeans, and the activated immunity in the GmATG7-silenced plant is a result of impaired autophagy.

Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) stands as one of the pivotal afforestation tree species and timber resources in southern China. Nevertheless, the occurrence of seed abortion and a notably high proportion of astringent seeds significantly curtail the yield and quality of elite seeds, resulting in substantial economic losses. The development of astringent seeds is accompanied by significant physiological and biochemical alterations. Here, the first combined lipidomic and metabolomic analysis was performed to gain a comprehensive understanding of astringent seed traits. A total of 744 metabolites and 616 lipids were detected, of which 489 differential metabolites and 101 differential lipids were identified. In astringent seeds, most flavonoids and tannins, as well as proline and γ-aminobutyric acid, were more accumulated, along with a notable decrease in lipid unsaturation, indicating oxidative stress in the cells of astringent seeds. Conversely, numerous elemental metabolites were less accumulated, including amino acids and their derivatives, saccharides and alcohols, organic acids and nucleotides and their derivatives. Meanwhile, most lipid subclasses, mainly associated with energy storage (triglyceride and diglyceride) and cell membrane composition (phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine), also exhibited significant reductions. These results reflected a disruption in the cellular system or the occurrence of cell death, causing a reduction in viable cells within astringent seeds. Furthermore, only one lipid subclass, sphingosine phosphate (SoP), was more accumulated in astringent seeds. Additionally, lower accumulation of indole-3-acetic acid and more accumulation of salicylic acid (SA) were also identified in astringent seeds. Both SA and SoP were closely associated with the promotion of programmed cell death in astringent seeds. Collectively, our study revealed significant abnormal changes in phytohormones, lipids and various metabolites in astringent seeds, allowing us to propose a model for the development of astringent seeds in Chinese fir based on existing research and our findings. This work enriches our comprehension of astringent seeds and presents valuable bioindicators for the identification of astringent seeds.

The protein phosphatase 2C (PP2C), a key regulator of the ABA signaling pathway, plays important roles in plant growth and development, hormone signaling, and abiotic stress response. Although the PP2C gene family has been identified in many species, systematic analysis was still relatively lacking in ramie (Boehmeria nivea L.). In the present study, we identified 63 BnPP2C genes from the ramie genome, using bioinformatics analysis, and classified them into 12 subfamilies, and this classification was consistently supported by their gene structures and conserved motifs. In addition, we observed that the functional differentiation of the BnPP2C family of genes was restricted and that fragment replication played a major role in the amplification of the BnPP2C gene family. The promoter cis-regulatory elements of BnPP2C genes were mainly involved in light response regulation, phytohormone synthesis, transport and signaling, environmental stress response and plant growth and development regulation. We identified BnPP2C genes with tissue specificity, using ramie transcriptome data from different tissues, in rhizome leaves and bast fibers. The qRT-PCR results showed that the BnPP2C1, BnPP2C26 and BnPP2C27 genes had a strong response to drought, high salt and ABA, and there were a large number of stress-responsive elements in the promoter region of BnPP2C1 and BnPP2C26. The results suggested that BnPP2C1 and BnPP2C26 could be used as the candidate genes for drought and salt tolerance in ramie. These results provide a reference for further studies on the function of the PP2C gene and advance the development of the mechanism of ramie stress response, with a view to providing candidate genes for the molecular breeding of ramie for drought and salt tolerance.

Small molecule kinase inhibitors (SMKIs) are of heightened interest in the field of drug research and development. There are 79 (as of July 2023) small molecule kinase inhibitors that have been approved by the FDA and hundreds of kinase inhibitor candidates in clinical trials that have shed light on the treatment of some major diseases. As an important strategy in drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods such as docking, molecular dynamic, quantum mechanics/molecular mechanics, pharmacophore, virtual screening, and quantitative structure–activity relationship have been applied to the design and optimization of small molecule kinase inhibitors. In this review, we provide an overview of recent advances in CADD and SMKIs and the application of CADD in the discovery of SMKIs.

