Embryonic Genome Activation (EGA) Occurred at 1-Cell Stage of Embryonic Development in the Mud Crab, Scylla paramamosain, Revealed by RNA-Seq.

As a prerequisite for the success of embryo development, embryonic genome activation (EGA) is an important biological event in which zygotic gene products in the embryo are activated to replace maternal-derived transcripts. Although EGA has been extensively studied in a large number of vertebrates and invertebrates, there is a lack of information regarding this event in crustacean crab. In this study, the timing of EGA was confirmed by examining a transcriptomic dataset of early embryonic development, including mature oocytes and embryos through six early developmental stages, and signaling pathways associated with EGA were identified in the mud crab, S. paramamosain. The comprehensive transcriptomic data identified a total of 53,915 transcripts from these sequencing samples. Notable transcriptomic change was evident at the 1-cell stage, indicated by a 36% transcript number shift and a reduction in transcript fragment length, compared to those present in the mature oocytes. Concurrently, a substantial increase in the expression of newly transcribed transcripts was observed, with gene counts reaching 3485 at the 1-cell stage, indicative of the onset of EGA. GO functional enrichment revealed key biological processes initiated at the 1-cell stage, such as protein complex formation, protein metabolism, and various biosynthetic processes. KEGG analysis identified several critical signaling pathways activated during EGA, including the "cell cycle," "spliceosome," "RNA degradation", and "RNA polymerase", pathways. Furthermore, transcription factor families, including zinc finger, T-box, Nrf1, and Tub were predominantly enriched at the 1-cell stage, suggesting their pivotal roles in regulating embryonic development through the targeting of specific DNA sequences during the EGA process. This groundbreaking study not only addresses a significant knowledge gap regarding the developmental biology of S. paramamosain, especially for the understanding of the mechanism underlying EGA, but also provides scientific data crucial for the research on the individual synchronization of seed breeding within S. paramamosain aquaculture. Additionally, it serves as a reference basis for the study of early embryonic development in other crustacean species.

Effects of soy protein isolate interaction with brown rice starch on the multiscale structure of brown rice bread.

BACKGROUND: Gluten-free bread (GFB) has technical bottlenecks such as hard texture, rough taste and low nutrition in practical production. In order to solve these problems, this study used germinated brown rice starch as the main raw material, and investigated the effects of soybean isolate protein (SPI) on the multiscale structure of germinated brown rice starch and bread quality. RESULTS: A gluten-free rice bread process simulation system was established, and the interaction between SPI and starch in the simulation system was characterized. The result shows that the interaction forces between SPI and germinated brown rice starch were mainly represented by hydrogen bonds, and with the addition of SPI, the crystallinity of starch showed a downward trend. At the same time, when the amount of SPI was 3%, the appearance quality was the best and the specific volume of bread was 1.08 mL g-1. When the amount of SPI was 6%, the texture quality was the best. Compared with the bread without SPI, the hardness of the bread with 6% SPI was reduced by 0.13 times, the springiness was increased by 0.03 times, the color was the most vibrant, the L* value being 1.02 times the original, and the baking loss was reduced to 0.98 times the original. CONCLUSIONS: The interaction force between SPI and germinated brown rice starch and its effect on bread quality were clarified, and these results inform choices about providing a theoretical basis for the subsequent development of higher-quality GFB. © 2024 Society of Chemical Industry.

Effect of high hydrostatic pressure treatment on food composition and applications in food industry: A review.

Nowadays, with the diversification of nutritious and healthy foods, consumers are increasingly seeking clean-labeled products. High hydrostatic pressure (HHP) as a cold sterilization technology can effectively sterilize and inactivate enzymes, which is conducive to the production of high-quality and safe food products with extended shelf life. This technology reduces the addition of food additives and contributes to environmental protection. Moreover, HHP enhances the content and bioavailability of nutrients, reduces the anti-nutritional factors and the risk of food allergen concerns. Therefore, HHP is widely used in the processing of fruit and vegetable juice drinks, alcoholic, meat products and aquatic products, etc. A better understanding of the influence of HHP on food composition and applications can guide the development of food industry and contribute to the development of non-thermally processed and environmentally friendly foods.

