ARHGAP4 promotes colon cancer metastasis through the TGF-ß signaling pathway and may be associated with T cell exhaustion.

BACKGROUND: Colon cancer is a prevalent invasive neoplasm in the gastrointestinal system with a high degree of malignancy. Despite extensive research, the underlying mechanisms of its recurrence and metastasis remain elusive.Rho GTPase activating protein 4 (ARHGAP4), a member of the small GTPases protein family, may be closely related to tumor metastasis, and its expression is increased in colon cancer. However, the role of ARHGAP4 in colon cancer metastasis is uncertain. This study investigates the impact of ARHGAP4 on the metastasis of colon cancer cells. Our objective is to determine the role of ARHGAP4 in regulating the invasive behavior of colon cancer cells. METHODS: We downloaded colon adenocarcinoma (COAD) data from the Cancer Genome Atlas (TCGA), and performed differential analysis and survival analysis. By using the CIBERSORT algorithm, we evaluated the proportion of infiltrating immune cells in colon cancer. We further analyzed whether ARHGAP4 is associated with T cell exhaustion. Finally, we investigated the impact of ARHGAP4 knockdown on the migration and invasion of colon cancer cells through in vitro cell experiments. Additionally, we utilized western blotting to assess the expression of protein related to the TGF-ß signaling pathway and epithelial-mesenchymal transition (EMT). RESULTS: We found that ARHGAP4 is upregulated in colon cancer. Subsequent survival analysis revealed that the high-expression group had significantly lower survival rates compared to the low-expression group. Immune infiltration analysis showed that ARHGAP4 was not only positively correlated with CD8+ T cells, but also positively correlated with T cell exhaustion markers programmed cell death 1 (PDCD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte activating 3 (LAG-3). In vitro cell experiments, the knockdown of ARHGAP4 inhibited the migration and invasion of colon cancer cells. Among EMT-related proteins, when ARHGAP4 was knocked down, the expression of E-cadherin was increased, while the expression of N-cadherin and Vimentin was decreased. Meanwhile, the expression of TGF-ß1, p-Smad2, and p-Smad3, which are associated with the TGF-ß/Smad pathway, all decreased. CONCLUSION: ARHGAP4 promotes colon cancer metastasis through the TGF-ß/Smad signaling pathway and may be associated with T cell exhaustion. It plays an important role in the progression of colon cancer and may serve as a potential target for diagnosis and treatment of colon cancer.

Evolving ω-amine transaminase AtATA guided by substrate-enzyme binding free energy for enhancing activity and stability against non-natural substrates.

In the field of chiral amine synthesis, ω-amine transaminase (ω-ATA) is one of the most established enzymes capable of asymmetric amination under optimal conditions. However, the applicability of ω-ATA toward more non-natural complex molecules remains limited due to its low transamination activity, thermostability, and narrow substrate scope. Here, by employing a combined approach of computational virtual screening strategy and combinatorial active-site saturation test/iterative saturation mutagenesis strategy, we have constructed the best variant M14C3-V5 (M14C3-V62A-V116S-E117I-L118I-V147F) with improved ω-ATA from Aspergillus terreus (AtATA) activity and thermostability toward non-natural substrate 1-acetylnaphthalene, which is the ketone precursor for producing the intermediate (R)-(+)-1-(1-naphthyl)ethylamine [(R)-NEA] of cinacalcet hydrochloride, showing activity enhancement of up to 3.4-fold compared to parent enzyme M14C3 (AtATA-F115L-M150C-H210N-M280C-V149A-L182F-L187F). The computational tools YASARA, Discovery Studio, Amber, and FoldX were applied for predicting mutation hotspots based on substrate-enzyme binding free energies and to show the possible mechanism with features related to AtATA structure, catalytic activity, and stability in silico analyses. M14C3-V5 achieved 71.8% conversion toward 50 mM 1-acetylnaphthalene in a 50 mL preparative-scale reaction for preparing (R)-NEA. Moreover, M14C3-V5 expanded the substrate scope toward aromatic ketone compounds. The generated virtual screening strategy based on the changes in binding free energies has successfully predicted the AtATA activity toward 1-acetylnaphthalene and related substrates. Together with experimental data, these approaches can serve as a gateway to explore desirable performances, expand enzyme-substrate scope, and accelerate biocatalysis.IMPORTANCEChiral amine is a crucial compound with many valuable applications. Their asymmetric synthesis employing ω-amine transaminases (ω-ATAs) is considered an attractive method. However, most ω-ATAs exhibit low activity and stability toward various non-natural substrates, which limits their industrial application. In this work, protein engineering strategy and computer-aided design are performed to evolve the activity and stability of ω-ATA from Aspergillus terreus toward non-natural substrates. After five rounds of mutations, the best variant, M14C3-V5, is obtained, showing better catalytic efficiency toward 1-acetylnaphthalene and higher thermostability than the original enzyme, M14C3. The robust combinational variant acquired displayed significant application value for pushing the asymmetric synthesis of aromatic chiral amines to a higher level.

OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-ß/Smad signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms. METHODS: Real-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-ß/Smad signaling pathway-related proteins was investigated using western blotting. RESULTS: In this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-ßR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-ß / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels. CONCLUSION: The protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-ß/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance.

Graduate Student Literature Review: Network of flavor compounds formation and influence factors in yogurt.

Yogurt is popular as a natural and healthy food, but its flavor greatly affects acceptability by consumers. Flavor compounds of yogurt is generally produced by the metabolism of lactose, protein and fat, and the resulting flavors include carbonyls, acids, esters and alcohols, etc. Each flavor compounds could individually provide the corresponding flavor, or it can be combined with other compounds to form a new flavor. The flavor network was formed among the metabolites of milk components, and acetaldehyde, as the central compounds, played a role in connecting the whole network. The flavor compounds can be affected by many factors, such as the use of different raw milks, ways of homogenization, sterilization, fermentation, post ripening, storage condition and packaging materials, etc., which can affect the overall flavor of yogurt. This paper provides an overview of the volatile flavor compounds in yogurt, the pathways of production of the main flavor compounds during yogurt fermentation, and the factors that influence the flavor of yogurt including type of raw milk, processing, and storage. It also tries to provide theoretical guidance for the product of yogurt in ideal flavor, but further research is needed to provide a more comprehensive description of the flavor system of yogurt.

Association of maternal hypertension during pregnancy with brain structure and behavioral problems in early adolescence.

Emerging evidence suggests an association between maternal hypertension during pregnancy and mental health in the offspring. However, less is known about the role of hypertensive pregnancy in behavioral symptoms and brain structures of the offspring as well as in their developmental changes. Here, we utilized neuroimaging and behavioral data from 11,878 participants aged 9-10 years and their 2-year follow-up from the Adolescent Brain Cognitive Development (ABCD) study to investigate the long-term effects of maternal hypertension during pregnancy on early adolescent behavior and brain anatomy. Specifically, adolescents born of mothers with maternal hypertension are at risk of long-lasting behavioral problems, as manifested by higher externalizing and internalizing behavior scores at both 9-10 years and 11-12 years. These participants additionally presented with a higher cortical thickness, particularly in the fronto-parieto-temporal areas at 9-10 years. Four regions, including the left parahippocampus, left lateral orbitofrontal lobe, right superior temporal lobe and right temporal pole, remained thicker 2 years later. These findings were partially validated in rats modeled with Nω-nitro-L-arginine methyl ester (L-NAME) preeclampsia. Therefore, clinicians and women who experience hypertension during pregnancy should be warned of this risk, and healthcare providers should recommend appropriate clinical interventions for pregnancy-induced hypertension.

The prevalence and risk factors of facial pressure injuries related to adult non-invasive ventilation equipment: A systematic review and meta-analysis.

To systematically assess the prevalence of facial pressure injuries related to adult non-invasive ventilation equipment, and risk factors of facial pressure injuries. PubMed, Cochrane Library, Web of Science, Embase, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database and Weipu Database were comprehensively searched for observational studies investigating the prevalence and risk factors of facial pressure injuries related to adult non-invasive ventilation equipment from inception to May 16th, 2022. Filter articles based on inclusion and exclusion criteria. The quality of the included studies was evaluated independently by two investigators. Meta-analysis was conducted using Stata 16.0 software package. In total, 2835 articles were screened and data from 12 studies were used in meta-analysis. The prevalence of facial pressure injuries related to adult non-invasive ventilation equipment was 25% (95% confidence interval, CI:15% to 37%, I2  = 97.34%, P < 0.0001). After controlling for confounding variables, the following risk factors of facial pressure injuries: use equipment form, with diabetes, fever, cumulative time of using equipment, facial skin oedema and Glasgow score. Understanding the risk factors of facial pressure injuries can provide the healthcare personnel with the theoretical basis for the management and treatment of the patients.