The growing occurrence of detrimental algal blooms resulting from industrial and agricultural activities emphasizes the urgency of implementing efficient removal strategies. In this study, we have successfully synthesized stable and biocompatible carbon dots (R-CDs) capable of generating reactive oxygen species (ROS) upon exposure to natural light irradiation. Phaeocystis globosa Scherffel (PGS) was selected as a representative model for conducting anti-algal experiments. Remarkably, in the presence of R-CDs, the complete eradication of harmful algae within a simulated light exposure period of 27 h was achieved. Furthermore, fluorescence lifetime imaging microscopy (FLIM) was first employed to study the physiological processes involved in the oxidative stress induced by PGS when subjected to ROS attack. The findings of this study demonstrate the potential of R-CDs as a highly promising anti-algal agent. This elucidation of the mechanism contributes to a comprehensive understanding of the efficacy and effectiveness of such agents in combating algal growth, further inspiring the development of other anti-algal agents.

Sedoheptulose-1,7-bisphosphatase (SBPase, EC 3.1.3.37) is a key enzyme in the plant Calvin cycle and one of the main rate-limiting enzymes in the plant photosynthesis pathway. Many studies have demonstrated that the SBPase gene plays an important role in plant photosynthetic efficiency, yield, and stress responses; however, few studies have been conducted on the function and expression of the GhSBPase gene in upland cotton. In this study, our results showed that the coding sequence (CDS) of GhSBPase gene was 1182 bp, encoding a protein with 393 amino acids. The GhSBPase protein had adenosine monophosphate (AMP) binding site and a FIG (FBPase/IMPase/glpX) domain, and had six Cys residues and a CGGT(A/Q)C motif that were involved in redox regulation in plants. Evolutionarily, the GhSBPase protein clustered into the dicotyledon subgroup and was most closely related to the tomato SlSBPase protein. Western-blot analysis further indicated that the GhSBPase gene was indeed the gene encoding the SBPase protein in upland cotton. The GhSBPase protein was localized in chloroplast, which was consistent with its function as a key enzyme in photosynthesis. The GhSBPase gene was specifically highly expressed in leaves, and its expression level was significantly lower in a yellow-green leaf mutant than in the wild type. Moreover, the GhSBPase expression was in response to drought, salt, high- and low-temperature stress, and exhibits different expression patterns. The GhSBPase promoter had the cis-acting elements in response to abiotic stress, phytohormone, and light. In addition, the GhSBPase expression was positively correlated with the chlorophyll fluorescence parameters, suggesting that changes in the expression of the GhSBPase had potential applicability in breeding for enhanced cotton photosynthetic efficiency. These results will help to understand the function of the GhSBPase gene in photosynthesis and the adaptability of plants to external stress and provide important gene information for the high-yield breeding of crops in the future.

Pulmonary arterial hypertension (PAH) is a group of severe, progressive, and debilitating diseases with limited therapeutic options. This study aimed to explore novel therapeutic targets in PAH through bioinformatics and experiments. Weighted gene co-expression network analysis (WGCNA) was applied to detect gene modules related to PAH, based on the GSE15197, GSE113439, and GSE117261. GSE53408 was applied as validation set. Subsequently, the validated most differentially regulated hub gene was selected for further ex vivo and in vitro assays. PARM1, TSHZ2, and CCDC80 were analyzed as potential intervention targets for PAH. Consistently with the bioinformatic results, our ex vivo and in vitro data indicated that PARM1 expression increased significantly in the lung tissue and/or pulmonary artery of the MCT-induced PAH rats and hypoxia-induced PAH mice in comparison with the respective controls. Besides, a similar expression pattern of PARM1 was found in the hypoxia- and PDGF--treated isolated rat primary pulmonary arterial smooth muscle cells (PASMCs). In addition, hypoxia/PDGF--induced PARM1 protein expression could promote the elevation of phosphorylation of AKT, phosphorylation of FOXO3A and PCNA, and finally the proliferation of PASMCs in vitro, whereas PARM1 siRNA treatment inhibited it. Mechanistically, PARM1 promoted PAH via AKT/FOXO3A/PCNA signaling pathway-induced PASMC proliferation.