[Retracted] Salidroside mitigates hypoxia/reoxygenation injury by alleviating endoplasmic reticulum stress­induced apoptosis in H9c2 cardiomyocytes.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell apoptotic assay data shown in Fig. 1D on p. 3763 were strikingly similar to data that had already been submitted for publication in Fig. 3A in different form in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 3760­3768, 2018; DOI: 10.3892/mmr.2018.9403].

Defect-engineering of liquid-phase exfoliated 2D semiconductors: stepwise covalent growth of electronic lateral hetero-networks.

Two-dimensional (2D) in-plane heterostructures display exceptional optical and electrical properties well beyond those of their pristine components. However, they are usually produced by tedious and energy-intensive bottom-up growth approaches, not compatible with scalable solution-processing technologies. Here, we report a new stepwise microfluidic approach, based on defect engineering of liquid-phase exfoliated transition metal dichalcogenides (TMDs), to synthesize 2D hetero-networks. The healing of sulfur vacancies in MoS2 and WS2 is exploited to controllably bridge adjacent nanosheets of different chemical nature with dithiolated conjugated molecular linkers, yielding solution-processed nm-scale thick networks with enhanced percolation pathways for charge transport. In-plane growth and molecular-driven assembly synergistically lead to molecularly engineered heterojunctions suppressing the formation of tightly bound interlayer excitons that are typical of conventional TMD blends, promoting faster charge separation. Our strategy offers an unprecedented route to chemically assemble solution-processed heterostructures with functional complexity that can be further enhanced by exploiting stimuli-responsive molecular linkers.

Neutrophils Recruited by NKX2-1 Suppression via Activation of CXCLs/CXCR2 Axis Promote Lung Adenocarcinoma Progression.

NK2 Homeobox 1 (NKX2-1) is a well-characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2-1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2-1 is observed in high-grade LUAD. Meanwhile, single-cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell-cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2-1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT-PCR. ATAC-seq revealed the restrictive regulation of NKX2-1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2-1 modulates the infiltration of tumor-promoting neutrophils by inhibiting CXCLs/CXCR2-dependent mechanisms. Hence, targeting CXCR2 in NKX2-1-low tumors is a potential antitumor therapy that may improve LUAD patient outcomes.

[Involvement of microRNA-145/TGF-ß in the regulation of swimming exercise on vascular calcification in type 2 diabetic rats].

The present study aimed to explore the effect of swimming exercise on vascular calcification in type 2 diabetic rats and its related molecular mechanism. Male Sprague Dawley (SD) rats were randomly divided into normal control (NC), diabetes control (DC) and diabetes+exercise (DE) groups. The DC and DE groups were intraperitoneally injected with streptozotocin (STZ) and fed with high-fat diet to establish type 2 diabetes mellitus model. The NC and DC groups did not exercise, and the DE group performed swimming exercise for 8 weeks. ELISA was used to detect the serum glycated hemoglobin A1c (HbA1c) level. The aortas of rats were taken as sample. Assay kits were used to detect vascular calcium content and alkaline phosphatase (ALP) activity. Von Kossa staining was used to detect calcium deposition. qRT-PCR was used detect the expression of microRNA-145 (miR-145). Western blot was used to detect the protein expression levels of smooth muscle contraction markers, calcification marker and related proteins. The results showed that, compared with the NC group, the blood glucose, serum HbA1c level, vascular calcium content and ALP activity in the DC group were significantly increased, the protein expression levels of smooth muscle contraction markers smooth muscle protein 22α (SM22α) and α-smooth muscle actin (α-SMA) were significantly down-regulated, and the protein expression level of calcification marker osteopontin (OPN) was significantly up-regulated; Compared with the DC group, the serum HbA1c level, vascular calcium content and ALP activity in the DE group were significantly decreased, the protein expression levels of SM22α and α-SMA were significantly up-regulated, and the protein expression level of OPN was significantly down-regulated; Compared with the NC group, the expression of miR-145-5p in the DC group was significantly down-regulated, and the protein expression levels of transforming growth factor-ß (TGF-ß), SMAD2, ERK1/2 and p-ERK1/2 were significantly up-regulated; Compared with the DC group, the expression of miR-145-5p was significantly up-regulated in the DE group, while the expressions of TGF-ß, ERK1/2 and p-ERK1/2 were significantly down-regulated. These results suggest that miR-145/TGF-ß signaling is involved in the improving effects of 8-week swimming exercise on glucose metabolism disorder, vascular smooth muscle cell phenotype switching and vascular calcification in type 2 diabetes mellitus.

Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.

Traditional Use, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Persicae Semen: A Review.

Persicae Semen (Taoren), the seed of mature peaches consumed as both food and medicine, is native to the temperate regions of China, distributed in the provinces of North and East China, and currently cultivated worldwide. The primary components of Persicae Semen include volatile oil, protein, amino acids, amygdalin, and prunasin, all of which have pharmacological properties, such as anti-inflammatory, antioxidant, and immune regulatory effects, and are clinically used in the treatment of gynecological, cardiovascular, cerebrovascular, orthopedic, and digestive system diseases. This review provides a comprehensive perspective on the resource status, ethnopharmacology, phytochemistry, pharmacology, and toxicology, as well as the trend of Persicae Semen patent, global distribution, and clinical applications. This review will help facilitate the development and utilization of Persicae Semen in clinical settings.

Transcription factor TaNF-YB2 interacts with partners TaNF-YA7/YC7 and transcriptionally activates distinct stress-defensive genes to modulate drought tolerance in T. Aestivum.

BACKGROUND: Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses. RESULTS: TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance. CONCLUSIONS: TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.

Pulmonary microbial spectrum in late-stage SARS-CoV-2 infection: a case series.

Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19.

To explore the protective effect of gastrodin on PC12 cells against oxidative stress induced by lead acetate based on network pharmacology.

Objective: Screening and predicting potential targets for gastrodin antioxidant stress based on network pharmacology methods, and exploring the effect of gastrodin on lead acetate induced oxidative stress in PC12 cells through cell experiments. Methods: Through the Pharmaper database Predict the target of action of gastrodin. Through OMIM and GeneCards to collect oxidative stress targets from database, and intersect with drug targets to obtain drug disease intersection targets; Construct a PPI network diagram using the STRING database. Perform GO enrichment analysis and KEGG pathway enrichment analysis on intersection targets through the DAVID platform. Lead acetate (PbAc) exposure was used to establish a lead poisoning cell model, and intracellular ROS levels, ALB, AKT1, and Caspase-3 levels were measured. Results: A total of 288 targets of gastrodin action, 638 targets related to oxidative stress, and 62 drug disease intersection targets were obtained, among which core targets such as ALB, AKT1, CASP3 may be closely related to oxidative stress. KEGG pathway analysis showed that gastrodin antioxidant stress mainly involved in lipid, cancer pathway and other signaling pathways. The results of the cell experiment showed that 50 µM is the optimal effective concentration for PbAc induced ROS production in PC12 cells. Gastrodin significantly increased the ROS content of PC12 cells treated with PbAc, Upregulation of ALB expression and downregulation of AKT1 and CASP3 expression. Conclusions: Gastrodin may alleviate PbAc-induced ROS in PC12 cells, indicating potential protective effects against oxidative stress. Further studies are needed to confirm these findings and explore the underlying mechanisms.

Dietary Selenium Insufficiency Induces Cardiac Inflammatory Injury in Chicks.

BACKGROUND: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency. OBJECTIVES: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life. METHODS: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway. RESULTS: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1ß), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks. CONCLUSIONS: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB.

Transformation of a Viral Capsid from Nanocages to Nanotubes and Then to Hydrogels: Redirected Self-Assembly and Effects on Immunogenicity.