Instrumentation-Compact Digital Microfluidic Reaction Interface-Extended Loop-Mediated Isothermal Amplification for Sample-to-Answer Testing of Vibrio parahaemolyticus.

Vibrio parahaemolyticus is usually spread via consumption of contaminated seafood and causes vibriosis. By combination of digital microfluidic (DMF) and loop-mediated isothermal amplification (LAMP), we provided an automated instrumentation-compact DMF-LAMP device for sample-to-answer detection of V. parahaemolyticus. For the first time, how much the proper mixing might facilitate the DMF-LAMP process is explored. The results illustrated that increasing the number of flow configurations and decreasing the fluid-reversibility will extend the interfacial surface available for diffusion-based mass transfer within a droplet microreactor, thus contributing to the overall amplification reaction rate. Noticeably, the DMF-LAMP amplification plateau time is shortened by proper mixing, from 60 min in static mixing and traditional bulk LAMP to 30 min in 2-electrode mixing and 15 min in 3-electrode mixing. The device achieved much higher detection sensitivity (two copies per reaction) than previously reported devices. V. parahaemolyticus from spiked shrimps is detected by Q-tip sampling associated with 3-electrode mixing DMF-LAMPs. The detectable signal occurs within only 3 min at a higher concentration and, at most, is delayed to 18 min, with a detection limit of <0.23 × 103 CFU/g. Thus, the developed DMF-LAMP device demonstrates potential for being used as a sample-to-answer system with a quick analysis time, high sensitivity, and sample-to-answer format.

A three-dimensional pinwheel-shaped paper-based microfluidic analytical device for fluorescence detection of multiple heavy metals in coastal waters by rational device design.

Here, we present the rational design of a pinwheel-shaped three-dimensional microfluidic paper-based analytical device (3D-µPAD) for specific, sensitive and multiplexed detection of heavy metals in coastal waters. A more homogeneous permeation of fluids along the chip than common design, even under unskilled performance, has been achieved by the elaborate chip design of the hydrostatic balancing inlet port and uniformly stressed reversible sealing. With the combination of ion imprinted polymer grafted CdTe quantum-dots and fluid accumulation pad, 4 metals (Cu2+, Cd2+, Pb2+, and Hg2+) in 1 analysis and 25-fold enrichment for each metal can be simultaneously performed within 20 min, with detection limits of 0.007-0.015 µg/L. It has the ability to selectively recognize these 4 metals in mixtures and immunizing to interferences from components found in coastal waters, which provided results that were in agreement with values gained from atomic absorption. The inexpensive and portable nature as well as the highly sensitive and flexible performance of the new developed 3D-µPAD could make it attractive as an on-site testing approach for marine environmental monitoring.

Long-term holographic phase-contrast time lapse reveals cytoplasmic circulation in dehydrating plant cells.

The intracellular dynamics of onion epidermal cells during the dehydration process is observed by holographic microscopy. Both the nucleus and cytoplasm are accurately revealed by quantitative phase imaging while dehydration takes place. Indeed, we notice that the contrast of phase images increases with the decrease in cellular water content. We foresee that such a dehydrating process can be effective for improving phase contrast, thus permitting better imaging of plant cells with the scope of learning more about cellular dynamics and related phenomena. Exploiting this concept, we observe intracellular cytoplasmic circulation and transport of biological material.

Neutralizing TGF-ß promotes anti-tumor immunity of dendritic cells against pancreatic cancer by regulating T lymphocytes.