The progress of space science and technology has ushered in a new era for humanity’s exploration of outer space. Recent studies have indicated that the aerospace special environment including microgravity and space radiation poses a significant risk to the health of astronauts, which involves multiple pathophysiological effects on the human body as well on tissues and organs. It has been an important research topic to study the molecular mechanism of body damage and further explore countermeasures against the physiological and pathological changes caused by the space environment. In this study, we used the rat model to study the biological effects of the tissue damage and related molecular pathway under either simulated microgravity or heavy ion radiation or combined stimulation. Our study disclosed that ureaplasma-sensitive amino oxidase (SSAO) upregulation is closely related to the systematic inflammatory response (IL-6, TNF-α) in rats under a simulated aerospace environment. In particular, the space environment leads to significant changes in the level of inflammatory genes in heart tissues, thus altering the expression and activity of SSAO and causing inflammatory responses. The detailed molecular mechanisms have been further validated in the genetic engineering cell line model. Overall, this work clearly shows the biological implication of SSAO upregulation in microgravity and radiation-mediated inflammatory response, providing a scientific basis or potential target for further in-depth investigation of the pathological damage and protection strategy under a space environment.

ATP-binding cassette transporter G (ABCG) has been shown to be engaged in export of broad-spectrum compounds with structural differences, but little is known concerning its role in cutin formation of cotton (Gossypium spp.). In this study, we conduct a genome-wide survey and detected 69, 71, 124 and 131 ABCG genes within G. arboretum, G. raimondii, G. hirsutum and G. barbadense, separately. The above ABCGs could be divided into four groups (Ia, Ib, Ic, II). Some ABCG genes such as GhABCG15, whose homologous gene transports cuticular lipid in Arabidopsis, was preferentially expressed in the development of fiber. A weighted gene co-expression network analysis (WGCNA) demonstrated that GhABCG expression was significantly associated with the amount of 16-Hydroxypalmitate (a main component of cutin precursor) in cotton fibers. Further, silencing of GhABCG15 by virus-induced gene silencing (VIGS) in cotton generated brightened and crinkled leaves as well as reduced thickness of cuticle and increased permeability. Chemical composition analysis showed the cutin content in GhABCG15-silenced leaves had decreased while the wax content had increased. Our results provide an insight for better understanding of the role of the Gossypium ABCG family and revealed the essential role of GhABCGs in cotton cutin formation.

Chilling injury owing to low temperatures severely affects the growth and development of maize (Zea mays.L) seedlings during the early and late spring seasons. The existing maize germplasm is deficient in the resources required to improve maize’s ability to tolerate cold injury. Therefore, it is crucial to introduce and identify excellent gene/QTLs that confer cold tolerance to maize for sustainable crop production. Wild relatives of maize, such as Z. perennis and Tripsacum dactyloides, are strongly tolerant to cold and can be used to improve the cold tolerance of maize. In a previous study, a genetic bridge among maize that utilized Z. perennis and T. dactyloides was created and used to obtain a highly cold-tolerant maize introgression line (MIL)-IB030 by backcross breeding. In this study, two candidate genes that control relative electrical conductivity were located on MIL-IB030 by forward genetics combined with a weighted gene co-expression network analysis. The results of the phenotypic, genotypic, gene expression, and functional verification suggest that two candidate genes positively regulate cold tolerance in MIL-IB030 and could be used to improve the cold tolerance of cultivated maize. This study provides a workable route to introduce and mine excellent genes/QTLs to improve the cold tolerance of maize and also lays a theoretical and practical foundation to improve cultivated maize against low-temperature stress.