The ability to manipulate the self-assembly of proteins is essential to understanding the mechanisms of life and beneficial to fabricating advanced nanomaterials. Here, we report the transformation of the MS2 phage capsid from nanocages to nanotubes and then to nanotube hydrogels through simple point mutations guided by interfacial interaction redesign. We demonstrate that site 70, which lies in the flexible FG loop of the capsid protein (CP), is a "magic" site that can largely dictate the final morphology of assemblies. By varying the amino acid at site 70, with the aid of a cysteine-to-alanine mutation at site 46, we achieved the assembly of double-helical or single-helical nanotubes in addition to nanocages. Furthermore, an additional cysteine substitution on the surface of nanotubes mediated their cross-linking to form hydrogels with reducing agent responsiveness. The hierarchical self-assembly system allowed for the investigation of morphology-related immunogenicity of MS2 CPs, which revealed dramatic differences among nanocages, nanotubes, and nanotube hydrogels in terms of immune response types, antibody levels and T cell functions. This study provides insights into the assembly manipulation of protein nanomaterials and the customized design of nanovaccines and drug delivery systems.

Activity reconstitution of Kre33 and Tan1 reveals a molecular ruler mechanism in eukaryotic tRNA acetylation.

RNA acetylation is a universal post-transcriptional modification that occurs in various RNAs. Transfer RNA (tRNA) acetylation is found at position 34 (ac4C34) in bacterial tRNAMet and position 12 (ac4C12) in eukaryotic tRNASer and tRNALeu. The biochemical mechanism, structural basis and functional significance of ac4C34 are well understood; however, despite being discovered in the 1960s and identification of Kre33/NAT10 and Tan1/THUMPD1 as modifying apparatuses, ac4C12 modification activity has never been reconstituted for nearly six decades. Here, we successfully reconstituted the ac4C12 modification activity of yeast Kre33 and Tan1. Biogenesis of ac4C12 is primarily dependent on a minimal set of elements, including a canonical acceptor stem, the presence of the 11CCG13 motif and correct D-arm orientation, indicating a molecular ruler mechanism. A single A13G mutation conferred ac4C12 modification to multiple non-substrate tRNAs. Moreover, we were able to introduce ac4C modifications into small RNAs. ac4C12 modification contributed little to tRNA melting temperature and aminoacylation in vitro and in vivo. Collectively, our results realize in vitro activity reconstitution, delineate tRNA substrate selection mechanism for ac4C12 biogenesis and develop a valuable system for preparing acetylated tRNAs as well as non-tRNA RNA species, which will advance the functional interpretation of the acetylation in RNA structures and functions.

Characterization of structural and functional properties of soybean 11S globulin during renaturation after denaturation induced by changes in pH.

BACKGROUND: This study explored the denaturation of 11S globulin, a protein known for its diverse functional properties in soy protein applications, at pH 3.0 and pH 10.0, followed by a gradual return to pH 7.0 to facilitate renaturation. It investigated the structural and functional changes during renaturation induced by a change in pH, revealing the stabilization mechanism of 11S globulin. RESULTS: The findings revealed that during pH adjustment to neutral, the denatured soybean 11S globulin - resulting from alkaline (pH 10.0) or acidic (pH 3.0) treatments - experienced a refolding of its extended tertiary structure to varying extents. The particle size and the proportions of α-helix and ß-sheet in the secondary structure aligned progressively with those of the natural-state protein. However, for the alkali-denatured 11S, the ß-sheet content decreased upon adjustment to neutral, whereas an increase was observed for the acid-denatured 11S. In terms of functional properties, after alkaline denaturation, the foaming capacity (FC) and emulsifying activity index (EAI) of 11S increased by 1.4 and 1.2 times, respectively, in comparison with its native state. The solubility, foamability, and emulsifiability of the alkali-denatured 11S gradually diminished during renaturation but remained superior to those of the native state. Conversely, these properties showed an initial decline, followed by an increase during renaturation triggered by pH neutralization. CONCLUSIONS: This research contributes to the enhancement of protein functionality, offering a theoretical foundation for the development of functional soy protein products and expanding their potential applications. © 2024 Society of Chemical Industry.