Previous fundamental or clinical trials of dendritic cell (DC) vaccine against pancreatic ductal adenocarcinoma (PDAC) revealed the burgeoning neoadjuvant immunotherapy. Microarray studies indicated that multiple ingredients of the transfer growth factor beta (TGF-ß) pathway were overexpressed in PDAC, which inhibited the intratumoral immune response. To explore whether the DC volume in tumor microenvironment contributes to the differentiation of T cell cohort and test the hypothesis that combining DC vaccine with TGF-ß inhibitors will elevate the anti-tumor immune response, we managed to co-culture T cells in vitro with pancreatic cancer cells and DCs in different concentrations, and combine TGF-ß blockage with DC vaccine therapy in a murine model of pancreatic cancer. In in vitro studies, we discovered that CD8+ T cytotoxic cell (Tc) presented a significant advantage and lower volume of CD4+ T helper cell (Th) existed with a certain elevated DC concentration (p < 0.05), associated with declined interleukin (IL)-10 and increased interferon (IFN)-γ, which suggested with the DC volume increasing, the enhancing immune effect may represent a great advantage in such a system (p < 0.05). When interfered with anti-TGF-ß antibody or TGF-ß cytokine, respectively, in the co-culture system, we found IFN-γ producing was extremely higher and T cell apoptosis relatively descent with TGF-ß blockage (p < 0.05). The murine PDAC model demonstrated a survival advantage treated with anti-TGF-ß antibody combined with DC vaccine when compared with monotherapy controls (p < 0.05). Therefore, these findings indicated that, through neutralizing TGF-ß associated with DC vaccine, the anti-tumor immunity is highly elevated and this combinational therapy will provide an efficacious prospect.

[Transverse characteristics of normodivergent patients in different sagittal skeletal patterns].

PURPOSE: This study aimed to measure and analyze the transverse indicators of normodivergent patients with different sagittal skeletal malocclusions, to explore the transverse characteristics of different sagittal skeletal malocclusions. METHODS: Lateral cephalograms and CBCT of 90 normodivergent patients with skeletal Class Ⅰ, Ⅱ and Ⅲ in their permanent dentition were collected. Dolphin software was applied to measure the widths of the basal bone, alveolar bone, dental arch and buccolingual inclination angle of the corresponding teeth in the maxillary and mandibular canine, premolar and molar areas. SPSS 22.0 software package was applied for statistical analysis of the data. RESULTS: The widths of the mandibular basal bone in canine, premolar and molar areas of skeletal Class Ⅲ were (27.15±2.74), (39.30±2.82) and (59.97±2.93) mm, respectively. The widths of the mandibular alveolar bone of skeletal Class Ⅲ were (25.38±1.78), (34.51±2.28) and (47.72±2.73) mm, respectively. The dental arch widths of the maxillary premolar and mandibular canine areas of skeletal Class Ⅲ were (48.70±2.35) and (30.69±2.31)mm, respectively. The above data of skeletal Class Ⅲ were significantly larger than those of skeletal Class Ⅰ and Ⅱ(P＜0.01). The dental arch widths of the maxillary canine, maxillary molar and mandibular molar areas of skeletal Class Ⅲ were (38.88±1.90), (59.51±3.40) and (56.01±2.86)mm, respectively, which were significantly larger than those of skeletal Class Ⅱ(P＜0.05). The maxillomandibular width difference of basal bone in the canine, premolar and molar areas of skeletal Class Ⅲ were (4.69±2.84), (2.31±2.39) and (3.27±2.05) mm, respectively, which were significantly less than that of skeletal Class Ⅰ and Ⅱ(P＜0.01). Compared with skeletal Class Ⅰ, the maxillary canines and first molars of skeletal Class Ⅱ had larger lingual inclination level, while the maxillary first premolars and first molars of skeletal Class Ⅲ had larger buccal inclination level, the mandibular canines and the mandibular first premolars of skeletal Class Ⅲ had larger lingual inclination level(P＜0.01). CONCLUSIONS: For normodivergent patients, the width of the mandibular base bone, alveolar bone, and maxillary and mandibular dental arch in skeletal Class Ⅲ is the widest, which is more likely to have width discrepancy in basal bone. In skeletal Class Ⅲ, the maxillary teeth are buccally inclined, and the mandibular teeth are ingually inclined. In skeletal Class Ⅱ, the maxillary teeth are lingually inclined, and the mandibular teeth are compensatory upright.

Trophoblast fusion in fetal growth restriction is inhibited by CTGF in a cell-cycle-dependent manner.