Soybean stem elongation and thickening are related to cell wall composition. Plant morphogenesis can be influenced by blue light, which can regulate cell wall structure and composition, and affect stem growth and development. Here, using proteomics and metabolomics, differentially expressed proteins and metabolites of hypocotyls grown in the dark and under blue light were studied to clarify the effects of blue light on the cell wall structure and carbohydrate metabolism pathway of soybean hypocotyls. Results showed that 1120 differential proteins were upregulated and 797 differential proteins were downregulated under blue light treatment, while 63 differential metabolites were upregulated and 36 differential metabolites were downregulated. Blue light promoted the establishment of cell wall structure and composition by regulating the expression of both the enzymes and metabolites related to cell wall structural composition and nonstructural carbohydrates. Thus, under blue light, the cross-sectional area of the hypocotyl and xylem were larger, the longitudinal length of pith cells was smaller, elongation of the soybean hypocotyl was inhibited, and diameter was increased.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious and pathogenic coronavirus that emerged in late 2019 and caused a pandemic of respiratory illness termed as coronavirus disease 2019 (COVID-19). Cancer patients are more susceptible to SARS-CoV-2 infection. The treatment of cancer patients infected with SARS-CoV-2 is more complicated, and the patients are at risk of poor prognosis compared to other populations. Patients infected with SARS-CoV-2 are prone to rapid development of acute respiratory distress syndrome (ARDS) of which pulmonary fibrosis (PF) is considered a sequelae. Both ARDS and PF are factors that contribute to poor prognosis in COVID-19 patients. However, the molecular mechanisms among COVID-19, ARDS and PF in COVID-19 patients with cancer are not well-understood. In this study, the common differentially expressed genes (DEGs) between COVID-19 patients with and without cancer were identified. Based on the common DEGs, a series of analyses were performed, including Gene Ontology (GO) and pathway analysis, protein–protein interaction (PPI) network construction and hub gene extraction, transcription factor (TF)–DEG regulatory network construction, TF–DEG–miRNA coregulatory network construction and drug molecule identification. The candidate drug molecules (e.g., Tamibarotene CTD 00002527) obtained by this study might be helpful for effective therapeutic targets in COVID-19 patients with cancer. In addition, the common DEGs among ARDS, PF and COVID-19 patients with and without cancer are TNFSF10 and IFITM2. These two genes may serve as potential therapeutic targets in the treatment of COVID-19 patients with cancer. Changes in the expression levels of TNFSF10 and IFITM2 in CD14+/CD16+ monocytes may affect the immune response of COVID-19 patients. Specifically, changes in the expression level of TNFSF10 in monocytes can be considered as an immune signature in COVID-19 patients with hematologic cancer. Targeting N6-methyladenosine (m6A) pathways (e.g., METTL3/SERPINA1 axis) to restrict SARS-CoV-2 reproduction has therapeutic potential for COVID-19 patients.

The mirid bug Cyrtorhinus lividipennis (Reuter) is an important predator that consumes eggs and young nymphs of the brown planthopper Nilaparvata lugens as a primary food source and thus becomes an important member of the rice ecosystem. We identified and characterized the ClPSP gene in C. lividipennis encoding the phosphoserine phosphatase enzyme. The ClPSP has an open reading frame (ORF) of 957 bp encoding a protein with a length of 294bp and it possesses a haloacid dehalogenase-like (HAD) hydrolase, phosphoserine phosphatase, eukaryotic-like (HAD_PSP_eu) conserved domain. Furthermore, the in silico analysis of the ClPSP gene unveiled its distinct characteristics and it serves as a key player in the modulation of amino acids. The ClPSP showed expression in all developmental stages, with higher expression observed in the ovary and fat body. Silencing the ClPSP by RNA interference (RNAi) significantly decreased PSP enzyme activity and expression compared to dsGFP at two days after emergence (2DAE). The dsPSP treatment altered free hemolymph amino acid compositions, resulting in a significant reduction of serine (Ser) and Arginine (Arg) proportions and a significant increase of Threonine (Thr), Cystine (Cys), and Tyrosine (Tyr) in the C. lividipennis female at 2 DAE. Additionally, a hindered total protein concentration in the ovary and fat body, and reduced vitellogenin (Vg) expression, body weight, and number of laid eggs, were also observed. The same treatment also prolonged the preoviposition period and hindered ovarian development. Our data, for the first time, demonstrated the influential role of the PSP gene in modulating the fecundity of C. lividipennis and provide a platform for future insect pest control programs using the PSP gene in modulating fecundity.

Fruit black spot (FBS), a fungal disease of pecan (Carya illinoinensis (Wangenh) K. Koch) caused by the pathogen Pestalotiopsis microspora, is a serious disease and poses a critical threat to pecan yield and quality. However, the details of pecan responses to FBS infection at the transcriptional level remain to be elucidated. In present study, we used RNA-Seq to analyze differential gene expression in three pecan cultivars with varied resistance to FBS infection: Xinxuan-4 (X4), Mahan (M), and Wichita (W), which were categorized as having low, mild, and high susceptibility to FBS, respectively. Nine RNA-Seq libraries were constructed, comprising a total of 58.56 Gb of high-quality bases, and 2420, 4380, and 8754 differentially expressed genes (DEGs) with |log2Fold change| ≥ 1 and p-value < 0.05 were identified between M vs. X4, W vs. M, and W vs. X4, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analyses were performed to further annotate DEGs that were part of specific pathways, which revealed that out of 134 total pathways, MAPK signaling pathway, plant–pathogen interaction, and plant hormone signal transduction were highly enriched. Transcriptomic profiling analysis revealed that 1681 pathogen-related genes (PRGs), including 24 genes encoding WRKY transcription factors, potentially participate in the process of defense against Pestalotiopsis microspora infection in pecan. The correlation of WRKY TFs and PRGs was also performed to reveal the potential interaction networks among disease-resistance/pathogenesis-related genes and WRKY TFs. Expression profiling of nine genes annotated as TIFY, WRKY TF, and disease-resistance protein-related genes was performed using qRT-PCR, and the results were correlated with RNA-Seq data. This study provides valuable information on the molecular basis of pecan–Pestalotiopsis microspora interaction mechanisms and offers a repertoire of candidate genes related to pecan fruit response to FBS infection.

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders characterized by the progressive decline of cognitive functions, and is closely associated with the dysfunction of synapses, which comprise the basic structure that mediates the communication between neurons. Although the protein architecture and machinery for protein translation at synapses are extensively studied, the impact that local changes in the mRNA reservoir have on AD progression is largely unknown. Here, we investigated the changes in transcriptomic profiles in the synaptodendrosomes purified from the cortices of AD mice at ages 3 and 6 months, a stage when early signatures of synaptic dysfunction are revealed. The transcriptomic profiles of synaptodendrosomes showed a greater number of localized differentially expressed genes (DEGs) in 6-month-old AD mice compared with mice 3 months of age. Gene Ontology (GO) analysis showed that these DEGs are majorly enriched in mitochondrial biogenesis and metabolic activity. More specifically, we further identified three representative DEGs in mitochondrial and metabolic pathways—Prnp, Cst3, and Cox6c—that regulate the dendritic spine density and morphology in neurons. Taken together, this study provides insights into the transcriptomic changes in synaptodendrosomes during AD progression, which may facilitate the development of intervention strategies targeting local translation to ameliorate the pathological progression of AD.

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in the cardiovascular system, clinical applications centered on NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process, based on computational modeling and flow-mediated dilation, to assess endothelial function and vulnerability of atherosclerotic plaque. Then, emerging bioimaging technologies that have the potential to experimentally measure arterial NO concentration were discussed, including Raman spectroscopy and electrochemical sensors. In addition to diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the NO release platform to treat endothelial dysfunction and atherosclerosis and inhaled NO therapy to treat pulmonary hypertension and COVID-19. Two potential methods to improve the effectiveness of existing NO therapy were also discussed, including the combination of NO release platform and computational modeling, and stem cell therapy, which currently remains at the laboratory stage but has clinical potential for the treatment of CVD.