Fetal growth restriction (FGR) is a relatively common complication of pregnancy, and insufficient syncytialization in the placenta may play an important role in the pathogenesis of FGR. However, the mechanism of impaired formation of the syncytiotrophoblast layer in FGR patients requires further exploration. In the present study, we demonstrated that the level of syncytialization was decreased in FGR patient placentas, while the expression of connective tissue growth factor (CTGF) was significantly upregulated. CTGF was found to inhibit trophoblast fusion via regulating cell cycle progress of BeWo cells. Furthermore, we found that CTGF negatively regulates cell cycle arrest in a p21-dependent manner as overexpression of p21 could rescue the impaired syncytialization induced by CTGF-overexpression. Besides, we also identified that CTGF inhibits the expression of p21 through ITGB4/PI3K/AKT signaling pathway. Our study provided a new insight for elucidating the pathogenic mechanism of FGR and a novel idea for the clinical therapy of FGR.

Identification, molecular evolution, codon bias, and expansion analysis of NLP transcription factor family in foxtail millet (Setaria italica L.) and closely related crops.

The NODULE-INCEPTION-like protein (NLP) family is a plant-specific transcription factor (TF) family involved in nitrate transport and assimilation in plants, which are essential for improving plant nitrogen use efficiency. Currently, the molecular nature and evolutionary trajectory of NLP genes in the C4 model crop foxtail millet are unknown. Therefore, we performed a comprehensive analysis of NLP and molecular evolution in foxtail millet by scanning the genomes of foxtail millet and representative species of the plant kingdom. We identified seven NLP genes in the foxtail millet genome, all of which are individually and separately distributed on different chromosomes. They were not structurally identical to each other and were mainly expressed on root tissues. We unearthed two key genes (Si5G004100.1 and Si6G248300.1) with a variety of excellent characteristics. Regarding its molecular evolution, we found that NLP genes in Gramineae mainly underwent dispersed duplication, but maize NLP genes were mainly generated via WGD events. Other factors such as base mutations and natural selection have combined to promote the evolution of NLP genes. Intriguingly, the family in plants showed a gradual expansion during evolution with more duplications than losses, contrary to most gene families. In conclusion, this study advances the use of NLP genetic resources and the understanding of molecular evolution in cereals.

Stereoselective synthesis of (R)-(+)-1-(1-naphthyl)ethylamine by ω-amine transaminase immobilized on amino modified multi-walled carbon nanotubes and biocatalyst recycling.

Immobilized enzymes exhibit favorable advantages in biocatalysis, such as high operation stability, feasible reusability, and improved organic solvents tolerance. Herein, an immobilized ω-amine transaminase AtATA@MWCNTs-NH2 is successfully prepared using amino modified multi-walled carbon nanotubes as carrier and glutaraldehyde as crosslinker. Under the optimum immobilization conditions, the activity recovery is 78.7%. Compared with purified enzyme AtATA, AtATA@MWCNTs-NH2 possesses superior stability, even in harsh conditions (e.g., high temperature, acidic or alkali environment, and different kind of organic solvents). To simplify the separation and extraction of products, we choose methanol (10%, v/v) as the cosolvent, replacing DMSO (20%, v/v) in our previous work, for the catalytic reaction of AtATA@MWCNTs-NH2. AtATA@MWCNTs-NH2 can be used for stereoselective synthesis (R)-(+)- 1(1-naphthyl)ethylamine ((R)-NEA) for 15 cycles, with the e.e.p (enantiomeric excess) > 99.5%. The catalytic process of AtATA@MWCNTs-NH2 achieves cycle production of (R)-NEA using methanol as cosolvent.

Extra villous trophoblast-derived PDL1 can ameliorate macrophage inflammation and promote immune adaptation associated with preeclampsia.

INTRODUCTION: Severe preeclampsia (sPE) is a systemic syndrome that may originate from chronic inflammation. Maintaining maternal-fetal hemostasis by the co-inhibitory molecule programmed death ligand 1 (PDL1) can be favorable for ameliorating inflammation from immune cells. Apart from programmed death 1 (PD1) expression, decidual macrophages (dMs) produce inflammatory cytokines, in response to cells which express PDL1. However, strong evidence is lacking regarding whether the PDL1/PD1 interaction between trophoblasts and decidual macrophages affects inflammation during sPE development. METHODS: To determine whether the trophoblast-macrophage crosstalk via the PDL1/PD1 axis modulates the inflammatory response in sPE-like conditions, at first, maternal-fetal tissues from sPE and normal patients were collected, and the PDL1/PD1 distribution was analyzed by Western blot, immunohistochemistry/ immunofluorescence and flow cytometry. Next, a coculture system was established and flow cytometry was used to identify how PDL1 was involved in macrophage-related inflammation under hypoxic stress. Transcriptional analysis was performed to clarify the inflammation-associated pathway induced by the PDL1/PD1 interaction. Finally, the Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) mouse model was used to examine the effect of PDL1 on macrophage-related inflammation by measuring PE-like symptoms. RESULTS: In maternal-fetal tissue from sPE patients, placental extravillous trophoblasts (EVTs) and dMs had a surprisingly increase of PDL1 and PD1 expression, respectively, accompanied by a higher percentage of CD68 +CD86 + dMs. In vitro experiments showed that trophoblast-derived PDL1 under hypoxia interacted with PD1 on CD14 +CD80 +macrophages, leading to suppression of inflammation through the TNFα-p38/NFκB pathway. Accordingly, the PE-like mouse model showed a reversal of PE-like symptoms and a reduced F4/80 + CD86 + macrophage percentage in the uterus in response to recombinant PDL1 protein administration, indicating the protective effect of PDL1. DISCUSSION: Our results initially explained an immunological adaptation of trophoblasts under placental hypoxia, although this protection was insufficient. Our findings suggest the possible capacity of modulating PDL1 expression as a potential therapeutic strategy to target the inflammatory response in sPE.

N6-methyladenosine dynamics in placental development and trophoblast functions, and its potential role in placental diseases.

N6-methyladenosine (m6A) is the most abundant modification controlling RNA metabolism and cellular functions, but its roles in placental development are still poorly understood. Here, we characterized the synchronization of m6A modifications and placental functions by mapping the m6A methylome in human placentas (n = 3, each trimester), revealing that the dynamic patterns of m6A were associated with gene expression homeostasis and different biological pathways in placental development. Then, we generated trophoblast-specific knockout mice of Wtap, a critical component of methyltransferase complex, and demonstrated that Wtap was essential for trophoblast proliferation, placentation and perinatal growth. Further in vitro experiments which includes cell viability assays and series molecular binding assays demonstrated that WTAP-m6A-IGF2BP3 axis regulated the RNA stability and translation of Anillin (ANLN) and VEGFA, promoting trophoblast proliferation and secretion. Dysregulation of this regulatory axis was observed in placentas from pregnancies with fetal growth restriction (FGR) or preeclampsia, revealing the pathogenic effects of imbalanced m6A modifications. Therefore, our findings provide novel insights into the functions and regulatory mechanisms of m6A modifications in placental development and placental-related gestational diseases.

A cellulose-based light-management film incorporated with benzoxazine resin/tannic acid exhibiting UV/blue light double blocking and enhanced mechanical property.

Cellulose, as a biomass resource, has attracted increasingly attention and extensive research by virtue of its widely sources, ideal degradability, good mechanical properties and easy modification due to its rich hydroxyl groups. Nevertheless, it is still a challenge to attain high performance cellulose-based composite film materials with diverse functional combinations. In this work, we developed a multifunctional cellulose-based film via a facile impregnation-curing strategy. Here, benzoxazine resin (BR) is used as an optically functional component to endow the microfibrillated cellulose (MFC) film with powerful light management capabilities including UV and blue light double shielding, high transmittance, and high haze. Meanwhile, the introduction of tannic acid (TA) substantially enhanced the mechanical properties of the film, including tensile strength and toughness, by constructing energy-sacrificial bonds. An effective self-healing of the film was achieved by controlling the degree of BR curing. The final films exhibited 98.24 % UV shielding and 89.98 % blue light blocking, good mechanical properties including a tensile strength of 202.21 MPa and tensile strain of 7.1 %, as well as desirable thermal healing properties supported by incompletely cured BR. This work may provide new insights into the high-value utilization of biomass resources.