Pharmacologic studies have revealed that polycyclic polyprenylated acylphloroglucinols (PPAPs) collectively exhibit a broad range of biological activities, including antineoplastic potential. Here, six new PPAPs, named garcixanthochymones F–K (3, 5, 7, 8, 11, and 15), together with nine known analogues were isolated from the fruits of Garcinia xanthochymus. Their structures were elucidated based on the spectroscopic data, including UV, HRESIMS, and NMR, and quantum chemical calculations. All the isolated PPAPs were tested for anti-proliferative activity against four human tumor cell lines, including SGC7901, A549, HepG2, and MCF-7. Most of the PPAPs possessed high anti-proliferative activity with IC50 values in the range of 0.89 to 36.98 μM, and significant apoptosis was observed in MCF-7 cells exposed to compounds 2 and 5. Besides, docking results showed that compounds 2 and 5 could strongly combine with the Src homology 2 (SH2) domain of STAT3 via hydrogen bond and hydrophobic interaction, which is one of the key oncogenes and crucial therapeutic targets. Furthermore, compounds 2 and 5 efficiently downregulated the expression of p-STAT3Tyr705 and pivotal effector proteins involved in oncogenic signaling pathways of MCF-7 cells.

In the methyl-D-erythritol-4-phosphate (MEP) pathway, 1-deoxy-D-xylose-5-phosphate synthase (DXS) is considered the key enzyme for the biosynthesis of terpenoids. In this study, PmDXS (MK970590) was isolated from Pinus massoniana. Bioinformatics analysis revealed homology of MK970590 with DXS proteins from other species. Relative expression analysis suggested that PmDXS expression was higher in roots than in other plant parts, and the treatment of P. massoniana seedlings with mechanical injury via 15% polyethylene glycol 6000, 10 mM H2O2, 50 μM ethephon (ETH), 10 mM methyl jasmonate (MeJA), and 1 mM salicylic acid (SA) resulted in an increased expression of PmDXS. pET28a-PmDXS was expressed in Escherichia coli TransB (DE3) cells, and stress analysis showed that the recombinant protein was involved in resistance to NaCl and drought stresses. The subcellular localization of PmDXS was in the chloroplast. We also cloned a full-length 1024 bp PmDXS promoter. GUS expression was observed in Nicotiana benthamiana roots, stems, and leaves. PmDXS overexpression significantly increased carotenoid, chlorophyll a, and chlorophyll b contents and DXS enzyme activity, suggesting that DXS is important in isoprenoid biosynthesis. This study provides a theoretical basis for molecular breeding for terpene synthesis regulation and resistance.

p53 is a well-known tumor suppressor gene and one of the most extensively studied genes in cancer research. p53 functions largely as a transcription factor and can trigger a variety of antiproliferative programs via induction of its target genes. We identified PHLDA3 as a p53 target gene and found that its protein product is a suppressor of pancreatic neuroendocrine tumors (PanNETs) and a repressor of Akt function. PHLDA3 is frequently inactivated by loss of heterozygosity (LOH) and methylation in human PanNETs, and LOH at the PHLDA3 gene locus correlates with PanNET progression and poor prognosis. In addition, in PHLDA3-deficient mice, pancreatic islet cells proliferate abnormally and acquire resistance to apoptosis. In this article, we briefly review the roles of p53 and Akt in human neuroendocrine tumors (NETs) and describe the relationship between the p53-PHLDA3 and Akt pathways. We also discuss the role of PHLDA3 as a tumor suppressor in various NETs and speculate on the possibility that loss of PHLDA3 function may be a useful prognostic marker for NET patients indicating particular drug therapies. These results suggest that targeting the downstream PHLDA3-Akt pathway might provide new therapies to treat NETs.

Inflammation and oxidative stress play crucial roles in the etiology of type 2 diabetes mellitus. In this study, we examined the anti-diabetic effects of triterpenoid saponins extracted from Stauntonia chinensis on stimulating glucose uptake by insulin-resistant human HepG2 cells. The results showed that saponin 6 significantly increased glucose uptake and glucose catabolism. Saponin 6 also enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and activated the insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Therefore, our results suggest that saponins from S. chinensis improve glucose uptake and catabolism in hepatic cells by stimulating the AMPK and the IR/IRS-1/PI3K/Akt signaling pathways. The results also imply that saponins from S. chinensis can enhance glucose uptake and insulin sensitivity, representing a promising treatment for type 2 diabetes mellitus.

Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.

Chinese chestnut (Castanea mollissima Blume) can be infested by Dryocosmus kuriphilus Yasumatsu, resulting in gall formation and yield losses. Research on the control of gall wasps using genomics approaches is rarely reported. We used RNA-seq to investigate the dynamic changes in the genes of a chestnut species (C. mollissima B.) during four gall-formation stages caused by D. kuriphilus. A total of 21,306 genes were annotated by BLAST in databases. Transcriptome comparison between different gall-formation stages revealed many genes that were differentially expressed compared to the control. Among these, 2410, 7373, 6294, and 9412 genes were differentially expressed in four gall-formation stages: initiation stage (A), early growth stage (B), late growth stage (C), and maturation stage (D), respectively. Annotation analysis indicated that many metabolic processes (e.g., phenylpropanoid biosynthesis, secondary metabolism, plant⁻pathogen interaction) were affected. Interesting genes encoding putative components of signal transduction, stress response, and transcription factors were also differentially regulated. These genes might play important roles in response to D. kuriphilus gall formation. These new data on the mechanism by which D. kuriphilus infests chestnuts could help improve chestnut resistance.

Notch signaling as a conserved cell fate regulator is involved in the regulation of cell quiescence, proliferation, differentiation and postnatal tissue regeneration. However, how Notch signaling regulates porcine satellite cells (PSCs) has not been elucidated. We stably transfected Notch1 intracellular domain (N1ICD) into PSCs to analyze the gene expression profile and miRNA-seq. The analysis of the gene expression profile identified 295 differentially-expressed genes (DEGs) in proliferating-N1ICD PSCs (P-N1ICD) and nine DEGs on differentiating-N1ICD PSCs (D-N1ICD), compared with that in control groups (P-Control and D-Control, respectively). Analyzing the underlying function of DEGs showed that most of the upregulated DEGs enriched in P-N1ICD PSCs are related to the cell cycle. Forty-four and 12 known differentially-expressed miRNAs (DEMs) were identified in the P-N1ICD PSCs and D-N1ICD PSCs group, respectively. Furthermore, we constructed the gene-miRNA network of the DEGs and DEMs. In P-N1ICD PSCs, miR-125a, miR-125b, miR-10a-5p, ssc-miR-214, miR-423 and miR-149 are downregulated hub miRNAs, whose corresponding hub genes are marker of proliferation Ki-67 (MKI67) and nuclear receptor binding SET domain protein 2 (WHSC1). By contrast, miR-27a, miR-146a-5p and miR-221-3p are upregulated hub miRNAs, whose hub genes are RUNX1 translocation partner 1 (RUNX1T1) and fibroblast growth factor 2 (FGF2). All the hub miRNAs and genes are associated with cell proliferation. Quantitative RT-PCR results are consistent with the gene expression profile and miRNA-seq results. The results of our study provide valuable information for understanding the molecular mechanisms underlying Notch signaling in PSCs and skeletal muscle development.

Introduction of metals as biomaterials has been known for a long time. In the early development, sufficient strength and suitable mechanical properties were the main considerations for metal implants. With the development of new generations of biomaterials, the concepts of bioactive and biodegradable materials were proposed. Biological function design is very import for metal implants in biomedical applications. Three crucial design criteria are summarized for developing metal implants: (1) mechanical properties that mimic the host tissues; (2) sufficient bioactivities to form bio-bonding between implants and surrounding tissues; and (3) a degradation rate that matches tissue regeneration and biodegradability. This article reviews the development of metal implants and their applications in biomedical engineering. Development trends and future perspectives of metallic biomaterials are also discussed.