Docosahexaenoic acid insufficiency impairs placental angiogenesis by repressing the methylene-bridge fatty acylation of AKT in preeclampsia.

INTRODUCTION: Preeclampsia (PE), characterised by hypertension in pregnancy, is regarded as a placental metabolism-related syndrome affecting 5-8% of pregnancies worldwide. The insufficiency of polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), is a causative factor of PE pathogenesis. However, its molecular aetiology is yet to be comprehensively elucidated. METHODS: CRISPR/Cas9 was used to construct Fads2 knockout mice. Gas chromatography-mass spectrometry was used to detect placental fatty acid levels. Gene Expression Omnibus was used to analyze placental FADS2 mRNA levels. CCK-8 assay was used to assess cell growth capacity. Cell migration and invasion abilities were measured by transwell and wound healing assay. Tube forming assay was used to test angiogenesis ability. The co-immunoprecipitation assay was used to validate interactions between two proteins. AKT inhibitor MK-2206 and methylene-bridge fatty acylation inhibitor tryptophan were used to rescue experiments. RESULTS: Compared to those in women with normal pregnancies, the DHA levels in the placentas of patients with PE decreased with the downregulation of FADS2, the key desaturase in the synthesis of PUFAs. Pregnant Fads2+/- mice exhibited PE-like symptoms, including proteinuria and elevated systolic arterial blood pressure, due to defective placental angiogenesis. Mechanistically, FADS2 knockdown in trophoblasts decreased cellular DHA levels and repressed the methylene-bridge fatty-acylation of AKT, inhibiting AKT-VEGFA signalling, which is crucial for angiogenesis. DISCUSSION: Our results suggest that placental DHA insufficiency downregulates placental angiogenesis via inhibiting fatty acylating AKT and AKT-VEGFA signalling, a novel insight into abnormal fatty acid metabolism in PE.

Cellulose-based light-management film exhibiting flame-retardant and thermal-healing properties.

The increased use and expansion of biomass applications offer a viable approach to diminish reliance on petroleum-derived resources and promote carbon neutrality. Cellulose, being the most abundant natural polymer on Earth, has garnered considerable attention. This study introduces a straightforward method to fabricate a cellulose-based multifunctional composite film designed for efficient light management, specifically featuring flame retardant and thermal-healing capabilities. The film incorporates a microfibrillated cellulose (MFC) matrix with functional components, namely benzoxazine resin (BR) and 2-hydroxyethyl methacrylate phosphate (HEMAP). Utilizing dynamic covalent crosslinking, the composite films exhibit satisfactory self-healing properties. The combined effects of BR and HEMAP contribute to the effective flame retardancy of the composite film. Furthermore, the resulting film shields ultraviolet and blue light, offering comfortable interior lighting by mitigating harsh light and extending light propagation. The film also demonstrates favorable water resistance and high tensile strength. The exceptional multifunctional properties, coupled with its safety and extended service life, position it as a potential optical management film for smart building materials.

Establishment and Application of a Novel Genetic Detection Panel for SNPs in Mongolian Gerbils.

The Mongolian gerbil is a distinctive experimental animal in China, as its genetic qualities possess significant value in the field of medical biology research. Here, we aimed to establish an economical and efficient panel for genetic quality detection in Mongolian gerbils using single-nucleotide polymorphism (SNP) markers. To search for SNPs, we conducted whole-genome sequencing (WGS) in 40 Mongolian gerbils from outbred populations. Reliable screening criteria were established to preliminarily select SNPs with a wide genome distribution and high levels of polymorphism. Subsequently, a multiple-target regional capture detection system based on second-generation sequencing was developed for SNP genotyping. Based on the results of WGS, 219 SNPs were preliminarily selected, and they were established and optimized in a multiple-amplification system that included 206 SNP loci by genotyping three outbred populations. PopGen.32 analysis revealed that the average effective allele number, Shannon index, observed heterozygosity, expected heterozygosity, average heterozygosity, polymorphism information content, and other population genetic parameters of the Capital Medical University (CMU) gerbils were the highest, followed by those of Zhejiang gerbils and Dalian gerbils. Through scientific screening and optimization, we successfully established a novel, robust, and cost-effective genetic detection system for Mongolian gerbils by utilizing SNP markers for the first time.