Our aims of the research were to study the antimicrobial effect of dimethylaminododecyl methacrylate (DMADDM) modified denture base resin on multi-species biofilms and the biocompatibility of this modified dental material. Candida albicans (C. albicans), Streptococcus mutans (S. mutans), Streptococcus sanguinis (S. sanguinis), as well as Actinomyces naeslundii (A. naeslundii) were used for biofilm formation on denture base resin. Colony forming unit (CFU) counts, microbial viability staining, and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) array were used to evaluate the antimicrobial effect of DMADDM. C. albicans staining and Real-time PCR were used to analyze the morphology and expression of virulence genes of C. albicans in biofilm. Lactate dehydrogenase (LDH) array and Real-time PCR were conducted to examine the results after biofilm co-cultured with epithelial cell. Hematoxylin and eosin (HE) staining followed by histological evaluation were used to study the biocompatibility of this modified material. We found that DMADDM containing groups reduced both biomass and metabolic activity of the biofilm significantly. DMADDM can also inhibit the virulence of C. albicans by means of inhibiting the hyphal development and downregulation of two virulence related genes. DMADDM significantly reduced the cell damage caused by multi-species biofilm according to the LDH activity and reduced the expression of IL-18 gene of the cells simultaneously. The in vivo histological evaluation proved that the addition of DMADDM less than 6.6% in denture material did not increase the inflammatory response (p > 0.05). Therefore, we proposed that the novel denture base resin containing DMADDM may be considered as a new promising therapeutic system against problems caused by microbes on denture base such as denture stomatitis.

Sensory bladder disorders encompass several distinct conditions with overlapping symptoms, which pose diagnostic challenges. This study aimed to evaluate urine biomarkers for differentiating between various sensory bladder disorders, including non-Hunner's interstitial cystitis (NHIC), detrusor overactivity (DO), hypersensitive bladder (HSB), and urodynamically normal women. A retrospective analysis of 191 women who underwent a videourodynamic study (VUDS) was conducted, with some also receiving cystoscopic hydrodistention to confirm the presence of NHIC. Participants were categorized into four groups: DO (n = 51), HSB (n = 29), NHIC (n = 81), and normal controls (n = 30). The urine levels of inflammatory and oxidative stress biomarkers were measured. The DO patients exhibited elevated IP-10 levels, while the HSB patients had decreased TAC and 8-OHdG levels. The NHIC patients showed lower IL-2 and higher TNF-α levels. A TNF-α ≥ 1.05 effectively identified NHIC, with an AUROC of 0.889, a sensitivity of 98.8%, and a specificity of 81.3%. An IP-10 ≥ 6.31 differentiated DO with an AUROC of 0.695, a sensitivity of 56.8%, and a specificity of 72.3%. An 8-OHdG ≤ 14.705 and a TAC ≤ 528.7 identified HSB with AUROCs of 0.754 and 0.844, respectively. The combination of 8-OHdG and TAC provided an AUROC of 0.853 for HSB. These findings suggest that TNF-α, IP-10, TAC, 8-OHdG, and IL-2 are promising non-invasive biomarkers for distinguishing between these conditions, which may improve diagnosis and management. [ABSTRACT FROM AUTHOR]

The process of aging inevitably leads to an increase in age-related comorbidities, including chronic kidney disease (CKD). In many aspects, CKD can be considered a state of accelerated and premature aging. Aging kidney and CKD have numerous common characteristic features, ranging from pathological presentation and clinical manifestation to underlying mechanisms. The shared mechanisms underlying the process of kidney aging and the development of CKD include the increase in cellular senescence, the decrease in autophagy, mitochondrial dysfunction, and the alterations of epigenetic regulation, suggesting the existence of potential therapeutic targets that are applicable to both conditions. In this review, we provide a comprehensive overview of the common characteristics between aging kidney and CKD, encompassing morphological changes, functional alterations, and recent advancements in understanding the underlying mechanisms. Moreover, we discuss potential therapeutic strategies for targeting senescent cells in both the aging process and CKD. [ABSTRACT FROM AUTHOR]